patent_id
stringlengths 7
8
| description
stringlengths 125
2.47M
| length
int64 125
2.47M
|
|---|---|---|
11857688 | DETAILED DESCRIPTION OF THE INVENTION Certain terminology is used herein for convenience only and is not to be taken as a limitation on the present invention. Relative language used herein is best understood with reference to the drawings, in which like numerals are used to identify like or similar items. Further, in the drawings, certain features may be shown in somewhat schematic form. It is also to be noted that the phrase “at least one of”, if used herein, followed by a plurality of members herein means one of the members, or a combination of more than one of the members. For example, the phrase “at least one of a first widget and a second widget” means in the present application: the first widget, the second widget, or the first widget and the second widget. Likewise, “at least one of a first widget, a second widget and a third widget” means in the present application: the first widget, the second widget, the third widget, the first widget and the second widget, the first widget and the third widget, the second widget and the third widget, or the first widget and the second widget and the third widget. FIG.1shows an illustrative embodiment of an inpatient room1in a hospital that is accessible through a door6separating the inpatient room from a hallway, for example. The room1is provided with a patient bed4and a tray table5that can extend over the patient lying in the bed4. Although not shown, the room1can also include other fixtures and features commonly found in inpatient rooms such as a television, health-monitoring equipment such as a heart-rate monitor, telephone, nightstand, etc. . . . Further, although the present disclosure focuses on the decontamination of items within an inpatient hospital room1for the sake of clarity and brevity, the technology disclosed herein can be used to decontaminate objects located anywhere, such as in hotel rooms any other public accommodations. Also disposed within the room1shown inFIG.1is a decontamination apparatus10operable to at least partially decontaminate, or at least render pathogen reduced, contaminated surfaces such as the tray table5within that room1. The decontamination process can be initiated manually, and performed by the decontamination apparatus10on demand, and/or can optionally be initiated automatically according to a predetermined schedule when the room1is unoccupied, as determined utilizing a plurality of sensors as described below. Rendering the surfaces “pathogen reduced” with the decontamination apparatus10does not necessarily require the subject surfaces to be 100% sterile, free of any and all living organisms that can viably reproduce. Instead, to be considered pathogen reduced, there must be a lower level of living contagions on the decontaminated surfaces capable of reproducing or otherwise causing an infection after performance of the decontamination process than the level that existed on the surfaces prior to performance of the decontamination process. For example, the exposed surfaces in the bathroom can be considered to be pathogen reduced if at least a 1 log10reduction of such contagions on the surfaces remain infectious (i.e., no more than 1/10th of the biologically-active contagions originally on the exposed surfaces remain active or infectious at a time when the decontamination process is completed) occurs. According to yet other embodiments, the surfaces can be considered pathogen reduced once at least a 3 log10reduction (i.e., 1/1,000th) of such contagions on the surfaces is achieved. Generally, the decontamination apparatus10includes one or a plurality of sources12that direct a disinfecting agent toward the surface(s) to be rendered pathogen reduced, a redundant occupant sensing system that determines whether the room1is occupied or not, and a controller16that interferes with emission of the disinfecting agent by the source(s)12if the room1is, or becomes occupied based on a signal from the occupant sensing system. Each source12can be any apparatus that emits a disinfecting agent that, when exposed to the surfaces to render those exposed surfaces pathogen reduced. For the illustrative embodiments described herein and shown in the drawings, each source12is an ultraviolet source that is to be energized to emit UVC light as the disinfecting agent, and the surface to be rendered pathogen reduced is the tray table5. As shown, each source12includes at least one, and optionally a plurality of UVC bulbs14(FIG.2) coupled to a reflective shield18coupled to an underside of a housing20. The housing20can be pivotally coupled to a distal end of an articulated arm22or other suitable support that allows the housing20, and accordingly the bulbs14, to be pivoted about a rotational axis in the directions indicated by arrow21and otherwise positioned in a suitable position relative to the tray table5to achieve the desired level of decontamination within a predetermined period of time, once activated. According to the embodiment inFIG.1, each arm22has a portion including an adjustable length extending generally away from a base portion25, which can be facilitated by an external member24that telescopically receives an internal member26, or other suitable length adjustment mechanism (e.g, sliding track, etc. . . . ). A locking member27such as a spring-biased pin urged toward a locking position, etc. . . . can be provided to one or both of the external and internal members24,26to maintain a desired length of the arm22, once manually established. A hinge28or other connector suitable to allow angular adjustment of the arm22relative to the base25can be disposed between the base25and the arm22. A bendable joint30can also be provided anywhere along the length of the arm22, such as adjacent to the distal end of the arm22where the housing20is supported. The joint30can be formed from a plastically-deformable flexible material that can be manually bent to position the housing20, yet be sufficiently rigid to maintain the position of the housing relative to the arm22once the bending force has been removed. Further, a hinge32can also optionally be positioned along the arm22before and/or after the joint30to allow further adjustment of the position of the housing20and bulbs to achieve the desired coverage of the tray table5with UVC light. As with any of the hinges described herein, the hinge(s)32can be selectively lockable, meaning a locking member such as a set screw, for example, can be loosened to allow the structures coupled to opposite sides of the hinge(s)32to be pivotally adjusted relative to each other. Once the desired adjustment has been completed, the set screw or other locking member can be tightened to interfere with further pivotal adjustment of the structures relative to each other. The base25supports the arms22at a desired elevation above the floor7of the room1. The base25supports the controller16that can be manipulated by a user to control operation of the decontamination apparatus10(e.g., independently control operation of each source12to emit UVC light, optionally to cause one source12to remain energized longer than another one of the sources12), and optionally houses an on-board power supply such as a rechargeable battery bank37storing electric energy that can be used to energize the bulbs14and power the controller16. Being relatively heavy, the battery bank37can be housed within a recess defined by a lower cap39of the base25comprising an arcuate bottom surface41that rests on the floor7. The arcuate bottom surface41allows the decontamination apparatus to wobble, if necessary, to properly position the bulbs14for a decontamination process. The base25, or another portion for the decontamination apparatus can optionally be provided with an accelerometer, tip sensor, gyroscope or other type of monitoring device that can sense when the decontamination apparatus10has been picked up, falls over, moved or otherwise disturbed. In such events, an active decontamination process can be terminated and a new decontamination process can be prevented from being initiated. The lower cap39can be threadedly connected to the base25so as to be removable, and optionally interchangeable. For removable embodiments, the lower cap39can be unscrewed from the base25to grant access to the battery bank37. A depleted battery bank37can then be removed from the decontamination apparatus10and replaced with a charged battery bank37. For embodiments where the battery bank37is integrated into the lower cap39, the lower cap with the depleted battery bank37can be replaced in its entirety with another lower cap39with a charged battery bank37. According to alternate embodiments, the decontamination apparatus can include a power cord that is to be plugged into an AC mains electric outlet supplied by an electric power utility to obtain the electric energy needed to power the decontamination apparatus10. The base25can also optionally be provided with a connector, shown inFIG.1as a hook35that is generally shaped to resemble an upside-down “L”. The hook35can be placed over a receiver or other portion of a cart hauling cleaning supplies, for example, or any other transport vehicle, to allow transportation of the decontamination apparatus10throughout the hospital for use in a plurality of different rooms1. The embodiments of the base25are described above as a static structure that supports the arms22at a desired elevation above the floor7of the room1and optionally housing a battery bank37. However, alternate embodiments of the base25′ are schematically shown inFIGS.5-8. The base25′, according to such alternate embodiments, includes a plurality (e.g., three in the illustrated embodiment) of arcuate panels82, each pivotally coupled by a hinge84or other adjustable fastener to static portion86of the base25′ to which the arms22are coupled. Each panel82has an arcuate shape across a lateral dimension, to form approximately one third (⅓) of the total circumference of the substantially-tubular base25′ when adjusted to the stowed configuration. In the stowed configuration, each panel82extends substantially vertically upward from the static portion86of the base25′ to define an internal chamber88into which the arms22, and optionally the bulbs14, are at least partially recessed while the decontamination apparatus10is in the stowed configuration. Inward-facing surfaces of each panel82can optionally be coated with, or otherwise formed from a light-colored material (e.g., white, off white, cream, light gray, etc. . . . ) and/or a reflective material (e.g., metallic, reflective plastic, etc. . . . ) to enhance the reflectivity of UVC light emitted by the bulbs14while at least partially recessed in the chamber88. Thus, in the stowed configuration after being used to decontaminate a surface in a hospital room, for example, where the inward-facing surfaces of the panels82could be exposed to a biologically-active pathogen, the bulbs14can be activated to emit UVC light. This UVC light will be reflected by the inward-facing surfaces of the panels82, thereby promoting complete exposure of the entire internal periphery of the chamber88. Such activation of the bulbs14can decontaminate the inward-facing surfaces of the panels82, thereby mitigate the risk of spreading the pathogen from one environment to another as the decontamination apparatus10is transported there between. The base25′ can be converted from the stowed configuration to a deployed configuration, shown inFIGS.7and8, in which the decontamination apparatus10is ready for use. Such a conversion can be achieved by pivotally adjusting the panels82about their respective hinges84, such that the panels82extend downward from the static portion86at an angle (e.g., between about 45° and 90° from horizontal). The inward-facing surfaces of the panels82are adjusted to become substantially outward-facing surfaces in the deployed configuration, thereby exposing those surfaces to the elements within the room in which the decontamination apparatus10is located. In the deployed configuration, the panels82act as legs that separate the static portion86from an underlying ground surface, and elevate the static portion86and arms22to a height above the underlying ground surface suitable for performing the desired decontamination process. The reflective shield18inFIG.2includes an arcuate or paneled region34that is configured to reflect UVC light emitted upwardly from the bulbs14in a downward direction, generally towards the tray table5where the UVC light can decontaminate the exposed surfaces thereof. The arcuate or paneled region34can include a continuous curvature in multiple planes or a plurality planar and reflective structures arranged to form a somewhat curved profile to achieve the desired light pattern for the tray table5or other object being decontaminated. For example, and as schematically illustrated inFIGS.9-11, the reflective shield18can include a reflective surface94that faces the bulbs14that has a gradually varying, or at least a variable, radius of curvature in a transverse direction relative to a longitudinal axis47along the length of that longitudinal axis47(FIG.2). For example, the radius of curvature of the reflective surface of the reflective shield18can be greatest at a central region96(FIG.11) adjacent to the location of a focal indicator40, described below. The radius of curvature in the transverse direction is less than the radius of curvature at this central region at locations further toward opposite, longitudinal ends46of the reflective shield18along the longitudinal axis47. The radius of curvature can optionally be the smallest at those longitudinal ends46. Although the radius of curvature is used to describe the shape of the reflective surface of the reflective shield18, it is to be understood that the cross-sectional shape of the reflective surface does not necessarily have a constant radius of curvature. In other words, the cross sectional shape of the reflective surface94taken along line10-10inFIG.9, a cross section that is depicted inFIG.10, can be a downward-opening parabolic shape, or other desired arcuate shape that more-narrowly focuses UVC light emitted by the bulbs14in the transverse direction adjacent to the longitudinal ends46than adjacent to the central region along the longitudinal axis47. To help with adjustment of the housing20and/or reflective shield18, a focal indicator40can optionally be provided to the reflective shield18and/or housing20. Locating the focal indicator40between the UVC bulbs14as shown inFIG.2allows the focal indicator to identify a general direction that is representative of the direction in which the UVC light from the UVC bulbs14will be focused. The focal indicator40can include a light emitting diode (“LED”), laser light, or other optical indicator that can project light that will illuminate a region of a surface on which the UVC light from the UVC bulbs14is centered. An example of such a region is illustrated inFIG.1by the broken lines45appearing on the tray table5. Thus, a user can essentially aim the UVC light toward the surfaces to be rendered pathogen reduced, and get a sense of the portion of the tray table5that will be suitably exposed to the UVC light during a decontamination apparatus to be considered pathogen reduced within a predetermined period of time for the power of the bulbs14employed. FIG.8shows an alternate embodiment of the reflective shield18′. Unlike the embodiments described above involving a separate reflective shield18provided to each source12, the present embodiment includes a collapsible shield18′ that is configured to reflect UVC light emitted by a plurality (e.g., two illustrated inFIG.8) of bulbs14. As shown, the reflective collapsible shield18′ includes an aluminized or otherwise metalized Mylar (e.g., stretched polyester film, also commonly referred to as biaxially-oriented polyethylene terephthalate or “BoPET”, for short) sheet90spanning a distance between poles92extending in different, optionally diverging or opposite directions from the static portion86of the base25′. Mylar is one example of a suitable reflective surface that is collapsible, but the present disclosure is not so limited, as any reflective surface that can be collapsed to fit within the chamber88of the base25′ in the stowed configuration will suffice. One or each of the poles92can optionally be spring biased, urged by gravity or otherwise urged toward their diverging orientations in which the sheet90is pulled substantially taut to form a reflective surface extending between the poles92. To convert the decontamination apparatus10to its stowed configuration, the poles92are adjusted toward each other, allowing the sheet90to be folded in a fan-like manner to fit within the chamber88formed by the panels82of the base25′, as shown inFIG.6. The embodiment of the source12shown inFIG.2includes a plurality of elongated UVC bulbs14that emit UVC light as the disinfecting agent. Since such a source12emits only UVC light, it is dedicated for performing the decontamination process described herein. But regardless of the configuration of the UVC bulbs14, the source12can optionally include an intensity sensor48that senses an intensity of the UVC light emitted by each UVC bulb14present. For the sake of brevity, the present technology will be described hereinafter with reference to the elongated UVC bulbs14, although any other desired configuration of UVC bulb is a viable alternative. The intensity of the UVC light emitted by the UVC bulbs14will diminish over time. To promote thorough decontamination of the exposed surfaces in the room1with a reasonable cycle time for the decontamination process, the intensity sensors48include a photosensitive component such as a photodiode, charge coupled device, etc. . . . , operatively coupled to the controller16to monitor the intensity of the UVC light from the UVC bulbs14. A signal indicative of the sensed intensity is transmitted to the controller16, which is operatively connected to at least receive signals transmitted by the intensity sensor48and the sensors of the redundant occupant sensing system as described below. Based at least in part on the signal from the intensity sensor48, the controller16can issue a notification that one or more of the UVC bulbs14is nearing the end of its useful life, and should be replaced. Such a notification can include the illumination of a visible indicator in the form of a LED50provided to the source12itself, or to an appropriate LED52(FIG.4) provided to the controller16, which can optionally be remotely located from the source12but in communication with the source12via a communication channel such as a hardwired or wireless connection, or optionally integrated as part of the source12itself. According to alternate embodiments, the controller16can optionally be in wireless communication with a portable fob17(FIG.1) having limited control features. For the illustrated embodiment appearing inFIG.1, for example, the portable fob17allows an operator to issue a START command by selecting a start button19to commence a decontamination cycle from a location that is remote (e.g., externally of the room in which the decontamination apparatus10is located) from the decontamination apparatus10. The portable fob17and/or the controller16can optionally be configured to commence decontamination cycles of varying durations based, at least in part, on the number of times the start button19is selected. Although the illustrated embodiment of the portable fob17inFIG.1includes a start button19, it can optionally lack a stop button or any other feature that would allow the operator to terminate the decontamination cycle, on demand, from the remote location. FIG.3shows a partially-cutaway side view of the source12taken along line3-3inFIG.2. To promote the longevity of the UVC bulbs14provided to the source12, a coupling77is arranged between the housing20and the hinge32. The coupling77defines an interior passage79in which an electric fan81is located. The Electric fan81can be powered with electric energy supplied by the battery bank37, with electric energy supplied from the AC mains wall outlet, etc. . . . to direct cooling air over the UVC bulbs14. Further, one or a plurality of proximity sensors58, interchangeably referred to as range sensors58, can be arranged, optionally as an array, to sense a proximity of the housing, which is indicative of the proximity of the bulbs14, to the tray table5or other object to be rendered pathogen reduced. For example, the proximity sensors58can sense light from a light source that is reflected from the tray table5to determine the approximate spacing of the housing and20and/or bulbs14from the tray table5. Other embodiments of the proximity sensors59can utilize a sensed capacitance value to determine such a proximity. According to yet other embodiments, an ultrasonic range finder includes an ultrasonic transceiver that emits high-frequency sound waves (e.g., frequencies, such as those above 20 kHz, or otherwise above the upper limit of the human audio spectrum) and evaluates the echo which is received back by the sensor58, measuring the time interval between sending the signal and receiving the echo to determine the distance to the object to be rendered pathogen reduced. Regardless of the technology utilized, arranging the proximity sensors58in an array or at least positioning one proximity sensor58at a known location promotes proper positioning of the bulbs14relative to the surface of the tray table5to achieve the desired level of decontamination utilizing a decontamination process with a predetermined duration. In other words, a scenario where one end of each bulb14is relatively close to the surface of the tray table5and the other, opposite end of each bulb14is relatively far from the surface of the tray table can be avoided through use of the proximity sensors58. If a significant departure from the uniform spacing of the bulbs14from the tray table5is detected, a warning can be audibly broadcast from a speaker61provided to the controller16, presented as the illumination of a LED on the controller and/or the offending source12, etc. . . . to help the operator correctly orient the source12. According to other embodiments, the proximity sensors58can be utilized to ensure the source12is positioned close enough to the tray table5to achieve the desired level of decontamination during performance of the decontamination process. The controller16can optionally be configured to automatically (e.g., without human intervention directed specifically toward specifying the length of the decontamination process) adjust the duration of the decontamination process based, at least in part, on the distance separating the source12from the tray table5. For example, the one or more proximity sensors58senses a distance separating the tray table5from the source12, and transmits a signal indicative of this distance to the controller16. Based on this signal, the controller16can determine the approximate value of the separation, and determine a length of the decontamination process such that the desired level of decontamination is achieved once the decontamination with the adjusted length is completed. As a specific example, based on the signal from the proximity sensor(s)58, the controller16can determine whether the source12, or at least the bulbs14are within eighteen (18 in.) inches of the tray table5. If so, a range indicator49such as the LED shown inFIG.2provided to the source12can be illuminated green to indicate that the source12is sufficiently close to the tray table5for a sixty (60 sec.) second decontamination process. The controller16can then initialize an internal timer to sixty (60 sec.) seconds so the controller16can terminate the decontamination process sixty (60 sec.) seconds after the decontamination process began. Likewise, if the controller16determines that the source12is separated from the tray table5by a distance greater than eighteen (18 in.) inches, but less than twenty four (24 in.) inches, the range indicator49can be illuminated yellow and the controller can initialize the timer for a ninety (90 sec.) second decontamination process. The embodiments described above utilize one or a plurality of electronic proximity sensors58that use a sensed capacitance value, reflected light, reflected sound and the like to determine the distance separating the bulbs14from the tray table5. However, other embodiments of the decontamination apparatus10can include a probe58′ that can be used instead of, or optionally in addition to the proximity sensor(s)58to establish a separation of a suitable distance between the bulbs14and the tray table5surface to achieve the desired level of decontamination. The probe58′ can be an elongated finger that is pivotally coupled to the housing20. As the bulbs14supported adjacent to that housing20are being positioned relative to the tray table5, the probe58′ is pivoted relative to the housing20to extending toward the tray table5, in a direction that is approximately perpendicular to a plane in which the bulbs14are arranged. Establishing contact between a distal tip71of the probe58′ and the tray table15establishes a separation between the tray table5and the bulbs14that is a predetermined distance approximately equal to a length of the probe58′. In addition to, or instead of adjusting the duration of the decontamination process based on the proximity of the source12relative to the tray table5, the controller16can be adapted to adjust the duration of the decontamination process based, at least in part, on the intensity of the UVC light emitted by the bulbs14as detected by the intensity sensor(s)48. For example, if the source12is separated from the tray table5by a distance of less than 18 inches, but the intensity of the UVC light from the bulbs14has declined to a value of approximately 80% of the intensity of the UVC light originally emitted by the bulbs14, when new, the controller cause the range indicator49to be illuminated yellow and set the duration of the decontamination process to be ninety (90 sec.) seconds. For embodiments where the controller16is located remotely (e.g., not physically connected to or supported by the base or other portion of the decontamination apparatus10) from the decontamination apparatus10, the controller can optionally be supported on a wall of the room1, for example. For such embodiments, the controller16can be wirelessly connected to communicate with a transceiver provided in place of the controller16on the decontamination apparatus. The redundant occupant sensing system includes a plurality of sensors that each independently senses a different property indicative of the presence or absence of a room occupant. With reference once again toFIG.1, the redundant occupant sensing system includes a door sensor54that is operatively connected to communicate with the controller16via a wireless (e.g., Bluetooth, IEEE 802.1x, other short-range communication protocol, etc. . . . ) communication channel and detects a status of the door6as being open and/or closed. The door sensor54transmits a signal to be received by the controller16, which can interpret the signal to determine if the door6is open, closed, or has changed from open to closed or closed to open. The signal can be embodied by the transmission of an electric signal over a wireless communication channel, or a hardwired connection between the door sensor54and the controller16, or the interruption or establishment of a signal received by the controller16. Other sensors included in the redundant occupant sensing system can likewise be positioned at appropriate locations within the room1, such as integrated into the controller16, to detect other properties that would indicate the presence or absence of an occupant. Such other sensors can be discrete sensors, or integrated into a common sensor assembly, which can optionally be housed as part of the controller16as shown inFIG.4(sensors integrated into the controller16inFIG.4are represented schematically as broken lines). Regardless of their location and configuration, each of the plurality of sensors in the redundant occupant sensing system must sense a property that the room1is unoccupied and communicate this status to the controller16before the decontamination process can begin as described below. The unoccupied status, as sensed by the redundant occupant sensing system, must also be maintained while the source(s)12of the decontamination apparatus10is/are operational, otherwise the controller16will terminate operation of operational sources12. An example of another of the sensors included in the integrated sensor assembly of the redundant occupant sensing system is an immediate proximity sensor51that can detect the presence of an occupant within a predetermined distance from the decontamination apparatus10without making physical contact with the occupant. The proximity sensor can utilize any suitable technology such as an electromagnetic field or electromagnetic radiation (infrared, for instance), to determine the distance of an object such as an occupant from the proximity sensor51to determine whether the room1is occupied. Such a sensor operates by monitoring the electromagnetic field or evaluating the return signal for changes, which would be indicative of the presence of an occupant. Yet other embodiments can utilize an optical sensor that relies on reflected light or the interruption of a beam of light to detect the presence of an occupant, or a capacitive sensor that senses changes in the value of a capacitance sensed within a region of the room1where an occupant is likely to be located. Regardless of the sensing mechanism utilized, the proximity sensor signals transmitted to the controller16identify changes in the proximity sensor signal that indicate a change has occurred since an earlier proximity sensor signal was transmitted (e.g., when the proximity sensor51was normalized under known conditions, such as when the room was unoccupied and the decontamination apparatus10was initially powered on). Another sensor that can optionally be included as part of the integrated sensor assembly is a sound sensor55. The sound sensor can include a microphone or other sound-sensitive circuit that transmits a signal indicative of the magnitude and/or frequency of sounds audible within the room1. Similar to the proximity sensor51and the other sensors of the redundant occupant sensing system, the sound sensor55is operatively connected to communicate with the controller16and transmit signals to the controller16that are interpretable to indicate changes in the sound level within the bathroom1. These changes can be relative to the sound level within the room1at a time of an earlier sound level is measured, or when the sound sensor55is normalized such as when the system is initially powered on when the room is known to be unoccupied. A light sensor57can also optionally be included as part of the sensor assembly to detect changes in light within the room1. The light sensor57can include a photosensitive component such as a photodiode, charge coupled device, etc. . . . , that monitors the intensity of visible light and/or UVC light within the room. Again, a signal indicative of the sensed light levels within the room1is transmitted to the controller16, which can determine whether a change in light level has occurred, which would suggest an occupant has entered the room1. Contrarily, the light sensor57can also sense dramatic reductions in the light within the room1, and optionally such reductions throughout the entirety of the room1(e.g., by utilizing a plurality of light sensors57facing different directions). The controller16can be initialized and configured to initiate the decontamination process under such circumstances, based on the assumption that the ambient lighting in the room1has been turned off when the last occupant has left as described below. Further, a motion sensor65can also optionally be included in the sensor assembly to sense movement within the room1. Such motion sensors65can be sense a property such as changes in the thermal signature at various locations within the room1. Utilizing the temperature gradients to detect motion is advantageous in that inanimate movement in the room (e.g., a towel falling from a rack) will not trigger the motion sensor65to transmit a signal indicative of movement. Other embodiments of the motion sensor65include a photoelectric sensor that utilizes a beam of light or and laser that travels from a source to a detector. When an occupant crosses the path of light, the light is blocked and the sensor detects the obstruction. Such motion sensors65can optionally be positioned at particularly revealing locations such as approximately 1-3 ft. above the floor at the door6, for example. Projecting a beam of light at such a location will almost certainly be broken if an occupant enters the room1through the door6. Certain embodiments of the decontamination system10will include at least one of the aforementioned sensors (door, proximity, sound, light and movement), and optionally a plurality, or all of these sensors. However, alternate embodiments can utilize any other suitable sensor(s) that can transmit a signal indicative of the presence of a living occupant within the room1without departing from the scope of the present disclosure. For example, a carbon dioxide sensor can be utilized to sense a change in the carbon dioxide level in the room1cause by an occupant exhaling. Other embodiments can utilize a heartbeat monitor that can remotely sense the pulses of a beating heart without making physical contact with an occupant. Yet other embodiments can utilize a pressure sensor operatively connected to the bed4to sense when an occupant is resting thereon, for example. An illustrative embodiment of the controller16is shown inFIG.4. As shown, the controller16includes a focus button85that, when pushed, temporarily energizes or otherwise activates the focal indicator40to illuminate that portion of the tray table5that is to be decontaminated. Also included are manual override buttons60,62that, when pressed, cause the decontamination process to be manually initiated and stopped on demand, respectively. If the start button60is selected, the controller16implements a delay of a predetermined duration (e.g., 10 seconds) that is sufficient to allow the person who pressed the start button60to exit the room1before the UVC bulbs14are illuminated as part of the decontamination process. An audible warning such as a repeating beep can be broadcast by a speaker61provided to the controller16to warn of the impending start of the decontamination process. As mentioned above, the start button19on the fob17can optionally be selected once the operator has exited the room1instead, thereby remotely activating the decontamination cycle. According to alternate embodiments, however, the controller16can optionally be configured to operate in an occupied mode, in which the one or plurality of sensors of the occupant sensing system are deactivated to allow the sources12to remain active in the room1while the room1is occupied by a person. Under certain circumstances, personnel may where personal protective equipment (“PPE”) that shields their person from UVC light emitted by the sources12. The PPE allows personnel to safely work in the environment of the tray table5or other surface being decontaminated while the decontamination apparatus10is operational without the risk of being exposed to significant levels of UVC light. In an effort to prevent operation of the decontamination apparatus10in the occupied mode, each person wearing PPE within the room1while the decontamination apparatus10is active can wear or possess a badge that can be wirelessly detected within the room1by the decontamination apparatus10. Movement by personnel equipped with the badge can be ignored by the controller16such that the controller16will not prematurely terminate the decontamination cycle. If, however, movement is sensed outside of the vicinity of such a badge (e.g., movement occurs in a region of the room1where a badge is not also present or at least nearby), the controller16can determine that an unprotected occupant has entered the room and terminate the decontamination cycle. Thus, in use, personnel can optionally wear the PPE and activate the decontamination apparatus10in the occupied mode while continuing to safely work within the room1in which the decontamination apparatus10is located. Alternately, the decontamination apparatus10can be activated in a standard mode, either locally with a delay or remotely from outside of the room1, and the decontamination apparatus10can remain active unless the controller16senses the presence of an occupant. Following the expiration of the delay, each of the sensors included in the redundant occupant sensing system is normalized, indicating a state where it is assumed that the room1is unoccupied. If, at any time during the decontamination process any of the sensors senses a property that is indicative of a change from the state in which the sensors were normalized, the controller16determines that the room has become occupied, and immediately terminates the decontamination process. To identify the cause of termination, one or a plurality of labeled visible indicators64such as discrete LEDs, a liquid crystal display (“LCD”), or any other suitable notification device provided to the controller16can be activated. For example, the proximity indicator66can be illuminated to indicate that the proximity sensor triggered termination; the sound indicator68can be illuminated to indicate that the sound sensor triggered termination; the light indicator70can be illuminated to indicate that the light sensor triggered termination; the motion indicator72can be illuminated to indicate that the motion sensor triggered termination; and the door indicator74can be illuminated to indicate that the door sensor54triggered termination. The specific visible indicators64included as part of the controller16can correspond to the specific sensors present. Rather than being activated remotely utilizing the fob17or locally with the delay, the decontamination apparatus10(specifically, the controller16) can optionally be configured to initiate a decontamination process in response to sensing a change in the sensed light levels in its ambient environment according to alternate embodiments. For example, the controller16can optionally be initialized through pressing the start button19on the fob17three times in quick succession. In response to receiving such a communication from the fob17, the controller16can enter a standby mode and sense the current light level in the room1. In response to sensing a dramatic drop in the light level relative to the originally-sensed light level, the controller16can optionally sound an audible alarm during the delay before subsequently energizing the bulbs14. Regardless of the operational mode of the decontamination apparatus10, if premature termination of the decontamination process occurs before the decontamination process is complete (e.g., before the UVC bulbs14have been illuminated for the time required to achieve the desired level of pathogen reduction), a cycle status indicator75can be illuminated in a manner indicative of such termination. For example, the cycle status indicator75can be illuminated red, and/or made to flash to call an operator's attention to the premature termination of the decontamination process. The manual pressing of a reset button76can be required by the controller16before the decontamination process can be restarted. Requiring the reset button76to be pushed will allow an operator to ensure that the condition resulting in termination of the decontamination apparatus has been cleared before resetting the controller16. According to alternate embodiments, the cycle status indicator75can optionally be provided to the housing20of each source12as shown inFIG.2. If a decontamination process is interrupted, each specific source12that was interrupted and did not successfully complete the decontamination process can be identified through the state of the cycle status indicator75thereon. Premature termination of the decontamination apparatus can be saved in a log stored on a computer-readable medium (e.g., SD card inserted into SD card port80provided to the controller16, built in hard drive or other non-transitory computer-readable medium provided to the controller16, remote hard drive or other non-transitory medium remotely located over a hospital communication network) in communication with the controller16. Such a log can maintain data concerning the cause of an interruption, a time of an interruption, information indicative of the specific room in which premature termination of the decontamination process occurred, and any other data pertaining to the decontaminated state of the room1. Such data can be utilized to diagnose problems such as a faulty sensor included in the redundant occupant sensing system, and to promote regular decontamination of the room1. The controller16can optionally be configured to restart a prematurely-terminated decontamination cycle without manual user intervention. For example, once all of the conditions sensed by the sensors in the redundant occupant sensing system return to their normalized values, the controller16can initiate a timer to establish a restart delay. If all of the conditions remain at their normalized values for the duration of the restart delay, the controller16can automatically restart the decontamination process by once again activating the UVC bulbs14for the predetermined cycle time. This process of restarting the decontamination process can optionally be repeated until the decontamination process has been completed successfully. If an automatically restarted decontamination process is successfully completed, the cycle status indicator75can reflect the successful completion of the decontamination process. In the absence of any conditions interrupting the decontamination process, the decontamination process will remain active, with the UVC bulbs14illuminated and the redundant occupant sensing system monitoring conditions within the room1for any changes that would indicate the entrance of an occupant for a predetermined cycle time. The predetermined cycle time can be manually input and programmed into the controller16via a timer input system78provided to the controller16, or can be established through an administration terminal and delivered to the controller16via a portable computer-readable medium such as an SD card inserted into an SD card slot80provided to the controller16. According to alternate embodiments, actions such as adjusting the duration of the decontamination process and actions other than manually initiating the decontamination process can be carried out over a communication network from a remotely-located administration terminal. The cycle time can be independently established to a custom duration for each object to be decontaminated depending on factors such as the size of the room, the number and intensity of the UVC bulbs14to be utilized, the distance separating the source12from the surface being decontaminated, etc. . . . to achieve the level of decontamination desired to be achieved. For instance, According to alternate embodiments, a default value that can be used for most installations can be utilized. The default value can be selected to be “overkill”, meaning that the default duration will be longer than required to achieve the desired level of decontamination for most installations based, at least in part, on assumptions about the size of the room, the number and intensity of the UVC bulbs14to be utilized, the distance separating the source12from the surfaces to be decontaminated, etc. . . . Once the decontamination process has been successfully completed, the cycle status indicator75can be illuminated as a solid (i.e., non-flashing) green color or otherwise notify an observer that the decontamination process has been successfully completed. Additionally, successful completion of the decontamination process can be logged on the computer-readable medium in communication with the controller16, documenting a time when the room was last successfully decontaminated. Illustrative embodiments have been described, hereinabove. It will be apparent to those skilled in the art that the above devices and methods may incorporate changes and modifications without departing from the general scope of this invention. It is intended to include all such modifications and alterations within the scope of the present invention. Furthermore, to the extent that the term “includes” is used in either the detailed description or the claims, such term is intended to be inclusive in a manner similar to the term “comprising” as “comprising” is interpreted when employed as a transitional word in a claim. | 45,157 |
11857689 | DETAILED DESCRIPTION The present invention provides various embodiments of a flexible UV light generation system or assembly that includes a plurality of UV-LEDs arranged across a surface area of the flexible UV light generation sheet or assembly. It will be appreciated that the disclosed UV light generation systems are useful in disinfection, sterilization, purification, and other treatment applications. The disclosed flexible UV light generation sheets and assemblies are useful as part of or to construct a UV treatment systems or UV light generation systems. The arrangement on the surface area achieves a wide distribution, and in one embodiment a uniform distribution, of the UV emission field by transmissively scattering and/or diffusely reflecting the UV light. The inventors have found that a uniform distribution is more advantageous in disinfection, purification, and sterilization systems because void or dark areas are reduced or may be eliminated. For example, a dark area could allow an impurity or pathogen to pass through without being disinfected, purified, sterilized, or otherwise treated. Example flexible UV light generation systems include those comprising a flexible circuit having multiple UV-LEDs. The flexible circuit may include a plurality of conductors, with each UV-LED positioned in independent electrical communication with at least one of the plurality of conductors. It will be appreciated that the multiple UV-LEDs may be arranged as an array and that the term array, as used herein, may correspond to a spatial distribution of a plurality of objects, such as UV-LEDs and conductors, with one or more of the objects connected to and/or attached to other objects in the array, such as by electrical connections. An array may be regular or non-regular, meaning the objects may be uniformly distributed or non-uniformly distributed. An example array may correspond to a ribbon cable, flexible circuit, or flat flexible cable having UV-LEDs attached along various positions of the ribbon cable, flexible circuit, or flat flexible cable. The flexible circuit may be flexible and supported or otherwise attached to another flexible layer, such as a flexible UV diffuse reflective layer or a flexible UV transmissive scattering layer. In some embodiments that include a UV diffuse reflective layer, the UV diffuse reflective layer may include a plurality of openings, arranged to position each opening adjacent to a corresponding UV-LED, such that the corresponding UV-LED is exposed through the opening to allow UV light generated by the corresponding UV-LED to pass through the opening. In one embodiment to achieve a uniform distribution, the UV light generation system is arranged to position at least a first UV-LED of the multiple UV-LEDs in a configuration that is directly opposed to a UV diffuse reflecting layer, such as a highly diffuse UV reflecting layer. In one embodiment to achieve a uniform distribution, the UV light generation system is arranged to position at least a first UV-LED of the multiple UV-LEDs in a configuration that is not directly opposed to any other of the multiple UV-LEDs. In one embodiment to achieve a uniform distribution, the UV light generation system includes a UV transmissive scattering layer or overlayer, such as a high haze film, to scatter or defocus UV light generated by the UV-LEDs. Optionally, these embodiments may be combined to provide advantageous positioning of UV-LEDs and inclusion of a UV transmissive scattering layer. In one embodiment, the UV transmissive scattering overlayer does not include UV absorbing filler material. The stream being treated may be a gas or liquid stream that contains impurities such as pathogens, toxins, particulates, and combinations thereof. Treatment may be useful for reducing the impurities, or preferably eliminating the impurities, to produce a clean stream by disinfection, purifying, or sterilization. In one embodiment a liquid stream, such as water, blood, milk, or oil, is treated for use in sensitive applications that require high purity. In another embodiment, a gas stream is treated for use in sensitive applications that require high purity. In another embodiment, a gas stream comprising solid particles, such as food stuffs or seeds, is treated to disinfect, purify, or sterilize impurities. The gas stream may contain air or nitrogen and concentration of solid particles may vary from 0.1 to 99.9% in the gas stream. It should be understood that the impurities may be less than the solid particles. A UV light generation sheet may have a width and a length that are of the same or similar dimensions in a generally rectangular configuration. A flexible UV light generation sheet may alternatively be constructed as a ribbon or tape, such as a rectangular configuration in which a width is considerably smaller than a length, such as where the length is 5 times greater (or more) than the width. Other sheet shapes are possible, such as circular, oval, and polygonal, as well as any other conceivable shape that may be constructed from a web of material. A UV light generation sheet or system may optionally be flexible, allowing arrangement of the UV light generation sheet or system to define a fluid pathway, for example. To achieve flexibility, associated components of the UV light generation sheet or system may be flexible. As an example, a UV diffuse reflective layer, underlayer, or overlayer may optionally be flexible. As another example, a UV transmissive scattering layer, underlayer, or overlayer may optionally be flexible. In one embodiment, to define the fluid pathway the UV light generation sheet or system is wrapped, such as helically wrapped, laterally wrapped, or otherwise circumferentially arranged around the fluid pathway. The wrapped UV light generation sheet or system may form a tubular shape that corresponds to the fluid pathway. UV light generation sheet or system embodiments may be wrapped in a non-overlapping or overlapping configuration. In other embodiments, one or more UV light generation sheets or systems may be helically wrapped to define a fluid pathway. Any desirable configuration may be used herein, such as a planar configuration, a convex configuration, a concave configuration, and combinations of these. Materials in UV light generation sheets and systems may individually and/or collectively have elastic, compressive, or bending moduli suitable for the overall structure to be flexible. Example elastic, compressive, or bending moduli for flexible assemblies and materials exhibit an elastic modulus of between 0.001 GPa and 3.0 GPa. In some embodiments, materials included in a UV light generation sheet or system may exhibit an elastic, compressive, or bending modulus outside of this range. For example, conductors used for providing current and/or voltage to one or more UV LEDs may have a relatively larger elastic modulus, but may still exhibit flexibility along one or more axes, such as by way of a suitable bending modulus or compressive modulus, sufficient for inclusion in a flexible assembly. In general, the term flexible refers to materials that elastically bend in response to a force rather than fracture or undergo inelastic deformation, and the term flexible may be used interchangeably herein with the terms pliable and bendable. In some embodiments, flexible materials may be bent to a radius of curvature of 1 cm or less (e.g., 1 mm to 1 cm) without undergoing fracture or inelastic deformation. Various ASTM and ISO standards are useful for determining or specifying flexibility features of different materials including ASTM standards D747, D790, D5045, D7264, E111, E1290, E1820, and E2769 and ISO standards 170, 178, 12135, and 12737, which are hereby incorporated by reference. Example configurations include a tube-like configuration, where the flexible UV light generation sheet or system is arranged to enclose an interior space, such as by wrapping the flexible UV light generation sheet or system around a hollow or solid tube or other cylindrical structure, such as a mandrel. Depending on the configuration, UV light generated by the UV-LEDs may be directed into the interior space or opposite to the interior space. Other configurations useful with some embodiments, include pouch-like configurations where two portions or sections of a flexible UV light generation sheet or system are placed adjacent to one another such that material or fluid may be inserted between the two portions or sections. In some embodiments, one or more flexible UV light generation sheets or systems may be arranged as a liner of a vessel or container and used to generate UV light within the interior space of the vessel or container. It will be appreciated that the flexible UV light generation sheet or system does not need to completely enclose an interior space. For example, in some embodiments, the vanes in a static mixer or one outer wall may be covered with a flexible UV light generation sheet or system. In another embodiment, the enclosed space may not be defined. For example, a flexible UV light generation sheet or system could be mounted one end with the opposite end free to move in a fluid stream, similar to a flag. The flag configuration may use or correspond to a flexible UV light generation sheet that has UV-LEDs mounted on one side or both sides. FIG.1provides a schematic cross-sectional side-view illustration of a flexible UV light generation sheet100in accordance with some embodiments. A UV-LED150is electrically connected to individual segments of conductor110to allow current to be applied for UV light generation. Below conductor110is a support layer130and above conductor110is a UV diffuse reflective layer120. Support layer130may optionally be one or more UV diffuse reflective layers. UV diffuse reflective layer120is positioned so light from UV-LED150can be emitted out of flexible UV light generation sheet100. Support layer130is positioned below UV-LED150and may also be UV reflective such that stray light is reflected back. Openings140may be included in UV diffuse reflective adjacent layer120to allow light from the UV-LED150to be emitted there through. The openings140may have a variety of shapes including circles, ovals, triangles, squares, rectangles, diamonds, and other similar shapes. The size of the opening may also vary but is sufficient to allow light from a UV-LED150to pass through and may have an opening size from 0.5 to 20 mm, e.g. from 2 to 10 mm, or from 3 to 6 mm. In one embodiment, the openings140may be formed by gaps created between adjacent longitudinal sides of one or more UV diffuse reflective layers that are wrapped to form the sheet. Optionally, conductor110may be segmented, such as at openings140, to allow different contacts of electrical components to be attached to the individual segments. As illustrated, a lens or focusing element is not positioned above UV-LED150. When no lens or focusing element is used, the configuration advantageously permits UV light intensity to spread over a wider area and achieve a more uniform distribution of UV light intensity over a wider area, minimizing dim regions that may occur when lensing or focusing elements are included. FIG.2Aprovides a schematic cross-sectional end-view illustration andFIG.2Bprovides a cross-sectional top-view illustration of a flexible UV light generation sheet200in accordance with some embodiments.FIG.2Ashows a flexible UV light generation sheet200in which conductors210are optionally included in a ribbon or a flexible flat cable and may be joined or attached to one another by way of electrically insulating material surrounding at least a portion of one or more conductors. UV diffuse reflective layer220may be positioned above conductors210, such that UV diffuse reflective layer220covers at least a portion of conductors210and/or any insulating material surrounding the conductors. It will be appreciated that UV diffuse reflective layer220may be in individual sections positioned above each conductor210or may a continuous layer positioned above any number of conductors210. Support layer230may be positioned below the conductors210, and below UV-LEDs250, such that support layer230covers at least a portion of the conductors210and UV-LEDs250and/or any insulating material surrounding the conductors and UV-LEDs. Optionally, support layer230is a UV diffuse reflective layer. It will be appreciated that support layer230may be in individual sections positioned below each conductor210or may a continuous layer positioned below any number of conductors210and UV-LEDs250. It will be appreciated that a support layer may be an optional feature of the flexible UV light generation sheets described herein, as the structure of the UV-LEDs, conductors, a UV transparent scattering or UV diffuse reflective layer, and any additional layers, such as overlayers, may provide sufficient structure to the flexible UV light generation sheet such that a separate support layer is not needed. Optionally, UV diffuse reflective layer220or support layer230may be provided as a jacketing material of conductors210. FIG.2Bmay correspond to a perpendicular view from those shown inFIG.1andFIG.2A. In flexible UV light generation sheet200, conductors210are included and shown extending from edges of flexible UV light generation sheet200. Conductors210are at least partially covered by a UV diffuse reflective layer220. UV-LEDs250are illustrated as positioned above several conductors210, with an additional conductor210used as a common or current return line. Similar toFIG.1, UV-LEDs250may be positioned at openings in UV diffuse reflective layer220and bridging segments of conductors210. It will be appreciated that, as illustrated inFIG.2B, UV-LEDs250may be individually electrically addressable. Allowing the UV-LEDs to be individually electrically addressable may provide good control to adjust the UV light within the fluid pathway to achieve a uniform UV emission. It will be appreciated thatFIGS.2A and2Bprovide an array of multiple UV-LEDs250with a plurality of conductors210, such as a non-regular array. As an alternative to driving LEDs in series with a common current, LEDs may be driven in parallel with a common voltage.FIG.3Aprovides a cross-sectional schematic illustration of a flexible UV light generation sheet300including a ribbon cable. The ribbon cable includes a plurality of round conductors310, each depicted as a stranded core cable. It will be appreciated that solid core conductors are also useful. A UV-LED350is depicted as positioned adjacent to and in electrical communication with two different conductors, in contrast to the configuration illustrated inFIGS.1,2A, and2B, where a UV-LED is positioned to bridge segments of a single conductor.FIG.3Bprovides a cross-sectional schematic illustration of a flexible UV light generation sheet300where one conductor, for example the center conductor, may be used as a heat sink, for example, to allow heat generated by one or more UV-LEDs to flow away from the UV-LEDs. FIG.4provides a cross-sectional schematic illustration of a flexible UV light generation sheet400including a ribbon cable with a plurality of conductors410, UV-LEDs450and adjacent layer420. An additional overlayer460is depicted as positioned above UV diffuse reflective layer420and above UV-LEDs450. Overlayer460is a UV transparent layer, allowing UV light generated by UV-LEDs450to transmit out from flexible UV light generation sheet400. In addition, incident UV light may transmit through overlayer460and be reflected by adjacent layer420back through overlayer460and into the medium above the flexible UV light generating sheet400. Optionally, additional overlayer460may be a UV transmissive scattering layer, allowing UV light generated by UV-LEDs450to transmit out from flexible UV light generation sheet400and be scattered to more uniformly distribute the light. A UV transmissive scattering layer, also referred to as a UV haze layer or UV transmissive scattering layer, diffuses light over a wide range of angles. ASTM standard D1003, hereby incorporated by reference, describes details of haze and transparency measurements, and defines haze as the ratio of diffuse transmittance to total luminous transmittance, which may correspond to the percentage of light passing through a layer that deviates from the incident beam greater than 2.5 degrees on average. Optionally, overlayer460may correspond to an encapsulating layer, which may provide water resistance or other environmental protection to underlying components. Advantageous properties of an overlayer may include electrically insulation, low water and oxygen transmission rates, high mechanical toughness, and high thermal conductivity. Optionally a UV diffuse reflective underlayer430is positioned below the UV-LEDs to redirect any backward scattered light in the forward direction above the UV-LEDs. In this embodiment, little if any light is lost and less power is required to disinfect the fluid stream. FIG.5provides an alternative embodiment of a flexible UV light generation sheet500including a ribbon cable with a plurality of conductors510and UV-LEDs550.FIG.5is similar toFIG.4except that the overlayer560is below adjacent reflector layer520.FIG.6provides a further alternative embodiment of a flexible UV light generation sheet similar toFIG.4andFIG.5except that the adjacent reflective layer520has been removed. In this embodiment, incident light would transmit through the overlayer660and be reflected by underlayer630. In some embodiments, a flexible UV light generation sheet makes use of a flexible circuit rather than a ribbon or flat flexible cable for providing electrical connections to one or more UV-LEDs. For example,FIG.7Aprovides a schematic cross-sectional illustration of a flexible circuit-based UV light generation sheet700. Here, flexible UV light generation sheet700includes flexible circuit715, which corresponds, for example to a flexible conductive trace712supported on a flexible substrate film714. As an example, flexible conductive trace712may correspond to a thin copper layer and flexible film714may correspond to a polymer film, such as polyimide. UV-LEDs750may be positioned in electrical communication with portions of flexible conductive trace712and supported by flexible film714. An overlayer760, such as a UV transparent layer or a UV transmissive scattering layer, may be included, depending on the particular configuration. The overlayer760may protect the UV-LEDs from the environment including, for example, immersion in water. Advantageous properties may include electrically insulation, low water and oxygen transmission rates, high mechanical toughness, and high thermal conductivity. A reflective underlayer730, and a reflective layer720, may be included, depending on the particular configuration. Another embodiment depicting a flexible UV light generation sheet700using a flexible circuit rather than a ribbon or flat flexible cable is shown inFIG.7B. Here, flexible UV light generation sheet700includes flexible circuit715, which corresponds, for example to a flexible conductive trace712supported on a flexible film714. As an example, flexible conductive trace712may correspond to a thin copper layer and flexible film714may correspond to a polymer film, such as polyimide. UV-LEDs750may be positioned in electrical communication with portions of flexible conductive trace712and supported by flexible film714. Openings may be included in in flexible film714, to allow UV light generated by UV-LEDs750to be transmitted away from flexible UV light generation sheet700. Alternatively, flexible film714may be transparent to the emitted light from UV-LEDs so openings are not required. A reflective underlayer730, and a reflective layer720, may be included, depending on the particular configuration. UV Light Generation Assembly Configurations A variety of UV light generation systems using the flexible UV light generation sheets described herein are contemplated. As an example,FIG.8Adepicts a UV light generation system800A including a flexible UV light generation sheet805wrapped in a helical configuration around a tubular structure815. In one embodiment, the UV light generation sheet805has opposing longitudinal sides that are adjacent or partially overlap. The tubular shape may correspond to the fluid path825. In this way, flexible UV light generation sheet may be arranged to enclose a fluid path825, corresponding to an interior region of tubular structure815, for example. The fluid path825may be useful for flowing liquids or gases through a region illuminated by UV light for disinfecting or purifying the liquids or gases. Optionally, particles or objects may be suspended in the fluid and exposed to the UV light for disinfecting or purifying the particles or objects. Optionally, flexible UV light generation sheet805and tubular structure815are flexible, allowing treatment system800A to adopt a bent or curved configuration. Optionally, tubular structure815is a mandrel used to form a tubular shape when the flexible UV light generation sheet is wrapped. In this embodiment, the mandrel is removed to form a fluid pathway. In embodiments, tubular structure815is a UV transparent tube, permitting UV light generated by UV-LEDs of flexible UV light generation sheet805to transmit into an interior of tubular structure815. In this embodiment, the UV transparent tube may be considered part of the UV light generation system. In one embodiment, UV-LEDs of flexible UV light generation sheet805are arranged to position at least a first UV-LED in a configuration that is not directly opposed, across the fluid path825, to any other UV-LED. Incidentally, UV-LEDs of flexible UV light generation sheet805are arranged to position at least a first UV-LED in a configuration that is directly opposed, across the fluid path825, to a UV diffuse reflective layer of flexible UV light generation sheet805. This allows the UV light to reflect and become more uniformly distributed in the fluid pathway. InFIG.8A, conductors810are also illustrated as extending from flexible UV light generation sheet805and may be connected to circuits or power sources. It will be appreciated that for direction of UV light into fluid path825, UV-LEDs will be positioned facing tubular structure815. UV-LEDs are on the side of the sheet facing the interior and are not visible from the exterior as shown inFIG.8A. FIG.8Bis a perspective view to show the interior region of the UV light generation sheet805. For purposes of illustration the tubular structure815is not shown inFIG.8B. The UV light generation sheet805has openings840that align with UV-LEDs850on the conductors (not shown inFIG.8B). The UV light generation sheet805may be constructed of a diffuse UV reflective layer820. It will be appreciated that additional overlayers or underlayers may optionally be included in UV light generation sheet805, e.g., such as a reinforcing underlayer, a UV transparent overlayer, and/or a UV transmissive scattering overlayer. In one embodiment, the UV transparent overlayer has a UV transmission of at least 80% at 250 nm. As shown inFIGS.8A and8B, the sheet805is wrapped closely together and may partially overlap to prevent a gap between the adjacent longitudinal sides. Optionally, a surface at the fluid pathway may be coated with or treated with TiO2or another UV active photocatalytic material. Other photocatalytic materials include metal oxides such as SiO2, ZnO, Bi2WO6, Bi2OTi2O, Fe2O3, Nb2O5, BiTiO3, SrTiO3, or ZnWO4, and other metal catalysts such as CuS, ZnS, WO3, or Ag2CO3. Upon exposing TiO2or another light active photocatalytic material UV light generated by LEDs, electrons and holes may be generated to allow oxidation and/or reduction of material coming into contact with the TiO2or active photocatalytic material. For example, contacting a light activated photocatalyst with water or oxygen may result in generation of reactive oxygen species, such as hydroxyl radicals (OH) and superoxide (O2−). These reactive oxygen species may be useful for degrading or destroying pathogens, toxins, or impurities. An alternative arrangement of a UV light generation treatment system800B including flexible UV light generation sheet805is depicted inFIG.8C, where instead of being helically wrapped around the fluid path825, the flexible UV light generation sheet805is longitudinally wrapped around the fluid path825. It will be appreciated that in the illustration depicted inFIG.8Cthe longitudinal wrap around fluid path825is shown as incomplete for purposes of illustration. In practice, ends of flexible UV light generation sheet805may optionally be attached and/or joined to form a complete enclosed fluid path825. This prevents a gap between the sides of the sheet805inFIG.8C. InFIG.8C, conductors810are also illustrated as extending from flexible UV light generation sheet805. There are various openings840in the UV light generation sheet805that are positioned to align with the UV-LEDs850connected to the conductors810. It will be appreciated that additional overlayers or underlayers may optionally be included in UV light generation sheet805, e.g., such as a reinforcing underlayer, a UV transparent overlayer, and/or a UV transmissive scattering overlayer. In addition, the UV light generation sheet805shown inFIG.8Cmay be wrapped around a transparent tube. FIGS.9A and9Bdepict schematic cross-sectionals illustration of UV light generation systems900A and900B, such as using the flexible UV light generation sheet depicted inFIG.5, including UV diffuse reflective layer920, underlayer930, UV-LEDs950, flex circuit915and overlayer960, which may be positioned in various adjacencies, depending on the configuration. It will be appreciated thatFIGS.9A and9Bmay represent a cross-sectional views of treatment system800ofFIGS.8A and8B, for example. Light generated by UV-LEDs950is directed into a fluid path defined as an interior space surrounded by the flexible UV light generation sheet. When UV light reaches the UV diffuse reflective layer920, the UV light is reflected back into the fluid path, allowing for high levels of UV light intensity to be generated in the fluid path. In embodiments, reflective layer920is a highly diffuse reflective material, such as a material that reflects 98% or more of incident UV light, such as UV light having wavelengths between 100 nm and 400 nm, or any subrange thereof. As illustrated, each UV-LED950is positioned in a configuration that is not directly opposed to any other UV-LED950. Stated another way, each UV-LED950is positioned in a configuration that is directly opposed to reflective layer920to allow UV light to reflect off reflective layer920and become more uniformly distributed. It will be appreciated that, in the configuration illustrated inFIGS.9A-9B, the flexible UV light generation sheet may not include openings in a UV diffuse reflective layer. Overlayer960is UV transparent and optionally UV scattering (e.g., hazy) or comprises photocatalysts on the surface. Overlayer960may optionally provide for protection of underlying or adjacent layers, and may, for example, provide protection against penetration by water or another fluid. FIG.10depicts a schematic cross-sectional illustration of a light generation treatment system1000. Such a configuration may be constructed similar to the system800illustrated inFIGS.8A and8B, where a flexible UV light generation sheet is helically wrapped around a tubular structure or where a flexible UV light generation sheet is longitudinally wrapped around a tubular structure. However, for light generation treatment system1000, the structure of the flexible UV light generation sheet is reversed from the other embodiments. This enables the generation of a uniform UV emission field at a distance from the outer surface. For example, treatment system1000includes overlayer1060, UV-LEDs1050, reflective underlayer1030, and interior region1025. InFIG.10, UV-LEDs1050are depicted as arranged to direct light away from a central shaft1025defined by the flexible UV light generation sheet. Advantageously, overlayer1060may be a UV transmissive scattering layer allowing light generated by UV-LEDs1050to be scattered diffusely across a range of directions. Overlayer1060may also serve as an encapsulating layer, providing water repellency and environmental protection to underlying UV-LEDs, conductors, and other components. Interior region1025may correspond to a tubular structure, such as a hollow tube or solid cylindrical structure, for example. An adhesive may be used to mount the flexible UV light generation sheet to the interior region1025. As an example, interior region may include a central shaft. Alternatively, the interior region may be open. In one example of a construction method an open interior region1025may be formed by wrapping a flexible UV light generation sheet around a mandrel. Herein the light generation sheet may be formed by first wrapping the reflective underlayer1030around the mandrel without an adhesive. A second underlayer1030may then be wrapped around the first underlayer1030which includes a thin adhesive layer so as to secure the form factor of the two underlayers1030in the shape of the mandrel but allowing the mandrel to be removed thereby forming an open interior region1025. Such a configuration is useful, for example, in embodiments where the flexible UV light generation treatment system1000is inserted into a container or fluid pathway and used to expose fluid, particles, or objects in the container or fluid pathway to UV light. Treatment system1000may correspond to a rod or stick that may be moved within the container or fluid pathway to target impurities in the stream. The movement may also induce turbulence and/or promote mixing. FIG.11corresponds to two flexible UV light generation sheets opposing each other and depicts a schematic cross-sectional illustration of a flexible UV light generation sheet useful for generating a uniform UV emission field at a distance from the flexible UV light generation sheet. As illustrated, the flexible UV light generation sheet1100includes an underlayer1120, UV-LEDs1150supported by the substrate and an overlayer1160positioned over underlayer1120and UV-LEDs1150. Underlayer1120may correspond, for example, to a UV diffuse reflective layer. It will be appreciated that additional layers may be included in flexible UV light generation sheet1100. For example multiple flexible UV light generation sheets may be used together to form a system. Flexible UV light generation sheet1100may be useful, for example, for lining walls of a container or vessel to allow fluids, particles, or objects within the container or vessel to be exposed to UV light for disinfection, purification, or other treatment purposes. Optionally, devices within a container or vessel, such as used for mixing a fluid or objects or particles suspended in a fluid, may have one or more surfaces lined with flexible UV light generation sheet1100to allow exposure of the fluid, objects, or particles to UV light for disinfection or purification purposes. As an example, one or more walls of a vessel, conduit, or pipe may be lined with flexible UV light generation sheet1100and/or a surface of a mixing vane may be lined with flexible UV light generation sheet1100. As another example, one or more flexible UV light generation sheets may be arranged in a pouch or pocket configuration, where a surface of a first flexible UV light generation sheet faces a surface of a second flexible UV light generation sheet. Such a configuration may correspond to two separate flexible UV light generation sheets or may correspond to a single flexible UV light generation sheet folded back on itself to form a pouch or pocket like configuration. As an example, for a rectangular pouch configuration, three sides of facing rectangular flexible UV light generation sheets may be joined or attached to make a rectangular pouch. Other shapes are possible. As another example, multiple flexible UV light generation sheets may be combined to form a UV light generation system1200, as depictedFIG.12. InFIG.12, UV light generation system1200includes a first flexible UV light generation sheet1205and a second flexible UV light generation sheet1210. First flexible UV light generation1205sheet may correspond to flexible UV light generation sheet900as depicted inFIG.9. Second flexible UV light generation sheet1210may correspond to flexible UV light generation sheet1000as depicted inFIG.10. As illustrated, first flexible UV light generation sheet1205and second flexible UV light generation sheet1210are arranged so that second flexible UV light generation sheet1210is positioned inside first flexible UV light generation sheet1210. In addition, the UV-LEDs of each flexible UV light generation sheet are depicted as not directly opposed one another UV-LEDs. For example, UV light from UV-LEDS of first flexible UV light generation sheet1205is directed towards a scattering layer or a reflective layer of second flexible UV light generation sheet1210. Similarly, UV light from UV-LEDS of second flexible UV light generation sheet1210is directed towards a reflective layer of first flexible UV light generation sheet1205. In this way, an annular region1215may be formed between first flexible UV light generation sheet1205and second flexible UV light generation sheet1210, such as to allow fluid to flow between them and be treated by UV light. As another example, a flexible UV light generation sheet may optionally be a two-sided sheet. Flexible two-sided flexible UV light generation sheet1300is depicted inFIGS.13A and13B.FIG.13Ashows a cross-sectional schematic illustration of two-sided flexible UV light generation sheet1300including reflective layer1320and scattering overlayer1360covering reflective layer1320and UV-LEDs1350. As illustrated, UV-LEDs1350are mounted on both sides of two-sided flexible UV light generation sheet1300with the reflective layer1320and scattering overlayer positioned on each side of two-sided flexible UV light generation sheet1300. In this embodiment, UV-LEDs1350positioned on a first side of the two-sided flexible sheet1300do not back to any UV-LEDs positioned on a second side of the two-sided flexible sheet1300. Flexible UV light generation sheet1300may be correspond to a flag type configuration, where flexible UV light generation sheet1300is fixed on one end with the other end free to move, such as in a fluid.FIG.13Balso shows a supporting structure1370and that flexible UV light generation sheet1300is supported only, for example, on one end by supporting structure1370. In some embodiments, however, a flexible UV light generation sheet may be supported on two or more or all ends by various supporting structures. Supporting structure1370may include power and communications connections, such as power/voltage supplies, control circuitry, or communications feeds, for example between UV-LEDs and/or UV photodetectors and external circuitry by way of one or more conductors. It will be appreciated thatFIG.13Bdepicts a regular array of multiple UV-LEDs1350and that any conductors included with the array are not illustrated. UV Diffuse Reflective Layer A variety of materials are useful as a UV diffuse reflective layer for various flexible UV light generation sheets and treatment systems described herein. For example, a UV diffuse reflective layer may comprise one or more polymers or a polymer layer, such as a polymer selected from the group consisting of a fluoropolymer, a polyimide, a polyolefin, a polyester, a polyurethane, a polyvinyl, polymethyl methacrylate, or variations or derivatives thereof. Example polymers include, but are not limited to, polyethylene terephthalate (PET), polyethylene naphthalate (PEN), poly ether ketone (PEEK), cyclic olefin copolymer (COC), polycarbonate (PC), polyphenylene sulfide (PPS), polyetherimide (PEI), polyamideimide (PAI), polychloroprene, polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), vinylidene chloride-vinyl chloride copolymers, vinyl chloride copolymers, vinylidene fluoride polymers, polyvinylidene fluoride (PVDF), fluorinated ethylene propylene (FEP), perfluoroalkoxy alkane (PFA), or polytetrafluoroethylene (PTFE). In one embodiment, the UV diffuse reflective layer may comprise an expanded polytetrafluoroethylene (ePTFE). In some embodiments, a UV reflective layer comprises a thin metal film. In some embodiments, a UV reflective layer comprises a dielectric stack. In some embodiments, a UV diffuse reflective layer exhibits a diffuse reflectivity of 50% or greater, 60% or greater, 70% or greater, 80% or greater, 90% or greater, 95% or greater, 97% or greater, 98% or greater, or 99% or greater for UV light, such as light having wavelengths between 200 nm and 400 nm. Example UV diffuse reflective layers include those exhibiting a diffuse reflectivity (diffuse reflective scattering) percentage for UV light, such as light having wavelengths between 200 nm and 400 nm, 50% or more (i.e., 50-100%), 60% or more, 70% or more, 80% or more, or 90% or more. In some embodiments, a UV diffuse reflective layer functions as an encapsulating, water resistance, or environmental protection layer. A variety of exemplary materials that may be used as either a reflective layer, such as a reflective layer or a reflective underlayer. In publication “Reflectivity Spectra for Commonly Used Reflectors” by Martin Janacek, incorporated herein by reference, the author lists several materials which have greater than 97% reflectivity. In one embodiment the UV diffuse reflective layer comprises ePTFE. The ePTFE material comprises a microstructure of polymeric nodes and fibrils that demonstrates exceptional diffuse reflectivity in the UV spectrum. An exemplary ePTFE for the UV diffuse reflective layer, Gore DRP®, is produced by W.L. Gore & Associates of Newark, DelawareFIG.18shows a plot of total reflectivity from 250 nm to 800 nm of various thicknesses of skived PTFE along with Gore DRP®. This material is described in U.S. Pat. No. 5,596,450 or 6,015,610, the entire contents and disclosures of which is hereby incorporated by reference. While packed granular based PTFE material provides good diffuse reflectance properties, the node and fibril structure of ePTFE provides a much higher diffuse reflectance property and has higher mechanical strength. The UV diffuse reflective layer may be thin and lightweight. Making the UV diffuse reflective layer lighter and less expensive to employ expands the applications for the flexible UV light generation sheet. In one embodiment the UV diffuse reflective layer, including any coating or filler, may have a thickness from 0.01 mm to 2 mm, e.g., from 0.05 to 1.5 mm or from 0.1 to 1.2 mm. In one embodiment, the UV diffuse reflective layer has a high index of light reflection at a thickness of less than 0.3 mm. UV Transparent and Scattering Layers A variety of materials are useful as a UV transparent layers or UV transmissive scattering layer for various flexible UV light generation sheets and systems described herein. As noted above, UV transparent layers and scattering layers are useful, for example, as overlayers. In embodiments, a UV transparent layer or UV transmissive scattering layer may comprise one or more polymers or a polymer layer, such as a polymer selected from the group consisting of a fluoropolymer, a polyimide, a polyolefin, a polyester, a polyurethane, a polyvinyl, polymethyl methacrylate, or variations or derivatives thereof. Example polymers include, but are not limited to, polyethylene terephthalate (PET), polyethylene naphthalate (PEN), poly ether ether ketone (PEEK), cyclic olefin copolymer (COC), polycarbonate (PC), polyphenylene sulfide (PPS), polyetherimide (PEI), polyamideimide (PAI), polychloroprene, polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), vinylidene chloride-vinyl chloride copolymers, vinyl chloride copolymers, vinylidene fluoride polymers, polyvinylidene fluoride (PVDF), fluorinated ethylene propylene (FEP), perfluoroalkoxy alkane (PFA) or polytetrafluoroethylene (PTFE). In some embodiments, a polymer useful as a UV transparent layer corresponds to a PTFE, such as an ePTFE, which is a highly inert hydrophobic material. Accordingly, the PTFE is chemically resistant and liquid-proof which is useful when the UV transparent layer or UV transmissive scattering layer is in contact with the fluid stream. In some embodiments, a UV transparent layer or UV transmissive scattering layer functions as an encapsulating, water resistance, or environmental protection layer. Preferably, a UV transparent layer has a very low optical absorption (e.g., less than 10%, less than 5%, or less than 1%) so that a very high percentage of the light is transmitted through the UV transparent layer. In some embodiments, a UV transparent layer exhibits a transparency for UV light of 50% or greater, 75% or greater, or 90% or greater, such as light having wavelengths between 100 nm and 400 nm. In one embodiment, the UV transparent overlayer has a UV transmission of at least 80% at 250 nm. In addition to low optical absorption, an optional but desirable property for an overlayer is haze or scattering character. Haze is forward scattering of light greater than 2.5 degrees from the optical transmission axis. This property will defocus the light thereby increasing the uniformity of the photon density in the fluid stream. In embodiments, UV transmissive scattering layers comprise UV transparent materials. Inclusion of surface features or one or more fibrils, nodes, pores, and the like in a transparent material provides more opportunities for scattering of light at surfaces or transitions between materials of different indices of refraction (e.g., air and polymer), and may provide a scattering character or haze to a material. Haze and scattering are further described in ASTM standard D1003, hereby incorporated by reference. Exemplary overlayer materials are described in U.S. Pat. Nos. 5,374,473 and 7,521,010, the entire contents and disclosures of which is hereby incorporated by reference. The patents describe a compressed ePTFE article which has improved properties over conventional cast or skived PTFE.FIG.19shows a plot of transmission vs. wavelength for three samples (S1, S2, S3) of a compressed ePTFE article as described in the patents, along with FEP, PFA and ETFE (Tefzel™). The compressed ePTFE articles have a thickness of 0.5 mil, while the FEP, PFA and ETFE have a thickness of 1 mil. In general, thinner thicknesses will have higher transmission percentages due to lower absorption losses. However, T=1−R−A (Transmission calculates as 100% minus reflection losses R minus absorption losses A) and in these films the reflection coefficient is much larger than the absorption coefficient (as calculated from this equation using optical transmission and reflection data on the same films). So even higher transmission numbers can be attained by not using air in the transmission path from the LED to the fluid medium.FIG.20shows a plot of haze vs. wavelength for the same six articles. It will be appreciated that in these samples the higher percent transmission material has the lower haze. Depending on the application, one may choose to use a material with more scattering to promote light diffusion and reduce dark spots in the fluid stream even though the total optical power has been reduced. The overlayer material may have an optical transmission coefficient (T) of greater than 70% and a haze coefficient (H) of greater than 20% or preferably T>80% and H>50%. An overlayer may be adhered or laminated to a UV diffuse reflective layer, a flex circuit, a substrate or supporting layer, the UV-LEDs, or any other material or layer in a flexible UV light generation sheet. In one embodiment, an overlayer covers openings in a UV diffuse reflective layer that expose corresponding UV-LEDs. Example UV transparent layers and UV transmissive scattering layers may have thicknesses of 7 microns to 100 microns. UV transparent tube. In one embodiment, the assembly comprises a UV transparent tube and the flexible UV light generation sheet is wrapped around the tube. In one embodiment the flexible UV light generation sheet is wrapped along the outer surface of the tube. In other embodiments, the flexible UV light generation sheet is wrapped and is placed along the inner surface. The flexible UV light generation sheet is flexible and lack a structural rigidity to maintain the fluid pathway. A tube provides the necessary rigidity for the fluid pathway. This may be advantageous for in-line use for disinfection, purification, sterilization, or other treatment systems. The tube should be sufficient to withstand the temperature of the stream being treated and chemically resistant as needed. In one embodiment, the UV transparent tube comprises a polymer, such as a fluoropolymer, a polyimide, a polyolefin, a polyester, a polyurethane, a polyvinyl, polymethyl methacrylate, polyethylene terephthalate (PET), polyethylene naphthalate (PEN), poly ether ether ketone (PEEK), cyclic olefin copolymer (COC), polycarbonate (PC), polyphenylene sulfide (PPS), polyetherimide (PEI), polyamideimide (PAI), polychloroprene, polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), vinylidene chloride-vinyl chloride copolymers, vinyl chloride copolymers, vinylidene fluoride polymers, polyvinylidene fluoride (PVDF), fluorinated ethylene propylene (FEP), perfluoroalkoxy alkane (PFA) or polytetrafluoroethylene (PTFE). The material may be selected to provide a rigidity to the flexible UV light generation sheet. However, in other embodiments, the UV transparent tube may also be flexible. Composite Structures It will be appreciated that the various layers and components described above may be joined, adhered, or otherwise configured in a variety of manners to form a composite structure. For example, any one or more of a support layer, a substrate, a conductor, a UV-LED, a UV diffuse reflective layer, a UV transparent layer, a UV transmissive scattering layer, an encapsulating layer, and other components may be attached or positioned adjacent to one another using any suitable means. In some embodiments, layers may be laminated to one another to allow for layers to be joined or attached in a composite structure. Example lamination processes include thermal-based lamination processes and adhesive-based lamination processes. In some embodiments, layers or components may be attached or adjoined using one or more adhesives. Optionally, a continuous adhesive layer is positioned between two objects to allow the two objects to be adjoined, such as where an adhesive layer is positioned completely between the two objects at all points where the two objects are adjacent to one another. Optionally, a discontinuous adhesive layer, i.e. adhesive dots or adhesive lines, is positioned between two objects to allow the two objects to be adjoined, such as where a one or more adhesive layers are positioned between the two objects at only a subset of points where the two objects are adjacent to one another. Example adhesives include, but are not limited to, acrylics, polyamides, polyacrylamides, polyesters, polyolefins, polyurethanes, polysilicones or the like. Useful adhesives include those that do not impact the flexibility of the joined materials. In embodiments, advantageous adhesives include UV stable adhesives. As used herein, the term “UV stable” indicates that a material, such as an adhesive, is resistant to UV light, allowing long term use without degrading. In some embodiments, a UV stable material may not significantly degrade when exposed to long durations of UV light, such as years or more. Suitable UV stable adhesives include silicones, acrylates or adhesives with UV absorbers or inhibitors added thereto. In addition, UV stable material may advantageously be non-absorbing (i.e., transparent) in the UV region or may exhibit only small amounts of absorption. Example UV stable materials include PTFE, ePTFE, fluorinated ethylene propylene (FEP) or perfluoroalkoxy alkane (PFA). Example UV stable adhesives include thermoplastic fluoropolymers. Preferred adhesives are FEP, a copolymer of tetrafluoroethylene and hexafluoropropylene; PFA, a copolymer of tetrafluoroethylene monomers containing perfluoroalkoxy side chains, and EFEP, a copolymer of ethylene, tetrafluoroethylene, and hexafluoropropylene. Alternatively, copolymer resins of tetrafluoroethylene and perfluoroethylene-alkyl ether monomers (e.g., PAVE, PMVE, and/or CNVE) can be made with compositions and molecular weights to act as adhesives that exhibit excellent thermal and UV resistance (pressure sensitive, thermoplastic, or crosslinked). Such copolymer resins are disclosed, for example, in U.S. Pat. Nos. 7,488,781; 8,063,150; 8,623,963; 7,462,675; and 7,049,380. UV-LED Configurations UV-LEDs may be incorporated in the flexible UV light generation sheets and treatment systems described herein in a variety of manners. To distribute the UV light within the fluid pathway the UV-LEDs are arranged to form a regular spacing about the flexible UV light generation sheet. In other embodiment, non-regular spacing of the UV-LEDs may also be used. Multiple UV-LEDs are arranged in a parallel or series configuration. For example,FIG.14provides an example circuit diagram1400showing multiple UV-LEDs1450. As illustrated, an LED power supply1405is shown driving three sets of three series connected UV-LEDs1450, such that each UV-LED1450in a series is driven by the same amount of current.FIG.15provides another example circuit diagram1500showing multiple UV-LEDs1550. As illustrated, LED power supply1505drives the UV-LEDs1550in parallel, such that each UV-LED1550is driven by the same voltage, for example. It will be appreciated that the configuration illustrated inFIG.14depicts not only UV-LEDs connected in series, but also series connected UV-LEDs that are also connected in a parallel configuration. In some embodiments, UV-LEDs incorporated into flexible UV light generation sheets and treatment systems correspond to surface mounting devices, which may be advantageous for some implementations. For example, in some embodiment where flat flexible cable-based conductors are used, surface mounting of UV-LEDs may have dimensions that match the pitch between conductors, allowing for seamless integration and manufacture of a flexible UV light generation sheet. In some embodiments, UV-LEDs useful with the flexible UV light generation sheets and treatment systems described herein include UVA LEDs, exhibiting emission between wavelengths of 315 nm and 400 nm. In some embodiments, UV-LEDs useful with the flexible UV light generation sheets and treatment systems described herein include UVB LEDs, exhibiting emission between wavelengths of 280 nm and 315 nm. In some embodiments, UV-LEDs useful with the flexible UV light generation sheets and treatment systems described herein include UVC LEDs, exhibiting emission between wavelengths of 100 nm and 280 nm. Exemplary UV-LEDs emit UV light with wavelengths between 260 nm and 265 nm, between 270 nm and 280 nm, 305 and 315 nm. It will be appreciated, however, that the wavelength of UV light and the associated UV-LEDs may be selected that best matches or at least partially overlaps a destruction effectiveness curve of a target toxin or target pathogen, for example. As an example, a germicidal effectiveness curve forEscherichia colimay exhibit a peak at about 265 nm, and use of UV-LEDs emitting at this wavelength may provide an advantage for destroying these pathogens or toxins in the fluid pathway. A variety of UV-LED structure types are suitable for use with the flexible UV light generation sheets and treatment systems described herein. In some embodiments, a UV-LED, one or more UV-LEDs or each UV-LED corresponds to a surface-mount device. Use of surface-mount devices are advantageous when making a flexible UV light generation sheet or a treatment system using a flat flexible cable, as certain flat flexible cables have standard pitches between conductors or widths that may match commercially available surface-mount type UV-LEDs. Other advantages provided by the use of surface-mount structures include the ability to use pick-and-place machinery to assemble portions of a flexible UV light generation sheet or treatment system. Other types of UV-LED structures are useful for some embodiments described herein, including through-hole LEDs, miniature LEDs, high-power LEDs, round, square, etc. In addition, any LED structure capable of generating UV light of a desired wavelength or wavelength region are useful with the embodiments described herein. For example, in some embodiments, a UV-LED has an AlGaN-structure, AlN structure, a GaN structure, or combinations of these. It is to be understood that other UV light emitting semiconductors, such as laser diodes, for example VCSELs (vertical cavity surface emitting lasers), are considered UV-LEDs for the purposes of this patent application Feedback and Intensity Control It will be appreciated that exposure of toxins or pathogens to a particular dose of UV light may result in destruction of the toxins or pathogens, while lower doses may not completely destroy the toxins or pathogens. Similarly, if the toxin or pathogen is present in higher concentrations, the particular dose may not sufficiently destroy the toxins or pathogens. Advantageously, flexible UV light generation sheets and treatment systems described herein optionally include feedback mechanisms that permit control over the dose or output intensity of UV light generated. As an example, in some embodiments, a flexible UV light generation sheet or treatment system may include one or more UV sensors. For example, in the configurations illustrated inFIGS.1-13B, one or more UV-LEDs may be substituted for a UV sensitive photodetector, such as a photodiode, that is positioned in electrical communication with a monitoring circuit that is used to provide feedback for increasing or decreasing a current and/or voltage used to drive one or more UV-LEDs in order to maintain a suitable UV light field. FIG.16provides an example circuit diagram1600in which multiple UV-LEDs1650are driven by LED power supply1605. A UV sensitive photodetector1670is depicted as connected to a power monitor circuit1680that may be used to monitor a UV light intensity or power as output by the UV-LEDs1650. By monitoring a UV light intensity or power, the power monitor circuit1680may provide information, used, such as by the power monitor circuit or another computer or control circuitry, to adjust the voltage or current generated by LED power supply1605. In this way, the intensity of UV light can be monitored and adjusted to accommodate a target UV light dose or intensity useful for destroying toxins or pathogens. Methods of Making Treatment Systems It will be appreciated that a variety of techniques may be employed for making the treatment systems and flexible UV light generation sheets described herein.FIGS.17A-17Fprovide schematic overviews of an example aspects of an embodiment of a method of making a flexible UV light generation sheet.FIGS.17A-17Fprovide schematic cross-sectional front views (1), side views (2), and top views (3) of a flexible UV light generation sheet during steps of a fabrication method. InFIG.17A, multiple conductors1702are illustrated, each corresponding to a flat conductor of a flat flexible cable1704. For purposes of illustration, only a section of a conductor cable is shown, but it will be appreciated that conductors of any number and size may be useful with various embodiments of the invention. Optionally, the jacketing surrounding the conductors may be UV transmissive or reflective polymers. InFIG.17B, the flat flexible cable1704is positioned adjacent to a substrate1706. InFIG.17C, a UV diffuse reflective layer1708is positioned adjacent to the flat flexible cable1704. InFIG.17D, openings1710are created at locations over two of the flat conductors1702, through both the UV diffuse reflective layer1708and the jacketing of the flat flexible cable1704. In addition, inFIG.17D, two of the flat conductors1702are segmented. Openings may be created using known processes in the industry, such as laser ablating or mechanical cutting. InFIG.17E, UV-LEDs1712are positioned in each opening and joined to the respective flat conductor segments1702. UV-LEDs may be attached using known processes in the industry, such as soldering or epoxying. InFIG.17F, an overlayer1714is provided adjacent to the UV diffuse reflective layer, such as a UV transmissive scattering layer or a UV transparent layer. The attachment of the substrate, reflective, or transparent layers may be facilitated with the use of adhesives. It will be appreciated that, for some embodiments, a separate substrate may not be required. For example a jacketing of a conductor may provide a suitable support structure for the conductors. Alternatively or additionally, an overlayer may not be required for some embodiments. It will further be appreciated that some embodiments may not require a UV diffuse reflective layer and so the UV diffuse reflective layer may be substituted for a UV transparent layer or a UV transmissive scattering layer. The so formed flexible UV light generation sheets may be arranged in a configuration for exposing a fluid to UV light generated by the flexible UV light generation sheet. For example, the flexible UV light generation sheet may be arranged to enclose a fluid pathway. As another example, the flexible UV light generation sheet may be arranged to form a tubular shape. Optionally, the flexible UV light generation sheet may be helically wrapped, longitudinally wrapped, or circumferentially wrapped around a tube or central shaft. Optionally, the flexible UV light generation sheet may be arranged along an interior surface of a vessel or along a surface of a structure positioned within a vessel. An overview of a method2100for the assembly of a UV light generating sheet, such as depicted inFIG.7A, is shown inFIG.21. At block2105, multiple UV-LEDs are attached to the flexible circuit via known practices in the industry, such as surface mounting technology, which includes chip on board and SMD attachment. The UV-LEDs may be in semiconductor die form and flip-chipped or wirebonded to the flex circuit conductive traces in a chip on board process. Alternatively, the UV-LEDs may be already packaged in a SMD (surface mount device) carrier package, where the UV-LED packages are attached to the flexible circuit with conductive adhesives or solders. In some embodiments, the flexible circuit is made by a method that includes removing portions of a jacketing of the ribbon cable or flat flexible cable to expose UV-LEDs or attachment locations for the UV-LEDs. It will be appreciated that the flexible circuit may be substituted by a ribbon cable or other flexible conductor assembly, as described above. The UV LEDs have a predetermined spacing that is used to create the openings in block2115. At block2110, an adhesive layer is applied to a surface of the UV diffuse reflective sheet. As described herein the adhesive layer for each layer or sheet may be a continuous layer of film or a pattern of dots or lines. Preferable adhesives are thermoplastic fluoropolymers such as FEP (melting point (mp) 260° C.), PFA (mp 305° C.), THV (mp 120-230° C.), and EFEP (mp 158-196° C.). In other embodiments, an adhesive layer may alternatively or additionally be applied to the top of the flexible circuit. Openings are cut into the UV diffuse reflective sheet at block2115. Next, the UV diffuse reflective sheet is positioned to align openings with the UV-LEDs, at block2120. By a similar method, an adhesive layer is applied to one surface of a transparent overlayer sheet, as depicted at block2125. In block2130, the transparent overlayer sheet is positioned adjacent to a surface of the UV diffuse reflective sheet opposite to the flexible circuit. At block2145, the assembly is cured in an oven or preferably in a heated press at a temperature from 125 to 325° C. In one optional embodiment, the underlayer sheet can be added by a similar method at blocks2135and2140. Although optional block2135indicates that the adhesive layer may be attached to the underlayer sheet, the adhesive layer may alternatively or additionally be applied to the bottom of the flexible circuit. The assembly of the double-sided UV light generating sheet, such as the flag configurations shown inFIGS.13A and13B, is similar to method2100as depicted inFIG.21. In this case the UV-LEDs are mounted on two sides of the flexible circuit and there is no optional reflective underlayer sheet. In this design, the UV-LEDs are not back-to-back so, for practical purposes, the UV diffuse reflective sheet next to the top UV-LEDs functions as the UV diffuse reflective sheet underlying the UV-LEDs on the opposite side. Alternatively, a single-sided UV light generating sheet may be folded back on to itself to create the flag configurations inFIGS.13A and13B. A method for making a light generating tube, such as depicted inFIGS.8A and8B, involves wrapping a light generating sheet around a mandrel, such as a mandrel of the desired tubular shape. The wrapping may be helical, longitudinal, or circumferential to form the desired tubular shape. The mandrel is a cylindrical rod made of a material, such as a metal, that can withstand the cure temperatures used in the method. The wrapped sheet is then further wrapped with an underlayer, such as a reinforcing layer, optionally with an adhesive, and cured to solidify the assembly. Further protective coatings may be applied over the tube assembly. Cure steps may optionally be done at different points in the method. The mandrel is then removed from the tube assembly to create the fluid path. A method2200is shown inFIG.22for wrapping a light generating sheet in tubular form. A flexible circuit comprising multiple UV-LEDs is assembled, in a manner described herein, at block2205. An adhesive is applied to one surface of a UV diffuse reflective layer at block2210, and openings are cut in the UV diffuse reflective layer at block2215. The flexible circuit is aligned with the UV diffuse reflective layer at block2220such that the openings align with the UV-LEDs to form a UV light generating sheet. The UV light generating sheet is then wrapped around a mandrel at block2225. An underlayer, which optionally may be a reinforcing layer with reflective properties, is wrapped around the UV light generating sheet with an adhesive, as shown at blocks2230and2235. Additional layers or coatings may optionally be added to the outside of the tubular assembly. At block2240, the assembly is then cured, for example in an oven, and the mandrel is removed, at block2245. In one embodiment, a lower melting point fluoropolymer adhesive EFEP is used so the curing temperature does not harm the flexible circuit. The product embodiment of this method may correspond to, for example, that shown inFIG.9A. Another method2300is shown inFIG.23, which may form a product corresponding to, for example, that shown inFIG.9B. At block2305, a transparent overlayer (e.g., layer960inFIG.9B), is wrapped around a mandrel to form a tube, optionally with an adhesive applied at block2310. The transparent overlayer can be made of materials described previously. The transparent overlayer can optionally be multilayer wrapped several times with an adhesive to secure the transparent overlayer to itself but not to the mandrel. In other embodiments, the transparent overlayer is a tube that is slid over the mandrel. The transparent overlayer is optionally cured at this stage. In an exemplary method, a preferred transparent overlay material is the aforementioned compressed ePTFE material, the adhesive is FEP, and the tubular structure is cured at 280° C. (a temperature greater than the adhesive melting temperature but less than the melting temperature of the transparent overlay material). An alternative method of fabricating the transparent overlayer (e.g., layer960inFIG.9B), is to slide a pre-manufactured FEP tube over the mandrel. In this example, the following cure temperature steps should be less than the melting temperature of the FEP so as to enable the mandrel to be removed from the tubular assembly. After the transparent tube is formed, the rest of the method is similar to that described inFIG.22. For example, a flexible circuit comprising multiple UV-LEDs is assembled at block2315. An adhesive is applied to one surface of a UV diffuse reflective layer at block2320, and openings are cut in the UV diffuse reflective layer at block2325. The flexible circuit is aligned with the reflective layer at block2330such that the openings in the layer align with the UV-LEDs to form the UV light generating sheet. The UV light generating sheet is then wrapped around the transparent overlayer at block2335. An additional underlayer, which optionally may be a reinforcing layer or UV diffuse reflective layer, is wrapped around the assembly using an adhesive layer, as shown at blocks2340and2345. Additional layers or coatings may optionally be added to the outside of the UV light generating sheet. At block2350, the assembly is then cured, for example in an oven, and the mandrel is removed, at block2355. The methods shown byFIGS.21-23create openings in the UV diffuse reflective sheet. In other embodiments, openings may be created by gaps between adjacent longitudinal sides as described by the methods inFIGS.24-26. Regardless of the method of making UV light generating system, once in use the process may comprise energizing the multiple UV-LEDs to generate UV light, wherein at least a portion of the generated UV light from the multiple UV-LEDs passes through the corresponding openings and into the fluid pathway. In one embodiment, reflective layers may be wrapped by the method that is shown byFIGS.24A-24E. A mandrel2402, e.g., a cylindrical rod, is used to form a tubular UV light generation system2400and once formed the mandrel2402is removed to form the fluid path. In one embodiment as shown inFIG.24A, a transparent material2404is wrapped around the mandrel2402to form an overlayer. The wrapping is done to prevent gaps between the adjacent longitudinal sides of the transparent material2404. Optionally, adjacent longitudinal sides of the transparent material overlap. In other embodiments, a transparent overlayer that is tubular may be fitted around the mandrel2402, by sliding the transparent overlayer over the mandrel2402. The overlayer may have an adhesive surface of a continuous transparent adhesive or by a pattern of adhesive dots or adhesive lines facing outward. Next, a UV diffuse reflective layer2406is wrapped around the mandrel2402, or overlayer if present. When being wrapped, a gap2408is formed between adjacent, e.g., nearby, longitudinal sides of the UV diffuse reflective layer2406. The UV diffuse reflective layer2406is wrapped along the length of the mandrel to the desired size. The UV diffuse reflective layer2406may have an adhesive surface of a transparent adhesive or by a pattern of adhesive dots or adhesive lines facing outward. In one embodiment, the UV diffuse reflective layer2406is flexible and may be made of a UV stable material, e.g., expanded polytetrafluoroethylene. The gap2408may be substantially uniform between the adjacent sides to provide a separation distance between the adjacent sides from 0.5 to 100 mm, preferably 0.5 to 20 mm, e.g., 1 to 25 mm, or from 3 to 15 mm. A flexible circuit2410having multiple UV-light emitting diodes2412is positioned to align the UV-light emitting diodes2412with the gap2408. This allows the UV light to be transmitted into the interior of the UV light generating system2400when in use. Although one flexible circuit is shown inFIG.24C, in further embodiments, multiple flexible circuits may be used adjacent to the UV diffuse reflective layer2406. When multiple flexible circuits are used, UV-light emitting diodes are offset to achieve a wide distribution of UV light within the UV light generating system2400. InFIG.24D, an underlayer2414is wrapped over the UV diffuse reflective layer and flexible circuit. The wrapping is done to prevent gaps between the adjacent longitudinal sides of the underlayer2414. Optionally, adjacent longitudinal sides of underlayer2414overlap. One or more curing processes may optionally be included in the method depicted inFIGS.24A-24E, and followingFIG.24E, the mandrel2402may be removed to create an internal fluid path. Optionally, flexible circuit2410may itself include a diffuse UV reflective overlayer with openings included at the positions of UV LEDs2412, as described above. Such a flexible circuit may alternatively be wrapped in a helical fashion around the mandrel2402, or overlayer2404if present, with the gap2408having a width that is greater than or equal to the width of flexible circuit2410to allow flexible circuit2410to fit into the helical gap2408, as indicated inFIG.24F. This configuration may be used in place of or in addition to that depicted inFIG.24D. This configuration benefits from a longer flexible circuit2410that may include more UV-LEDs and enables tighter curvatures with the tube assembly in a bent configuration. In a further embodiment, the method may involve wrapping a second UV diffuse reflective layer2516as shown inFIGS.25A-25F. As discussed above, a first UV diffuse reflective layer2506is wrapped around the mandrel2502, and optionally, the transparent material2504that forms the overlayer, such that a first gap2508is present between adjacent, e.g. nearby, longitudinal sides of first UV diffuse reflective layer2506. InFIG.25C, the second UV diffuse reflective layer2516is wrapped around the first UV diffuse reflective layer2506. In one embodiment, the second UV diffuse reflective layer2516is counter-wrapped in a direction that is opposite to the first UV diffuse reflective layer2506. In further embodiments, additional UV diffuse reflective layers may be used. The second gap2518between adjacent, e.g., nearby, longitudinal sides of the second UV diffuse reflective layer2516overlap with the first gap2508to form openings2520. As discussed herein, the openings2520may have a variety of shapes and sizes. The openings2520correspond to the pitch of the spacing of UV-LEDs2512on a flex circuit2510. In one example, a 0.5 inch wide, 0.01 inch thick, ePTFE layer was wrapped at a pitch of 17 mm with a gap of 4 mm in the right hand direction and then a second ePTFE layer was crossed wrapped in the left hand direction at a pitch of 17 mm with a gap of 4 mm. The resulting opening in the reflective layers is 4 mm diamond on a pitch of 17 mm. In one embodiment, the overlap of the first gap and second gap may create several different openings. For example, there may be additional openings on the back side (not shown inFIG.25D) that are spaced halfway between the openings on the top side. FIG.25Dshows the flex circuit2510having UV-LEDs2512laid straight in a longitudinal manner. In one embodiment, multiple flex circuits may be used. In another embodiment, the method includes helically wrapping a flex circuit having UV-LED in a helical fashion around the tube, the spacing of the UV-LEDs being such that they align with the openings. This embodiment benefits from a longer flexible circuit that enables tighter curvatures with the tube assembly in a bent configuration. As shown inFIG.25F, optional underlayer2514is wrapped around the assembly, which may have reflective or diffuse reflective properties. To complete the tubular UV light generation system2500assembly, the assembly is then cured and the mandrel2502is removed to create the internal fluid path. As previously described, an optional embodiment for the transparent overlayer is to include photocatalysts such as TiO2 on the surface that is exposed to the fluid medium. In previously described embodiments, the overlayer is positioned above the UV-LED such that the emitted light path is from LED to photocatalyst to fluid medium. Since the photocatalysts in touch with the fluid medium are generally more effective at generating reactive oxygen species that can disinfect the fluid stream, it may be desirable to have an optical path from LED through fluid stream to surface photocatalysts (e.g., on other side of tube).FIGS.26A and26Bdepict an embodiment of forming the transparent overlayer that will enable the light emitted from the UV-LED to impinge on the photocatalysts from the fluid medium side. A first transparent overlayer2603is wrapped around mandrel2602with a gap2605as shown inFIG.26A. A second overlayer2607, comprising a photocatalytic surface layer, optionally of the same width as gap2605, is then wrapped in the gap of transparent overlayer2603as shown inFIG.26B. At this stage in the process the transparent overlayer equivalent toFIG.24AorFIG.25Ais finished and the various steps described inFIG.24B-24F or25B-25Fcan be implemented to finish construction of the photocatalytic light generating tube. An optional embodiment is described inFIG.24Fwith the addition of a photocatalytic layer to the UV reflective layer2406. ADDITIONAL EXAMPLES Additional non-limiting examples are further described. E1. A method of making an ultraviolet (UV) light generation system, the method comprising: wrapping a first UV diffuse reflective layer in a first direction around a mandrel with a first gap between adjacent longitudinal sides of the first UV diffuse reflective layer, wherein the first UV diffuse reflective layer is flexible; and positioning a flexible circuit including multiple UV-light emitting diodes (UV-LEDs) adjacent to the first UV diffuse reflective layer, wherein the positioning of the flexible circuit includes aligning the multiple UV-LEDs to correspond to the first gap. E2. The method of E1, further comprising wrapping a second UV diffuse reflective layer in a second direction around the mandrel and the first UV diffuse reflective layer with a second gap between adjacent longitudinal sides of the second UV diffuse reflective layer, wherein the second UV diffuse reflective layer is flexible, and wherein a portion of the first gap and a portion of the second gap overlap to generate a plurality of openings. E3. The method of E2, wherein the positioning the flexible circuit includes aligning the multiple UV-LEDs to correspond to the plurality openings. E4. The method of E2, wherein each of the multiple UV-LEDs is positioned to direct generated UV light through a corresponding opening. E5. The method of any one of E1-E4, wherein wrapping of the first UV diffuse reflective layer includes helically wrapping. E6. The method of any one of E1-E5, wherein each of the multiple UV-LEDs is positioned to direct generated UV light through the first gap. E7. The method of any one of E1-E6, wherein aligning the multiple UV-LEDs includes aligning one or more UV-LEDs of a first flexible circuit at a first subset of the plurality of openings and aligning one or more UV-LEDs of a second flexible circuit at a second subset of the plurality of openings. E8. The method of E7, wherein the first subset of the plurality of openings and the second subset of the plurality of openings are positioned on opposite sides of the mandrel. E9. The method of E7, wherein the first subset of the plurality of openings and the second subset of the plurality of openings are offset from one another. E10. The method of any one of E1-E9, further comprising generating the flexible circuit. E11. The method of E10, wherein generating the flexible circuit includes attaching the multiple UV-LEDs. E12. The method of E11, wherein attaching the multiple UV-LEDs includes surface mounting the multiple UV-LEDs on the flexible circuit. E13. The method of E10, wherein the flexible circuit comprises a ribbon cable or flat flexible cable and wherein generating the flexible circuit includes attaching the multiple UV-LEDs to the ribbon cable or flat flexible cable. E14. The method of E13, wherein generating the flexible circuit further includes removing portions of a jacketing of the ribbon cable or flat flexible cable. E15. The method of any one of E1-E14, further comprising wrapping an underlayer around the mandrel, the first UV diffuse reflective layer, and the flexible circuit. E16. The method of E15, wherein the underlayer is a reinforcing underlayer. E17. The method of E15, wherein the underlayer is a UV diffuse reflective underlayer. E18. The method of E15, further comprising applying an adhesive between the underlayer the flexible circuit and the first UV diffuse reflective layer. E19. The method of any one of E1-E18, further comprising wrapping an overlayer around the mandrel, wherein wrapping the first UV diffuse reflective layer around the mandrel includes wrapping the first UV diffuse reflective layer around the overlayer and the mandrel. E20. The method of any one of E1-E18, further comprising positioning a tubular overlayer around the mandrel, wherein wrapping includes wrapping the first UV diffuse reflective layer around the tubular overlayer and the mandrel. E21. The method of any one of E19 or E20, wherein the overlayer or tubular overlayer is a UV transparent overlayer, preferably having a UV transmission of at least 80% at 250 nm. E22. The method of any one of E19 or E20, wherein the overlayer or tubular overlayer is a UV transmissive scattering overlayer. E23. The method of any one E19 or E20, wherein the overlayer or tubular overlayer comprises a photocatalyst, preferably comprises TiO2. E24. The method of any one of E19 or E20, further comprising applying an adhesive between the first UV diffuse reflective layer and the overlayer or tubular overlayer, preferably wherein the adhesive is a fluorinated ethylene propylene (FEP) adhesive. E25. The method of any one of E1-E24, further comprising energizing the multiple UV-LEDs to generate UV light, wherein at least a portion of the generated UV light from the multiple UV-LEDs passes through the corresponding openings and into the fluid pathway. E26. The method of any one of E1-E25, further comprising removing the mandrel. E27. An ultraviolet (UV) light generation system made by the method of any one of E1-E26. E28. An ultraviolet (UV) light generation system comprising: a first UV diffuse reflective layer arranged about a fluid pathway, wherein adjacent longitudinal sides of the first UV diffuse reflective layer are separated by a first gap, wherein the first gap runs in a first direction, and wherein the first UV diffuse reflective layer is flexible; a second UV diffuse reflective layer arranged about the first UV diffuse reflective layer, wherein adjacent longitudinal sides of the second UV diffuse reflective layer are separated by a second gap, wherein the second gap runs in a second direction, wherein the second UV diffuse reflective layer is flexible, and wherein the first and second gap overlap to generate a plurality of openings; and a flexible circuit including multiple UV-light emitting diodes (UV-LEDs), wherein the flexible circuit is positioned adjacent to the second UV diffuse reflective layer to align the multiple UV-LEDs at the plurality of openings. E29. The UV light generation system of E28, wherein the first UV diffuse reflective layer is cylindrically wrapped about the fluid pathway, or wherein the second UV diffuse reflective layer is cylindrically wrapped about the first UV diffuse reflective layer, or both. E30. The UV light generation system of E28 or E29, wherein the first UV diffuse reflective layer is helically wrapped about the fluid pathway, or wherein the second UV diffuse reflective layer is helically wrapped about the first UV diffuse reflective layer, or both. E31. The UV light generation system of any one of E28-E30, further comprising an overlayer arranged about and defining the fluid pathway, wherein the first UV diffuse reflective layer is wrapped about the overlayer. E32. The UV light generation system of E31, wherein the overlayer is a UV transparent overlayer, preferably having a UV transmission of at least 80% at 250 nm. E33. The UV light generation system of E31, wherein the overlayer is a UV transmissive scattering overlayer. E34. The UV light generation system of E31, wherein the overlayer comprises a photocatalyst, preferably comprises TiO2. E35. The UV light generation system of E31, wherein the overlayer covers at least a portion of the plurality of openings. E36. The UV light generation system of E31, wherein the overlayer is UV stable. E37. The UV light generation system of E31, wherein the overlayer is adhered to the first UV diffuse reflective layer or laminated to the first UV diffuse reflective layer, preferably the overlayer comprises a photocatalyst, and more preferably comprises TiO2. E38. The UV light generation system of any one of E28-E37, wherein the first UV diffuse reflective layer does not include UV absorbing filler material, or wherein the second UV diffuse reflective layer does not include UV absorbing filler material, or both. E39. The UV light generation system of any one of E28-E38, wherein the first UV diffuse reflective layer is UV stable, or wherein the second UV diffuse reflective layer is UV stable or both. E40. The UV light generation system of any one of E28-E39, further comprising an underlayer wrapped around the flexible circuit, the first UV diffuse reflective layer, and the second UV diffuse reflective layer. E41. The UV light generation system of E40, wherein the underlayer is a reinforcing underlayer. E42. The UV light generation system of E40, wherein the underlayer is a UV diffuse reflective underlayer. E43. The UV light generation system of any one of E28-E42, wherein the multiple UV-LEDs are positioned to direct generated UV light into the fluid pathway. E44. The UV light generation system of any one of E28-E43, wherein at least a first UV-LED of the multiple UV-LEDs is positioned in a configuration about the fluid pathway that is not directly opposed to any other of the multiple UV-LEDs. E45. The UV light generation system of any one of E28-E44, wherein the fluid pathway corresponds to a tubular shape. E46. The UV light generation system of any one of E28-E45, wherein the fluid pathway corresponds to a liquid pathway and wherein exposing a liquid stream in the liquid pathway to UV light generated by the multiple UV-LEDs reduces impurities within the liquid stream or reduces impurities associated with particles suspended in the liquid stream. E47. The UV light generation system of any one of E28-E46, wherein the fluid pathway corresponds to a gas pathway and wherein exposing a gas stream in the gas pathway to UV light generated by the multiple UV-LEDs reduces impurities within the gas stream or reduces impurities associated with particles suspended in the gas stream. E48. The UV light generation system of any one of E28-E47, wherein the flexible circuit further includes a UV sensitive photodetector, wherein the UV sensitive photodetector is positioned at one of the plurality of openings. E49. The UV light generation system of any one of E28-E48, further comprising an adhesive layer for adhering two or more components of the UV light generation system to one another. E50. The UV light generation system of E49, wherein the adhesive layer adheres a layer, an overlayer, or an underlayer to other components of the UV light generation system. E51. The UV light generation system of E49, wherein the adhesive layer corresponds to a UV transparent layer, preferably wherein the adhesive is a fluorinated ethylene propylene (FEP) adhesive. E52. The UV light generation system of E49, wherein the adhesive layer is UV stable. E53. The UV light generation system of any one of E28-E52, wherein the flexible circuit corresponds to a ribbon cable or a flat flexible cable. E54. The UV light generation system of any one of E28-E53, wherein each of the multiple UV-LEDs are individually electrically addressable. E55. The UV light generation system of any one of E28-E54, wherein at least a portion of UV light generated by the multiple UV-LEDs is reflected by a UV diffuse reflective layer of the UV light generation system. E56. The UV light generation system of any one of E28-E55, wherein the multiple UV-LEDs are positioned about the UV light generation system in a configuration to generate a uniform UV emission field within the fluid pathway. E57. The UV light generation system of any one of E28-E56, wherein the fluid pathway includes straight or curved sections. E58. The UV light generation system of any one of E28-E57, wherein one or more layers, underlayers, or overlayers of the UV light generation system are flexible or exhibit an elastic modulus of between 0.001 GPa and 3.0 GPa. E59. The UV light generation system of any one of E28-E58, wherein one or more layers, underlayers, or overlayers of the UV light generation system comprise polytetrafluoroethylene or expanded-polytetrafluoroethylene (e-PTFE). E60. The UV light generation system of any one of E28-E59 made by the method of any one of E1-E27. E61. The method of any one of E1-E27, wherein the UV light generation system comprises the UV light generation system of any one of E28-E59. E62. A method of making an ultraviolet (UV) light generation system, the method comprising: generating a plurality of openings in a UV diffuse reflective layer, wherein the UV diffuse reflective layer is flexible; and positioning a flexible circuit adjacent to the UV diffuse reflective layer, wherein the flexible circuit includes multiple UV-light emitting diodes (UV-LEDs), and wherein the multiple UV-LEDs are aligned at corresponding openings in the UV diffuse reflective layer. E63. The method of E62, wherein generating the plurality of openings includes removing portions the UV diffuse reflective layer. E64. The method of E62 or E63, further comprising generating the flexible circuit. E65. The method of E64, wherein generating the flexible circuit includes attaching the multiple UV-LEDs on a flexible circuit. E66. The method of E65, wherein attaching the multiple UV-LEDs includes surface mounting the multiple UV-LEDs on the flexible circuit. E67. The method of E64, wherein the flexible circuit comprises a ribbon cable or flat flexible cable and wherein generating the flexible circuit includes attaching the multiple UV-LEDs to the ribbon cable or flat flexible cable. E68. The method of E64, wherein generating the flexible circuit further includes removing portions of a jacketing of the ribbon cable or flat flexible cable. E69. The method of any one of E62-E68, wherein the flexible circuit is a two-sided flexible circuit, wherein generating the plurality of openings in the UV diffuse reflective layer includes generating a first plurality of openings in a first UV diffuse reflective layer and generating a second plurality of openings in a second UV diffuse reflective layer UV, and wherein positioning the flexible circuit includes aligning a first portion of the multiple UV-LEDs that are present on a second side of the two-sided flexible circuit with corresponding openings of the first UV diffuse reflective layer and aligning a second portion of the multiple UV-LEDs that are present on a second side of the two-sided flexible circuit with corresponding openings of the second UV diffuse reflective layer, thereby making a two-sided UV light generation system. E70. The method of any one of E62-E69, further comprising arranging the UV diffuse reflective layer and the flexible circuit such that at least portions of the flexible circuit are positioned back-to-back, thereby making a two-sided UV light generation system. E71. The method of any one of E62-E70, further comprising arranging a second UV light generation system adjacent to the UV light generation system such that at least a portion of the flexible circuit is positioned adjacent to a portion of a second flexible circuit of the second UV light generation system, thereby making a two-sided UV light generation system. E72. The method of any one of E62-E71, further comprising positioning a UV diffuse reflective underlayer adjacent to the flexible circuit. E73. The method of E72, further comprising applying an adhesive between the UV diffuse reflective underlayer and the UV diffuse reflective layer. E74. The method of E72, wherein the UV diffuse reflective underlayer is flexible. E75. The method of any one of E62-E74, further comprising positioning an overlayer adjacent to the UV diffuse reflective layer. E76. The method of E75, wherein the overlayer is a UV transparent overlayer, preferably having a UV transmission of at least 80% at 250 nm. E77. The method of E75, further comprising applying an adhesive between the overlayer and the UV diffuse reflective layer, preferably wherein the adhesive is a fluorinated ethylene propylene (FEP) adhesive. E78. The method of E75, wherein the overlayer is flexible. E79. The method of E75, wherein the overlayer comprises a photocatalyst, preferably a TiO2 surface coating or wherein the UV transparent overlayer is attached to a TiO2 overlayer. E80. The method of E75, further comprising applying a TiO2 surface coating to the overlayer or attaching a TiO2 further overlayer to the overlayer. E81. The method of E75, wherein the overlayer is a UV transmissive scattering overlayer. E82. The method of any one of E62-E81, further comprising heating the UV diffuse reflective layer. E83. The method of any one of E62-E82, further comprising applying pressure to the UV diffuse reflective layer. E84. The method of E82, wherein heating the UV diffuse reflective layer includes heating the UV diffuse reflective layer and an underlayer, an overlayer, or both an underlayer or an overlayer. E85. The method of any one of E62-E84, further comprising energizing the multiple UV-LEDs to generate UV light, wherein at least a portion of the generated UV light from the multiple UV-LEDs passes through the corresponding openings in the UV diffuse reflective layer. E86. The method of any one of E62-E85, further comprising wrapping the flexible circuit and the UV diffuse reflective layer around a mandrel. E87. The method of E86, wherein wrapping includes helically, longitudinally, or circumferentially wrapping the flexible circuit and the UV diffuse reflective layer around the mandrel. E88. The method of E86, further comprising wrapping an underlayer around the flexible circuit and the UV diffuse reflective layer. E89. The method of E88, wherein the underlayer is a reinforcing underlayer. E90. The method of E88, wherein the underlayer is a UV diffuse reflective underlayer. E91. The method of E88, further comprising applying an adhesive between the underlayer and the flexible circuit, preferably wherein the adhesive is a fluorinated ethylene propylene (FEP) adhesive. E92. The method of any one of E62-E91, further comprising wrapping an overlayer around the mandrel, wherein wrapping the flexible circuit and the UV diffuse reflective layer around the mandrel includes wrapping the flexible circuit and the UV diffuse reflective layer around the overlayer and the mandrel. E93. The method of any one of E62-E91, further comprising positioning a tubular overlayer around the mandrel, wherein wrapping includes wrapping the flexible circuit and the UV diffuse reflective layer around the tubular overlayer and the mandrel. E94. The method of any one of E92 or E93, wherein the overlayer or the tubular overlayer is a UV transparent overlayer, preferably having a UV transmission of at least 80% at 250 nm. E95. The method of any one of E92 or E93, wherein the overlayer or the tubular overlayer is a UV transmissive scattering overlayer. E96. The method of any one of E92 or E93, further comprising applying an adhesive between the UV diffuse reflective layer and the overlayer or the tubular overlayer, preferably wherein the adhesive is a fluorinated ethylene propylene (FEP) adhesive. E97. The method of any one of E62-E96, further comprising removing the mandrel. E98. An ultraviolet (UV) light generation system made by the method of any one of E62-E97. E99. An ultraviolet (UV) light generation system comprising: a flexible circuit including multiple ultraviolet light emitting diodes (UV-LEDs); and a UV diffuse reflective layer adjacent to the multiple UV-LEDs, wherein the UV diffuse reflective layer is flexible, wherein the UV diffuse reflective layer includes multiple openings, and wherein each UV-LED is positioned at a corresponding opening. E100. The UV light generation system of E99, further comprising an overlayer adjacent to the UV diffuse reflective layer. E101. The UV light generation system of E100, wherein the overlayer is a UV transparent overlayer, preferably having a UV transmission of at least 80% at 250 nm. E102. The UV light generation system of E100, wherein the overlayer is a UV transmissive scattering overlayer. E103. The UV light generation system of E100, wherein the overlayer comprises a photocatalyst, preferably a TiO2 surface coating or wherein the UV transparent overlayer is attached to a TiO2 overlayer. E104. The UV light generation system of E100, wherein the overlayer covers multiple openings in the UV diffuse reflective layer. E105. The UV light generation system of E100, wherein the overlayer does not include UV absorbing filler material. E106. The UV light generation system of E100, wherein the overlayer is UV stable. E107. The UV light generation system of E100, wherein the overlayer is adhered to the UV diffuse reflective layer or laminated to the UV diffuse reflective layer. E108. The UV light generation system of any one of E99-E107, wherein the UV diffuse reflective layer is UV stable. E109. The UV light generation system of any one of E99-E108, further comprising an underlayer positioned adjacent to the UV flexible circuit. E110. The UV light generation system of E109, wherein the underlayer is a reinforcing underlayer. E111. The UV light generation system of E109, wherein the underlayer is a UV diffuse reflective underlayer. E112. The UV light generation system of any one of E99-E111, arranged to define an enclosed region, wherein the multiple UV-LEDs are positioned to direct generated UV light into the enclosed region. E113. The UV light generation system of E112, arranged to position at least a first UV-LED of the multiple UV-LEDs in a configuration about the enclosed region that is not directly opposed to any other of the multiple UV-LEDs. E114. The UV light generation system of E112, wherein the enclosed region corresponds to a fluid pathway. E115. The UV light generation system of E113, wherein the UV light generation system is arranged to form a tubular shape corresponding to the fluid pathway. E116. The UV light generation system of E113, wherein the UV light generation system is wrapped helically, longitudinally, or circumferentially around the fluid pathway. E117. The UV light generation system of E113, wherein the fluid pathway corresponds to a liquid pathway and wherein exposing a liquid stream in the liquid pathway to UV light generated by the multiple UV-LEDs reduces impurities within the liquid stream or reduces impurities associated with particles suspended in the liquid stream. E118. The UV light generation system of E113, wherein the fluid pathway corresponds to a gas pathway and wherein exposing a gas stream in the gas pathway to UV light generated by the multiple UV-LEDs reduces impurities within the gas stream or reduces impurities associated with particles suspended in the gas stream. E119. The UV light generation system of E112, wherein at least two portions of the UV light generation system are positioned to oppose one another and define the enclosed region. E120. The UV light generation system of any one of E99-E119, arranged along an interior surface of a vessel, wherein the multiple UV-LEDs are positioned to direct generated UV light into an interior of the vessel. E121. The UV light generation system of any one of E99-E120, arranged along a surface of a structure positioned within a vessel, wherein the multiple UV-LEDs are positioned to direct generated UV light into an interior of the vessel. E122. The UV light generation system of any one of E99-E121, arranged around a central shaft, wherein the multiple UV-LEDs are positioned to direct generated UV away from the central shaft. E123. The UV light generation system of E122, wherein the UV light generation system is wrapped helically, longitudinally, or circumferentially around the central shaft. E124. The UV light generation system of E122, wherein the multiple UV-LEDs are positioned around the central shaft in a configuration to generate a uniform UV emission field at a circumferential distance from the central shaft. E125. The UV light generation system of any one of E99-E124, arranged as a two-sided sheet, wherein the multiple UV-LEDs are positioned to direct generated UV light outward and away from the two-sided sheet. E126. The UV light generation system of E125, wherein UV-LEDs positioned on a first side of the two-sided sheet do not back to any UV-LEDs positioned on a second side of the two-sided sheet. E127. The UV light generation system of any one of E99-E126, wherein the flexible circuit further includes a UV sensitive photodetector, wherein the UV sensitive photodetector is positioned at one of the multiple openings of the UV diffuse reflective layer. E128. The UV light generation system of any one of E99-E127, further comprising an adhesive layer for adhering two or more components of the UV light generation system to one another. E129. The UV light generation system of E128, wherein the adhesive layer adheres an overlayer or an underlayer to other components of the UV light generation system. E130. The UV light generation system of E128, wherein the adhesive layer corresponds to a UV transparent layer. E131. The UV light generation system of E128, wherein the adhesive layer is UV stable. E132. The UV light generation system of any one of E99-E131, wherein the flexible circuit corresponds to a ribbon cable or a flat flexible cable. E133. The UV light generation system of any one of E99-E132, wherein each of the multiple UV-LEDs are individually electrically addressable. E134. The UV light generation system of any one of E99-E133, wherein at least a portion of UV light generated by the multiple UV-LEDs is reflected by a UV diffuse reflective layer of the UV light generation system. E135. The UV light generation system of any one of E99-E134, wherein the multiple UV-LEDs are positioned about the UV light generation system in a configuration to generate a uniform UV emission field at a distance away from the UV diffuse reflective layer. E136. The UV light generation system of any one of E99-E135, including one or more flat, concave, or convex sections. E137. The UV light generation system of any one of E99-E136, wherein the array corresponds to a regular array or a non-regular array. E138. The UV light generation system of any one of E99-E137, wherein one or more layers, underlayers, or overlayers of the UV light generation system are flexible or exhibit an elastic modulus of between 0.001 GPa and 3.0 GPa. E139. The UV light generation system of any one of E99-E138, wherein one or more layers, underlayers, or overlayers of the UV light generation system comprise polytetrafluoroethylene or expanded-polytetrafluoroethylene (e-PTFE). E140. The UV light generation system of any one of E99-E139 made by the method of any one of E62-E98. E141. The method of any one of E62-E98, wherein the UV light generation system comprises the UV light generation system of any one of E99-E139. E142. A method of making an ultraviolet (UV) light generation system, the method comprising: wrapping a first UV diffuse reflective layer in a first direction around a mandrel with a first gap between adjacent longitudinal sides of the first UV diffuse reflective layer, wherein the first UV diffuse reflective layer is flexible; wrapping a second UV diffuse reflective layer in a second direction around the mandrel and the first UV diffuse reflective layer with a second gap between adjacent longitudinal sides of the second UV diffuse reflective layer, wherein the second UV diffuse reflective layer is flexible, and wherein a portion of the first gap and a portion of the second gap overlap to generate a plurality of openings and positioning a flexible circuit including multiple UV-light emitting diodes (UV-LEDs) adjacent to the first UV diffuse reflective layer, wherein the positioning of the flexible circuit includes aligning the multiple UV-LEDs to correspond to the plurality of openings. E143. The method of E142, wherein each of the multiple UV-LEDs is positioned to direct generated UV light through a corresponding opening. Various modifications and additions can be made to the exemplary embodiments of the disclosed treatment systems discussed without departing from the scope of the present invention. While the embodiments described above refer to particular features, the scope of this invention also includes embodiments having different combinations of features and embodiments that do not include all of the above described features. It will be appreciated that features of the various embodiments and examples described herein may be combined with one another in any suitable combination and that the disclosed embodiments are not limiting. For example, features in one embodiment may optionally be imported into another embodiment if it is possible to do so. | 102,299 |
11857690 | DESCRIPTION OF EMBODIMENTS In general, an aseptic filler includes a sterilizing portion that receives a container supplied to the aseptic filler and sterilizes the supplied container, a filling portion that fills the sterilized container with a sterilized content in an aseptic atmosphere, and a sealing portion that seals the container filled with the content in an aseptic atmosphere. However, the configuration of the aseptic filler varies depending on the container that is to be aseptically filled. For example, when the container is a bottle, the aseptic filler includes a heating portion that receives a preform supplied to the aseptic filler and heats the preform to a molding temperature, a molding portion that molds the heated preform into a container, an inspecting portion that inspects the molded bottle, a bottle sterilizing portion that sterilizes the inspected bottle, an air rinsing portion that air-rinses the sterilized bottle, a filling portion that fills the sterilized bottle with a content sterilized by a content sterilization apparatus in an aseptic atmosphere, a sealing portion that seals the bottle filled with the content with a lid material in an aseptic atmosphere, and a discharging portion that discharges the sealed bottle. The aseptic filler for a bottle may not include the inspecting portion and the air rinsing portion. There is an aseptic filler that has a preform sterilizing portion that sterilizes the supplied preform before heating. The aseptic filler having the preform sterilizing portion may not include the bottle sterilizing portion. When the container is a paper container, the aseptic filler includes a bottom part forming portion that receives a sleeve supplied to the aseptic filler, sterilizes surfaces to be the outer surface of the paper container, and forms a bottom part, a sterilizing portion that sterilizes the inner surface of the paper container with the bottom part formed, a filling portion that fills the paper container with the inner surface sterilized with a sterilized content, and a sealing portion that seals the paper container filled with the content. Aseptic fillers for different containers have different configurations. Each portion of the aseptic filler is shielded in a chamber. With the aseptic filler for a bottle, the heating portion and the molding portion may be shielded in a single chamber. The sealing portion and the discharging portion may also be shielded in a single chamber. Further, the filling portion, the sealing portion and the discharging portion may also be shielded in a single chamber. With the aseptic filler for a paper container, the bottom part forming portion, the sterilizing portion, the filling portion and the sealing portion are shielded in a single chamber. However, the bottom part forming portion, the sterilizing portion, the filling portion and the sealing portion may be each shielded in a different chamber. The configuration of each portion varies depending on the container to be handled by the aseptic filler, and the chamber shielding each portion also varies depending on the container to be handed by the aseptic filler. During operation of the aseptic filler for a bottle, aseptic air sterilized by an aseptic filter is supplied to the chamber for the bottle sterilizing portion, the chamber for the air rinsing portion, the chamber for the filling portion, the chamber for the sealing portion and the chamber for the discharging portion, and the aseptic condition of the aseptic filler is maintained by establishing a positive pressure in each chamber. The positive pressure established is the highest in the chamber for the filling portion and decreases as it goes upstream, specifically, is set to be lower in the chamber for the air rinsing portion and even lower in the chamber for the bottle sterilizing portion. For example, provided that the pressure in the chamber for the filling portion is 20 Pa to 40 Pa, the pressures in the other chambers are lower than the pressure in the chamber for the filling portion. With the aseptic filler having a preform sterilizing portion, the heating portion and the molding portion are also each covered by a chamber, and aseptic air is supplied into the chamber for the heating portion and the chamber for the molding portion to maintain a positive pressure in the chambers. The interiors of the chamber for the bottle sterilizing portion, the chamber for the air rinsing portion, the chamber for the filling portion, the chamber for the sealing portion and the chamber for the discharging portion are subjected to a COP treatment and a SOP treatment before operation of the aseptic filler. To this end, as shown inFIG.1, in a chamber1for the aseptic filler, a rotary nozzle2that sprays a cleaning liquid and a sterilizer containing peracetic acid, and a twin-fluid nozzle3that sprays a sterilizer containing hydrogen peroxide are provided. The rotary nozzle2is a nozzle that sprays a liquid supplied thereto into the chamber1while being rotated by the pressure of the liquid being supplied. The twin-fluid nozzle3is supplied with a sterilizer containing hydrogen peroxide and compressed air, and sprays the sterilizer containing hydrogen peroxide into the chamber1under the pressure of the compressed air. The nozzles provided in the chamber1are not limited to the rotary nozzle2and the twin-fluid nozzle3, but can be any nozzle having a different structure that can spray a cleaner, an aseptic water and a sterilizer containing hydrogen peroxide into the chamber1. With the aseptic filler for a bottle, a sterilizer is sprayed into the chamber for the bottle sterilizing portion during operation of the aseptic filler, and therefore, the interior of the chamber for the bottle sterilizing portion need not be subjected to the SOP treatment. With the aseptic filler having the preform sterilizing portion, the interior of the chamber covering the heating portion and the molding portion is subjected to the SOP treatment. With an aseptic filler intended for a container other than a bottle, the sterilizing portion, the filling portion and the sealing portion may be shielded in a single chamber. In such a case, the interior of the single chamber is subjected to the COP treatment and the SOP treatment. Before the SOP treatment of the interior of each chamber, the chamber for the filling portion that performs filling with the content and the chambers downstream thereof are subjected to the COP treatment. The interior of any chamber that is badly contaminated with the content scattered in the chamber is cleaned by spraying warm water, hot water, or a cleaning liquid such as an alkaline cleaning liquid or an acidic cleaning liquid, into the chamber. The contamination of the chambers for the molding portion and the bottle sterilizing portion is limited, so that these chambers need not be subjected to the COP treatment. When changing the content after a continuous operation of the aseptic filler filling containers with a content, or if the interior of a chamber is contaminated with droplets of the content after a continuous operation for a long time, the operation of the aseptic filler is stopped, and the chambers of the aseptic filler are subjected to the COP treatment and the SOP treatment. The interior of any chamber that is not contaminated with the content is subjected to only the SOP treatment. For the COP treatment for cleaning the interior of the chamber1contaminated with the content, an alkaline cleaning liquid is first sprayed into the chamber1. The alkaline cleaning liquid contains an inorganic basic compound such as sodium hydroxide or potassium hydroxide, or an organic basic compound such as ethanolamine or diethylamine, and may further contain a metal-ion blocking agent such as an alkali metal salt, an alkaline earth metal salt or an ammonium salt of an organic acid, or an ethylenediamine tetraacetic acid, an anionic surfactant, a cationic surfactant, a nonionic surfactant such as a polyoxyethylene alkylphenyl ether, a solubilizer such as sodium cumenesulfonate, a metal salt of an acid-based polymer such as polyacrylic acid, a corrosion inhibitor, a preservative, an antioxidant, a dispersant, a defoaming agent or the like. After the alkaline cleaning liquid is sprayed, an acidic cleaning liquid may be sprayed. The acidic cleaning liquid is an inorganic acid such as hydrochloric acid, nitric acid or phosphoric acid, or an organic acid such as acetic acid, formic acid, octanoic acid, oxalic acid, citric acid, succinic acid or gluconic acid, and may contain an anionic surfactant, a cationic surfactant, a nonionic surfactant such as a polyoxyethylene alkylphenyl ether, a solubilizer such as sodium cumenesulfonate, an acid-based polymer such as polyacrylic acid, a corrosion inhibitor, a preservative, an antioxidant, a dispersant, a defoaming agents or the like. When the contamination with the content remains after the spray of the alkaline cleaning liquid, the spray of the acidic cleaning liquid is performed. Alternatively, the spray of the alkaline cleaning liquid may be omitted, and only the spray of the acidic cleaning liquid may be performed. The spray of the alkaline cleaning liquid and the spray of the acidic cleaning liquid may be alternately performed. The cleaning may be performed using water at room temperature, warm water or hot water, without using the alkaline cleaning liquid and the acidic cleaning liquid. Alternatively, after the cleaning with the alkaline cleaning liquid and the acidic cleaning liquid, the cleaning with water at room temperature, warm water or hot water may be performed, which also serves to wash the alkaline cleaning liquid and the acidic cleaning liquid away. These cleaning liquids can be used in any combination in any order. Here, the warm water herein is water at a temperature equal to or higher than 40° C. and lower than 100° C., and the hot water herein is water at a temperature equal to or higher than 100° C. and equal to or lower than 130° C. If the alkaline cleaning liquid is heated to 50° C. or higher, the alkaline cleaning liquid has a sterilizing effect. Therefore, by spraying the alkaline cleaning liquid heated to 50° C. or higher into the chamber1, a sterilizing effect is also expected. After the cleaning liquid is sprayed into the chamber1, transfer devices that convey the containers are driven to remove any cleaning liquid deposited on the transfer devices. When the cleaning liquid is the alkaline cleaning liquid or acidic cleaning liquid for example, the alkaline cleaning liquid or acidic cleaning liquid may be washed away by additionally using room temperature water, warm water or hot water as a cleaning liquid. The water used may be aseptic water. In order to prevent the interior of the chamber from being contaminated with bacteria contained in the water sprayed thereto, aseptic water is preferably used. The aseptic water herein is water sterilized by being heated at 121.1° C. or higher for 4 minutes or longer or by being passed through an aseptic filter. If a sterilizer containing peracetic acid is used in the subsequent sterilizer spray, the water may be non-aseptic water. This is because the sterilizer containing peracetic acid sterilizes any water remaining in the chamber1. The temperature of the water sprayed into the chamber after the interior of the chamber is cleaned with the alkaline cleaning liquid or acidic cleaning liquid is 20° C. to 100° C., preferably 60° C. to 100° C. By setting the temperature of the water to 60° C. or higher, not only the improvement of the cleaning ability but also a sterilizing effect against heat-resistant fungi and heat-resistant yeast damaged by chemical agents such as alkali used in the COP treatment is expected. Driving of the transfer devices that convey bottles will be described with reference toFIG.2.FIG.2is a schematic plane view of the interior of a filling portion chamber4of an aseptic filler for bottles according to an embodiment of the present invention.FIG.2shows a part of the aseptic filler a filling portion, a sealing portion and a discharging portion of which are shielded by a single filling portion chamber. A bottle, which is a sterilized container, is passed from a wheel10in an air rinsing portion chamber6that shields an air rinsing portion to the interior of the filling portion chamber4. Viewed from the upstream side to the downstream side of the conveyance path of the bottle5, an introduction wheel11, a filling wheel12, an intermediate wheel13, a capper wheel14and a discharging wheel15are arranged in the listed order. These wheels11to15are driven to rotate at substantially the same circumferential velocity. Grippers having a shape like a pair of scissors that hold and release a neck portion of the bottle5are arranged at predetermined intervals around each of the wheels11to15. The grippers can rotate about the central axes of the respective wheels11to15along with the respective wheels11to15. Although the gripper is a well-known component and therefore will not be described in detail, the grippers are opened and closed at a position where the wheels are adjacent to each other by the action of a cam or the like, and the bottle5is thereby passed from the gripper on the upstream-side wheel to the gripper on the downstream-side wheel. In this way, the bottle5continuously travels from the introduction wheel11to the discharging wheel15via the filling wheel12, the filling wheel12and the like. A filling nozzle, which rotates along with the filling wheel12, is connected to the filling wheel12, which is attached, in a horizontal orientation, to a vertical shaft installed on a base, and grippers are provided around the filling wheel12. In addition, a plurality of pipe-shaped filling nozzles for filling bottles5with a drink or the like are arranged around the charging wheel12in association with the grippers. Each filling nozzle is arranged in a vertical orientation with the mouth at the lower end thereof facing the mouth portion of the bottle5gripped by the gripper. The filling nozzle may be fixed with respect to the filling wheel12or may be able to reciprocate in the vertical direction. If the filling nozzle can reciprocate in the vertical direction, the filling nozzle can be inserted into the bottle5to supply a drink or the like as a content into the bottle5. After the drink or the like is sterilized, the drink or the like is stored in a storage tank (not shown) and is supplied from the storage tank to the filling nozzles through a pipe line. In order to distribute the drink or the like supplied from the storage tank to the filling nozzles rotating, the vertical shaft is provided with an upper rotary joint and an upper manifold. The drink or the like from the storage tank enters a cavity in the vertical shaft and is discharged from the filling nozzles into the bottles5via the upper rotary joint and the upper manifold. The filling nozzle is provided with a valve that allows a desired amount of the drink or the like to be supplied into the bottle5. The aseptic filler includes a CIP treatment apparatus that performs the CIP treatment for cleaning the interior of the drink supply piping from the storage tank to the filling nozzles, and a SIP treatment apparatus that performs the SIP treatment for sterilization. For the CIP treatment and the SIP treatment, a cup-shaped closing device of the filling nozzle is provided to open and close the mouth at the lower end of the filling nozzle. The cup-shaped closing devices of the filling nozzles are arranged around the filling wheel12in association with the grippers and the filling nozzles. The cup-shaped closing device of the filling nozzle can be moved by a cam device, an air cylinder device or the like in the radial direction of the filling wheel12and the vertical direction. The cup-shaped closing device of the filling nozzle is retracted inwardly in the radial direction when supplying the drink or the like from the charging nozzle into the bottle5, and is moved outwardly in the radial direction to directly below the filling nozzle and then raised to block the mouth of the filling nozzle when closing the filling nozzle. In addition to the cup-shaped closing devices of the filling nozzles, components of the CIP treatment apparatus include a lower manifold, a lower rotary joint, a cleaning liquid tank, and a pump. The lower rotary joint is attached to the vertical shaft. The lower manifold is fixed to the base. The cup-shaped closing device of the filling nozzle, the upper manifold, the lower manifold and the like are connected to each other by a pipe line. These components of the CIP treatment apparatus rotate along with the filling wheel12. Around the capper wheel14shown inFIG.2, cappers are provided to cap the mouth portions of the bottles5filled with the drink or the like, although not shown. The capper rotates along the capper wheel14and screws a sterilized cap onto the mouth portion of the bottle5. The wheels11to15in the chamber cleaned with the cleaning liquid are rotated. After the spray of the cleaning liquid into the filling portion chamber4, the wheels11to15transferring the bottles5are rotated, and any cleaning liquid deposited on devices rotating along with the wheels11to15is removed by the action of the centrifugal force produced by the rotation of the wheels11to15. The wheels11to15are rotated at a half or more of the rotating speed of the wheels during operation of the aseptic filler, preferably at the operating speed during manufacture. The wheels in the chambers are rotated at the same time at substantially the same number of revolutions. When each chamber is provided with a motor, and the rotation of the wheels can be controlled for each chamber, the wheels are rotated on a chamber basis. By rotating the wheels according to the stages of the COP treatment and the SOP treatment for each chamber, the COP treatment and the SOP treatment for each chamber can be quickly performed. By rotating the wheels, any aseptic water on devices and the wall in the chamber can be quickly removed. While the CIP treatment or SIP treatment of the interior of the drink supply piping is being performed, the clutch of the filling wheel12may be disengaged, and the other wheels than the filling wheel12may be rotated. The sterilizer is then sprayed to the interior of the filling portion chamber4to sterilize devices and the wall in the filling portion chamber4. When a sterilizer containing peracetic acid is sprayed, it is necessary to prevent a decrease of the sterilizing effect by preventing the concentration of peracetic acid in the sterilizer from decreasing because of the water remaining in the chamber. Before the sterilizer containing peracetic acid is sprayed, heated air is preferably blown into the filling portion chamber4to completely remove the remaining water. However, this takes a long time. By rotating the wheels11to15, which are the transfer devices for the bottles5, any cleaning liquid deposited on the wheels11to15and devices attached to the wheels11to15can be removed, and a decrease of the sterilizing effect of the sterilizer containing peracetic acid can be prevented. When rotating the wheels11to15, the wheels11to15may be intermittently rotated. By intermittently rotating the wheels, the cleaning liquid deposited on the wheels11to15and devices attached to the wheels11to15can be efficiently removed because of the accelerations that occur when the wheels start rotating and stop rotating. In addition, spindles of the cappers may be moved up and down, thereby removing water remaining on bellows protecting the spindles. In the aseptic filler for bottles, the removal of the cleaning liquid by driving the transfer devices that convey containers is also performed in the chambers for other than the filling portion, the sealing portion and the discharging portion such as the heating portion, the molding portion, the sterilizing portion, the air rinsing portion and the like. The wheels are also rotated in the chambers other than the filling portion chamber4. However, in the chamber for the heating portion, an endless chain for transferring preforms can be operated to remove aseptic water deposited on the endless chain and spindles thereof. In the chamber for the molding portion, wheels can be rotated to remove aseptic water deposited on the wheels, and dies, extension rods, valve blocks and the like thereof. When removing the cleaning liquid by driving the transfer devices that convey containers, air is preferably blown into a chamber of the aseptic filler. By blowing heated aseptic air into a chamber, the removal of the cleaning liquid can be accelerated and completed in a shorter time. The air blown into the chamber is preferably heated. Further, the air blown into the chamber may be aseptic air. This is achieved by a heated aseptic air supply apparatus16provided on top of the chamber1shown inFIG.1supplying heated aseptic air into the chamber1. The heated aseptic air is produced by a heating apparatus18heating air from a blower17and sterilizing the heated air through an aseptic filter19. The heated aseptic air supply apparatus16includes the blower17, the heating apparatus18and the aseptic filter19. After the cleaning liquid is removed in the chamber subjected to the COP treatment that involves spray of the cleaning liquid, the interior of the chamber is subjected to the SOP treatment. In the aseptic filler for bottles, the interiors of the chambers covering the heating portion and the molding portion of the aseptic filler having the preform sterilizing portion are not contaminated with the content, the COP treatment for the chambers may be omitted, and the interiors of the chambers may be subjected only to the SOP treatment. In the SOP treatment, a sterilizer containing peracetic acid is sprayed into the chamber, aseptic water is then sprayed to wash the sterilizer containing peracetic acid, a sterilizer hydrogen peroxide is then sprayed into the chamber, and the sterilizer containing hydrogen peroxide is then removed by being dried. Alternatively, the sterilizer containing peracetic acid and the sterilizer containing hydrogen peroxide may be alternately sprayed. For example, the sterilizer containing peracetic acid is sprayed and then washed away with aseptic water, the aseptic water is then removed by driving the transfer devices that convey containers, and the sterilizer containing hydrogen peroxide is then sprayed and removed by being dried. There is a SOP treatment that includes a step of spraying a sterilizer containing hydrogen peroxide, a step of removing the sterilizer containing hydrogen peroxide by drying the sterilizer, a step of spraying a sterilizer containing peracetic acid, and a step of washing the sterilizer containing peracetic acid away with aseptic water. The spray of the sterilizer containing peracetic acid and the spray of the sterilizer containing hydrogen peroxide may be alternately performed, or may be each performed multiple times. When aseptic water is sprayed after the sterilizer containing peracetic acid is sprayed, and the sterilizer containing hydrogen peroxide is then sprayed, the transfer devices that convey containers is driven after the spray of the aseptic water to remove the aseptic water. The parts of the interior of the chamber that has come into contact with the sterilizer containing peracetic acid are perfectly sterilized by the sterilizer containing peracetic acid. However, there is a possibility that a small clearance into which the sterilizer cannot enter, a part the sprayed sterilizer cannot reach, or a part (such as a HEPA filter) that should not be actively sterilized with the sterilizer containing peracetic acid be not sterilized, or a peracetic acid-resistant bacterium (such asPaenibacillusorBacillus cereus) be not killed. Therefore, in order to sterilize a small clearance into which the sterilizer containing peracetic acid cannot enter or a part that the sprayed sterilizer containing peracetic acid cannot reach, which can be left unsterilized by the sterilizer containing peracetic acid, with hydrogen peroxide gas produced from the sterilizer containing hydrogen peroxide, the spray of the sterilizer containing peracetic acid and the spray of the sterilizer containing hydrogen peroxide may be alternately performed. The sterilizer containing peracetic acid herein is a sterilizer mainly composed of peracetic acid, and the concentration of peracetic acid is 500 ppm or higher, preferably from 1000 ppm to 5000 ppm. The sterilizer further contains at least hydrogen peroxide and acetic acid. If the sterilizer containing peracetic acid is heated to 40° C. to 95° C., preferably to 50° C. to 95° C., the sterilizing effect is improved. After the sterilizer containing peracetic acid is sprayed into the chamber, aseptic water is sprayed into the chamber. By spraying aseptic water, the sterilizer containing peracetic acid is washed away from the interior of the chamber. The water used to wash the sterilizer containing peracetic acid away has to be aseptic water. This is intended to maintain the sterilized state by the sterilizer containing peracetic acid. The transfer devices that convey containers in the chamber from which the sterilizer containing peracetic acid has been washed away with aseptic water is driven. With the aseptic filler for bottles, after the spray of the aseptic water into the chamber, the wheels11to15for transferring the bottles5are rotated, and any aseptic water deposited on the wheels11to15and devices rotating along with the wheels11to15is removed by the action of the centrifugal force produced by the rotation of the wheels11to15. After the aseptic water is removed, the sterilizer containing hydrogen peroxide is sprayed into the chamber of the aseptic filler. Before the spray of the sterilizer containing hydrogen peroxide into the chamber, the interior of the chamber is preferably dried as much as possible. If the interior is wet, there is a possibility that the hydrogen peroxide be dissolved in the remaining aseptic water so that the concentration of hydrogen peroxide in the sterilizer decreases, and the sterilizing effect be not exerted. In order to efficiently remove the aseptic water remaining in each chamber in a short time, the wheels in each chamber are rotated. In this regard, the rotation speed of the wheels is preferably raised to the operating speed during production. The wheels may be intermittently rotated. While the wheels are rotating, aseptic air is preferably supplied to prevent bacteria from entering from the outside. Further, the aseptic air is preferably heated in order to accelerate the removal of the aseptic water. The aseptic air can be heated to 50° C. to 200° C. By rotating the wheels, aseptic water deposited on the wheels and devices rotating along with the wheels can be removed. In addition, the rotation of the wheels causes a flow of air around the wheels, and the flow of air collides with the wall surface of the chamber, thereby promoting the downward flow of the aseptic water on the wall surface and accelerating the removal of the aseptic water on the wall surface. If the pressure in the filling portion chamber4is raised to 30 Pa to 200 Pa by suppling the aseptic air, the aseptic water is efficiently removed. The aseptic water in the other chambers is efficiently removed by raising the pressure in the same manner. As described above, heated aseptic air is preferably blown into the chamber while the wheels are rotating. However, if heated aseptic air is blown into the chamber after the wheels stop rotating, the removal of the aseptic water remaining in the chamber can be more quickly removed. After the aseptic water in the chamber is removed, the sterilizer containing hydrogen peroxide is sprayed into the chamber. The sprayed sterilizer containing hydrogen peroxide appropriately contains 20 mass % to 65 mass of hydrogen peroxide. If the content is less than 20 mass %, the sterilizing power may be insufficient, and if the content is more than 65 mass %, handling becomes difficult for safety reasons. By spraying the sterilizer containing hydrogen peroxide, any part that has not been sterilized by the spray of the sterilizer containing peracetic acid is sterilized, and any bacteria that has not been killed by the sterilizer containing peracetic acid is killed. After the spray of the sterilizer containing hydrogen peroxide into the chamber, heated aseptic air is blown into the chamber in order to gasify the hydrogen peroxide and sterilize the interior of the chamber. The temperature of the heated aseptic air can be 50° C. to 200° C. By blowing the heated aseptic air into the chamber, the hydrogen peroxide in the sterilizer containing hydrogen peroxide remaining in the chamber is gasified to sterilize any small clearance that the sterilizer containing peracetic acid has not been able to enter or any part that the sprayed sterilizer containing peracetic acid has not reached or kill any peracetic acid-resistant bacteria. After it is checked that the sterilizer containing hydrogen peroxide in the chamber has been removed by blowing the heated aseptic air into the chamber, the interior of the chamber having been heated by the blowing of the heated aseptic air is ventilated and cooled by blowing aseptic air at room temperature into the chamber to remove any remaining hydrogen peroxide. While the aseptic filler for bottles has been mainly described above, with the aseptic fillers for other containers than bottles, such as cups, trays, paper containers and pouches, the cleaning liquid or aseptic water can be removed in a shorter time and the productivity of the aseptic filler can be improved by driving the transfer devices that convey containers. FIG.3is a schematic elevation view of an aseptic filler for trays according to an embodiment of the present invention. Although the aseptic filler inFIG.3is shown as handling trays as containers, the aseptic filler having the same configuration can handle any cup-like container with a flange. A tray20supplied to the aseptic filler is held by a retainer21. The retainer21has a flat plate portion, and a fitting opening, into which the tray20is fitted, is formed in the flat plate portion. The tray20is held with a container portion thereof being inserted in the fitting opening of the retainer21and a flange22thereof resting on the flat plate portion. A large number of retainers21are provided, and a succession of trays are conveyed with the flanges22being horizontally oriented. The retainers21are attached to the transfer devices continuously traveling. The transfer devices continuously traveling are attached to an endless chain24at predetermined distances, the endless chain24horizontally running between sprocket wheels23aand23b. Once the endless chain24is driven, the endless chain24holding the retainers21continuously runs, and thereby transferring the trays20in the aseptic filler. As the trays20are conveyed in a chamber25of the aseptic filler shown inFIG.3, the trays20are sterilized, filled with a content, and sealed. The chamber25houses a sterilizing portion, a filling portion and a sealing portion. The tray20supplied to the chamber25is held on the retainer21and preheated by hot air blasted from above and below by a preheating nozzle26. The preheated tray20is sterilized with a sterilizer blasted from above and below by a sterilizer blasting nozzle27. The tray20blasted with the sterilizer is retained for a predetermined time. After that, heated aseptic air is blasted from a dry air nozzle28to activate the sterilizer deposited on the surface of the tray20to sterilize the tray20and then remove the sterilizer by drying the sterilizer After that, the tray20is filled with a sterilized content by a filling apparatus29, and the tray20filled with the content is thermally sealed with a sterilized lid material by a sealing apparatus30. The sealed tray20is discharged from the chamber25. Before operation of the aseptic filler, the interior of the chamber25is subjected to the COP treatment and the SOP treatment. In this process, when removing the cleaning liquid used for the COP treatment or removing the aseptic water used for the SOP treatment, the transfer devices that convey the trays20are driven to remove the cleaning liquid and the aseptic water deposited on the transfer devices. That is, the endless chain24that conveys the retainers21yet to hold trays20is driven. By driving the endless chain24, the cleaning liquid or aseptic water deposited on the endless chain24and the retainers21can be removed in a short time. FIG.4is a schematic elevation view of an aseptic filler for paper containers according to an embodiment of the present invention. A sleeve31, which is a cylindrical body having a substantially rectangular cross section having a wall composed of at least a plurality of layers of paper, is introduced into a chamber33by a sleeve supply device32. The sleeve31except for a part to be used to close the sleeve31is fitted onto a mandrel35provided on a turret34. Further, a sterilization apparatus36sterilizes the inner surface of the part of the sleeve31that is to be closed and has not been fitted onto the mandrel35and the outer surface of the sleeve31. After the sterilization, any remaining sterilizer is removed by hot air blasted by a drier device37. Further, the sleeve31is folded along a line that defines the bottom part of the paper container by a bottom part folding device, and the part having been heated by the drier device37is crimped by a bottom part sealing device38. In this way, the sleeve31is closed at one of the open ends thereof and shaped into a paper container having the shape of a bottomed cylinder. The formed paper containers are intermittently conveyed by a conveyor39, and a nozzle blasts a sterilizer gas generated by a sterilizer gas generator40to the inner surfaces of the paper containers. The sterilizer blasted to the paper containers is removed by hot air blasted from hot air nozzles41to the inner surfaces of the paper containers. The sterilized paper container is filled with a content sterilized by an apparatus separately provided by a filling device42. Further, the paper container is folded by a top part folding device along a line defining a top part thereof, the inner surface of the top part is heated by a top part heating device43, and the heated part is crimped by a top part sealing device44. In this way, the paper container is sealed. The sealed paper container is discharged from the chamber33. As the paper container is conveyed in the chamber33of the aseptic filler shown inFIG.4, the paper container is formed, and the formed paper container is sterilized, filled with a content, and sealed. The chamber33houses a paper container forming portion, a sterilizing portion, a filling portion and a sealing portion. Before operation of the aseptic filler, the interior of the chamber33is subjected to the COP treatment and the SOP treatment. In this process, when removing the cleaning liquid used for the COP treatment or removing the aseptic water used for the SOP treatment, the transfer devices that convey the paper containers are driven to remove the cleaning liquid and the aseptic water deposited on the transfer devices. That is, the turret34with the mandrels35on which sleeves are yet to be fitted is rotated, and the conveyor39for transferring paper containers that is yet to hold paper containers is driven. By driving the turret34and the conveyor39, the cleaning liquid or aseptic water deposited on the turret34and the conveyor39can be removed in a short time. FIG.5is a schematic elevation view of an aseptic filler for pouches according to an embodiment of the present invention. The aseptic filler for pouches shown inFIG.5is an apparatus that is supplied with a film, sterilizes the supplied film, shapes the film into a pouch, fills the pouch with a sterilized content and seals the pouch. Therefore, the aseptic filler includes a feeder device for a packaging film45, and a nozzle46that blasts a sterilizer to both surfaces of the packaging film45. The feeding device for the packaging film45is a driving device for continuously feeding the packaging film45from a feed roll of the packaging film45, and includes an infeed roller, various kinds of guide rollers arranged along the traveling path of the packaging film45, and guide rollers that hold the packaging film45therebetween. There are arranged guide rollers that guide the packaging film45fed from the feed roll to the sterilizer blasting nozzle46, a preheating device47that heats the packaging film45before a sterilizer is blasted to the packaging film45, and a heated air blasting apparatus48that blasts heated air to both surfaces of the packaging film45after the sterilizer is blasted to the packaging film45. The sterilized packaging film45is changed in direction by a roller49and conveyed to a filling and sealing portion50. The filling and sealing portion50is shielded by a chamber51, and the interior of the chamber51is subjected to the COP treatment and the SOP treatment before operation of the aseptic filler. The packaging film45conveyed into the filling and sealing portion50is changed in conveyance direction to the downward direction by a roller52. After that, a former53folds over the opposite side edges of the packaging film45along the conveyance direction. The folded packaging film45passes between a pair of lengthwise sealing rollers54(FIG.5shows only the one on the near side). Meanwhile, the lengthwise sealing rollers54heat and weld the overlaid parts of the opposite side edges of the packaging film45, thereby forming the packaging film45into a cylindrical shape. After that, a pair of crosswise sealing rollers55heat and weld the packaging film45at regular intervals in the conveyance direction, thereby sealing the packaging film45in the crosswise direction. The cylindrical packaging film45to be sealed crosswise is continuously supplied with various kinds of sterilized contents through a supply pipe56, and the crosswise sealing is sealed with liquid sandwiched between that seals the packaging film45at parts in which there is the content. After that, a notch for each pouch is formed in the packaging film45as required, and perforations are formed for each pouch in the crosswise direction, or the packaging film45is cut into pouches at the crosswise sealed parts by a cutting roller57. The resulting pouches fall into a discharging portion. Before operation of the aseptic filler, the interior of the chamber51is subjected to the COP treatment and the SOP treatment. Before performing the SOP treatment, the packaging film45is introduced into the chamber51. This is because the packaging film51cannot be introduced into the chamber51subjected to the SOP treatment without opening the chamber51. In this process, when removing the cleaning water used for the COP treatment or removing the aseptic water used for the SOP treatment, the rollers for nipping and transferring a packaging film45, the lengthwise sealing rollers54, the crosswise sealing rollers55and the cutting roller57, which are transfer devices for transferring the packaging film45, are driven to remove the cleaning liquid and the aseptic water deposited on the transfer devices. That is, by driving the rollers, which are transfer devices for the film45to be shaped, while feeding the film to the rollers, the cleaning liquid or aseptic water deposited on the rollers, which are transfer devices, can be removed in a short time. The packaging film45is conveyed into the chamber51after a sterilizer is blasted to the packaging film45by a sterilizer blasting apparatus46. In order to perform the SOP treatment of the interior of the chamber51with reliability, the packaging film45to be conveyed into the chamber51has to be sterilized before being conveyed into the chamber51. Although the present invention is configured as described above, the present invention is not limited to the embodiment described above, and various modifications are possible without departing from the scope and spirit of the present invention. REFERENCE SIGNS LIST 1chamber2rotary nozzle3twin-fluid nozzle4filling portion chamber11introduction wheel12filling wheel14capper wheel15discharging wheel | 40,503 |
11857691 | DETAILED DESCRIPTION Referring initially toFIGS.1A and1B, there is provided a disinfectant system in the form of an autonomous device100for performing a disinfectant operation within an enclosed space101defined by the walls, ceiling and floor of a room102when a predefined condition, in the form of the absence of a human being (not shown) within room102, is met. The purpose of the system is environmental decontamination and specifically to inactivate pathogenic organisms. Device100includes a disinfectant module103for carrying out the disinfectant operation when there is an absence of a human being within room102. A sensing module104is provided for sensing the presence of a substantially stationary human being within room102. Sensing module104includes:An energy emission detecting sensor105to detect energy emitted by humans;An energy reflection, shadowing, transmission or absorption detecting sensor106to detect energy reflected, shadowed, transmitted or absorbed by humans;A chemical detecting sensor107to detect chemicals emitted by humans;An electric field sensor108to detect local electric field disturbances, such as those created by the presence of a human;A physical disturbance sensor109to detect local physical disturbances, such as a pressure sensor to detect the presence of a human; andAn active or passive signal detecting sensor110to detect other active or passive signals from instrumented subjects. Disinfectant module103includes a disinfectant source120, which is preferably an ultra violet (UV) light source in the form of an ultra violet C (UV-C) source. One of the advantageous aspects of disinfecting using UV light is that once the light turns off, it is safe for a person to enter the space into which UV light was previously directed. Equally as advantageous is that as soon as UV-C source120is activated, it provides immediate germicidal activity. As such, the disinfectant operation is an interruptible process in the sense that the process can be paused to allow the space to be used, and recommenced once the person has left the space. Furthermore, the output of UV-C source120can be tailored. UV light sources can include any modules which emit UV radiation. In embodiments, these include, but not limited to, mercury vapour tubes (low and medium pressure) and UV LEDs. As noted above in this embodiment, the UV-C spectrum will be utilised from 200-280 nm for peak germicidal activity. In other embodiments, other sources of electromagnetic radiation at a wavelength and intensity that is microbiocidal are utilized including, for example, UV-A, UV-B or 405 nm light. In yet other embodiments, a combination of the aforementioned sources of electromagnetic radiation at a wavelength and intensity that is microbiocidal are utilized. In alternate embodiments, other types of disinfectant operations are used, for example, microbiocidal chemicals released into the air in room102. The disinfectant operation will be delivered to room102in a piecemeal manner as device100can utilize short opportunities that may arise from occupants briefly leaving room102. In alternate embodiments, the disinfectant operation will be delivered to room102in other than a piecemeal manner. In addition, the system can deliver a full dose when a space is purposely evacuated, such as for terminal decontamination after a patient is discharged from a room. Device100includes a dosage control module130which maintains a running record of the amount of UV energy that has been delivered to space101during the immediate history, for example the past 24 hours. This information is used to determine how long the UV lamps will be activated when a safe opportunity arises. The system will maintain a specific target dose level for room102. Target dose refers to how many Joules of UV radiation is delivered to the room over some nominal period (for example, 24 hours). This target dose will vary from space to space and will be determined from factors including: room size and geometry; UV lamp power; materials present; and time of occupancy of the space, amongst others. In some embodiments, there is an option to input data to the system which could affect target dosage, for example, whether a patient is carrying a high risk transmittable bacterial infection (such asClostridium difficile, for example). The disinfectant operation includes a timing component and an intensity component, the latter of which is based on the intensity of source120. Recalibration of disinfectant module103includes adjusting the timing component and/or the intensity component based on the set amount of time and within that time, how long the disinfectant operation was running and at what intensity. It will be appreciated that the minimum level of disinfecting will substantially prevent the spread of infections to human beings. However, in other embodiments, greater levels of disinfection will be utilised. The highest such level is complete sterilisation of room102. However, in most scenarios, total sterilisation is not required and will not be sought due to power conservation reasons. As noted above sensor105detects energy emissions in order to identify the shape and form of a human being. Sensor105includes a non-contact thermal imaging sensor. In other embodiments, sensor105includes a non-contact thermal temperature sensor. In another embodiment, sensor105includes an infrared sensor in the form of a long wavelength infrared camera. In yet other embodiments, sensor105is a combination of one or more of: a non-contact thermal imaging sensor; a non-contact thermal temperature sensor; and an infrared sensor. Long wavelength infrared cameras utilise thermal computer vision image processing for detecting infrared thermal heat signatures of human beings within room102. Long wavelength infrared (8-14 μm wavelength) cameras include Forward Looking Infrared (FLIR) Lepton cores. Such cameras are suitable for providing a thermographic video feed. This video feed is used as the subject of image processing functions tailored for detecting the thermal signature of a human body. Additionally, in some embodiments, infrared sensors also include a non-contact temperature sensor, such as a non-imaging thermal sensor. In one embodiment, the long wavelength infrared camera provides the primary sensing and the non-contact temperature sensor provides additional sensing to supplement the primary sensing, adding an additional layer of safety and efficacy to the system. In other embodiments, the non-contact temperature sensor provides the primary sensing. Sensor105is also able to detect energy emissions in order to identify macro-movement of a human being. In such embodiments, sensor105includes a non-image passive infrared (PIR) sensor for providing motion sensing. In other embodiments, other than PIR sensors are used. In other embodiments, tracking of macro-movements is carried out using a combination of imaging processing and long wavelength infrared cameras. Sensor105is further able to detect energy emissions in order to identify sound produced by a human being. In such embodiments, sensor105includes an array of microphones. Furthermore, sensor105is able to detect energy emissions in order to identify vibrations produced by a human being. In such embodiments, sensor105includes an accelerometer. Sensor106detects energy reflection, shadowing, transmission or absorption in order to identify the shape and form of a human being. Sensor106includes an imaging sensor in the form of a visible light camera. In an alternate embodiment, the imaging sensor is a short wavelength infrared camera. In yet other embodiments, sensor106is a radar sensor. Furthermore, sensor106is able to detect energy reflection, shadowing, transmission or absorption in order to identify macro-movement of a human being. In such embodiments, sensor106includes a ranging sensor, in the form of a radar sensor. In an alternate embodiment, the ranging sensor is an ultrasonic sensor. In yet another embodiment, the ranging sensor is a laser sensor. In yet another embodiment, the ranging sensor includes one or more of: a radar sensor, an ultrasonic sensor and a laser sensor. Sensor106is able to detect energy reflection, shadowing, transmission or absorption in order to identify micro-movement of a human being. In such embodiments, sensor106includes a non-contact sensor in the form of a Doppler sensor, more specifically in the form of a Doppler radar sensor. In another embodiment, the Doppler sensor is a Doppler ultrasonic sensor. In yet another embodiment, the Doppler sensor includes a Doppler laser sensor for laser scanning. In yet another embodiment, the Doppler sensor includes one or more of: a Doppler radar sensor, a Doppler ultrasonic sensor and a Doppler laser sensor. As alluded to above, sensor107aims to detect the metabolic activity of a human being, particularly in the form of chemical elements that are emitted by the human body and chemical reactions signifying the presence of a live human being. Sensor107includes a carbon dioxide detecting sensor. In another embodiment, sensor107includes a humidity sensor for sensing water vapour. In yet another embodiment, sensor107includes a volatile organic compounds (VOC) sensor. In an alternate embodiment, sensor107includes a combination of: carbon dioxide detection, humidity sensing and VOC sensing. Sensor108is able to detect local electric field disturbances in the presence of a human being. Sensor108includes a capacitance sensor which itself includes electrodes to for detecting the local changes in capacitance. As noted previously, sensor109aims to detect local physical disturbances caused by contact from a human being and necessitates physical contact with a human being in order to sense that human being. Sensor109takes the form of one or more pressure contact sensors used, for example, on hospital beds. Such contact sensors necessitate manual fitting of an additional device physically separated from device100. As noted above, other active or passive signal detecting sensors110are also utilised where required. These include devices or labels attachable to human beings including transponders or beacons such as radio-frequency identification (RFID) tags, infrared beacons, ultrasonic beacons and radiofrequency beacons, amongst others. It will be appreciated that different embodiments will utilise different combinations of sensors105to110depending on the requirements or certain situations and environments. Furthermore, in different embodiments, each of sensors105to110includes one or more of the specific sensor devices discussed above. Furthermore still, in different embodiments, each of sensors105to110includes a plurality of one or more of the specific sensor devices discussed above. That is:Energy emission detecting sensor105in different embodiments includes a combination of shape and form sensors (which in different embodiments includes a combination of different imaging sensors), macro-movement sensors, sounds sensors, vibration sensors and temperature change sensors.Energy reflection, shadowing, transmission or absorption detecting sensor106in different embodiments includes a combination of shape and form sensors (which in different embodiments includes a combination of visible light imaging sensors, short wavelength IR cameras and ultra-wide band radar sensors), macro-movement sensors (which in different embodiments includes a combination of ranging sensors such as radar, ultrasonic and laser) and micro-movement sensors (which in different embodiments includes a combination of Doppler sensors such as radar, ultrasonic and laser).Chemical detecting sensor107in different embodiments includes a combination of metabolic activity sensors such as carbon dioxide sensors, humidity sensors and VOC sensors.Electric field sensor108in different embodiments includes a combination of different electrical property sensors such as capacitance change sensors.Physical disturbance sensor109in different embodiments includes a combination of different pressure contact sensors.Active or passive signal detecting sensor110in different embodiments includes a combination of different devices or labels attachable to human beings, including transponders or beacons such as RFID tags, infrared beacons, ultrasonic beacons and radiofrequency beacons, amongst others. Most non-contact human detection sensors rely on some small amount of motion in order to detect human presence. Using a combination of sensors as discussed above (such as infrared sensors and micro-movement sensors) applied to room102, the system is able to detect the presence of a person even if they are completely still and covered, for example, under bedding. It is again emphasised that a many number of sensors can be utilised to provide varying levels of certainty of a correct reading. Given the adverse health effects of exposing UV or indeed some disinfectant chemicals to a person, there must be a high threshold that must be met to all but ensure that there are no person or persons present when the disinfection operation is occurring. As such, the level of certainty of a correct reading will generally increase with the increased usage of different numbers and types of sensors in varying positions around a room. The sensors will be positioned to monitor the entire enclosed space101. In some embodiments, the sensors are positioned to be monitoring in the direction of the emitted UV radiation or disinfectant chemicals. This ensures the direct path of emitted disinfectant is being constantly sensed for any human presence. In other embodiments, the sensors will be positioned to be monitoring in a direction other than that of the emitted disinfectant. In yet other embodiments, some sensors will be positioned to be monitoring in the direction of the emitted disinfectant and other sensors will monitor in other directions. The size and layout of room102, as well as the objects within it, will factor into the position of the sensors. Device100further includes a processing module140, in the form of a microprocessor that is in electrical communication with disinfectant module103, sensor module104and dosage control module130. Processing module140utilises algorithms to receive sensor data from sensor module104and mathematically calculate the probability that a human being is present in room102. Processing module140also utilises algorithms to determine the confidence that a discernible thermal mass detected by sensor module104is indeed a human being. Low confidence readings may have a high probability of being inaccurate. To avoid inaccurate readings governing the system, all sensor data shall pass through a probability filter which will discard low confidence readings. For example, there may be heated objects or medical devices within room102which emit significant amounts of infrared radiation. Mask subtraction techniques can be implemented to minimise false positive triggers. This involves subtracting a thermographic image of room102when unoccupied from future image frames of interest, filtering out any warm stationary, non-human objects which may be emitting IR radiation. Also there may be mechanical movement (such as fans) in the room that may affect a micro movement sensor. In some embodiments, algorithms that look for the distinctive pattern of human breathing are implemented to overcome this. In some embodiments, image processing is used to isolate any thermal body which may be a human body. In some of those embodiments, feature detection and recognition algorithms will be incorporated into this image processing. Ratios of feature sizes (width:height) and the total number of pixels a mass occupies all provide valuable data. If the probability is such that a person is not in the room, processing module140will communicate with disinfectant module103that it can commence the disinfectant operation, whilst also communicating with dosage control module130. Dosage control module130essentially monitors how long source120is activated and how much power is used by source120. The situation may be such that device100should shut off even if the room is absent of human beings at a point when room102is deemed to be completely sterilized or at an appropriate level of disinfection, as will be determined by dosage control module130. Furthermore, dosage module130can also provide an indication that deems room102to require a terminal clean, whereby the system prompts a staff member to arrange for the terminal clean. In embodiments, dosage module130includes UV power sensors for sensing exactly how much UV light has been exposed in the room. This sensing will provide further information from which dosage module130can make a judgement on the UV required in room102. In other embodiments utilizing chemical disinfectants, dosage module130includes chemical sensors to sense how much disinfectant has been circulated and makes a judgement in a similar fashion to embodiments using UV. The system will necessarily have a high safety threshold as information from several sensing technologies will be fused together to accurately protect against false negative triggers, that is, the system falsely believing the space is empty. It is noted that, in embodiments, an additional layer of manual protection is included. For example, once the system is ready to start the disinfectant operation, that is where no human presence is sensed in room102, system100will require an authorisation check before actually starting disinfectant operation. This authorisation check takes the form of an RFID tag that can be swiped at an authorisation point to confirm it is safe to proceed with the disinfectant operation. In other embodiments, the authorisation check takes the form of passcode to be entered into another authorisation point such as a keypad. However, it is emphasised that if the presence of a live human being is detected, providing the authorisation check will not result in the disinfectant operation. This will only occur if no human presence is sensed in room102. Some of the sensors, particularly the infrared sensors are able to detect if its field of view has been obscured or blocked. An absence of this feature could lead to the system suggesting un-occupancy of a space when in fact the cameras field of view has simply been blocked by some article. Device100includes a housing111that, in some embodiments, contains disinfectant module103and sensing module104. It will be appreciated that, in various embodiments, the substantive material of housing111is plastics, metal, a combination of plastics and metal, or others materials. In the embodiment illustrated inFIG.1B, housing111is configured to be mountable to one or more walls or surfaces of room102. In other embodiments, housing111is configured to be mountable or retrofitted to the ceiling of room102. In other embodiments, housing111contains any combination of the disinfectant module103, sensing module104, processing module140and dosage control module130. In yet other embodiments, each module has a separate housing, or some modules may be combined in the same housing while other modules are separately housed. In other embodiments where processing module140is physically spaced apart from housing111, processing module140is in wireless communication with disinfection module103, sensor module104and dosage control module130. However, in other embodiments, processing module140is hardwired to each of disinfection module103, sensor module104and dosage control module130. In various other embodiments, each of sensors105to110are housed in different spaced apart locations in different physical housings. In yet other various embodiments, some of those sensors are housed together, and others are not. For example, in one embodiment, sensor105, sensor106and sensor107are in one housing, sensor108is in another housing, and sensors109and110are in a further separate housing. Furthermore, in some embodiments, the different types of sensors within sensors105to110are in a combination of different housings. There are a many number of permutations of sensors and components in general being housed separately or together with certain other components and it will be appreciated to a person skilled in the art that this will depend on many factors including the layout of room102itself. Processor module140calculates required intensity and exposure time by assessing and factoring in how many people have been in the space and for how long. Device100is designed to be confined to space101being monitored, and in different embodiments, is either permanently fixed in place, semi-portable or mobile. The placement of device100is generally determined during the installation phase. It is noted that inFIG.1B, room102includes three wall-mounted devices100. However, it will be appreciated that more or less than three devices but can be more or less as required. Referring toFIG.2, in this embodiment, device100also includes a regular white light fluorescent room lamp145but connected to a separate power circuit and separately controlled. Referring toFIG.3, in this embodiment, device100is permanently physically mounted to a wall of room102. Referring toFIG.4, in this embodiment, device100is free standing and portable so the UV delivery can be somewhat adjusted in space101. However, it is crucial that any portable units are not moved outside of the monitored space as this could lead to the UV sources being activated in the presence of people. In such embodiments, safety mechanisms are built into device100so that any unauthorized movement of a portable device100will disable the disinfectant operation until such time as an authorization process is completed to re-activate device100. Similarly, such embodiments include a localisation technology to ensure the units remain positioned within the space being monitored by the system or to identify if the portable units have been moved outside space101that is being monitored. In some embodiments, this technology involves the use of beacons or fiducial markers on housing111of the portable device100which must be detected by an overseeing vision system or a type of electronic ranging system. This is to ensure that any portable unit moved outside of the monitored space are automatically deactivated so there is no chance of them being incorrectly activated in the presence of people. Referring toFIGS.1A and1Band more specifically toFIG.5, an information display unit150is included to display information regarding delivered UV and what level of decontamination can expected at any given time. In embodiments, suggestions can also be made as to when a room should be completely evacuated and allowed to run a full terminal disinfection cycle, these suggestions made in conjunction with dosage control module130. Display unit150shall clearly indicate useful information on the graphics screen near a main entrance door151to room102. In some embodiments, display unit150will incorporate a further entrance/exit sensor152to sense whether or not the entrance door is open or closed. This is critical in terms of safety, as the disinfectant operation cannot be turned on if the door is open as significant amounts of UV radiation could leak out into the corridor and potentially make contact with people. Display unit150also houses a doorway presence sensor153. This sensor will monitor a region154just outside of door151for shutting off the disinfectant operation before a person enters room102. In the illustrated embodiment, display unit150includes sensors152and153, but it will be appreciated that in other embodiments, these sensors will be independent and spaced apart from display unit150. Each portable device100will have wireless communication capabilities. Referring toFIG.6, a simplistic flow chart of the general operative steps of the disinfectant system is illustrated. The system will first check if entrance door151(is open or closed). If the door is open, the disinfectant operation ceases and continues to cease while the door is open. Once entrance door151is closed the system will check that no human beings or animals are sensed inside the room. As mentioned above, this process involves the output from the sensors being received and processed by the microprocessor to determine statistically if there is likely to be one or more human beings in room102. If the microprocessor determines that there are no human beings in room102, the system (by way if the microprocessor) will check dosage control module130to determine if room102has already received the maximum required dosage of disinfection and, if that is the case, the disinfectant operation ceases. Otherwise, the disinfectant operation will commence and continue to commence until a condition above is met to cease the operation. It will be appreciated that in other embodiments, the system is safe to operate regardless of whether entrance door151is open or closed. In such embodiments, the system will strictly rely on checking that no humans or animals are sensed inside room102. Although the systems and methods described herein are mainly directed towards sensing the presence or absence of live human beings, it will be appreciated that the sensing could be used for other mammals and other warm-blooded creatures. For example, applications of the system could be used at a veterinarian practice for sensing the presence (or lack of a presence) of humans and animals. Furthermore, the systems and methods described herein are mainly directed to use in hospitals or healthcare facilities. However, it is appreciated that other industries where contamination is of concern, such as the food processing and packaging industry, can utilize embodiments of the invention. System100, in particular processing module140, incorporates computer components and software to control the functioning of the system. As such, appropriate safety protocols are included within the system to avoid a software error/bug from incorrectly turning a UV source on. Furthermore, in embodiments, the system includes a data logging component for monitoring and recording in a database events and aspects of those events (such as timing and frequency of disinfectant operations). Such data is used for analysing a range of aspects of the system and the environment, such as work flows and power usage efficiencies, amongst others. The systems described herein provide many advantages over the prior art, including:The disinfectant operation can be run whenever there is no person in the room, not just between occupancies of patients. For example, when a patient (and any other person in the room) goes and to rehabilitation, or goes to the bathroom, or leaves the room for any reason, the system can take advantage of the absence by performing the disinfectant operation during those times of absence. The room is constantly monitored to ensure than any moments of absence at any time can be utilised for this opportunistic disinfection.The constant monitoring and disinfecting at all available times makes for a more efficient use of time, as the manual operation requirement is significantly, and in some cases entirely, removed. This is due to the system not requiring to be set up prior to every single use, and substantially negating the need to move the equipment.The use of non-contact sensing alleviates the need to have the devices built into existing objects in the room. This make the system particularly suited to retrofitting into existing spaces.Workflows in a hospital environment are under significant time pressure, and any process that detrimentally impact on workflows will not be feasible. The system not only avoids disrupting workflows, it even improves workflows when compared to existing space disinfection systems. With existing devices, staff and/or operators are required to manually check the room, retrieve the disinfectant device, move the device into the room and manually activate the device. This labour-intensive manual work is significantly reduced and in some cases completely removed due to the present systems described.Specifically regarding the integrated setup using multiple specifically positioned devices (such as the setup ofFIG.1B), each device is placed so that substantially all of the surfaces in a room are disinfected. As such, the possibility of surfaces not receiving adequate disinfection is significantly reduced.The system is extremely safe in that it is designed to very accurately sense the presence of a person and shut off the disinfectant operation if a person is present or enters a room. Given the use of UV in the disinfectant operation, the system has no choice but to provide such a high safety threshold, given the health implications of being exposed to UV radiation. The use of multiple sensors to all but ensure the absence of a human being in the proposed area to disinfect allows this very high safety threshold to be met.The operator of prior known UV disinfectant devices no longer has to travel to storage areas, transport the large device to a space of interest, set up, run, ensure no one enters the space, pack up and finally transport back to storage. With the systems described herein, the operator may only need to close the door of a room and the system functions autonomously. In some embodiments, there may not even be a need for an operator due to the autonomous function of the system activating the disinfectant operation whenever there is no human presence sensed in the room.The system using such opportunistic disinfection of the present systems leads to an overall reduction in germ levels at all times. The system keeps the bioburden in check and generally at a level which has been shown to reduce HAIs. Interpretation Unless specifically stated otherwise, as apparent from the following discussions, it is appreciated that throughout the specification discussions utilizing terms such as “processing,” “computing,” “calculating,” “determining”, analyzing” or the like, refer to the action and/or processes of a computer or computing system, or similar electronic computing device, that manipulate and/or transform data represented as physical, such as electronic, quantities into other data similarly represented as physical quantities. In a similar manner, the term “processor” may refer to any device or portion of a device that processes electronic data, e.g., from registers and/or memory to transform that electronic data into other electronic data that, e.g., may be stored in registers and/or memory. A “computer” or a “computing machine” or a “computing platform” may include one or more processors. The methodologies described herein are, in one embodiment, performable by one or more processors that accept computer-readable (also called machine-readable) code containing a set of instructions that when executed by one or more of the processors carry out at least one of the methods described herein. Any processor capable of executing a set of instructions (sequential or otherwise) that specify actions to be taken are included. Thus, one example is a typical processing system that includes one or more processors. Each processor may include one or more of a CPU, a graphics processing unit, and a programmable DSP unit. The processing system further may include a memory subsystem including main RAM and/or a static RAM, and/or ROM. A bus subsystem may be included for communicating between the components. The processing system further may be a distributed processing system with processors coupled by a network. If the processing system requires a display, such a display may be included, e.g., a liquid crystal display (LCD) or a cathode ray tube (CRT) display. If manual data entry is required, the processing system also includes an input device such as one or more of an alphanumeric input unit such as a keyboard, a pointing control device such as a mouse, and so forth. The term memory unit as used herein, if clear from the context and unless explicitly stated otherwise, also encompasses a storage system such as a disk drive unit. The processing system in some configurations may include a sound output device, and a network interface device. The memory subsystem thus includes a computer-readable carrier medium that carries computer-readable code (e.g., software) including a set of instructions to cause performing, when executed by one or more processors, one of more of the methods described herein. Note that when the method includes several elements, e.g., several steps, no ordering of such elements is implied, unless specifically stated. The software may reside in the hard disk, or may also reside, completely or at least partially, within the RAM and/or within the processor during execution thereof by the computer system. Thus, the memory and the processor also constitute computer-readable carrier medium carrying computer-readable code. Furthermore, a computer-readable carrier medium may form, or be included in a computer program product. In alternative embodiments, the one or more processors operate as a standalone device or may be connected, e.g., networked to other processor(s), in a networked deployment, the one or more processors may operate in the capacity of a server or a user machine in server-user network environment, or as a peer machine in a peer-to-peer or distributed network environment. The one or more processors may form a personal computer (PC), a tablet PC, a set-top box (STB), a Personal Digital Assistant (PDA), a cellular telephone, a web appliance, a network router, switch or bridge, or any machine capable of executing a set of instructions (sequential or otherwise) that specify actions to be taken by that machine. Note that while diagrams may only show a single processor and a single memory that carries the computer-readable code, those in the art will understand that many of the components described above are included, but not explicitly shown or described in order not to obscure the inventive aspect. For example, while only a single machine is illustrated, the term “machine” shall also be taken to include any collection of machines that individually or jointly execute a set (or multiple sets) of instructions to perform any one or more of the methodologies discussed herein. Thus, one embodiment of each of the methods described herein is in the form of a computer-readable carrier medium carrying a set of instructions, e.g., a computer program that is for execution on one or more processors, e.g., one or more processors that are part of web server arrangement. Thus, as will be appreciated by those skilled in the art, embodiments of the present invention may be embodied as a method, an apparatus such as a special purpose apparatus, an apparatus such as a data processing system, or a computer-readable carrier medium, e.g., a computer program product. The computer-readable carrier medium carries computer readable code including a set of instructions that when executed on one or more processors cause the processor or processors to implement a method. Accordingly, aspects of the present invention may take the form of a method, an entirely hardware embodiment, an entirely software embodiment or an embodiment combining software and hardware aspects. Furthermore, the present invention may take the form of carrier medium (e.g., a computer program product on a computer-readable storage medium) carrying computer-readable program code embodied in the medium. The software may further be transmitted or received over a network via a network interface device. While the carrier medium is shown in an exemplary embodiment to be a single medium, the term “carrier medium” should be taken to include a single medium or multiple media (e.g., a centralized or distributed database, and/or associated caches and servers) that store the one or more sets of instructions. The term “carrier medium” shall also be taken to include any medium that is capable of storing, encoding or carrying a set of instructions for execution by one or more of the processors and that cause the one or more processors to perform any one or more of the methodologies of the present invention. A carrier medium may take many forms, including but not limited to, non-volatile media, volatile media, and transmission media. Non-volatile media includes, for example, optical, magnetic disks, and magneto-optical disks. Volatile media includes dynamic memory, such as main memory. Transmission media includes coaxial cables, copper wire and fiber optics, including the wires that comprise a bus subsystem. Transmission media also may also take the form of acoustic or light waves, such as those generated during radio wave and infrared data communications. For example, the term “carrier medium” shall accordingly be taken to included, but not be limited to, solid-state memories, a computer product embodied in optical and magnetic media; a medium bearing a propagated signal detectable by at least one processor of one or more processors and representing a set of instructions that, when executed, implement a method; and a transmission medium in a network bearing a propagated signal detectable by at least one processor of the one or more processors and representing the set of instructions. It will be understood that the steps of methods discussed are performed in one embodiment by an appropriate processor (or processors) of a processing (i.e., computer) system executing instructions (computer-readable code) stored in storage. It will also be understood that the invention is not limited to any particular implementation or programming technique and that the invention may be implemented using any appropriate techniques for implementing the functionality described herein. The invention is not limited to any particular programming language or operating system. It should be appreciated that in the above description of exemplary embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, Figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed embodiment. Thus, the claims following the Detailed Description are hereby expressly incorporated into this Detailed Description, with each claim standing on its own as a separate embodiment of this invention. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those skilled in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination. Furthermore, some of the embodiments are described herein as a method or combination of elements of a method that can be implemented by a processor of a computer system or by other means of carrying out the function. Thus, a processor with the necessary instructions for carrying out such a method or element of a method forms a means for carrying out the method or element of a method. Furthermore, an element described herein of an apparatus embodiment is an example of a means for carrying out the function performed by the element for the purpose of carrying out the invention. In the description provided herein, numerous specific details are set forth. However, it is understood that embodiments of the invention may be practiced without these specific details. In other instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description. Similarly, it is to be noticed that the term coupled, when used in the claims, should not be interpreted as being limited to direct connections only. The terms “coupled” and “connected,” along with their derivatives, may be used. It should be understood that these terms are not intended as synonyms for each other. Thus, the scope of the expression a device A coupled to a device B should not be limited to devices or systems wherein an output of device A is directly connected to an input of device B. It means that there exists a path between an output of A and an input of B which may be a path including other devices or means. “Coupled” may mean that two or more elements are either in direct physical or electrical contact, or that two or more elements are not in direct contact with each other but yet still co-operate or interact with each other. Thus, while there has been described what are believed to be the preferred embodiments of the invention, those skilled in the art will recognize that other and further modifications may be made thereto without departing from the spirit of the invention, and it is intended to claim all such changes and modifications as falling within the scope of the invention. For example, any formulas given above are merely representative of procedures that may be used. Functionality may be added or deleted from the block diagrams and operations may be interchanged among functional blocks. Steps may be added or deleted to methods described within the scope of the present invention. | 41,719 |
11857692 | The figures depict various embodiments for purposes of illustration only. One skilled in the art will readily recognize from the following discussion that alternative embodiments of the structures and methods illustrated herein may be employed without departing from the principles described herein. DETAILED DESCRIPTION Discussed herein are systems and methods associated with automating, optimizing, and customizing air and/or water quality and cleaning solutions. For example, in some cases, an autonomous system may be configured to provide tunable output irradiance via ultraviolet (UV) luminaries. In other cases, the autonomous system may be configured to provide independent and decoupled UV light sources or luminaries with distinctive spectral responses. In this manner, the systems, discussed herein, allow for combining different light sources in the same structure, expanding functionality of a single system, reducing power consumption, and increasing overall lifespan of environmental quality systems. In an example implementation, the environmental quality system may include one or more luminaires coupled to a controller for providing tunable irradiance. In some cases, the controller may be configured to allow an operator to tune the irradiance or light output by the luminaries within specific spectrum ranges based on, for instance, an intended use of the environmental quality system, characteristics of an environment of the system, an industrial or business purposes of an associated facility, or the like. In some cases, the controller may be in communication with a user device and/or cloud based service to allow the operator to tune or otherwise update, edit, or change settings or characteristics associated with the irradiance output by the luminaries. In some examples, the environmental quality system may also be equipped with one or more sensors to detect or capture data associated with one or more environmental conditions associated with the system. For example, the system may be equipped with temperature sensors, humidity sensors, volatile organic compound (VOC) sensors, carbon dioxide sensors, particulate matter sensors, or the like. The data generated by the sensors may be provided to the controller and/or the cloud based service to detect the presence and/or determine identity of any anthropogenic activity, contaminants, components or compounds derived from the anthropogenic activity, and/or other compounds of interest present in the surrounding environment. The controller and/or cloud based service may then automatically tune or update the characteristics of the irradiation output by the system based on the current level anthropogenic activity, contaminants, and/or compounds of interest. For example, the controller or cloud based service may tune the characteristics of the irradiation output based on one or more predetermined heuristic and/or based on the output of one or more machine learned models or networks trained using the captured sensor data, data associated with anthropogenic activity, characteristics of the irradiation output, and/or the like. In some examples, the system may be configured to activate and deactivate the illuminators in response to the presence, levels, amount, percentage, density, concentrations of anthropogenic activity and/or contaminants, or the like in the surrounding environment. For example, if the concentration of anthropogenic activity meets or exceeds one or more thresholds, the system may activate or enable the illuminators to commence cleaning functions. Likewise, if the anthropogenic activity falls below the one or more thresholds or one or more additional thresholds, the system may deactivate or disable the illuminators (it should be understood that the activation and deactivation thresholds may differ). In this manner, the system may provide need based cleaning that may prolong the usable lifespan of the illuminators and, accordingly, the system, thereby reducing overall installation costs. Additionally, by disabling the illuminators when the anthropogenic activity is low (e.g., below the designated thresholds), the system may also reduce the overall operating expenses associated with the environmental quality system. In some examples, the illuminators may be polychromatic light sources that operate within a wide UV spectrum. The system may also, in addition to or lieu of the polychromatic light sources, include illuminators within the visible spectrum that may be used in combination and tuned to distinctive bands of the UV spectrum. In one specific example, the system may utilize a group of ultraviolet A (UVA) illuminators, a group of ultraviolet C (UVC) illuminators, a group of far UV excimer illuminators, and a group of low pressure mercury vapor illuminators. In this manner, the system may utilize illuminators that are less expensive to install, have lower operating costs (e.g., energy consumption), and increased life span when compared with conventional systems. In some cases, the system may also include one or more surfaces exposed to the illuminators that are coated or otherwise treated with a photocatalytic oxidizing (PCO) coating to assist with the PCO processes that apply to air and/or water applications by modulating distinctive irradiation spanning from the UVA bands through, for example, the UVC bands. For example, the surfaces may be coated with a catalyst, such as titanium dioxide which causes a reaction with UVC (and/or UVA) irradiation that converts the components derived from the anthropogenic activity, targeted contaminants or undesired chemical compounds into water, carbon dioxide, and/or other harmless detritus. In some cases, the coated surfaces may be a replaceable or removable section of the system, such as discussed in more detail below, that may allow for replacement or recoating to maintain desired levels of catalyzation with the UVC (and/or UVA) irradiation. In some cases, the environmental quality system may also be equipped with germicidal components that may operate concurrently with but in a decoupled fashion from the PCO components. For example, in some specific implementation, the environmental quality system may include a forced ventilation stage that utilizes a metallic impeller or other high temperature resistant material that may be irradiated by the illuminators to cause a reaction that may disinfect the air. In some cases, the impeller may be heat treated (calcination at about 500 degrees Celsius) after a nanostructured ceramic coating (e.g., titanium dioxide) is applied onto the surface using a known industrial coating processes. As an alternative, a polymeric impeller may be utilized and coated with a ceramic coating via a sol-gel method and treated at lower temperatures than a metallic impeller. In one example, the impeller or similar component is irradiated or illuminated by the UV light source tuned to one or more UV bands in order to activate the photocatalytic oxidation or PCO response of the nanostructured ceramic layer. Under these operating conditions, the environmental quality system generates hydroxyl radicals that constitutes a mechanism responsible for the air and/or water purification functionality of the current example. In some cases, UVC or germicidal light sources or illuminators may be placed within a chamber housing with the fan impeller as well as in an intake and exhaust manifold/ducts associated with the environmental quality system in order to disinfect the air or water flowing through the system at multiple locations. In some implementations, the system may be configured to project UVC light outwards (such as upwards) and along the laminar flow patterns defined by the exhaust geometry. In this manner, the system may act as a chamber-based air or water disinfection unit as well as an upper-air disinfection unit. Furthermore, the UVC light source can be installed onto a motorized actuator allowing it to be oriented inwards, towards the chamber inner walls, or outwards, based on the operating conditions described above. In some implementations, a controller balances the dosage of UV irradiance applied to the impeller or other PCO elements. In some cases, the system may be equipped with sensors to generate data that may be utilized to correlate and/or determine anthropogenic activity (such as CO2 sensors and particle matter PM 1.0, 2.5 and 10.0 micrometers). The determined anthropogenic activity may then be used by the controller to govern the germicidal irradiance/dosage regime (such as via an output of a machine learned model or network, hierarchal design, thresholding, or the like). The above-described operation of the embodiment addresses the important mismatch in life-span and reliability performance between UVC and UVA light sources of conventional systems. The environmental quality system, discussed herein, may maintain strict control over the individual UV band irradiance/dosage to drastically increase the reliability performance of the system and extend its overall life-span in comparison to conventional systems. In some implementations, in addition to servicing as an environmental quality system, the systems discussed herein may operate as a horticultural system. For instance, in these examples, the controller exerts direct control over visible-spectrum, UVA, UVB, UVC and/or far-UV illuminators, as discussed herein, in order to exploit growth cycles of the crops (photo morphology and photoperiodicity). In these cases, the use of specialized sensors or detectors (e.g., a multi-range particulate matter sensor) allows for the controller to adjust a germicidal dosage when airborne particulates are detected (which positively correlate to the presence of spores responsible of powdery mildew deposits). In this manner, the horticultural system may apply ad-hoc germicidal treatment of an air or water mass nearby the crops only when the airborne spores and/or pollen grains are detected. Under other operating condition, the horticultural system may be used for surface disinfection of the plant tissues and nearby surfaces in order to contain the spread of some powdery molds, spider mites, other microorganisms, and/or the like. In the horticultural system, the horticultural illuminators will have a form factor similar to the environmental quality systems discussed below with respect toFIGS.1-20. In these cases, the illuminators or light sources may be oriented towards the actual crops, the PCO engine may make use of an elongated cross-flow impeller moving air upwards and through the actual system, while allowing for the mass of air exhausted via the system to be exposed to the irradiance of germicidal illuminators. In some cases, a portion of the housing of the horticultural illuminators may also house UV illuminators (e.g. UVB illuminators combined with UVC illuminators) that may influence the growth cycle of the crop and may be used to irradicate mites and other pathogens. FIG.1is an example pictorial diagram of an environmental quality system100according to some implementations. In the current example, the environmental quality system100may include a controller102mounted on a support and heat dissipation structure104together with illuminators and/or illuminator power state drivers106(1)-(X). In some examples, the support and heat dissipation structure104may include a mechanical support structure that defines a shape and overall form factor of the assembly of the system100. The structure104may also serve for heat extraction and, accordingly, be constructed out of metal or a heat conductive polymer. The support structures104may define the array of illuminators as far as positioning and orientation of individual light sources. The support structure104also provides couplings or components for the installation of the system100, such as using hooks, bars, brackets and other known attachment components. In some examples, the support structure104may be installed as an auto-supported configuration or stand-alone system. The support structure104may also constitute a sub-system assembly that is designed as a drop-in solution that accommodates standard form factors such as troffers, high-bay and low-bay configurations, as well as bulb-like shapes. The support structure104also defines the points of attachment for external covers, weather-proofing components, lenses such as focusing lenses, reflectors and/or diffusers. The support structure104may also, in some examples, serves as a structure for the adaptation of exoskeletons and/or similar mechanical structures. An example of an adaptation may include the use of a stationary or articulated mounting bracket that support one or a plurality of forced ventilation devices, such as one or more fans or blades. In the current example, the drivers106may be configured to provide power or otherwise energize the illuminators at a level based on one or more signals generated by the controller102. For example, the drivers106may be onboard the illuminators and/or external power sources proximate to the illuminators, such as direct current (DC) power supplies, specialized drivers (e.g., constant-voltage, constant-current, a combination thereof, or other configurations as used in the solid-state lighting industry). In some cases, the drivers106may have higher voltage output capabilities, such as to excite gas discharge devices, such as low- and medium-pressure lamps, as well as the electrostatic discharge devices. In some cases, the drivers106may include ferro-resonance topologies, fly-back converters in various configurations (such as discontinued-mode, critical-conduction mode and continuous-mode, single-ended primary-inductance converters (SEPIC), boost and buck or boost/buck converters, and/or the like). In some cases, the illuminators may be powered directly via batteries, when applicable. In the current example, the controller102may be configured to modulate the output of each individual illuminator or light source in accordance with a dosage protocol for various operating modes either established prior to use or on-the-fly by the controller102. The modulation may be controlled by the controller102by generating or switching the signals that controls the power stage circuitry or the output of the drivers106that power the illuminators or light sources. For example, the controller102may utilize a pulse width modulation technique which include some sort of feedback to the controller102. For example, the feedback may include monitoring luminous output, junction temperature, metalclad board temperature, or the like. For example, as discussed herein, the irradiance levels outputted by each type of illuminator correlates to the injected current into the source and hence, the individual illuminator's irradiation output. The dosage delivered by the system100is also a function of the time at which the irradiance regime is sustained and the distance between the illuminator and the target being irradiated, say a region within certain physical constraints, a target body, a volume of air within a filtration system or the like. Hence, the close relationship between the location/distribution of the illuminators or light sources on the support structure104with respect to the target. It follows that this relationship is strongly influenced by the type of application or use of the system100. The ability to control each type of illuminator independently allows for the embodiment to deliver distinctive and decoupled irradiance levels for each specific UV band and, accordingly, a dosage protocols regimen that is UV band specific. In some cases, the controller102may utilize input provided by sensors108to adjust the operating mode and/or dosage protocols, by adjusting the irradiance levels of each type of illuminator in substantially real time based on various environmental factors. In these cases, the controller102may include a processor (e.g., microprocessor, microcontroller, DSP processor or the like) together with, for example, one or more machine learned models or networks, algorithms, hierarchies, thresholds, or the like. For instance, a linear regression technique that adjusts the dosage levels based on a direct feed of data generated by one or multiple sensors or a performance assessment algorithm, which makes use of a photodetector in order to adjust the irradiance levels of the different light source in order to compensate for their inherent degradation over time. In some implementations, the controller102may receive sensor data from the sensors108, input the sensor data into one or more machine learned model or otherwise process the sensor data to adjust or select the mode of operation or dosage protocols suitable for the current environmental conditions. The one or more machine learned model(s) may be generated using various machine learning techniques. In some cases, the machine learned models or networks may be trained using dosage protocols, environmental data associated with input and outputs to the environmental quality system100and the like. For example, the models may be generated using one or more neural network(s) and/or similar classification algorithms. A neural network may be a biologically inspired algorithm or technique which passes input data through a series of connected layers to produce an output or learned inference. Each layer in a neural network can also comprise another neural network or can comprise any number of layers (whether convolutional or not). As can be understood in the context of this disclosure, a neural network can utilize machine learning, which can refer to a broad class of such techniques in which an output is generated based on learned parameters. Artificial neural networks may be trained with evidence-based data that resulted from direct experimentation and/or scientific publications. As an illustrative example, one or more neural network(s) may generate any number of learned inferences or heads from the captured sensor and/or image data. In some cases, the neural network may be a trained network architecture that is end-to-end. In one example, the machine learned models may include segmenting and/or classifying extracted deep convolutional features of the sensor and/or image data into semantic data. In some cases, appropriate truth outputs of the model in the form of semantic per-pixel classifications (e.g., vehicle identifier, container identifier, driver identifier, and the like). Although discussed in the context of neural networks, any type of machine learning can be used consistent with this disclosure. For example, machine learning algorithms can include, but are not limited to, regression algorithms (e.g., ordinary least squares regression (OLSR), linear regression, logistic regression, stepwise regression, multivariate adaptive regression splines (MARS), locally estimated scatterplot smoothing (LOESS)), instance-based algorithms (e.g., ridge regression, least absolute shrinkage and selection operator (LASSO), elastic net, least-angle regression (LARS)), decisions tree algorithms (e.g., classification and regression tree (CART), iterative dichotomiser 3 (ID3), Chi-squared automatic interaction detection (CHAID), decision stump, conditional decision trees), Bayesian algorithms (e.g., naïve Bayes, Gaussian naïve Bayes, multinomial naïve Bayes, average one-dependence estimators (AODE), Bayesian belief network (BNN), Bayesian networks), clustering algorithms (e.g., k-means, k-medians, expectation maximization (EM), hierarchical clustering), association rule learning algorithms (e.g., perceptron, back-propagation, hopfield network, Radial Basis Function Network (RBFN)), deep learning algorithms (e.g., Deep Boltzmann Machine (DBM), Deep Belief Networks (DBN), Convolutional Neural Network (CNN), Stacked Auto-Encoders), Dimensionality Reduction Algorithms (e.g., Principal Component Analysis (PCA), Principal Component Regression (PCR), Partial Least Squares Regression (PLSR), Sammon Mapping, Multidimensional Scaling (MDS), Projection Pursuit, Linear Discriminant Analysis (LDA), Mixture Discriminant Analysis (MDA), Quadratic Discriminant Analysis (QDA), Flexible Discriminant Analysis (FDA)), Ensemble Algorithms (e.g., Boosting, Bootstrapped Aggregation (Bagging), AdaBoost, Stacked Generalization (blending), Gradient Boosting Machines (GBM), Gradient Boosted Regression Trees (GBRT), Random Forest), SVM (support vector machine), supervised learning, unsupervised learning, semi-supervised learning, etc. Additional examples of architectures include neural networks such as ResNet50, ResNet101, VGG, DenseNet, PointNet, and the like. In some cases, the system may also apply Gaussian blurs, Bayes Functions, color analyzing or processing techniques and/or a combination thereof. In some examples, the sensors108may include various or multiple types of sensors to determine various environmental conditions. For example, the sensors108may include temperature sensors108(A), VOC sensors108(B), humidity sensors108(C), CO2sensors108(D), particulate matter sensors108(E), as well as other sensors108(F) that may be usable to determine one or more environmental conditions. In some specific examples, the particulate matter sensors may include particular matter counters PM1.0, PM2.5 and/or PM10.0 or similar to determine the presence and amount of respiratory virus and other pulmonary diseases in the environment. The CO2sensors108(D) may be configured to generate data usable by the controller102to determine the presence and amount of anthropogenic activity. VOC sensors108(B) may include total volatile organic counters and derivatives thereof to generate data usable to assess air quality levels, such as in indoor applications. The temperature sensors108(A) and the humidity sensors108(C) may generate data usable to determine an effectiveness of an UVC germicidal/disinfection system. In some cases, the sensors108may also include an optical recognition sensor associated with a machine vision system (e.g., OpenCV and/or a pattern recognition algorithm such as You-Only-Look-Once (YOLO), or the like) to detect and quantify the number of individuals within a certain perimeter or environment and/or an ozone detector to generate data or signals that may be used to activate the UVC light sources or bands used to eliminate ozone presence from the mass of air being treated by the system100. The system100may also utilize an occupancy sensor based on passive infrared (PIR), Microwave, or similar detection techniques to determine the presence and/or number of humans within certain spatial constraints or environment. In some cases, an ambience light level detector or sensors may be used to determine when certain operating modes are to be initiated (such as differing operational modes during the day and at night). In some cases, the sensors108may be positioned within a facility, location, or environment associated with the environmental quality system100. In other cases, the sensors108may be coupled to the system100or the support structure104, such as at an intake location. In the current example, in contrast to conventional systems which are governed by pre-programmed runtime protocols or software routines, the system100operates in an autonomous fashion based on substantially real-time inputs and data that is used by the controller102together with machine learned models to generate or select operating modes and/or dosage protocols that are tailored for the specific environment and configured to extend the life-span of the UV illuminators (e.g., to turn off or reduce power provided by the drivers106when individual illuminators are unnecessary). As some example operational modes, the system100may include initially begin operation in factory programmed mode and/or a user programed or initiated mode. The initial mode allows for a quick configuration of the embodiment as per applicable standards that specify dosage limits that are influenced by geometrical constraints such as room size, distance to reflective objects and other surfaces, and the like. The system100may also include a discovery mode that operates in a continuous mode within some pre-established limit that are part of a fuzzy logic algorithm. The system100may also include an autonomous mode that operates under a supervised learning set of rules dictated by machine learning model and/or networks in the form of classification and/or linear regression models. In the autonomous operation mode, the embodiment relies solely on the input data provided by the sensors106associated with the system100as well on the input provided by onboard timers, counters and other logic gate inputs such as interrupt functions. In the current example, the controller102may be communicatively coupled to one or more communication interface(s)110. The one or more communication interfaces(s)110may enable communication between the system100and one or more other local or remote computing device(s) or remote services, such as remote sensors108, remote machine learning systems, remote processing systems, or the like. The communications interfaces(s)110may enable Wi-Fi-based communication such as via frequencies defined by the IEEE 802.11 standards, short range wireless frequencies such as Bluetooth, cellular communication (e.g., 2G, 3G, 4G, 4G LTE, 5G, etc.), satellite communication, dedicated short-range communications (DSRC), or any suitable wired or wireless communications protocol that enables the respective computing device to interface with the other computing device(s). FIG.2is an example pictorial diagram of an environmental quality system200according to some implementations. In the current example, the system200may receive air, generally indicated by arrows202, from an environment via an intake duct or manifold204. The air202from the environment may enter a chamber206including a propeller or impeller208of a fan210. The impeller208may be coated with a nanostructured ceramic (such as titanium dioxide). The fan210may cause the air202to flow within the chamber206in a circular motion for a period of time, generally indicated by arrow212. As the air202flows within the chamber206, one or more illuminators214may irradiate the air202as well as any anthropogenic compounds, contaminants or other chemical compounds present together within the air202. For example, the illuminators214may be wide angle UVA light sources (such as LEDs) to increase the irradiance coverage to the impeller208to assist with the PCO processes that apply to the air202(or water in other applications) by modulating distinctive irradiation spanning from the UVA bands through, for example, the UVC bands. In some cases, the nanostructured ceramic coating may act as a catalyst that causes a reaction with UVC irradiation and converts the anthropogenic components, contaminants or other chemical compounds into water, carbon dioxide, and/or other harmless detritus. As the air202exits the chamber206, the air may be irradiated again by the illuminators216positioned within the exhaust manifold218. The illuminators216may be a narrow angle UVC light source to project the irradiance far into the free space after the air202exits the exhaust manifold218, generally indicated by arrows220. In this manner, the air202may be irradiated multiple times to provide for improved air quality output. FIG.3is a flow diagram illustrating an example process associated with the environmental quality system discussed herein. The processes are illustrated as a collection of blocks in a logical flow diagram, which represent a sequence of operations, some or all of which can be implemented in hardware, software, or a combination thereof. In the context of software, the blocks represent computer-executable instructions stored on one or more computer-readable media that, which when executed by one or more processor(s), perform the recited operations. Generally, computer-executable instructions include routines, programs, objects, components, encryption, deciphering, compressing, recording, data structures and the like that perform particular functions or implement particular abstract data types. The order in which the operations are described should not be construed as a limitation. Any number of the described blocks can be combined in any order and/or in parallel to implement the processes, or alternative processes, and not all of the blocks need be executed. For discussion purposes, the processes herein are described with reference to the frameworks, architectures and environments described in the examples herein, although the processes may be implemented in a wide variety of other frameworks, architectures or environments. FIG.3is a flow diagram illustrating an example process300associated with an environmental quality system, such as the environmental quality system ofFIGS.1and2, according to some implementations. As discussed above, the environmental quality system may activate, deactivate, or adjust an irradiation level of one or more illuminations (e.g., UVA and/or UVC light sources) based on received sensor data, outputs of one or more machine learned models and/or networks, one or more thresholds (such as performance level indexes or weighted solutions), a combination thereof, or the like. At302, the environmental quality system may receive, from one or more sensors, sensor data associated with an environment (such as a building, vehicle, or the like). In some examples, the sensors may include temperature sensors, humidity sensors, volatile organic compound (VOC) sensors, carbon dioxide sensors, particulate matter sensors, other air quality sensors, or the like. At304, the environmental quality system may determine, based at least in part on the sensor data, an amount of particular matter in the environment. For example, the system may process the sensor data from one or more particulate matter sensors to determine an amount. At306, the environmental quality system may adjust or activate an irradiance level of UVC germicidal illuminators based at least in part on the amount of particulate matter and one or more particulate matter thresholds. In some cases, the system may input the sensor data into one or more machine learned models and receive the irradiance level (and/or a period of time to remain active for) as an output of the model. In other cases, the system may compare the amount of particulate matter to one or more performance levels or index-weighted heuristics (such as determined via testing, historical data or results, or via one more machine learned models and/or networks, a combination thereof, or the like). At308, the environmental quality system may determine, based at least in part on the sensor data, a level of CO2in the environment. For example, the system may process the sensor data from one or more CO2sensors to determine the level. At310, the environmental quality system may adjust or activate an irradiance level of UVC germicidal illuminators based at least in part on the level of CO2and one or more CO2thresholds. In some cases, the system may input the sensor data into one or more machine learned models and receive the irradiance level (and/or a period of time to active for) as an output of the model. In other cases, the system may compare the level of CO2(and/or other gases such as O3, CO, SO2, NH3, presence of heavy metals including lead) to one or more performance levels or index-weighted heuristics (such as determined via testing, historical data or results, or via one more machine learned models and/or networks, a combination thereof, or the like). At312, the environmental quality system may determine, based at least in part on the sensor data, an air quality metric associated with the environment. For example, the system may process the sensor data from a combination of sensors (such as temperature, humidity, and the like) to determine the air quality metric. At314, the environmental quality system may adjust or activate an irradiance level of UVC germicidal illuminators and/or UVA illuminators (and perhaps the air or water flow rate into the chamber) based at least in part on the air or water quality metric and one or more air quality thresholds. In some cases, the system may input the sensor data into one or more machine learned models and receive the irradiance level (and/or a period of time to active for) as an output of the model. In other cases, the system may compare the air or water quality metric to one or more performance levels or index-weighted heuristics (such as determined via testing, historical data or results, or via one more machine learned models and/or networks, a combination thereof, or the like). FIGS.4-7illustrates example400-700of a first environmental quality system402according to some implementations. In the current examples400-700, the environmental quality system402is a general-purpose lighting system that integrates visible spectrum illuminator or light sources, via for example light sockets410, that may be used for general purpose lighting while integrating a motorized forced-air mechanism404based on a cross-flow impeller406. This impeller406may be coated with a layer of a photocatalytic oxidizing ceramic with specialized microstructure exhibiting a desired PCO performance within the spectral emission of the illuminator408associated with the mechanism404. In the examples400-700, the illuminators408may be a series of LEDs sources tuned to a desired PCO performance of the ceramic coating and oriented towards the center axis of the impeller406. A separated set of illuminators416(e.g., germicidal LEDs) are oriented upwards such to increase a dwell time between the airflow propelled by the impeller406and the germicidal light sources. By increasing the dwell time, a desired dosage of germicidal UV irradiance may be applied to the circulating air within the system402. Moreover, a controller can also exert control or otherwise adjust the rotational speed of the impeller406and the intensity of the illuminators408to achieve the desired dosage. In some cases, the illuminators408(e.g., the germicidal LEDs) may be positioned upward with respect to the system402, generally indicated as416. As discussed herein, the system402may serve a dual purpose. For instance, the system402may operate as an air purifier by mineralizing organic compounds via the photocatalytic oxidizing surface irradiated with specialized illuminators (e.g., UVA, UVC, and/or combination thereof, or the like) and also as an air disinfection device by irradiating the treated air while in the PCO chamber or while being exhausted using a light source or second illuminators tuned within the germicidal spectrum (e.g., far-UV and UVC light sources). In some cases, the impeller406may be designed such that the impeller406may be replaced in-situ with ease. The replacement in-situ allows for the selection of an impeller406with the proper ceramic coating for the desired application or purpose of the system402. For instance, in a smell reduction strategy, an impeller406coated with silver doped titania oxide might be more effective than an impeller406coated with pure titania oxide coating. Accordingly, the illuminators408may also be tuned, spectral shifted, or otherwise optimized to enhance the PCO activity specific to the coating of the impeller406. In some cases, the impeller406may be a cross-flow fan, backward centrifugal fan, axial fan, or other type of fan. In the current example, the air may be input via an in-take manifold412on the bottom of surface of the system402and output via one or more exhaust manifolds414(or air flow diverter) on top of the system402as shown. The system402may also include ventilation fins422along a main body418that may include a reflective film along the top surface. The system402may also include a ventilated compartment420for housing various environmental sensors, as discussed herein, usable to determine the dosage protocol or levels associated with the illuminators408and/or416as well as, in some cases, the controller. FIGS.8-11illustrates example800f-1100of a second environmental quality system802according to some implementations. In the current example, the system802may include an air quality components integrated into a ceiling or industrial style fan. In this example, the blades804of the fan may be equipped with the air quality components, as discussed below. For instance, the blades804may be modified with respect to conventional fan blades in order to accommodate for upper air disinfection via specialized illuminators or light sources806(e.g., LEDs or the like) positioned directly on the blades804and oriented upwards. In some cases, additional illuminators810may be accommodated or located within a transverse slot808that may be machined into the blades defining a cavity that allows the illuminators810to irradiate directly on a treated surface812(e.g., coated with a PCO layer) of the system802in closed proximity to the illuminators810. During nominal operation, the upper air germicidal illuminators806disinfect the air mass engulfing the blades804with a dosage defined by the intensity of the illuminators806and the rotational speed of the blades804(which define the dwell time in which air mass flow interacts with the electromagnetic source of irradiance). Similarly, the transverse slot808machined into the blades804diverts a portion of the air interacting with the blade804—turbulent mixing at the point of entry and exit of this chamber, generally indicated by arrows814, which is treated via the PCO engine defined by the illuminators810and treated surface812integrated into this cavity defined by the slot808. In the current example, the system802may also include a wing816placed on the top surface of the blade804. Alternatively, the wing816may be positioned below the bottom surface of the blade804. The wing816defines a cavity818that accommodates additional illuminators820positioned to irradiate a bottom surface822of the wing816. The bottom surface822may also be treated (e.g., coated with a PCO layer) to establish a PCO engine (in which the air flow through this chamber is defined by the rotational speed of the fan). As discussed herein, the controller (not shown) may tune the irradiance spectrum of the illuminators818and/or810together with the rotational speed of the blades804in order to increase the efficacy of the PCO engines. It should be understood, that in the current example both a transverse slot808system and a wing816system are integrated into the blades804of the system802. However, it should be understood that in some implementations, the blades804may include either the transverse slot808system or a wing816system. In some cases, different blades804of the system802may incorporate different systems (e.g., some blades804include the transverse slot808system and other blades804include the wing816system). FIGS.12-15illustrates examples1200-1500of a third environmental quality system according to some implementations. In these examples, a portable environmental quality system1202is shown. The current example system1202may be similar to other implementations discussed herein while having a reduced size, dimensions, or footprint to allow for increased portability. Accordingly, the system1202is a compact and lower power unit (such as operating with direct current power) and suitable for portable and automotive applications (such as public transportation systems). The system1202may include POC illuminators1204configured within a chamber1206housing an impeller1208to irradiate directly on a treated surface (e.g., coated with a PCO layer) of the impeller1208or other surface of the chamber1206in closed proximity to the illuminators1206. The system1202may also include germicidal illuminators1210to irradiate the air, indicated by arrows1212, being output by the exhaust manifold1214. In some cases, the germicidal illuminators1210disinfect the air mass1212exhausted by the system1202with a dosage defined by the intensity of the illuminators1212and the speed of the airflow. Similarly, POC illuminators1204treat the airflow within the chamber1206with a dosage defined by the intensity of the illuminators1204and a speed of a perpendicular inward airflow, generally indicated by arrows1216, within the chamber1206. A controller may control characteristics of the illuminators1204and1210as well as a speed of a mechanical drive unit1218coupled to the impeller1208. In this manner, the controller may determine a dosage protocol from sensor data generated by sensors, generally indicated by1220. The controller may then determine based on the dosage protocol control signals for the illuminators1204and1210and the mechanical drive unit1218. In this example, the mechanical drive unit1218may be powered by a power source1222. In the current example, the system1202includes a base1230and a cover1224. The cover may include a main intake grid1226for allowing air from the environment to enter the chamber1206and a sensor intake grid1228to allow the sensor1220to sample the air from the environment. FIGS.16-19illustrates examples1600-1900of a fourth environmental quality system according to some implementations. In the current example, an environmental quality system1602may include an upper air germicidal illuminator with integrated PCO treatment unit and may operator similarly to the environmental quality system402discussed above. For example, the system1602may operate with one or more cross-flow impellers1604and the system1602is designed as an upper air unit per ASHRAE definitions, in which germicidal illuminators are installed at a designated height (such that individuals within an environment are not direct exposure to the germicidal wavelength irradiation). In the current example, germicidal illuminators1606are oriented upwards projecting the irradiation towards the ceiling and upper portion of an environment. In some cases, the germicidal illuminators1606may irradiate air as the air is exhausted from the impeller chamber via an exhaust manifold1608. The system1602also incorporates a PCO engine intended to serve as source for the mineralization of total volatile organic matter and odors and the like (e.g., by way of mineralization via the photocatalytic oxidation activity of a ceramic coating applied onto the fan's impeller, as discussed herein). In this particular example, the impeller1604has a form of a cross-flow fan and may be coated with a with a photocatalytic oxidizing layer that may mineralize the VOC and odors within the air when irradiated by the POC illuminators1610. As discussed above, a controller together with one or more machine learned models or networks may determine a dosage protocol based at least in part on sensor data representing a current state of the environment. The controller may then apply the dosage protocol based at least in part by adjusting characteristics of the illuminators1606and/or1610as well as a rational speed of the impeller1604. As one illustrative example, in the event that the environment is unoccupied as determined by the sensor data, the system1602may operate as air purification unit, thereby running the PCO illuminators1610and the impeller1604(e.g., the PCO engine) while disabling the germicidal illuminators1606. In the event that anthropogenic activity is detected, the germicidal portion of the embodiment is activated. In the current example, a housing1612of the system1602may have an airfoil shaping envelop structure1618. The housing1612may include an intake area1614and two exhaust manifolds1608and1616on either side of the airfoil shaping envelop structure1618. In the above examples and implementations ofFIGS.2-20the environmental quality systems are discussed with respect to treating air. However, it should be understood by one skilled in the art that the systems, methods, and processes may be applied to treating fluids (such as water) in a similar manner. Accordingly, the systems ofFIGS.1-20may be applied to treat or process air, gases, fluids, water, and the like as discussed herein. For example, the systems may include an intake area for receiving the fluids or gases and exhaust manifold for outputting the fluids or gases. The system may also include by a PCO engine and/or germicidal engine including illuminators and/or an impeller and/or chamber treated with a photocatalytic oxidation layer. As one illustrative example, a water based environmental quality system may be tuned based on environmental sensing (e.g., one or more water quality sensors, such as temperature sensors, color sensors, particle sensors, pH sensors, conductivity sensors, and the like) as well as know variables, such as pH level, electrical conductivity in water, total dissolved solids level, turbidity, dissolved gases, color sensing, and the like. The water based system may include distinctive UV illuminators or light sources, a volume defined by a chamber geometry, in which maximum irradiance levels are attained, and, in some instances, secondary illuminators or light sources and one or more mechanical actuator in the form of propellers, submersed pumps, external pumps, or the like. The water based system may also operate in modes as previously described above (e.g., as a germicidal disinfection devices and as a purifier via the reaction of the UV irradiance in different bands interacting with photocatalytic oxidizing coatings applied to the inner walls of the chamber, rotating or moving parts of the mechanical actuator such as impellers or propellers, and similar components). In one implementation, the water based system is fully submersible with the illuminators or light sources such as LEDs housed within watertight compartment with one or more transparent windows or panels. The windows may have above a threshold level of UV transmittance (such as high purity fused quartz glass components). Moreover, the compartment may be configured in the form of a subcomponent of the treatment chamber, such that medium treated (water or any other liquid or gas) may be exposed to maximum irradiance levels while reducing the energy input to the system. Due to low energy consumption, this system is ideal for battery operations and photovoltaic or other renewable energy sources applications in which there limited or absence of “mains or shore” power sources as rural or remote locations, swimming pools, fish tanks, or even applications such as the water treatment in airplanes or ships. In another embodiment, the water based system may be adapted to water filtration systems, as pre-filtering or post-filtering stage such as the ones used in commercial and residential applications and typically installed at the service entrance of the facility. An example of such implementation consists of a well pump and storage system, which makes use of a filtering stage to reduce suspended sediments that, if nor removed, will absorbed a high amount the UV irradiance. The water based system, in some cases, may be inserted into the same vessel or tank defining the filtering stage or adapted as a self-contained assembly in the form of a secondary or post-filtering stage. The water based system may also be constructed in the form of individual and fully contained standalone assemblies (herein “UV treatment cells”) that may be interconnected in tandem configurations or parallel configurations such that a targeted UV dosage is attained as function of a certain flow requirement. If more than one mechanical actuator is used in the system or assembly to control the flow rate, these mechanical actuators may be synchronized via a user control unit, such as described above with respect toFIGS.1-20. In this example, the control unit may sense the water parameters and if determined that an above average (elevated) dosage is required due the detection of specific (e.g., more UV resilient) microorganisms or certain chemical compounds, additional UV treatment cells are activated. The use of the UV treatment cells allows for automating the control of the dosage imparted to the medium being treated and for the implementation of very effective energy conservation schemes or operating modes. It follows that a tandem or series results into the most simplistic configuration in which one or more UV treatment cells are used, as the follow is maintained constant through the cell array, the UV illuminators or light sources are simply modulated in output or simply, turned ON or OFF as needed. But, when multiple UV treatment cells are connected in parallel, the use of control valves associated to individual or cluster of cells might be required in order to maintain and control the required flow rates. Although the subject matter has been described in language specific to structural features, it is to be understood that the subject matter defined in the appended claims is not necessarily limited to the specific features described. Rather, the specific features are disclosed as illustrative forms of implementing the claims. EXAMPLE CLAUSES A. An adaptive autonomous lighting luminaire or system that operates within the full UV spectrum by independently exerting control of groups of light sources with distinctive irradiation and spectral responses. B. An adaptive autonomous lighting luminaire or system that operates within the full UV spectrum by independently exerting control of groups of light sources to generate polychromatic irradiance output. C. A lighting luminaire or system operating within the full UV spectrum relying on the use of different sensors associated to a controller; the controller configured to adjust the irradiance levels within the different UV bands being implemented in a decoupled and independent way. D. The lighting luminaire of claim C, wherein: the controller implements the UV bands as at least one of the following: only UVA, only UVC, UVC+222 nm, or UVA+UVC. E. A lighting luminaire or system exerting independent and decoupled control over distinctive groups of UV light sources with unique reliability performance level and distinctive lifespan to provide ad-hoc control of each group of distinctive UV light sources such that the overall reliability performance and life-span of the assembly is increased. F. A lighting luminaire or system that operates within the full UV spectrum and exerts control over different groups of specialized UV lighting sources with the purpose of optimizing the energy consumption of the lighting luminaire or system by delivering dosage specific to each UV band of interest on an “as needed” basis. G. A photocatalytic oxidation reactor engine comprising a photocatalytic oxidation reactor irradiated with UVA LEDs or a combination of UVA+UVC light at irradiance levels determined by the output signal/data provided by indoor air quality or environmental sensors, while concurrently controlling the irradiance levels of decoupled germicidal light sources built into the luminaire or lighting system; the control of the light sources is also governed by the response of one or more sensors that assess the levels of nearby anthropogenic activity. H. A system for use in horticultural applications in which groups of light sources within specific UV bands irradiate the crops and associated surfaces to control the growth rate of the crops by impacting the crops photo morphism cycles and by delivering the proper UVC dosage as part of a germicidal surface disinfection strategy. I. The system of H, fitted with secondary UVC light sources that are activated once airborne spores and other pathogens are detected using particulate matter sensors type PM 1.0/2.5/10.0 micrometer particle counters. These secondary light sources are either associated with an air disinfection chamber or are operated as direct radiators projecting light upwards into the surroundings of the luminaire of lighting system. J. An air disinfection system or germicidal UVC system in which the irradiance output levels are adjusted to match optimum operating conditions based on environmental data provided by temperature and humidity sensors associated to the luminaire of lighting system. K. A system utilizing specialized sensors associated to a luminaire or lighting system grouped mainly into sensors that directly correlate to indoor air quality levels and sensors that correlate to anthropogenic activity, allowing to control a PCO reactor and germicidal UV light sources in a decoupled and independent way, based on the output of these groups of sensors. L. The system of K, further comprising an occupancy sensors to control optional visible light spectrum sources. M. The system of K, further comprising, a smart controller based on a microprocessor or microcontroller-based architecture that, in combination with the output produce by the occupancy sensors, allows for the use of machining learning models and/or networks that allow for the selection of the irradiance levels and dosage applied within the different UV bands. N. An adaptive autonomous lighting luminaire or system of A, B, C, or D, fitted with a communication board that provides connectivity to the luminaire of lighting system in the form of wired and wireless interface and allows for the embodiment to be controlled via downloadable applications, building management systems, SCADA consoles and/or cloud-based services. O. An adaptive autonomous lighting luminaire or system of A, B, C, or D, further comprising an adaptation module or sub-system that is coupled to standard lighting form factors including at least one of a high-bay fixture, a low-bay fixture, a troffer, or an acorn bulb-like fixture. P. A environmental quality system comprising a controller configured to control the dosage applied to an air mass flowing through or near the system, by controlling the rotational speed of the fan used as source of forced ventilation and the output intensity of the light sources under consideration. Q. The environmental quality system of P, wherein the controller is configured for self-adjusting and/or self-regulating based on data received from sensors and a logic controller associated with a physical environment surrounding the environmental quality system. R. A fan impeller coated with a photocatalytic oxidizing (PCO) ceramic layer that can be replaced in-situ, such that an impeller optimized coating can be used instead, based on the measured air quality characteristics. This allowing for these novel devices to be upgraded after installed in the fields. S. An adaptive autonomous lighting luminaire or system that operates within the full UV spectrum by independently exerting control of groups of light sources with distinctive irradiation and spectral responses including a PCO engine associated with a fluid tank exposed to direct sunlight, allowing for the use of photovoltaic or similar renewable energy sources. T. The adaptive autonomous lighting luminaire or system of S that operates via renewable energy sources include at least one of photovoltaic or hydroelectric. U. The adaptive autonomous lighting luminaire or system of T wherein the system is installed within the fluids of the tank and operates at reduced energy consumption when submerged. V. The adaptive autonomous lighting luminaire or system of T wherein the system is installed in a drain or supply valve associated with the tank. W. The adaptive autonomous lighting luminaire or system of S that operates via battery packs or power storage device for portable applications and energy constrained application such as commercial aviation and similar implementations. While the example clauses described above are described with respect to one particular implementation, it should be understood that, in the context of this document, the content of the example clauses can also be implemented via a method, device, system, a computer-readable medium, and/or another implementation. Additionally, any of examples A-W may be implemented alone or in combination with any other one or more of the examples A-W. | 56,208 |
11857693 | DESCRIPTION OF THE EMBODIMENTS The technical scheme of the present invention will be further illustrated in detail in combination with embodiments and comparative examples as below, but the invention is not limited to these specific embodiments. Methods used in the embodiments are ordinary methods, unless otherwise specifically illustrated. Hydrogels are detected by the following detection methods in the invention. Detection of Gelation Time: (1) Preparation of samples to test: The first component containing nucleophilic functional groups is dissolved in a buffer solution at pH 7-12 to obtain a solution A, which is transferred into one syringe of a two-component mixer. The second component containing electrophilic functional groups is then dissolved in a buffer solution at pH 2-8 to obtain a solution B, which is transferred into the other syringe of the two-component mixer. The two-component mixer is installed for standby use. (2) Detection of gelation time: The two-component mixer is pushed evenly. The solution A and the solution B are sprayed onto a watch glass after being mixed in the two-component mixer. Timing is started at the same time until a gel is formed completely (no flowing liquid), the time is recorded as the gelation time. Detection of Swelling Ratio: Swelling ratio refers to the percentage increase in mass when swelling saturation is achieved in PBS solution after effective cross-linking of the hydrogel. It is determined following the steps below: (1) Preparation of samples to test: The solution A and the solution B are charged onto the two-component mixer and injected into a watch glass to form a gel according to the preparation method of samples to test as described in the above detection of gelation time. The resulting gel is cut into cubic gel of 1 cm*1 cm*1 cm. The hydrogel samples are precisely weighed. (2) A PBS buffer solution at pH 7.4 is formulated. (3) Detection of swelling ratio: samples prepared in (1) are transferred into a ground triangular flask, into which is also added the PBS solution at pH 7.4 which has been preheated to 37±1° C. The amount of the PBS solution is at least 40 times the mass of the samples. The ground triangular flask containing samples is then transferred into an incubator at 37±1° C. 24 h later, samples are taken out and removed the surface moisture with a filter paper, and weighed. The swelling ratio of the gel is calculated following the formula below. Swelling ratio of gel=(sample weight after swelling−sampling amount)/sampling amount×100% Detection of Bursting Strength: In addition to the gelation time and the swelling ratio, the bursting strength of hydrogel is also an important index of the material, which reflects the mechanical properties of the hydrogel during use. The detection method is as below: (1) Taking fresh hog casing, in which a hole with a diameter of about 0.16 cm±0.02 cm is cut, ready for use. (2) The solution A and the solution B are charged onto the two-component mixer according to the preparation method of samples to test as described in the above detection of gelation time. (3) The two-component mixer is pushed to form a hydrogel of specified thickness on the hole of the casing; after the gel is formed completely, pressure is applied evenly under the casing until the gel is broken or peeled off, and the maximum pressure is recorded. Detection of Degradation Time In Vitro: (1) Preparation of samples to test: The solution A and the solution B are charged onto the two-component mixer and injected into a watch glass to form a gel according to the preparation method of samples to test as described in the above detection of gelation time. The resulting gel is cut into cubic gel of 1 cm*1 cm*1 cm. (2) A PBS buffer solution at pH 7.4 is formulated. (3) Detection of degradation time in vitro: the samples prepared in (1) are placed into a closed container with a PBS buffer solution, and transferred into an incubator at 37±1° C. The change of samples in the buffer solution is observed until it is invisible to the naked eyes, that is, the degradation time of the gel in vitro. Cytotoxicity Test: The solution A and the solution B are charged onto the two-component mixer and injected into a watch glass to form a gel according to the preparation method of samples to test as described in the above detection of gelation time. Except for the swelling absorption capacity, extraction is conducted by adding 1.0 ml extracting medium per 0.1 g, in which the extracting medium is an MEM culture medium containing serum, the extracting temperature is 37±1° C., and the extracting time is 24±2 h. The cytotoxicity test is performed with the extract as the test solution according to the test method specified in GB/T16886.5-2017, and rated according to United States Pharmacopeia. Intradermal Reaction Test: The solution A and the solution B are charged onto the two-component mixer and injected into a watch glass to form a gel according to the preparation method of samples to test as described in the above detection of gelation time. Except for the swelling absorption capacity, extraction is conducted by adding 1.0 ml extracting medium per 0.1 g, in which the extracting medium is saline and cottonseed oil, the extracting temperature is 37±1° C., and the extracting time is 72±2 h. The intradermal reaction test is performed with the extract as the test solution according to the test method specified in GB/T 16886.10-2017. Acute Systemic Toxicity Test: The solution A and the solution B are charged onto the two-component mixer and injected into a watch glass to form a gel according to the preparation method of samples to test as described in the above detection of gelation time. Except for the swelling absorption capacity, extraction is conducted by adding 1.0 ml extracting medium per 0.1 g, in which the extracting medium is saline and cottonseed oil, the extracting temperature is 37±1° C., and the extracting time is 72±2 h. The acute systemic toxicity test is performed with the extract according to the test method for intraperitoneal injection specified in GB/T 16886.11-2011. Antibacterial Test: The bacterial suspension is in direct contact with the antibacterial products. The antibacterial rate is calculated to determine whether the antibacterial products have antibacterial capacities. Bacteria:Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa. Preparation of Medical Sealant Glue Capable of Promoting Wound Healing Embodiments 1-9 and comparative examples 1-3, following the mass ratios shown in Tables 1-1 and 1-2 below, the first component containing nucleophilic functional groups is dissolved in buffer solutions at different pH values as shown in Table 1-2 below to obtain the solution A, which is transferred into one syringe of a two-component mixer, and the second component containing electrophilic functional groups is then dissolved in buffer solutions at different pH values as shown in Table 1-2 below to obtain the solution B, which is transferred into the other syringe of the two-component mixer. The two-component mixer is installed, and a nozzle is installed on it to push the two-component mixer and eject the liquid in the two syringes after being mixed in the two-component mixer, thus rapidly forming the medical sealant glue capable of promoting wound healing. TABLE 1-1The composition of the medical sealant glue capable of promoting wound healingComposition of theEmbodi-Embodi-Embodi-Embodi-Embodi-Embodi-Embodi-sealant gluement 1ment 2ment 3ment 4ment 5ment 6ment 7FirstDendritic8.549componentpolyethylene(mg)imine (1500Dalton)Dendritic264.510polypropyleneimine (2500Dalton)Dendritic136.510poly-L-lysine(2000 Dalton)Dendritic6.59polyamide(2000 Dalton)Adipose-0.50.5derivedmesenchymalstem cellsPlacenta-0.3derivedmesenchymalstem cellsBone marrow1.0mesenchymalstem cellsHyaluronic0.50.31.0acidChitosan1.50.61.5hydrochlorideChitosan1.20.750.61.5acetateChitosan3.00.751.5lactateCompar-Compar-Compar-ativeativeativeComposition of theEmbodi-Embodi-exam-exam-exam-sealant gluement 8ment 9ple 1ple 2ple 3FirstDendritic13132014.5componentpolyethylene(mg)imine (1500Dalton)Dendritic6.5polypropyleneimine (2500Dalton)Dendriticpoly-L-lysine(2000 Dalton)Dendritic6.5polyamide(2000 Dalton)Adipose-0.50.50.50.5derivedmesenchymalstem cellsPlacenta-derivedmesenchymalstem cellsBone marrowmesenchymalstem cellsHyaluronic0.5acidChitosan1.51.51.5hydrochlorideChitosanacetateChitosan1.5lactate TABLE 1-2The composition of the medical sealant glue capable of promoting wound healingComposition of theEmbodi-Embodi-Embodi-Embodi-Embodi-Embodi-Embodi-sealant gluement 1ment 2ment 3ment 4ment 5ment 6ment 7Second(2-arm-PEG-SS)30050component(3000 Dalton)(mg)(2-arm-PEG-SG)1005075(4000 Dalton)(2-arm-PEG-SA)7515075(3500 Dalton)(2-arm-PEG-SSet)15075150(3500 Dalton)Buffer solutions for the4424444second component (pH)Buffer solutions for the1012710101010first component (pH)Compar-Compar-Compar-ativeativeativeComposition of theEmbodi-Embodi-exam-exam-exam-sealant gluement 8ment 9ple 1ple 2ple 3Second(2-arm-PEG-SS)150component(3000 Dalton)(mg)(2-arm-PEG-SG)(4000 Dalton)(2-arm-PEG-SA)(3500 Dalton)(2-arm-PEG-SSet)150150150150(3500 Dalton)Buffer solutions for the47.4444second component (pH)Buffer solutions for the107.4131010first component (pH) The physicochemical properties and biological properties of the medical sealant glue are detected respectively according to the processes for detecting the gelation time, the swelling ratio, the bursting strength, and the degradation time in vitro, the cytotoxicity test, the intradermal reaction test, the acute systemic toxicity test and the antibacterial test, with the results shown in Table 2 and Table 3. TABLE 2Detection results of the medical sealant glue capable of promoting wound healingDetectionresults ofthe sealantEmbodi-Embodi-Embodi-Embodi-Embodi-Embodi-Embodi-gluement 1ment 2ment 3ment 4ment 5ment 6ment 7Gelation15101111time (s)Swelling201003525951048ratio (%)Bursting220100250215115245231strength(mmHg)Degradation12521.51101.53000.5time (days)CytotoxicityGrade 1Grade 1Grade 1Grade 1Grade 1Grade 1Grade 1IntradermalGrade 1Grade 1Grade 1Grade 1Grade 1Grade 1Grade 1reactionAcuteNoNoNoNoNoNoNosystemictoxicity(Yes orNo)DetectionCompar-Compar-Compar-results ofativeativeativethe sealantEmbodi-Embodi-exam-exam-exam-gluement 8ment 9ple 1ple 2ple 3Gelation17.5Ungelled0.51time (s)Swelling3123/12545ratio (%)Bursting220218/215212strength(mmHg)Degradation2120/0.25120time (days)CytotoxicityGrade 1Grade 1/Grade 1Grade 1IntradermalGrade 1Grade 1/Grade 1Grade 1reactionAcuteNoNo/NoNosystemictoxicity(Yes orNo) As can be seen from the data in the table above, the gelation time of the medical sealant glue is mainly related to pH values of the acidic buffer solution and the basic buffer solution. When the concentration and proportion of the nucleophilic component and the electrophilic component are in certain ranges, the pH of the acidic buffer solution is 4, and the pH of the basic buffer solution is 10, the medical sealant glue can gelatinize within 1 s. The comparison of Embodiments 1-9 shows that, the bursting strength of the medical sealant glue is related to the concentration of the nucleophilic component and the electrophilic component. This is because that, with the increase of the concentration of the nucleophilic component and the electrophilic component, the formed network structure becomes denser, and there are more crosslinking points, so that the medical sealant glue has greater bursting strength. The comparison of Embodiments 1-9 shows that, the swelling ratio and the degradation time of the medical sealant glue are related to polyethylene glycol-modified functional groups, the concentration of the nucleophilic component, the concentration of the electrophilic component, and the ratio of the two components. As the length of hydrophobic chain segments of polyethylene glycol-modified functional groups increases, the swelling ratio of the medical sealant glue decreases gradually, and the degradation time extends gradually, too; as the concentration of the nucleophilic component and the electrophilic component increases, the swelling ratio of the medical sealant glue decreases gradually, and the degradation time extends gradually, too. The comparison of Embodiments 1-9 and Comparative example 2 shows that, as the remaining active amino component in the system increases, the swelling ratio of the medical sealant glue increases gradually, and the degradation time is gradually reduced. It is known from Comparative example 1 that, when the pH values of the acidic buffer solution and the basic buffer solution are not in the specified ranges, the medical sealant glue is unable to gelatinize. The comparison of Embodiments 1-9 and Comparative examples 1-3 shows that, the medical sealant glue has a good biocompatibility. The cytotoxicity test, the intradermal reaction test and the acute systemic toxicity test of the medical sealant glue all conform to the biocompatibility requirement of the medical sealant glue. TABLE 3Detection results of the medical sealant glue capable of promoting wound healingDetectionresults ofthe sealantEmbodi-Embodi-Embodi-Embodi-Embodi-Embodi-Embodi-gluement 1ment 2ment 3ment 4ment 5ment 6ment 7AntibacterialStaphylococcusYesYesYesYesYesYesYesTest (Yesaureusor No)EscherichiaYesYesYesYesYesYesYescoliPseudomonasYesYesYesYesYesYesYesaeruginosaDetectionCompar-Compar-Compar-results ofativeativeativethe sealantEmbodi-Embodi-exam-exam-exam-gluement 8ment 9ple 1ple 2ple 3AntibacterialStaphylococcusYesYes/YesNoTest (Yesaureusor No)EscherichiaYesYes/YesNocoliPseudomonasYesYes/YesNoaeruginosa The comparison of Embodiments 1-9 and Comparative example 3 in Table 3 shows that, the medical sealant glue has antibacterial effect only when it contains chitosan. Skin Wound Healing Test in Mice Test Grouping and Test Method 36 SPF male Kunming mice with a weight range of 18-22 g were randomly divided into two groups, 18 mice in each group, including a control group and a test group. After 1 week of adaptive feeding, a skin wound model of mice was established as below: mice were anesthetized with ether, and sheared at the back; the back side hair was shaved clean with a razor, and then the skin was cleaned and disinfected with 70% ethanol. Circular marks each slightly larger than 1 cm in diameter were made respectively at the left and right sides of the spine at the same location. Under aseptic conditions, a skin biopsy punch with a diameter of 1 cm is used to create a full-thickness skin wound within the circular mark. After modeling, the wounds were exposed, and the mice were fed separately. The day of injury was recorded as day 0. After successful modeling, mice in the test group were sprayed with the medical sealant glue of Embodiment 1 on the skin wound once a day; and mice in the control group were sprayed with saline at the same amount as that of the medical sealant glue used in the test group once a day. The profile of wound healing was observed within 20 days. Determination of Skin Wound Healing Rate in Mice The wounds of the mice were photographed every two days after the injury. The wound area of mice was calculated with Image-Pro Plus Version 6.0, until the wounds heal. Healing rate=(Original wound area−Unhealed wound area)/Original wound area×100% Standard of wound healing (complete epithelialization of the wound surface): healing area is greater than 95% of the original wound area, or the wound area is less than 5% of the original wound area, that is, complete healing. The profile of skin wound healing in mice of the control group and the test group is shown in Table 4. TABLE 4Effect of the medical sealant glue capable of promotingwound healing on the skin wound healing rate in miceWound healing rate (%)DaysControl GroupTest Group27.41 ± 0.879.54 ± 0.81414.85 ± 1.6820.23 ± 1.14621.45 ± 2.2332.56 ± 2.53833.68 ± 3.9359.47 ± 4.961075.42 ± 2.3794.62 ± 2.041280.27 ± 2.9596.87 ± 1.451484.51 ± 2.54/1688.76 ± 3.72/1891.55 ± 3.42/2092.86 ± 1.48/ It can be seen from Table 4 that, for the mice treated with the medical sealant glue capable of promoting wound healing, the healing rate achieved more than 95% on day 12, at which the wound has been healed; while for the mice in the control group, the healing rate is still below 95% on day 20, at which the wound has not been healed. Hence, it can be seen that the medical sealant glue capable of promoting wound healing of the invention has the effect of promoting wound healing. The above disclosures are only several specific embodiments of the invention, but the invention is not limited thereto. Any change that can be considered by persons skilled in the art shall fall within the protection scope of the present invention. | 16,868 |
11857694 | DETAILED DESCRIPTION Described herein generally are devices and methods for occluding vascular or other luminal defects. Devices as used herein can describe embolics and embolic devices generally. In one embodiment, an embolic device can be embolic particles. Embolic particles can be generally sphere-shaped or a particle-shaped “bead” or “microsphere” made of a biocompatible substance. The embolic particles can be injected through a microcatheter. Embolic particles as described herein can be delivered to a vascular defect or other lumen by various delivery methods. In one embodiment, a method can start by accessing the aneurysm with a catheter or microcatheter. A flow diverting stent (FDS) is then deployed across the neck of the aneurysm. The flow diverting stent allows the microcatheter to be “jailed” in place. After the microcatheter has been jailed, one or more embolic devices such as, but not limited to beads, foams, particles, or other agents can be delivered through the microcatheter. These embolic devices are physically larger than the maximum pore size of the flow diverting stent. The microcatheter is then removed thereby trapping the embolics within the aneurysm behind the flow diverting stent. In one embodiment, the embolic particles can be sized to be small enough to travel through a microcatheter without clogging or occluding the mircocatheter, yet large enough so that the particles do not migrate through the flow diverting stent's mesh structure. In one embodiment, the embolic particles can be small enough to fit through a microcatheter. The microcatheter can have a size of at most about 0.0155″, at most about 0.0160″, at most about 0.0165″, at most about 0.0170″, at most about 0.0175″, at most about 0.018″, at most about 0.019″, or at most about 0.02″. In one embodiment, the microcatheter can be a 0.0165″ (about 420 microns) microcatheter. In another embodiment, a microcatheter can be a Headway Duo. Also, in one embodiment, the embolic particles can be large enough, or have a large enough average diameter, that they do not migrate through a particular sized mesh. In some embodiments, the mesh can be a mesh opening of a flow diverting stent. The embolic particles described herein, unlike conventional particles can have diameters large enough to be delivered using such a mesh. In some embodiments, the mesh of a flow diverting stent can include a mesh opening of about 0.006″ (about 150 microns). In other embodiments, the mesh size can be at most about 0.04″, at most about 0.05″, at most about 0.06″, at most about 0.07″, at most about 0.08″, or at most about 0.09″. In some embodiments, the flow diverting stent can be a flow re-direction endoluminal device, referred to by the tradename FRED® (MicroVention, Inc. Tustin, CA). In one embodiment, the size range for the embolic is about 200 microns to about 500 microns. In other embodiments, in order maximize the size of the embolic particles, the embolic particles can be expansible. In such embodiments, the embolic particles can start at a smaller diameter so that they can be delivered through a smaller microcatheter and then expand at the physiological site to provide maximum volumetric filling. In one embodiment, for example, the embolic particles can have an initial diameter of about 200 microns to about 500 microns and, after deployment, can expand to about 400 microns to about 1500 microns. Expansible embolic particles deliverable through a smaller microcatheter can have a number of advantages. First, a smaller microcatheter is easier to navigate through tortuous anatomy, particularly to distal locations. Second, a smaller microcatheter can be used in conjunction with standard flow diverting stent delivery systems (for example, the Headway 27 or Headway 21) in a standard 6F guide catheter, thus avoiding the need to increase the guide catheter size or making a second puncture on the contralateral side, saving the patient from additional injury or potential access site complications. Third, a smaller microcatheter may ensure a tighter seal and smaller opening where the microcatheter is jailed by the flow diverting stent thus reducing the possibility of migration of the embolic during delivery. The embolic particles described herein may be formed of any material that can expand once delivered to an occlusion site such as a vascular defect. The expansile embolic particles can be any particle containing ionic groups that are pretreated with the appropriate low or high pH solutions to shrink the diameter of the particle. The embolic particles can be formed by reacting a monomer or prepolymer solution including (i) at least one monomer or macromer, (ii) an monomer including ionic groups, (iii) optionally a crosslinker, and (iv) initiator(s) in a non-solvent to form polymer particles which can be subsequently treated. The embolic particles can also be formed from a monomer or prepolymer solution or mixture comprising: (i) one or more macromer(s), for example, a macromer that contains at least two functional groups amenable to polymerization, (ii) one or more ionic monomers, and (iii) optionally one or more multifunctional crosslinkers. In some embodiments, a polymerization initiator may be utilized. In one embodiment, the particle embolics can comprise (i) one or more monomers that contain both a singular functional group amenable to polymerization and ionizable groups and (ii) one or more monomeric or macromeric crosslinkers. In one embodiment, expansile embolic particles can include various combinations of macromers and optionally monomers. For example, one, two, three or more macromers can be included in the embolic particles. Further, one, two, three or more monomers can be included in the embolic particles. In one embodiment, the macromer can include a plurality of functional groups suitable or amenable to polymerization. In some embodiments, the macromer can be linear. In other embodiments, the macromer can have one or more branches. In still other embodiments, the macromer can be an ethylenically unsaturated macromer. Macromers can include polyethers. Polyether macromers can include linear or branched poly(ethylene glycol), poly(propylene glycol), poly(tetramethylene oxide), derivatives thereof, or combinations thereof. Macromers can also include linear or branched poly(vinyl alcohol). Macromers described herein can have molecular weights of about 200 grams/mole, 400 grams/mole, 600 grams/mole, 800 grams/mole, 1,000 grams/mole, 2,000 grams/mole, 3,000 grams/mole, 4,000 grams/mole, 5,000 grams/mole, 10,000 grams/mole, 15,000 grams/mole, 20,000 grams/mole, 25,000 grams/mole, 30,000 grams/mole, 35,000 grams/mole, between about 200 grams/mole and about 35,000 grams/mole, between about 200 grams/mole and about 30,000 grams/mole, between about 200 grams/mole and about 1,000 grams/mole, between about 1,000 grams/mole and about 15,000 grams/mole, at least about 200 grams/mole, at most about 30,000 g/mole, or at most about 35,000 grams/mole. In one embodiment, macromers can have a molecular weight of about 10,000 g/mole. When used as a crosslinker, a macromer can have a low molecular weight of about 200 grams/mole, 400 grams/mole, 600 grams/mole, 800 grams/mole, 1,000 grams/mole, or between about 200 grams/mole and about 1,000 grams/mole. Derivatives of these polyethers can be prepared to render them amenable to polymerization. While any type of chemistry can be utilized, for example nucleophile/N-hydroxysuccinimde esters, nucleophile/halide, vinyl sulfone/acrylate or maleimide/acrylate; another type of chemistry can be free radical polymerization. As such, polyethers with a plurality of ethylenically unsaturated groups, such as acrylate, acrylamide, methacrylate, methacrylamide, and vinyl, can be used. In one embodiment, a polyether macromer can be poly(ethylene glycol) diacrylamide with a molecular weight of about 10,000 g/mole. In another embodiment the macromer is poly(ethylene glycol) diacrylamide, poly(ethylene glycol) diacrylate, poly(ethylene glycol) dimethacrylate, poly(ethylene glycol) dimethacrylamide, derivatives thereof, or combinations thereof. Macromers can be included at a concentration in the solvent of about 0% w/w, about 1% w/w, about 2% w/w, about 3% w/w, about 4% w/w, about 5% w/w, about 6% w/w, about 7% w/w, about 8% w/w, about 9% w/w, about 10% w/w, about 11% w/w, about 12% w/w, about 13% w/w, about 14% w/w, about 15% w/w, about 16% w/w, about 17% w/w, about 18% w/w, about 19% w/w, about 20% w/w, about 25% w/w, about 30% w/w, about 35% w/w, about 40% w/w, about 45% w/w, about 50% w/w, about 60% w/w, about 70% w/w, between about 5% w/w and about 10% w/w, between about 5% w/w and about 20% w/w, between about 5% w/w and about 25% w/w, between about 5% w/w and about 15% w/w, between about 6% w/w and about 8% w/w, or between about 14% w/w and about 16% w/w. In some embodiments, a macromer need not be used. In one embodiment, the macromer can be included at a concentration of about 7% w/w in the solvent. In one embodiment, the macromer can be included at a concentration of about 15% w/w in the solvent. In one embodiment, the macromer can be included at a concentration of about 16.5% w/w in the solvent. In one embodiment, the macromer can be included at a concentration of about 17% w/w in the solvent. In some embodiments, if one of the monomer(s) and/or macromers(s) is a solid, a solvent can be utilized in the preparation of the particles for use as embolics. If liquid monomers and macromers are utilized, a solvent may not be required. In some embodiments, even when using liquid monomers and/or macromers, a solvent may still be used. Solvents may include any liquid that can dissolve or substantially dissolve a macromer, monomers, multifunctional crosslinkers, and/or initiators. Any aqueous or organic solvent may be used that dissolves the desired monomer(s), macromer(s), multifunctional crosslinker(s) and/or polymerization initiators. In one embodiment, the solvent can be water. In another embodiment, the solvent can be dimethyl formamide. Additionally, solutes, e.g. sodium chloride, may be added to the solvent to increase the rate of polymerization. Solvent concentration can be varied to alter the swelling properties of the particles. Solvent concentrations can be about 25% w/w, about 35% w/w, about 45% w/w, about 55% w/w, about 65% w/w, about 75% w/w, about 85% w/w, about 95% w/w, between about 40% w/w and about 80% w/w, between about 30% w/w and about 90% w/w, or between about 50% w/w and about 70% w/w of the solution. In one embodiment, the solvent concentration can be about 50% w/w, about 51% w/w, about 52% w/w, about 53% w/w, about 54% w/w, about 55% w/w, about 56% w/w, about 57% w/w, about 58% w/w, about 59% w/w, or about 60% w/w. In another embodiment, the solvent concentration can be about 65% w/w, about 66% w/w, about 67% w/w, about 68% w/w, about 69% w/w, about 70% w/w, about 71% w/w, about 72% w/w, about 73% w/w, about 74% w/w, or about 75% w/w. In some embodiments, the concentration of the solvent ranges from about 20% w/w to about 80% w/w or about 50% w/w to about 60% w/w. In one embodiment, the solvent concentration can be about 57% w/w. In one embodiment, the solvent concentration can be about 70% w/w. In one embodiment, the solvent concentration can be about 71.6% w/w. In one embodiment, the solvent concentration can be about 72% w/w. In general, monomers can contain moieties such as acrylate, acrylamide, methacrylate, methacrylamide or other moieties amenable to polymerization. In one embodiment, the polymer particles are comprised of one or more macromers combined with one or more monomers. Optionally, one or more monomers can be added to the macromer to impart desired chemical and/or mechanical properties to the polymer particle. To reduce the diameter and to allow control of the rate of expansion of the embolic particles, monomers with ionic moieties, e.g. carboxylic acids and amines, can be polymerized into the particle embolic. In some embodiments, monomer(s) can be acidic and ethylenically unsaturated. Such monomers can include acrylic acid, methacrylic acid, 3-sulfopropyl acrylate, 3-sulfopropyl methacrylate, derivatives thereof, combinations thereof, and salts thereof. Preferred basic, ionizable, ethylenically unsaturated monomers include aminoethyl methacrylate, aminopropyl methacrylate, derivatives thereof, combinations thereof, and salts thereof. Monomers including positive or negative moieties can be present in solution at concentrations of about 0.5% w/w, about 1% w/w, about 2% w/w, about 3% w/w, about 4% w/w, about 5% w/w, about 6% w/w, about 7% w/w, about 8% w/w, about 9% w/w, about 10% w/w, about 15% w/w, about 20% w/w, about 21% w/w, about 22% w/w, about 23% w/w, about 24% w/w, about 25% w/w, about 26% w/w, about 27% w/w, about 28% w/w, about 29% w/w, about 30% w/w, about 40% w/w, about 50% w/w, about 55% w/w, about 60% w/w, about 65% w/w, about 70% w/w, about 80% w/w, between about 1% w/w and about 15% w/w, between about 1% w/w and about 5% w/w, between about 15% w/w and about 35% w/w, or between about 20% w/w and about 30% w/w. In other embodiments, monomers can be present in the solvent at a range of between about 40% w/w and about 60% w/w. In one embodiment, sodium acrylate can be included at a concentration of about 12% w/w in the solvent. In one embodiment, N-(2-aminoethyl)-methacrylate can be included at a concentration of about 3% w/w in the solvent. In one embodiment, N-(3-aminopropyl) methacrylamide can be included at a concentration of about 24% w/w in the solvent. In one embodiment, the monomer is not n-isopropyl acrylamide. In other embodiments, the polymer particles described herein do not include n-isopropyl acrylamide. If desired, uncharged, reactive moieties can be introduced into the particles. For example, hydroxyl groups can be introduced into the particles with the addition of 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, glycerol monomethacrylate, glycerol monoacrylate, sorbitol monomethacrylate, sorbitol monoacrylate, a carbohydrate similar to sorbitol and amenable to polymerization, derivatives thereof, or combinations thereof. Alternatively, uncharged, relatively un-reactive moieties can be introduced into the particles. For example, acrylamide, methacrylamide, methyl methacrylate, derivatives thereof, or combinations thereof can be added to the polyether macromer. In some embodiments, the monomer(s) can be selected to vary the number of hydroxyl groups in the polymeric particles to enable the particles to remain suspended in radiopaque contrast solution used in the preparation of the particle for clinical use. Further, in other embodiments, monomers may be selected to impart visualization using medically relevant imaging techniques. Visualization of the embolic particles under fluoroscopy can be imparted by the incorporation of solid particles of radiopaque materials such as barium, bismuth, tantalum, platinum, gold, and other dense metals into the hydrogel or by the incorporation of iodine-containing molecules polymerized into the embolic structure. In one embodiment, visualization agents for fluoroscopy are barium sulfate and iodine-containing molecules. Visualization of the embolic particles under computed tomography imaging can be imparted by incorporation of solid particles of barium or bismuth or by the incorporation of iodine-containing molecules polymerized into the embolic structure. Metals visible under fluoroscopy generally result in beam hardening artifacts that preclude the usefulness of computed tomography imaging for medical purposes. In some embodiments, visualization agents for fluoroscopy are barium sulfate or iodine-containing molecules. Concentrations of barium sulfate to render the embolic particles visible using fluoroscopic and computed tomography imaging can range from about 30% to about 60% w/w in the solvent of the prepolymer solution. Concentrations of iodine to render the embolic particles visible using fluoroscopic and computed tomography imaging can range from about 80 to about 300 mg 1/g of particles in the solvent of the prepolymer solution. Visualization of the embolic particles under magnetic resonance imaging can be imparted by the incorporation of solid particles of superparamagnetic iron oxide or gadolinium molecules polymerized into the embolic structure. In one embodiment, a visualization agent for magnetic resonance can be superparamagnetic iron oxide with a particle size of 10 microns. Concentrations of superparamagnetic iron oxide particles to render the embolic particles visible using magnetic resonance imaging range from 0.1% to 1% w/w in the solvent of the prepolymer solution. In some embodiments, a visualization agent can be a monomer and incorporated into the polymeric structure. Monomers incorporating visualization characteristics can include one or more halogen atoms. For example, monomers can include 1, 2, 3, 4, 5, 6, 7 or more halogen atoms. In some embodiments, the halogen atoms can be Br or I. In one embodiment, the halogen atoms are I. In one embodiment, a monomer including a visualization agent or the characteristics of a visualization agent can have a structure: In the above structure, one or more iodine atoms can be replaced by bromine. In another embodiment, a monomer including a visualization agent or the characteristics of a visualization agent can have a structure: Again, in the above structure, one or more iodine atoms can be replaced by bromine. In another embodiment, a monomer including a visualization agent or the characteristics of a visualization agent can have a structure: Again, in the above structure, one or more iodine atoms can be replaced by bromine. Such uncharged moieties if included can be present in the final particle (not including solvents, initiators, and salts) at about 0% w/w, about 10% w/w, about 20% w/w, about 30% w/w, about 40% w/w, about 50% w/w, about 60% w/w, about 61% w/w, about 62% w/w, about 63% w/w, about 64% w/w, about 65% w/w, about 66% w/w, about 67% w/w, about 68% w/w, about 69% w/w, about 70% w/w, about 71% w/w, about 72% w/w, about 73% w/w, about 74% w/w, about 75% w/w, about 80% w/w, about 90% w/w, between about 50% w/w and about 90% w/w, between about 60% w/w and about 70% w/w, between about 65% w/w and about 70% w/w, or between about 67% w/w and about 69% w/w. In one embodiment, an uncharged moiety can be present at about 68% w/w of the final particle. In one embodiment, multifunctional crosslinkers may be incorporated that contain at least two functional groups suitable to polymerization and at least one linkage susceptible to breakage under physiological conditions to impart biodegradation to the polymer particle. Linkages susceptible to breakage in a physiological environment include those susceptible to hydrolysis, including esters, thioesters, carbamates, oxalates, and carbonates, and those susceptible to enzymatic action, including peptides that are cleaved by matrix metalloproteinases, collagenases, elastases, and cathepsins. Multiple crosslinkers could be utilized to control the rate of degradation in a manner that is not possible with only one. Crosslinkers described herein include a plurality of polymerizable groups and can join monomers and macromers together thereby permitting the formation of solid embolic particles. Biodegradation can be imparted to the embolic particles by utilizing a crosslinker with linkages susceptible to degradation in a physiological environment. Over time, in vivo the linkages can break thereby unbinding the polymer chains. The judicious selection of monomers permits the formation of water-soluble degradation products that diffuse away and are cleared by the host. Linkages susceptible to hydrolysis, such as esters, thioesters, carbamates, oxalates, and carbonates, or peptides degraded by enzymes are preferred methods of imparting biodegradation to the embolic particles. Adding multifunctional crosslinkers containing more than one moiety amenable to polymerization can create a more cohesive hydrogel polymer by adding crosslinking to the molecular structure. In some embodiments the polymer particles are comprised of a macromer combined with one or more multifunctional crosslinkers such as, but not limited to, glycerol dimethacrylate, glycerol diacrylate, sorbitol dimethacrylate, sorbitol acrylate, a derivatized carbohydrate similar to sorbitol, derivatives thereof, or combinations thereof. In a preferred embodiment the multifunctional crosslinker is N,N′-methylenebisacrylamide. In one embodiment, a biodegradable crosslinker can have a structure: wherein each n is independently 1-20. In one embodiment, a biodegradable crosslinker can have a structure: In another embodiment, a biodegradable crosslinker can have a structure: wherein d, e, f, and g are each independently 1-20. In another embodiment, a biodegradable crosslinker can have a structure: If used, a crosslinker can be present in amount of about 0.1% w/w, about 0.25% w/w, about 0.5% w/w, about 0.75% w/w, about 1.0% w/w, about 1.25% w/w, about 1.5% w/w, about 1.75% w/w, about 2% w/w, about 3% w/w, about 4% w/w, about 5% w/w, about 6% w/w, about 7% w/w, about 10% w/w, about 20% w/w, about 25% w/w, about 30% w/w, between about 0% w/w and about 10% w/w, between about 0% w/w and about 2% w/w, between about 0.5% w/w and about 1.5% w/w, between about 0.25% w/w and about 1.75% w/w, or between about 0.1% w/w and about 2% w/w. In one embodiment, a crosslinker is not used. In one embodiment, a crosslinker can be present at about 1% w/w. In one embodiment, the crosslinker can be N,N′-methylenebisacrylamide. Any amounts of macromer(s), monomer(s), and multifunctional crosslinker(s) can be used that allows for a desired particle. Total concentration of reactive compounds or solids in the solvent can be about 5% w/w, about 10% w/w, about 11% w/w, about 12% w/w, about 13% w/w, about 14% w/w, about 15% w/w, about 16% w/w, about 17% w/w, about 18% w/w, about 19% w/w, about 20% w/w, about 21% w/w, about 22% w/w, about 23% w/w, about 24% w/w, about 25% w/w, about 30% w/w, about 31% w/w, about 32% w/w, about 33% w/w, about 34% w/w, about 35% w/w, about 36% w/w, about 37% w/w, about 38% w/w, about 39% w/w, 40% w/w, about 50% w/w, about 60% w/w, about 70% w/w, between about 10% and 60%, between about 15% w/w and about 50% w/w, or between about 20% w/w and about 40% w/w. In one embodiment, the total concentration of reactive compounds in the solvent can be about 20% w/w. In one embodiment, the total concentration of reactive compounds in the solvent can be about 28% w/w. In one embodiment, the total concentration of reactive compounds in the solvent can be about 37% w/w. In one embodiment, polymer embolic particles can be prepared from monomers having a single functional group and/or macromers having two or more functional groups suitable for polymerization. Functional groups can include those suitable to free radical polymerization, such as acrylate, acrylamide, methacrylate, vinyl, and methacrylamide. Other polymerization schemes can include, but are not limited to nucleophile/N-hydroxysuccinimide esters, nucleophile/halide, vinyl sulfone/acrylate or maleimide/acrylate. Selection of the monomers is governed by the desired chemical and mechanical properties of the resulting particle. The prepolymer solution or components in the appropriate solvent can be polymerized by reduction-oxidation, radiation, heat, or any other method known in the art. Radiation cross-linking of the prepolymer solution can be achieved with ultraviolet light or visible light with suitable initiators or ionizing radiation (e.g. electron beam or gamma ray) without initiators. Cross-linking can be achieved by application of heat, either by conventionally heating the solution using a heat source such as a heating well, or by application of infrared light to the monomer solution. In some embodiments, free radical polymerization of the polymerizable components requires an initiator to start the reaction. In one embodiment, the cross-linking method utilizes azobisisobutyronitrile (AIBN) or another water soluble AIBN derivative (2,2′-azobis(2-methylpropionamidine) dihydrochloride). Other cross-linking agents useful according to the present description include N,N,N′,N′-tetramethylethylenediamine, ammonium persulfate, benzoyl peroxides, and combinations thereof, including azobisisobutyronitriles. In yet another embodiment the initiator is the combination of N,N,N′,N′-tetramethylethylenediamine and ammonium persulfate at a concentration of 5% w/w and 1.8% w/w or 10% w/w and 2.5% w/w, respectively. In one embodiment, the prepolymer solution can be prepared by dissolving macromer(s), monomer(s), crosslinker(s), and initiator(s) in the solvent. The embolic particles can be prepared by emulsion polymerization in some embodiments. A non-solvent for the prepolymer solution, typically mineral oil when the monomer solvent is water, may be sonicated or sparged with inert gas to remove any entrapped oxygen. The mineral oil and a surfactant can be added to the reaction vessel. An overhead stirrer is placed in the reaction vessel. The reaction vessel is then sealed, degassed under vacuum, and sparged with argon. The initiator component, such as in one non-limiting embodiment N,N,N′,N′-tetramethylethylenediamine, is added to the reaction vessel and stirring commenced. Ammonium persulfate can be added to the polymerization solution and both are then added to the reaction vessel, where the stirring suspends droplets of the polymerization solution in the mineral oil. The rate of stirring can affect the size of the resulting embolic particles. In some embodiments, faster stirring can produce smaller particles and slower stirring can produce larger particles. Stirring rates can be about 100 rpm, about 200 rpm, about 300 rpm, about 400 rpm, about 500 rpm, about 600 rpm, about 700 rpm, about 800 rpm, about 900 rpm, about 1,000 rpm, about 1,100 rpm, about 1,200 rpm, about 1,300 rpm, between about 200 rpm and about 1,200 rpm, between about 400 rpm and about 1,000 rpm, at least about 100 rpm, at least about 200 rpm, at most about 250 rpm, at most about 500 rpm, at most about 1,000 rpm, at most about 1,300 rpm, or at most about 1,200 rpm to produce particles with desired diameters. In one embodiment, stirring rates can range from 200 to 1,200 rpm to produce particles with diameters ranging from 10 to 1,500 microns. Polymerization can be allowed to proceed as long as necessary to produce particles. Polymerization can be allowed to proceed for about 1 hr, 2 hrs, 2.5 hrs, 3 hrs, 4 hrs, 5 hrs, 6 hrs, 7 hrs, 8 hrs, 9 hrs, 10 hrs, 11 hrs, 12 hrs, 18 hrs, 24 hrs, 48 hrs, 72 hrs, 96 hrs, between about 1 hr and about 12 hrs, between about 1 hr and about 6 hrs, between about 4 hrs and about 12 hrs, between about 6 hrs and about 24 hrs, between about 12 hrs and about 72 hrs, or at least about 6 hours. Polymerization can be run at a temperature to produce embolic particles with desired diameters. Polymerization can be run at a temperature of about 10° C., about 15° C., about 20° C., about 25° C., about 30° C., about 35° C., about 40° C., about 45° C., about 50° C., about 60° C., about 70° C., about 80° C., about 90° C., about 100° C., between about 10° C. and about 100° C., between about 10° C. and about 30° C., at least about 20° C., at most about 100° C., or at about room temperature. In one embodiment, polymerization occurs at room temperature. After the polymerization is complete, the polymeric embolic particles can be washed to remove any solute, mineral oil, unreacted monomer(s), unreacted crosslinker(s), unreacted macromer(s), and/or unbound oligomers. Any solvent may be utilized, but care should be taken if aqueous solutions are used to wash particles with linkages susceptible to hydrolysis. Preferred washing solutions include acetone, hexane, alcohols, water+surfactant, water, and saline. In another embodiment, the washing solution is a combination of hexane followed by water. In another embodiment, the washing solution is saline. In further embodiments, the washing solution is water and a surfactant. Optionally, the washed embolic particles can then be dyed to permit visualization before injection into a microcatheter. A dye bath can be made by dissolving sodium carbonate and the desired dye in water. Embolic particles are added to the dye bath and stirred. After the dying process, any unbound dye is removed through copious washing. After dying and additional washing, the microspheres are packaged into vials or syringes, and sterilized. Dyes can include any of the dyes from the family of reactive dyes which bond covalently to the embolic particles. Dyes can include reactive blue 21, reactive orange 78, reactive yellow 15, reactive blue No. 19, reactive blue No. 4, C.I. reactive red 11, C.I. reactive yellow 86, C.I. reactive blue 163, C.I. reactive red 180, C.I. reactive black 5, C.I. reactive orange 78, C.I. reactive yellow 15, C.I. reactive blue No. 19, C.I. reactive blue 21, any of the color additives approved for use by the FDA part 73, subpart D, or any dye that can irreversibly bond to the polymer matrix of the embolic particles. Desired treated polymer particle diameters can be about 10 μm, about 20 μm, about 30 μm, about 40 μm, about 50 μm, about 100 μm, about 200 μm, about 300 μm, about 400 μm, about 500 μm, about 600 μm, about 700 μm, about 800 μm, about 900 μm, about 1,000 μm, about 1,100 μm, about 1,200 μm, about 1,300 μm, about 1,400 μm, about 1,500 μm, about 1,600 μm, about 1,700 μm, about 1,800 μm, about 1,900 μm, about 2,000 μm, between about 50 μm and about 1,500 μm, between about 100 μm and about 1,000 μm, at least about 50 μm, at least about 80 μm, less than about 600 μm, less than about 1,000 μm, less than about 1,200 μm, or less than about 1,500 μm. In one embodiment, the diameter is less than about 1,200 μm. Desired expanded polymer particle diameters can be about 80 μm, about 100 μm, about 200 μm, about 400 μm, about 500 μm, about 600 μm, about 700 μm, about 800 μm, about 900 μm, about 1,000 μm, about 1,100 μm, about 1,200 μm, about 1,300 μm, about 1,400 μm, about 1,500 μm, about 1,600 μm, about 1,700 μm, about 1,800 μm, about 1,900 μm, about 2,000 μm, about 2,100 μm, about 2,200 μm, about 2,300 μm, about 2,400 μm, about 2,500 μm, about 2,600 μm, about 2,700 μm, about 2,800 μm, about 2,900 μm, about 3,000 μm, about 3,100 μm, about 3,200 μm, about 3,300 μm, about 3,400 μm, about 3,500 μm, about 3,600 μm, about 3,700 μm, about 3,800 μm, about 3,900 μm, about 4,000 μm, between about 80 μm and about 3,600 μm, between about 400 μm and about 4,000 μm, at least about 400 μm, at least about 2,000 μm, less than about 3,000 μm, less than about 3,500 μm, less than about 4,000 μm, or less than about 3,700 μm. In one embodiment, the expanded polymer particle diameter is about 3,600 μm. In one embodiment, the concentration of macromer(s) in the final embolic particle products can be about 58% w/w. In one embodiment, poly(ethylene glycol) diacrylamide is present in the final embolic particle products at about 58% w/w. In one embodiment, the crosslinker can be N,N′-methylenebisacrylamide. In other embodiments, no crosslinker is included in the desiccated embolic particle products. In one embodiment, the concentration of one or more monomers in the final embolic particle products can be about 42% w/w. In one embodiment, the one or more monomers can be sodium acrylate and 2-amino ethyl methacrylate. In one embodiment, the one or more monomers can be sodium acrylate. A skilled artisan understands how to calculate final concentrations based on amount in solvent already discussed. The embolic particles can then be treated to delay the rate at which they expand in a physiological environment. For embolic particles containing acidic moieties, incubation in acidic solution is performed. For embolic particles containing basic moieties, incubation in basic solution is performed. Alternatively, incubation in sodium chloride solutions with higher osmolarity than physiological may decrease the diameter of the embolic particles. Another method is to formulate the embolic particles with ionic sensitivity. The embolic can be packaged in a concentrated saline solution with a much higher salt concentration than the human body, thus shrinking the embolic. When delivered to the body, the osmotic balance will be restored to the embolic particles as the concentrated saline solution washes away by dilution from the blood. Thus, the embolic particles become exposed to a lower ionic strength environment, causing them to swell to a larger diameter. A third method is to dehydrate the embolic particles and acid treat them so that they become responsive to physiologic pH. The embolic particles can then be packaged in a low pH, aqueous solution, such as water, or a non-aqueous, biocompatible solution such as mineral oil, alcohol, poly(ethylene glycol) 400, dimethyl sulfoxide, or lipiodol for delivery. A fourth method is to dehydrate the embolic particles and basic treat them so that they become responsive to physiologic pH. The embolic particles can then be packaged in a high pH, aqueous solution, such as water, or a non-aqueous, biocompatible solution such as mineral oil, alcohol, poly(ethylene glycol) 400, dimethyl sulfoxide, or lipiodol for delivery. The final polymer embolic particle preparation is delivered to the site to be embolized via a catheter or similar delivery device. In some embodiments, a radiopaque contrast agent is thoroughly mixed with the particle preparation in a syringe and injected through a catheter until blood flow is determined to be occluded from the site by interventional imaging techniques. The embolic particles described herein can be sterilized without substantially degrading the polymer. After sterilization, at least about 50%, about 60%, about 70%, about 80%, about 90%, about 95% about 99% or about 100% of the polymer can remain intact. In one embodiment, the sterilization method can be autoclaving and can be utilized before administration. The embolic particles can remain substantially stable once injected. For example, the polymer particles can remain greater than about 60%, about 70% about 80%, about 90%, about 95%, about 99% or about 100% intact after about 5 days, about 2 weeks, about 1 month, about 2 months, about 6 months, about 9 months, about a year, about 2 years, about 5 years, about 10 years, or about 20 years. The polymer particles described herein can be compressible yet durable enough not to break apart or fragment. Substantially no change in circularity or diameter of particles may occur during delivery through a microcatheter. In other words, after delivery through a microcatheter, the polymer particles described herein remain greater than about 60%, about 70%, about 80%, about 90%, about 95%, about 99% or about 100% intact yet expand to a size larger than when delivered. The embolic particles can be cohesive enough to stick to tissue and/or remain in place through friction with the tissue. In other embodiments, the particles can act as a plug in a vessel held in place by the flow and pressure of blood. The embolic particles described herein can have a characteristic expansion time and that characteristic expansion time can be predictable and/or predetermined. This characteristic expansion time can be the amount of time required for the embolic particles to expand from their initial or first diameter to their larger, second expanded diameter. This time can be about 5 min, about 10 min, about 15 min, about 20 min, about 25 min, about 30 min, between about 5 min and about 20 min, between about 10 min and about 25 min, between about 5 min and about 30 min, at least about 5 min, or at least about 10 min. Also, this characteristic expansion time can provide a user, for example a physician, sufficient time to deliver the particles to the desired in situ location without the particles expanding and clogging a microcatether or other deliver device. In one embodiment, a desiccated polymeric embolic particle can include a reaction product of a polyether and sodium acrylate. In another embodiment, a polymeric embolic particle can include a polyether at about 58% w/w and sodium acrylate at about 42% w/w. In another embodiment, a desiccated polymeric embolic particle can include a reaction product of a polyether, aminopropyl methacrylamide, and sulfopropyl acrylate. In another embodiment, a polymeric embolic particle can include a polyether at about 40% w/w, aminopropyl methacrylamide at about 1% w/w, and sulfopropyl acrylate at about 59% w/w. The following represent non-limiting embodiments. Embodiment 1: An embolic composition comprising: embolic particles including acidic groups that are treated with a low pH solution to form treated embolic particles, wherein the treated embolic particles have a first diameter and a second diameter, and wherein the second diameter is larger than the first diameter when the treated polymer particle is subjected to a physiological condition. Embodiment 2: The embolic composition of Embodiment 1, wherein the first diameter is between about 40 μm and about 1,200 μm. Embodiment 3: The embolic composition of Embodiment 1 or 2, wherein the first diameter is smaller than the diameter of a microcatheter. Embodiment 4: The embolic composition of Embodiment 1, 2, or 3, wherein the second diameter is between about 80 μm and about 3,600 μm. Embodiment 5: The embolic composition of Embodiment 1, 2, 3, or 4, wherein the second diameter is larger than the diameter of the microcatheter. Embodiment 6: The embolic composition of Embodiment 1, 2, 3, 4, or 5, wherein the embolic particles include a reaction product of a prepolymer solution including at least one macromer and at least one monomer including ionic groups. Embodiment 7: The embolic composition of Embodiment 1, 2, 3, 4, 5, or 6, wherein the monomer containing ionic groups is sodium acrylate. Embodiment 8: The embolic composition of Embodiment 1, 2, 3, 4, 5, 6, or 7, wherein the at least one macromer is poly(ethylene glycol) diacrylamide, poly(ethylene glycol) diacrylate, poly(ethylene glycol) dimethacrylate, poly(ethylene glycol) dimethacrylamide, or a combination thereof. Embodiment 9: The embolic composition of Embodiment 1, 2, 3, 4, 5, 6, 7, or 8, wherein the prepolymer solution further includes a biodegradable crosslinker. Embodiment 10: The embolic composition of Embodiment 9, wherein the biodegradable crosslinker has a structure: wherein each n is independently 1-20; wherein d, e, f, and g are each independently 1-20; or Embodiment 11: The embolic composition of Embodiment 1, 2, 3, 4, 5, 6, 7, 8, or 9, wherein the embolic particles further include a visualization agent. Embodiment 12: The embolic composition of Embodiment 11, wherein the visulaization agent is an monomer including a visualization agent and has a structure Embodiment 13: The embolic composition of Embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, wherein the physiological condition is physiological pH. Embodiment 14: A method of making polymer particles comprising: treating polymer particles formed by reacting a prepolymer solution including at least one macromer, an acrylic monomer, and an initiator in non-solvent to form treated polymer particles; wherein the treated polymer particle has a first diameter and a second diameter, wherein the second diameter is larger than the first diameter when the treated polymer particle is subjected to a physiological condition. Embodiment 15: The method of Embodiment 14, wherein the non-solvent is a mineral oil, hexane, or water. Embodiment 16: The method of Embodiment 14 or 15, wherein the initiator is ammonium persulfate, tetramethylethylene diamine, or a combination thereof. Embodiment 17: The method of Embodiment 14, 15, or 16, wherein the first diameter is between about 40 μm and about 1,200 μm. Embodiment 18: The method of Embodiment 14, 15, 16, or 17, wherein the first diameter is smaller than the diameter of a microcatheter. Embodiment 19: The method of Embodiment 14, 15, 16, 17, or 18, wherein the second diameter is between about 80 μm and about 3,600 μm. Embodiment 20: The method of Embodiment 14, 15, 16, 17, 18, or 19, wherein the second diameter is larger than the diameter of the microcatheter. Embodiment 21: The method of Embodiment 14, 15, 16, 17, 18, 19, or 20, wherein the at least one macromer is poly(ethylene glycol) diacrylamide, poly(ethylene glycol) diacrylate, poly(ethylene glycol) dimethacrylate, poly(ethylene glycol) dimethacrylamide, or a combination thereof. Embodiment 22: The method of Embodiment 14, 15, 16, 17, 18, 19, 20, or 21, wherein the treating is acid treating and the monomer containing ionic groups is sodium acrylate. Embodiment 23: The method of Embodiment 14, wherein the treating is base treating and the monomer containing ionic groups includes amino groups. Example 1 Biostable Embolic Particle Preparation A prepolymer solution was prepared by dissolving 9.2 g poly(ethylene glycol) 10,000 diacrylamide and 6.6 g sodium acrylate in 39.8 g of distilled water. This solution was filtered and flushed with argon. Then, 500 mL of mineral oil was sparged with argon for 6 hr in a sealed reaction vessel equipped with an overhead stirring element. N,N,N′,N′tetramethylethylenediamine (3 mL) was added to the reaction vessel and overhead stirring started at 230 RPM. An initiator solution was made by dissolving 1.0 g ammonium persulfate in 2.0 g distilled water. The solution was filtered and 1 mL added to the prepolymer solution. After mixing, the solution was added to the reaction vessel. After 5 to 10 min, 0.1 mL of SPAN®80 was added and the resulting suspension was allowed to polymerize over 4 hrs. Example 2 Purification of the Embolic Particle Preparation After the polymerization was complete, the mineral oil was decanted from the reaction vessel and the polymer embolic particles were washed four times with fresh portions of hexane to remove the mineral oil. The particles were then transferred to a separatory funnel with phosphate buffered saline (PBS) and separated from residual mineral oil and hexane. The resulting mixture was washed twice with PBS. To dye the embolic particles, 50 g of sodium carbonate and 0.1 g reactive black 5 dye (Sigma-Aldrich Co. LLC, St. Louis, MO) were dissolved in 1,000 mL of de-ionized water. Then, drained embolic particles were added and allowed to stir for 1 hr. The dyed particle preparation was washed with de-ionized water until all residual dye was removed. The dyed embolic particles were separated in sizes using sieving. Sieves were stacked from the largest size (on top) to the smallest size (on bottom). A sieve shaker was utilized to aid the sieving process. The embolic particles were placed on the top sieve along with PBS. Once all the embolic particles had been sorted, they were collected and placed in bottles according to their size. Dyed particles were incubated in 0.1 N HCl for 30 minutes to protonate available carboxylic acid groups. Significant decrease in the diameter was observed. The acid was removed and replaced with distilled water for storage. Example 3 Preparation of a Biodegradable Crosslinker Preparation of tetramesyl pentaerythritol (b): To a 3 L three-neck round bottom flask fitted with a Dean-Stark trap was added pentaerythritol (a, MW˜797 g/mol, 99.9 g, 125 mmol) and toluene (1.5 L) sequentially. The solution was subjected to an azeotrope distillation and water was removed from the Dean-Stark trap. The flask was cooled to room temperature before triethylamine (94.6 mL, 530 mmol) was added. Then the flask was placed in a 0° C. ice bath. A 250 mL addition funnel was attached to the flask. To the addition funnel was added anhydrous toluene (80 mL) and mesyl chloride (40 mL, 530 mmol) sequentially. The mesyl chloride solution was added dropwise to the cooled solution. The reaction was left to stir at room temperature overnight, resulting in the formation of a white precipitate. At the end of the reaction, the solution was filtered over a fritted glass funnel to remove the precipitate. The filtrate was concentrated using a rotary evaporator to afford the crude material as a pale yellow oil (86.37 g). Preparation of tetraamino pentaerythritol (c): To a solution of ammonium hydroxide (30%, 1250 mL, 22.02 mol) was added dropwise tetramesyl pentaerythriol (b, 86.37 g, 77.8 mmol) in anhydrous acetonitrile (500 mL). The reaction was stirred under room temperature for three days. Upon completion, it was degassed for 2 days using an air pump. Then the pH of the residue was adjusted to 14 using 0.1 M NaOH aqueous solution. The aqueous phase was extracted with dichloromethane (500 mL×1, and 1 L×1). The organic phase was then dried over sodium sulfate and concentrated using a rotary evaporator to afford the product as a pale yellow oil (56.31 g). Preparation of NHS-activated (4-hydroxyphenylmethacrylamide) (e): To a solution of (4-hydroxyphenylmethacrylamide) (d, 10 g, 56.4 mmol) in anhydrous acetonitrile (39.5 mL) was added anhydrous pyridine (9.9 mL, 113 mmol) and disuccinimidyl carbonate (36.1 g, 141 mmol) sequentially. The solution was stirred for 18 hours at room temperature. Upon completion, the reaction was poured over dichloromethane (40 mL) and filtered over a Buchner funnel. The filtrate was collected and the solvent was removed on a rotary evaporator. The residue was suspended in 30 mL ethyl acetate. The ethyl acetate fraction was washed with 5% citric acid solution (30 mL×2) and saturated NaCl solution (30 mL×1) before being dried over Na2SO4. The solvent was removed on a rotary evaporator to afford the product as a pinkish solid (12.96 g, 72.2% yield). Preparation of a biodegradable crosslinker (f): To a solution of tetraamino pentaerythritol (c, 10.0 g, 12.6 mmol) and trimethylamine (7.0 mL, 50.4 mmol) in dichloromethane (67 mL) was added NHS-activated (4-hydroxyphenylmethacrylamide) (e, 16.0 g, 50.4 mmol) under argon. The solution was stirred for 3 hours 15 minutes. Upon completion, it was passed through a silica gel plug. The elution was using a rotary evaporator, and the residue was separated using flash chromatography to afford the product. Example 4 Preparation of a Biodegradable Crosslinker To 10 g (67.6 1 mnol) of 2,2′-ethylenedioxy-bis-ethylamine was added 10 g (70.4 mmol) of glycidyl methacrylate and 3.0 g of silica gel (Aldrich 645524, 60 Angstrom 200-425 mesh), with good stirring. After stirring for 1 hr, another 9 g (63.4 mmol) of glycidyl methacrylate was added and the suspension was stirred for an additional 1.5 hr. The reaction mixture was diluted with 200 mL of reagent grade chloroform and filtered through a 600 mL fritted glass Buchner funnel of medium porosity, to remove silica gel. LC-MS analysis of the resultant chloroform solution showed almost no mono-glycidyl amino alcohol and mostly bis-glycidyl amino alcohol at (M+H)+433.2 and was concentrated to about 50 g in vacuo. The resultant heavy syrup was diluted to 100 mL with acetonitrile and stored at −80° C. Example 5 Preparation of a Biodegradable Crosslinker TMP-Chloroacetamide (E): To 13.2 g of TMP amine in 250 mL of dry THF was added 6.32 g (80 mmols) of pyridine and this solution was added to 6.44 g of chloroacetyl chloride in 250 mL of THF with good stirring, at 4-1° C. under Ar. After stirring for 15 min, the reaction mixture was warmed to room temperature and the THF and other volatile materials were removed in vacuo. The resulting solids were dissolved into 200 mL of chloroform, washed with 100 mL of saturated aqueous sodium bicarbonate, dried over magnesium sulfate, and the solvent was removed in vacuo. TMP-NH-Gly-Methacrylate (F): Approximately 15 grams of (E) was dissolved into 75 mL of anhydrous DMF and added 18 g of cesium methacrylate was added. The resulting suspension heated at 40-50° C. for 2 hr. After precipitation with 500 mL of chloroform, the inorganic salts were collected by filtration and the filtrate was concentrated to an oil in vacuo to give 18 g of a reddish brown oil. This oil was polymerized with AIBN at 80° C., in isopropyl alcohol to a nice hard pellet. Chromatography on 6 g of this through a plug of the above silica with 1,200 mL of 2-20% methanol in chloroform, gave 6 g of light red colored material. This material can be used to prepare polymer filaments. The material can have a structure wherein d, e, f, and g are each independently 1-20. Example 6 Preparation of a Biodegradable Crosslinker To 653 mg (1 mmol) of tetrapeptide Alanine-Proline-Glycine-Leucine (APGL) in 5 mL dry DMF was added 190 mg (1.1 mmol) of APMA-HCl, followed by 174 μL (1 mmol) of DIPEA, at room temperature with good stirring, under Ar. After 2 hr, the reaction mixture was treated with 20 mg of BHT and briefly exposed to air. LC-MS analysis showed (M+H)+at 680 and (M+Na)+at 702. Then, 5 mL of the reaction mixture was added dropwise to 200 mL of ether with good stirring and the solids which formed were collected by centrifugation. The resulting pellet was dissolved into 20 mL of (CHCl3/MeOH/MeOH+5% aqueous ammonia) 90/5/5, and applied to 50 g of silica gel in a 5×20 cm column (Aldrich 645524, 60 Angstrom 200-425 mesh). The silica gel column was developed with 500 mL of (CHCl3/MeOH/MeOH with 5% aqueous ammonia), 90/5/5. The peptide containing eluent (TLC, same solvent) was concentrated in vacuo to yield 110 mg of pale yellow oil, LCMS, as above. The pale yellow oil was dissolved in 10 mL of methanol and stored at −80° C. Example 7 Preparation of a Degradable Radiopaque Monomer Tetrabutylammonium diatrizoate: To a stirring suspension of diatrizoic acid (50 g, 81.4 mmol) in methanol (552 mL) was slowly added tetrabutylammonium hydroxide (40% aqueous solution, 52.8 mL). The turbid suspension turned clear after the addition of tetrabutylammonium hydroxide was finished. The solvent was removed using a rotary evaporator to obtain a cream-colored viscous residue. To this residue was added an appropriate amount of toluene, which was then removed using a rotary evaporator. Toluene was added to the residue once more and removed again. The solid obtained was dried in a vacuum oven overnight at 40° C. to afford a white solid (64.1 g, 92% yield). (WO 95/19186) Diatrizoyl HEMA: To a stirring solution of KI (796.8 mg, 4.38 mmol) and 2-chloro ethylmethacrylate (4.32 mL, 32.1 mmol) in anhydrous DMF (122.6 mL) was added tetrabutylammonium diatrizoate (25 g, 29.2 mmol) under argon. The flask was then placed in a 60° C. oil bath. Additional KI (199 mg) and 2-chloro ethylmethacrylate (1 mL) was added to the reaction at 13 hours, 38 hours and 41 hours reaction times. The reaction was pulled out of the oil bath at 44 hours and cooled under room temperature. The reaction was poured over saturated NaHCO3aqueous solution (120 mL) and a white precipitate formed. The aqueous phase was extracted once with a mixture of ethyl acetate (280 mL) and methanol (50 mL). The organic phase was washed with saturated sodium chloride aqueous solution (300 mL×1). The organic phase was subjected to rotary evaporation to obtain a cream-colored wet solid. The solid was suspended in a mixture of methyl tert-butyl ether and chloroform (7:3, v/v), and the resulting suspension was filtered to obtain a white solid. The solid dried under reduced pressure to obtain the first crop of product as a white solid (11.898 g). The previous NaHCO3phase was filtered and a white solid was collected. The solid was washed with a mixture of methyl tert-butyl ether and chloroform (7:3, v/v) and dried under reduced pressure to afford the second crop (3.071 g). The first and second crops were combined to afford the final product as a white solid (14.969 g, 70.6% yield). Example 8 Preparation of a Degradable Radiopaque Monomer To 400 mL of methanol was added 104 g (170 mmol) of diatrizoic acid followed by 28 g of cesium carbonate (65 mmol). After stirring for 45 min the methanol was removed in vacuo and the solids suspended in 500 mL of diethyl ether. The solids were then collected and dried on a Buchner funnel and further dried in vacuo, to yield 120 g, (95%) (Cesium Diatriozate, 1). To 24 mL of HEMA (200 mmol) in 1,000 mL of dry ether was added 16.8 mL (213 mmol) of pyridine at 4-10° C., under Ar. To this solution was added 21.3 mL (200 mmol) of 1-chloroethyl chlorocarbonate, drop wise with stirring over 0.5 hr. After stirring 0.5 hr at 4-10° C., the heavy precipitate was removed by filtration and the filtrate was concentrated to oil in vacuo, yielding 44 g (100%) (HEMA-1-Chloroethyl carbonate, 2). To 44 g (200 mmol) of (2) in 400 mL of anhydrous DMF was added 30 g (40 mmol) of (1) at 100° C. under Ar, with good stirring. After 15 min another 40 g (54 mmol) of (1) was added at 100° C., under Ar, with good stirring followed by a final 30 g (40 mmol), under the same conditions, for a total of 110 g (1) (134 mmol). The reddish brown reaction mixture was heated at 100° C. for an additional hour and the solvent was removed in vacuo. The reddish brown solid residue was suspended in 1,000 mL of dry ether and the solids collected on a Buchner funnel. After the solids were dried in vacuo, they were suspended in 500 mL distilled water at 2,000 rpm and the mixture pH was adjusted to 8-9 with cesium carbonate. After stirring for 10 min, the suspension was filtered and the solids washed 3 times with 100 mL of distilled water, dried overnight in vacuo and crushed to a fine powder. Solid residue was again suspended in 1,000 mL of dry ether and the solids were collected on a Buchner funnel. After the solids were dried in vacuo again and crushed to a fine powder again, they were purified by silica gel chromatograph using a 1.5 Kg column and a 0-10% gradient of methanol in dichloromethane, over 1 hr. This yielded 26 grams (18%), very pale yellow crystalline solid (1-((2-(methacryloyloxy)ethoxy)carbonyloxy)ethyl-3,5-diacetamido-2,4,6-triiodobenzoate, 3). Example 9 Preparation of a Non-Degradable Radiopaque Monomer Diatriazoyl Acetate (A): To 30.8 g of diatrizoic acid suspended in 100 mL of acetic anhydride was added 2 g of concentrated sulfuric acid and the resulting suspension stirred at 90 degrees centigrade for one hour before the reaction mixture was cooled to room temperature and then poured onto 500 g of ice. After agitating the ice for 15 min, the oily mass was treated with 100 mL of half saturated sodium bicarbonate whilst agitating. The solids which had formed were collected on a Buchner funnel and dried overnight in vacuo to give 9 g of light brown diatriazoyl acetate solids. Diatriazoyl Chloride (B): Nine grams of ditriazoyl acetate was suspended in 100 mL of thionyl chloride using overhead stirring. The reaction mixture was brought to reflux in an oil bath and refluxed for one hour. The thionyl chloride was mostly removed in vacuo at 40° C. at which point solids were re-suspended in 100 mL of ethyl acetate which was removed in vacuo. This process was repeated twice more at which point the solids were placed under vacuum overnight. Ethylenediamine mono-diatriazoyl amide (C): 6.3 g of the acid chloride (10 mmol) in 300 mL of methylene chloride was added to 6.7 grams of ethylene diamine (100 mmol) over one hour with stirring at 4-10° C. under Ar. The formed solids were collected on a Buchner funnel and washed with 100 mL of methylene chloride and dried overnight in vacuo. The dried solids now largely free of ethylenediamine were taken up in 600 mL of water filtered through a fritted disk funnel and the water removed in vacuo. The residue was triturated with acetonitrile which was then evaporated in vacuo to remove traces of water. LC-MS showed 640 which is (M+Na)+and 656.9, (M+K)+. Ethylene diamine-1-diatriazoylamide-2-methacrylamide (D): To 650 mg of (C) (1 mmol) suspended in 100 mL of THF/CHCl3/ethanol, 1/3/1 was added 0.18 mL (1.04 mmol) of diisopropylethylamine followed by 0.12 mL (1.26 mmol) of methacryoyl chloride with stirring under Ar. The reaction mixture was stirred for 1 hr at which point reaction mixture was filtered with a fritted Buchner funnel. TLC with 10% methanol in methylene chloride showed potential product in solids and filtrate. LC-MS of combined filtrate and solids after solvent removal in vacuo showed (M+H)+at 725.0, (M+Na)+at 747.0 as well as (M−H)−at 723.0 and (M+Na-2H)−at 744.9 all on an HPLC peak at 8.9 min in a 15 min run. Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. The terms “a,” “an,” “the” and similar referents used in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention. Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims. Certain embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Of course, variations on these described embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor expects skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context. In closing, it is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the present invention. Other modifications that may be employed are within the scope of the invention. Thus, by way of example, but not of limitation, alternative configurations of the present invention may be utilized in accordance with the teachings herein. Accordingly, the present invention is not limited to that precisely as shown and described. | 61,076 |
11857695 | Plasma treated MGO coatings of the invention produced with hydrocarbon plasma step and oxygen plasma etching (Plasma MGO coating); Graphene oxide paper (GO paper); Reduced graphene oxide coating with no plasma treatment (Reduced GO); and Modified graphene oxide coating produced with hydrocarbon plasma step and without oxygen plasma etching (Reduced MGO coating). Plasma MGO coating of the invention exhibits the lowest surface roughness, and smoothest surface, and therefore has better antibacterial properties than the other surfaces. DETAILED DESCRIPTION OF THE INVENTION All publications, patents, patent applications and other references mentioned herein are hereby incorporated by reference in their entireties for all purposes as if each individual publication, patent or patent application were specifically and individually indicated to be incorporated by reference and the content thereof recited in full. Definitions and General Preferences Where used herein and unless specifically indicated otherwise, the following terms are intended to have the following meanings in addition to any broader (or narrower) meanings the terms might enjoy in the art: Unless otherwise required by context, the use herein of the singular is to be read to include the plural and vice versa. The term “a” or “an” used in relation to an entity is to be read to refer to one or more of that entity. As such, the terms “a” (or “an”), “one or more,” and “at least one” are used interchangeably herein. As used herein, the term “comprise,” or variations thereof such as “comprises” or “comprising,” are to be read to indicate the inclusion of any recited integer (e.g. a feature, element, characteristic, property, method/process step or limitation) or group of integers (e.g. features, element, characteristics, properties, method/process steps or limitations) but not the exclusion of any other integer or group of integers. Thus, as used herein the term “comprising” is inclusive or open-ended and does not exclude additional, unrecited integers or method/process steps. As used herein, the term “disease” is used to define any abnormal condition that impairs physiological function and is associated with specific symptoms. The term is used broadly to encompass any disorder, illness, abnormality, pathology, sickness, condition or syndrome in which physiological function is impaired irrespective of the nature of the aetiology (or indeed whether the aetiological basis for the disease is established). It therefore encompasses conditions arising from infection, trauma, injury, surgery, radiological ablation, age, poisoning or nutritional deficiencies. As used herein, the term “treatment” or “treating” refers to an intervention (e.g. the administration of an agent to a subject) which cures, ameliorates or lessens the symptoms of a disease or removes (or lessens the impact of) its cause(s) (for example, the reduction in accumulation of pathological levels of lysosomal enzymes). In this case, the term is used synonymously with the term “therapy”. Additionally, the terms “treatment” or “treating” refers to an intervention (e.g. the administration of an agent to a subject) which prevents or delays the onset or progression of a disease or reduces (or eradicates) its incidence within a treated population. In this case, the term treatment is used synonymously with the term “prophylaxis”. As used herein, an effective amount or a therapeutically effective amount of an agent defines an amount that can be administered to a subject without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio, but one that is sufficient to provide the desired effect, e.g. the treatment or prophylaxis manifested by a permanent or temporary improvement in the subject's condition. The amount will vary from subject to subject, depending on the age and general condition of the individual, mode of administration and other factors. Thus, while it is not possible to specify an exact effective amount, those skilled in the art will be able to determine an appropriate “effective” amount in any individual case using routine experimentation and background general knowledge. A therapeutic result in this context includes eradication or lessening of symptoms, reduced pain or discomfort, prolonged survival, improved mobility and other markers of clinical improvement. A therapeutic result need not be a complete cure. Improvement may be observed in biological/molecular markers, clinical or observational improvements. In a preferred embodiment, the methods of the invention are applicable to humans, large racing animals (horses, camels, dogs), and domestic companion animals (cats and dogs). In the context of treatment and effective amounts as defined above, the term subject (which is to be read to include “individual”, “animal”, “patient” or “mammal” where context permits) defines any subject, particularly a mammalian subject, for whom treatment is indicated. Mammalian subjects include, but are not limited to, humans, domestic animals, farm animals, zoo animals, sport animals, pet animals such as dogs, cats, guinea pigs, rabbits, rats, mice, horses, camels, bison, cattle, cows; primates such as apes, monkeys, orangutans, and chimpanzees; canids such as dogs and wolves; felids such as cats, lions, and tigers; equids such as horses, donkeys, and zebras; food animals such as cows, pigs, and sheep; ungulates such as deer and giraffes; and rodents such as mice, rats, hamsters and guinea pigs. In preferred embodiments, the subject is a human. As used herein, the term “equine” refers to mammals of the family Equidae, which includes horses, donkeys, asses,kiangand zebra. The term “object” as used herein refers to an object with a metal, metal allow or polymer surface that is suitable for treatment with plasma enhanced chemical vapour deposition to graft oxygen-based functional groups on to the surface. The metal may be titanium or a titanium alloy, for example Ti-6Al-4V, Ti-30Nb-1Fe-1Hf, Ti-6Al-7Nb and Ti-15Sn-4Nb-2Ta-0.2Pd. The polymer may be a polymer suitable for use as a prosthetic implant, such as polyether ether ketone (PEEK). In one embodiment, the object is an implantable object, such as a prosthetic implant. Examples of prosthetic devices are hip and knee (and other joint) replacements used in the case of joint degeneration or for various types of arthritis, spinal fusion instruments for treatment of vertebral segments instabilities, and fracture fixation devices such as plates, screws and intramedullary rods. The term “first oxygen plasma” as used herein typically refers to a RF-generated oxygen plasma generated in a reactor configured to perform low pressure plasma discharges. Typically, the first oxygen plasma is obtained by feeding the plasma source with oxygen at a flow rate of 40-60 sccm and an RF power of 250-350 W. The term “plasma enhanced chemical vapour deposition” refers to a vapor deposition process used to deposit thin films from a gas state (vapor) to a solid state on a substrate. Chemical reactions are involved in the process, which occur after creation of a plasma of the reacting gases. The term “oxygen-based functional groups” refers to a class of functional groups in which oxygen or molecule containing oxygen is present as the reactive entity. Typically, the oxygen-based functional groups include hydroxyl, carbonyl, or carboxyl molecules. The functional groups are grafted on to the object surface to develop characteristic chemical reactions with other molecules in the environment. As an example, in the case of a titanium surface, the pre-treatment with an oxygen plasma leads to improvement of graphene oxide adhesion to the titanium and prevention of biological fluids permeating the graphene oxide flakes which can lead to their detachment. The term “suspension of particulate graphene oxide” refers to a suspension of graphene oxide particles having an average dimension of less than 1 μm. The suspension may be prepared by exfoliating crystalline graphite in strong acid to produce a suspension of highly oxidised graphene oxide flakes (Hummer process), and size reduction of the suspension to provide a homogenous suspension of graphene oxide. Size reducing may be performed by sieving the suspension to remove any flakes having a dimension of greater than 1 m, or by sonicating the suspension to size-reduce the flakes. Typically, the suspension has a graphene oxide concentration of about 1-10, 3-5 or about 4, mg/ml. The term “hydrocarbon plasma” as used herein typically refers to plasma comprising hydrocarbon precursors that is typically generated in a reactor configured to perform low pressure plasma discharges. The hydrocarbon precursors may be various alkanes, for example methane and ethane. Other hydrocarbon precursors that may be employed include benzene and acetylene. The plasma is generally RF-generated. Typically, the hydrocarbon plasma is obtained by feeding the plasma source with a hydrocarbon at a flow rate of 60-100 sccm and an RF power of 150-250 W. The hydrocarbon plasma may include non-hydrocarbon precursors, for example hydrogen to modulate the softness of the DLC coating or CO2to add oxygen functionalities. The term “second oxygen plasma” as used herein typically refers to a RF-generated oxygen plasma generated in a reactor configured to perform low pressure plasma discharges. Typically, the second oxygen plasma is obtained by feeding the plasma source with oxygen at a flow rate of 10-30 sccm and an RF power of 50-150 W. The term “plasma reactor” as used herein typically refers to a plasma reactor configured to generate low pressure plasma discharges. The reactor is typically formed by a load-lock chamber to introduce the medical device into the plasma chamber for treatment. The load lock chamber is typically pumped down from atmospheric pressure down to 10-6 mbar. The evacuation of the load-lock chamber ensures a negligible degree of contaminants to enter in the plasma chamber with the introduction of the objects to be treated. The plasma chamber in one embodiment consists of a stainless teal ellipsoidal chamber with a diameter of ˜500 mm to avoid interferences of the chamber walls during the plasma treatment. The plasma chamber is typically equipped with a plasma source which is a commercial COPRA GTE 200 plasma source (from CCR Technology GmbH—Germany). The source is typically equipped with an inner matching network to couple the external RF generator, minimize the reflected RF power and optimize the transfer of the RF power to the plasma. The plasma source is also typically equipped with a magnetic coil. A maximum RF power is transferred to the plasma when the magnetic field is tuned to form a wave resonance (cyclotron resonance) leading to a strong increase of the ionization processes. In this configuration the plasma is generated inside the plasma source and propagated outside through the source output till to the sample surface. The samples are typically then exposed to an after-glow high density plasma but reasonably low power avoiding heat transfer during the depositions. The plasma reactor is typically equipped with a motorized manipulator to ensure a perfect positioning of the medical device under the plasma source. The term “etch and flatten” as used herein refers to process in which the coating on the object is etched to flatten the surface formed by the deposited coating. This is illustrated inFIG.3. As the graphene oxide coating can be rough, the coating has peaks and troughs of differing height and depths. Etching of the surface involves many of the peaks being etched away, and in one embodiment provides a substantially flattened surface comprising the stabilising amorphous hydrocarbon coating that in parts is etched away revealing pockets of graphene oxide as illustrated inFIG.3. Exemplification The invention will now be described with reference to specific Examples. These are merely exemplary and for illustrative purposes only: they are not intended to be limiting in any way to the scope of the monopoly claimed or to the invention described. These examples constitute the best mode currently contemplated for practicing the invention. The invention is explained through the synthesis of a multilayered coating for prosthetic implants to avoid bacterial adhesion and proliferation and promote osteo-integration. The deposition of the coating is composed by four steps: 1) preparation of the titanium (or other metal or polymeric based implant) based surface for the deposition of the film; 2) deposition of a first coating composed by GO; 3) deposition of a second coating of amorphous carbon/diamond like carbon with specific crosslinking properties and functional groups density aimed at stabilizing the GO on the prosthetic implant surface, and 4) further plasma treatment with different gas precursors to facilitate targeted surface functionalization.FIG.1shows the structure changes in GO coating after plasma treatment (fragmentation) followed by oxygen treatment to increase the concentration of carboxyl group. This procedure will extend the effect of “oxidative stress” that provide free radicals that leads the destruction of bacterial cells. Different treatment could lead to the reduction of carboxyl groups and increase the amorphous carbon content to discourage bacterial adhesion. The methods combined can create areas at the microscale that alternating in action or can be applied at different surfaces depending on the implant type and the required action. Hence. the coatings represent multiple anti-bacterial actions. The cross-linking amorphous carbon layer present bacteriostatic properties while the GO with carboxyl groups represent bactericidal effects. Carboxyl groups only present at the edges of the graphene oxide sheets. There density depends on the length of these GO layers. Plasma treatment can reduce the length of the GO layers by breaking them into separate smaller fragments then with oxygen plasma, it creates the environment for more carboxyl groups (FIG.1). Plasma Reactor The plasma reactor is generally designed to perform low pressure plasma discharges. The reactor is typically formed by a load-lock chamber to introduce the medical device into the plasma chamber for treatment. The load lock chamber may be pumped down from atmospheric pressure down to 10-6 mbar. The evacuation of the load-lock chamber ensures a negligible degree of contaminants to enter in the plasma chamber with the introduction of the objects to be treated. The plasma chamber may consist of a rather big stainless teal ellipsoidal chamber with a diameter of ˜500 mm to avoid interferences of the chamber walls during the plasma treatment. The plasma chamber may be equipped with a plasma source which is a commercial COPRA GTE 200 plasma source (from CCR Technology GmbH—Germany). The source may be equipped with an inner matching network to couple the external RF generator, minimize the reflected RF power and optimizing the transfer of the RF power to the plasma. The plasma source may also be equipped with a magnetic coil. A maximum RF power is generally transferred to the plasma when the magnetic field is tuned to form a wave resonance (cyclotron resonance) leading to a strong increase of the ionization processes. In this configuration the plasma is generated inside the plasma source and propagated outside through the source output till to the sample surface. The samples are generally then exposed to an after-glow high density plasma but reasonably low power avoiding heat transfer during the depositions. Finally the plasma reactor is generally equipped with a motorized manipulator to ensure a perfect positioning of the medical device under the plasma source. Pretreatment of the Prosthetic Implant Surface A prosthetic implant under consideration is generally made from metallic alloys based on titanium which continue to be one of the most important components for orthopaedic implants in industry due the high strength, rigidity, fracture toughness and their reliable mechanical performances. However, other type of metals or polymers (PEEK) would also qualify albeit the treatment conditions will slightly vary, accordingly. Prosthetic implants are medical devices used to replace parts of human hard tissue. Examples of prosthetic devices are hip and knee replacements used in the case of joint degeneration or for various types of arthritis, spinal fusion instruments solve vertebral segments instabilities, and fracture fixation devices such as plates, screws and intramedullary rods. Titanium alloys are very versatile materials due to the excellent mechanical properties and the low modulus of elasticity. We initially form a very stable passivating oxide layer on the titanium/implant surface that ensures strong adhesion with the following GO layer. However, alone, this oxide layer provide high biocompatibility and good corrosion resistance. In addition the same oxide layer helps the process of osteo-integration which makes this material an excellent candidate for use in orthopaedics. The deposition of a graphene oxide on the surface of the titanium alloy was demonstrated to possess bactericidal and bacteriostatic properties depending on the coating process. Pre-treatment of the Ti alloy is a prerequisite to avoid detachment of the GO based coatings. For this purpose, an oxygen plasma treatment is performed in the low pressure plasma reactor. The plasma pre-treatment is intended to remove all the organic contaminations and graft favourable functional groups to stably bind the GO flakes to the Ti surface. As observed, the Ti surface is formed by Ti oxide which is very stable compound. For this reason the plasma treatment consists of an oxygen plasma obtained by feeding the plasma source with 50 sccm of pure O2 at an RF power of 300 W. These conditions lead to the formation of an oxygen plasma rich in oxygen radicals which are able both to eliminate the organic contaminants form the Ti surface and induce oxygen based functional group grafting on the Ti alloy surface. The treatment was performed for a time of 30 min to optimally functionalize the alloy surface. This also ensures perfect surface homogeneity allowing optimal deposition of the GO film. Deposition of the GO Layer After treatment the medical device undergoes a coating with a GO layer. The Graphene Oxide is generally obtained from exfoliation of crystalline graphite through a chemical processing in a strong acid solution (Hummer process—Hummers, William S.; Offeman, Richard E. (Mar. 20, 1958). “Preparation of Graphitic Oxide”. Journal of the American Chemical Society. 80 (6): 1339. doi:10.1021/ja01539a017). The exfoliation process leads to a solution of strongly oxidized graphene flakes. Originally the graphene is composed by a single layer of carbon atoms arranged in a hexagonal crystalline lattice. The graphene monolayer is a 2D material characterized by outstanding specific surface. The exfoliation process of graphite leads to the formation of a population of particulate where the mean flake dimension generally ranges from few nanometres up to ˜30 μm, 95% of the flakes are in the form of monolayers. However, differently from the pure ideal graphene, the graphene oxide appears to be strongly oxidized. The chemical composition of GO is typically Carbon: 49-56%, Hydrogen: 0-1%, Nitrogen: 0-1%, Sulfur: 0-2%, Oxygen: 41-50% where about the half of the carbon atoms are usually in an oxidized from. The graphene oxide is in the form of an aqueous solution at a pH of 2.2, 2.5 and a concentration of 4 mg/ml. The solution is drop cast on the medical device. Without any surface pre-treatment the GO coating could undergo a detachment from the Ti substrate with release of GO debris in the host biological environment. This case is sketched inFIG.2. To avoid this undesired event, Ti is pretreated with an oxygen plasma as described above leading to improvement of the GO film adhesion to Ti and preventing biological fluids to permeate the GO flakes leading to their detachment. The GO flakes, undergo screening and sieving process in order to separate the large agglomerations and large particles to keep particles under 1 micron in size. C-Based Film Deposition and Further Functionalization The pre-treatment of the Ti substrate induces an interaction between Ti and the first flakes of GO which came into contact with Ti. This treatment, however, has no effect on the topmost layers of the GO coating. To further improve the stability of the GO coating on the Ti alloy, a deposition of an amorphous hydrogenated carbon (aCH) film is made. The deposition of the film is performed utilizing the plasma reactor described above. The deposition conditions are 80 sccm of CH4 precursor using a RF power of 200 W for a duration of 15 min. The pressure inside the reactor was 0.015 mbar with an ion density of 1012/cm3thanks to the high efficient coupling between the RF excitation power and the plasma. In these conditions the energy of the ionized species impinging the Ti surface is 15 eV while the estimated current density at the Ti surface is 0.35 mA/cm2. We also observe that the plasma produced by the COPRA is quasi-neutral meaning that it is composed by roughly the same number of ions and electrons. This allows efficient deposition processes even if the conductivity of the substrates is not ensured as in the case of GO deposited Ti surfaces being GO a highly resistive material. After the deposition of the aCH film. The situation is schematically represented inFIG.3A The aCH coating enables the GO flakes stabilization maintaining a high biocompatibility of the Ti surface. Particularity of this film is the usual absence of specific polarities which make it reject the colonization of micro-organisms such as bacteria with bacteriostatic properties. This is mainly due to the difficulty of bacteria at conditioning the substrate to deposit the protein-based film (the extracellular matrix in the case of cells, the biofilm in the case of bacteria). Since no polar groups are present on the aCH surface, the interaction of this surface with proteins is rather low. To further improve the bactericidal properties of the surface, a surface etching with oxygen is performed. The oxygen plasma has two main effects: (1) as shown inFIG.2(B)the oxygen plasma flattens the Ti coated surface. The plasma treatment is carefully adjusted to etch the asperities of the aCH+GO coating. The power and the density of the plasma (around 100 W, 20 sccm O2). Adjusted to etch part of the topmost part of the deposited coatings. When roughness is present, the plasma etching proceeds from the top of the severities down to the valleys. By carefully controlling the plasma process, we were able to remove part of the aCH+Go coating leading to an overall flattening of the sample surface as shown inFIG.2B. The flattening effect has an important influence on the bacterial adhesion since rough surfaces encourage the adhesion of the microorganisms to the substrate. On the contrary, flat surfaces render the adhesion process more difficult. As shown inFIG.2B, part of the aCH film is still present on the sample surface. This aCH film is now creating a network maintaining the GO flakes stabilized on the Ti surface. (2) as a second important effect of the oxygen plasma we obtain the grafting of oxygen based functional groups. It is proven that GO shows a bactericidal activity thanks to the oxidative stress induced by the amount of radicals present on its surface (please seeFIG.1). Oxygen plasma will increase the number of radicals in the exposed GO parts of the coating. Concerning the other parts made of aCH, the plasma will graft the oxygen-based groups leading to an overall anti-bacterial surface. GO alone, or treated with N2 plasma, is favourable for osteo-integration. Hence an added step for surface functionalization is needed when a double effect (limiting bio films and osteo-integration) is needed. There will be a process of optimization regarding the double effects of the hybrid coatings. Thicker aCH coatings will ensure longer anti-bio film effects while thinner coatings allow for faster exposure of the GO film necessary for osteo-integration. Biofilm Quantification with Crystal Violet Assay Crystal violet (CV) assay was used to measure biofilm formation on GO coated/uncoated glass coupons. Coupons with biofilm were washed and transferred to new plates. For fixation of the biofilms, 1 mL 99% methanol was added for 15 minutes, after which supernatants were removed and the plates were air-dried for 45 minutes. Then, 1 mL of a 0.4% (w/v) CV solution (Sigma-Aldrich, 61135-100 G) was added to all wells to stain the biofilms. After 20 minutes, the excess CV was removed by washing the plates under running tap water. Finally, bound CV was released by adding 200 μL of 33% acetic acid (Sigma). The supernatant was added to wells of a 96-well plate and the absorbance was measured at 490 nm. For sterilization, the samples were left 10 minutes on each side under UV lights in biosafety cabinet. Finally, all steps were carried out at room temperature. Surface Roughness Assay Surface roughness was measured using an AFM technique. The AFM instrument was Dimension 3100 (Veeco Digital Instruments by Bruker) equipped with a NanoScope IIIa controller and Quadrex signal processor for 16-bit resolution on all 3 axes. The samples were examined under atmospheric pressure and at room temperature with the use of Tapping mode. Minimum Inhibitory Concentration Assay MIC is defined as the lowest concentration of an antimicrobial agent that will inhibit the visible growth of a microorganism after overnight incubation. MIC was assessed for five bacterial strains includingKlebsiella pneumoniae, Pseudomonas aeruginosaand PA-UHG-1,Staphylococcus epidermidisand MRSA. First, for each strain, a 0.5 McFarland standard inoculum, which corresponds approximately 108 CFU/mL was prepared. Then, it was diluted by 100 in sterile MH broth to give an inoculum of approximately 106 CFU/m. This inoculum was used in the 15 minutes following its preparation. In the meantime, serial dilution of liquid GO (0.4 wt %=0.4 g of GO/100 g of solvent) was arranged with the following concentrations: 40 mg/100 g, 20 mg/100 g, 10 mg/100 g, 5 mg/100 g, 2.5 mg/100 g, 1.25 mg/100 g, 0.63 mg/100 g, 0.31 mg/100 g, 0.16 mg/100 g, 0.08 mg/100 g, 0.04 mg/100 g, 0.02 mg/100 g. Using a sterile Costar U bottom 96-well plate, 10 μL of each GO dilution were loaded in 12 wells, then, 90 μL of the bacterial inoculum were added to the same wells and mixed carefully (approximately 1.105 CFU/well). The experiment was performed in replicate (n=3). Table 1 shows the MIC results for 5 bacterial strains. (−) sign means no bacterial growth, (+) apparent bacterial growth, (0) means unchanged. This Table shows that the antibacterial process is MGO concentration dependent. But the working concentrations of 2.5 and 1.25 mg MGO/g solvents was taken into consideration when manufacturing the MGO coatings. TABLE 1MGO concentration in solvent(mg of MGO/g of solvent)Bacteria1052.51.250.620.310.16Klebsiella00−−+++pneumoniaAeruginosaMRSA00−−+++StaphylococcusEpidermidis00−−−++PseudomonasPA-UHG-100−−−++00−−+++ EQUIVALENTS The foregoing description details presently preferred embodiments of the present invention. Numerous modifications and variations in practice thereof are expected to occur to those skilled in the art upon consideration of these descriptions. Those modifications and variations are intended to be encompassed within the claims appended hereto. | 27,806 |
11857696 | Reference characters in the written specification indicate corresponding items shown throughout the drawing figures. DETAILED DESCRIPTION Referring toFIGS.1,3, and4, a shield20for protecting a recurrent laryngeal nerve22is shown according to one embodiment. The shield20is shaped to correspond to the shape and structure of the recurrent laryngeal nerve22(e.g., adjacent the thyroid23). The shape of the shield20accommodates the branching of the recurrent laryngeal nerve22into an external branch24and an internal branch26. The shape of the shield20permits the recurrent laryngeal nerve22to maintain its normal, pre-surgical shape while being protected by the shield20. This shape of the shield20negates the need to straighten or otherwise manipulate the recurrent laryngeal nerve22to cover it with the shield. This is advantageous because manipulating the recurrent laryngeal nerve22may damage the nerve and/or cause scarring. The shaped nature of the shield20may provide a further advantage in that the shield need not be shaped to fit the recurrent laryngeal nerve22. For example, the shield20may be of a material that is fragile and susceptible to tearing, bunching, or the like. A rectangular, square, or other such shape that is not tailored to the recurrent laryngeal nerve may bunch up during application over the recurrent laryngeal nerve complicating positioning. The shield may bunch up and adhere to itself such that the shield cannot cover the recurrent laryngeal nerve. In some embodiments, a parathyroid gland can be covered or contacted with a shield comprising amniotic tissue. A shield comprised of amniotic tissue that is configured to cover or contact a parathyroid gland can be in the form of a square, rectangle, a circle, oblong, or irregular shape. In general, such squares, rectangles, circles, oblongs, or irregular shapes can be at least about 1 centimeter (cm) square, at least about 1 centimeter in width (for a rectangle or oblong), or about 1 centimeter in diameter (for a circle). Examples of shields that can be used to cover or contact a parathyroid gland include but are not limited to squares of from 0.5 cm×0.5 cm to 2 cm×2 cm, or rectangles or oblongs of from 0.5 cm to 2 cm×0.5 cm to 2 cm, or circles having diameters of from about 0.5 cm to 2 cm. In some embodiments, the shield20or parathyroid gland shield comprises extraembryonic tissue. For example, the shield20or parathyroid gland shield may be entirely or partially of human amniotic tissue. The shield20or parathyroid gland shield may be of commercially available amniotic tissue such as Surgraft® Dehydrated Amniotic Sheet, BIOVANCE® Human Amniotic Membrane Allograft, AMNIOEXCEL® Amniotic Allograft Membrane, Biotissue® AmnioGraft®, AMNIOX® amniotic membrane products, or Wright™ ACTISHIELD™. In alternative embodiments, the shield is of one or more of human amniotic tissue, human chorionic tissue, animal amniotic tissue, or animal chorionic tissue. For example, the shield20or parathyroid gland shield may comprise a combination of human amniotic tissue and human chorionic tissue. In still further alternative embodiments, the shield20is of biologic tissue suitable for protecting the recurrent laryngeal nerve22or the parathyroid gland shield is suitable for protecting a parathyroid gland. The biologic tissue may have one or more of the following characteristics: (1) man-made biologic; (2) surface roughness (e.g., mean roughness Ra or root mean square roughness RMS) of not more than 200% greater than that of suitable human amniotic tissue, and more preferably of not more than 50% greater than that of suitable human amniotic tissue, and even more preferably of not more than 25% greater than that of suitable human amniotic tissue (where suitable human amniotic tissue constitutes any of the following commercially available products: Surgraft® Dehydrated Amniotic Sheet, BIOVANCE® Human Amniotic Membrane Allograft, AMNIOEXCEL® Amniotic Allograft Membrane, Biotissue® AmnioGraft®, AMNIOX® amniotic membrane products, and Wright™ ACTISHIELD™); (3) dissolvable or absorbable within a few days; (4) thin (e.g., have a thickness such that the tissue is translucent or transparent); (5) malleable; (6) transparent; (7) translucent; (8) non-inflammatory; (9) non-immunogenic such that it poses little if any risk of foreign body reaction; and (10) flexible such that the tissue takes on the shape of surrounding tissue (e.g., the tissue retains the general curved shape but is sufficiently flexible to conform to the tissues on which the tissue lays). In still further embodiments, the shield20or parathyroid gland shield comprises a combination of biologic tissue and other tissue (e.g., human amniotic tissue, human chorionic tissue, animal amniotic tissue, and/or animal chorionic tissue). The shield20may comprise compounds and/or materials to assist in protection of the recurrent laryngeal nerve22and/or assist in healing of the recurrent laryngeal nerve and/or surrounding tissues following the procedure. Similarly, the parathyroid gland shield may comprise compounds and/or materials to assist in protection of the parathyroid gland and/or assist in healing of the parathyroid gland and/or surrounding tissues following the procedure. For example, and without limitation, the shield may comprise an extracellular Matrix (ECM), growth factors, fibronectin, proteoglycans, laminin, and/or other proteins. The shield20or parathyroid gland shield may downregulate TGF-B, inhibit MMP's, suppress inflammatory cytokines, promote angiogenesis, suppress cell death (e.g., parathyroid gland cell death), and/or decrease fibroblast formation. Regardless of material, the shield20or parathyroid gland shield is typically cut from a sheet of the material before it is provided to a surgeon. This allows a surgeon to use the shield20or parathyroid gland shield without cutting out the shield from a sheet which takes time and can be difficult to do without damaging the material. The shield20or parathyroid gland shield may be cut from a sheet of material during a manufacturing process using a die cutting system or the like. This provides for more accurate shaping and a reduction in damage to the shield material in comparison to other techniques such as using scissors or a scalpel to cut the shape of the shield. Typically, the sheet will be of a relatively uniform thickness resulting in a shield20or parathyroid gland shield having a relatively uniform thickness. For example, and without limitation, the thickness of the shield20or parathyroid gland shield does not deviate at any one point more than 20% from the average thickness of the shield. The shield20protects the recurrent laryngeal nerve22from rubbing and/or friction. The shield20further protects the recurrent laryngeal nerve22from desiccation by covering the nerve. The shield20further protects the recurrent laryngeal nerve22from electrical injury from instruments by providing an insulating layer and/or alternative electrical path. The shield20still further protects the recurrent laryngeal nerve22from bacteria or other pathogens by serving as a barrier when applied. When constructed of amnion, the shield20may further have anti-bacterial properties in addition to forming a barrier. As shown inFIGS.1and4, the shape of the shield20includes several features to accommodate the recurrent laryngeal nerve22to provide at least the benefits described herein (e.g., being shaped to match the recurrent laryngeal nerve22such that the shield's dimensions need not be modified before being applied to the recurrent laryngeal nerve22). The shield20includes a first end edge28and a second end edge30opposite the first end edge28. The shield20diverges away from the first end edge28and toward the second end edge30. A first curved side edge32extends between the first28and second30end edges, and a second curved side edge34extends between the first28and second30end edges. Resulting from the divergence, the shield20includes a narrow region36and a flared region38. The narrow region36is narrower than the flared region38. The second end edge30of the flared region extends adjacent the larynx40of the subject when the shield is applied to the recurrent laryngeal nerve22. The external24and internal26branches of the recurrent laryngeal nerve22enter the larynx40, and the second end edge30and the shield20are shaped such that the second end edge30is adjacent the larynx24and the flared region38covers the branching of the recurrent laryngeal nerve22. The curvature of each of the first and second curved side edges32,34follows the curvature of the upper aspect42of the recurrent laryngeal nerve22. The shield20has a length L of between 3.5 centimeters and 4.5 centimeters, inclusive. In some embodiments, the length L is approximately 4 centimeters. In some embodiments, the shield20has a maximum width W of between 0.5 centimeters and 1.5 centimeters, inclusive. In some embodiments, the maximum width W is approximately 1 centimeter. The shield20is sized to overlay and cover the recurrent laryngeal nerve22. In some embodiments, the shield20is sized such that the shield20overlays either side of recurrent laryngeal nerve22by approximately 2-4 millimeters. The overlay allows the shield20to adhere to the underlying tissues as a result of water surface tension and to move with the recurrent laryngeal nerve22rather than move across or separately from the underlying tissues. It should be noted that ideally the shield20is reversible such that the shield20may be applied to either a right or a left recurrent laryngeal nerve22. The shield20may be flipped over as needed to align with either nerve. Alternatively, the shield20may be available in a right or left version. Referring now toFIG.2, an alternative embodiment of a shield120is shown. The shield120is similar to or the same as the shield20discussed with reference toFIG.1with like part numbers referring to like features (e.g., the first end edge28is the same as the first end edge128). The shield120includes a second end edge130that extends along a 30 degree angle A that corresponds to the typical angle of the recurrent laryngeal nerve22as it enters the larynx40. Referring toFIG.4, the shield20or120is used in covering a portion of the recurrent laryngeal nerve22of a subject. Advantageously, the shield20is provided pre-cut to the surgeon for use in protecting the recurrent laryngeal nerve such that the handling of the shield is reduced. In some embodiments, the shield20is provided to a surgeon as a part of a kit for use with a procedure of the type described herein. In one embodiment, the kit includes the shield20for covering the recurrent laryngeal nerve and a cotton tip swab for applying the shield. The cotton tip swab can be treated or otherwise pre-prepared to be adapted for use with the shield. For example, the cotton tip swab may be a sterilized cotton tip swab. The covering of the recurrent laryngeal nerve occurs during a neck surgery. The neck surgery comprises performing a procedure on the subject after covering the portion of the recurrent laryngeal nerve with the shield. The procedure comprises performing surgery on one or more of a thyroid, parathyroid, esophagus, trachea, larynx, pharynx, cervical spine, cervical lymph node, or carotid artery. For example, during a thyroidectomy, the recurrent laryngeal nerve22is exposed. The shield20will typically be applied promptly after exposure of the recurrent laryngeal nerve22. This protects the recurrent laryngeal nerve22during the remainder of the thyroidectomy and the completion of the neck surgery. In this example, the remainder of the thyroidectomy constitutes the procedure. In some cases, the procedure may be prolonged, e.g., by a neck dissection to remove local lymph nodes. In such cases, the shield20protects the recurrent laryngeal nerve22throughout (e.g., prevents desiccation and decreases the likeliness of electrical injury or direct instrument trauma during a prolonged procedure). The surgeon refrains from removing the shield20from the recurrent laryngeal nerve22during the neck surgery and the shield20is left in the subject post-surgery. During the procedure, such as the remainder of the thyroidectomy or any of the other procedures, the surgeon refrains from moving the shield20relative to the recurrent laryngeal nerve22. When placing the shield20over the recurrent laryngeal nerve22, the flared region38overlays the external and internal branches24,26of the recurrent laryngeal nerve22. The narrow region36covers a portion of the recurrent laryngeal nerve22prior to the branching. The second end edge30of the shield20extends adjacent the larynx40. The recurrent laryngeal nerve22is in its pre-surgical shape upon being covered. In other words, the recurrent laryngeal nerve22is not reshaped (e.g., straightened) before being covered by the shield20. The shape of the shield20also facilitates the placement of the shield20while avoiding creases or folds in the shield20. Further, when placing the shield20over the recurrent laryngeal nerve22, the first curved side32and the second curved side34follows the curvature of the curved upper aspect of the recurrent laryngeal nerve22. In an example of placing the shield20, a first end margin44of the shield20is grasped and a second end margin46of the shield20is grasped. The shield20is oriented relative to the recurrent laryngeal nerve22such that the second end edge30of the shield20is adjacent the larynx40of the subject and such that the curvature of each of the first32and second34side edges corresponds to the curvature of the curved upper aspect of the recurrent laryngeal nerve22. The shield20is brought into contact with the recurrent laryngeal nerve22such that a portion of the shield20contacts the nerve22while the grasping of at least one of the two end margins is maintained. For example, a cotton-tip swab is used to press an intermediate portion of the shield20to the recurrent laryngeal nerve22. Next, the grasp on at least one of the two end margins is released. For example, the shield20is applied from the intermediate portion outward toward the two opposite ends. After the recurrent laryngeal nerve22is covered, at least partially, by the shield20, surgery procedure is performed (e.g., the removal of the thyroid in a thyroidectomy) by the surgeon. This allows the shield20to protect the recurrent laryngeal nerve20throughout the procedure and during any other portion of the operation (e.g., such as a neck dissection for lymph node removal) and/or after the procedure is completed. As such, the shield20reduces the chances of damage to the recurrent laryngeal nerve22and/or other negative outcomes of the type described herein. In some embodiments, the shield20is left in place at the conclusion of the operation to protect the exposed surface of the recurrent laryngeal nerve from the movement of muscles and other tissues which lay across the exposed surface of the recurrent laryngeal nerve which is subject to trauma from friction during movement of the neck during the healing process. The shield20may also prevent scar formation between the recurrent laryngeal nerve and overlying tissues which ordinarily would not be adjacent to the recurrent laryngeal nerve. At the conclusion of the operation, the recurrent laryngeal nerve is exposed and laying upon the top surface of underlying tissues. When the wound is closed, the tissues above are laid down on the recurrent laryngeal nerve and thus the recurrent laryngeal nerve is exposed within the interface of the two tissue bodies. In such a situation, movement of the patient's neck (even minor movement) causes the recurrent laryngeal nerve to be rubbed on and traumatized by the overlying muscles and tissues. This can cause injuries to the recurrent laryngeal nerve during the first 24 hours after the procedure until the tissues begin to stick together and no longer slide relative to each other at the interface between the underlying and overlying tissues. The shield20minimizes or prevents such rubbing and may reduce or prevent such injuries. Although discussed with respect to certain exemplary operations herein, the shield20is suitable for use during any operation in which the recurrent laryngeal nerve is exposed. For example, other procedures may include anterior cervical spine fusion, Carotid endarterectomy, central neck dissection for lymph nodes and/or cancers of various types, cricopharyngeal myotomy, esophagectomy (cervical approach), excision of Zenker's diverticulum, hemithyroidectomy or other partial thyroidectomy, lateral neck dissection for lymph nodes and/or cancer of various types, modified radical neck dissection (or radical neck dissection), neck biopsy, parathyroidectomy of all forms, partial laryngectomy, substernal goiter resection, and thyroidectomy partial or total. Also provided herein are methods for covering or contacting a parathyroid gland with a parathyroid gland protective injection. Such parathyroid gland protective injections can comprise liquids or flowable liquids that can be delivered to the parathyroid gland and/or adjacent regions with a syringe or other device. Parathyroid gland protective injections provided herein can be used either alone or in conjunction with a parathyroid shield. In some embodiments, the parathyroid gland protective injections can comprise delivery of injectable liquid or flowable forms of amniotic tissue around and/or on a parathyroid gland. Suitable forms of injectable amniotic tissue include liquid or flowable forms of extraembryonic tissue (e.g. one or more of human amniotic tissue, human chorionic tissue, non-human amniotic tissue, or non-human chorionic tissue). Suitable forms of injectable amniotic tissue include but are not limited to flowable amniotic membrane allografts that are typically injected into joints are available in 0.5 cc, 1 cc, and 2 cc vials from various manufacturers (e.g. SurForce®, Surgenex, Scottsdale, Arizona, 85260) and can be adapted for use in the methods for protecting parathyroid glands provided herein. In some embodiments, the parathyroid gland protective injections can comprise delivery of stem cell, a stem cell exudate, or a combination thereof around and/or on a parathyroid gland. In some embodiments, the stem cell and/or stem cell exudate is an autologous stem cell and/or an autologous stem cell exudate. In some embodiments, the stem cell and/or stem cell exudate is an allogeneic stem cell and/or an allogeneic stem cell exudate. Non-limiting examples of autologous or allogenic stem cells and stem cell exudates include bone marrow, molar, peripheral blood, adipose, amniotic fluid, and umbilical cord blood stem cells and stem cell exudates. Stem cell exudates that can be used include stem cell conditioned media and components thereof. Stem cell conditioned media can be obtained by culturing the stem cells in media from about 16 hours to about five days (Pawitan J A. 2014; 2014:965849. doi: 10.1155/2014/965849). In certain embodiments, the stem cell exudate comprises one or more growth factors, cytokines, and/or antiinflammatory agents. Such growth factors include but are not limited to VEGF, FGF2, EGF, HGF, PIGF, SDF-1, PDGF, TGF-beta1, and PDEGF (Ibid). Such cytokines include but are not limited to IL-8, IL-9, UPA, thrombospondins 1 and 2, serpin E-1, SDF-1, TIMP-1, IGFBP, ADM, and DKK 1 (Ibid). Antiinflammatory agents include but are not limited to IL-10, IL-1ra, IL-13 and IL-27 (Zagoura et al. Gut. 2012 June; 61(6):894-906. doi:10.1136/gutjnl-2011-300908). The covering or contacting of the parathyroid gland can occur during a neck surgery (e.g., following a thyroidectomy or during or following a parathyroid surgery) or in reconstructive surgery (e.g., following an injury to the neck). The neck surgery procedures where the parathyroid gland can be covered or contacted as disclosed herein can comprise performing surgery on one or more of a thyroid, parathyroid, esophagus, trachea, larynx, pharynx, cervical spine, cervical lymph node, or carotid artery. For example, during a thyroidectomy and during parathyroid surgery, the parathyroid glands exposed and/or perturbed. The parathyroid shield and/or parathyroid gland protective injection can be applied at any stage during the procedure but is most typically performed once actions that will expose and/or perturb the parathyroid gland are complete (e.g., after a thyroidectomy or after commencement of the procedure on the thyroid). In some embodiments, the parathyroid is covered or contacted by a step comprising laying the layer of extraembryonic tissue over the parathyroid gland. In some embodiments, the covering or contacting of the parathyroid glands comprises injecting parathyroid gland protective injection (e.g., with extraembryonic tissue, stem cells, stem cell exudates, and/or any combination thereof) on and/or adjacent the parathyroid gland. In some embodiments, the parathyroid gland that is covered or contacted is ischemic or pre-ischemic. In some embodiments, the parathyroid gland(s) are removed and autotransplanted to another location and covered or contacted and the shield or injected material is left in the subject post-surgery. In some embodiments, the parathyroid gland is left in situ (e.g. is not transplanted) during the surgery and covered or contacted with the parathyroid shield and/or parathyroid gland protective injection. In some embodiments, the surgeon refrains from removing the parathyroid gland shield or parathyroid gland protective injection from the parathyroid gland during the neck or reconstructive surgery and the shield or injected material is left in the subject post-surgery. In certain embodiments, the subject's parathyroid function as measured by parathyroid hormone (PTH) levels and serum calcium levels is monitored before surgery to establish a baseline PTH and calcium levels and/or at various intervals post-surgery (e.g., at about 1, 2, 3, or more months post-surgery). It is anticipated that subjects receiving a parathyroid shield and/or a parathyroid gland protective injection will return to baseline or near baseline levels of parathyroid function (e.g., at least about 50%, 75%, or 90% of baseline PTH and calcium levels) more quickly (e.g., within about 1, 2, 3, or more months post-surgery) in comparison to control cohort subjects who have undergone similar procedures but have not received a parathyroid shield and/or a parathyroid gland protective injection. In view of the foregoing, it will be seen that the several advantages of the disclosure are achieved and attained. The embodiments were chosen and described in order to best explain the principles of the disclosure and its practical application to thereby enable others skilled in the art to best utilize the disclosure in various embodiments and with various modifications as are suited to the particular use contemplated. As various modifications could be made in the constructions and methods herein described and illustrated without departing from the scope of the disclosure, it is intended that all matter contained in the foregoing description or shown in the accompanying drawings shall be interpreted as illustrative rather than limiting. Thus, the breadth and scope of the present disclosure should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims appended hereto and their equivalents. | 23,533 |
11857697 | DEFINITIONS As used herein, the term “pluripotent stem cells (PSCs),” also commonly known as PS cells, encompasses any cells that can differentiate into nearly all cells, i.e., cells derived from any of the three germ layers (germinal epithelium), including endoderm (interior stomach lining, gastrointestinal tract, the lungs), mesoderm (muscle, bone, blood, urogenital), and ectoderm (epidermal tissues and nervous system). PSCs can be the descendants of totipotent cells, derived from embryonic stem cells (including embryonic germ cells) or obtained through induction of a non-pluripotent cell, such as an adult somatic cell, by forcing the expression of certain genes. As used herein, the term “embryonic stem cells (ESCs),” also commonly abbreviated as ES cells, refers to cells that are pluripotent and derived from the inner cell mass of the blastocyst, an early-stage embryo. For purpose of the present invention, the term “ESCs” is used broadly sometimes to encompass the embryonic germ cells as well. As used herein, the term “induced pluripotent stem cells (iPSCs),” also commonly abbreviated as iPS cells, refers to a type of pluripotent stem cells artificially derived from a normally non-pluripotent cell, such as an adult somatic cell, by inducing a “forced” expression of certain genes. As used herein, the term “precursor cell” encompasses any cells that can be used in methods described herein, through which one or more precursor cells acquire the ability to renew itself or differentiate into one or more specialized cell types. In some embodiments, a precursor cell is pluripotent or has the capacity to becoming pluripotent. In some embodiments, the precursor cells are subjected to the treatment of external factors (e.g., growth factors) to acquire pluripotency. In some embodiments, a precursor cell can be a totipotent (or omnipotent) stem cell; a pluripotent stem cell (induced or non-induced); a multipotent stem cell; an oligopotent stem cells and a unipotent stem cell. In some embodiments, a precursor cell can be from an embryo, an infant, a child, or an adult. In some embodiments, a precursor cell can be a somatic cell subject to treatment such that pluripotency is conferred via genetic manipulation or protein/peptide treatment. In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. As used herein, the term “directed differentiation” describes a process through which a less specialized cell becomes a particular specialized target cell type. The particularity of the specialized target cell type can be determined by any applicable methods that can be used to define or alter the destiny of the initial cell. Exemplary methods include but are not limited to genetic manipulation, chemical treatment, protein treatment, and nucleic acid treatment. As used herein, the term “cellular constituents” are individual genes, proteins, mRNA expressing genes, and/or any other variable cellular component or protein activities such as the degree of protein modification (e.g., phosphorylation), for example, that is typically measured in biological experiments (e.g., by microarray or immunohistochemistry) by those skilled in the art. Significant discoveries relating to the complex networks of biochemical processes underlying living systems, common human diseases, and gene discovery and structure determination can now be attributed to the application of cellular constituent abundance data as part of the research process. Cellular constituent abundance data can help to identify biomarkers, discriminate disease subtypes and identify mechanisms of toxicity. As used herein, the term “organoid” is used to mean a 3-dimensional growth of mammalian cells in culture that retains characteristics of the tissue in vivo, e.g. prolonged tissue expansion with proliferation, multilineage differentiation, recapitulation of cellular and tissue ultrastructure, etc. DETAILED DESCRIPTION OF THE INVENTION Experiments conducted during the course of developing embodiments for the present invention aimed to increase the understanding of how multiple growth factor signaling pathways interact to promote maintenance of distal epithelial progenitors in an undifferentiated state. Second, experiments were aimed to elucidate the mechanisms by which distal epithelial progenitor cells of the human fetal lung are maintained and could be expanded and passaged in culture. Third, experiments were aimed to use new information gained from ex vivo culture of mouse and human fetal bud-tip progenitors in a predictive manner, in order to differentiate, de novo, distal epithelial lung progenitor-like cells from hPSCs. Using isolated epithelial distal-tip progenitor cells from mouse and human fetal lungs during branching morphogenesis, experiments screened growth factors implicated in lung development individually and in combination for their ability to promote tissue expansion and maintenance of progenitor identity in vitro. The results demonstrated that FGF7 promoted robust growth and expansion of both mouse and human epithelial progenitors, but could not maintain the progenitor population, which underwent differentiation. In the mouse, FGF signaling (FGF7+/−FGF10) plus either CHIR-99021 (to stabilize β-catenin) or All-trans Retinoic Acid (RA) increased mRNA and protein expression of the distal epithelial progenitor marker, SOX9, and led to growth/expansion and improved epithelial architecture in vitro. Synergistic activity of all 4 factors (FGF7/FGF10/CHIR-99021/RA; 4-factor; ‘4F’ conditions) led to the highest mRNA expression of Sox9 in mice, whereas in human fetal lung buds we found that only 3-factors ‘3F’ (FGF7, CHIR-99021, RA) were required to maintain growth, allow tissue expansion, and maintain expression of distal epithelial progenitor genes, including SOX9, ID2 and NMYC. Together, these results suggested that FGF, WNT and RA signaling act synergistically to maintain distal progenitor identity in vitro in both mouse and human distal-tip progenitor cells, but that these pathways affected epithelial progenitors in subtly different ways between species. Unexpectedly, such results also revealed that distal epithelial progenitor cells in the human lung express SOX2, which is exclusively expressed in the proximal airway in mice (Hashimoto et al., 2012; Que et al., 2007), identifying an important molecular difference between mouse and human progenitor cells. When applied to hPSC-derived foregut spheroid cultures, it was observed that 3F conditions promoted robust epithelial growth into larger organoid structures. hPSC-derived organoids grown in 3F media developed a patterned epithelium, with proximal airway-like domains and distal epithelial bud-like domains that possessed SOX9/SOX2+ cells with a molecular profile similar to the human fetal lung buds. Taken together, these studies provide an improved mechanistic understanding of human lung epithelial progenitor cell regulation, and highlight the importance of using developing tissues to provide a framework for improving differentiation of hPSCs into specific lineages. Accordingly, the invention disclosed herein generally relates to methods and systems for growing, expanding and/or obtaining 3-dimensional lung-like epithelium comprising cells having SOX9 protein activity and SOX2+ protein activity. In particular, the invention disclosed herein relates to methods and systems for growing human cells having SOX9 protein activity and SOX2+ protein activity in vitro, and for promoting pluripotent stem cell derived ventral-anterior foregut spheroid tissue into 3-dimensional lung-like epithelium comprising cells having SOX9 protein activity and SOX2+ protein activity. In some embodiments, the ventral-anterior foregut spheroid tissue is derived from definitive endoderm cells. In some embodiments, the definitive endoderm cells are derived from pluripotent stem cells. In some embodiments, the pluripotent stem cells are embryonic stem cells and/or induced pluripotent stem cells and/or or cells obtained through somatic cell nuclear transfer. In some embodiments, an important step is to obtain stem cells that are pluripotent or can be induced to become pluripotent. In some embodiments, pluripotent stem cells are derived from embryonic stem cells, which are in turn derived from totipotent cells of the early mammalian embryo and are capable of unlimited, undifferentiated proliferation in vitro. Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Methods for deriving embryonic stem cells from blastocytes are well known in the art. For example, three cell lines (H1, H13, and H14) have a normal XY karyotype, and two cell lines (H7 and H9) have a normal XX karyotype. Additional stem cells that can be used in embodiments in accordance with the present invention include but are not limited to those provided by or described in the database hosted by the National Stem Cell Bank (NSCB), Human Embryonic Stem Cell Research Center at the University of California, San Francisco (UCSF); WISC cell Bank at the Wi Cell Research Institute; the University of Wisconsin Stem Cell and Regenerative Medicine Center (UW-SCRMC); Novocell, Inc. (San Diego, Calif.); Cellartis AB (Goteborg, Sweden); ES Cell International Pte Ltd (Singapore); Technion at the Israel Institute of Technology (Haifa, Israel); and the Stem Cell Database hosted by Princeton University and the University of Pennsylvania. Indeed, embryonic stem cells that can be used in embodiments in accordance with the present invention include but are not limited to SA01 (SA001); SA02 (SA002); ES01 (HES-1); ES02 (HES-2); ES03 (HES-3); ES04 (HES-4); ES05 (HES-5); ES06 (HES-6); BG01 (BGN-01); BG02 (BGN-02); BG03 (BGN-03); TE03 (13); TE04 (14); TE06 (16); UC01 (HSF1); UC06 (HSF6); WA01 (H1); WA07 (H7); WA09 (H9); WA13 (H13); WA14 (H14). In some embodiments, the stem cells are further modified to incorporate additional properties. Exemplary modified cell lines include but not limited to H1 OCT4-EGFP; H9 Cre-LoxP; H9 hNanog-pGZ; H9 hOct4-pGZ; H9 in GFPhES; and H9 Syn-GFP. More details on embryonic stem cells can be found in, for example, Thomson et al., 1998, Science282 (5391):1145-1147; Andrews et al., 2005, Biochem Soc Trans33:1526-1530; Martin 1980, Science209 (4458):768-776; Evans and Kaufman, 1981, Nature292(5819): 154-156; Klimanskaya et al., 2005, Lancet365 (9471): 1636-1641). Alternative, pluripotent stem cells can be derived from embryonic germ cells (EGCs), which are the cells that give rise to the gametes of organisms that reproduce sexually. EGCs are derived from primordial germ cells found in the gonadal ridge of a late embryo, have many of the properties of embryonic stem cells. The primordial germ cells in an embryo develop into stem cells that in an adult generate the reproductive gametes (sperm or eggs). In mice and humans it is possible to grow embryonic germ cells in tissue culture under appropriate conditions. Both EGCs and ESCs are pluripotent. For purpose of the present invention, the term “ESCs” is used broadly sometimes to encompass EGCs. In some embodiments, iPSCs are derived by transfection of certain stem cell-associated genes into non-pluripotent cells, such as adult fibroblasts. Transfection is typically achieved through viral vectors, such as retroviruses. Transfected genes include the master transcriptional regulators Oct-3/4 (Pouf51) and Sox2, although it is suggested that other genes enhance the efficiency of induction. After 3-4 weeks, small numbers of transfected cells begin to become morphologically and biochemically similar to pluripotent stem cells, and are typically isolated through morphological selection, doubling time, or through a reporter gene and antibiotic selection. As used herein, iPSCs include but are not limited to first generation iPSCs, second generation iPSCs in mice, and human induced pluripotent stem cells. In some embodiments, a retroviral system is used to transform human fibroblasts into pluripotent stem cells using four pivotal genes: Oct3/4, Sox2, Klf4, and c-Myc. In alternative embodiments, a lentiviral system is used to transform somatic cells with OCT4, SOX2, NANOG, and LIN28. Genes whose expression are induced in iPSCs include but are not limited to Oct-3/4 (e.g., Pou5fl); certain members of the Sox gene family (e.g., Sox1, Sox2, Sox3, and Sox15); certain members of the Klf family (e.g., Klf1, Klf2, Klf4, and Klf5), certain members of the Myc family (e.g., C-myc, L-myc, and N-myc), Nanog, and LIN28. More details on induced pluripotent stem cells can be found in, for example, Kaji et al., 2009, Nature458:771-775; Woltjen et al., 2009, Nature458:766-770; Okita et al., 2008, Science322(5903):949-953; Stadtfeld et al., 2008, Science322(5903):945-949; and Zhou et al., 2009, Cell Stem Cell4(5):381-384. In some embodiments, examples of iPS cell lines include but not limited to iPS-DF19-9; iPS-DF19-9; iPS-DF4-3; iPS-DF6-9; iPS(Foreskin); iPS(IMR90); and iPS(IMR90). The lungs of mammals including those of humans, have a soft, spongelike texture and are honeycombed with epithelium, having a much larger surface area in total than the outer surface area of the lung itself. Breathing is largely driven by the muscular diaphragm at the bottom of the thorax. Contraction of the diaphragm pulls the bottom of the cavity in which the lung is enclosed downward, increasing volume and thus decreasing pressure, causing air to flow into the airways. Air enters through the oral and nasal cavities; it flows through the pharynx, then the larynx and into the trachea, which branches out into the main bronchi and then subsequent divisions. During normal breathing, expiration is passive and no muscles are contracted (the diaphragm relaxes). The rib cage itself is also able to expand and contract to some degree through the use of the intercostal muscles, together with the action of other respiratory and accessory respiratory muscles. As a result, air is transported into or expelled out of the lungs. In humans, the trachea divides into two main bronchi that enter the roots of the lungs. The bronchi continue to divide within the lung, and after multiple divisions, give rise to bronchioles. The bronchial tree continues branching until it reaches the level of terminal bronchioles, which lead to alveolar sacs. Alveolar sacs, are made up of clusters of alveoli, like individual grapes within a bunch. The individual alveoli are tightly wrapped in blood vessels and it is here that gas exchange actually occurs. Deoxygenated blood from the heart is pumped through the pulmonary artery to the lungs, where oxygen diffuses into blood and is exchanged for carbon dioxide in the haemoglobin of the erythrocytes. The oxygen-rich blood returns to the heart via the pulmonary veins to be pumped back into systemic circulation. Human lungs are located in two cavities on either side of the heart. Though similar in appearance, the two are not identical. Both are separated into lobes by fissures, with three lobes on the right and two on the left. The lobes are further divided into segments and then into lobules, hexagonal divisions of the lungs that are the smallest subdivision visible to the naked eye. The connective tissue that divides lobules is often blackened in smokers. The medial border of the right lung is nearly vertical, while the left lung contains a cardiac notch. The cardiac notch is a concave impression molded to accommodate the shape of the heart. Each lobe is surrounded by a pleural cavity, which consists of two pleurae. The parietal pleura lies against the rib cage, and the visceral pleura lies on the surface of the lungs. In between the pleura is pleural fluid. The pleural cavity helps to lubricate the lungs, as well as providing surface tension to keep the lung surface in contact with the rib cage. Lungs are to a certain extent “overbuilt” and have a tremendous reserve volume as compared to the oxygen exchange requirements when at rest. Such excess capacity is one of the reasons that individuals can smoke for years without having a noticeable decrease in lung function while still or moving slowly; in situations like these only a small portion of the lungs are actually perfused with blood for gas exchange. Destruction of too many alveoli over time leads to the condition emphysema, which is associated with extreme shortness of breath. As oxygen requirements increase due to exercise, a greater volume of the lungs is perfused, allowing the body to match its CO2/O2exchange requirements. Additionally, due to the excess capacity, it is possible for humans to live with only one lung, with the one compensating for the other's loss. The environment of the lung is very moist, which makes it hospitable for bacteria. Many respiratory illnesses are the result of bacterial or viral infection of the lungs. Inflammation of the lungs is known as pneumonia; inflammation of the pleura surrounding the lungs is known as pleurisy. Vital capacity is the maximum volume of air that a person can exhale after maximum inhalation; it can be measured with a spirometer. In combination with other physiological measurements, the vital capacity can help make a diagnosis of underlying lung disease. The lung parenchyma is strictly used to refer solely to alveolar tissue with respiratory bronchioles, alveolar ducts and terminal bronchioles. However, it often includes any form of lung tissue, also including bronchioles, bronchi, blood vessels and lung interstitium. Following gastrulation (embryonic day E7.5 in mice), the definitive endoderm undergoes complex morphogenetic movements that ultimately lead to the formation of the primitive gut tube. The foregut represents the most anterior (cranial) region of this tube, while the midgut and hindgut are located at progressively more posterior regions, towards the caudal end of the embryo (see, e.g., Wells, et al., Annu. Rev. Cell Dev. Biol. 15, 393-410). Transcription factor genes such as Foxa1, Foxa2, Gata4 and Gata6, which are expressed early in the endoderm, are crucial for the survival, differentiation and morphogenesis of the foregut (see, e.g., Kuo, et al., Genes Dev. 11, 1048-1060; Morrisey, et al., Genes Dev. 12, 3579-3590; Ang, et al., Cell 78, 561-574; Wan, et al., J. Biol. Chem. 280, 13809-13816). By E8.0-9.5, the local expression of transcription factors along the anteroposterior (AP) axis of the gut endoderm marks organ-specific domains (or fields). For example, the homeodomain protein gene Nkx2.1 [also known as thyroid transcription factor 1 (Titf1) or T/EBP] is expressed in the thyroid and respiratory fields (see, e.g., Kimura, et al., Genes Dev. 10, 60-69), Hex (hematopoietically expressed homeobox) is expressed in the thyroid and liver fields (see, e.g., Martinez Barbera, et al., Development 127, 2433-2445), and the Pdx1 (pancreas-duodenal-associated homeobox gene) is expressed in the pancreatic and duodenal fields (see, e.g., Offield, et al., Development 122, 983-995). In addition, morphogenetic movements foster dynamic interactions between the endoderm and neighboring structures, such as the heart, notochord or the septum transversum (the mesodermal cells that give rise to the diaphragm). Exposure of the endoderm to diffusible signals from these structures at crucial developmental windows is essential for endodermal cell fate specification (see, e.g., Kumar and Melton, Curr. Opin. Genet. Dev. 13, 401-407; Bort, et al., Development 131, 797-80). Fibroblast growth factor 4 (Fgf4), bone morphogenetic protein 2 (Bmp2) and retinoic acid (RA) are among the signals that confer AP identity to the early endoderm. They render the endoderm competent to respond to signals from the adjacent mesoderm or from nearby structures to initiate morphogenesis (see, e.g., Tiso, eta al., Mech. Dev. 118, 29-37; Stafford and Prince, Curr. Biol. 12, 1215-1220; Wells and Melton, Development 127, 1563-1572). In zebrafish, disrupted retinoic acid (RA) signaling during gastrulation results in the loss of liver and pancreatic (posterior) fates, while thyroid and pharynx (anterior) fates remain unaltered. Conversely, excess RA induces hepatic and pancreatic cell fates at more anterior domains (see, e.g., Stafford and Prince; Curr. Biol. 12, 1215-1220). In mice and rats, RA signaling initiates soon after gastrulation (see, e.g., Rossant, et al., Genes Dev. 5, 1333-1344), but does not seem to be as crucial for foregut AP identity as it is in the zebrafish. The invention disclosed herein relates to methods and systems for promoting ventral-anterior foregut spheroid tissue into 3-dimensional lung-like epithelium comprising cells having SOX9 protein activity and SOX2+ protein activity. In some embodiments, PSCs, such as ESCs and iPSCs, undergo directed differentiation in a step-wise manner first into definitive endoderm (DE), then into ventral-anterior foregut spheroid tissue (e.g., SOX2+ anterior foregut 3D spheroid structures), then into 3-dimensional lung-like epithelium comprising cells having SOX9 protein activity and SOX2+ protein activity. As such, in some embodiments, methods are provided for the directed differentiation of pluriopotent cells (e.g., iPSCs or ESCs) into definitive endoderm, and the obtaining of such definitive endoderm. In some embodiments, methods are provided for the directed differentiation of the obtained definitive endoderm into ventral-anterior foregut spheroid tissue, and obtaining of such ventral-anterior foregut spheroid tissue. In some embodiments, methods are provided for the directed differentiation of the obtained ventral-anterior foregut spheroid tissue into 3-dimensional lung-like epithelium comprising cells having SOX9 protein activity and SOX2+ protein activity, and the obtaining of such 3-dimensional lung-like epithelium tissue. Such methods are not limited to a particular manner of accomplishing the directed differentiation of PSCs into definitive endoderm. Indeed, any method for producing definitive endoderm from pluripotent cells (e.g., iPSCs or ESCs) is applicable to the methods described herein. In some embodiments, pluripotent cells are derived from a morula. In some embodiments, pluripotent stem cells are stem cells. Stem cells used in these methods can include, but are not limited to, embryonic stem cells. Embryonic stem cells can be derived from the embryonic inner cell mass or from the embryonic gonadal ridges. Embryonic stem cells or germ cells can originate from a variety of animal species including, but not limited to, various mammalian species including humans. In some embodiments, human embryonic stem cells are used to produce definitive endoderm. In some embodiments, human embryonic germ cells are used to produce definitive endoderm. In some embodiments, iPSCs are used to produce definitive endoderm. In some embodiments, one or more growth factors are used in the differentiation process from pluripotent stem cells to DE cells. The one or more growth factors used in the differentiation process can include growth factors from the TGF-β superfamily. In such embodiments, the one or more growth factors comprise the Nodal/Activin and/or the BMP subgroups of the TGF-β superfamily of growth factors. In some embodiments, the one or more growth factors are selected from the group consisting of Nodal, Activin A, Activin B, BMP4, Wnt3a or combinations of any of these growth factors. In some embodiments, the embryonic stem cells or germ cells and iPSCs are treated with the one or more growth factors for 6 or more hours; 12 or more hours; 18 or more hours; 24 or more hours; 36 or more hours; 48 or more hours; 60 or more hours; 72 or more hours; 84 or more hours; 96 or more hours; 120 or more hours; 150 or more hours; 180 or more hours; or 240 or more hours. In some embodiments, the embryonic stem cells or germ cells and iPSCs are treated with the one or more growth factors at a concentration of 10 ng/ml or higher; 20 ng/ml or higher; 50 ng/ml or higher; 75 ng/ml or higher; 100 ng/ml or higher; 120 ng/ml or higher; 150 ng/ml or higher; 200 ng/ml or higher; 500 ng/ml or higher; 1,000 ng/ml or higher; 1,200 ng/ml or higher; 1,500 ng/ml or higher; 2,000 ng/ml or higher; 5,000 ng/ml or higher; 7,000 ng/ml or higher; 10,000 ng/ml or higher; or 15,000 ng/ml or higher. In some embodiments, concentration of the growth factor is maintained at a constant level throughout the treatment. In other embodiments, concentration of the growth factor is varied during the course of the treatment. In some embodiments, the growth factor is suspended in media that include fetal bovine serine (FBS) with varying HyClone concentrations. One of skill in the art would understand that the regimen described herein is applicable to any known growth factors, alone or in combination. When two or more growth factors are used, the concentration of each growth factor may be varied independently. In some embodiments, populations of cells enriched in definitive endoderm cells are used. In some embodiments, the definitive endoderm cells are isolated or substantially purified. In some embodiments, the isolated or substantially purified definitive endoderm cells express the SOX2+ marker. Methods for enriching a cell population with definitive endoderm are also contemplated. In some embodiments, definitive endoderm cells can be isolated or substantially purified from a mixed cell population by contacting the cells with a reagent that binds to a molecule that is present on the surface of definitive endoderm cells but which is not present on the surface of other cells in the mixed cell population, and then isolating the cells bound to the reagent. Additional methods for obtaining or creating DE cells that can be used in the present invention include but are not limited to those described in U.S. Pat. No. 7,510,876; U.S. Pat. No. 7,326,572; Kubol et al., 2004, Development 131:1651-1662; D'Amour et al., 2005, Nature Biotechnology 23:1534-1541; and Ang et al., 1993, Development 119:1301-1315. In some embodiments, directed differentiation toward ventral-anterior foregut spheroid tissue, 3-dimensional lung tissue, and lung organoid tissue is achieved by selectively activating or inhibiting certain signaling pathways in the iPSCs and/or DE cells. In some embodiments, the activated and/or inhibited signaling pathways are those active in lung development, including but not limited to the BMP signaling pathway, the TGFβ signaling pathway, the Wnt signaling pathway, the FGF signaling pathway, and the Hedgehog signaling pathway in a step-wise manner. In some embodiments, directed differentiation of definitive endoderm into 3-dimensional lung-like epithelium tissue is accomplished first through directed differentiation of definitive endoderm into ventral-anterior foregut spheroid tissue, then directed differentiation of the ventral-anterior foregut spheroid tissue into 3-dimensional lung-like epithelium tissue. Such techniques are not limited to a particular manner of inducing formation of ventral-anterior foregut spheroid tissue from definitive endoderm. In some embodiments, inducing formation of ventral-anterior foregut spheroid tissue from definitive endoderm is accomplished through selectively activating the Wnt signaling pathway and the FGF signaling pathway, and inhibiting the BMP signaling pathway, and the TGFβ signaling pathway in the DE cells. In some embodiments, activating and/or inhibiting one or more signaling pathways within the definitive endoderm cells comprises culturing the definitive endoderm cells with a Wnt signaling pathway agonist, a FGF signaling pathway agonist, a BMP signaling pathway inhibitor, and a TGF signaling pathway inhibitor. In some embodiments, activating and/or inhibiting one or more signaling pathways within the definitive endoderm cells comprises culturing the definitive endoderm cells with CHIR99021, FGF4, Noggin, and SB431542. Such techniques are not limited to a particular manner of inducing formation of 3-dimensional lung-like epithelium from the ventral-anterior foregut spheroid tissue. In some embodiments, inducing formation of 3-dimensional lung-like epithelium from the ventral-anterior foregut spheroid tissue occurs through activating the FGF signaling pathway, the retinoic acid signaling pathway, and the Wnt signaling pathway within the ventral-anterior foregut spheroid tissue. In some embodiments, the obtained tissue comprising 3-dimensional lung-like epithelium comprises cells having SOX9 protein activity and SOX2+ protein activity. In some embodiments, selective activation of the Wnt signaling pathway is accomplished with a Wnt agonist (“W”). The Wnt signalling pathway is defined by a series of events that occur when a Wnt protein binds to a cell-surface receptor of a Frizzled receptor family member. This results in the activation of Dishevelled family proteins which inhibit a complex of proteins that includes axin, GSK-3, and the protein APC to degrade intracellular β-catenin. The resulting enriched nuclear β-catenin enhances transcription by TCF/LEF family transcription factors. A Wnt agonist (e.g., a small molecule or agonist that activates the Wnt signaling pathway) is defined as an agent that activates TCF/LEF-mediated transcription in a cell. Wnt agonists are therefore selected from true Wnt agonists that bind and activate a Frizzled receptor family member including any and all of the Wnt family proteins, an inhibitor of intracellular β-catenin degradation, and activators of TCF/LEF. Said Wnt agonist is added to the iPSCs and/or DE cells for purposes of directed differentiation of such cells toward lung organoids in an amount effective to stimulate a Wnt activity in a cell by at least 10%, more preferred at least 20%, more preferred at least 30%, more preferred at least 50%, more preferred at least 70%, more preferred at least 90%, more preferred at least 100%, relative to a level of said Wnt activity in the absence of said molecule, as assessed in the same cell type. As is known to a skilled person, a Wnt activity can be determined by measuring the transcriptional activity of Wnt, for example by pTOPFLASH and pFOPFLASH Tcfluciferase reporter constructs (see, e.g., Korinek et al., 1997. Science 275:1784-1787). A Wnt agonist may comprise a secreted glycoprotein including Wnt-1/Int-1; Wnt-2/Irp (Int-1-related Protein); Wnt-2b/13; Wnt-3/Int-4; Wnt-3a (R&D systems); Wnt-4; Wnt-5a; Wnt-5b; Wnt-6 (Kirikoshi H et al. 2001. Biochem Biophys Res Com 283: 798-805); Wnt-7a (R&D systems); Wnt-7b; Wnt-8a/8d; Wnt-8b; Wnt-9a/14; Wnt-9b/14b/15; Wnt-10a; Wnt-10b/12; Wnt-11; and Wnt-16. An overview of human Wnt proteins is provided in “THE WNT FAMILY OF SECRETED PROTEINS”, R&D Systems Catalog, 2004. Further Wnt agonists include the R-spondin family of secreted proteins, which is implicated in the activation and regulation of Wnt signaling pathway and which is comprised of 4 members (R-spondin 1 (NU206, Nuvelo, San Carlos, Calif.), R-spondin 2 ((R&D systems), R-spondin 3, and R-spondin-4); and Norrin (also called Norrie Disease Protein or NDP) (R&D systems), which is a secreted regulatory protein that functions like a Wnt protein in that it binds with high affinity to the Frizzled-4 receptor and induces activation of the Wnt signaling pathway (Kestutis Planutis et al. (2007) BMC Cell Biol. 8: 12). Compounds that mimic the activity of R-spondin may be used as Wnt agonists of the invention. It has recently been found that R-spondin interacts with Lgr5. Thus, Lgr5 agonists such as agonistic anti-Lgr5 antibodies are examples of Wnt agonists that may be used in the invention. A small-molecule agonist of the Wnt signaling pathway, an aminopyrimidine derivative, was identified and is also expressly included as a Wnt agonist (Liu et al. (2005) Angew Chem Int Ed Engl. 44, 1987-90). Known GSK-inhibitors comprise small-interfering RNAs (siRNA; Cell Signaling), lithium (Sigma), kenpaullone (Biomol International; Leost, M. et al. (2000) Eur. J. Biochem. 267, 5983-5994), 6-Bromoindirubin-30-acetoxime (Meijer, L. et al. (2003) Chem. Biol. 10, 1255-1266), SB 216763 and SB 415286 (Sigma-Aldrich), and FRAT-family members and FRAT-derived peptides that prevent interaction of GSK-3 with axin. An overview is provided by Meijer et al., (2004) Trends in Pharmacological Sciences 25, 471-480. Methods and assays for determining a level of GSK-3 inhibition are known to a skilled person and comprise, for example, the methods and assay as described in Liao et al 2004, Endocrinology, 145(6): 2941-9. In some embodiments the Wnt agonist is a Gsk3 inhibitor. In some embodiments, the Gsk3 inhibitor is selected from the group consisting of CHIR 99021, CHIR 98014, BIO-acetoxime, BIO, LiCl, SB 216763, SB 415286, AR A014418, 1-Azakenpaullone, and Bis-7-indolylmaleimide. In some embodiments the Gsk3 inhibitor is CHIR 99021 or CHIR 98014 at a concentration of at least about 4 μM to about 10 μM i. In some embodiments the Gsk3 inhibitor comprises an RNAi targeted against Gsk3. In some embodiments, the Wnt agonist added to the iPSCs and/or DE cells for purposes of directed differentiation of such cells toward lung organoids is CHIR 99021. In some embodiments, CHIR 99021 is preferably added to the iPSCs and/or DE cells for purposes of directed differentiation of such cells toward lung organoids at a concentration of at least 200. In some embodiments, selective activation of the FGF signaling pathway is accomplished with a FGF agonist (“F”) (e.g., a small molecule or agonist that activates the FGF signaling pathway). In some embodiments, the FGF agonist added to the iPSCs and/or DE cells for purposes of directed differentiation of such cells toward lung organoids is able to bind to FGFR2 or FGFR4. An FGF able to bind to FGFR2 (FGF receptor) or FGFR4 is preferably FGF4, FGF7 or FGF10, most preferably FGF10. FGF10 is a protein that belongs to the fibroblast growth factor (FGF) family of proteins. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGFs stimulate cells by interacting with cell surface tyrosine kinase receptors (FGFR). Four closely related receptors (FGFR1-FGFR4) have been identified. FGFR1-FGFR3 genes have been shown to encode multiple isoforms, and these isoforms can be critical in determining ligand specificity. Most FGFs bind more than one receptor (Ornitz J Biol. Chem. 1998 Feb. 27; 273 (9):5349-57). However, FGF10 and FGF7 are unique among FGFs in that they interact only with a specific isoform of FGFR2, designated FGFR2b which is expressed exclusively by epithelial cells (Igarashi, J Biol. Chem. 1998 273(21):13230-5). FGF10 is a preferred FGF able to bind to FGFR2 or FGFR4. Preferred concentrations for FGF10 are 20, 50, 100, 500 ng/ml, not higher than 500 ng/ml. FGF (e.g., FGF10) is preferably added to the iPSCs and/or DE cells for purposes of directed differentiation of such cells toward lung organoids when required. Such methods are not limited to a particular manner of activating the RA signaling pathway. In some embodiments, activating the RA signaling pathway comprises culturing the ventral-anterior foregut spheroid tissue with a small molecule or agonist that activates the RA signaling pathway. In some embodiments, the small molecule or agonist that activates the RA signaling pathway is all-trans retinoic acid. In some embodiments, the small molecule or agonist that activates the RA signaling pathway is AC 261066 (RARβ2 agonist), AC 55649 (selective RARβ2 agonist), adapalene (RARβ and RARγ agonist), AM 580 (retinoic acid analog; RARα agonist), AM 80 (RARα agonist; anticancer), BMS 753 (RARα-selective agonist), BMS 961 (selective RARγ agonist), CD 1530 (potent and selective RARγ agonist), CD 2314 (selective RARβ agonist), CD 437 (RARγ-selective agonist), Ch 55 (potent RAR agonist), isotretinoin (endogenous agonist for retinoic acid receptors), tazarotene (receptor-selective retinoid; binds RARβ and RARγ), and TTNPB (retinoic acid analog; RAR agonist). In some embodiments, 3-dimensional lung-like epithelium comprises cells having SOX9 protein activity and SOX2+ protein activity produced in vitro from the described methods can be used to screen drugs for lung tissue uptake and mechanisms of transport. For example, this can be done in a high throughput manner to screen for the most readily absorbed drugs, and can augment Phase 1 clinical trials that are done to study drug lung tissue uptake and lung tissue toxicity. This includes pericellular and intracellular transport mechanisms of small molecules, peptides, metabolites, salts. In some embodiments, 3-dimensional lung-like epithelium comprises cells having SOX9 protein activity and SOX2+ protein activity produced in vitro from the described methods can be used to identify the molecular basis of normal human lung development. In some embodiments, 3-dimensional lung-like epithelium comprises cells having SOX9 protein activity and SOX2+ protein activity produced in vitro from the described methods can be used to identify the molecular basis of congenital defects affecting human lung development. In some embodiments, 3-dimensional lung-like epithelium comprises cells having SOX9 protein activity and SOX2+ protein activity produced in vitro from the described methods can be used to correct lung related congenital defects caused by genetic mutations. In particular, mutation affecting human lung development can be corrected using iPSC technology and genetically normal 3-dimensional lung-like epithelium comprises cells having SOX9 protein activity and SOX2+ protein activity produced in vitro from the described methods. In some embodiments, 3-dimensional lung-like epithelium comprises cells having SOX9 protein activity and SOX2+ protein activity produced in vitro from the described methods can be used to generate replacement tissue. In some embodiments, 3-dimensional lung-like epithelium comprises cells having SOX9 protein activity and SOX2+ protein activity produced in vitro from the described methods can be used to generate replacement lung tissue for lung related disorders. In some embodiments, a diagnostic kit or package is developed to include 3-dimensional lung-like epithelium comprises cells having SOX9 protein activity and SOX2+ protein activity produced in vitro from the described methods and based on one or more of the aforementioned utilities. EXAMPLES The following examples are illustrative, but not limiting, of the compounds, compositions, and methods of the present invention. Other suitable modifications and adaptations of the variety of conditions and parameters normally encountered in clinical therapy and which are obvious to those skilled in the art are within the spirit and scope of the invention. Example I This example demonstrates isolation and in vitro culture of murine distal lung bud epithelium. During branching morphogenesis, the distal epithelial bud tips are comprised of progenitor cells that remain in the progenitor state until the branching program is complete (Chang et al., 2013) and will give rise to all the mature cell types of the lung epithelium (Rawlins et al., 2009). However, the mechanisms maintaining distal progenitors in an undifferentiated state remain unclear. This population of progenitor cells is known to express several transcription factors, including Sox9, Nmyc and Id2 (Chang et al., 2013; Moens et al., 1992; Okubo et al., 2005; Perl et al., 2005; Rawlins et al., 2009; Rockich et al., 2013). In order to study this population of cells, epithelial buds were mechanically isolated from lungs of embryonic day (E) 13.5 Sox9-eGFP mice and cultured in a Matrigel droplet (FIG.1A). Sox9-eGFP heterozygous lung bud tips were confirmed to have the same level of Sox9 mRNA as their wild type counterparts by QRT-PCR analysis (FIG.2A). The isolated Sox9+ population was confirmed by GFP expression (FIG.1B). Example II This example demonstrates FGF7 promotes growth and expansion of distal epithelial lung buds. Experiments were conducted to identify culture conditions that could support the growth and expansion of distal epithelial buds in culture. Signaling events were identified from the literature essential for normal mouse lung epithelial development, including FGF signaling (FGF7 and 10) (Bellusci et al., 1997b; Cardoso et al., 1997; Min et al., 1998; Nyeng et al., 2008; Sekine et al., 1999; Volckaert et al., 2013); Wnt signaling (Elluru and Whitsett, 2004; Goss et al., 2009; Harris-Johnson et al., 2009; Kadzik et al., 2014; Mucenski et al., 2005; 2003; Shu et al., 2005); BMP signaling (Weaver et al., 2000; 1999) and RA signaling (Chen et al., 2010; Desai et al., 2006; 2004; Malpel et al., 2000). Many of these signaling events have previously been used for in vitro differentiation of hPSC-derived lung tissue (Firth et al., 2014; Ghaedi et al., 2013; Gilpin et al., 2014b; Gotoh et al., 2014; Huang et al., 2013; Konishi et al., 2015; Mou et al., 2012; Wong et al., 2012). A low-throughput screen was performed to identify factors that could promote growth of distal bud tips in culture. The screen included FGF7, FGF10, BMP4, All Trans Retinoic Acid (hereafter referred to as ‘RA’) and CHIR-99021, which inhibits GSK3β and stabilizes β-catenin (βCAT) leading to activation of βCAT-dependent signaling (FIG.1C). Treating buds with no growth factors (basal media, control) or individual growth factors showed that FGF7 promoted growth, expansion a survival of isolated buds for up to two weeks (FIG.1C). An experiment was also conducted in which all 5 factors (5F) were combined together, with one factor removed at a time (FIG.1D). Buds grew robustly in 5F media, whereas removing FGF7 from the 5F media (5F-FGF7) led to a loss of growth, even after 5 days in culture (FIG.1D). It was interesting to note that the same concentration of FGF7 and FGF10 did not have the same effect on lung bud outgrowth, since both ligands act on the FGF Receptor 2 (IIIb) isoform (FGFR2IIIb) (Ornitz et al., 1996; X. Zhang et al., 2006), and both ligands are present in the lung during branching morphogenesis (Bellusci et al., 1997b; Tichelaar et al., 2000; White et al., 2006). Previous studies have offered evidence showing that FGF10 has structural similarities with FGF7, but is differentially regulated by components of the extracellular matrix, which may influence the ease of diffusion of the ligand (Makarenkova et al., 2009). To test the possibility that diffusion of ligand through the matrix may explain experimental differences, we treated buds with a 50-fold excess of FGF10 (500 ng/mL compared to 10 ng/mL). A high concentration of FGF10 led to modest growth of buds and was sufficient to keep buds alive in culture for up to 5 days, but cultures did not exhibit the same level of growth as those treated with low levels of FGF7 (FIG.1D). Initial experimental conditions used FGF7 concentrations based on previous literature (long/mL;FIG.1) (Huang et al., 2013). Experiments next tested if FGF7 affected growth in a concentration dependent manner by treating isolated buds with increasing concentrations of FGF7 and performing an EdU incorporation assay (FIGS.2B and2C). After one week in culture, cultures were pulsed with EdU for 1 hour prior to Fluorescence Activated Cell Sorting (FACS). Results showed that treating cultures with 50-100 ng/mL of FGF7 increased proliferation significantly above cultures that only received 1-10 ng/mL of FGF7 (FIG.2C). Despite this increase in proliferation, cultures at lower doses of FGF7 appeared qualitatively healthy (FIG.2B). Additionally, expansion of buds in 10 ng/mL FGF7 was more robust than 1 ng/mL, and cultures appeared less compact and dense compared to higher doses (FIG.2B). Based on these results, FGF7 was used at a concentration of 10 ng/mL for the remainder of the experiments. Example III This example demonstrates FGF7 promotes growth of Sox9+progenitors followed by cellular differentiation over time in culture. In order to determine if FGF7 was promoting expansion of Sox9+ distal progenitors cells, experiments performed a lineage trace utilizing Sox9-CreER; Rosa26Tomatomice. Tamoxifen was given to timed pregnant dams at E12.5, and epithelial lung buds were isolated 24 hours later, at E13.5 (FIG.2E). Isolated distal buds that were lineage labeled were placed in vitro in basal media (control) or with FGF7. Experiments observed that the Sox9-CreER; Rosa26Tomatolineage labeled population expanded over time (FIG.2F). After two weeks in culture, FGF7-treated bud cultures were dense and contained cell that stained positive for mature markers of both alveolar cell types (AEC1-AQP5; AEC2-SFTPB) and bronchiolar cell types (Clara cells—SCGB1A1; multi-ciliated cells-Acetylated Tubulin; basal stem cells—P63) although cells in culture were scattered throughout the tissue and appeared to lack spatial organization (FIG.1E). None of the cells observed after two weeks in culture were positive for both SFTPC and SCGB1A1, an expression pattern that has been shown to mark bronchioalveolar stem cells (FIG.2D)(Lee et al., 2014). Many of these cell types in culture had similar morphologies as cells found at postnatal day 0 of the in vivo mouse lung (FIG.1F). Experiments next examined the changes of differentiation marker expression over time using QRT-PCR and observed that the length of time in culture led to significant increases in mature alveolar markers Aqp5 and Sftpb, as well as an upward trend in the expression of the club cell marker Scgb1a1. However, time in culture had a less dramatic effect on expression of proximal cell markers Foxj1, p63, and Sox2. The expression of the distal progenitor marker Sox9 was significantly reduced after 3 days in culture and continued to go down as the time in culture increased (FIG.1H). Collectively, this data strongly indicates that FGF7 promoted an initial expansion of Sox9+ distal epithelial progenitor cells that subsequently underwent differentiation with longer times in culture. Example IV This example demonstrates that FGF7, CHIR-99021 and RA act synergistically to maintain the distal progenitor identity in mouse lung buds in vitro. Given that FGF7 promoted robust expansion of distal buds in vitro, but was also permissive for differentiation, experiments were conducted to identify additional growth factors that interacted with FGF signaling to maintain the undifferentiated SOX9+ distal progenitor cell state in vitro. To do this, experiments were conducted that returned to the strategy of using 5F media, and removed one additional growth factor at a time to examine the effect on growth, and expression of Sox9 and Sox2 as markers of distal progenitor and proximal airway cells, respectively. Removing any single factor (FGF10, CHIR-99021, RA or BMP4) from ‘5F’ culture media did not affect the ability of isolated buds to expand (FIG.3A; 5F control condition presented inFIG.1D). QRT-PCR analysis of buds after 5 days in culture showed that removing BMP4 led to a statistically significant increase in Sox9 expression levels when compared to other culture conditions (FIG.3B), and led to gene expression levels that were closest in expression levels of freshly isolated wild type (WT) E13.5 lung buds (FIG.3B). Sox2 gene expression was generally low in freshly isolated E13.5 lung buds, and in all culture conditions after 5 days in vitro (FIG.3B). Experiments were also conducted that assessed markers for several genes expressed in differentiating cells (FIG.4A-B), and noted that the removal of BMP4 from the 5F media also resulted in a significant increase in Sftpb, and reduced expression in the proximal markers p63, Foxj1 and Scgb1a1 (FIG.4A-B). Collectively, this data indicated that removing BMP4 from the media was ideal for supporting an environment with low expression proximal airway markers and high Sox9. Experiments next screened combinations of the remaining factors to determine a minimal set that promoted tissue expansion while maintaining the identity of distal epithelial progenitor cells. All conditions included FGF7 (10 ng/mL) due to its ability to potently support proliferation and tissue expansion (FIG.1, andFIG.2). FGF10 (10 ng/mL), CHIR-99021 (3 uM) and RA (50 nM) were added in combination with FGF7 and the effect on growth, gene and protein expression was observed after two weeks in culture (FIG.3C-E). It was found that all conditions supported robust growth (FIG.3C) and expression of Sox9, Id2 and Nmyc, while maintaining low levels of Sox2 (FIG.3D). In support of this observation, lineage tracing experiments utilizing Sox9-CreER; Rosa26Tomatomice, in which Tamoxifen was administered to timed pregnant dams at E12.5 and epithelial lung buds were isolated at E13.5, showed an expansion of labeled progenitors over the 2 week period in culture (FIG.4E). It was noted that explanted buds treated with 4F or 3-Factor conditions (1F′; FGF7, CHIR-99021, RA) maintained Sox9 mRNA expression at the highest levels, similar to those expressed in freshly isolated epithelial buds at E13.5 (FIG.3D). Additional QRT-PCR analysis of differentiation markers further suggested that 3F and 4F conditions promoted optimal expression of distal progenitor identity markers while keeping proximal airway marker gene expression low (FIG.4C-D). Immunofluorescence and whole mount immunostaining of buds after 2 weeks in culture supported QRT-PCR data and showed that 3F and 4F conditions supported robust SOX9 protein expression (FIG.3E-F). To determine if SOX9+ cells maintained in culture were multipotent and retained the ability to differentiate, experiments were conducted that expanded isolated buds in 4F media for 5 days and then removed FGF10, CHIR-99021 and RA (retaining FGF7 only) for 4 days to determine if SOX9 protein/mRNA expression was reduced and if cells could differentiate (FIG.4F-J). Compared to controls, which received 4F media for the entire experiment, buds grown in FGF7 exhibited a reduction of SOX9 protein and mRNA expression (FIG.4G-H). It was noted that many AQP5+ and SFTPC+ cells co-expressed SOX9 in 4F media, whereas tissue grown in FGF7 did not co-express SOX9, suggesting differentiation towards a more mature AECI or AECII-like cell (FIG.4H). These results Indicated that SOX9+ cells maintained in culture retain the ability to down-regulate distal progenitor gene expression and undergo multi-lineage differentiation. Example V This example demonstrates In vitro growth, expansion and maintenance of human fetal distal epithelial lung progenitors. Given that almost nothing is known about the functional regulation of human fetal distal lung epithelial progenitor cells, experiments were conducted to determine if conditions that maintained mouse distal epithelial progenitors also supported human fetal distal lung progenitor growth and expansion in vitro. Distal epithelial lung buds were enzymatically and mechanically isolated from the lungs of 3 different biological samples at 12 weeks of gestation (84-87 days; n=3) and cultured in a Matrigel droplet (FIG.5A-B). Surprisingly, while characterizing the isolated buds, whole mount immunostaining revealed that human bud-tip epithelial progenitors express both SOX9 and SOX2 at 12 weeks (FIG.5C). This is in stark contrast to mice, where SOX9 is exclusively expressed in the distal lung-bud epithelium and SOX2 is exclusively expressed in the proximal airway epithelium (Perl et al., 2005; Rockich et al., 2013). Further investigation of paraffin embedded fetal lungs ranging from 10-19 weeks of gestation revealed that SOX2/SOX9 double-positive cells are present in distal epithelial cells until about 14 weeks gestation (FIG.5DandFIG.6C). By 16 weeks, SOX9 and SOX2 became localized to the distal and proximal epithelium, respectively, and were separated by a SOX9/SOX2-negative transition zone, which continued to lengthen throughout development (FIG.6C). Similar to isolated mouse lung bud cultures, it was observed that FGF7 promoted robust growth in vitro after 2 and 4 weeks, but resulted in reduced growth after 6 weeks in culture (FIG.5E). However, all other groups tested permitted expansion and survival of buds in culture for 6 weeks or longer (FIG.5E). Human fetal buds exposed to 3F or 4F supported robust protein and mRNA expression of the distal progenitor markers SOX9, ID2 and NMYC (FIG.5F-H). In contrast, culture in only 2 factors (FGF7+CHIR-99021, or FGF7+RA) did not support robust distal progenitor marker expression (FIG.5F-H). Buds cultured in 3F or 4F media also had lower expression of the proximal airway markers P63 and SCGB1A1 (FIG.6A-B). In stark contrast to results in distal progenitors from mice, SOX2 was also robustly expressed in the 3F and 4F conditions in human fetal buds (FIG.5H). Whole mount protein staining of SOX2 and SOX9 in buds treated with 3F media confirmed that almost all cells co-express SOX2 and SOX9, similar to native human lung buds in fetal lungs younger than 16 weeks. Such analysis demonstrated that 3F and 4F media functioned in a similar manner in human fetal buds, and suggested that the addition of FGF10 to the media did not have a significant effect on bud growth or differentiation. Experiments were conducted to further examine the effect of FGF10 on human fetal lung buds in culture by exposing them to high concentrations of FGF10 (500 ng/mL). It was observed that high concentrations of FGF10 induced only modest growth when compared to control conditions (basal media) (FIG.6D). On the other hand, the addition of a Rho-kinase inhibitor (Y27632) in combination with FGF10, but not alone, promoted growth of buds into larger cyst-like structures (FIG.6D). These results further support the notion that even at high concentrations, FGF10 alone does not have strong mitogenic effects on the human distal progenitor epithelium in vitro. Collectively, such data showed that a combination of FGF7, RA and activation of Wnt signaling (via CHIR-99021) is a minimal essential combination that promotes growth and maintain distal progenitor identity over time in culture. Example VI This example demonstrates that 3F media induces a distal lung bud progenitor-like population of cells in hPSC-derived lung organoids. Given the robustness by which 3F media supported mouse and human lung bud progenitor growth and identity, experiments sought to determine whether these culture conditions could promote a distal epithelial lung progenitor-like population from hPSCs. NKX2.1+ ventral foregut spheroids were generated as previously described (Dye et al., 2016a; 2015), and were cultured in a droplet of Matrigel and overlaid with media containing 3F (FGF7, CHIR-99021, RA). Spheroids were considered to be “day 0” on the day they were placed in Matrigel. Organoids (called Human Lung Organoids; HLOs) grown in 3F media exhibited robust and stereotyped growth patterns and survived in culture for over 16 weeks (FIG.7A-B,FIG.8A-B). Epithelial structures grew first as cystic structures over the course of 2 weeks, followed by a period of epithelial folding that occurred between weeks 3-4 (FIG.7A;FIG.8C-D). Around 5-6 weeks in culture, the epithelial structures began forming bud-like structures that resembled human fetal epithelial distal bud tips that underwent bifurcations (FIG.7A-B;FIG.8D—bottom row). HLOs were passaged by gently removing Matrigel and replating in a fresh droplet while preserving structural integrity. In this way, HLOs were able to grow for over 16 weeks in culture while retaining their original shape. HLOs could also be passaged using mechanical shear through a 27-gauge needle, followed by embedding in fresh Matrigel and 3F media (FIG.8E). Following passage, HLOs robustly re-established many small cysts that were expanded and serially passaged every 7-10 days many times (FIG.8F). The majority of HLO cysts formed from needle passaging were composed of cells with SOX2 and SOX9 nuclear co-staining (FIG.8G), suggesting that a population of SOX2/SOX9 double positive cells can be expanded easily in culture. HLOs cultured in 3F media exhibited robust Nkx2.1 protein expression, a lung epithelial marker, in all cells (FIG.7C); however, it is worth noting that mRNA expression levels of Nkx2.1 were significantly lower than expression levels in the native human fetal lung (FIG.9E). In addition to the cystic epithelial phenotype noted above, it was also observed organoids that possessed a dense phenotype (FIG.9A-D). Dense organoids made up the majority of structures in FGF7-only growth conditions, whereas they made up about ˜20% of cultures in 3F media. Approximately 35% of organoids in 3F media were made up of mixed structures (dense+epithelial) (FIG.9B). Dense structures consisted of cells expressing AECI cell markers HOPX and PDPN that were negative for ECAD (FIG.9C-D), consistent with adult human AECI cells (Kaarteenaho et al., 2010). No staining for the mature AECII marker SFTPB was observed in dense structures (FIG.9C). Because of interest in studying the regulation of distal tip progenitor-like cells, experiments focused on epithelial organoids for the remainder of the analysis. Example VII This example demonstrates 3F HLOs maintain regions of SOX9+/SOX2+ distal progenitor-like cells for over 115 days in culture and exhibit proximal-distal patterning. After 40 days in culture, 3F HLOs display clear proximal-distal patterning that mimics what is seen in the developing human lung. Small buds at the periphery of the HLOs stain positive for SOX2 and SOX9 (FIG.7D), similar to what is seen in the native human fetal lung during early branching (FIG.5D;FIG.6C), whereas interior regions of the HLOs are positive only for SOX2 staining (FIG.7D). SOX9+/SOX2+ peripheral regions persist until at least 115 days in culture (FIG.7E), although the bud regions become more cystic as the HLOs age past 8 weeks. QRT-PCR analysis confirmed that SOX2, NMYC, and ID2 expression levels are not significantly different between the embryonic human lung and 54 day HLOs (FIG.7F) while the expression of mature markers are reduced in HLOs compared to human fetal lungs (FIG.9G-H). Similarly, QRT-PCR analysis of isolated human buds versus isolated bud regions from HLOs confirmed that HLO buds have a similar transcriptional profile to isolated 12-week human buds (FIG.7G). Example VIII This example demonstrates interior regions of 3F HLOs contain secretory cells. Interior regions of the HLOs showed protein staining for SCGB1A1, a marker of club cells, and MUCSAC, a marker of goblet cells, two prominent secretory cell types of the human proximal airway (FIG.7H-I). It was also observed Acetylated-Tubulin (AcTub) accumulation on the apical surface of many cells, a marker of multiciliated cells (FIG.7H); however, these cells did not have bona fide cilia. It was also observed the build-up of a dark, sticky substance within HLOs beginning around 6-7 weeks of culture (FIG.7A), and Periodic Acid Shift, Alcian Blue (PAS/AB) staining suggested that this was secreted mucous. Staining clearly shows cells within the HLOs that are positive for mucin, as well as secreted mucus in the lumen of HLOs, similar to what is seen in the adult human lung (FIG.7J). Example IX This example demonstrates that removal of CHIR-99021 and RA promotes differentiation within HLOs. Based on results in the mouse showing that FGF7 was permissive for differentiation (FIG.1), experiments were conducted that hypothesized that removing CHIR-99021 and RA from HLOs grown in 3F media would reduce the number of progenitor cells and increase differentiation of mature cell types within HLO cultures. Foregut spheroids were collected and grown in 3F media for 42 days and were cultured for an additional 26 days in 3F media (control) or media containing FGF7 only (FIG.10A). Morphologically, HLOs cultured in FGF7 lost the peripheral bud-like regions compared to 3F HLOs (FIG.10B). At the end of the experiment, cultures were collected and assessed for gene and protein expression. While 3F HLOs maintained budded peripheral regions containing cells with nuclear SOX9 and SOX2, HLOs grown in FGF7-only did not exhibit any SOX9/SOX2 double positive cells and instead contained regions with cells containing cytoplasmic SOX9 and separate regions where cells expressed nuclear SOX2 (FIG.10C). QRT-PCR analysis of SOX9 showed no change in the amount of SOX9 transcript, but a significant increase in SOX2 transcript in the FGF7 treated HLOs was observed (FIG.10D). HLOs treated with FGF7 also exhibited an increase in many mature cell types as observed both by protein staining and QRT-PCR analysis. Most strikingly, FGF7-only HLOs exhibited a large increase in the number of MUC5AC positive cells, a dramatic increase the amount of mucous within the HLO lumens (FIG.10E), as well as a significant increase in gene expression of MUC5AC (FIG.10F). Interestingly, there was not an obvious increase in the number of SCGB1A1+ cells observed by protein staining (FIG.10I). Although expression levels of SCGB1A1 were increased almost 100-fold in FGF7-only HLOs over the 3F controls, this difference was not statistically significant (FIG.10F). FGF7 treated HLOs also contained cells that stained positive for P63, a marker of basal stem cells (FIG.10G), and exhibited a significant increase in mRNA expression of P63 (FIG.10H). In contrast, P63+ cells were conspicuously absent from 3F epithelial HLOs. (FIG.10G-H, see alsoFIG.7H). Although mRNA expression of the proximal ciliated cell marker FOXJ1 increased significantly in HLOs treated with FGF7-only (FIG.10O), obvious FOXJ1 protein expression was not detected by immunofluorescence (negative data not shown). In addition to an increase expression of multiple proximal airway cell markers, HLOs grown in FGF7-only exhibited an increase in both protein and mRNA expression of the AECII marker SFTPC (FIG.10K-L) and possessed cells that stained positive for the AECI marker PDPN, and had increased gene expression of the AECI marker HOPX (FIG.10M-N). Together, these results demonstrate that HLOs grown in 3F media have the ability to generate multiple mature lung cell lineages when CHIR-99021 and RA is removed from the media. Example X This example describes the materials and methods for Examples I-IX. Mouse Models: All animal research was approved by the University of Michigan Committee on Use and Care of Animals. Lungs from Sox9-eGFP (MGI ID:3844824), Sox9CreER; RosaTomato/Tomato(MGI ID:5009223 and 3809523)(Kopp et al., 2011), or wild type lungs from CD1 embryos (Charles River) were dissected at embryonic day (E) 13.5, and buds were isolated as described below and as previously described (del Moral and Warburton, 2010). Human Fetal Lung Tissue: All research utilizing human fetal tissue was approved by the University of Michigan institutional review board. Normal human fetal lungs were obtained from the University of Washington Laboratory of Developmental Biology, and epithelial lung buds were dissected as described below. All experiments were repeated using tissues from 3 individual lungs; 84 day post fertilization of unknown gender, 87 day post fertilization male, and 87 day post fertilization of unknown gender. All tissues were shipped in Belzer's solution at 4 degrees Celsius and were processed and in culture within 24 hours of isolation. Cell Lines and Culture Conditions: Mouse and Human Primary Cultures: Isolated mouse buds were cultured in 4-6 μl droplets of matrigel, covered with media, and kept at 37 degrees Celsius with 5% Carbon Dioxide. Isolated human fetal lung buds were cultured in 25-50 μl droplets of matrigel, covered with media, and kept at 37 degrees Celsius with 5% Carbon Dioxide. Generation and Culture of hPSC-Derived Lung Organoids: The University of Michigan Human Pluripotent Stem Cell Research Oversight (hPSCRO) Committee approved all experiments using human embryonic stem cell (hESC) lines. hESC line UM63-1 (NIH registry #0277) was obtained from the University of Michigan and hESC line H9 (NIH registry #0062) was obtained from the WiCell Research Institute. ES cell lines were routinely karyotyped to ensure normal karyotype and ensure the sex of each line (H9-XX, UM63-1-XX). Cells are monitored formycoplasmainfection monthly using the MycoAlertMycoplasmaDetection Kit (Lonza). Stem cells were maintained on hESC-qualified Matrigel (Corning Cat#354277) using mTesR1 medium (Stem Cell Technologies). hESCs were maintained and passaged as previously described (Spence et al., 2011) and ventral foregut spheroids were generated as previously described (Dye et al., 2016a; 2015). Following differentiation, free-floating foregut spheroids were collected from differentiated stem cell cultures and plated in a matrigel droplet on a 24-well tissue culture grade plate. Isolation and Culture of Mouse Lung Epithelial Buds Mouse buds were dissected from E13.5 embryos. For experiments using Sox9CreER; RosaTomato/Tomatomice, 50 ug/g of tamoxifen was dissolved in corn oil and given by oral gavage on E12.5, 24 hours prior to dissection. Briefly, in sterile environment, whole lungs were placed in 100% dispase (Corning Cat#354235) on ice for 30 minutes. Lungs were then transferred using a 25 uL wiretrol tool (Drummond Scientific Cat#S5-000-2050) to 100% FBS (Corning Cat#35-010-CV) on ice for 15 minutes, and then transferred to a solution of Dulbecco's Modified Eagle Medium: Nutrient Mixture F12 (DMEM/F12, ThermoFisher SKU#12634-010) with 10% FBS and 1× Pennicillin-Streptomycin (ThermoFisher Cat#15140122) on ice. To dissect buds, a single lung or lung lobe was transferred by wiretrol within a droplet of media to a 100 mm sterile petri dish. Under a dissecting microscope, the mesenchyme was carefully removed and epithelial bud tips were torn away from the bronchial tree using tungsten needles (Point Technologies, Inc.). Care was taken to remove the trachea and any connective tissue from dissected lungs. Isolated bud tips were picked up using a p20 pipette and added to an eppendorf tube with cold Matrigel (Corning Ref#354248) on ice. The buds were picked up in a p20 pipette with 4-6 uL of Matrigel and plated on a 24-well tissue culture well (ThermoFisher Cat#142475). The plate was moved to a tissue culture incubator and incubated for 5 minutes at 37 degrees Celsius and 5% CO2 to allow the Matrigel droplet to solidify. 500 uL of media was then added to the dish in a laminar flow hood. Media was changed every 2-3 days. Isolation and Culture of Human Fetal Lung Epithelial Buds Distal regions of 12 week fetal lungs were cut into ˜2 mm sections and incubated with dispase, 100% FBS and then 10% FBS as described above, and moved to a sterile petri dish. Mesenchyme was removed by repeated pipetting of distal lung pieces after dispase treatment. Buds were washed with DMEM until mesenchymal cells were no longer visible in the media. Buds were then moved to a 1.5 mL eppendorf tube containing 200 uL of Matrigel, mixed using a p200 pipette, and plated in ˜20 uL droplets in a 24 well tissue culture plate. Plates were placed at 37 degrees Celsius with 5% CO2 for 20 minutes while droplets solidified. 500 uL of media was added to each well containing a droplet. Media was changed every 2-3 days. EdU Quantification by Flow Cytometry Epithelial lung buds were dissected from e13.5 CD1 mice and plated in a matrigel droplet as described above. 3-4 individual buds from one mouse were placed in each droplet and were pooled to serve as a single biological replicate. Three droplets (corresponding to 3 independent biological samples) were assigned to each experimental group, receiving either 1, 10, 50 or 100 ng/mL of FGF7 for 7 days. Media was changed every 2-3 days. Cells were incubated with EdU for 1 hour and stained with the Click-It EdU Alexa Fluor 488 system (ThermoFisher Cat# C10337) according to the manufacturer's instructions. As a control, wells that received 10 ng/mL of FGF7 for 7 days were taken through the EdU steps but were not stained were used to set the gates. For analysis, lung buds were broken into a single cell suspension. 1 mL of accutase (Sigma Cat# A6964) was added to a 15 mL conical tube containing pooled epithelial buds and cells were incubated at 37 degrees Celsius with frequent visual inspection until clumps of cells were no longer visible. 3 mL of basal media (see below) was added to each tube, and cells were centrifuged at 300 g for 5 minutes at 4 degrees Celsius. The supernatant was then withdrawn, and cells were resuspended with 1 mL sterile PBS, filtered through a 70 uM strainer to remove any cell clumps and transferred to a cell sorting tube. Flow cytometric analysis was performed on a BD FACSARIA III cell sorter (BD biosciences). Culture Media, Growth Factors and Small Molecules Low-Serum Basal Media All mouse bud, human fetal bud, and hPSC-derived human lung organoids were grown in low-serum basal media (basal media) with added growth factors. Basal media consisted of Dulbecco's Modified Eagle Medium: Nutrient Mixture F12 (DMEM/F12, ThermoFisher SKU#12634-010) supplemented with 1× N2 supplement (ThermoFisher Catalog#17502048) and 1λ B27 supplement (ThermoFisher Catalog#17504044), along with 2 mM Glutamax (ThermoFisher Catalog#35050061), 1× Pennicillin-Streptomycin (ThermoFisher Cat#15140122) and 0.05% Bovine Serum Albumin (BSA; Sigma product# A9647). BSA was weighed and dissolved in DMEM F/12 media before being passed through a SteriFlip 0.22 uM filter (Millipore Item# EW-29969-24) and being added to basal media. Media was stored at 4 degrees Celsius for up to 1 month. On the day of use, basal media was aliquoted and 50 ug/mL Ascorbic acid and 0.4 uM Monothioglycerol was added. Once ascorbic acid and monothioglycerol had been added, media was used within one week. Growth Factors and Small Molecules Recombinant Human Fibroblast Growth Factor 7 (FGF7) was obtained from R&D systems (R&D #251-KG/CF) and used at a concentration of 10 ng/mL unless otherwise noted. Recombinant Human Fibroblast Growth Factor 10 (FGF10) was obtained either from R&D systems (R&D #345-FG) or generated in house (see below), and used at a concentration of 10 ng/mL (low) or 500 ng/mL (high) unless otherwise noted. Recombinant Human Bone Morphogenic Protein 4 (BMP4) was purchased from R&D systems (R&D Catalog #314-BP) and used at a concentration of 10 ng/mL. All-trans Retinoic Acid (RA) was obtained from Stemgent (Stemgent Catalog#04-0021) and used at a concentration of 50 nM. CHIR-99021, a GSK3β inhibitor that stabilizes β-CATENIN, was obtained from STEM CELL technologies (STEM CELL Technologies Catalog#72054) and used at a concentration of 3 uM. Y27632, a ROCK inhibitor (APExBIO Cat# A3008) was used at a concentration of 10 uM. Generation and Isolation of Human Recombinant FGF10 Recombinant human FGF10 was produced in-house. The recombinant human FGF10 (rhFGF10) expression plasmid pET21d-FGF10 inE. colistrain BL21trxB(DE3) was a gift from James A. Bassuk at the University of Washington School of Medicine (Bagai et al., 2002).E. colistrain was grown in standard LB media with peptone derived from meat, carbenicillin and glucose. rhFGF10 expression was induced by addition of isopropyl-1-thio-β-D-galactopyranoside (IPTG). rhFGF10 was purified by using a HiTrap-Heparin HP column (GE Healthcare, 17040601) with step gradients of 0.5M to 2M LiCl. From a 200 ml culture, 3 mg of at least 98% pure rFGF-10 (evaluated by SDS-PAGE stained with Coomassie Blue R-250) was purified. rFGF10 was compared to commercially purchased human FGF10 (R&D Systems) to test/validate activity based on the ability to phosphorylate ERK1/2 in an A549 alveolar epithelial cell line (ATCC Cat#CCL-185) as assessed by western blot analysis. RNA Extraction and Quantitative RT-PCR Analysis RNA was extracted using the MagMAX-96 Total RNA Isolation System (Life Technologies). RNA quality and concentration was determined on a Nanodrop 2000 spectrophotometer (Thermo Scientific). 100 ng of RNA was used to generate a cDNA library using the SuperScript VILO cDNA master mix kit (Invitrogen) according to manufacturer's instructions. qRT-PCR analysis was conducted using Quantitect SYBR Green Master Mix (Qiagen) on a Step One Plus Real-Time PCR system (Life Technologies). Expression was calculated as a change relative to GAPDH expression using arbitrary units, which were calculated by the following equation: [2^(GAPDH Ct−Gene Ct)]×10,000. A Ct value of 40 or greater was considered not detectable. A list of primer sequences used can be found in Table 1. TABLE 1qRT-PCR primer sequencesGeneSEQSEQSpeciesTargetForward Primer SequenceID NO:Reverse Primer SequenceID NO:Mouseaqp5TAGAAGATGGCTCGGAGCAG1CTGGGACCTGTGAGTGGTG2Mousefoxj1TGTTCAAGGACAGGTTGTGG3GATCACTCTGTCGGCCATCT4MousegapdhTGTCAGCAATGCATCCTGCA5CCGTTCAGCTCTGGGATGAC6Mouseid2AGAAAAGAAAAAGTCCCCAAATG7GTCCTTGCAGGCATCTGAAT8MousenmycAGCACCTCCGGAGAGGATA9TCTCTACGGTGACCACATCG10Mousep63AGCTTCTTCAGTTCGGTGGA11CCTCCAACACAGATTACCCG12MouseScgb1a1ACTTGAAGAAATCCTGGGCA13CAAAGCCTCCAACCTCTACC14Mousesftp-bACAGCCAGCACACCCTTG15TTCTCTGAGCAACAGCTCCC16Mousesox2AAAGCGTTAATTTGGATGGG17ACAAGAGAATTGGGAGGGGT18Mousesox9TCCACGAAGGGTCTCTTCTC19AGGAAGCTGGCAGACCAGTA20HumanFoxj1CAACTTCTGCTACTTCCGCC21CGAGGCACTTTGATGAAGC22HumangapdhAATGAAGGGGTCATTGATGG23AAGGTGAAGGTCGGAGTCAA24HumanhopxGCCTTTCCGAGGAGGAGAC25TCTGTGACGGATCTGCACTC26Humanid2GACAGCAAAGCACTGTGTGG27TCAGCACTTAAAAGATTCCGTG28Humanmuc5ac*GCACCAACGACAGGAAGGATGAG29CACGTTCCAGAGCCGGACAT30Humannkx2.1CTCATGTTCATGCCGCTC31GACACCATGAGGAACAGCG32HumannmycCACAGTGACCACGTCGATTT33CACAAGGCCCTCAGTACCTC34Humanp63CCACAGTACACGAACCTGGG35CCGTTCTGAATCTGCTGGTCC36Humanscgb1a1ATGAAACTCGCTGTCACCCT37GTTTCGATGACACGCTGAAA38Humansftp-bCAGCACTTTAAAGGACGGTGT39GGGTGTGTGGGACCATGT40Humansox2GCTTAGCCTCGTCGATGAAC41AACCCCAAGATGCACAACTC42Humansox9GTACCCGCACTTGCACAAC43ATTCCACTTTGCGTTCAAGG44Humansp-cAGCAAAGAGGTCCTGATGGA45CGATAAGAAGGCGTTTCAGG46Note:All primer sequences were obtained from primerdepot.nci.nih.gov (human) ormouseprimerdepot.nci.nih.gov (mouse) unless otherwise noted. All annealing temperaturesare near 60° C.*MUC5AC Huang, SX et al. Efficient generation of lung and airway epithelial cells fromhuman pluripotent stem cells. Nature Biotechnol. 1-11 (2013). doi: 10.1038/nbt.2754 Tissue Preparation, Immunohistochemistry and Imaging Paraffin Sectioning and Staining Mouse bud, human bud, and HLO tissue was fixed in 4% Paraformaldehyde (Sigma) for 2 hours and rinsed in PBS overnight. Tissue was dehydrated in an alcohol series, with 30 minutes each in 25%, 50%, 75% Methanol:PBS/0.05% Tween-20, followed by 100% Methanol, and then 100% Ethanol. Tissue was processed into paraffin using an automated tissue processor (Leica ASP300). Paraffin blocks were sectioned 5-7 uM thick, and immunohistochemical staining was performed as previously described (Spence et al., 2009). A list of antibodies, antibody information and concentrations used can be found in Table 2. PAS Alcian blue staining was performed using the Newcomer supply Alcian Blue/PAS Stain kit (Newcomer Supply, Inc.) according to manufacturer's instructions. TABLE 2Antibody informationDilutionDilution(WholePrimary AntibodySourceCatalog #Used for Species(Sections)mount)CloneGoat anti-CC10 (SCGB1A1)Santa Cruzsc-9770Mouse, Human1:200C-20BiotechnologyGoat anti-SOX2Santa CruzSc-17320Mouse, Human1:2001:100polyclonalBiotechnologyMouse anti-AcetylatedSigma-AldrichT7451Mouse, Human1:10006-11B-1Tubulin (ACTTUB)Mouse anti-E-CadherinBD Transduction610181Mouse, Human1:50036/E-(ECAD)LabratoriesCadherinMouse anti-Surfactant ProteinSeven HillsWmab-1B9Mouse, Human1:250monoclonalB (SP-B)BioreagentsRabbit anti-Aquaporin 5AbcamAb78486Mouse1:500polyclonal(Aqp5)Rabbit anti-Clara CellSeven HillsWrab-3950Mouse, Human1:250polyclonalSecretory Protein (CCSP;BioreagentsSCGB1A1)Rabbit anti-HOPXSanta CruzSc-30216Human1:250polyclonalBiotechnologyRabbit anti-NKX2.1Abcamab76013Human1:200EP1584YRabbit anti-PDPNSanta CruzSc-134482Human1:500polyclonalBiotechnologyRabbit anti-Pro-SurfactantSeven HillsWrab-9337Human, Mouse1:500polyclonalprotein C (Pro-SPC)BioreagentsRabbit anti-P63Santa Cruzsc-8344Mouse, Human1:200H-129BiotechnologyRabbit anti-SOX9MilliporeAB5535Mouse, Human1:5001:250polyclonalRat anti-Ki67Biolegend652402Mouse1:10016A8*Biotin-Mouse anti MUC5ACAbcamab79082Human1:500MonoclonalSecondary AntibodySourceCatalog #DilutionDonkey anti-goat 488Jackson Immuno705-545-1471:500Donkey anti-goat 647Jackson Immuno705-605-1471:500Donkey anti-goat Cy3Jackson Immuno705-165-1471:500Donkey anti-mouse 488Jackson Immuno715-545-1501:500Donkey anti-mouse 647Jackson Immuno415-605-3501:500Donkey anti-mouse Cy3Jackson Immuno715-165-1501:500Donkey anti-rabbit 488Jackson Immuno711-545-1521:500Donkey anti-rabbit 647Jackson Immuno711-605-1521:500Donkey anti-rabbit Cy3Jackson Immuno711-165-1021:500Donkey anti-goat 488Jackson Immuno705-545-1471:500Donkey anti-goat 647Jackson Immuno705-605-1471:500Donkey anti-goat Cy3Jackson Immuno705-165-1471:500Donkey anti-mouse 488Jackson Immuno715-545-1501:500Donkey anti-mouse 647Jackson Immuno415-605-3501:500Donkey anti-mouse Cy3Jackson Immuno715-165-1501:500Donkey anti-rabbit 488Jackson Immuno711-545-1521:500Donkey anti-rabbit 647Jackson Immuno711-605-1521:500Donkey anti-rabbit Cy3Jackson Immuno711-165-1021:500Streptavidin 488Jackson Immuno016-540-0841:500 Whole Mount Staining For whole mount staining tissue was placed in a 1.5 mL eppendorf tube and fixed in 4% paraformaldehyde (Sigma) for 30 minutes. Tissue was then washed with PBS/0.05% Tween-20 (Sigma) for 5 hours, followed by a 2.5-hour incubation with blocking serum (PBS-Tween-20 plus 5% normal donkey serum). Primary antibodies were added to blocking serum and tissue was incubated for at least 24 hours at 4 degrees Celcius. Tissue was then washed for 5 hours with several changes of fresh PBS-Tween-20. Secondary antibodies were added to fresh blocking solution and tissue was incubated for 12-24 hours, followed by 5 hours of PBS-Tween-20 washes. Tissue was then dehydrated to 100% methanol and carefully moved to the center of a single-well EISCO concave microscope slide (ThermoFisher Cat#S99368) using a glass transfer pipette. 5-7 drops of Murray's clear (2 parts Benzyl alcohol, 1 part Benzyl benzoate [Sigma]) were added to the center of the slide, and slides were coverslipped and sealed with clear nail polish. Imaging and Image Processing Images of fluorescently stained slides were taken on a Nikon A-1 confocal microscope. When comparing groups within a single experiment, exposure times and laser power were kept consistent across all images. All Z-stack imaging was done on a Nikon A-1 confocal microscope and Z-stacks were 3-D rendered using Imaris software. Brightness and contrast adjustments were carried out using Adobe Photoshop Creative Suite 6 and adjustments were made uniformly among all images. Brightfield images of live cultures were taken using an Olympus S2×16 dissecting microscope. Image brightness and contrast was enhanced equally for all images within a single experiment using Adobe Photoshop. Images were cropped where noted in figure legends to remove blank space surrounding buds or cultures. Brightfield images of Alcian Blue stains were taken using an Olympus DP72 inverted microscope. Quantification and Statistical Analysis All plots and statistical analysis were done using Prism 6 Software (GraphPad Software, Inc.). For statistical analysis of qRT-PCR results, at least 3 biological replicates for each experimental group were analyzed and plotted with the standard error of the mean. If only two groups were being compared, a two-sided student's T-test was performed. In assessing the effect of length of culture with FGF7 on gene expression in mouse buds (FIG.1G), a one-way, unpaired Analysis of Variance (ANOVA) was performed for each individual gene over time. The mean of each time point was compared to the mean of the expression level for that gene at day 0 of culture. If more than two groups were being compared within a single experiment, an unpaired one-way analysis of variance was performed followed by Tukey's multiple comparison test to compare the mean of each group to the mean of every other group within the experiment. For all statistical tests, a significance value of 0.05 was used. For every analysis, the strength of p values is reported in the figures according the following: P>0.05 ns, P≤0.05*, P≤0.01**, P≤0.001***, P≤0.0001****. Details of statistical tests can be found in the figure legends. Example XI This example demonstrates that iPSC-derived lung organoids can engraft into a mouse lung (see,FIG.11). Having now fully described the invention, it will be understood by those of skill in the art that the same can be performed within a wide and equivalent range of conditions, formulations, and other parameters without affecting the scope of the invention or any embodiment thereof. All patents, patent applications and publications cited herein are fully incorporated by reference herein in their entirety. INCORPORATION BY REFERENCE The entire disclosure of each of the patent documents and scientific articles referred to herein is incorporated by reference for all purposes. Complete citations for the references cited within the application are provided within the following reference list. Indeed, each of the following references are herein incorporated by reference in their entireties:Abler, L. L., Mansour, S. L., Sun, X., 2009. Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung. Dev. Dyn. 238, 1999-2013. doi:10.1002/dvdy.22032Bagai, S., Rubio, E., Cheng, J.-F., Sweet, R., Thomas, R., Fuchs, E., Grady, R., Mitchell, M., Bassuk, J. A., 2002. Fibroblast growth factor-10 is a mitogen for urothelial cells. J. Biol. Chem. 277, 23828-23837. doi:10.1074/jbc.M201658200Bellusci, S., Furuta, Y., Rush, M. G., Henderson, R., Winnier, G., Hogan, B. L., 1997a. Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis. Development 124, 53-63.Bellusci, S., Grindley, J., Emoto, H., Itoh, N., Hogan, B. L., 1997b. Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung. Development 124, 4867-4878.Bellusci, S., Henderson, R., Winnier, G., Oikawa, T., Hogan, B. L., 1996. Evidence from normal expression and targeted misexpression that bone morphogenetic protein (Bmp-4) plays a role in mouse embryonic lung morphogenesis. Development 122, 1693-1702.Branchfield, K., Li, R., Lungova, V., Verheyden, J. M., McCulley, D., Sun, X., 2015. A three-dimensional study of alveologenesis in mouse lung. Developmental Biology. doi:10.1016/j.ydbio.2015.11.017Cardoso, W. V., Itoh, A., Nogawa, H., Mason, I., Brody, J. S., 1997. FGF-1 and FGF-7 induce distinct patterns of growth and differentiation in embryonic lung epithelium. Dev. Dyn. 208, 398-405. doi:10.1002/(SICI)1097-0177(199703)208:3<398::AID-AJA10>3.0.CO; 2-XChang, D. R., Martinez Alanis, D., Miller, R. K., Ji, H., Akiyama, H., McCrea, P. D., Chen, J., 2013. Lung epithelial branching program antagonizes alveolar differentiation. Proceedings of the National Academy of Sciences. doi:10.1073/pnas.1311760110Chen, F., Cao, Y., Qian, J., Shao, F., Niederreither, K., Cardoso, W. V., 2010. A retinoic acid-dependent network in the foregut controls formation of the mouse lung primordium. J. Clin. Invest. 120, 2040-2048. doi:10.1172/JCI40253Cornett, B., Snowball, J., Varisco, B. M., Lang, R., Whitsett, J., Sinner, D., 2013. Wntless is required for peripheral lung differentiation and pulmonary vascular development. Developmental Biology 379, 38-52. doi:10.1016/j.ydbio.2013.03.010D'Amour, K. A., Agulnick, A. D., Eliazer, S., Kelly, O. G., Kroon, E., Baetge, E. E., 2005. Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 23, 1534-1541. doi:10.1038/nbt1163del Moral, P.-M., Warburton, D., 2010. Explant culture of mouse embryonic whole lung, isolated epithelium, or mesenchyme under chemically defined conditions as a system to evaluate the molecular mechanism of branching morphogenesis and cellular differentiation. Methods Mol. Biol. 633, 71-79. doi:10.1007/978-1-59745-019-5_5Desai, T. J., Chen, F., Lu, J., Qian, J., Niederreither, K., Done, P., Chambon, P., Cardoso, W. V., 2006. Distinct roles for retinoic acid receptors alpha and beta in early lung morphogenesis. Developmental Biology 291, 12-24. doi:10.1016/j.ydbio.2005.10.045Desai, T. J., Malpel, S., Flentke, G. R., Smith, S. M., Cardoso, W. V., 2004. Retinoic acid selectively regulates Fgf10 expression and maintains cell identity in the prospective lung field of the developing foregut. Developmental Biology 273, 402-415. doi:10.1016/j.ydbio.2004.04.039Domyan, E. T., Ferretti, E., Throckmorton, K., Mishina, Y., Nicolis, S. K., Sun, X., 2011. Signaling through BMP receptors promotes respiratory identity in the foregut via repression of Sox2. Development 138, 971-981. doi:10.1242/dev.053694Domyan, E. T., Sun, X., 2010. Patterning and plasticity in development of the respiratory lineage. Dev. Dyn. 240, 477-485. doi:10.1002/dvdy.22504Dye, B. R., Dedhia, P. H., Miller, A. J., Nagy, M. S., White, E. S., Shea, L. D., Spence, J. R., Rossant, J., 2016a. A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids. Elife 5, e19732. doi:10.7554/eLife.19732Dye, B. R., Hill, D. R., Ferguson, M. A., Tsai, Y.-H., Nagy, M. S., Dyal, R., Wells, J. M., Mayhew, C. N., Nattiv, R., Klein, O. D., White, E. S., Deutsch, G. H., Spence, J. R., 2015. In vitro generation of human pluripotent stem cell derived lung organoids. Elife 4. doi:10.7554/eLife.05098Dye, B. R., Miller, A. J., Spence, J. R., 2016b. How to Grow a Lung: Applying Principles of Developmental Biology to Generate Lung Lineages from Human Pluripotent Stem Cells. Curr Pathobiol Rep 1-11. doi:10.1007/s40139-016-0102-xElluru, R. G., Whitsett, J. A., 2004. Potential role of Sox9 in patterning tracheal cartilage ring formation in an embryonic mouse model. Arch. Otolaryngol. Head Neck Surg. 130, 732-736. doi:10.1001/archoto1.130.6.732Firth, A. L., Dargitz, C. T., Qualls, S. J., Menon, T., Wright, R., Singer, O., Gage, F. H., Khanna, A., Verma, I. M., 2014. Generation of multiciliated cells in functional airway epithelia from human induced pluripotent stem cells. Proceedings of the National Academy of Sciences 111, E1723-30. doi:10.1073/pnas.1403470111Ghaedi, M., Calle, E. A., Mendez, J. J., Gard, A. L., Balestrini, J., Booth, A., Bove, P. F., Gui, L., White, E. S., Niklason, L. E., 2013. Human iPS cell-derived alveolar epithelium repopulates lung extracellular matrix. J. Clin. Invest. 123, 4950-4962. doi:10.1172/JCI68793Gilpin, S. E., Ren, X., Okamoto, T., Guyette, J. P., Mou, H., Rajagopal, J., Mathisen, D. J., Vacanti, J. P., Ott, H. C., 2014a. Enhanced lung epithelial specification of human induced pluripotent stem cells on decellularized lung matrix. Ann. Thorac. Surg. 98, 1721-9-discussion 1729. doi:10.1016/j.athoracsur.2014.05.080Gilpin, S. E., Ren, X., Okamoto, T., Guyette, J. P., Mou, H., Rajagopal, J., Mathisen, D. J., Vacanti, J. P., Ott, H. C., 2014b. Enhanced Lung Epithelial Specification of Human Induced Pluripotent Stem Cells on Decellularized Lung Matrix. Ann. Thorac. Surg. 98, 1721-1729.Goss, A. M., Tian, Y., Tsukiyama, T., Cohen, E. D., Zhou, D., Lu, M. M., Yamaguchi, T. P., Morrisey, E. E., 2009. Wnt2/2b and β-Catenin Signaling Are Necessary and Sufficient to Specify Lung Progenitors in the Foregut. Developmental Cell 17, 290-298. doi:10.1016/j.devce1.2009.06.005Gotoh, S., Ito, I., Nagasaki, T., Yamamoto, Y., Konishi, S., Korogi, Y., Matsumoto, H., Muro, S., Hirai, T., Funato, M., Mae, S.-I., Toyoda, T., Sato-Otsubo, A., Ogawa, S., Osafune, K., Mishima, M., 2014. Generation of alveolar epithelial spheroids via isolated progenitor cells from human pluripotent stem cells. Stem Cell Reports 3, 394-403. doi:10.1016/j.stemcr.2014.07.005Green, M. D., Chen, A., Nostro, M.-C., d'Souza, S. L., Schaniel, C., Lemischka, I. R., Gouon-Evans, V., Keller, G., Snoeck, H.-W., 2011. Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells. Nat Biotechnol 1-7. doi:10.1038/nbt.1788Harris-Johnson, K. S., Domyan, E. T., Vezina, C. M., Sun, X., 2009. beta-Catenin promotes respiratory progenitor identity in mouse foregut. Proceedings of the National Academy of Sciences 106, 16287-16292. doi:10.1073/pnas.0902274106Hashimoto, S., Chen, H., Que, J., Brockway, B. L., Drake, J. A., Snyder, J. C., Randell, S. H., Stripp, B. R., 2012. β-Catenin-SOX2 signaling regulates the fate of developing airway epithelium. Journal of Cell Science 125, 932-942. doi:10.1242/jcs.092734Herriges, J. C., Verheyden, J. M., Zhang, Z.,Sui, P., Zhang, Y., Anderson, M. J., Swing, D. A., Zhang, Y., Lewandoski, M., Sun, X., 2015. FGF-Regulated ETV Transcription Factors Control FGF-SHH Feedback Loop in Lung Branching. Developmental Cell 35, 322-332. doi:10.1016/j.devce1.2015.10.006Hines, E. A., Sun, X., 2014. Tissue crosstalk in lung development. J Cell Biochem 115, 1469-1477. doi:10.1002/jcb.24811Huang, S. X. L., Islam, M. N., O'Neill, J., Hu, Z., Yang, Y.-G., Chen, Y.-W., Mumau, M., Green, M. D., Vunjak-Novakovic, G., Bhattacharya, J., Snoeck, H.-W., 2013. efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nat Biotechnol 1-11. doi:10.1038/nbt.2754Kaarteenaho, R., Lappi-Blanco, E., Lehtonen, S., 2010. Epithelial N-cadherin and nuclear β-catenin are up-regulated during early development of human lung. BMC Dev Biol 10, 113. doi:10.1186/1471-213X-10-113Kadzik, R. S., Cohen, E. D., Morley, M. P., Stewart, K. M., Lu, M. M., Morrisey, E. E., 2014. Wnt ligand/Frizzled 2 receptor signaling regulates tube shape and branch-point formation in the lung through control of epithelial cell shape. Proceedings of the National Academy of Sciences 111, 12444-12449. doi:10.1073/pnas.1406639111Kim, C. F. B., Jackson, E. L., Woolfenden, A. E., Lawrence, S., Babar, I., Vogel, S., Crowley, D., Bronson, R. T., Jacks, T., 2005. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121, 823-835. doi:10.1016/j.ce11.2005.03.032Kim, H. Y., Nelson, C. M., 2012. Extracellular matrix and cytoskeletal dynamics during branching morphogenesis. Organogenesis 8, 56-64. doi:10.4161/org.19813Konishi, S., Gotoh, S., Tateishi, K., Yamamoto, Y., Korogi, Y., Nagasaki, T., Matsumoto, H., Muro, S., Hirai, T., Ito, I., Tsukita, S., Mishima, M., 2015. Directed Induction of Functional Multi-ciliated Cells in Proximal Airway Epithelial Spheroids from Human Pluripotent Stem Cells. Stem Cell Reports 0. doi:10.1016/j.stemcr.2015.11.010Kopp, J. L., Dubois, C. L., Schaffer, A. E., Hao, E., Shih, H. P., Seymour, P. A., Ma, J., Sander, M., 2011. Sox9+ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas. Development 138, 653-665. doi:10.1242/dev.056499Lange, A. W., Sridharan, A., Xu, Y., Stripp, B. R., Perl, A.-K., Whitsett, J. A., 2015. Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung. Journal of Molecular Cell Biology 7, 35-47. doi:10.1093/jmcb/mju046Lee, J.-H., Bhang, D. H., Beede, A., Huang, T. L., Stripp, B. R., Bloch, K. D., Wagers, A. J., Tseng, Y.-H., Ryeom, S., Kim, C. F., 2014. Lung Stem Cell Differentiation in Mice Directed by Endothelial Cells via a BMP4-NFATc1-Thrombospondin-1 Axis. Cell 156, 440-455. doi:10.1016/j.ce11.2013.12.039Longmire, T. A., Ikonomou, L., Hawkins, F., Christodoulou, C., Cao, Y., Jean, J. C., Kwok, L. W., Mou, H., Rajagopal, J., Shen, S. S., Dowton, A. A., Serra, M., Weiss, D. J., Green, M. D., Snoeck, H.-W., Ramirez, M. I., Kotton, D. N., 2012. Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells. Cell Stem Cell 10, 398-411. doi:10.1016/j.stem.2012.01.019Lu, B. C., Cebrian, C., Chi, X., Kuure, S., Kuo, R., Bates, C. M., Arber, S., Hassell, J., MacNeil, L., Hoshi, M., Jain, S., Asai, N., Takahashi, M., Schmidt-Ott, K. M., Barasch, J., D'Agati, V., Costantini, F., 2009. Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis. Nat Genet 41, 1295-1302. doi:10.1038/ng.476Mahoney, J. E., Mori, M., Szymaniak, A. D., Varelas, X., Cardoso, W. V., 2014. The Hippo Pathway Effector Yap Controls Patterning and Differentiation of Airway Epithelial Progenitors. Dev. Cell 1-14. doi:10.1016/j.devce1.2014.06.003Makarenkova, H. P., Hoffman, M. P., Beenken, A., Eliseenkova, A. V., Meech, R., Tsau, C., Patel, V. N., Lang, R. A., Mohammadi, M., 2009. Differential interactions of FGFs with heparan sulfate control gradient formation and branching morphogenesis. Sci Signal 2, ra55-ra55. doi:10.1126/scisignal.2000304Malpel, S., Mendelsohn, C., Cardoso, W. V., 2000. Regulation of retinoic acid signaling during lung morphogenesis. Development 127, 3057-3067. Metzger, R. J., Klein, O. D., Martin, G. R., Krasnow, M. A., 2008. The branching programme of mouse lung development. Nature 453, 745-750. doi:10.1038/nature07005Min, H., Danilenko, D. M., Scully, S. A., Bolon, B., Ring, B. D., Tarpley, J. E., DeRose, M., Simonet, W. S., 1998. Fgf-10 is required for both limb and lung development and exhibits striking functional similarity toDrosophilabranchless. Genes & Development 12, 3156-3161.Moens, C. B., Auerbach, A. B., Conlon, R. A., Joyner, A. L., Rossant, J., 1992. A targeted mutation reveals a role for N-myc in branching morphogenesis in the embryonic mouse lung. Genes Dev. 6, 691-704. doi:10.1101/gad.6.5.691Morrisey, E. E., Cardoso, W. V., Lane, R. H., Rabinovitch, M., Abman, S. H., Ai, X., Albertine, K. H., Bland, R. D., Chapman, H. A., Checkley, W., Epstein, J. A., Kintner, C. R., Kumar, M., Minoo, P., Mariani, T. J., McDonald, D. M., Mukouyama, Y.-S., Prince, L. S., Reese, J., Rossant, J., Shi, W., Sun, X., Werb, Z., Whitsett, J. A., Gail, D., Blaisdell, C. J., Lin, Q. S., 2013. Molecular determinants of lung development. Ann Am Thorac Soc 10, S12-6. doi:10.1513/AnnalsATS.201207-036OTMorrisey, E. E., Hogan, B. L. M., 2010. Preparing for the First Breath: Genetic and Cellular Mechanisms in Lung Development. Developmental Cell 18, 8-23. doi:10.1016/j.devce1.2009.12.010Motoyama, J., Liu, J., Mo, R., Ding, Q., Post, M., Hui, C. C., 1998. Essential function of Gli2 and Gli3 in the formation of lung, trachea and oesophagus. Nat Genet 20, 54-57. doi:10.1038/1711Mou, H., Zhao, R., Sherwood, R., Ahfeldt, T., Lapey, A., Wain, J., Sicilian, L., Izvolsky, K., Musunuru, K., Cowan, C., Rajagopal, J., 2012. Generation of Multipotent Lung and Airway Progenitors from Mouse ESCs and Patient-Specific Cystic Fibrosis iPSCs. Cell Stem Cell 10, 385-397. doi:10.1016/j.stem.2012.01.018Mucenski, M. L., Nation, J. M., Thitoff, A. R., Besnard, V., Xu, Y., Wert, S. E., Harada, N., Taketo, M. M., Stahlman, M. T., Whitsett, J. A., 2005. β-Catenin regulates differentiation of respiratory epithelial cells in vivo.Mucenski, M. L., Wert, S. E., Nation, J. M., Loudy, D. E., Huelsken, J., Birchmeier, W., Morrisey, E. E., Whitsett, J. A., 2003. beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis. J. Biol. Chem. 278, 40231-40238. doi:10.1074/jbc.M305892200Nyeng, P., Norgaard, G. A., Kobberup, S., Jensen, J., 2008. FGF10 maintains distal lung bud epithelium and excessive signaling leads to progenitor state arrest, distalization, and goblet cell metaplasia. BMC Dev Biol 8, 2. doi:10.1186/1471-213X-8-2Okubo, T., Knoepfler, P. S., Eisenman, R. N., Hogan, B. L. M., 2005. Nmyc plays an essential role during lung development as a dosage-sensitive regulator of progenitor cell proliferation and differentiation. Development 132, 1363-1374. doi:10.1242/dev.01678Ornitz, D. M., Xu, J., Colvin, J. S., McEwen, D. G., MacArthur, C. A., Coulier, F., Gao, G., Goldfarb, M., 1996. Receptor specificity of the fibroblast growth factor family. J. Biol. Chem. 271, 15292-15297. doi:10.1074/jbc.271.25.15292Ornitz, D. M., Yin, Y., 2012. Signaling Networks Regulating Development of the Lower Respiratory Tract. Cold Spring Harb Perspect Biol 4, a008318-a008318. doi:10.1101/cshperspect.a008318Perl, A.-K. T., Kist, R., Shan, Z., Scherer, G., Whitsett, J. A., 2005. Normal lung development and function after Sox9 inactivation in the respiratory epithelium. genesis 41, 23-32. doi:10.1002/gene.20093Que, J., Okubo, T., Goldenring, J. R., Nam, K. T., Kurotani, R., Morrisey, E. E., Taranova, O., Pevny, L. H., Hogan, B. L. M., 2007. Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm. Development 134, 2521-2531. doi:10.1242/dev.003855Rawlins, E. L., 2010. The building blocks of mammalian lung development. Dev. Dyn. 240, 463-476. doi:10.1002/dvdy.22482Rawlins, E. L., Clark, C. P., Xue, Y., Hogan, B. L. M., 2009. The Id2+ distal tip lung epithelium contains individual multipotent embryonic progenitor cells. Development 136, 3741-3745. doi:10.1242/dev.037317Rock, J. R., Hogan, B. L. M., 2011. Epithelial Progenitor Cells in Lung Development, Maintenance, Repair, and Disease. Annu. Rev. Cell Dev. Biol. 27, 493-512. doi:10.1146/annurev-cellbio-100109-104040Rockich, B. E., Hrycaj, S. M., Shih, H.-P., Nagy, M. S., Ferguson, M. A. H., Kopp, J. L., Sander, M., Wellik, D. M., Spence, J. R., 2013. Sox9 plays multiple roles in the lung epithelium during branching morphogenesis. Proceedings of the National Academy of Sciences. doi:10.1073/pnas.1311847110Sekine, K., Ohuchi, H., Fujiwara, M., Yamasaki, M., Yoshizawa, T., Sato, T., Yagishita, N., Matsui, D., Koga, Y., Itoh, N., Kato, S., 1999. Fgf10 is essential for limb and lung formation. Nat Genet 21, 138-141. doi:10.1038/5096Shu, W., Guttentag, S., Wang, Z., Andl, T., Ballard, P., Lu, M. M., Piccolo, S., Birchmeier, W., Whitsett, J. A., Millar, S. E., Morrisey, E. E., 2005. Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung. Dev Biol 283, 226-239.Spence, J. R., Lange, A. W., Lin, S.-C. J., Kaestner, K. H., Lowy, A. M., Kim, I., Whitsett, J. A., Wells, J. M., 2009. Sox17 Regulates Organ Lineage Segregation of Ventral Foregut Progenitor Cells. Developmental Cell 17, 62-74. doi:10.1016/j.devce1.2009.05.012Spence, J. R., Mayhew, C. N., Rankin, S. A., Kuhar, M. F., Vallance, J. E., Tolle, K., Hoskins, E. E., Kalinichenko, V. V., Wells, S. I., Zorn, A. M., Shroyer, N. F., Wells, J. M., 2011. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470, 105-109. doi:10.1038/nature09691Tichelaar, J. W., Lu, W., Whitsett, J. A., 2000. Conditional expression of fibroblast growth factor-7 in the developing and mature lung. Journal of Biological Chemistry. doi:10.1074/jbc.275.16.11858Varner, V. D., Nelson, C. M., 2014. Cellular and physical mechanisms of branching morphogenesis. Development 141, 2750-2759. doi:10.1242/dev.104794Volckaert, T., Campbell, A., Dill, E., Li, C., Minoo, P., De Langhe, S., 2013. Localized Fgf10 expression is not required for lung branching morphogenesis but prevents differentiation of epithelial progenitors. Development 140, 3731-3742. doi:10.1242/dev.096560Weaver, M., Dunn, N. R., Hogan, B. L., 2000. Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis. Development 127, 2695-2704. Weaver, M., Yingling, J. M., Dunn, N. R., Bellusci, S., Hogan, B. L., 1999. Bmp signaling regulates proximal-distal differentiation of endoderm in mouse lung development. Development 126, 4005-4015.White, A. C., Xu, J., Yin, Y., Smith, C., Schmid, G., Ornitz, D. M., 2006. FGF9 and SHH signaling coordinate lung growth and development through regulation of distinct mesenchymal domains. Development 133, 1507-1517. doi:10.1242/dev.02313Wong, A. P., Bear, C. E., Chin, S., Pasceri, P., Thompson, T. O., Huan, L.-J., Ratjen, F., Ellis, J., Rossant, J., 2012. Directed differentiation of human pluripotent stem cells into mature airway epithelia expressing functional CFTR protein. Nat Biotechnol. doi:10.1038/nbt.2328Yin, Y., Wang, F., Ornitz, D. M., 2011. Mesothelial- and epithelial-derived FGF9 have distinct functions in the regulation of lung development. Development 138, 3169-3177. doi:10.1242/dev.065110Yin, Y., White, A. C., Huh, S.-H., Hilton, M. J., Kanazawa, H., Long, F., Ornitz, D. M., 2008. An FGF-WNT gene regulatory network controls lung mesenchyme development. Developmental Biology 319, 426-436. doi:10.1016/j.ydbio.2008.04.009Zhang, M., Wang, H., Teng, H., Shi, J., Zhang, Y., 2010. Expression of SHH signaling pathway components in the developing human lung. Histochem. Cell Biol. 134, 327-335. doi:10.1007/s00418-010-0738-2Zhang, X., Ibrahimi, O. A., Olsen, S. K., Umemori, H., Mohammadi, M., Ornitz, D. M., 2006. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J. Biol. Chem. 281, 15694-15700. doi:10.1074/jbc.M601252200Zhang, Y., Yokoyama, S., Herriges, J. C., Zhang, Z., Young, R. E., Verheyden, J. M., Sun, X., 2016. E3 ubiquitin ligase RFWD2 controls lung branching through protein-level regulation of ETV transcription factors. Proceedings of the National Academy of Sciences 201603310. doi:10.1073/pnas.1603310113Zhao, R., Fallon, T. R., Saladi, S. V., Pardo-Saganta, A., Villoria, J., Mou, H., Vinarsky, V., Gonzalez-Celeiro, M., Nunna, N., Hariri, L. P., Camargo, F., Ellisen, L. W., Rajagopal, J., 2014. Yap tunes airway epithelial size and architecture by regulating the identity, maintenance, and self-renewal of stem cells. Developmental Cell 30, 151-165. doi:10.1016/j.devce1.2014.06.004. EQUIVALENTS The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein. | 102,744 |
11857698 | EMBODIMENTS OF THE INVENTION AND EXPERIMENTAL DATA The present invention is now illustrated with reference to the following non-limiting examples and accompanying figures. Example 1 Example 1 describes a method used to produce bone graft substitutes of the present invention. Reagents 0.14M NaF solutionAbsolute (100%) ethanoltetraethyl orthosilicate (TEOS, (Si(OC2H5)4))Calcium nitrate tetrahydrate (Ca(NO3)2·4H2O)Triethyl phosphate ((C2H5)3PO4) Calcium nitrate tetrahydrate was dissolved in 0.14 M solution of NaF, after which ethanol was added. This mixture was then stirred for 5 minutes and then triethyl phosphate ((C2H5)3PO4) added. Finally the TEOS was combined slowly with this solution and allowed to stir for thirty seconds. 4 ml of the solution was cast into cylindrical moulds (Ø11 mm×50 mm height, via syringe). Each mould was then covered with film and placed into glass container. Each sample was then gelled for 48 hours at 60° C. Each sample was then placed into 60% ethanol. After 24 hours the solution was changed for 80% ethanol. After another 24 hours it was changed once again for 95% ethanol. Finally the solution was replaced with 100% ethanol. Each sample was dried using the CPD method using a Tousimis® 931 critical point drier. Each sample was run through three stasis cycles of eight hours each. After critical drying each sample was then calcined at 700° C. for three hours. Example 2 Six samples were prepared using the method of example 1. Table 1 shows the chemical composition and density of samples 1-6. All samples were produced with the following molar ratios of H2O, ethanol and TEOS of 17.26:16.71:1.00. TABLE 1Chemical compositionsSiO2P2O5CaODensityComposition(mol %)(mol %)(mol %)(g cm−3)Sample 138.006.0056.000.126Sample 240.006.0054.000.190Sample 342.256.0051.75NotdeterminedSample 444.696.0049.310.122Sample 547.506.0046.500.248Sample 650.806.0043.200.132 The data presented in table 1 shows both the compositions of and densities of five compositions of bioactive aerogels. This data demonstrates the ability to produce a range of compositions. It is also clear that very low densities can be achieved for the bone graft substitutes of the present invention. Density is an important property for bone graft substitutes. The ability to produce bone graft substitutes having low densities represents one of the key advantages of the present invention. Bone graft substitutes with low densities may provide rapid remodelling times and significantly reduce any potential pH rise associated with the ion exchange processes. Example 3 Further analysis of sample 2 was conducted, and key properties measured. These are set out in Table 2 below. The average pore diameter and pore volume were obtained from N2adsorption using the NLDFT method. The surface area was obtained from N2adsorption using the BET method. The density was measure by calculating the volume of the sample and weighing the sample. Sample 2 was produced according to the method outlined in example 1. TABLE 2Key properties of Sample 2PropertyValueDensity0.19g cm−3Average Pore Diameter16.0nmSurface Area892m2g−1Pore Volume4.92cm3g−1 Table 2 shows a number of properties of sample 2 measured using N2adsorption analysis. This data supports the previous data showing low densities and confirms pores in the nm scale and a high pore volume. Current sol-gel glasses used as bone graft materials have a maximum surface area of around 450 m2g−1. The data for sample 2 show that bone graft substitutes of the present invention can have a surface area of nearly double the maximum of currently used bone graft substitutes. The surface area data show another advantage of the bone graft substitutes of the present invention. It has been shown that the high surface areas of silicate based bone graft substitutes lead to superior in-vivo performance. Without wishing to be bound by theory it is proposed that the higher surface area allows for improved adhesion of proteins and cells that are involved with osseointegration and remodelling. Example 4 FIG.1shows the N2adsorption isotherm of sample 2. Bioactivity testing (ability to precipitate hydroxyapatite) was carried out on sample 2 using a simulated body fluid test. FIG.2shows the absorbance spectra after 3 hours of immersion in simulated body fluid. The precipitation of hydroxyapatite is confirmed by the presence of two bands at 560 and 600 cm−1. This is an industry standard test to demonstrate that a material is bioactive. This test is widely accepted to demonstrate that a material which is bioactive in simulated body fluid would, once in the body, be able to form bone on its surface. This is an essential property for bone substitute materials. FIGS.3and4show a scanning electron micrograph of sample 2 after calcination. The structure of the unreacted sample 2 shows silica spheres forming a bioactive aerogel structure. This data demonstrates that the bone graft substitutes of the present invention are bioactive and exhibit low densities and high surface areas, compared to typically used bones graft substitutes. Example 5 31P magic angle spinning nuclear magnetic resonance (MAS-NMR) was performed on a Bruker 600 MHz spectrometer at the 242.9 MHz resonance frequency. The powder samples were packed into a 4 mm rotor and spun at 12 kHz. The measurements were done using 60 s recycle delay and 85% H3PO4was used to reference the chemical shift scale. FIGS.7-11show the31P NMR spectra of samples 1, 2, 4, 5 and 6 (from table 1) respectively. Measurements were taken after 3 hours, 6 hours, 1 day and 3 days immersion in SBF solution. A typical31P shift at 2.9 ppm is beginning to appear after 3 hours with all samples and is clearly visible after 6 hours. This demonstrates that the material has the ability to form hydroxyapatite (or similar) structures on its surface. This is a standard test used to demonstrate the bioactivity of a material. Example 7 Example 7 provides a method which can be used for producing bone graft substitutes of the present invention. Reagents 0.14M NaF solutionAbsolute (100%) ethanoltetraethyl orthosilicate (TEOS, (Si(OC2H5)4))Brushite (CaHPO4·2H2O) Brushite is dissolved in 0.14 M solution of NaF, after which ethanol is added. This mixture is then stirred for 5 minutes. Finally the TEOS is combined slowly with the solution and is allowed to stir for thirty seconds. 4 ml of the solution is cast into cylindrical moulds (Ø11 mm×50 mm height, via syringe). Each mould is then covered with film and placed into glass container. Each sample is then gelled for 48 hours at 60° C. Each sample is then placed into 60% ethanol. After 24 hours the solution is changed for 80% ethanol. After another 24 hours it is changed once again for 95% ethanol. Finally the solution is replaced with 100% ethanol. Each sample is dried using the CPD method using a Tousimis® 931 critical point drier. Each sample is run through three stasis cycles of eight hours each. After critical drying each sample is then calcined at 700° C. for three hours. Example 8 The compositions outlined in table 3 may be produced by the method of example 6. TABLE 3Chemical compositionsSiO2P2O5CaOComposition(mol %)(mol %)(mol %)Sample 760.0013.3326.67Sample 865.0011.6623.34Sample 970.0010.0020.00 Example 9 Example 9 provides a method which can be used for producing bone graft substitutes of the present invention. Reagents 0.14M NaF solutionAbsolute (100%) ethanoltetraethyl orthosilicate (TEOS, (Si(OC2H5)4))Brushite (CaHPO4·2H2O)Calcium nitrate tetrahydrate (Ca(NO3)2·4H2O) Brushite is dissolved in 0.14 M solution of NaF, after which ethanol is added. The mixture is then stirred for 5 minutes, calcium nitrate tetrahydrate is then added to the mixture and left to dissolve for 5 minutes. Finally the TEOS is combined slowly with the solution and allowed to stir for thirty seconds. 4 ml of the solution is cast into cylindrical moulds (Ø11 mm×50 mm height, via syringe). Each mould is then covered with film and placed into glass container. Each sample is then gelled for 48 hours at 60° C. Each sample is then placed into 60% ethanol. After 24 hours the solution is changed for 80% ethanol. After another 24 hours it is changed once again for 95% ethanol. Finally the solution is replaced with 100% ethanol. Each sample is dried using the CPD method using a Tousimis® 931 critical point drier. Each sample is run through three stasis cycles of eight hours each. After critical drying each sample is then calcined at 700° C. for three hours. | 8,582 |
11857699 | DESCRIPTION OF EMBODIMENTS As used herein the term “substantially” and its equivalents refer to being at least 70% of a stated value, desirably within at least 80% of a stated value, and more desirably within 90% or 95% of a stated value. As used herein the terms “about” or “approximate” and their equivalents refer to being within (plus and/or minus) at least 20% of a stated value, desirably within at least 10% of a stated value, and more desirably within 5% of a stated value. As used herein the terms “layer” and “coating” may be used interchangeably to refer to a deposition of material over, underneath, or within a substrate, such as a textile substrate. As used herein masking agent shall refer to any suitable non-biological, e.g., synthetic, hydrophilic polymer and any suitable biological hydrophilic polymer. However, it should be understood that other masking agents may be used. With reference toFIGS.1ato1d, four stages of manufacture of a vascular prosthesis16are illustrated. In each of theFIGS.1ato1dtwo perspective views of the conduit10and/or the vascular prosthesis16are provided. The left hand views show an inlet10cbeing forwardly disposed in the views, and the right hand views show an outlet10dbeing forwardly disposed in the views. FIG.1ashows a conduit10which is suitable for implant in the human or animal body. The conduit10is a cylindrical conduit10and comprises a wall10f. The wall10fcomprises an inner surface10aand an outer surface10b. The conduit10also comprises an inlet10cand an outlet10d. In the embodiment described here, substantially all of the conduit10is porous10e. However, it should be understood that at least a section of the conduit10could be porous10e. In this embodiment, the conduit10is a woven, fibrous polymer conduit10. The woven nature of the conduit10leads to substantially all of the conduit10being porous10e. The conduit10comprises polyethylene terephthalate (PET). However, it should be understood that the conduit10could comprise other materials, such as polytetrafluoroethylene (PTFE). Other suitable polymers for medical textile applications may include, but are not limited to polyolefin, polyester, poly(ether amide), poly(ether ester), poly(ether urethane), poly(ester urethane), poly(ethylene-styrene/butylene-styrene), and other block copolymers. In the embodiment illustrated and described here, the weft yarn pick-rate of the conduit10is approximately 45 ppcm. However, it should be understood that the weft yarn pick-rate of the conduit10could be between approximately 25 ppcm and approximately 50 ppcm. The conduit10is moveable between a contracted state and an extended state. FIG.1athus depicts an unprocessed conduit10. In its unprocessed form, blood (an example of a fluid) can flow between the outer surface10bof the wall10fand the inner surface10aof the wall10f. That is, if fluid flows into the inlet10c, the blood will leak through the porous section10eof the conduit10. The conduit10depicted inFIG.1amust therefore be sealed prior to use as an implantable vascular prosthesis16. The conduit10depicted inFIG.1ahas been cut to a predetermined size. For example, the length of the conduit10may need to be altered depending on the size of vascular prosthesis16required. Furthermore, if the vascular prosthesis16is to be connected to at least one heart assist component (an example of a further prosthesis), this may also require a different size, or length of conduit10to be used. The conduit10is also weighed during this step of the manufacturing process. In the embodiment illustrated here, the conduit10has a substantially uniform cross section throughout. However, it should be understood that the conduit10could have an irregular cross section throughout. For example, if the conduit10is to be connected between a further prosthesis, such as a heart valve, and an end of a severed blood vessel, the conduit10could have an irregular cross section throughout. As described in more detail below, in some embodiments the conduit10could be configured to have differing degrees of flexibility, either by selectively adding sealant14to different sections of the conduit10, or in other ways. As described above, it is desirable for the inner surface10aof the wall10fof the conduit10to remain free from, or substantially devoid of, the material used to seal the conduit10. The reason for this is to ensure that the inner surface10aof the wall10fof the conduit10, remains of a porous10e, woven nature, to ensure that when the vascular prosthesis16is implanted in the human or animal body, biological tissue will grow into the inner surface10aof the wall10fof the conduit10. This is important to ensure that ingrowing biological tissue forms a pseudointima (an example of an inner biological tissue layer within a vascular prosthesis). Furthermore, in addition to the promotion of biological tissue growth on the inner surface10aof the wall10fof the conduit10, it is also advantageous if the biological tissue layer growing on the inner surface10aof the wall10fof the conduit10has good adhesion to the inner surface10a. If the adhesion between the biological tissue layer and the inner surface10ais insufficient, complications can arise such as haemorrhagic dissection. FIG.1bshows the conduit10after the addition of a masking agent12. In this embodiment, the masking agent12forms a masking agent layer on the inner surface10aof the wall10fof the conduit10. The masking agent layer is designed to protect the inner surface10aof the conduit10during the manufacturing process illustrated and described herein. Specifically, the masking agent12is designed to mitigate presence of sealant14on the inner surface10aof the wall10fof the conduit10. Prior to the addition of the masking agent12to the conduit10, the conduit10is weighed. The weight of the conduit10is then used, at least in part, to determine the amount of masking agent12to add to the conduit10. In this embodiment, the masking agent12is applied from a masking agent solution. The masking agent solution is a polymer solution. In the embodiment illustrated and described here, the polymer solution comprises approximately 7% w/v PVP (an example of a water-soluble polymer) in water (an example of a solvent). However, it should be understood that other polymers, such as glycerol, methyl cellulose and/or PEG could be used. Furthermore, it will be understood that the polymer solution could comprise between approximately 5% w/v PVP in solution and approximately 30% w/v PVP in solution. Moreover, the polymer solution could comprise between approximately 5% w/v polymer in solution and approximately 30% w/v polymer in solution. It should be understood that the masking agent12could comprise approximately 1% w/v of glycerol in solution. Without wishing to be bound by theory, it is thought that an advantage of adding glycerol to the masking agent12is that it mitigates cracking of the masking agent12when the masking agent12is added to the conduit10. In the embodiment described here, the masking agent12comprises PVP with a molecular weight of approximately 10,000 g/mol. However, it should be understood that the masking agent12could comprise PVP with a molecular weight of between approximately 6,000 g/mol and approximately 15,000 g/mol. While in the embodiment described here the masking agent12comprises PVP, it should be understood that the masking agent12could comprise glycerol, methyl cellulose, PEG, PEO, and/or PEG hydrogel. In the embodiment illustrated and described here, the masking agent12is biocompatible. However, it should be understood that, in some embodiments the masking agent12need not be biocompatible. For example, as described in more detail below, if substantially all of the masking agent12is to be removed from the conduit10, then the masking agent12need not be biocompatible. In some embodiments, the masking agent12need not be removed, and in some embodiments only a part of the masking agent12is removed. In these arrangements, it is advantageous that the masking agent12is biocompatible, which allows the conduit10to be implanted in the human or animal body. In this embodiment, the masking agent12is biodegradable. Therefore, any residual masking agent12present on the conduit10will biodegrade when the conduit10is implanted in the human or animal body. However, the masking agent12could be non-biodegradable. In this embodiment, substantially all of the masking agent12is removed from the conduit10prior to implantation, and therefore it is not necessary for the masking agent12to be biodegradable. In some embodiments, it may be advantageous for the masking agent12to be biodegradable. With reference toFIG.1b, the masking agent12is applied to the conduit10from a polymer solution. However, it will be appreciated that the masking agent12could be applied to the conduit10in other ways. In this embodiment, the masking agent solution is applied to the conduit10by immersing the conduit10in the masking agent solution for approximately 1 minute, while agitating the conduit10. However, it should be understood that the masking agent solution could be added to the conduit10in other ways, such as by dipping, spray coating, or by brushing. Furthermore, it should be understood that the masking agent12could be added to the conduit10without agitating the conduit10. During the step of immersing the conduit10in the masking agent solution, the conduit10is moved between the contracted state and the extended state. However, it should be understood that the conduit10could be immersed in the masking agent solution while the conduit10is in the contracted state and/or the extended state. In this embodiment, when the masking agent solution is added to the conduit10, solvent is then evaporated from the masking agent solution. Solvent is therefore removed from the masking agent solution, and the masking agent12remains on the conduit10. In this embodiment, during the addition of the masking agent12to the conduit10, a directed flow of air (an example of a gas) is provided to the conduit10. The directed flow of air is directed towards the outer surface10bof the wall10fof the conduit10, such that the masking agent12is preferentially formed on the inner surface10aof the wall10fof the conduit10. It should be understood that while directed air flow is used here, other gases could be used. In this embodiment, the masking agent12is formed, or added, substantially on the inner surface10aof the wall10fof the conduit10. However, it should be understood that the masking agent12could be added to the outer surface10bof the wall10fof the conduit10. The masking agent12is added to the porous section10eof the conduit10, although in other embodiments the masking agent12could be added to at least a part of the porous section10eof the conduit10. In this embodiment, the masking agent12forms a masking agent layer substantially on the inner surface10aof the wall10fof the conduit10. However, it should be understood that the masking agent12could be added to other parts of the conduit10, and that the masking agent12could form a masking agent layer on other parts of the conduit10. In the manufacturing process illustrated and described here, the residual masking agent12on the outer surface10bof the wall10fof the conduit10is removed prior to the addition of the sealant14, in order to improve the adhesion between the sealant14(when applied to the conduit10) and the outer surface10bof the wall10fof the conduit10. In this embodiment, the residual masking agent12on the outer surface10bis removed by ablating (an example of a first masking agent removal step). However, it should be understood that the masking agent12could be removed by applying a solvent, by heating, by etching, by plasma etching, by abrading, and/or by other techniques. In the embodiment shown inFIG.1b, the masking agent12is formed on substantially all of the inner surface10aof the wall10fof the conduit10. FIG.1cshows the conduit10after the addition of the masking agent12and the sealant14. In the embodiment described here, the sealant14is added to the conduit10from a sealant solution. In the embodiment described here, the sealant solution is a polymer solution comprising room temperature vulcanising silicone elastomer and xylene. However, it should be understood that the sealant solution could comprise at least one of polycarbonate, silicone, silicone elastomer, polyurethane, TPU, one or more thermoplastic elastomers, and/or aliphatic polycarbonate. It should also be understood that while the sealant14is added to the conduit10from a polymer solution comprising xylene, heptane could be used in place of xylene. Furthermore, in some embodiments the sealant solution may comprise a polar solvent, such as dimethylacetamide (DMAC) or tetrahydrofuran (THF). When the sealant solution is applied to the conduit10, solvent is evaporated from the sealant solution, which results in the formation of the sealant14. While in the embodiment illustrated and described here the sealant14is added to the conduit10from a sealant solution, it will be understood that the sealant14could be added to the conduit10in other ways and need not be added from a sealant solution. The sealant14is added to the porous section10eof the conduit10. Therefore, in this embodiment, the sealant14is added to substantially all of the conduit10, as in this embodiment the conduit10is entirely porous10e. In other embodiments, the sealant14could be added to a part of the porous section10e. The presence of the masking agent12prevents the sealant14from adhering, or forming on, the inner surface10aof the wall10fof the conduit10. The sealant14is applied to the conduit10by spraying the sealant14onto the outer section10bof the conduit10. However, it should be understood that other techniques for adding the sealant14to the conduit10could be used, such as brushing, wiping, immersing, dipping, vapour depositing, such as chemical vapour depositing, electrostatic spinning, and/or by casting. In this embodiment, the sealant14is applied to the conduit10, while the conduit10is in the extended state. However, it should be understood that the sealant14could be applied to the conduit10while the conduit10is in the contracted state or when the conduit10is moved between the contracted state and the extended state. In this embodiment, the sealant14is added to the conduit10while the conduit10is rotated about its longitudinal axis at approximately 60 rpm. However, it should be understood that the conduit10could be rotated about its longitudinal axis at up to approximately 2,000 rpm. In the embodiment described here, the sealant14comprises approximately 8 mg/cm2of silicone. However, it should be understood that the sealant could comprise between approximately 4 mg/cm2of silicone and approximately 19 mg/cm2of silicone. Spraying and/or brushing the sealant14onto the outer surface10bof the wall10fof the conduit10is advantageous over some sealant application techniques because the sealant14is applied substantially only to the outer surface10bof the conduit10and is not substantially applied to the inner surface10aof the conduit10. In this arrangement, the masking agent12, and the addition of the sealant14to the conduit10by way of spraying, and/or brushing, the sealant14onto the conduit10, mitigate presence of the sealant14on the inner surface10aof the wall10fof the conduit10. However, it should be understood that other sealant14application techniques, such as wiping the sealant14onto the conduit10, could be used. In the embodiment illustrated and described here, it is advantageous if, when the sealant14is applied to the conduit10, the masking agent12is not substantially covered, or blocked, by the sealant14. The reason for this is that, if at least a part of the masking agent12is to be removed from the conduit10, it is easier to remove the masking agent12if at least some of the masking agent12is exposed. For example, when removing at least a part of the masking agent12from the conduit10by applying a solvent, it is easier to do so if at least some of the masking agent12is exposed. In the embodiments described here, a significant amount of the masking agent12is exposed, and it is therefore relatively straightforward to use a variety of masking agent12removal techniques. In this embodiment, the addition of the sealant14to the porous section10eof the conduit10forms a sealing layer on the outer surface10bof the wall10fof the conduit10. In this embodiment, the sealant14is biocompatible. In this embodiment, the sealant14, when applied to the conduit10, is configured to mitigate against environmental stress cracking. FIG.1dshows a vascular graft16(an example of a vascular prosthesis16). In this embodiment, substantially all of the masking agent12has been removed from the conduit10. The leaking of blood (an example of a fluid) through the wall10fof the conduit10is now mitigated due to the addition of the sealant14to the conduit10. Furthermore, the inner surface10aof the wall10fof the conduit10retains the porous, woven properties of the conduit10, such that the inner surface10aof the wall10fof the conduit10allows for the ingrowth of biological tissue and also allows for biological tissue to have good adhesion thereto. The presence of the sealant14obviates the flow of blood through the wall10fof the conduit10, although it will be understood that blood can flow between the inlet10cand the outlet10d. In the embodiment described here and shown inFIG.1d, substantially all of the masking agent12has been removed from the conduit10by applying water to the conduit10at a temperature of approximately 95° C. (an example of a second masking agent removal step). In this second masking agent removal step, the masking agent12has been removed from the conduit10after the step of adding the sealant14to the conduit10has been carried out. In this process, water (an example of a solvent) has been used to remove substantially all of the masking agent12from the conduit10. However, the masking agent12need not be removed substantially entirely from the conduit10. Water need not be used as the solvent, as other solvents could be used to achieve the removal of the masking agent12. It should be understood that the masking agent12could be removed from the conduit10in other ways, such as by etching, plasma etching, ablating, and/or abrading. While the masking agent12has been substantially removed from the conduit10at a temperature of approximately 95° C., it should be understood that the masking agent12could be removed from the conduit10at a temperature of between approximately 15° C. and approximately 140° C. In the embodiment described here, the step of removing the masking agent12from the conduit10is also used to cure the sealant14in a more efficient manner. In the embodiment depicted inFIG.1d, the masking agent removal step, carried out as described above, is carried out for approximately 51 minutes while the conduit10is agitated. Without wishing to be bound by theory, agitating the conduit10is thought to improve the efficiency of the masking agent12removal step. Whilst in this embodiment the masking agent removal step is carried out for approximately 51 minutes, it will be understood that the masking agent removal step could be carried out for between approximately 40 minutes and approximately 300 minutes. It will also be understood that multiple masking agent removal steps could be carried out. In the embodiment illustrated and described here, the step of removing substantially all of the masking agent12from the conduit10does not result in the removal of the sealant14from the conduit10. As described in detail above, the manufacturing process comprises a first masking agent removal step, designed to improve the adhesion of the sealant14to the conduit10, and a second masking agent removal step, designed primarily to remove the masking agent12from the inner surface10aof the wall10fof the conduit10. However, it will be understood that multiple masking agent removal steps could be carried out. It should also be understood that for some embodiments of the invention it may not be necessary to carry out a masking agent removal step. In the embodiment illustrated and described here, the vascular prosthesis16is reversibly sealable. That is, the sealant14could be removed from the conduit10and the sealant14could be applied to the conduit10. For example, this could be necessary in the event of a manufacturing error. Similarly, the masking agent12may be added, and removed from, and subsequently added to the conduit10. This could be necessary when carrying out more than one masking agent addition step. In the embodiment illustrated and described here, the vascular prosthesis16can be sterilised by way of a gamma sterilisation process. However, it should be understood that the vascular prosthesis16could be sterilised by way of an electron beam sterilisation process. Another option for sterilising the vascular prosthesis16is to carry out ethylene oxide sterilisation. It will be appreciated that other sterilisation techniques could be applied to the vascular graft16, either as an alternative to, or in addition to those described here. The vascular prosthesis16depicted inFIG.1dis configured to be implantable inside the human or animal body and is made from substantially entirely biocompatible materials. The vascular prosthesis16can be implanted in the human or animal body without being harmful or toxic to surrounding biological tissue. The vascular prosthesis16illustrated inFIG.1dis flexible, which allows the vascular prosthesis16to be manipulated by a medical practitioner in a more efficient way. In this embodiment, the addition of the sealant14to substantially all of the porous section10eof the conduit10has converted the unprocessed conduit10to a vascular prosthesis16. FIGS.2aand2bshow the inner surface10aof the wall10fof the conduit10in more detail.FIGS.2aand2bshow the porous nature of the conduit10. The conduit10is a woven structure and, in this embodiment, is generally a 1/1 twill weave type. As described above, the unprocessed woven conduit10will allow blood to leak through the gaps in the fibres of the conduit10, and it must therefore be sealed prior to implantation in the human or animal body. The woven nature of the conduit10means that it is flexible. After applying the masking agent12and the sealing layer14, the vascular graft16remains flexible, which helps to make the vascular graft16easier to manipulate and handle by, for example, a medical practitioner. FIGS.3aand3bshow a detailed view of the inner surface10aof the wall10fof the conduit10after the addition of the masking agent12. In this embodiment, the masking agent12has been added to the conduit10from a polymer solution (an example of a masking agent solution) comprising approximately 5% w/v PVP in solution. In this embodiment, the conduit10has been immersed in the polymer solution. However, as described in more detail above, the masking agent12could be added to the conduit10in other ways and the polymer solution could comprise between approximately 5% w/v and approximately 30% w/v of polymer in solution. In the embodiment illustrated inFIGS.3aand3b, the conduit10has been immersed in the masking agent solution for approximately 1 minute. However, it should be appreciated that the conduit10could be immersed in the masking agent solution for other durations of time. In the embodiment shown inFIGS.3aand3b, the masking agent12substantially blocks the porous section10eof the conduit10. When the sealant14is applied to the conduit10, the masking agent12mitigates the presence of the sealant14on the inner surface10aof the wall10fof the conduit10. In this embodiment, the masking agent12forms an oleophobic layer (an example of a masking layer). Without wishing to be bound by theory, it is thought that the oleophobic properties of the masking layer helps to mitigate the presence of the sealant14on the inner surface10aof the wall10fof the conduit10. It should be understood that in some embodiments the masking agent12need not form an oleophobic layer. FIGS.4aand4bshow the inner surface10aof the wall10fof the conduit10after the sealant14has been added to the outer surface10bof the wall10fof the conduit10.FIGS.4aand4bhighlight the effectiveness of the masking agent12in mitigating the presence of sealant14on the inner surface10aof the wall10fof the conduit10. In this embodiment, the masking agent12has been applied to the conduit10from a masking agent solution comprising approximately 7% w/v of PVP in solution. In the embodiment illustrated inFIGS.4ato5b, the sealant has been added to the outer surface10bof the wall10fof the conduit10by spray coating a sealant solution onto the outer surface10bof the wall10fof the conduit10. FIGS.5aand5bshow the presence of the sealant14on the outer surface10bof the wall10fof the conduit10of the embodiment shown inFIGS.4aand4b. In the embodiment shown inFIGS.5aand5b, the sealant solution comprises approximately 15% w/v of silicone in xylene. FIGS.4aand4b, andFIGS.5aand5b, highlight the contrast between the inner surface10aand the outer surface10bof the wall10fof the conduit10after the application of the sealant14to the conduit10. The outer surface10bof the conduit10is now substantially covered in the sealant14, whereas the inner surface10aof the wall10fof the conduit10has retained the woven, porous properties of the conduit10, because the inner surface10aof the wall10fof the conduit10is substantially devoid of the sealant14. The masking agent12has mitigated the presence of the sealant14on the inner surface10aof the wall10fof the conduit10. In this embodiment, the inner surface10aof the wall10fis configured to facilitate the growth of biological tissue thereon, and to allow for good adhesion between ingrowing biological tissue and the inner surface10a. Presence of the sealant14on the inner surface10aof the wall10fof the conduit10could have an adverse impact on the ingrowth of biological tissue on the inner surface10aof the wall10fof the conduit10, and on the adhesion between the biological tissue and the inner surface10aof the wall10fof the conduit10. FIG.6ashows a detailed view of the outer surface10bof the wall10fof the conduit10after the addition of the sealant14. In this embodiment, the sealant14is configured to mitigate movement of fluid through the wall10fof the conduit10. The wall10fof the conduit10is substantially blood impermeable (i.e., blood cannot pass or leak through the wall10fat an appreciable rate) after the addition of the sealant14. FIG.6bshows a detailed view of the inner surface10aof the wall10fof the conduit10after the addition of the sealant14to the conduit10. In the embodiment shown inFIGS.6aand6b, the masking agent12has been applied to the conduit10from a polymer solution comprising approximately 30% w/v PVP in solution, prior to the addition of the sealant14. As described above, the masking agent12can be applied to the conduit10from a polymer solution comprising between approximately 5% w/v and approximately 30% w/v of polymer in solution. One desirable feature for a sealed graft is that it may have sufficiently low levels of permeability to remain predominantly leak proof during the implant procedure. The applicable test method, as prescribed in ISO 7198, Whole Graft Permeability recommends testing using reverse osmosis (RO) filtered water at a test pressure of 120 mmHg. This parameter was based on a de facto standard established by the manufacturers of biologically sealed grafts (gelatin and collagen). A limit of 0.16 ml/min/cm2may be used to ensure that the graft meets and exceeds sealing capability of aforementioned grafts. Different applications, however, may have different permeability requirements, and such different permeability requirements are within the scope of the present invention. Further embodiments were prepared according to the manufacturing process illustrated inFIGS.1ato6band described above. The further embodiments are described in Table 1 below. The manufacturing process used to create the further embodiments listed in Table 1 is substantially the same as that illustrated and described in relation toFIGS.1ato6b, with the exception that different masking agents12and sealants14were used. Commercial textile vascular grafts were used for the tests described hereinafter. Details for commercial graft samples are described below: First Commercial Samples of Woven Graft Fabrics:(a) Warp yarn: twisted, texturized, PET, 2 ply/44 denier per ply (or bundle)/27 filaments per ply or bundle.(b) Weft yarn: twisted, texturized, PET, 2 ply/, 44 denier per ply (or bundle)/27 filaments per ply or bundle.(c) Picks per cm, about 40 to 46. Second Commercial Samples of Woven Graft Fabrics:(a) Warp yarn: 80 Denier, 2 ply/40 denier per ply (or bundle)/27 filaments per ply (or bundle), PET, Spun Draw, texturized, 7.5 Twists per inch, Z twist.(b) Weft yarn: 2 ply/40 Denier per ply (or bundle), 2 ply/40 denier per ply (or bundle)/27 filaments per ply or bundle, PET, TXT, S & Z Twist.(c) Picks per inch, about 155. The tests done below in Table 1 were performed on the first commercial samples of woven graft fabrics. TABLE 1SealantSealantLeak RateMasking AgentSealantCoatingCoverageLeak Rate≤0.16PolymerSolventPolymerSolventMethod(mg/cm2)(ml/min/cm2)ml/min/cm27% w/vWater30% w/vXyleneBrush × 111.330.19NoPVPSilicone7% w/vWater30% w/vXyleneBrush × 18.300.19NoPVPSilicone4% w/vWaterTPU andTHFBrush × 12.005.79NoPVPSilicone4% w/vWaterTPU andTHFBrush × 23.700.46NoPVPSilicone30% w/vWater30% w/vXyleneBrush × 15.31.78NoPVPSilicone30% w/vWater30% w/vXyleneBrush × 15.23.49NoPVPSilicone30% w/vWater30% w/vXyleneBrush × 17.6>12.24NoPVPSilicone25% w/vWater30% w/vXyleneBrush × 1——NoPVP andSilicone18% w/vGlycerol7% w/vWater30% w/vXyleneBrush × 14.80YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 28.90YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 38.30YesPVPSilicone7% w/vWater30% w/vHeptaneBrush × 17.60.69NoPVPSilicone7% w/vWater30% w/vHeptaneBrush × 213.80.02YesPVPSilicone7% w/vWater30% w/vHeptaneBrush × 318.60YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 18.00.09YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 211.50.14YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 211.50.05YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 315.60YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 17.10.01YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 29.70.03YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 29.10.03YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 312.60.02YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 16.00.22NoPVPSilicone7% w/vWater30% w/vXyleneBrush × 214.30.03YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 29.80.10YesPVPSilicone7% w/vWater30% w/vXyleneBrush × 313.80.06YesPVPSilicone12% w/vWater30% w/vXyleneBrush × 211.06.25NoPVPSilicone12% w/vWater30% w/vXyleneBrush × 211.31.81NoPVPSilicone7% w/vWater15% w/vXyleneSpray × 13.57.24NoPVPSilicone7% w/vWater15% w/vXyleneSpray × 25.60.07YesPVPSilicone7% w/vWater15% w/vXyleneSpray × 35.30.57NoPVPSilicone7% w/vWater15% w/vXyleneSpray × 16.75.11NoPVPSilicone7% w/vWater15% w/vXyleneSpray × 18.70.01YesPVPSilicone7% w/vWater15% w/vXyleneSpray × 16.40.02YesPVPSilicone7% w/vWater15% w/vXyleneSpray × 148.41NoPVPSilicone7% w/vWater15% w/vXyleneSpray × 16.38.99NoPVPSilicone7% w/vWater15% w/vXyleneSpray × 13.85.05NoPVPSilicone7% w/vWater15% w/vXyleneSpray × 18.11.17NoPVPSilicone7% w/vWater15% w/vXyleneSpray × 17.90.14YesPVPSilicone7% w/vWater15% w/vXyleneSpray × 18.25.94NoPVPSilicone7% w/vWater15% w/vXyleneSpray × 18.81.08NoPVPSilicone7% w/vWater15% w/vXyleneSpray × 111.40.01YesPVPSilicone7% w/vWater15% w/vXyleneSpray × 16.85.93NoPVPSilicone7% w/vWater15% w/vXyleneSpray × 17.40.16YesPVPSilicone7% w/vWater15% w/vXyleneSpray × 111.90YesPVPSilicone6% w/vWater15% w/vXyleneSpray × 17.80.04YesPVP andSilicone1% w/vGlycerol A hobby spray gun was used for all spray application tests where sealants were sprayed onto graft samples. The spray distance from the graft samples was approximately 50 mm. Grafts were held horizontally on mandrel and rotated in a rotisserie. Spray rates were not measured but were controlled by a combination of the nozzle traverse rate (estimated at 2 seconds/cm), graft rotation speed (estimated between one and three revolutions per second) and overall spray volume rate. Craft bristle brushes were used for all brush application tests where sealants were brushed onto graft samples. As indicated in Table 1, if the wall10fhas a Leak Rate≤0.16 ml/min/cm2then the conduit10is considered suitable for implantation and is considered substantially impermeable. In some further embodiments, the masking agent12comprises glycerol. Without wishing to be bound by theory, the presence of glycerol in the masking agent12is thought to mitigate cracking of the masking agent12when applied to the conduit10. Masking agents described herein prevent sealants, such as the liquid silicone elastomer dispersion, from penetrating throughout the thickness of the graft wall and reaching the lumen or blood contacting surface of the graft. Sealants, such as silicone, are believed to adhere to graft fibres on the external surface of the graft through two mechanisms:a. Where graft fibres have had the mask agent ablated or otherwise free of the masking agents, the liquid silicone elastomer dispersion adheres to the surface of the graft fibres, such as PET fibres.b. Where surface fibres are individually sheathed by the masking agent, these fibres are encapsulated and a mechanical interlocking takes place rather than surface adhesion. Silicone will adhere to the PET fibre surface where there is no masking agent, but will also encapsulate PET fibres which are sheathed in masking agent. The masking agent is believed to act like a slurry when applied to a textile and can flow and cover gaps between the yarn bundles and also seep between the yarn fibers. It acts as a viscous mixture moving through the fabric and settling and collecting at areas of low energy. Rather than attaching to individual fibers it continues to move and pool until a masking agent drying process initiates and through the evaporation of its solvent, such as water, the masking agent then solidifies wherever it has gathered. The elastomeric sealant (e.g., silicone) may not adequately attach to the textile surface where excessive concentrations of masking agent are present. If the masking agent is too viscous and has fully encapsulated an area of fabric and then dried, there may be no exposed yarn filaments for the silicone to mechanically encapsulate and lock onto. Without this mechanical encapsulation of the yarn by the silicone, then the adhesion may be poor and possibly non-existent once the masking agent is removed. While the masking agent may appear to thinly coat the individual filaments as it moves or washes through the textile, the concentrations remaining in these washed through areas after drying are not sufficient to prevent subsequent encapsulation and adhesion of the silicone adhesive to the yarn bundles. Any synthetic hydrophilic polymer and any biological hydrophilic polymer, e.g., gelatin, partially hydrolysed collagen, dextran, hyaluronic acid, alginates and starches (e.g., hydroxyethyl starch) and chitosan may be used as masking agents. Pluronic F127 PEG, which is soluble in cold water but insoluble in warm water, may also be used as a masking agent. Desirably, masking agents derived from animal products may are removed prior to vascular applications. As such, the masking agents, including animal derived masking agents, if any, are removed from the final product, such grafts may suitable be used in vascular applications. Furthermore, as the masking agents are removed from the textile graft prior to any applications with a patient, including vascular applications, the masking agents need not be biocompatible. Desirably, the masking agent is highly soluble in water. It can be any polymer which can swell in a liquid which has a Hildebrand Solubility Parameter (Delta SI units) of 24 or higher. Masking agents useful with the present invention may have molecular weights from about 400 or 1,000 to about 1,000,000. Desirably, the molecular weight may vary from about 3,000 to about 30,000, and more desirably from about 6,000 to about 15,000 One useful sealant may be a dispersion of silicone in a nonpolar ‘solvent’ or carrier medium. Useful cross linking is through acetoxy ‘room temp vulcanisation’ chemistry but two part platinum cure chemistry could also be used as well as ultraviolet (UV) curing. For samples employing a polymer supplied as a dispersion, for example NuSil MED 6605 and Med 6606, discrete amounts of polymer dispersion were decanted by weight into individual pots for either direct coating onto the graft or further addition of solvent, by weight. All silicone dispersions used were acetoxy curing. Curing schedules are recommended at 72 hours, however due to the extremely thin cross section/large surface area of the graft, full cures have been observed apparent within 24 hours. Subsequent washing of the device in water may speed up the curing and ensure full cross linking. These times are, however, non-limiting, and other cure times and conditions may suitably be used. The preferred polymers for coating, in order to achieve a soft and flexible graft with handling characteristics similar to that of a gelatin sealed graft, are those with very low Shore hardness values. The preferred silicone elastomers, MED 6605 and MED 6605 have Durometer Type A values of 25 and 20 respectively. Both of these grades can provide grafts with suitable flexibility and handling characteristics, when thin coatings are applied. As multiple coatings are applied, stiffness may increase and flexibility may reduce. Harder grades can be used as an alternative to thicker coatings in order to create stiffer grafts if required. Alternative coatings, such as TPU-Silicones (Advansource Chronosil 75A or Aor-Tech Elast-Eon E5-130) can be used however, these have Durometer Hardness of 75A and 77A respectively, therefore may create grafts which may be stiffer, if desired, than current gelatin sealed grafts. Such stiffer grafts may have some benefits for specific applications, however, may not meet expectations for conventional surgeon handling. Additional useful sealant materials include, but are not limited to:(a) Applied Silicone Corporation, PN 40021, Implant grade high strength RTV Silicone Elastomer Dispersion in Xylene. This material is suitable for use in fabricating high strength, elastic membranes of any shape and thickness using processes such as dipping, casting, spraying or brushing. After evaporating the solvent, the silicone is room temperature vulcanized (RTV) by exposure to ambient air. The key features of this material are high strength, low durometer, (Shore A 24) and is supported by ISO 10993 testing and compendium to support regulatory submissions.(b) AdvanSource Biomaterials Corporation, ChronoFlex AR, polycarbonate based thermoplastic urethanes. These materials may be used for moulding, casting and dip-coating and are fully synthesized in liquid providing high strength & elongation while maintaining the inherent polycarbonate advantage of long-term permanent durability and resistance to environmental stress cracking (ESC). Additionally, they may be electrospun or used in water emulsion processes. Examples of specific useful materials include, but are not limited to, ChronoFlex C80A 5% and ChronoFlex AR 23%. Suitable sealants are low durometer elastomers (desirably less than or equal to about 40A durometer or shore hardness 40A, more desirably less than or equal to about 30A durometer or shore hardness 30A, even more desirably less than or equal to about 20A durometer or shore harness 20A) and have good biostability. One parameter which may be considered in the choice of sealant is the stiffness or elastic modulus. Usually with elastomers the modulus is not linear thus at each elongation the stress (or force) is measured. A material with lower stress @% strain will provide less resistance to extension and will therefore feel more flexible and closer to matching the handling of a gelatin sealed graft. Preferred materials are low stress silicone rubbers, such as NuSil MED 6605 and MED 6606, with Stress @Strain values<180@200%. Useful Polyurethane and Silicone-polyurethane grades, include, but are not limited to: TABLE 2Stress (psi) at %MaterialManufacturerGradeelongationSiliconeNuSilMED 660650 @ 100%RubberSiliconeNuSilMED 6605160 @ 300%RubberSiliconeAppliedDispersion PN170 @ 300%RubberSilicone40021TPU-SiliconeAdvansourceChronoSil570 @ 200%adjustedTPU-siliconeBiomericsQuadrasil Elast-725 @ 200%EON E5-130TPU-aliphaticAdvansourceChronoflex AL800 @ 200%polycarbonate75ATPU-10%AdvansourceChronoSil 75A834 @ 200%silicone10% Si The present invention is not limited to the use of silicone as the polymeric sealant. Other useful coating materials for both medical and non-medical textiles may include, for example, polytetrafluoroethylene, polyethylene, poly(hydroxyethly methacrylate), poly(vinyl alcohol), polycaprolactone, poly(D, L-lactic acid), poly(L-lactic acid), poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolic acid-cotrimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), copoly(ether-esters), polyalkylene oxalates, polyphosphazenes, polyiminocarbonates, aliphatic polycarbonate, polyethylene oxide, polyethylene gylcol, poly(propylene oxide), polyacrylamide, polyacrylic acid (30-60% solution), polymethacrylic acid, poly(N-vinyl-2-pyrollidone), polyurethane, poly(aminoacid), cellulosic polymer (e.g. sodium carboxymethyl cellulose, hydroxyethyl celluslose), collagen, carrageenan, alginate, starch, dextrin, gelatin, poly(lactide), poly(glycolide), polydioxanone, polycaprolactone, polyhydroxybutyrate, poly(phospazazene), poly(phosphate ester), poly(lactide-co-glycolide), poly(glycolide-co-trimethylene carbonate), poly(glycolide-co-caprolactone), polyanhydride, polyamide, polyesters, polyether, polyketone, polyether elastomer, parylene, polyether amide elastomers, polyacrylate-based elastomer, polyethylene, polypropylene, and/or and derivatives thereof. Other useful coating materials, in particular for but not limited to non-medical textiles, may include natural rubbers, natural gums, acrylic polymers, polybutadienes, styrene-butadiene copolymers or rubbers, butadiene-acrylonitrile copolymers, polyisobutylenes, isoprene-isobutylene copolymers, polysulfide rubbers, chloroprene rubbers (neoprene), chlorosulfonated polyethylene, fluorinated polymers, vinyl resins, and the like. Further, coating materials may include metallic materials and powdered materials. FIG.7depicts a further embodiment of the conduit10. As best shown inFIG.7, the conduit10comprises a number of crimps10g. In this embodiment, a support member18is added to the outer surface10b, of the wall10fof the conduit10. In particular, the support member18is added by multiple stages of sealant application. For example, the sealant may be added to the outer surface of the conduit10as described above, then the support member18may be disposed over the sealed graft, followed by applying another stage of sealant application, which after drying and/or curing will aid in the securement of the support member18to the conduit10. However, it should be understood that the support member18could be added to the conduit10in other ways. The step of adding the support member18to the outer surface10bof the wall10fof the conduit10is carried out prior to the step of adding the sealant14to the conduit10. The sealant14is configured to attach the support member18to the conduit10. In this embodiment, the support member18is added to the conduit10and the sealant14is then added to the conduit10in order to seal the conduit10, and to attach the support member18to the conduit10. Moreover, it should be understood that it is within the scope of the present invention to have multiple applications of masking agent and/or sealant either after or prior to drying and/or curing the prior application. The support member18is a flexible, polymer wire, which in this embodiment is wrapped around the outer surface10bof the wall10fof the conduit10and is arranged to nest between the crimps10gof the conduit10. One of the advantages of adding the support member18to the conduit10, as illustrated and described here, is that the conduit10is made more robust while retaining much of its flexible characteristics. As stated above, the conduit10is able to be manipulated by a medical practitioner in a more efficient way because the conduit10is flexible. In the embodiment illustrated inFIG.7, the support member18is made from polyethylene terephthalate (PET). However, it is understood that the support member18could comprise at least one of: a polymer material, a metal material, a shape memory alloy, and a superelastic alloy. In some embodiments, the support member18could comprise at least one of: polyethylene terephthalate, polytetrafluoroethylene, polyurethane, polycarbonate, silicone, stainless steel, titanium, nickel, and nickel titanium (Nitinol). FIG.8shows an alternative embodiment of a conduit10manufactured according to the process illustrated inFIGS.1ato1d. The conduit10depicted inFIG.8has been manufactured in the same way as that depicted inFIG.1d, with the following differences. The conduit10has three sections10h,10i,10j. Sealant14a,14band14chas been selectively added to the sections10h,10i,10j, such that each section10h,10i,10j, has a different amount of sealant14a,14b,14c, present thereon. In this embodiment, each of the sections10h,10i,10jhave a substantially different degree of flexibility. The first section10hhas a higher degree of flexibility than the second section10i. Similarly, the second section10ihas a higher degree of flexibility than the third section10j. As shown inFIG.8, the crimps10gof the first section10hare more visible than in the second section10iand third section10j, because the second and third sections10i,10j, have a higher amount of sealant added thereto, which causes the crimps10gin these sections10i,10j, to be less pronounced. In applications where a further prosthesis is connected to an end of the vascular prosthesis16, the end of the third section10jis more suited for connection to the further prosthesis. An example of how the vascular graft16may be used will now be provided. The vascular graft16described inFIGS.1ato6b, which may be thought of as a sealed, processed conduit10, is capable of being implanted in the human or animal body over the long term. This is because the vascular graft16is biocompatible, that is it will not illicit a foreign body response in the human or animal body, and it is not toxic to surrounding biological tissue. The masking agent12is configured to biodegrade in the body. Therefore, any residual masking agent12present on the conduit10will biodegrade in the body. However, as described in more detail above, the masking agent12need not be biodegradable, as in some embodiments the masking agent12will be removed substantially entirely from the conduit10. In other embodiments, the masking agent12need not be removed from the conduit10. The vascular graft16can be used to bypass a region, or a section of a blood vessel. For example, if a medical practitioner identifies a blocked, a diseased region or partially blocked region of a blood vessel, they may decide to bypass that region by using the vascular graft16. In this example, the inlet10cof the vascular graft16may be attached to one point of the blood vessel, and the outlet10dof the vascular graft16may be attached to another point of the blood vessel. In another example, the blood vessel could be diseased, or have been severed or bisected in order to connect the vascular graft16to two ends of the severed blood vessel. Because the vascular graft16is sealed, blood may flow through the vascular graft16in order to bypass the blocked, diseased, or partially blocked region of the blood vessel, and the leaking of blood through the walls10fof the conduit10is mitigated by the presence of the sealant14. Once the vascular graft16is in place, biological tissue will grow into the inner section10aof the vascular graft16in order to form a pseudointima. Over time, the psuedointima will form, adhering to the inner section10aof the vascular graft16. During this time, the vascular graft16prevents leakage of blood through the wall10fand acts as a scaffold for the ingrowing biological tissue. The vascular graft16may also be used to connect a further prosthesis, such as a heart assist device, a biological heart valve or a synthetic heart valve, to a blood vessel. For example, the inlet10cof the vascular graft16may be connected to an outlet of a synthetic heart valve, and the outlet10dof the vascular graft16may be connected to an end of a blood vessel. The advantage of this use of the vascular graft16is that a heart assist component can be used with a wide variety of shapes and sizes of blood vessels, as the vascular graft16can be provided in a range of sizes. The medical practitioner is then able to select which particular vascular graft16will interface well with the synthetic heart valve and the blood vessel. This avoids the need for a range of different configurations of heart assist device to be used, as a standard part can be used and customised by adding different types and sizes of vascular graft16. It will be appreciated that, depending on the nature of the heart assist device, multiple vascular grafts16could be used with the heart assist device. While the embodiments illustrated and described here show a cylindrical conduit10with an inlet10cand an outlet10d, other shapes of conduit10could be used. For example, a Y shaped, T-shaped, or a multi-channel conduit10could be used. FIG.9ais a perspective view of a perforated mandrel20useful with the systems and/or kits of the present invention for processing textile substrates in accordance with the present invention. As depicted inFIGS.9aand9b, the mandrel20may be a hollow mandrel having an open lumen24. One or both ends26of the mandrel20may be open ends. Alternatively, one or both ends26of the mandrel20may be closed ends (not shown). As depicted inFIGS.9aand9c, perforations or holes23may be disposed within the tubular wall of the mandrel20. The mandrel20may be used for a variety of purposes. For example, the mandrel20could be used to deliver the masking agent or the water-soluble material to a tubular textile, such as a graft. In such a use, a tubular textile (not shown) may be disposed over the outer surface22of the mandrel20. The masking agent or the water-soluble material may be delivered into the open lumen24of the mandrel20, for example into the open lumen24via an open end26. The opposed end may be closed or open, such as in the case of a circulating system for the fluid masking agent or water-soluble material. The fluid masking agent or water-soluble material would flow through the perforations or holes23and onto and into the graft (not shown) disposed over the mandrel20. The mandrel20may have a controlled amount of fluid masking agent or water-soluble material within the lumen24to control the amount of fluid masking agent or water-soluble material exposed to the graft (not shown). The fluid masking agent or water-soluble material contained within the mandrel20may be forced onto the graft through the use of a pressure differential (higher pressure within the lumen24than outside the lumen24) or through rotational forces when the mandrel20is disposed on or within a rotating or spinning device. A mandrel not having the perforations20(not shown) may be used to dispose a layer of fluid masking agent or water-soluble material over the outer surface of the mandrel. The masking layer may be viscous enough or partially cured to remain on the mandrel until a graft is disposed over the mandrel. The masking layer may then be releasably disposed over the inner surface of the graft. The mandrel20may also be used for control of fluid migration. For example, the pressure within the lumen24may be lower than the pressure outside of the lumen24. Such a negative pressure or vacuum may be used to migrate the masking agent or water-soluble material away from the outer surface of a graft (not shown). The mandrel20may also be used for drying the fluid masking agent or water-soluble material. A warm gas, such as air, may be introduced into the lumen24, flow through the perforations or holes23, and dry the fluid masking agent or water-soluble material. Alternatively, a heat source may be disposed outside of the mandrel20, and the flow of heat, such as heated air, may be controlled through the application of a negative pressure at the lumen24. A mandrel, either the same or different, may be used throughout different applications and techniques described herein, such as, but not limited to, masking agent application and/or dispersion, masking agent drying, sealant application and/or dispersion, sealant drying and/or curing, textile washing, and the like. A tubular textile may be substantially disposed over a mandrel or only a portion of the tubular textile may be disposed over a mandrel. For example, one end of a tubular textile may be supported by a mandrel and the other end of the tubular textile may be supported by a different mandrel, and the like. The substantially water-insoluble sealant may also be applied to the graft while the graft is on a solid or non-perforated mandrel or on a perforated mandrel20. The substantially water-insoluble sealant may be applied to the graft by any suitable means, such as by brushing, spraying, roller coating, spinning the substantially water-insoluble sealant thereon. Furthermore, if desired the substantially water-insoluble sealant may be cured with the graft disposed over a mandrel. Further, other materials, such as colorants, therapeutic agents, dyes, fluorescent indicators, and the like maybe applied to the graft. Therapeutic agents may include, but are not limited to: anti-thrombogenic agents (such as heparin, heparin derivatives, urokinase, and PPack (dextrophenylalanine proline arginine chloromethylketone); anti-proliferative agents (such as enoxaprin, angiopeptin, or monoclonal antibodies capable of blocking smooth muscle cell proliferation, hirudin, and acetylsalicylic acid); anti-inflammatory agents (such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, and mesalamine); antineoplastic/antiproliferative/anti-miotic agents (such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin and thymidine kinase inhibitors); anesthetic agents (such as lidocaine, bupivacaine, and ropivacaine); anti-coagulants (such as D-Phe-Pro-Arg chloromethyl keton, an RGD peptide-containing compound, heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet peptides); vascular cell growth promoters (such as growth factor inhibitors, growth factor receptor antagonists, transcriptional activators, and translational promotors); vascular cell growth inhibitors (such as growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin); cholesterol-lowering agents; vasodilating agents; agents which interfere with endogenous or vascoactive mechanisms; and combinations thereof. Masking Agent Drying and Uniformity Tests Tests were performed to determine how long it took for a standard woven graft immersed in PVP to dry at different concentrations, and if PVP dried in a homogeneous fashion throughout the textile. A series of tests at different concentrations of PVP were done to determine if the concentration made a difference on the drying nature of the substance. The tests used 15%, 10% & 5% PVP solution profiles. First, a 15% solution of PVP was made with 15 g of PVP and 100 mL of water. This was agitated until PVP was fully dissolved into solution. Graft samples were prepared by cutting approximately 50 mm of a commercial tubular graft. The graft samples were, if necessary, dried and were weighed. Graft samples were then soaked in the 15% PVP solution. The wet grafts were weighed to provide initial weights. The samples were placed vertically near a running fan. The graft samples were weighed at 5-minute intervals until there was a constant weight being displayed. The graft samples were cut into 4 labelled pieces. Each quarter piece was weighed. The quarter pieces were then washed, dried, re-weighed when fully dry. The lengths of the dry-washed graft were measured. Next, 50 mL of water was added to the 15% PVP solution in order to make a 10% PVP solution. The above textile processing steps were repeated for the 10% PVP solution Next 150 mL of water was added to the 10% PVP solution to make a 5% PVP solution. The above textile processing steps were repeated for the 5% PVP solution. Results: 15% PVP Profile TABLE 3Time (min)Weight (g)Dry1.70904.81754.229103.81153.399203.056252.775302.543352.36402.235452.152502.122552.117602.113652.113Length measuredLength (mm)Initial51Final52QuarterWith PVPWithout PVPwt % PVP in piece10.5070.41817.620.5190.42118.930.5690.46119.040.5160.42717.2Total2.1111.72718.2Total expected2.1131.709 Table 3 showed that the 15% PVP coated graft took over an hour to dry fully in ambient air, it also showed that there was a slight increase in the length of the graft after being coated, washed and dried. After drying, the samples averaged 18.2 weight percent PVP. Further, the distribution of PVP among the samples was substantially consistent. Graft samples or pieces 2 and 3 had slightly higher PVP levels. These pieces had a seam of the graft on them, so it appeared that the seam was probably absorbing more PVP. Thus, about 15 to about 21 weight percent PVP was deposited onto the graft when immersed in the 15% PVP solution. Results: 10% PVP Profile TABLE 4Time (min)Weight (g)Dry1.69904.89154.292103.881153.491203.159252.849302.580352.124402.040452.000501.994551.994Length measuredLength (mm)Initial48Final51QuarterWith PVPWithout PVPwt % PVP in piece10.5430.46913.620.5980.5114.730.3940.33415.240.4590.39414.2Total1.9941.70714.4Total expected1.9941.699 Table 4 showed that the 10% PVP covered graft took just under an hour to dry completely, and that the 10% PVP solution covering, washing and drying had also caused a slight increase in the length of the graft. The slightly higher weight % of PVP in pieces 2 and 3 also suggested that the seam of the graft absorbed more of the PVP than the rest of the graft. After drying, the samples averaged 14.4 weight percent PVP. Thus, about 10 to about 18 weight percent PVP was deposited onto the graft when immersed in the 10% PVP solution. Results: 5% PVP Profile TABLE 5Time (min)Weight (g)Dry1.51403.19752.735102.385152.070201.820251.650301.590351.588401.588Length measuredLength (mm)Initial47Final47QuarterWith PVPWithout PVPwt % PVP in piece10.3570.3482.520.4230.4064.030.4320.4124.640.3710.3544.6Total1.5831.524.0Total expected1.5881.514 Table 5 showed that the 5% PVP covered graft took the least time to dry completely, and that its length did not seem to alter after coating, washing and drying, the PVP did to a minor degree to ‘sink’ to the bottom of this graft. Thus, about 2 to about 8 weight percent PVP was deposited onto the graft when immersed in the 5% PVP solution. Conclusions The 15% PVP covered graft took the most time to dry by approximately 25 minutes. In terms of drying evenly anyone of these concentrations was acceptable. Various drying techniques are suitable for use with the present invention. For example, textile grafts and/or textile substrates may be dried at room temperature to remove the solvent(s) from the deposited masking agent solution and/or from the sealant solution. Forced air, such as use of a fan or fans or other sources of air movement and/or sources of pressurized air, may be used to facilitate drying. The forced air, if any, may be applied at any suitable angle or combination of angles. The air may or may not flow into the interior lumen of the graft. For example, forced air may be directed towards outer surface of a tubular graft, either perpendicularly, substantially perpendicularly, at an acute angle, and/or at an obtuse angle. Moreover, forced air may be directed towards the interior lumen of the tubular graft, such as towards one open end of the tubular graft, or even from within the interior lumen of the tubular graft. The direction of air flow and the amount of extend of the air flow may be varied to control drying times and even to control resultant physical properties of the graft. Forced air flow may also be useful in aiding migration of the masking agent towards the interior portions of the graft and away from exterior portions of the graft. In other words the masking agent desirably retracts when drying. This would aid in the securement of the sealant material at the exterior portions of the textile graft while also aiding in the blocking of sealant migration towards the interior portions of the graft. The present invention, however, is not limited to the use of air as a drying medium, and other suitable media, including gaseous media, may be used. Further, the present invention is not limited to room temperature drying, and elevated drying temperatures above room temperature may suitably be used. Moreover, a fluid, such as water, including heated water, may be used with the present invention as described below. The use of heated water aids in the removal of the water-soluble masking agent from the textile product. Further, the use of heated water may also aid in curing of the sealant or sealing agent. Furthermore, drying and/or curing the sealant material may also be controlled using forced air or other medium, ambient forced air or other medium, heated forced air or other medium, non-forced ambient air or other medium, non-forced heated air or other medium, and the like. Not only may curing times of the sealant material be controlled, but also, to some extent, the properties of the sealant layer may be controlled. The sealant material may be selected, dried or cured, and or selectively deposited, such that the sealant material, as is cures, shrinks about the textile substrate, e.g., the outer surface of the textile graft. Masking Agent Removal Tests Different washing methods for the grafts were performed to determine which method would extract the highest levels of PVP and if the chosen method has any effect on the length and crimp of the graft. Two wash processes were considered, an Ultrawave ultrasonic bath and a domestic washing machine. Procedures Part 1: No Sealant Coating This trial was first done on 6 grafts that were not coated with silicone in order to establish if 100% of the PVP could be removed with the chosen washing methods. Grafts were prepared by cutting approximately 6×60 mm lengths of commercial woven grafts. All 6 grafts were measured, weighed, and labelled with notches cut into the side. A 15% PVP solution was made with 15 g of PVP and 100 mL of water. All 6 samples were submerged in the 15% PVP in solution. All 6 samples were dried vertically near a running fan. All dried samples were weighed. An ultrasonic bath was set to 40 degrees Celsius. Samples 1, 2, and 3 were submerged into the ultrasonic bath. Samples 1-3 were left in the ultrasonic bath for 15 minutes. These samples were removed from the ultrasonic bath and were dried vertically near a fan. The dried 1-3 samples were weighed and their lengths were measured and recorded. Samples 4, 5, and 6 were placed in a washing bag and then into a washing machine. The washing machine was set to a 40 degrees Celsius, 800 RPM, 51 minute wool wash setting. Samples 4-6 were removed from the washing machine and were allowed to dry. Samples 4-6 were weighed and their lengths were recorded. Part 2: Silicone in Heptane Sprayed Sealant Coating Samples 1-3 were re-washed, dried, measured and weighed. Samples 1-3 were then submerged in the 15% PVP solution. All 6 samples were dried vertically near a running fan. The dried samples were weighed. All 6 samples were stretched out and sprayed with silicone in heptane coating. The 6 samples were then allowed to return to their relaxed states under a fume hood and were allowed to dry. An ultrasonic water bath was set to 40 degrees Celsius. Once dry, samples 1-3 were submerged in the ultrasonic bath for 15 minutes. These samples were removed from the bath and were dried vertically near a fan. The dried samples 1-3 were weighed, and their lengths were measured and recorded. Once dry, samples 4-6 were placed in a washing bag and then into a washing machine. The washing machine was set to a 40 degree Celsius, 800 RPM, 51 minute wool wash setting. The samples were removed from the washing machine and were allowed to dry. Once dry, the samples 4-6 were weighed, and their lengths were measured and recorded. Results TABLE 6No Sealant CoatingUltrasonic Bath at 40 DegreesWashing Machine Wool SettingMeasurementSample 1Sample 2Sample 3Sample 4Sample 5Sample 6Initial2.7473.1772.4562.6412.7722.846Weight (g)Dried PVP3.5084.0483.1793.4453.5683.658weight (g)Washed2.7793.2122.4672.6412.7722.847Weight (g)PVP left (g)0.0320.0350.0110.0000.0000.001Initial62.56157575663.5Length (mm)Final Length62.56257575663.5(mm) The majority of the samples that were put in the washing machine were cleared of PVP while the samples that were put in the ultrasonic bath all still had some minor PVP on them after washing. TABLE 7Silicone in Heptane Sprayed Sealant CoatingUltrasonic Bath at 40 DegreesWashing Machine Wool SettingMeasurementSample 1Sample 2Sample 3Sample 4Sample 5Sample 6Initial2.7473.1772.4562.6412.7722.847Weight (g)Dried PVP3.5103.9113.1233.3893.5383.57weight (g)Dried PVP +3.7374.083.3233.5833.8433.825Coatingweight (g)Washed2.7793.2122.4672.6412.7722.847Weight (g)Silicone0.2270.1690.2000.1940.3050.255applied (g)PVP + silicone0.2520.1860.2140.2060.3120.266left on graft (g)PVP left (g)0.0250.0170.0140.0120.0070.011Initial62.56157575663.5Length (mm)Length after817973797979coating (mm)Final706662616465Length (mm)Ratio of PVP3.44.33.33.92.52.8Applied toSiliconeApplied,wt./wt.Ratio of0.290.230.300.260.400.36SiliconeApplied toPVP Applied,wt./wt.Percent PVP96.797.797.998.499.198.5Removed, wt. % Although there was some PVP left on the grafts that went in the washing machine, there is significantly less PVP left on them as opposed to the grafts washed in the ultrasonic bath. In all cases, greater than about 90 weight percent of the PVP was removed. Indeed, in all cases greater than about 95 weight percent of the PVP was removed. In Table 7, the weight ratio of PVP to silicone applied varied from about 2.5:1.0 to about 4.3:1.0. Conversely, the weight ratio of silicone to PVP applied varied from about 0.40:1.0 to about 0.23:1.0. Further, ratios are described in Table 11 below. The ratios described in Tables 7 and 11 are non-limiting. The weight ratio of PVP (or other masking agents) to silicone (or other sealant agents) may vary from about 10:1 wt. PVP (or other masking agents)/wt. silicone (or other sealant agents) to about 0.01:1 wt. PVP (or other masking agents)/wt. silicone (or other sealant agents), desirably from about 1:1 wt. PVP (or other masking agents)/wt. silicone (or other sealant agents) to about 0.05:1 wt. PVP (or other masking agents)/wt. silicone (or other sealant agents), more desirably from about 0.5:1 wt. PVP (or other masking agents)/wt. silicone (or other sealant agents) to about 0.1:1 wt. PVP/wt. silicone. Conversely, the weight ratio of silicone (or other sealant agents) to PVP (or other masking agents) may vary from about 0.1:1.0 wt. silicone (or other sealant agents)/wt. PVP (or other masking agents) to about 100:1 wt. silicone (or other sealant agents)/wt. PVP (or other masking agents, desirably from about 1:1 wt. silicone (or other sealant agents)/wt. PVP (or other masking agents to about 20:1 wt. silicone (or other sealant agents)/wt. PVP (or other masking agents, more desirably from about 2:1 wt. silicone (or other sealant agents)/wt. PVP (or other masking agents to about 10:1 wt. silicone (or other sealant agents)/wt. PVP (or other masking agents. Mask and Dye Tests MaterialsFabric—Diameter 22 mm, flat tube twill weave and Diameter 10 mm. Crimped twill weave.Silicone—NuSil Med16-6606 (Temporary implant grade).Solvent—n-Heptane, 50:50 with silicone dispersion.Dye—Easy Composites Royal blue pigment for RTV silicone, mixed to approx. 10% of silicone solid content. Sample Description For Flat 22 mm fabric samples, the following masking agent formulations were used:#71 A—Bare Fabric#71 B—6% PVP#71 C—6% PVP+1.5% Glycerol (by volume of Mask solution)#71 D—6% PVP+1.5% Glycerol+4% PVP (Total 10% PVP) The #71B-D flat fabric samples were immersed into the PVP solution and then removed. All #71 samples were mounted on suspended mandrels (Post masking, Pre-coating). For Crimped Diameter 10 mm fabric samples, the following masking agent formulations were used:#70 A—Bare Fabric#70 B—6% PVP#70 C—6% PVP+1.5% Glycerol (by volume of Mask solution)#70 D—6% PVP+1.5% Glycerol+4% PVP (Total 10% PVP) The #70B-D crimped fabric samples were immersed into the PVP solution and then removed. All #70 samples were mounted on suspended mandrels (Post masking, Pre-coating). Masking Agent Preparation Masking agents were prepared using the same method as described above, with the additional steps to add glycerol for samples B and C (both #70 and #71) and then additional PVP for samples D (both #70 and #71). Measured the target weight of PVP into plastic beaker on scale balance. A 100 ml masking agent solution was prepared therefore target mass of 4 g PVP required (4% concentration). Measured the target volume of de-ionised water into a 100 ml plastic measuring cylinder. A 100 ml Mask solution to be prepared therefore target volume of 96 ml required. Added de-ionised water into the PVP in plastic beaker. Placed magnetic stirrer in the water and place the beaker on the magnetic stirrer. Turned the magnetic stirrer on at a speed of 350-450 RPM, ensuring the stirrer is centred in the beaker. The stirring was done at room temperature. Stirring was continued until there was no visible PVP solute, or for a minimum of at least 2 minutes. After stirring the masking agent solution was removed from stirrer and used for graft preparation, samples B. Additional steps were used for samples C, i.e. added glycerol. Returned the plastic beaker to scale balance, tared, and added required quantity of glycerol to the mask agent solution. The target glycerol content was 1.5% by volume of masking agent solution. This corresponded to a target weight of 1.5 g. (Note this corresponded to 25% Glycerol to PVP). Set beaker on stirrer and stirred for at least 2 minutes. This masking agent solution used for samples C. Additional steps were used for samples D, i.e., additional PVP. Returned the plastic beaker to scale balance, tared, and added the required quantity of PVP to the masking agent solution. The target PVP content was 10% by volume of Mask solution. This corresponded to an additional 4 g PVP added. (Note this effectively reduced the glycerol to PVP ratio from 25% to 15%). This masking agent solution was used for samples D. Sealant Preparation The silicone sealant dispersion as-supplied had a 30% solid content, the dispersion was diluted by an additional 100% of solvent. This reduced the solid content to 15%. Additionally, a blue dye was added to the silicone dispersion to provide a visual indication of the coverage and depth of penetration of silicone into the fabric structure. In particular, 20 ml of silicone dispersion was measured out from its container, in the as-supplied state, and placed into a plastic beaker. An additional 20 ml of n-Heptane solvent was added. The mixture was beaked and was set on scales, tared, and drops of dye were added using dropper. The recommended dye concentration range was 0.3% to 5%, depending of section thickness, therefore a target of 5% was set in order to provide a strong blue colour for visualization. A deviation from this target was due to a calculation of the solid content being at 30% rather than 15%, therefore the actual concentration of dye to silicone was 10% rather than 5%. Sample Preparation The individual samples were prepared with masking agent formulations according to the following table. TABLE 86% PVP +10% PVP +No6%GlycerolGlycerolMaskPVP(@25% of PVP)(@15% of PVP)Flat Fabric71A71B71C71DCrimped70A70B70C70DFabric Samples B-D were immersed in the mask agent solution, as per the above table. The samples were assembled onto mandrel such that each fabric was held at diameter by sized end bungs, but remained unsupported on the inner surface. The inner surface of each fabric was not in contact with the mandrel to avoid affecting mask performance, location and concentrations. Dispersion drop assessment was undertaken as described below. Each sample was fully coated with at least 2 coats of silicone dispersion. The intention was to ensure sufficient silicone was present on the outer surface to effect a suitable coverage without concerns for lack of silicone during visual evaluations. Brush coating was done onto a rotating graft on rotisserie at approximately one revolution per second. Grafts were left overnight for solvent evaporation. Grafts were left to fully cure for recommended 72 hrs before being removed from mandrel for washing. The grafts were then placed in a delicate bag and put on 95° C. Tumble Machine Wash cycle for approximately 2 hours 30 mins. Samples were masked, coated, washed and cut opened flat. Dispersion Drop Assessment Prior to full coating, a single drop of polymer dispersion was applied to each sample, and video recorded in order to visually assess if there were noticeable differences in the behaviour of the dispersion on the masked fabric.Sample A—No Mask. Slow spread of the single drop of polymer dispersion across fabric. Appeared to be soaking into and through fabricSample B—6% PVP Mask. Rapid spread of the single drop of polymer dispersion across fabric. Appeared to spread more readily than soaking into and through fabricSample C—6% PVP+1.5% Glycerol Mask. First drop of the single drop of polymer dispersion had rapid spread across fabric. The second drop of the single drop of polymer dispersion was inconclusive, possibly due to sagging fabric holding the pool.Sample D—10% PVP+1.5% Glycerol Mask. Inconclusive-possibly due to sagging fabric holding the pool Dispersion Drop Assessment across face of the graftSample A—No Mask. Slower spread of the single drop of polymer dispersion across fabric. Appeared to soak into fabric.Sample B—6% PVP Mask. Rapid spread of the single drop of polymer dispersion across fabric. Coverage was more uneven with pooling of dispersion in valleys.Sample C—6% PVP+1.5% Glycerol Mask. Fabric clearly resisted dispersion soaking in.Sample D—10% PVP+1.5% Glycerol Mask. Fabric clearly resisted dispersion soaking in. In summary, this Dispersion Droplet Assessment showed that even the lower concentration of masking agent, (Samples B, 6% PVP), appeared to initiate a significantly different response when compared to a non-masked fabric. A “pooling” effect was seen on the flat fabrics, samples 71C, 71D, was most likely a result of the excess dispersion being unable to run off the fabric or through the fabric. This effect was perhaps also evident in the crimped fabric, particularly Samples 70B, 70D, where there was pooling of the dispersion in the valleys, highlighted by the darker colour, unlike the non-masked sample 70A, which appears far more uniform in colour/coverage. Assessment of Sealant Coverage and Penetration Following the wash cycle to remove the masking agent the grafts were cut lengthways to provide visualization of inner and outer surfaces. Each graft was visualized under optical microscopy on: (a) the outer surface—to confirm presence and uniformity of sealant coating; (b) the inner surface—to confirm presence or ingress of blue silicone, either through the fabric or between the yarn filaments; and (c) sectional view—to assess the level of penetration through the yarn bundles. Results Both samples without mask appeared to have permitted the dyed blue silicone dispersion into the yarn bundles and penetrate to the inner surface while the application of the mask appears to have prevented this ingress on all samples. TABLE 9Penetration ofPolymer toMask AppliedInner SurfaceFlat Fabric Samples71ANoneYes71B6% PVPNo71C6% PVP + GlycerolNo71D10% PVP + GlycerolNoCrimped Fabric Samples70ANoneYes70B6% PVPNo70C6% PVP + GlycerolNo70D10% PVP + GlycerolNo Photographs of crimped fabric sample 70D are provided inFIGS.10a-10c.FIG.10ais a photograph of a portion of the cross-section of the tubular wall of the crimped fabric sample 70D. As shown inFIGS.10a-10c, the fabric sample or textile graft30includes an outer textile surface32, an opposed inner textile surface34, and a textile wall36disposed therein between. As shown inFIGS.10aand10c, a sealing layer or coating38is disposed over the outer surface32. Moreover, as shown inFIG.10a, the sealing layer or coating38extends into a portion of the textile wall. As shown inFIGS.10aand10b, the inner surface34is substantially, including completely, free of the sealing layer or coating38. FIG.11shows a microphotograph or scanning electron microscope (SEM) photograph of a dried 40% PVP masking agent concentration applied to a graft sample40. The dried masking agent slurry44gathered and encapsulated the yarn structure42and had cracks46. It is evident that the silicone sealant would not be able to effect any permanent adhesion or encapsulation onto this surface fully encapsulated by the masking agent. The masking agent solution may encapsulate whole yarn bundles and individual yarn fibers, depending on the concentration of the masking agent solution. The higher concentrated masking agent solution (i.e. >30% w/w PVP, >20% w/w of PVP glycerol in water) seems to be too thick to flow into the yarn bundles and coat individual fibers, as seen inFIG.11. Additionally, high concentrations of masking solution dries as a thick, brittle mask layer, in which many samples develop micro cracks46throughout the masking layer44, as seen inFIG.11. If the masking agent solution concentration is low (<10% w/w PVP, with or without glycerol in water), the masking agent may encapsulate the yarn bundle and individual fibers, however, a limitation of using a low concentration of masking agent solution may be lack of complete, consistent coverage around each yarn bundle and/or fiber. If this is the case, portions of the fiber are exposed for a surface for potential sealant attachment. Some results show, using low concentrations of masking agent solution, the sealant encapsulates and traps the masking layer; therefore, the masking is not fully washed out of the final product. The key of an appropriate masking solution that works is to have a controlled application process of a targeted concentration for each application as set forth by the present invention. The overall mechanism of masking agent may include two main concepts, depending on the size of the void or gap: (1) a physical effect for macro pathways (i.e. voids between yarn bundles) and (2) chemical effect for micro pathways (i.e. voids between fibers and voids in micro cracks within the masking layer).(1) Physical Effect: Filling macro pathways is based on the physical ability for the masking agent solution to penetrate and flow into large voids between the yarn bundles. When the yarn bundles are completely encapsulated with a masking agent layer, the masking agent layer fills the voids between each yarn bundle and blocks entry into the yarn bundle. In turn, the sealant would not be able to penetrate within the macro pathways between each yarn or micro pathways between each fiber due to the presence of masking to fill these voids.(2) Chemical Effect: For micro pathways throughout the textile, whether micro pathways refer to micro cracks within the masking layer, micro voids between the yarn bundles or micro voids between individual fibers, the chemical mechanism of the masking solution's repulsion effect or ability to repel away from the sealant causes the sealant not to fill the micro voids. The repelling mechanism occurs when the oleophobic sealant tries to come into contact or close proximity with the highly hydrophilic masking layer. This is proven using solution solubility theory and solubility parameters developed by Joel H. Hildebrand. SI Hildebrand values (∂[SI]) demonstrate the masking solution and sealant solubility parameters indicating the solvency behavior of their specific solvents when they come into contact with one another. As noted in the Handbook of Solubility Parameters, CRC Press, 1983, the solvents in the masking solution (water and glycerol) are on the hydrophilic end of the solubility parameter range, whereas the solvent of the sealant (Heptane) is on the opposite end of the solubility parameter range. The ∂[SI] of water is 48.0, ∂[SI] of glycerol is 36.2, and ∂[SI] n-Heptane is 15.3. Thus, the masking agents of the present invention hinder undesirable migration of the sealant through, physical (e.g., blocking) and repulsion mechanisms. Thus, it may be desirable to use a sealant(s) whose solvent(s) has a solubility parameter of less than about 20 ∂[SI], for example from about 10 ∂[SI] to about 20 ∂[SI] and a masking agent solution(s) whose solvent(s) has a solubility parameter of greater than about 30 ∂[SI], for example from about 30 ∂[SI] to about 50 ∂[SI]. Conclusions The use of blue dye in the silicone dispersion provided an excellent visual assessment of silicone penetration into the fabric. Both samples coated without prior mask application demonstrated substantial ingress of blue silicone sealant through the fabric to the inner surface. All three masking agent formulations appeared to substantially prevent ingress of silicone to the inner surface. Silicone Sealing Tests for Commercial Vascular Grafts The following equipment and materials were used to test sealing commercial grafts according to the present invention.8 mm crimped polyester fabric commercial graft14 mm crimped polyester fabric commercial graftPolyvinylpyrrolidone (PVP) PowderNuSil MED-6606 RTV SiliconeN-HeptaneRoyal Blue PigmentDe-ionised waterMagnetic Stirrer Coating Variable Ranges The following values were used for the testing of the inventive sealing techniques of the present invention.PVP concentration in de-ionised water was varied on a weight basis at 1%, 2%, 4%, 6%, 8%, 10%, 15%, 20%, 25%, and 30%.Glycerol and silicone dispersion concentration was tested at PVP concentrations of 4%, 8%, 15%, and 30%. Glycerol concentrations were used on PVP concentrations of 5%, 15%, and 30%. These concentrations were percentage of glycerol to PVP. The variations of PVP, glycerol, and silicone tested were as follows: TABLE 10GlycerolSiliconeConcentrationConcentrationPVP Concentration (%)(% of PVP)(%)Sample1246810152025305153015301XX2XX3XX*4XX5XX6XX*7XX8XX9XX*10XX*11XXX12XXX13XXX14XXX15XXX*16XXX17XXX18XXX*19XXX20XXX21XXX22XXX23XXX24XXX25XXX*26XXX*Denotes samples to be applied to both types of grafts i.e., First and Second graft samples. Sample Preparation Each sample was made from of a section of the commercial grafts. The grafts were first cut to length by first fully stretching the graft to remove the crimps, and then a section of 180 mm length was cut with a single edge razor blade. Each sample was weighed. Mask Preparation A measured amount of de-ionised water was placed into a 100 ml plastic beaker. A magnetic stirrer was placed into the de-ionised water. While stirring, PVP and glycerol (if any) were added. Stirring continued until there was no solute visible. Masking Agent Application The graft samples were coated by immersing the graft samples within the mask solution and agitating the graft by gloved hands, so the samples were fully coated inside and out. Once the grafts were fully coated, excess mask solution, if any, was removed. Next, each graft was attached to a mandrel by using cable ties. One end of the graft was secured to the mandrel by a cable tie, then the graft was extended to 60% of its overall extended length (108 mm), and the other end of the graft was secured to the mandrel by another cable tie. The mandrel was then placed horizontally on a rotating mount and allowed to air dry. Once dry, the masked grafts were weighed. Sealant Preparation The silicone dispersion was supplied as a 30% solid content. Additional amounts of n-Heptane were added to reduce that solid content to 22.5% then 15. A blue dye was added to the silicone dispersion. Sealant Application The mandrel with the graft mounted was be placed on the rotary motor to slowly spin the graft. The sealant was applied with a paint brush starting at one end and working to the other end. This was repeated until there was an excess of sealant dispersion on the graft. Once the targeted level of silicone was applied onto the graft, the graft was transferred to a rotating mount and allowed to air dry. Once dry, the sealed graft was weighed. Masking Agent Removal Once the grafts were fully dried, the masking agents were removed. This was done by washing the grafts in a washing machine on a 90° C. wash (with no detergent). This caused the PVP to dissolve in the water and thus be removed from the graft. The 90° C. temperature also aided in complete curing of the silicone. When the wash was complete, the grafts were hung up to air dry. After drying, the finished grafts were weighed. Silicone Adherence A good coating adhesion can also be demonstrated if the graft coating maintains its integrity in a high pressurised state. Pressure can be used as a measure over all sizes of grafts because most of the overall hoop stress is borne by the stiffer fabric material of the graft. Furthermore, most of the forces acting on the silicone coating for delaminating it happen in the gaps between bundles of fibres as the weave structure does not change for different diameters of graft, then this area and consequently the force acting on that area will be consistent. Therefore, irrespective of the size of graft the same pressure will produce the same force to delaminate the silicone coating. To ensure the position of the bundles within the fabric are as uniform as possible over all diameters, the fabric was crimp removed so the graft is in its fully extended shape. In accomplishing this, the pressure applied was above the pressure that it takes to fully extend the graft. Since this pressure will be different for each size of graft, the graft that needs the highest pressure to fully extend itself (i.e., the one of smallest diameter) will be used as a worst-case scenario. Once this worst-case pressure is determined, a factor of safety (FOS) is applied and it is this FOS corrected pressure that is used as a minimum requirement for all grafts. If the graft can be pressurised to this FOS corrected pressure with no visual signs of the coating delaminating (bubbles forming), then it can be deduced that the coating has sufficient and acceptable adhesion/integrity. One method of testing for delamination is as follows:Connect the graft to a pressure rig, ensuring one end is plugged;Slowly apply pressure to the graft;Stop at 120 mmHg (clinical pressure) and look for signs of delamination (bubbles);Measure the leak rate and record it in mm/cm2/min;Increase the pressure in increments up to the FOS corrected figure is reached;If any signs of delamination are visible at any point stop the test, mark as failed;Hold at the FOS corrected pressure for 1 min; andIf no signs of delamination are present, mark graft as pass. The following pressure tests were conducted: The grafts were pressurised with water to observe if there were any signs of the silicone losing its bond from the graft. The pressure was to be increased slowly to a maximum pressure of 600 mmHg. The adherence was noted as follows:0—Silicone is well adhered to graft and showing no signs of failure;1—Graft reached the maximum pressure, but the leak rate has visibly increased;2—Silicone coating has started to fail, showing jets of water coming from the graft; and3—Silicone coating has failed, and a bubble has appeared on the surface. Penetration Depth The effectiveness of the mask was determined by how far the silicone wicked through the fabric. Desirably, the silicone will sit on the outside surface of the graft and not unduly penetrate the graft structure. If the masking agent was not effective, then the silicone was visible within the fabrics and on the inside edge. To visualise this, the grafts were cut lengthways and a cross section was examined under high magnification. The degree of penetration was noted as follows;0—Silicone only visible on the outer surface of the graft;1—Silicone is visible between fibres of the graft but only up to 50% of the thickness;2—Silicone is visible penetrating to the inside surface; and3—Silicone visible everywhere, the entire graft structure is blue. Test Results Summaries TABLE 11WEIGHT SUMMARIESRatioWeight of Graft SegmentAmountofAfterAfterAfterofAmountSealantMaskingSealantWashingMaskingoftoandandandAgentSealantMaskingSampleInitialDryingCuringDryingAppliedAppliedAgentName(g)(g)(g)(g)(g)(g)(g/g)10.7030.7141.4961.4850.0110.78271.120.7140.7391.4841.460.0250.74529.830.7410.7791.4361.3920.0380.65717.340.6730.7211.2391.1820.0480.51810.8A41.0891.1592.312.2290.071.15116.450.6890.7781.1991.10.0890.4214.760.6980.7781.2161.1290.080.4385.570.6940.8131.4541.3190.1190.6415.4A71.0261.1982.0471.860.1720.8494.980.6950.8641.4921.310.1690.6283.790.6880.9391.5411.2760.2510.6022.4100.6630.9691.5371.2070.3060.5681.9110.7390.7781.3821.3390.0390.60415.5A111.081.1192.0862.0410.0390.96724.8120.6580.7121.2621.2010.0540.5510.2130.7170.831.4861.3680.1130.6565.8140.7190.8161.4631.3570.0970.6473.7150.7170.8531.5131.3670.1360.664.9160.7010.8881.5021.2980.1870.6143.3A160.8961.1031.7311.5030.2070.6283.0170.7381.0671.8791.5310.3290.8122.5180.7191.1831.8811.3950.4640.6981.5190.7050.7541.5021.4460.0490.74815.3A190.8780.9241.6821.6320.0460.75816.5200.7170.7592.0632.0160.0421.30431.0210.7090.8091.461.3550.10.6516.5220.7410.8442.1212.0070.1031.27712.4230.7150.8551.4871.3330.140.6324.5240.6880.8672.031.8460.1791.1636.5250.7111.0571.8181.4510.3460.7612.2260.6991.0382.4642.1150.3391.4264.2A261.3562.0584.4483.6890.7022.393.4 The ratio of sealant to masking agent on a gram to gram or weight dry basis varied from about 1:1 to about 70:1. Useful ratios also include ratios of sealant to masking agent from about 2:1 to about 20:1, including from about 2:1 to about 10:1, on a dry weight basis. These ratios, however are non-limiting. The weight ratio of silicone (or other sealant agents) to PVP (or other masking agents) may vary from about 0.1:1.0 wt. silicone (or other sealant agents)/wt. PVP (or other masking agents) to about 100:1 wt. silicon (or other sealant agents)/wt. PVP (or other masking agents, desirably from about 1:1 wt. silicone (or other sealant agents)/wt. PVP (or other masking agents to about 20:1 wt. silicone (or other sealant agents)/wt. PVP (or other masking agents, more desirably from about 2:1 wt. silicone (or other sealant agents)/wt. PVP (or other masking agents to about 10:1 wt. silicone (or other sealant agents)/wt. PVP (or other masking agents. TABLE 12PENETRATION TEST RESULTSGlycerolPenetrationSamplePVPas % ofGrading ScaleNumber%PVP0-3Comment1103220334024602A460258026100171502A715028200292500Delaminated103000DelaminatedA10300Not Made11452A11452124302138521483021515511615300A1615301173050Delaminated1830300Delaminated194152A194152204152218152228151231515124151512530150Delaminated2630150DelaminatedA2630150Delaminated The results, which are tabulated in order of PVP masking agent concentrations, showed a clear correlation between higher levels of PVP and reduced penetration of the silicone sealant into the inner lumen of the graft samples. In general, PVP mask concentration of 10% or greater prevented the bulk penetration of silicone to more than 50% into the fabric thickness. In some samples, they were small “fingers” or “slivers” of silicone evident between the yarn bundles at the interstices created by warp and weft yarn bundles. Such interstitial silicone represented a very small percentage of the overall inner surface area of the fabric. Adhesion Test Results TABLE 13MeasuredMeasuredLeakageLeakage(ml/min)(ml/min)AdhesionGlycerol@120@600gradingSamplePVPas % ofmmHgmmHgScaleNumber(g)PVPResult 1Result 30-3110000220000340000460040A460333580191610040171504140A71503118200124619250Delaminated310300>5003A103001145010A114505012430000138598621483012211515532211615301.51A16153034190117305>10003183030>1001319415000A19415427020415000218150.55022815032315151.511024151503253015Delaminated3263015Delaminated3A263015Delaminated3 The above results, which are tabulated in order of PVP masking agent concentrations, show a clear correlation between higher levels of PVP and reduced adhesion of the silicone sealant to the fabric. Two mechanisms by which silicone penetrated into the inner surface of the fabric were observed, i.e., either through the yarn bundle fibers or by passing between the gaps in the yarn bundles. The lower concentrations of mask agent (>4% PVP) appeared to inhibit the flow of polymer through the yarn fibers, however it was not in all cases sufficient to substantially prevent the ingress of small “fingers” or “slivers” of silicone polymer between the gaps in the bundles, i.e., interstitial spaces between proximately juxtaposed yarns within the textile pattern. It appeared that slightly larger concentrations of mask agent (>15%) was required to completely block the passage of silicone polymer through between the gaps in the fiber bundles. Assessment of Handling The handling characteristics of grafts are the result of a series of complex interactions between the fabric structure, the graft diameter, the crimp pitch and form, the thickness profile of the polymer sealant and the amount of penetration of the sealant into the yarn bundles. The below assessment parameters, although subjective, aim to consider all of the following: bend radius at kink formation, flexibility, hoop stiffness (ability to remain fully open) and stretching. A grading score (1-4) was be used to assess handling characteristics;1—Graft judged more flexible than reference sample.2—Graft judged comparable to reference sample.3—Graft judged to be stiffer than reference sample but with useable characteristics.4—Graft judged too stiff for comparable use. The reference sample was considered to have excellent overall handling and at least comparable to currently commercially available gelatin sealed grafts. Polymer Sealant Coverage The amount of polymer sealant coverage on each sample was reported in mg/cm2and was calculated by dividing the overall mass of polymer applied to each individual graft by the surface area of the graft. Previous crimped prototypes have demonstrated both effective sealing and suitable handling characteristics with polymer coverages of at least about 8 mg/cm2ranging up to about 14 mg/cm2. Coverage levels above 14 mg/cm2increased the overall stiffness of the handling characteristics beyond that of a standard gelatin sealed graft, however increase stiffness and therefore increased amount of polymer coverage may be advantageous for some graft applications. Tensile Extension Force Samples were mounted between jaws of Lloyd Tensile Test machine with jaws spacing of 80 mm. The machine was zeroed and the jaws extended by 20% (16 mm) and the maximum measured force was recorded. The results recorded are tabulated below, ranked in order from low to high for force-to-extend by 20%. These results demonstrated a strong correlation between handling assessment and force-to-extend, with lower extension forces corresponding to improved handling characteristics. A review of the polymer coverage values indicated that coverage levels of up to 40 mg/cm2might be considered in order to achieve comparable handling characteristics to the reference sample (grading 2), as indicated by graft sample #15. All grafts which demonstrated delamination of the polymer sealant during pressurized adhesion tests are by a note (1) highlighted in italics. This list indicates that poor adhesion can result in low Extension Forces and improved handling characteristics. This result supports the theory that acceptable handling characteristics rely on lower levels of penetration of sealant into the yarn bundles. TABLE 14HandlingForce toExtendedSurfacePolymerAssessmentExtendSampleDia,Length,Area,Coverage,Grading,by 20%No.mmmmcm2mg/cm21 to 4(N)18 (1)813032.74310.2998610 (1)812531.43810.379385812030.13610.406725 (1)813032.74410.410646813533.93320.4824716813032.74020.4893817 (1)814035.24410.528058813032.74020.530747813233.24020.540579 (1)812531.44110.5706113814035.23920.588174812531.43820.6015612813533.93530.6936915813533.94020.7193314813032.74230.766253813533.94130.7870111813032.74130.907731813533.94431.007219813533.94331.030223814035.23831.03722814035.24131.111621812531.44331.123426 (1)813433.76341.157122812531.46441.893624 (1)811127.96642.171120811528.97043.023564B10620194.712.1ReferenceSampleNote:(1) demonstrated delamination of the polymer sealant during pressurized adhesion tests Conclusions Acceptable handling characteristics were achieved with lower levels of penetration of sealant into the yarn bundles. The use of the masking agents to limit the amount of polymer penetration into textile fabric can be utilized for improved handling characteristics. Polymer coverage levels of up to 40 mg/cm2were demonstrated to achieve comparable handling characteristics to the reference sample as assessed by surgeon users. Photographs of select samples from Tables 10-14 are reproduced inFIGS.12-19. Description of these figures follow. FIGS.12and13are SEM photographs of sample 2 from the above-described Tables. Sample 2 had the following characteristics:Masking Solution: 2% PVP, 0% Glycerol in water;Silicone Dispersant: 15% Silicone in heptane;Silicone Coverage: 41 mg/cm2;Silicone Penetration Grading: 3 (Silicone visible);Silicone Adherence Grading: 0 (Silicone is well adhered to graft and showing no signs of failure);Measured Leakage at 120 mmHg: 0 ml/min;Measured Leakage at 600 mmHg: 0 ml/min;Handling Assessment: 3 (Graft judged to be stiffer than Reference but with useable characteristics); andTensile Force to Extend Graft by 20%: 1.112 N. FIG.12is a SEM photograph of a cross-section of the textile50of Sample 2. The outer surface52of the textile50was fully coated with silicone sealant56. Fiber bundles58A were fully encapsulated by the silicone sealant56. The silicone sealant was disposed throughout the cross-section of the fiber bundle or the multi-filament yarn58. As depicted inFIG.13, the inner textile surface54also had noticeable amounts of silicone sealant60at the fiber bundles58. FIGS.14and15are photographs of sample 9 from the above-described Tables. Sample 9 had the following characteristics:Masking Solution: 25% PVP, 0% Glycerol in water;Silicone Dispersant: 15% Silicone in heptane;Silicone Coverage: 41 mg/cm2;Silicone Penetration Grading: 0 (Silicone only visible on the outer surface of the graft);Silicone Adherence Grading: 3 (Delaminated, Silicone coating has failed, and a bubble has appeared on the surface);Measured Leakage at 120 mmHg: Delaminated;Measured Leakage at 600 mmHg: Delaminated;Handling Assessment: 1 (Graft judged more flexible than Reference Sample); andTensile Force to Extend Graft by 20%: 0.571 N. FIG.14is a photograph of a cross-section of the textile50of Sample 9. The outer surface52of the textile50was fully coated with silicone sealant56. Individual textile bundles58were general free of silicone sealant penetration. There was, however, delamination of the silicone sealant56from the textile fibers at the outer surface as noted by delamination spaces. As depicted inFIG.15, the inner textile surface54and all fiber bundles58thereat were free of any noticeable amounts of silicone sealant60. FIGS.16-18are SEM photographs of sample 7 from the above-described Tables. Sample 7 had the following characteristics:Masking Solution: 15% PVP, 0% Glycerol in water;Silicone Dispersant: 15% Silicone in heptane;Silicone Coverage: 40 mg/cm2;Silicone Penetration Grading: 2 (Silicone is visible penetrating to the inside surface);Silicone Adherence Grading: 0 (Silicone is well adhered to graft and showing no signs of failure);Measured Leakage at 120 mmHg: 4 ml/min;Measured Leakage at 600 mmHg: 14 ml/min;Handling Assessment: 2 (Graft judged comparable to Reference Sample64B); andTensile Force to Extend Graft by 20%: 0.541 N. FIG.16shows an SEM photograph of a cross-section of the textile50of Sample 7. As shown inFIG.16, the textile fiber bundles58on the outer textile surface52were penetrated and encapsulated with silicone sealant56. The textile fiber bundles58at the inner textile surface54were free from silicone sealant60penetration. As shown inFIGS.17and18, the silicone sealant56penetrated and encapsulated the textile fiber bundles58at the outer textile surface. The fiber bundles58at the inner textile surface54were free from silicone sealant56. FIG.19is an SEM photograph of sample 15 from the above-described Tables. Sample 15 had the following characteristics:Masking Solution: 15% PVP, 5% Glycerol in water;Silicone Dispersant: 15% Silicone in heptane;Silicone Coverage: 40 mg/cm2;Silicone Penetration Grading: 2 (Silicone is visible penetrating to the inside surface);Silicone Adherence Grading: 1 (Graft reached the maximum pressure, but the leak rate has visibly increased);Measured Leakage at 120 mmHg: 3 ml/min;Measured Leakage at 600 mmHg: 22 ml/min;Handling Assessment: 2 (Graft judged comparable to Reference Sample64B); andTensile Force to Extend Graft by 20%: 0.719 N. FIG.19is a SEM photograph of a cross-section of the textile50of Sample 15. The silicone sealant56encapsulated the outer fibers of the fiber bundles58at the outer textile surface2. The fiber bundles58at the inner textile54were free from penetration of the silicone sealant56. Dyed silicone sealant (not shown) was visible ay the inner surface54. Glycerol Hydration of Masking Agents The use of glycerol within different masking agent formulations has been demonstrated on multiple formulations with the aim of hydrating or plasticizing the (PVP) masking agent and improving its ability to cover and fill the yarn structure and prevent the sealant dispersion from ingress to the inner surface. Masking Agent Sample Preparation Masking agents were prepared using following method: A target weight of PVP (MW 10,000) was introduced in a plastic beaker on a scale balance. A 100 ml masking agent solution was prepared at a target mass of 10 g PVP (10% concentration). The target volume of de-ionised water was introduced into a 100 ml plastic measuring cylinder. A target volume of 90 ml was required. The de-ionised water was added into the PVP in plastic beaker. A magnetic stirrer rod was placed in the water, and the beaker was placed on the magnetic stirrer. The magnetic stirrer was turned on at a speed of 350-450 RPM, the stirrer was centered in the beaker. The stirring was done at room temperature. Stirring continued until there was no visible PVP solute, but for at least 2 minutes. After stirring the masking agent solution, it can be removed from stirrer and used for control sample preparation. Additional steps were used for subsequent samples with added glycerol. The plastic beaker was returned to scale balance, tared, and the required quantity of glycerol was added to the masking agent solution. The target glycerol content was calculated as a percentage by mass of the PVP. The target weight of Glycerol added at each stage was 1 g, corresponding to cumulative weights of 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 g. Each beaker was stirred for at least 2 minutes after each added quantity of Glycerol. A summary of the samples prepared are shown below. TABLE 15VolumePVPPVP %GlycerolGlycerolSample Ref.of waterWeightw/vWeightas % of PVPControl90 ml10 g10%00A) 10% Glycerol90 ml10 g9.9%1g10%B) 20% Glycerol90 ml10 g9.8%2g20%C) 30% Glycerol90 ml10 g9.7%3g30%D) 40% Glycerol90 ml10 g9.6%4g40%E) 50% Glycerol90 ml10 g9.5%5g50%F) 60% Glycerol90 ml10 g9.4%6g60%G) 70% Glycerol90 ml10 g9.3%7g70%H) 80% Glycerol90 ml10 g9.3%8g80%I) 90% Glycerol90 ml10 g9.2%9g90%J) 100% Glycerol90 ml10 g9%10g100% Dispersion Drop Castings Three individual drops of each masking agent formulation were cast onto a dark coloured sheet to allow visual observation during the drying process. The drying was accelerated by using a desk fan at room temperature Assessments of the masking agents after drying were as follows: TABLE 16AssessmentAssessmentSample Ref.after 12 hoursafter 96 hoursControlLooked white,Dry, BrittleDry to touchA) 10% GlycerolLooked hydrated,Looked hydrated,Dry to touchDry to touchB) 20% GlycerolHydrated, Soft,Hydrated, Soft,Tacky to touchTacky to touchC) 30% GlycerolVery Sticky toSticky to touchtouchD) 40% GlycerolSticky, still wetSticky, still wetE) 50% GlycerolWet to touchWet to touchF) 60% GlycerolWet to touchWet to touchG) 70% GlycerolWet to touchWet to touchH) 80% GlycerolWet to touchWet to touchI) 90% GlycerolWet to touchWet to touchJ) 100% GlycerolWet to touchWet to touch Conclusions The control masking agent formulation (e.g., PVP-only) dried out fully within a few hours and became brittle. Use of this PVP-only masking agent may result in a stiff graft structure once mask is applied and dried. The use of 10% glycerol helped to hydrate the PVP masking agent solution, and appeared dry after 12 hours. A masking agent solution consisting of 20% glycerol retains some hydration at 12 hours and is soft/deformable to touch. A range of between about 1% and about 30% glycerol to PVP, by weight, provides appropriate ranges for use with the present invention. Moreover, the present invention is not limited to vascular prostheses in conduit-type shapes. The methods, coatings, and masking agents of the present invention may suitably be used with other textile products, including medical and non-medical (e.g., non-implantable) textile products. Other medical products may include ventricular assist devices, artificial heart conduits, medical sheets, patches, meshes, and the like. Non-medical textiles may include, but are not limited to, clothing, geotextiles, transportation textiles, military and/or defense textiles, safety and/or protective textiles, sports and/or recreation textiles, and the like. Further, textile products are not limited to tubular conduits, but may be of any shape including, but not limited to for example, sheets and/or tapes (e.g., two-dimensional products), or even three-dimensional shaped products other than conduit-shaped products. Useful polymeric materials and/or for fibers for non-medical or non-implantable textiles may include, but are not limited to, polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePFTE), polyolefins, polyesters, poly(ether amides), poly(ether esters), poly(ether urethanes), poly(ester urethanes), poly(ethylene-styrene/butylene-styrenes), and other block copolymers. Useful animal fibers for the non-medical or non-implantable textiles of the present invention may include, but are not limited to, wool, alpaca, angora, mohair, llama, cashmere, and silk. Useful natural fibers may include, but are not limited to, linen, cotton bamboo, hemp, corn, nettle, soy fiber, and the like. The masking agents and/or the sealants may be applied by brushing, spray-coating, dipping or immersing, and the like. The present invention, however is not limited to such techniques, and other techniques, such as chemical deposition, vapor deposition, chemical vapor deposition, physical vapor deposition, printing and the like, may suitably be used. These techniques are generally suitable for medical textiles. However, for large commercial scale textile production, including non-medical textiles, other techniques may also be used. For example, coating and/or masking materials for textile sheets or substrates may be applied by squeegee type coating, roller coating, knife coating, nip coating, dip coating, cast coating, chemical deposition, vapor deposition, and the like. Moreover, printing techniques, such as roller printing, stencil printing, screen printing, inkjet printing, lithographic printing, 3D printing, and the like may be used with the present invention for applying the masking agents and/or the sealing agents. Furthermore, mechanical devices may be employed to control the depth of penetration of the masking agent and/or sealing agent into the wall of the textile substrate of graft. For example, with a tubular graft an expandable balloon may be to control the depth of penetration of the masking agent into the graft wall. Modifications may be made to the foregoing embodiments within the scope of the present invention. The following embodiments or aspects of the invention may be combined in any fashion and combination and be within the scope of the present invention, as follows: Embodiment 1. A method of manufacturing a tubular graft comprising the steps of:providing a textile comprising a tubular wall disposed between a first open end and an opposed second open end, an inner surface and an opposed outer surface defining an interior wall portion therein between, the tubular wall comprising a textile construction of one or more filaments or yarns, the textile construction by itself being permeable to liquid;applying a substantially water-soluble material to at least a portion of the tubular wall; andapplying a substantially water-insoluble sealant to at least a part of the outer surface of the tubular wall, the substantially water-insoluble sealant being configured to mitigate movement of fluid through the wall of the conduit;wherein the water-soluble material is configured to mitigate penetration of the sealant to the inner surface of the conduit. Embodiment 2. The method of embodiment 1, wherein the step of applying the water-soluble material to at least a portion of the tubular wall comprises applying the water-soluble material to at least a portion of the inner surface and a portion of the interior portion of the tubular wall. Embodiment 3. The method of embodiment 1 or 2, wherein the step of applying the water-soluble material to at least a portion of the tubular wall comprises applying the water-soluble material to at least a portion of the outer surface of the tubular wall. Embodiment 4. The method of any preceding embodiment, wherein the water-soluble material is a solution of the water-soluble material and a solvent. Embodiment 5. The method of any preceding embodiment, wherein the solvent is selected form the group consisting of water, lower alcohols, and combinations thereof. Embodiment 6. The method of any preceding embodiment, wherein the solvent is at least partially removed prior to applying the substantially water-insoluble sealant. Embodiment 7. The method of any preceding embodiment, further comprising removal of at least a portion of the water-soluble material is by dissolution, abrading, peeling, degrading, and combinations thereof. Embodiment 8. The method of any preceding embodiment, wherein the water-soluble material is selected from the group consisting of polyvinylpyrrolidone, glycerol, methyl cellulose, poly(ethylene glycol), poly(ethylene glycol) hydrogel, polyethylene oxide, and combinations thereof. Embodiment 9. The method of any preceding embodiment, wherein the substantially water-insoluble sealant is an elastomeric material selected from the group consisting of moisture curing, light curing, thermo-curing, platinum catalyzed, anaerobic curing materials or a combination of these curing mechanisms. Embodiment 10. The method of embodiment 9, wherein the elastomeric material is selected from the group consisting of silicones, polyurethanes, polycarbonates, thermoplastic elastomers, and combinations thereof. Embodiment 11. The method of any preceding embodiment, wherein one of more of the substantially water-soluble coating or the substantially water-insoluble coating further comprises a component selected from the group consisting of a colorant, a therapeutic agent, a dye, and a fluorescent indicator. Embodiment 12. The method of any preceding embodiment, wherein the water-soluble material comprises polyvinylpyrrolidone having a molecular weight of between approximately 6,000 g/mol and approximately 15,000 g/mol. Embodiment 13. The method of any preceding embodiment, wherein applying the water-soluble material forms layer on substantially all of the inner surface of the tubular wall. Embodiment 14. The method of any preceding embodiment, further comprising curing the substantially water-insoluble sealant. Embodiment 15. The method of any preceding embodiment, further comprising curing the substantially water-insoluble sealant; and thereafter removing at least a portion of the water-soluble material. Embodiment 16. The method of embodiment 14, further comprising removing substantially all of the water-soluble material from the inner surface of the tubular wall. Embodiment 17. The method of any preceding embodiment, further comprising:removing at least a part of the water-soluble material from at least a part of the outer surface of the tubular wall prior to the applying the substantially water-insoluble sealant. Embodiment 18. The method of any one of embodiments 15 to 17, wherein the removing at least the portion of the water-soluble material is carried out at a temperature of between approximately 15° C. and approximately 140° C. Embodiment 19. The method of any one of embodiments 15 to 18, wherein the removing at least the portion of the water-soluble material further comprises the step of applying a solvent thereto. Embodiment 20. The method of embodiment 19, wherein the solvent comprises water, lower alcohols, and combinations thereof. Embodiment 21. The method of any one of embodiments 15 to 20, wherein the tubular textile is agitated, rotated, spun, and shaken, or the like, during the removal of the water-soluble material. Embodiment 22. The method of any one of embodiments 15 to 21, wherein the removal of the water-soluble material comprises dissolving, etching, plasma etching, ablating, abrading and combinations thereof of the water-soluble material. Embodiment 23. The method of any preceding embodiment, wherein the step of applying the water-soluble material further comprises spraying the water-soluble material, brushing the water-soluble material, immersing at least a portion of the tubular wall into a solution of the water-soluble material, and combinations thereof. Embodiment 24. The method of any preceding embodiment, wherein the substantially water-insoluble sealant is a polymer solution. Embodiment 25. The method of embodiment 24, wherein the polymer solution comprises an organic solvent. Embodiment 26. The method of embodiment 25, wherein the organic solvent comprises at least one of heptane and xylene. Embodiment 27. The method of any preceding embodiment, wherein the substantially water-insoluble sealant is applied by brushing, spraying, roller coating the substantially water-insoluble sealant thereon. Embodiment 28. The method of any preceding embodiment, wherein the method comprises one or more steps of selectively applying the substantially water-insoluble sealant to one or more portions of the tubular wall, such that the tubular wall comprises at least two sections having substantially different amounts of the substantially water-insoluble sealant thereon. Embodiment 29. The method of any one of embodiments 14 to 28, wherein the tubular wall having the coating of the substantially water-insoluble sealant is, after curing thereof, substantially impermeable to liquid. Embodiment 30. The method of any preceding embodiment, wherein, after curing of the substantially water-insoluble sealant, the tubular wall has a water permeability of about 0.16 ml/min/cm2at 120 mm Hg pressure or less than 0.16 ml/min/cm2at 120 mm Hg pressure. Embodiment 31. A textile comprising:a tubular wall disposed between a first open end and an opposed second open end and having an inner surface and an opposed outer surface, the tubular wall comprising a textile construction of one or more filaments or yarns, the textile construction by itself being permeable to liquid;wherein a portion of the inner surface comprises a coating of a substantially water-soluble material thereon;wherein the outer surface further comprises a coating of a substantially water-insoluble sealant disposed thereon; andwherein the tubular wall having the coating of the substantially water-insoluble sealant is, after curing thereof, substantially impermeable to liquid. Embodiment 32. The textile of embodiment 31, wherein the water-soluble material is selected from the group consisting of polyvinylpyrrolidone, glycerol, methyl cellulose, poly(ethylene glycol) poly(ethylene glycol) hydrogel, polyethylene oxide, and combinations thereof. Embodiment 33. The textile of embodiment 31 or 32, wherein the coating of the water-soluble material comprises an oleophobic layer. Embodiment 34. The textile of any one of embodiments 31 to 33, wherein the water-soluble material comprises polyvinylpyrrolidone having a molecular weight of between approximately 6,000 g/mol and approximately 15,000 g/mol. Embodiment 35. The textile of any one of embodiments 31 to 34, the water-soluble material comprises polyvinylpyrrolidone and glycerol. Embodiment 36. The textile of any one of embodiments 31 to 35, wherein the substantially water-insoluble sealant is an elastomeric material selected from the group consisting of moisture curing, light curing, thermo-curing, platinum catalyzed, anaerobic curing materials or a combination of these curing mechanisms. Embodiment 37. The textile of embodiment 36, wherein the elastomeric material is selected from the group consisting of silicones, polyurethanes, polycarbonates, thermoplastic elastomers, and combinations thereof. Embodiment 38. The textile of any one of embodiments 31 to 37, wherein one of more of the substantially water-soluble coating or the substantially water-insoluble coating comprises a component selected from the group consisting of a colorant, a therapeutic agent, a dye, and a fluorescent indicator. Embodiment 39. The textile of any one of embodiments 31 to 38, wherein, after curing of the substantially water-insoluble sealant, the tubular wall has a water permeability of about 0.16 ml/min/cm2at 120 mm Hg pressure or less than 0.16 ml/min/cm2at 120 mm Hg pressure. Embodiment 40. The textile of any one of embodiments 31 to 39, wherein the textile construction is selected from the group consisting of a weave of the one or more filaments or yarns, a knit of the one or more filaments or yarns, a braid of the one or more filaments or yarns, and a web of the one or more filaments or yarns. Embodiment 41. The textile of any one of embodiments 31 to 40, wherein the tubular wall is a crimped wall having a series of peaks and valleys. Embodiment 42. The textile of embodiment 41, wherein the substantially water-insoluble sealant is disposed at about 8 mg/cm2of area of the tubular wall or greater than 8 mg/cm2of area of the tubular wall. Embodiment 43. The textile of any one of embodiments 31 to 40, wherein the tubular wall is a non-crimped wall being substantially free of peaks and valleys. Embodiment 44. The textile of embodiment 43, wherein the substantially water-insoluble sealant is disposed at about 4 mg/cm2of area of the tubular wall or greater than 4 mg/cm2of area of the tubular wall. Embodiment 45. The textile of any one of embodiments 31 to 44, wherein the substantially water-insoluble sealant is disposed at about 14 mg/cm2of area of the tubular wall or less than 14 mg/cm2of area of the tubular wall. Embodiment 46. The textile of any one of embodiments 31 to 45,wherein one portion of the tubular wall has a first level of the substantially water-insoluble sealant to provide a first soft, flexible zone;wherein another portion of the tubular wall has a second level of the substantially water-insoluble sealant to provide a second zone having a stiffness greater than the first zone; andwherein the second level the substantially water-insoluble sealant is greater than the first level of the substantially water-insoluble sealant. Embodiment 47. The textile of any one of embodiments 31 to 46, wherein at least a portion of the coating of the substantially water-insoluble sealant engages at least a portion of the one or more filaments or yarns. Embodiment 48. The textile of any one of embodiments 31 to 47, where in the textile is an implantable medical device. Embodiment 49. The textile of embodiment 48, wherein the implantable medical device is selected from the group consisting of surgical vascular grafts, and endovascular graphs, meshes, patches, hernia plugs, vascular wraps, heart valves, filters, and the like. Embodiment 50. The textile of any one of embodiments 31 to 49, wherein the textile is a delivery medical device. Embodiment 51. The textile of embodiment 50, wherein the delivery medical device is a catheter. Embodiment 52. A textile structure comprising:a fluid permeable polymeric textile layer having opposing first and second surfaces and a length;a cross-linkable water-insoluble elastomeric layer on the first textile surface configured to render the liquid permeable polymeric textile layer substantially impermeable to fluid when cured; anda substantially dried water-soluble polymer layer on the second textile surface;wherein water-soluble polymer layer substantially inhibits migration of the water-insoluble elastomeric layer onto the second surface; andwherein the water-soluble polymer layer is substantially removable by exposure to water. Embodiment 53. The textile structure of embodiment 52, wherein the weight ratio of the cross-linkable water-insoluble elastomeric polymer to the water-soluble polymer is from about 0.1:1 to about 100:1. Embodiment 54. The textile structure of embodiment 53, wherein the weight ratio of the cross-linkable water-insoluble elastomeric polymer to the water-soluble polymer is from about 1:1 to about 20:1. Embodiment 55. A textile structure comprising:a fluid permeable polymeric textile layer having opposing first and second surfaces and a length;a crosslinked water-insoluble elastomeric polymer layer on the first textile surface forming a substantially fluid impermeable barrier, wherein the crosslinked water-insoluble elastomeric layer is adhered to the first textile surface by elastomeric shrinkage; anda water dissolvable polymer layer dried on the second textile surface;wherein the weight ratio of the crosslinked water-insoluble elastomeric polymer to the water dissolvable polymer is from about 0.1:1 to about 100:1. Embodiment 56. The textile construction of embodiment 55, wherein the weight ratio of the crosslinked water-insoluble elastomeric polymer to the water dissolvable polymer is from about 1:1 to about 20:1. Embodiment 57. A graft comprising:a tubular wall disposed between a first open end and an opposed second open end and having an inner surface and an opposed outer surface, the tubular wall comprising a textile construction of one or more filaments or yarns;wherein the outer surface comprises a coating of a substantially water-insoluble sealant disposed thereon;wherein the inner surface is substantially free of the substantially water-insoluble sealant; andwherein the tubular wall has a water permeability of about 0.16 ml/min/cm2at 120 mm Hg pressure or less than 0.16 ml/min/cm2at 120 mm Hg pressure. Embodiment 58. The graft of embodiment 57, wherein the textile construction is selected from the group consisting of a weave of the one or more filaments or yarns, a knit of the one or more filaments or yarns, a braid of the one or more filaments or yarns, and a web of the one or more filaments or yarns. Embodiment 59. The graft of embodiment 57 or 58, wherein the coating is disposed within an intermediate portion of the tubular wall between the inner surface and the opposed outer surface. Embodiment 60. The graft of any one of embodiments 57 to 59, wherein the tubular wall is a crimped wall having a series of peaks and valleys. Embodiment 61. The graft of any one of embodiments 57 to 60, wherein the substantially water-insoluble sealant is disposed at about 8 mg/cm2of area of the tubular wall or greater than 8 mg/cm2of area of the tubular wall. Embodiment 62. The graft of any one of embodiments 57 to 59, wherein the tubular wall is a non-crimped wall being substantially free of peaks and valleys. Embodiment 63. The graft of any one of embodiments 57 to 62, wherein the substantially water-insoluble sealant is disposed at about 4 mg/cm2of area of the tubular wall or greater than 4 mg/cm2of area of the tubular wall. Embodiment 64. The graft of any one of embodiments 57 to 63, wherein the substantially water-insoluble sealant is disposed at about 14 mg/cm2of area of the tubular wall or less than 14 mg/cm2of area of the tubular wall. Embodiment 65. The graft of any one of embodiments 57 to 64, wherein the substantially water-insoluble sealant is an elastomeric material selected from the group consisting of moisture curing, light curing, thermo-curing, platinum catalyzed, anaerobic curing materials or a combination of these curing mechanisms. Embodiment 66. The graft of embodiment 65, wherein the elastomeric material is selected from the group consisting of silicones, polyurethanes, polycarbonates, thermoplastic elastomers, and combinations thereof. Embodiment 67. The graft of any one of embodiments 57 to 66, wherein one of more of the substantially water-soluble coating or the substantially water-insoluble coating comprises a component selected from the group consisting of a colorant, a therapeutic agent, a dye, and a fluorescent indicator. Embodiment 68. The graft of any one of embodiments 57 to 67, wherein the substantially water-insoluble sealant is selected from the group consisting of silicone, room temperature vulcanizing silicone, thermoplastic polyurethane, aliphatic polycarbonate, one or more thermoplastic elastomers, polycarbonate, and combinations thereof. Embodiment 69. The graft of any one of embodiments 57 to 69,wherein one portion of the tubular wall has a first level of the substantially water-insoluble sealant to provide a first soft, flexible zone;wherein another portion of the tubular wall has a second level of the substantially water-insoluble sealant to provide a second zone having a stiffness greater than the first zone; andwherein the second level the substantially water-insoluble sealant is greater than the first level of the substantially water-insoluble sealant. Embodiment 70. An implantable or deliverable medical textile comprising:a wall having a textile construction and having a first surface and an opposed second surface;wherein the second surface comprises a coating of a substantially water-insoluble sealant disposed thereon;wherein the first surface is substantially free of the substantially water-insoluble sealant; andwherein the wall has a water permeability of about 0.16 ml/min/cm2at 120 mm Hg pressure or less than 0.16 ml/min/cm2at 120 mm Hg pressure. Embodiment 71. An assembly for producing an implantable or deliverable medical textile having a selectively applied water-insoluble sealant layer, comprising:a mandrel having a length, a hollow lumen disposed within a portion of the length, at least one open end, and a plurality of perforations through a wall of the mandrel;a reservoir in fluid communication with the open lumen of the mandrel; anda water-soluble polymer disposed within the reservoir. Embodiment 72. The assembly of embodiment 71, further comprising a tubular graft securably disposed over a portion of the mandrel having the plurality of perforations. Embodiment 73. The assembly of embodiment 71 or 72, further comprising a vacuum source in fluid communication with the hollow lumen of the mandrel. Embodiment 74. The assembly of embodiment 73, further comprising a manifold configured to provide selective fluid communication between the hollow lumen of the mandrel and the reservoir and/or the vacuum source. Embodiment 75. The assembly of any one of embodiments 71 to 74, further comprising a source of pressurized and/or blown air. Embodiment 76. The assembly of embodiment 75, wherein the pressurized and/or blown air is in fluid communication with the hollow lumen of the mandrel. Embodiment 77. The method, textile, graft, device or assembly of any preceding embodiment, further including a support member. Embodiment 78. The method of any one of embodiments 1 to 30, wherein the support member is added to the outer surface of the wall of the conduit. Embodiment 79. The method of embodiment 78, wherein the support member is wrapped around the outer surface of the wall of the conduit. Embodiment 80. The method of embodiment 79, wherein the conduit comprises a plurality of crimps, and the support member is arranged to nest between the plurality of crimps. Embodiment 81. The method of any one of embodiments 78 to 80, wherein a step of adding the support member to the conduit is carried out prior to the step of adding the sealant to the conduit. Embodiment 82. The method of any one of embodiments 78 to 81, wherein a step of adding the sealant to the conduit is used, at least in part, to attach the support member to the conduit. Embodiment 83. The method of any one of embodiments 78 to 82, wherein the support member is a flexible, polymer member. Embodiment 84. The method of any one of embodiments 78 to 83, wherein the flexible support member is present on a portion of the length of the graft. Embodiment 85. A method of manufacturing a vascular prosthesis, the method comprising the steps of:(i) providing a conduit comprising a wall, the wall of the conduit comprising an inner surface and an outer surface, at least a section of the conduit being porous;(ii) adding a masking agent to at least a part of the porous section of the conduit; and(iii) adding a sealant to at least a part of the porous section of the conduit, the sealant being configured to mitigate movement of fluid through the wall of the conduit; wherein the masking agent is configured to mitigate presence of the sealant on the inner surface of the conduit. Embodiment 86. The method of embodiment 85, wherein the sealant forms a sealing layer on at least a part of the outer surface of the wall of the conduit. Embodiment 87. The method of embodiment 85 or embodiment 86, wherein the sealant forms a sealing layer on substantially all of the outer surface of the wall of the conduit. Embodiment 88. The method of any preceding embodiments 85 to 87, wherein the masking agent forms a masking agent layer on at least a part of the inner surface of the wall of the conduit. Embodiment 89. The method of any preceding embodiments 85 to 88, wherein the masking agent forms a masking agent layer on substantially all of the inner surface of the wall of the conduit. Embodiment 90. The method of any preceding embodiments 85 to 89, wherein substantially all of the conduit is porous. Embodiment 91. The method of any preceding embodiments 85 to 90, wherein the method comprises one or more masking agent removal steps, the, or each, masking agent removal step comprising the step of removing at least a part of the masking agent from the conduit. Embodiment 92. The method of embodiment 91, wherein the method comprises the step of removing at least a part of the masking agent from at least a part of the outer surface of the wall of the conduit prior to the step of adding the sealant to the porous section of the conduit. Embodiment 93. The method of embodiment 91 or embodiment 92, wherein the method comprises the step of removing at least a part of the masking agent from the inner surface of the wall of the conduit subsequent to the step of adding the sealant to at least a part of the porous section of the conduit. Embodiment 94. The method of any one of embodiments 91 to 93, wherein the method comprises the step of removing substantially all of the masking agent from the conduit subsequent to the step of adding the sealant to at least a part of the porous section of the conduit. Embodiment 95. The method of any one of embodiments 91 to 94, wherein at least one of the masking agent removal steps is carried out at a temperature of between approximately 15° C. and approximately 140° C. Embodiment 96. The method of any one of embodiments 91 to 95, wherein at least one of the masking agent removal steps comprises the step of removing at least a part of the masking agent by applying a solvent thereto. Embodiment 97. The method of embodiment 96, wherein the solvent comprises water. Embodiment 98. The method of any one of embodiments 91 to 97, wherein the conduit is at least one of: agitated, rotated, spun, and shaken, or the like, during at least one of the masking agent removal steps. Embodiment 99. The method of any one of embodiments 91 to 98, wherein at least one of the masking agent removal steps is carried out by etching, plasma etching, ablating and/or abrading the masking agent. Embodiment 100. The method of any preceding embodiments 85 to 99, wherein the inner surface of the wall of the conduit is configured to promote the growth of biological tissue thereon. Embodiment 101. The method of any preceding embodiments 85 to 100, wherein the masking agent comprises a polymer. Embodiment 102. The method of embodiment 101, wherein the masking agent comprises a water-soluble polymer. Embodiment 103. The method of embodiment 101 or embodiment 102, wherein the masking agent comprises at least one of: polyvinylpyrrolidone, glycerol, methyl cellulose, poly(ethylene glycol), and poly(ethylene glycol) hydrogel. Embodiment 104. The method of any preceding embodiments 85 to 103, wherein the masking agent is biocompatible. Embodiment 105. The method of any preceding embodiments 85 to 104, wherein the masking agent forms a biocompatible masking agent layer when added to the conduit. Embodiment 106. The method of any preceding embodiments 85 to 105, wherein the masking agent is added to at least a part of the porous section of the conduit from a masking agent solution. Embodiment 107. The method of embodiment 106, wherein the masking agent solution is a polymer solution. Embodiment 108. The method of embodiment 106 or embodiment 107, wherein the step of adding the masking agent to at least a part of the porous section of the conduit is performed by spraying the masking agent solution onto at least a part of the porous section of the conduit. Embodiment 109. The method of embodiment 108, wherein the masking agent solution is added to the conduit by spraying the masking agent onto at least a part of the inner surface of the wall of the conduit. Embodiment 110. The method of any one of embodiments 106 to embodiment 109, wherein the step of adding the masking agent to at least a part of the porous section of the conduit is performed by immersing at least a part of the porous section of the conduit in the masking agent solution. Embodiment 111. The method of embodiment 110, wherein substantially all of the conduit is immersed in the masking agent solution. Embodiment 112. The method of any one of embodiments 106 to 111, wherein the masking agent solution comprises between approximately 5% weight/volume (w/v) of polymer in solution and approximately 30% w/v of polymer in solution. Embodiment 113. The method of any preceding embodiments 85 to 112, wherein the step of adding the sealant to at least a part of the porous section of the conduit does not result in the removal of the masking agent from the porous section of the conduit. Embodiment 114. The method of any preceding embodiments 85 to 113, wherein the masking agent is configured to biodegrade when the vascular prosthesis is implanted inside the human or animal body. Embodiment 115. The method of any preceding embodiments 85 to 114, wherein the conduit is a woven fibrous polymer conduit. Embodiment 116. The method of any preceding embodiments 85 to 115, wherein the sealant comprises a polymer. Embodiment 117. The method of embodiment 116, wherein the sealant is a water-insoluble polymer. Embodiment 118. The method of any preceding embodiments 85 to 117, wherein the sealant forms a sealing layer when added to the conduit, the sealing layer being a polymer layer. Embodiment 119. The method of any one of embodiments 116 to 118, wherein the sealant comprises at least one of: silicone, room temperature vulcanising silicone, thermoplastic polyurethane, aliphatic polycarbonate, one or more thermoplastic elastomers, and polycarbonate. Embodiment 120. The method of any preceding embodiments 85 to 119, wherein the sealant is added to the conduit from a sealant solution. Embodiment 121. The method of embodiment 120 wherein the sealant solution is a polymer solution. Embodiment 122. The method of embodiment 120 or embodiment 121, wherein the sealant solution comprises an organic solvent. Embodiment 123. The method of embodiment 122, wherein the sealant solution comprises at least one of heptane and xylene. Embodiment 124. The method of any preceding embodiments 85 to 123, wherein the sealant is added to at least a part of the porous section of the conduit by brushing and/or spraying the sealant thereon. Embodiment 125. The method of any preceding embodiments 85 to 124, wherein the sealant is configured to mitigate movement of blood through the wall of the conduit. Embodiment 126. The method of any preceding embodiments 85 to 125, comprising the further step of sterilising the vascular prosthesis. Embodiment 127. The method of embodiment 126, wherein the vascular prosthesis is sterilised by way of at least one of: a gamma sterilisation process, an electron beam sterilisation process, and an ethylene oxide sterilisation process. Embodiment 128. The method of any preceding embodiments 85 to 127, wherein the conduit is moveable between a contracted state and an extended state. Embodiment 129. The method of embodiment 128, wherein the step of adding the masking agent to at least a part of the porous section of the conduit is carried out, at least in part, while the conduit is in the contracted state, in the extended state, and/or when moved between the contracted state and the extended state. Embodiment 130. The method of embodiment 128 or embodiment 129, wherein the step of adding the sealant to at least a part of the porous section of the conduit is carried out, at least in part, while the conduit is in the contracted state, in the extended state, and/or when moved between the contracted state and the extended state. Embodiment 131. The method of any preceding embodiments 85 to 130, the method comprising one or more steps of weighing the conduit and/or measuring the length of the conduit, to determine, at least in part, the amount of masking agent, and/or or the amount of sealant, to add to at least a part of the porous section of the conduit. Embodiment 132. The method of any preceding embodiments 85 to 131, wherein the step of adding the masking agent to at least a part of the porous section of the conduit comprises the step of providing gas to the conduit. Embodiment 133. The method of embodiment 132, wherein the gas is directed towards the outer surface of the wall of the conduit. Embodiment 134. The method of embodiment 132 or embodiment 133, wherein the gas is air. Embodiment 135. The method of any preceding embodiments 85 to 134, wherein the method comprises the step of adding a support member to the conduit. Embodiment 136. The method of embodiment 135, wherein the support member is added to the outer surface of the wall of the conduit. Embodiment 137. The method of embodiment 136, wherein the support member is wrapped around the outer surface of the wall of the conduit. Embodiment 138. The method of embodiment 137, wherein the conduit comprises a plurality of crimps, and the support member is arranged to nest between the plurality of crimps. Embodiment 139. The method of any one of embodiments 135 to 138, wherein the step of adding the support member to the conduit is carried out prior to the step of adding the sealant to the conduit. Embodiment 140. The method of any one of embodiments 135 to 139, wherein the step of adding the sealant to the conduit is used, at least in part, to attach the support member to the conduit. Embodiment 141. The method of any one of embodiments 135 to 140, wherein the support member is a flexible, polymer member. Embodiment 142. The method of any preceding embodiments 85 to 141, wherein the method comprises one or more steps of selectively adding sealant to one or more sections of the conduit, such that the conduit comprises at least two sections comprising substantially different amounts of sealant thereon. Embodiment 143. A vascular prosthesis comprising:a conduit comprising a wall, the wall of the conduit comprising an inner surface and an outer surface, at least a section of the conduit being porous;wherein at least a part of the porous section comprises a sealant configured to mitigate movement of fluid through the wall of the conduit; andwherein the inner surface of the wall of the conduit is substantially devoid of the sealant. Embodiment 144. The vascular prosthesis of embodiment 143, wherein the sealant forms a sealing layer on at least a part of the outer surface of the wall of the conduit. Embodiment 145. The vascular prosthesis of embodiment 143 or embodiment 144, wherein the sealant forms a sealing layer on substantially all of the outer surface of the wall of the conduit. Embodiment 146. The vascular prosthesis of any one of embodiments 143 to 145, wherein substantially all of the conduit is porous. Embodiment 147. The vascular prosthesis of any one of embodiments 143 to 146, wherein the inner surface of the wall of the conduit is configured to promote the ingrowth of biological tissue thereon. Embodiment 148. The vascular prosthesis of any one of embodiments 143 to 147, wherein the conduit is a woven fibrous polymer conduit. Embodiment 149. The vascular prosthesis of any one of embodiments 143 to 148, wherein the sealant forms a sealing layer, the sealing layer being a polymer layer. Embodiment 150. The vascular prosthesis of any one of embodiments 143 to 149, wherein the sealant comprises at least one of: silicone, room temperature vulcanising silicone, thermoplastic polyurethane, aliphatic polycarbonate, one or more thermoplastic elastomers, and polycarbonate. Embodiment 151. The vascular prosthesis of any one of embodiments 143 to 150, wherein the sealant is configured to mitigate movement of blood through the wall of the conduit. Embodiment 152. The vascular prosthesis of any one of embodiments 143 to 151, wherein the vascular prosthesis is sterilised. Embodiment 153. The vascular prosthesis of embodiment 152, wherein the vascular prosthesis is sterilised by way of at least one of the following: a gamma sterilisation process, an ethylene oxide sterilisation process, and an electron beam sterilisation process. Embodiment 154. The vascular prosthesis of any one of embodiments 143 to 153, wherein the conduit is moveable between a contracted state and an extended state. Embodiment 155. The vascular prosthesis of any one of embodiments 143 to 154, wherein the conduit comprises a support member. Embodiment 156. The vascular prosthesis of embodiment 155, wherein the support member is located substantially adjacent to the outer surface of the wall of the conduit. Embodiment 157. The vascular prosthesis of embodiment 156, wherein the support member is wrapped around the outer surface of the wall of the conduit. Embodiment 158. The vascular prosthesis of embodiment 157, wherein the conduit comprises a plurality of crimps, the support member being arranged to nest between the plurality of crimps. Embodiment 159. The vascular prosthesis of any one of embodiments 155 to 158, wherein the sealant is arranged to, at least in part, attach the support member to the conduit. Embodiment 160. The vascular prosthesis of any one of embodiments 155 to 159, wherein the support member is a flexible, polymer member. Embodiment 161. The vascular prosthesis of any one of embodiments 143 to 160, wherein the conduit is configured to have at least two sections having substantially different amounts of sealant thereon. Embodiment 162. A kit of parts for manufacturing a vascular prosthesis, the kit of parts comprising:(i) a conduit comprising a wall, the wall of the conduit comprising an inner surface and an outer surface, at least a section of the conduit being porous;(ii) a masking agent; and(iii) a sealant; when applied to at least a part of the porous section of the conduit, the masking agent being configured to mitigate presence of the sealant on the inner surface of the conduit; and when applied to at least a part of the porous section of the conduit, the sealant being configured to mitigate movement of fluid through the wall of the conduit. Embodiment 163. The kit of parts of embodiment 162, wherein addition of the sealant to at least a part of the porous section of the conduit forms a sealing layer on at least a part of the outer surface of the wall of the conduit. Embodiment 164. The kit of parts of embodiment 162 or embodiment 163, wherein addition of the masking agent to at least a part of the porous section of the conduit forms a masking agent layer on at least part of the inner surface of the wall of the conduit. Embodiment 165. The kit of parts of any one of embodiments 162 to 164, wherein substantially all of the conduit is porous. Embodiment 166. The kit of parts of any one of embodiments 162 to 165, the kit of parts comprising a masking agent remover, the masking agent remover being operable to remove applied masking agent from the conduit. Embodiment 167. The kit of parts of embodiment 166, wherein the masking agent remover comprises a solvent. Embodiment 168. The kit of parts of embodiment 167, wherein the solvent comprises water. Embodiment 169. The kit of parts of any one of embodiments 166 to 168, wherein the masking agent remover is operable to remove applied masking agent from the conduit at a temperature of between approximately 15° C. and approximately 140° C. Embodiment 170. The kit of parts of any one of embodiments 162 to 169, the kit of parts comprising an abrading tool, the abrading tool being operable to remove applied masking agent from the conduit. Embodiment 171. The kit of parts of any one of embodiments 162 to 170, wherein the inner surface of the wall of the conduit is configured to promote the ingrowth of biological tissue thereon. Embodiment 172. The kit of parts of any one of embodiments 162 to 171, wherein the masking agent comprises a polymer. Embodiment 173. The kit of parts of embodiment 172, wherein the masking agent comprises a water-soluble polymer. Embodiment 174. The kit of parts of any one of embodiments 162 to 173, wherein masking agent applied to the conduit forms a masking agent layer, the masking agent layer being a polymer layer. Embodiment 175. The kit of parts of any one of embodiments 172 to 174, wherein the masking agent comprises at least one of: polyvinylpyrrolidone, glycerol, methyl cellulose, and poly(ethylene glycol) hydrogel. Embodiment 176. The kit of parts of any one of embodiments 162 to 175, wherein the masking agent is biocompatible. Embodiment 177. The kit of parts of any one of embodiments 162 to 176, wherein masking agent applied to the conduit forms a biocompatible masking agent layer. Embodiment 178. The kit of parts of any one of embodiments 162 to 177, wherein the kit of parts comprises a masking agent solution, the masking agent solution being operable to apply masking agent to the conduit. Embodiment 179. The kit of parts of embodiment 178, wherein the masking agent solution is a polymer solution. Embodiment 180. The kit of parts of embodiment 178 or embodiment 179, wherein the conduit is immersible in the masking agent solution. Embodiment 181. The kit of parts of any one of embodiments 178 to 180, wherein the masking agent solution comprises between approximately 5% w/v of polymer in solution and approximately 30% w/v of polymer in solution. Embodiment 182. The kit of parts of any one of embodiments 162 to 181, wherein when the masking agent and the sealant are applied to the conduit, the sealant is configured such that addition of the sealant to the conduit does not result in the removal of the applied masking agent from the conduit. Embodiment 183. The kit of parts of any one of embodiments 162 to 182, wherein the masking agent is configured to biodegrade when implanted inside the human or animal body. Embodiment 184. The kit of parts of any one of embodiments 162 to 183, wherein the conduit is a woven fibrous polymer conduit. Embodiment 185. The kit of parts of any one of embodiments 162 to 184, wherein the sealant comprises a polymer, optionally a water-insoluble polymer. Embodiment 186. The kit of parts of any one of embodiments 162 to 185, wherein the sealant, when applied to the conduit, forms a sealing layer, the sealing layer being a polymer layer. Embodiment 187. The kit of parts of embodiment 185 or embodiment 186, wherein the sealant comprises at least one of: silicone, room temperature vulcanising silicone, thermoplastic polyurethane, aliphatic polycarbonate, one or more thermoplastic elastomers, and polycarbonate. Embodiment 188. The kit of parts of any one of embodiments 162 to 187, wherein the kit of parts comprises a sealant solution operable to apply sealant to the conduit. Embodiment 189. The kit of parts of embodiment 188, wherein the sealant solution is a polymer solution. Embodiment 190. The kit of parts of embodiment 188 or embodiment 189, wherein the sealant solution comprises an organic solvent. Embodiment 191. The kit of parts of embodiment 190, wherein the sealant solution comprises at least one of heptane and xylene. Embodiment 192. The kit of parts of any one of embodiments 162 to 191, the kit of parts comprising a sealant applicator operable to apply sealant to the conduit, and/or a masking agent applicator operable to apply masking agent to the conduit. Embodiment 193. The kit of parts of embodiment 192, wherein the sealant applicator is an apparatus for spray coating the sealant, and/or a brush, or the like. Embodiment 194. The kit of parts of embodiment 192 or embodiment 193, wherein the masking agent applicator is a brush, an apparatus for spray-coating the masking agent, an apparatus for dipping or immersing the conduit in the masking agent, and/or an apparatus for wiping the masking agent onto the conduit. Embodiment 195. The kit of parts of any one of embodiments 162 to 194, wherein the sealant, when applied to at least a part of the porous section of the conduit, is configured to mitigate movement of blood through the wall of the conduit. Embodiment 196. The kit of parts of any one of embodiments 162 to 195, wherein the conduit is moveable between a contracted state and an extended state. Embodiment 197. The kit of parts of any one of embodiments 162 to 196, the kit of parts comprising a further prosthesis. Embodiment 198. The kit of parts of embodiment 197, wherein the further prosthesis is at least one of: a biological heart valve, a synthetic heart valve, a cardiac assist device, and a ventricular assist device, or the like. Embodiment 199. The kit of parts of any one of embodiments 162 to 198, the kit of parts comprising a weighing device and/or a device for measuring the length of the conduit. Embodiment 200. The kit of parts of any one of embodiments 162 to 199, the kit of parts comprising a gas flow apparatus operable to provide gas flow to the conduit. Embodiment 201. The kit of parts of embodiment 200, wherein the gas is air. Embodiment 202. A vascular system, the vascular system comprising:a vascular prosthesis manufactured according to any one of embodiments 85 to 142; anda further prosthesis;wherein the vascular prosthesis is connected to the further prosthesis, such that fluid can flow between the vascular prosthesis and the further prosthesis. Embodiment 203. The vascular system of embodiment 202, wherein the further prosthesis is at least one of: a biological heart valve, a synthetic heart valve, a cardiac assist device, and a ventricular assist device, or the like. Embodiment 204. A method of implanting a vascular prosthesis, the method comprising the steps of:providing a vascular prosthesis manufactured using the method of any one of embodiments 85 to 142;connecting an inlet of the vascular prosthesis to a first blood vessel; andconnecting an outlet of the vascular prosthesis to a second blood vessel;such that blood can flow between the first and second blood vessels through the vascular prosthesis. Embodiment 205. The method of embodiment 204, wherein the first and second blood vessels are formed from a blood vessel which is diseased, or has been severed, bisected, or the like. Embodiment 206. A method of implanting a vascular prosthesis, the method comprising the steps of:providing a vascular prosthesis according to any one of embodiments 143 to 161;connecting the vascular prosthesis to a first blood vessel; andconnecting the vascular prosthesis to a second blood vessel;such that blood can flow between the first and second blood vessels through the vascular prosthesis. Embodiment 207. The method of embodiment 206, wherein the first and second blood vessels are formed from a blood vessel which is diseased, or has been severed, bisected, or the like. Embodiment 207. A method of implanting a vascular system, the method comprising the steps of:providing a vascular system, the vascular system comprising:a vascular prosthesis manufactured according to any one of embodiments 85 to 142; anda further prosthesis;wherein the vascular prosthesis is connectable to the further prosthesis;connecting the vascular prosthesis to the further prosthesis, such that blood can flow therebetween;connecting an end of a blood vessel to the vascular prosthesis; andconnecting the further prosthesis to the heart;such that blood can flow between the blood vessel and the heart through the vascular system. Embodiment 209. The method of embodiment 208, wherein the further prosthesis is at least one of: a biological heart valve, a synthetic heart valve, a cardiac assist device, and a ventricular assist device, or the like. | 156,408 |
11857700 | DESCRIPTION OF THE PREFERRED EMBODIMENTS With reference toFIG.1, a medical implant in accordance with the present invention is shown in cross-sectional view at numeral10. The implant10comprises a (normally extensible) polylactic acid core11. The elastomeric core11has an inner bulk13and an outer surface14. The outer surface14of the core11is characterized by a plurality of microstructures15disposed on the surface portion of the core11. The microstructures15are dimensioned to permit the passage of fibroblasts thereinto. The microstructures15, in accordance with textured outer surfaces14are of three types, the first type17preferably dimensioned in the range of 1-15 microns in diameter19and 10-25 microns in height21. The second type23preferably dimensioned in the range of 25-50 microns in diameter25and 26-50 microns in height27. The third type29preferably dimensioned in the range of 100-500 microns in diameter31and 100-500 microns in height33. The arrangement of the microstructures is important because tissue ingrowth requires the migration of fibroblast cells into the pores to facilitate deposition of connective tissue between the microstructures. Such connective tissue, deposited between the microstructures, is integral with and part of the structure of the implant. It is believed that the irregular topography of the outer surface14of the implant induces non-inflammatory healing in the adjacent tissue layers comprising the surrounding body. With reference toFIG.2, a medical implant in accordance with the present invention is shown in cross-sectional view of a portion of a second preferred embodiment of an implant in accordance with the present invention at numeral100. The implant100comprises a (normally extensible) polylactic acid core110. The elastomeric core110has an inner bulk130and an outer surface140. The outer surface140of the core110is characterized by a plurality of microstructures150disposed on the surface portion of the core110. The microstructures150are dimensioned to permit the passage of endothelial cells thereinto. The microstructures150, in accordance with textured outer surfaces140are of three types, the first type170preferably dimensioned in the range of 1-15 microns in diameter190and 10-25 microns in height210. The second type230preferably dimensioned in the range of 25-50 microns in diameter250and 26-50 microns in height270. The third type290preferably dimensioned in the range of 100-500 microns in diameter310and 10-50 microns in height330. Drilled into feature290are holes350of depth equaling height330and diameter 10-50 microns370. With respect toFIG.3, a medical implant in accordance with the present invention is shown in cross-sectional view of the second preferred embodiment of an implant in accordance withFIG.2, and following implantation within the body, showing the hydration of the microstructure thereon200. The implant210is immersed in an aqueous environment220. Fine microstructure240is hydrophilic and water completely fills channels260. The full volume of microstructure240is hydrated280. Microstructure300is hydrophobic and water310partially fills channels320. The rest of the channel volume320is filled with lipid330. Only the tips340of microstructure300are hydrated. Surface350is resting against tissue, or is coated and hydrates more slowly. Alternatively, the microstructures could be disposed on both sides of the implant. Microstructure360is made hydrophilic by the inclusion of drilled holes or channels370. The inner surfaces380are partially hydrated. With respect toFIG.4, a medical implant in accordance with the present invention is shown in cross-sectional view of the second preferred embodiment of an implant in accordance withFIG.3, and following implantation within the body, showing the solvation400without particulate formation of the microstructure surface402thereon. The implant402is entirely encapsulated with healthy, non-fibrogenic tissue404. Remnants of microstructure406have the same thickness as the core408of the implant402. This state is by design, with the entire implant402going into dissolution at approximately the same time without particulate formation. The implant402is protected from particulate formation by reinforcement from encapsulating tissue404and uniform solvation of the absorbable polymer. Typically, the solvated monomers410exist as a diffuse soft cloud of monomers, which are metabolized by the surrounding tissue. Beyond the monomers410is water or tissue412. FIG.5depicts an implantable sheet500having a microstructured surface501on at least a portion thereon. In some embodiments, the microstructured surface covers the entire surface of the device, while in others the microstructured surface comprises a portion of the device. Microstructured surface501may comprise a preferential hydration zone, as described herein below. The device has a first side502and a second side503. In some embodiments, the first side comprises the microstructured surface while the second side is smooth. In other embodiments, the first and second sides each have a microstructured surface, where the surface have either the same or different morphology. The sheet has a core with a thickness504. In certain embodiments, the sheet comprises a polyester polyurethane, particularly a polyester polyurethane as described and exemplified herein. In the embodiments of a microstructured implant in accordance with the present invention, the choice of biodegradable material must be such that the structural integrity of the bioabsorbable portion of the implant is retained for 2-3 months following implantation in order to allow sufficient time for the implant to dissolve from the surface and avoid particulate disintegration. The implant surface is preferably completely hydrated at the time of implantation. This encompasses the inner and outer surfaces of the microstructures. The hydration can be achieved through textures that create a Wenzel-Cassie interface with tissue. The Wenzel-Cassie interface binds water to the implant surface. The hydration preferably comprises at least one water monolayer. A multiplicity of monolayers can also be layered on top of one another utilizing a stacked hierarchical surface texture. Water molecules are bound to the surface texture through dipole-dipole bonds and/or through van der Waals forces and/or through hydrogen bridges and thus can form extended water molecule layers. The use of an implant according to the present invention is foreseen for regulating an adsorption of proteins on the surface of the implant in terms of type, quantity and/or conformation of certain proteins by means of a defined surface, which is at least for the most part hydrated. The defined state can also have a defined surface charge and/or a defined predetermined composition of an oxide layer of the surface. The defined state is determined according to a desired regulation of the protein adsorption. Hence for different requirements for protein adsorption differing defined conditions can be established which are each attained by a suitable surface pattern. Suitable surface patterns develop in different location different surface energies, corresponding to separate locations of hydrophilicity and hydrophobicity. These alternating patterns of surface energy can promote certain types of protein adhesion, and subsequent tissue ingrowth. Through an implant according to the present invention the quantity of proteins and other elements adhering on the surface during an implantation of the implant can be changed. For example, undesired proteins can be reduced and desired proteins settled in an increased way. More neutrophils can be settled on the implant surface, which release cathelicidin and thus are responsible for a reduction of restenosis. The adsorption of thrombocytes can be decreased. Thus the risk of complications with implantation of an implant is significantly reduced and the growing-together behavior of the implant is improved. Complications from breaking or chipping of coatings on the implant, as is known from the state of the art, are excluded. Good results have been obtained with implants according to the invention in which the second surface microstructure is more hydrophobic than the first surface microstructure wherein the contact angle of the first microstructure is at least 10% less than the contact angle of the second microstructure, preferably by 20% or more. Alternatively, the zeta potential value of the surface in the second microstructure should be below the zeta potential value of the first microstructure. The zeta potential can serve to determine a defined state for the implant surface. The said potential values relate to a determination procedure by means of electrokinetic analysis. With the use of other determination procedures, the indications for potential values may possibly have to be adapted according to the procedural standards. In addition to using differences in hierarchical texture to achieve surface energy differences at discrete locations on the implant surface in order to create water pinning states, e.g., Wenzel-Cassie, such surface energy “textures” can promote healthy cellular ingrowth. Ingrowth prevents device mobilization. Implant motion can cause an inflammatory response resulting in the release of reactive oxygen species, which then cause rapid degradation of the implant and undesirable implant fragmentation. Protein deposition on an implant is highly sensitive to surface energy, and can also affect the shape or conformation of adsorbed proteins. The conformation of proteins adsorbed on an implant surface has an influence on the adhesion of neutrophils and fibroblasts and thus on the growing-together behavior of an implant and the surrounding tissue. Proteins are complex copolymers, whose three-dimensional structure is composed of several levels. Involved in the structural composition can be amino acid sequences, different .alpha.-helix and .beta.-sheet structures, the common structure of a multiplicity of polypeptides and the like. Natural conformation is desired, natural conformation is the shape proteins take when there are no outside influences affecting the three-dimensional structure of the proteins and influence the activity of these proteins. To be designated as an almost natural, or respectively natural-like conformation should be a conformation in which slight changes in the protein structure exist, but these changes have no influence or a negligible influence on the function and effect of the protein. Proteins comprise different regions, e.g. positively or negatively charged regions, hydrophilic and hydrophobic regions, which, depending upon spatial organization of the proteins, are exposed and can carry out specific biological functions. Through adsorption on a surface the protein conformation changes. Generally a protein has e.g. on a hydrophobic surface a greatly denatured conformation, while there exists on the hydrophilic surface a less denatured conformation. Protein conformation, because it coats the implant, can affect hydration and degradation profiles. The hydrophilic components of the proteins in the natural conformation usually lie outside and the hydrophobic components usually lie inside and are accessible for the hydrophobic surface only through a major conformational change. Information about the protein conformation can be gained through a measurement of the behavior of .alpha.-helix and .beta.-sheets or through a measurement of specific amino acids on the protein surface. With the present invention it was surprisingly discovered that e.g. endothelial cells can be settled on an implant surface according to the invention when fibrinogen is deposited at least approximately in its natural, or respectively natural-like, conformation. Endothelial cell infiltration promotes angiogenesis and healthy tissue association with the implant. The efficacy of fibrinogen on an implant surface according to the invention can be improved, since fibrinogen is adsorbed primarily in an advantageous conformation. In contrast thereto, fibrinogen on an implant surface in the unhydrated state is adsorbed in a denatured state, whereby a negative influence on the growing together of an implant results. In a denatured state fibrinogen has a changed three-dimensional structure and a changed spatial distribution of different fibrinogen regions not found in the natural state. A natural conformation also with other proteins promotes a positive growing together of the implant. The applicants have observed that a natural growing together of tissue promotes dissolution rather than fragmentation of the implant. During the implantation in a body, the body's own defense or resistance can recognize the difference between natural and denatured protein, in particular of fibrinogen, so that denatured protein is identified as a foreign body and an adverse reaction is triggered. Foreign body response results in the release of enzymes and reactive oxygen species that degrade the implant in a disordered and fragmentary manner. In use, the amount of adsorbed proteins on the implant can vary in the defined second state of the surface compared with the starting state of the implant surface. For example, the absolute amount of adsorbed proteins can be decreased and/or certain kinds of proteins can be adsorbed in an increased way and other kinds of proteins adsorbed in a decreased way. Thus the risk can be reduced of undesired deposits of proteins. The type of adhering proteins can thus be regulated in that a suitable defined second state is generated with the hydration and for example different oxides in the oxide layer or different surface charge. Through the production of an implant with a hydrated surface the adsorption of the proteins can be influenced. Less macroglobulin and/or apolipoprotein A can adhere on the surface and more apolipoprotein E, kininogen and/or plasminogen can be adsorbed. Above and beyond this, the conformation of proteins on the surface can be regulated. For example, fibrinogen can be settled on the implant surface in a way corresponding to its natural conformation, as explained above. Its natural effectiveness is thereby preserved and the deposit of endothelial cells promoted. Surface Texture Considerations A critical consideration in achieving the objectives of the present invention is to match the volume, areas, depth of penetration of hydration with the dimensions of the implant. In particular, in regions of the implant where a large volume to surface area ratio exists, microstructures should be disposed on the boundary surfaces to inhibit hydration of the bulk polymer in the region of high volume to surface area. This is achieved by a Wenzel-Cassie surface texture which traps water at a distance separate from surfaces boundary to large volumes. Other strategies include surface patterns of spatial periodic frequency suitable for encouraging protein deposition and cellular infiltration which can act as an insulating covering and reinforcement against implant fractionation into particulate. If this strategy is to be pursued, it is important that such cellular interaction not cause an inflammatory response, which could result in rapid uncontrolled enzymatic degradation of the implant, especially if such foreign body response is localized to particular regions of the implant. Other considerations include the manner in which the microstructural elements are laid down on the device. In the print construction of an implant, there are two principal modes: a droplet configuration and a line configuration. Drops are discrete in three dimensions, whereas lines are discrete in two dimensions. Lines generally draw water by capillary action, whereas spherical drops tend to resist water. In the droplet mode the drops can be spaced apart on a surface, and they can be joined together by a subsequent layer of drops in staggered form, or joined together by a line. The drops can be spaced closer together to slightly touch, creating an undulating profile, or they can be placed in close proximity so that they effectively merge before solidifying. In the creation of islands, they can be stacked in pyramid fashion in a vertical direction. In the line mode the lines are generally laid down in alignment with the previous line. However draping configurations can be achieved. For example, a partial wall can be formed of several aligned lines on top of which a line is placed such that it crosses this partial wall in undulatory fashion, such that adhesion between the wall and the line is only at points. After solidification, these draping feature typically are free to move away from the established wall structure. Draping features can be placed at points intermediate during the formation of a complete wall. In addition, a partial wall can be fenestrated by subsequent layers of droplets built up to form the edges of windows, the top edge of which is closed by the subsequent addition of lines. These lines typically will droop down into the established fenestrations. By varying the deposit speed of the final lines one can create a multiplicity of drooping lines into the fenestration of different lengths creating a curtain of drooping lines. Alternatively the microstructural elements can be deposited on a plane with a mold pattern. For example, the mold pattern can be a superhydrophobic pattern capable of generating a Wenzel-Cassie effect or a Wenzel-Baxter effect. Other surface textures can be achieved by incorporating on or in deposited microstructural element a variety of solid particulate. The solid particulate may be a permanent nanostructure, such as a nanotubule, a bucky ball, or any of variously known nanoparticulate geometries. The solid particulate may be soluble, such that when the patterned implant is placed in a solvent the particulate are partially or entirely removed without affecting the remaining portion of the implant. In addition, directed and random writing techniques can be combined. For example, at various points during the construction of a directed structure a spray or electrospinning technique could be employed to deposit randomly oriented fibrous or particulate masses. Selection of Polymers There are many materials that may be used to form a bioabsorbable implant. For example, the implant may comprise a bioabsorbable material selected from the group comprising polymers or copolymers of lactide, glycolide, caprolactone, polydioxanone, trimethylene carbonate, poly orthoesters, polyethylene oxide and polyester polyurethane. In addition to the foregoing bioabsorbable, non-toxic materials, high molecular weight polysaccharides from connective tissue such as chondroitin salts may be employed for the purpose of practicing the invention. Other polysaccharides may also prove suitable, such as chitin and chitosan. Additional bioabsorbable materials are in intense development and it is expected that many of the new materials will also be applicable for forming a textured bioabsorbable medical implant. The manufacturing method of the patterned absorbable implant can rely on the polymer constituents being in a liquid phase. The liquid phase is typically realized by dissolution of a solid polymer in a solvent or by melting. In the case of a melt phase, it is preferable to select polymers having relatively low melting points, to avoid exposing resorbable polymers to elevated temperatures. Resorbable polymers are typically susceptible to thermal degradation. A number of polymers are commonly used in the construction of implantable medical devices. Unless otherwise specified, the term “polymer” will be used to include any of the materials used to form the patterned implant matrix, including polymers and monomers which can be polymerized or adhered at point of application to form an integral unit. In a preferred embodiment the microstructural elements are formed of a polymer, such as a synthetic thermoplastic polymer, for example, ethylene vinyl acetate, polyanhydrides, polyorthoesters, polymers of lactic acid and glycolic acid and other a hydroxy acids, and polyphosphazenes, a protein polymer, for example, albumin or collagen, or a polysaccharide containing sugar units such as lactose. In a more preferred embodiment the polymers are absorbable polyurethane containing lactide diol blocks capable of resorbing in vivo. The lactide diol blocks are linked with ethylene diols and/or propylene diols via urethane or urea links. By varying the proportion of ethylene diol to propylene diol, as well as the choice of the linking diisocyanate, the surface energy of the resulting polymer can be modified to achieve a desired specification. Generally, these molecules are called polyester polyurethanes or polyesters urethanes. An example of a polyester urethane is an aliphatic polyester based poly ester urethane consisting of poly(l-lactic acid) and poly(ethylene succinate) prepared via chain-extension reaction of poly(l-lactic acid)-diol and poly(ethylene succinate)-diol using 1,6-hexamethylene diisocyanate as a chain extender. The poly(l-lactic acid)-diol is synthesized by direct polycondensation of l-lactic acid in the presence of 1,4-butanediol. Poly(ethylene succinate)-diol can be synthesized by condensation polymerization of succinic acid with excessive ethylene glycol. The polymer is biodegradable via hydrolysis or enzymatic cleavage. Non-polymeric materials can also be used to form the matrix and are included within the term “polymer” unless otherwise specified. Examples include organic and inorganic materials such as hydroxyapatite, calcium carbonate, buffering agents, and lactose, as well as other common excipients used in drugs, which are solidified by application of adhesive rather than solvent. In the case of polymers for use in making devices for cell attachment and growth, polymers are selected based on the ability of the polymer to elicit the appropriate biological response from cells, for example, attachment, migration, proliferation and gene expression. An alternative material is a polyester in the polylactide/polyglycolide family. These polymers have received a great deal of attention in the drug delivery and tissue regeneration areas for a number of reasons. They have been in use for over 30 years in surgical sutures, are Food and Drug Administration (FDA)-approved and have a long and favorable clinical record. A wide range of physical properties and degradation times can be achieved by varying the monomer ratios in lactide/glycolide copolymers: poly-L-lactic acid and poly-glycolic acid exhibit a high degree of crystallinity and degrade relatively slowly into shards. Copolymers of poly-L-lactic acid and Poly-glycolic acid are amorphous and rapidly degraded into a gel state. The advantage of the polyester urethane polymers over the polyester polymers is that the former degrade both into a gel state and are true surface-eroding polymer. As a consequence polyester urethanes have a preferred degradation state while retaining for a longer period the original patterns of the implant. However, there are application where each are preferred. The selection of the solvent for chemotaxic agents delivered on a resorbable polymer matrix depends on the desired mode of release of the chemotaxic agent. In the case of a totally resorbable device, a solvent is selected to deliver the chemotaxic agent alone and when delivered dissolves the deposited polymer matrix or is selected to contain a second polymer which is deposited along with the chemotaxic agent. In the first case, the printed chemotaxic droplet locally dissolves the underlying polymer matrix and begins to evaporate and thus is adherent to the surface of the immediate underlying polymer matrix layer. In the second case, the drug is effectively deposited in the a second polymer matrix after evaporation since the dissolved polymer is deposited along with the chemotaxic agent. The first case releases the chemotaxic agent rapidly and creates the highest concentration gradient when placed in vivo. The second case releases the chemotaxic agent more slowly since release depends in part of the resorption of the carrier polymer. In this second case, the concentration of chemotaxic agent is more uniform and constant over time. The solvent evaporation rate is primarily determined by the vapor pressure of the solvent. There is a range from one extreme over which the polymer is very soluble, for example, 30 weight percent solubility, which allows the polymer to dissolve very quickly, during the time required to print one layer, as compared with lower solubilities. The degree to which prior layers are dissolved during application of a subsequent layer depends on the solubility of the polymer in the solvent. Fine fibers are more completely dissolved than fibers with larger diameters. Polymer Concentration In general, microstructural element are a resorbable polymer such as polyester urethane or polyester of molecular weight 5,000-200,000, in a solvent such as chloroform or a mixture of chloroform and a less-volatile solvent such as ethyl acetate to minimize warping. The surface energy of these can be varied by varying the proportion of hydrophilic and hydrophobic blocks in the polymer. Alternatively, a different polymer may be used such as poly-lactic acid, poly-glycolic acid or polycaprolactone. The polymer concentration in a microstructural element solution will generally be at the limit of what can be accommodated by the nozzle, both to maximize the amount of solid polymer delivered and to minimize migration of the solvent away from the point of application in the formation of a patterned implant. Reduced solvent migration increases the resolution of the microstructural elements of prior deposited layers, e.g., reduces swelling or geometrical slumping. The upper limit of polymer concentration is 15% for poly-L-lactic acid of 100,000 MW. This concentration of polymer may in some cases make printing of commercially viable devices impossible. The cases where the polymer is sparingly soluble, a filler may be used. Microstructural element volume can be increased by including small crosslinked or otherwise less soluble particles in the printing solution. For example, polyglycolic acid is not soluble in chloroform or ethyl acetate. Nanoparticles of crosslinked polyester urethane can be included in the printing solution (particles up to microns in diameter can be accommodated through most nozzles) to increase the polymer content which is printed. The amount of matter which is printed into the implant can also be increased by including small inorganic particles in the polymer solution, for example, bone derived apatite. Manufacturing Methods A number of processes are known for preparing microstructured molds or extrusion surfaces useful in manufacturing textured polymeric surfaces, e.g., mechanical machining, various lithography techniques, and three-dimensional printing. Suitable manufacturing devices include both those with a continuous jet stream print head and a drop-on-demand stream print head. In the former case, a line of polymer is directed. In the second case, a drop of polymer is directed. Pointwise construction of microstructures is preferred. A high speed printer of the continuous type, for example, is the Dijit printer made and sold by Diconix, Inc., of Dayton, Ohio, which has a line printing bar containing approximately 1,500 jets which can deliver up to 60 million droplets per second in a continuous fashion and can print at speeds up to 900 feet per minute. Both raster and vector apparatuses can be used. A raster apparatus is where the printhead goes back and forth across the bed with the jet turning on and off. This can have problems when the material is likely to clog the jet upon settling. A vector apparatus is similar to an x-y printer. Although potentially slower, the vector printer may yield a more uniform finish. The object of three-dimensional printing is to create a solid state object by ink-jet printing a binder into selected areas of sequentially deposited layers of powder. In the present disclosure, this process is modified in that powder is not required. The drop or line that is initially liquid becomes a volumetric solid when deposited on a surface. In this sense, the process is more like ink in an ink-jet printing process, where a third dimension is created by the creation of successive layer of deposited polymer. Instructions for each layer can be derived directly from a computer-aided design (CAD) representation of the patterned implant. The area to be printed is obtained by computing the area of intersection between the desired plane and the CAD representation of the object. A first layer is joined to a second layer by the liquid state of the polymer being deposited during the time of creation of the second layer. The liquid state of the second layer partially melts or dissolves into the first solid layer to form the three dimensional structure in successive layers. While the layers become hardened or at least partially hardened as each of the layers is laid down, once the desired final implant configuration is achieved and the layering process is complete, in some applications it may be desirable that the form and its contents be heated or cured at a suitably selected temperature to further promote binding of the discrete lines or drops. Construction of a three-dimensional component by printing can be viewed as the knitting together of structural elements, e.g., drops or lines. These elements are called microstructural primitives. The dimensions of the primitives determine the length scale over which the microstructure can be varied. Thus, the smallest region over which the surface energy of the patterned implant can be varied has dimensions near that of individual microstructural primitives. Droplet primitives have dimensions that are very similar to the width of line primitives, the difference is whether the material is laid down in a continuous line or discrete drops. The dimensions of the line primitive depend on the polymer viscosity and surface tension. A line primitive of 10 micron width is in certain cases possible, more typically the dimension is 40-60 microns. Higher print head velocities and lower polymer viscosity produce finer lines. When solvents are used, the drying rate is an important variable in the production of patterned implants by three-dimensional printing. Very rapid drying of the solvent tends to cause warping of the printed component. Much, if not all, of the warping can be eliminated by choosing a solvent with a low vapor pressure. For example, patterned implants prepared by printing with a solution of polymer and chloroform have nearly undetectable amounts of warpage, while large parts made with methylene chloride exhibit significant warpage. It has been found that it is often convenient to combine solvents to achieve minimal warping and adequate bonding between the particles. Thus, an aggressive solvent can be mixed in small proportions with a solvent with lower vapor pressure. Bioactive Agents There are essentially no limitations on the bioactive agents that can be incorporated into the patterned implants of the present invention, although those agents which produce a chemotaxic effect are most desirable in wound healing or tissue scaffolding applications. Bioactive agents need not be incorporated as a liquid, they can be processed into particles using spray drying, atomization, grinding, or other standard methodology, or those agents which can be formed into emulsifications, microparticles, liposomes, or other small particles, and which remain stable chemically and retain biological activity in a polymeric matrix, are useful. Examples of chemotaxic agents generally include proteins and peptides, nucleic acids, polysaccharides, nucleic acids, lipids, and non-protein organic and inorganic compounds. Examples of other bioactive agents have biological effects including, but not limited to, anti-inflammatories, antimicrobials, anticancer, antivirals, hormones, antioxidants, channel blockers, and vaccines. It is also possible to incorporate materials not exerting a biological effect such as air, radiopaque materials such as barium, or other imaging agents. In a preferred embodiment for tissue regeneration matrices, cell growth, differentiation, and/or migration modulators are incorporated into specific regions of the device at the same level of resolution as the pores and channels. These may act in combination with surface texture, surface energy, and overall shape and distribution of the microstructural elements to achieve an extracellular matrix mimic with controllable tissue directing functionality. Of particular interest are surface-active agents which promote cell adhesion, such as an RGD peptide, or a material which inhibits cell adhesion, such as a surfactant, for example, polyethylene glycol or a Pluronic (polypropylene oxide-polyethylene oxide block copolymers). For example, it may be desirable to incorporate adhesion peptides such as the RGD adhesion peptide into certain channels (e.g., those for blood vessel ingrowth). An adhesion peptide, such as the peptide having a hydrophobic tail marketed by Telios (La Jolla, Calif.) as Peptide, can be dissolved in water and deposited onto the surfaces of pores in the patterned implant. The surface can be modified to prevent cellular adhesion. This may be desirable to prevent excessive soft connective tissue ingrowth into the device from the surrounding tissue, and can be accomplished, for example, by depositing an aqueous solution of a pluronic or poloxamer in the voids. The hydrophobic block of such copolymers will adsorb to the surface of the channels, with the hydrophilic block extending into the aqueous phase. Surfaces with adsorbed pluronics resist adsorption of proteins and other biological macromolecules. In certain embodiments, the patterned implant can contain one or more of bioactive substance(s) including, but are not limited to, hormones, neurotransmitters, growth factors, hormone, neurotransmitter or growth factor receptors, interferons, interleukins, chemokines, cytokines, colony stimulating factors, chemotactic factors, extracellular matrix components, and adhesion molecules, ligands and peptides; such as growth hormone, parathyroid hormone (PTH), bone morphogenetic protein (BMP), transforming growth factor-.alpha. (TGF-.alpha.), TGF-.beta.1, TGF-.beta.2, fibroblast growth factor (FGF), granulocyte/macrophage colony stimulating factor (GMCSF), epidermal growth factor (EGF), platelet derived growth factor (PDGF), insulin-like growth factor (IGF), scatter factor/hepatocyte growth factor (HGF), fibrin, collagen, fibronectin, vitronectin, hyaluronic acid, an RGD-containing peptide or polypeptide, an angiopoietin and vascular endothelial cell growth factor (VEGF). For example, the patterned implant can include a biologically effective amount of VEGF. Applications Using Microstructure Implants In certain embodiments, the patterned implant of the present disclosure can be implanted in a human subject. For example, in certain embodiments, the patterned implant of the present disclosure can be implanted in a subject by suturing the patterned implant to fat pads or muscle tissue in the lower abdomen. In certain embodiments, the patterned implant of the present disclosure can be used to enhance vascularization in ischemic settings, such as, by acting as an angiogenic tissue scaffold to promote neovascularization and ultimately increase blood flow to regions of tissues that are not receiving sufficient blood supply. In certain embodiments, the patterned implant of the present disclosure can be implanted in a region of a subject that requires an increase in blood flow. For example, the patterned implant can be implanted in and/or near an ischemic tissue. In certain embodiments, the patterned implant can be implanted to treat cardiac ischemia. The patterned implant can be implanted to revascularize from healthy coronary circulation or neighboring non-coronary vasculature. In certain embodiments, the patterned implant of the present disclosure can be used as a novel adjunct to coronary artery bypass grafting (CABG) in addressing cardiac ischemia. In certain embodiments, during CABG surgery, a surgeon can apply the patterned implant of the present disclosure across regions of incomplete reperfusion. For example, the patterned implant can be placed in order to revascularize from healthy coronary circulation or neighboring non-coronary vasculature (such as circulation from the left internal mammary artery) into the ischemic zone unlikely to be addressed by the CABG procedure. In certain embodiments, the patterned implant can be used to direct neovascularization around a section of an artery subject to reduced blood flow or occlusion. In this case, the patterned implant can be used to promote revascularization of a region of ischemic myocardium in addition to a CABG procedure. In many patients that suffer from acute myocardial ischemia and in another even larger cohort of patients with untreatable coronary disease, there remain areas of viable heart that do not naturally revascularized but can be revascularized by an angiogenic tissue scaffold. In certain embodiments, the patterned implant can potentially revascularize those inaccessible ischemic zones in these patients. The selection of an alternating hydrophobic/hydrophilic arrangement of fibers of the patterned implant can stimulate and spatially direct revascularization by directing blood flow from nearby unobstructed coronary vasculature to around and beyond a coronary obstruction leading to micro-perfused distal myocardium to protect cardiomyocytes viability and function. The patterned implant of the present disclosure can enhance neovascularization as well as influence vascular architecture through two potential mechanisms. The patterned implant can be incorporated into existing capillary beds to increase blood flow. Second, the patterned implant can deliver extracellular matrix constituents and secrete growth factors into tissue thereby providing a microenvironment that promotes angiogenesis. The patterned implant of the present disclosure is capable of enhancing neovascularization by spatially guiding the invading sprouts of an angiogenic capillary network upon implantation, without incorporation into the nascent vessels. The patterned implant of the present disclosure can be used in conjunction with various types of engineered tissue constructs to aid in the vascularization of ischemic tissue. In certain embodiments, the patterned implants of the present disclosure can be useful in other applications in which it would be beneficial to have an engineered material to aid in spatially guiding the direction of host cell and tissue invasion. Such applications can include, but are not limited to, nerve regeneration. In certain embodiments, the patterned implant can be seeded with a heterotypic cell suspension. For example, for nerve regeneration applications, the cell suspension can include neurons, neuronal stem cells, or cells that are associated with supporting neuronal function, or a combination thereof. In certain embodiments, the patterned implant can be used at a site of tissue damage, e.g., neuronal tissue damage. In certain embodiments, the patterned implant of the present disclosure can allow for maintenance of the viability and proper function of a surgical repair site. For example, the patterned implant can allow for maintenance of the viability and proper function of muscle tissue surrounding a hernia repair. In certain embodiments, the patterned implant of the present disclosure can enhance wound healing. In certain embodiments, the patterned implants can be useful in the treatment of chronic wounds such as, for example, diabetic foot ulcers. Additionally, the patterned implant of the present disclosure can be useful in the treatment of wounds sustained during military combat. In certain embodiments, the patterned implant can be implanted in a subject to treat peripheral vascular disease, diabetic wounds, and clinical ischemia. In certain embodiments, the patterned implant of the present disclosure can be used to enhance repair of various tissues. Examples of tissues that can be treated by the patterned implant of the present disclosure includes, but is not limited to, skeletal muscle tissue, skin, fat tissue, bone, cardiac tissue, pancreatic tissue, liver tissue, lung tissue, kidney tissue, intestinal tissue, esophageal tissue, stomach tissue, nerve tissue, spinal tissue, and brain tissue. In certain embodiments, a method of vascularizing a tissue of a subject includes providing a patterned implant comprising endothelial cells organized along lines and implanting the patterned implant into a tissue of the subject, wherein the implant promotes increased vascularity and perfusion in the subject. To facilitate a better understanding of the present disclosure, the following examples of certain aspects of some embodiments are given. In no way should the following examples be read to limit, or define, the entire scope of the disclosure. Example 1: Polymer Polymers suitable for constructing patterned implants of the present disclosure are preferably absorbable in situ. Polyester Urethanes are polyurethanes copolymerized with a lactide diol. Preparation of Lactide Diol The raw materials: Compound Source 1,6-Hexanediol Acros Toluene Acros D,L-Lactide SAFC L,L-Lactide Aldrich Tin-ethylhexanoate Sigma Aldrich Chloroform Sigma Aldrich Diethylether Sussmann This procedure is to be performed in closed vessels purged continuously with cryogenically distilled (dry) argon or nitrogen. 30 grams of 1,6-hexanediol is to be placed in 600 ml of toluene in a graduated 2 Liter flat bottom flask equipped with a magnetic stir rod. The flask is to be capped with a 2-hole stopper, one hole equipped with an input conduit and the other hole equipped with an output conduit connected to an oil trap (to prevent back flow of water vapor). The input conduit is to be connected to the nitrogen source and nitrogen flowed at approximately 5 Liters per hour. The flask is to be placed on a magnetic stirrer/hot top combination. The toluene solution is to be stirred while raising the solution temperature to 70° C., and thereafter in 10° C. increments until the hexanediol is completely dissolved. Upon dissolution, the solution volume is to be noted. Temperature and nitrogen flow is to be continued until the solution volume drops by 150 ml. Temperature can be raised to 130° C. to facilitate toluene vaporization. A sample of the solution is to be retrieved by syringe (to avoid contact with humid air), and the toluene removed by vacuum evaporation. A Karl Fischer water content measurement is to be performed on the solid hexanediol. The above distillation procedure is to be continued until the water content is <300 ppm H2O by weight. The solution is to be cooled and stored under nitrogen. Using the above setup, 150 grams of D,L-lactide and 150 grams of L,L-lactide are to be dissolved in 1750 ml of toluene by heating to 115° C., while stirring under nitrogen flow. Upon dissolution the solution volume is to be noted and the temperature is to be raised to 130° C. The nitrogen flow is to be continued until 400 ml of toluene is removed. A sample of the solution is to be retrieved by syringe (to avoid contact with humid air), and the toluene removed by vacuum evaporation. A Karl Fischer water content measurement is to be performed on the solid hexanediol. The above distillation procedure is to be continued until the water content is <300 ppm H2O by weight. The solution is to be cooled and stored under nitrogen. Weigh an appropriately sized flask (4 L). Note flask weight, preferably the weight includes closure means or the stopper with closed conduits disconnected. The hexanediol and lactide solutions are to be combined in the weighed flask, connected to nitrogen flow and stirred. The combined solution is to be heated in 10° C. increments to 70° C. After 15 minutes, 600 mg of tin ethylhexanoate is to be added drop-wise using a 1 cc syringe, while stirring vigorously. The temperature of the solution is to be raised to 120° C. in 10° C. increments. [If a temperature controlled heating mantle is used, the temperature rise will be sufficiently slow that the 10° C. heating increment can be ignored.] Turn off the nitrogen flow while keeping conduits connected such that the solution volume is closed from contact with air. While stirring and heating, react for 5 hours. Add an additional 400 mg of tin ethylhexanoate. Flush with nitrogen. Continue for an additional 3 hours. Add an additional 400 mg of tin ethylhexanoate. Flush with nitrogen. Continue for an additional 11 hours at 120° C. Reduce solution temperature to 70° C. Connect the output port of the oil trap to a vacuum source. Stop stirring and heat until toluene is removed. Discontinue vacuum. Add 800 ml of dry chloroform flush with nitrogen, stir at 70° C. until the solid is completely dissolved. The resulting turbid solution is to be filtered using a 0.2 micron PTFE filter. Remove the solvent from the filtrate under vacuum. A sample of the dried solid is to be measured for water content using Karl-Fischer. The water content is to be <300 ppm. If not within this specification, the solid can be dried by chloroform distillation. Preparation of Polyester Urethane Raw Materials Compound Amount of substance IPDI (Isophorone diisocyanate) 202.9 mmol 1,4-Butanediol 142.8 mmol Toluene 2000 mL Dibutyltin dilaurate 11.6 mmol PTMG 2000 (Terathane 2000) 20.1 mmol PLA Diol AP1756 40.3 mmol All operations are to be performed under nitrogen and dry solvents. Suggested Equipment: A 2 Liter, four-port graduated glass reactor with central port for introduction of motor propelled stir rod is recommended. The stir rod is preferably multi-tier with angled blades to avoid laminar mixing. The reactor is to be equipped with a heating mantle fitted with a thermocouple and a programmable temperature controller. [Preferably, the mantle has cooling capability as well, in which a fluid filled mantle is used in conjunction with a circulating control unit.] Preferably the reaction volume is not exposed to the thermocouple, but rather the thermocouple is embedded in the heating mantle. Due to the high viscosity of the final product and need for rapid and complete mixing, use of a magnetic stir rod is discouraged. The two free ports are to be equipped with conduits for delivery and removal of nitrogen. The output port is to be connected to an oil trap to prevent backflow of water vapor. Ideally the conduits contain valves to provide for transport of the reaction volume without exposure to air. The last port, the diagnostic port, is to be used for addition and retrieval of reaction volume. The nitrogen atmosphere should be delivered at positive partial pressure to compensate for the external stirring means and periodic opening of the diagnostic port. The partial pressure is indicated by the observation of nitrogen bubbles in the oil trap, and the rate of their creation can be used to set and maintain a reasonable nitrogen flow rate. Purge the reactor with nitrogen. Add 40.32 grams of PLA diol, obtained from the procedure above and 40.11 grams of Terathane 2000 and 810 ml of toluene using the above setup. Set the stir rate to 100 cycles per minute. The dissolution is accomplished by heating to 115° C., while stirring under nitrogen flow. Upon dissolution the solution volume is to be noted and the temperature is to be raised to 130° C. The nitrogen flow is to be continued until 200 ml of toluene is removed. Cool the reactor to 15° C. (or room temperature, if the mantle is not equipped with coolant). While stirring, add via the diagnostic port and under nitrogen flow, 30 ml toluene followed by 45.09 grams of IPDI. Stir for 30 minutes. Add drop wise, 6.74 ml dibutyltin dilaurate. Using the diagnostic port, remove a sample of the solution to measure the % NCO. The % NCO can be measured using dibutylamine back titration. By this method, it is traditional to take at least 3 NCO measurements, or you may do so until a desired standard deviation is obtained. Raise the temperature of the reactor to 75° C. React the mixture under nitrogen flow for 4 hours at 75° C. Take an NCO. React for another 1 hour, take an NCO. If the NCO at 5 hours is less than 95% of the measurement at 4 hours, continue to react for 1 hour durations until the NCO change is less than 5% between consecutive measurements. Using the setup of the preparation of the PLA diol, dissolve 12.872 g of butanediol in 230 ml of dry toluene. Dissolution is accomplished by heating to 75° C. Add the butanediol solution to the reactor. React the mixture under nitrogen flow for 9 hours at 75° C. Take an NCO. React for another 1 hour, take an NCO. If the NCO at 10 hours is less than 95% of the measurement at 9 hours, continue to react for 1 hour durations until the NCO change is less than 5% between consecutive measurements. During the course of this procedure, toluene may be added to reduce the viscosity of the reactant and improve mixing. Considerable torque can develop during this reaction. When the NCO has stabilized [this should be reproducible from batch to batch, if not water is entering the system], decant the reaction volume to a vacuum chamber. This is easier performed if the reaction volume is still hot. Apply vacuum and remove the toluene, and the resulting solid is to be dissolved in 1000 ml THF. The polymer is the precipitated in 15 L of pentane, filtered and repeated washed with pentane and dried under vacuum at 50° C. n-Pentane can be obtained from Acros and was used after redistillation and THF (also from Acros) was used as received. The resulting polyester urethane has a melt temperature of 132° C. and is soluble in most solvents, for example toluene and acetone. Example 2: Bioactive All of the synthesis that is detailed below are to be performed in a hermetically sealed glass reactor equipped with a stir rod and temperature controlled jacket. The headspace of the reactor is to be continuously flushed with dry nitrogen unless otherwise specified. Example 2a: Preparation of a Polyester Diisocyanate In this example a castor-derived hydroxyl-terminated ricinoleate derivative is used as the diol. One equivalent of polycin D-265 (212 g) is combined with 2 equivalent of toluene diisocyanate (174 g) at room temperature (22° C.). The mixture is stirred at 100 revolutions per minute and the temperature monitored. The mixture will begin to heat up by exothermic reaction and no heat is to be applied to the reactor until the temperature in the reactor ceases to rise. Then the mixture temperature should be increased in 5° C. increments per ½ hour until the mixture reaches 60° C. The reaction should be continued until the % NCO=10.9%. The target % NCO is reached when every hydroxyl group in the mixture is reacted with an NCO group. Ideally, the result is a single diol endcapped with two diisocyanates. This outcome can be enhanced by slow addition of the diol to the diisocyanate. The addition should be in 10 g increments, added when the exotherm from the previous addition has ceased. However, chain extended variations of the above ideal outcome are useful, their primary disadvantage being that the product is slightly higher in viscosity. The ideal % NCO is calculated by dividing the weight of the functional isocyanate groups (2×42 Dalton) per product molecule by the total weight of the product molecule (424 Dalton+2×174 Dalton) yielding approximately 10.9%. Alternatively, a lower molecular weight diol may be used, such as polycin D-290 where 1 equivalent of polycin D-290 is 193 g and the target % NCO is 84/(386+348)=11.4%. Alternatively, a higher molecular weight diol may be used, such as polycin D-140 where 1 equivalent of polycin D-140 is 400 g and the target % NCO is 84/(800+348)=7.3%. All polycin diols are available from Performance Materials (Greensboro, N.C.) and toluene diisocyanate is available from Sigma-Aldrich (Milwaukee, Wis.). Example 2b: Preparation of a Polyether Diisocyanate In this example a polyether hydroxyl-terminated copolymer of 75% ethylene oxide and 35% propylene oxide is used as the diol. One equivalent of UCON 75-H-450 (490 g) is combined with 2 equivalent of toluene diisocyanate (174 g) at room temperature (22° C.). The mixture is stirred at 100 revolutions per minute and the temperature monitored. The mixture will begin to heat up by exothermic reaction and no heat is to be applied to the reactor until the temperature in the reactor ceases to rise. Then the mixture temperature should be increased in 5° C. increments per ½ hour until the mixture reaches 60° C. The reaction should be continued until the % NCO=10.9%. The target % NCO is reached when every hydroxyl group in the mixture is reacted with an NCO group. Ideally, the result is a single diol endcapped with two diisocyanates. This outcome can be enhanced by slow addition of the diol to the diisocyanate. The addition should be in 10 g increments, added when the exotherm from the previous addition has ceased. However, chain extended variations of the above ideal outcome are useful, their primary disadvantage being that the product is slightly higher in viscosity. The ideal % NCO is calculated by dividing the weight of the functional isocyanate groups (2×42 Dalton) per product molecule by the total weight of the product molecule (980 Dalton+2×174 Dalton) yielding approximately 6.3%. Polyether copolymers of ethylene oxide and propylene oxide diols are available from Dow Chemical (Midland, Mich.). Example 2c: Preparation of a Polyester Triisocyanate In this example a castor-derived hydroxyl-terminated ricinoleate derivative is used as the triol. One equivalent of polycin T-400 (141 g) is combined with 2 equivalent of toluene diisocyanate (174 g) at room temperature (22° C.). The mixture is stirred at 100 revolutions per minute and the temperature monitored. The mixture will begin to heat up by exothermic reaction and no heat is to be applied to the reactor until the temperature in the reactor ceases to rise. Then the mixture temperature should be increased in 5° C. increments per ½ hour until the mixture reaches 60° C. The reaction should be continued until the % NCO=13.3%. The target % NCO is reached when every hydroxyl group in the mixture is reacted with an NCO group. Ideally, the result is a single diol endcapped with two diisocyanates. This outcome can be enhanced by slow addition of the diol to the diisocyanate. The addition should be in 10 g increments, added when the exotherm from the previous addition has ceased. However, chain extended variations of the above ideal outcome are useful, their primary disadvantage being that the product is slightly higher in viscosity. The ideal % NCO is calculated by dividing the weight of the functional isocyanate groups (2×42 Dalton) per product molecule by the total weight of the product molecule (282 Dalton+2×174 Dalton) yielding approximately 13.3%. The above reaction will yield a viscous product. A less viscous product can be obtained by adding propylene carbonate to the initial mixture. Additions up to 100% by weight of propylene carbonate are useful. Adjustment to the target NCO of the mixture must be performed using standard methods, or the propylene carbonate may be added after reaching the target % NCO. Propylene carbonate is available from Sigma-Aldrich (Milwaukee, Wis.). Example 2d: Preparation of a Polyether Triisocyanate In this example a polyether hydroxyl-terminated copolymer of 75% ethylene oxide and 35% propylene oxide is used as the triol. One equivalent of Multranol 9199 (3066 g) is combined with 3 equivalent of toluene diisocyanate (261 g) at room temperature (22° C.). The mixture is stirred at 100 revolutions per minute and the temperature monitored. The mixture will begin to heat up by exothermic reaction and no heat is to be applied to the reactor until the temperature in the reactor ceases to rise. Then the mixture temperature should be increased in 5° C. increments per ½ hour until the mixture reaches 60° C. The reaction should be continued until the % NCO=1.3%. The target % NCO is reached when every hydroxyl group in the mixture is reacted with an NCO group. Ideally, the result is a single diol endcapped with two diisocyanates. This outcome can be enhanced by slow addition of the diol to the diisocyanate. The addition should be in 10 g increments, added when the exotherm from the previous addition has ceased. However, chain extended variations of the above ideal outcome are useful, their primary disadvantage being that the product is slightly higher in viscosity. The ideal % NCO is calculated by dividing the weight of the functional isocyanate groups (3×42 Dalton) per product molecule by the total weight of the product molecule (9199 Dalton+3×174 Dalton) yielding approximately 1.3%. Multranol 9199 is available from Bayer (Pittsburgh, Pa.). Example 2e: Preparation of a Polyol Triisocyanate from Polyol Diol Any of the diisocyanates prepared in Examples 2a and 2b can be trimerized by the addition of a low molecular weight triol such as polycin T-400 or trimethylolpropane (TMP). In this example TMP is used, but the method is adaptable to any triol. Complete trimerization of the diisocyanates of Example 2a and 2b will result in viscous products. To yield a lower viscosity product propylene carbonate can be employed or less triol can be used. In the later case, a mixture of diisocyanate and triisocyanate is obtained. In this example the product of Example 2b is used as the polyether diisocyanate. One equivalent of Example 2b (682 g) is combined with 0.1 equivalent TMP (44.7 g) at room temperature (22° C.). The mixture is stirred at 100 revolutions per minute and the temperature monitored. The mixture will begin to heat up by exothermic reaction and no heat is to be applied to the reactor until the temperature in the reactor ceases to rise. Then the mixture temperature should be increased in 5° C. increments per ½ hour until the mixture reaches 60° C. The reaction should be continued until the % NCO=5.8%. The target % NCO is reached when every hydroxyl group in the mixture is reacted with an NCO group. The ideal % NCO is calculated by dividing the weight fraction of the functional isocyanate groups 10%(3×42 Dalton) and 90% (2×42) per product molecule by the total weight fraction of the product molecule (3×1364 Dalton+134 Dalton)+1364 yielding approximately 0.3%+5.5%=5.8%. TMP is available from Sigma-Aldrich (Milwaukee, Wis.). Example 2f: Preparation of a Modified Boswellia Extract Using the Triisocyanate of Example 2d The hydroxyl number of Boswellia extract will vary depending on extraction method, species of Boswellia extracted, and even variations within species. The goal is to obtain a product with no NCO functionality, so all reaction mixtures should be reacted until the final % NCO=0. In this example the product of Example 2d is used as the polyether triisocyanate mixture. One hundred grams of Example 4 is combined with 1 g of Boswellia extract at room temperature (22° C.) under 90% nitrogen and 10% nitric oxide atmosphere. The mixture is stirred at 100 revolutions per minute and the temperature monitored. The mixture will begin to heat up by exothermic reaction. When the temperature ceases to rise, a % NCO reading is taken. If % NCO>0 then an additional 1 g of Boswellia extract is to be added. By a series of Boswellia addition one calculates the change in % NCO as a function of 1 g additions of Boswellia extract, a linear plot is obtained from which the total amount of Boswellia extract addition necessary to bring the % NCO to zero is obtained. This amount of Boswellia extract is added to the mixture and the mixture is reacted so that % NCO=0 is obtained. Example 2g: Preparation of a Modified Boswellia Extract Using the Triisocyanate/Diisocyanate of Example 2e The hydroxyl number of Boswellia extract will vary depending on extraction method, species of Boswellia extracted, and even variations within species. The goal is to obtain a product with no NCO functionality, so all reaction mixtures should be reacted until the final % NCO=0. In this example the product of Example 2e is used as the polyether diisocyanate/triisocyanate mixture. One hundred grams of Example 2e is combined with 1 g of Boswellia extract at room temperature (22° C.) under 90% nitrogen and 10% nitric oxide atmosphere. The mixture is stirred at 100 revolutions per minute and the temperature monitored. The mixture will begin to heat up by exothermic reaction. When the temperature ceases to rise, a % NCO reading is taken. If % NCO>0 then an additional 1 g of Boswellia extract is to be added. By a series of Boswellia addition one calculates the change in % NCO as a function of 1 g additions of Boswellia extract, a linear plot is obtained from which the total amount of Boswellia extract addition necessary to bring the % NCO to zero is obtained. This amount of Boswellia extract is added to the mixture and the mixture is reacted so that % NCO=0 is obtained. Example 2h: Preparation of a Highly-Branched Modified Boswellia Extract with Absorbable Links Diol and triol can be combined to form a multi-branch polymer. In this instance, the Multranol 9199 triol is chain extended with polycin D-265 diol. The diisocyanate form of Example 2 is useful in chain extending the triisocyanate form of Example 4. We wish to have on average 2 diisocyanates for every 3 triisocyanates, which forms a 5 armed isocyanate. In this example 0.09 equivalents (292 g) of Example 2d is mixed with 0.04 equivalents (26.6 g) of Example 2b. The triisocyanates of Example 2d and diisocyanates of Example 2b are chain extended with 0.08 equivalents lysine diamine to form a 5 armed isocyanate. One hundred grams of this reaction product is combined with 1 g of Boswellia extract at room temperature (22° C.) under 90% nitrogen and 10% nitric oxide atmosphere. The mixture is stirred at 100 revolutions per minute and the temperature monitored. The mixture will begin to heat up by exothermic reaction. When the temperature ceases to rise, a % NCO reading is taken. If % NCO>0 then an additional 1 g of Boswellia extract is to be added. By a series of Boswellia addition one calculates the change in % NCO as a function of 1 g additions of Boswellia extract, a linear plot is obtained from which the total amount of Boswellia extract addition necessary to bring the % NCO to zero is obtained. This amount of Boswellia extract is added to the mixture and the mixture is reacted so that % NCO=0 is obtained. Lysine diamine is available from Sigma-Aldrich (Milwaukee, Wis.). Thus, although there have been described particular embodiments of the present invention of a new and useful Device with Microstructure Mediated Absorption Profile it is not intended that such references be construed as limitations upon the scope of this invention except as set forth in the following claims. | 63,536 |
11857701 | DETAILED DESCRIPTION OF THE INVENTION While the making and using of various embodiments of the present invention are discussed in detail below, it should be appreciated that the present invention provides many applicable inventive concepts that can be embodied in a wide variety of specific contexts. The specific embodiments discussed herein are merely illustrative of specific ways to make and use the invention and do not delimit the scope of the invention. To facilitate the understanding of this invention, a number of terms are defined below. Terms defined herein have meanings as commonly understood by a person of ordinary skill in the areas relevant to the present invention. Terms such as “a”, “an” and “the” are not intended to refer to only a singular entity, but include the general class of which a specific example may be used for illustration. The terminology herein is used to describe specific embodiments of the invention, but their usage does not delimit the invention, except as outlined in the claims. The instant invention describes a non-toxic anti-adhesion hydrogel barrier, particularly a barrier composed of non-synthetic, hydrophilic, biodegradable, biocompatible polysaccharides formed by constructing a unique interpenetrating, crosslinked network with a unique porosity, and also a method for preparing the same. The hydrogel barrier described herein solves the problems of a film, bulk sponge or nonwoven type anti-adhesion system, including adhesion to tissue or organs, physical strength, in vivo reposition flexibility, ease of handling (i.e., bending, folding, cutting, rolling, manipulating), and appropriate degradation timing. The highly hydrophilic, non-synthetic nature of the barrier of the present invention selectively inhibits fibroblast infiltration into a surgical microenvironment and because of its local anti-adhesive properties the barrier does not inhibit wound healing. The barrier of the present invention does not tear, break or stick to itself when folded or rolled and can be easily handled when using surgical instruments lending its use in a variety of operations. The unique features of the present invention are: (i) the barrier is comprised of tunable biopolymers for controllable mechanical robustness and degradation, (ii) barrier effectively reduces unwanted adhesions using non-synthetic components, and (iii) barrier has unique, controlled hierarchical porosity that can be backfilled with a variety of materials that may also be charged with small molecules (drugs, growth factors) to further inhibit unwanted response or to support healthy wound healing. No other technology has this combination of features. The unique benefits provided by the barriers described herein are (i) improved handling characteristics, for example the barrier is easily folded, cut, sutured, manipulated in biologically relevant conditions, (ii) persistence in desired area throughout healing duration, (iii) improved in vivo repositioning flexibility, and (iv) unique porous structure that exhibits a tunable release profile for material, small molecules or growth factors. No other methods in literature are similar to the technique presented herein. Current anti-adhesion technologies are described herein below U.S. Pat. No. 6,599,526 discloses a pericardial anti-adhesion patch comprising a collagenous material and a non-living cellular component for preventing adhesion during surgery. U.S. Pat. No. 6,566,345 discloses anti-adhesion compositions in the form of a fluid, gel or foam made of intermacromolecular complexes of polysaccharides such as carboxyl-containing polysaccharides, polyethers, polyacids, polyalkylene oxides, etc., and synthetic polymers. Korean Patent Publication No. 2003-0055102 discloses an anti-adhesion barrier for preventing inflammation and healing wounds comprising carboxymethylcellulose (CMC) and gellan gum. But, the anti-adhesion barriers in the form of a gel, fluid, foam, etc., are not accurately fixed at the wound site; they move downward because of gravity and, thus, are less effective in healing wounds and reducing adhesion. European Patent No. 092,733 discloses anti-adhesion barriers in the form of a membrane, gel, fiber, nonwoven, sponge, etc. prepared from crosslinking of carboxymethylcellulose (CMC) and polyethylene oxide (PEO). However, carboxymethylcellulose is less biocompatible than bio-originated materials. Since polyethylene glycol or other synthetic polymers are not biodegradable, only materials having a small molecular weight that are capable of being metabolized can be used. However, since materials having a small molecular weight are absorbed quickly, the role of the anti-adhesion barrier cannot be sustained sufficiently. U.S. Pat. No. 6,133,325 discloses membrane type anti-adhesion compositions made of intermacromolecular complexes of polysaccharides and polyethers. Korean Patent Publication No. 2002-0027747 discloses that a water-soluble polymer gel prepared from alternating copolymerization of a block copolymer of p-dioxanone and L-lactide with polyethylene glycol (PEG) can be utilized as an anti-adhesion barrier, drug carrier, tissue adhesive, alveolar membrane, etc. But, this gel type anti-adhesion barrier is also problematic in accurately fixing at wound sites as the abdominal internal organs or tissues are constantly moving. U.S. Pat. No. 6,630,167 discloses an anti-adhesion barrier prepared from crosslinked hyaluronic acid. Since hyaluronic acid is a polysaccharide found in animal and human tissues, it has superior biocompatibility. However, in an unmodified form, hyaluronic acid is degraded quickly, with a half life of only 1 to 3 days. This method in particular claims a crosslinking agent concentration of 10 to 80%, by weight, which is significantly greater than the 1% used in the presented technology. Crosslinking agents can be toxic at high concentrations and removing large concentrations of crosslinking agents can be difficult. U.S. Pat. No. 6,693,089 discloses a method of reducing adhesions using an alginate solution and Korean Patent Publication No. 2002-0032351 discloses a semi-IPN (semi-interpenetrating network) type anti-adhesion barrier using water-soluble alginic acid and CMC, in which alginates are selectively bound to calcium ions. However, these patents include ionically crosslinked alginate by calcium, which, when degraded quickly, releases a bulk charge of calcium ions into the surrounding tissues, further aggravating injured tissues. There is also the problem of non bio-material uses. There are publications regarding the treatment of cellulose acetate with siloxane. But, since celluloses are sensitive to pH, there is a difficulty in processing them. Also, although they are natural polymers, celluloses are not a constituent of the human body and are known to have the potential to cause a foreign body reaction. Furthermore, there remains the task of modifying their structure, e.g., through oxidation, so that they can be hydrolyzed inside the body. Anti-adhesion barriers that are currently on the market are in the form of a film, sponge, fabric, gel, solution, etc. In general, the film or sponge type is easier to fix at a specific site than the solution or gel type. Interceed™ from Johnson & Johnson is the first commercialized anti-adhesion barrier. It is a fabric type product made of ORC and adheres tightly to highly irregular organs or tissues. But, as mentioned earlier, ORC is a non-bio-oriented material and has poor biocompatibility. Also, because of a very large pore size, cells or blood proteins may easily penetrate the barrier, and the anti-adhesion barrier is deformed by external force during handling. Seprafilm is a film type anti-adhesion barrier made of HA and CMC by Genzyme Biosurgery. Seprafilm tends to roll when in contact with water and to be brittle when dry. Thus, wet hands have to be avoided and moisture should be minimized at the surgical site, which can be very difficult. HYDROSORB SHIELD® from MacroPore Biosurgery Inc., which is used for adhesion control in certain spinal applications, or SURGI-WRAP™ from Mast Biosurgery, USA which is used after open surgery, are transparent film type anti-adhesion barriers made of poly(L-lactide-co-D,L-lactide) (PLA, 70:30), a biodegradable polymer. With a long biodegradation period of at least 4 weeks and superior mechanical strength, they are known as easy-to-handle products. Films made of PLA or poly(glycolic acid) (PGA) are easy to roll to one side, but they do not adhere well to the three-dimensionally, highly irregular surfaces of organs or tissues. Also, since these materials are hydrophobic, they do not absorb moisture well, and, therefore, do not adhere well to the wet surface of organs or tissues. Also, when hydrolyzed in the body, these materials release acidic degradation products, which may cause further inflammation and adhesion. DuraGen® and DuraGen Plus® from Integra LifeSciences is a sponge type anti-adhesion barrier made of collagen from an animal source, which has been developed for surgery and neurosurgery. Since the collagen sponge absorbs moisture, it readily adheres to the surface of organs. However, these barriers have relatively weak physical strength and, because of excessive moisture absorption, tends to be too heavy to handle or transport to another site. In general, an anti-adhesion barrier has to satisfy the following requirements: i) infiltration or attachment of cells or blood should be avoided through precise control of pore size or use of materials non-adherent to blood or cells, ii) the anti-adhesion barrier should be able to be attached at the desired site for a specified period of time, iii) a foreign body reaction should be minimized to reduce inflammation, which is the cause of adhesion, iv) the biodegradation period should be able to be controlled, so that the barrier capacity can be sustained for a requisite period of time, v) the anti-adhesion barrier should be flexible and have superior mechanical properties, including tensile strength and wet strength, for ease of handling during surgery, and vi) there should be no deformation for a necessary period of time, because the wound should be covered exactly. Post-surgical adhesions tether tissues that should remain separate. Adhesions result from impaired autologous natural immune response. Surgical adhesions continue to plague the recovery period, with current technologies falling short of adhesion prevention. Incidence of adhesions following surgery is 80% (Yeo, 2007) resulting in chronic pain, limited motion, organ dysfunction, and even death (Cui et al., 2009). The healthcare costs associated with this are over $3.45 billion, annually (Wiseman, et al., 2010). Current approaches for preventing adhesions include better surgical practices (Holmdahl et al., 1997) (for e.g., powder free gloves, laparoscopic procedures, and reduction of dessication), biocompatible barrier devices (for e.g., polymer solutions, in situ crosslinkable hydrogels, pre-formed membranes), and pharmacotherapy agents like steroidal anti-inflammatory drugs (Dexamethasone; progesterone; hydrocortisone; prednisone), non-steroidal anti-inflammatory drugs (Ibuprofen; flurbiprofen; indomethacin; tolmetin; nimesulide), inhibitors of proinflammatory cytokines (Antibodies to transforming growth factor (TGF)-b1), antihistamine (Diphenhydramine; promethazine), free radical scavengers (Melatonin; vitamin E; superoxide dismutase), Anticoagulants (heparin), proteolytic agents (tissue-type plasminogen activator; streptokinase; urokinase; pepsin; trypsin; Neurokinin 1 receptor antagonist), and antiproliferative agents (mitomycin). The most effective anti-adhesion barrier on the market reduces adhesion formation by only 50%. Many products are based on synthetic materials because of superior handling capabilities and low manufacturing costs. However, these synthetic materials are rendered ineffective in the presence of blood or blood proteins. The invention presented herein addresses the problems listed above and provides an effective method of blocking the infiltration of unwanted inflammatory response while maintaining robust mechanical properties for surgical handling. Because the present invention is constructed of natural materials, the risk of further aggravation is minimized, while blood and blood proteins will not adhere. Barriers on the market made from natural materials also degrade too quickly, allowing for adhesion formation. The present technology has a tunable degradation rate so that the barrier persists during the healing process. Current products on the market that are most effective have poor handling properties. They are brittle when dry and are rendered inapplicable when wet. In an OR environment, a suitable solution would be able to maintain mechanical integrity when wet. The present invention offers superior handling properties when wet including in vivo repositioning capabilities and suturability. The present invention describes the development of composite, dual-functioning materials to be placed at the interface between healing tissues and the surrounding tissues. The invention improves upon anti-adhesive biomaterial barriers, to aid in wound healing, and to modulate the inflammatory response. The present inventors have develop and characterize anti-adhesive HA-based material (biocompatible, non-immunogenic, non cell-adhesive, inhibits protein absorption, mechanically stable, cost effective, clinically sized, and appropriate degradation rate). In addition the present inventors have developed a bilayer biofunctionalized HA-based film that is biocompatible, bioabsorbable, non-immunogenic, dual functioning, regenerative, anti-adhesive, mechanically stable, cost effective, and clinically sized. Finally, they develop an injectable solution version of anti-adhesive film that is biocompatible, effective at reducing adhesions, encapsulates ibuprofen or tranexamic acid and has tunable release rates. Hydrogels are generally polymer chain networks that are water-insoluble, but that absorb water. Often described as being “superabsorbent,” hydrogels are able to retain up to 99% water and can be made from natural or synthetic polymers. Often, hydrogels will have a high degree of flexibility due to their high water content. Common uses for hydrogels include: sustained drug release, as scaffolds (e.g., in tissue engineering), as a thickening agent, as a biocompatible polymer, in biosensors and electrodes and for tissue replacement applications. Natural hydrogels may be made from agarose, methylcellulose, hyaluronic acid (HA), and other naturally-derived polymers. HA is a linear polysaccharide with repeating disaccharide units composed of sodium D-glucuronate and N-acetyl-D-glucosamine. This naturally occurring glycosaminoglycan is a component of skin, synovial fluid, and subcutaneous and interstitial tissues. HA is metabolically eliminated from the body, and plays a role in protecting and lubricating cells and maintaining the structural integrity of tissues. Anionic carboxylic groups immobilize water molecules giving HA its viscoelastic and anti cell-adhesive properties. HA has been used in a variety of material designs for the prevention of postsurgical tissue adhesion. HA has been used as a dilute solution, a crosslinked hydrogel, or combined with CMC into sheets. HA is biocompatible, bioabsorbable/non-immunogenic (non-animal), very non-cell adhesive, polyanionic, hydrophilic, antifibrotic (1% HMW HA, Massie, 2005), pro-angiogenic and has been shown to reduce adhesion formation in animals and humans (Zawaneh, 2008; Diamond, 2006; Wiseman, 2010; Rajab, 2010). HA is clinically used to reduce adhesions: Seprafilm®, most effective and widely used anti-adhesion barrier on the market. Alginic acid is biocompatible, bioabsorbable/non-immunogenic (non-animal) (Skjak-Braek, 1992), very non-cell adhesive, polyanionic, hydrophilic, cost effective, abundant (brown seaweed), mechanically viable for handling/suturing in ionically crosslinked form, and is shown to be significantly effective at adhesion prevention in animal models (Namba, 2006; Cho, 2010a; Cho, 2010b). Attributes of alginate that statistically alter mechanical properties: (i) grade (Purification), (ii) gulcuronate to mannuronate ratio (High M ratio is pond-grown, primarily leaves, High G is deep sea harvested, primarily stems), and (iii) molecular weight/viscosity. However, highly purified alginate is very expensive˜$100/g, lower grade (inexpensive) alginates are not tested for molecular weight or G:M ratio, and purification processes are not standardized. Crystal templated hydrogels of alginate and HA were created by casting a droplet of solution containing a photocrosslinkable derivative of HA, a photocrosslinkable derivative of alginate with photoinitiator (PI) and urea (FIG.1). The solvent is evaporated and a urea seed crystal is touched to the droplet to nucleate urea crystallization. After crystallization the alginate and HA are photocrosslinked by UV exposure. Alginate may be further crosslinked ionically and rinsed with water to remove the urea leaving behind an alginate/HA hydrogel templated with the pattern of the urea crystals. The hydrogel may then be dehydrated for further surface modification using crosslinking agents (such as water soluble carbodiimides in ethanol/deionized water mixtures). The method for preparing the alginate/HA films as described in the present invention includes five steps: film casting, solvent evaporation, crystal growth, crosslinking, and rinsing. In the first step a syringe filter introduces a solution comprising alginate/GMHA/urea on a plate. The solution is then cast as a film at 25° C. at 70% relative humidity. Solvent evaporation is required to achieve the super-saturation conditions necessary for crystallization. Evaporation also greatly increases the biopolymer concentration and solution viscosity. The combination of high viscosity and hydrogen bonding suppresses spontaneous urea crystallization and facilitates super-saturation. Urea seed crystals are deposited on the tips of a fine pair of tweezers and is added to nucleate crystallization followed by exposure to UVA (500 mW/cm2) for 15 secs. Crystal growth began immediately and produced long dendritic branches that extended from the center to the edge of the film. Within seconds the entire volume of the hydrogel films were filled with urea crystals. These crystals comprised the urea crystal template. The films may optionally be crosslinked by an addition of one or more cross linking agents (for example an ionic crosslinking solution like CaCl2is added to the film to crosslink the alginate). The urea crystals are then rinsed out with double distilled water. The film formed thus is subjected to controlled dessication under force to remove water at 50% relative humidity. The dehydrated film may be subjected to further surface modification by creating one or more ester or less hydrolysable bonds by a variety of techniques (got e.g., soaking in a HA solution using water soluble carbodiimide for ester bonds). Alginate films alone degraded too quickly in chelating environment. Calcium ions chelated by multiple salts and can degrade within a few hours. (Islam, 2010). Adding GMHA decreases degradation, but without compromising the mechanical strength provided by alginate. Alginate film, alone, is too brittle and breaks with little manipulation. Adding urea introduces micron-sized pores which provide flexibility because spaces accept forces first. FIGS.2A-2Dshow the surface modification of templated alginate films.FIG.2Ashows fluorescent biotinylated HA crosslinked to surface labeled with FITC/Neutravadin. When not crosslinked, biotinylated HA washed away (4X).FIG.2Bis a glass slide forFIG.2A.FIGS.2Care is a SEM of the surface-modified film cross-sectional surface indicating pores filled, scale bar 2 μm and of a templated film, no surface modification, cross-sectional surface indicating unfilled porous, scale bar 1 μm, respectively. FIGS.3A-3Care images showing the integrity of the Alginate/HA film patterned with an urea crystallization pattern, pulling in tension (FIG.3A), crumpling and squeezing (FIG.3B), and returning to original geometry with no tearing or compromise of integrity (FIG.3C). The ASTM D638 tensile testing of urea patterned alginate/HA film and alginate/HA film with no patterning is shown inFIGS.4A and4B. The patterned film recoils in response to plastic deformation before failure. The non-patterned film breaks with a brittle fracture. Examples of alginate/HA urea-templated films are shown inFIGS.5A and5B, linear patterning with 4% urea, 5″ by 5″ film (5A), and radial patterning with 6% urea, 3″ by 3″ film (5B). FIG.6is a plot showing the ASTM D638 tensile testing of alginate films with increased concentration of urea crystallization. The trend indicates increased plasticity with increased crystallization patterning.FIG.7is a plot showing the ASTM D638 tensile testing of alginate films with increased concentration of HA. The trend indicates decreased tensile strength with increased HA, until a critical point, where the concentration of HA improves the tensile strength by providing crosslinked strength. Characterization of synthesized Alginate/HA films:FIGS.8A and8Bare plots showing the results of the wet sample degradation studies of an Alginate/HA film of the present invention conducted at 37° C. in PBS or 50 IU/mL of hyase, respectively. Briefly, the method involves determining a pre-test weight of the Alginate/HA film (or films) (Wo), after that the film is placed in PBS or the hyase at 37° C. and are removed at pre-defined time points and weighed (Wf). The procedure is repeated until the weight cannot be taken or the appropriate pre-defined end point time is reached. The degradation rate is calculated using the formula given below: % Weight Loss=100×(Wo−Wf)/Wo Dashed lines are representative of an estimated degradation since small bits can be seen visually for the duration of the study. Alginate alone films degrade due to chelating agents in the buffer. FIG.9is a schematic showing the steps involved in the evaluation of the anti-cell adhesion properties of an alginate/HA film of the present invention. A culture of fibroblast cells is taken, half of it is retained on a TCPS dish and the other half is retained on an Alginate/HA film that has been placed on a dish. After a 24 hour waiting period, both the dishes are stained with calcein/ethidium to label the live or dead cells. The cell adhesion or non cell adhesion is validated using one or more commonly used cell technologies. To study cell adhesion properties human dermal fibroblasts cells (P=3) were cultured on a PLL substrate, on alginate film, on alginate/modified HA film or alginate/modified HA film with HA surface modification alginate/HA film of the present invention (FIGS.9A-9D). A culture of fibroblast cells is taken and split in half and placed separately on two TCPS dishes. The film/substrate to be tested is placed on top of one of the dishes. After a 6 hour waiting period, both the dishes are stained with calcein/ethidium to label the live or dead cells.FIG.9Eis a plot of the % cell adhesion on the different substrates described inFIGS.9A to9D. Leaching studies showed no cytotoxic results from film, staining at 24 hours. The barrier disclosed hereinabove possesses significant advantages over currently existing technologies: (1) the barrier has improved handling characteristics, is easily folded, cut, sutured, manipulated in biologically relevant conditions; (2) barrier persists in desired area throughout healing duration; (3) barrier has improved in vivo repositioning flexibility; and (4) unique porous structure that exhibits a tunable release profile for material, small molecules, or growth factors. The unique anti-adhesive membrane described hereinabove could also be an innovative solution in the enormous wound care market. As a substrate for a non-adhesive, hydrophilic, yet absorbent wound dressing, the present invention can be used extensively in burn care, chronic non-healing wound care, and reconstructive plastic surgery. It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method, kit, reagent, or composition of the invention, and vice versa. Furthermore, compositions of the invention can be used to achieve methods of the invention. It will be understood that particular embodiments described herein are shown by way of illustration and not as limitations of the invention. The principal features of this invention can be employed in various embodiments without departing from the scope of the invention. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures described herein. Such equivalents are considered to be within the scope of this invention and are covered by the claims. All publications and patent applications mentioned in the specification are indicative of the level of skill of those skilled in the art to which this invention pertains. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and/or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” The use of the term “or” in the claims is used to mean “and/or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and/or.” Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, or the variation that exists among the study subjects. As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. The term “or combinations thereof” as used herein refers to all permutations and combinations of the listed items preceding the term. For example, “A, B, C, or combinations thereof” is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, MB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth. The skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context. All of the compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims. | 28,147 |
11857702 | EXAMPLES Example 1 Hydrophobic Metal Surface Covering Four metal capsules (nitinol) are washed beforehand by being vertically immersed in a beaker containing 95% ethanol. The beaker containing the capsules is subjected to ultrasound for 2 mins, then the beaker is left in a water bath at 60° C. for 1 hour. The capsules are removed from the washing solution and allowed to air dry. The capsules are then immersed vertically in a beaker containing 80 ml of 0.1% (mlv) stearylamine in dimethylformamide. The beaker containing the capsules is placed in a thermostatically controlled heating chamber at 27° C. on an orbital shaker for 1 hour. At the end of this time, the capsules are removed from the beaker and they are immersed in 3 successive baths of distilled water for washing. Finally, the capsules are immersed vertically in a beaker containing 80 ml of 0.2% (m/v) hyaluronic acid in distilled water. The beaker is stirred on an orbital shaker for 2 hours at room temperature. Finally, the capsules are removed and allowed to air dry for 24 hours. Crosslinking Four capsules are covered with hyaluronic acid according to the above method. The hyaluronic acid layer is crosslinked by various crosslinking agents:Capsule 1 (E1): non-crosslinked,Capsule 2 (E2): crosslinked by triethanolamine titanate chelate—TYZOR TE 200 mM,Capsule 3 (E3): crosslinked by 1,4-butanediol diglycidyl ether (BDDE) 200 mM, andCapsule 4 (E4): crosslinked by polyethylene glycol) diglycidyl ether (PEGDGE) 200 mM. The three metal capsules E2. E3, E4 are immersed vertically and in tubes containing 8 ml TYZOR TE 200 mM in distilled water, 8 ml 200 mM BDDE in 0.25N NaOH and 8 ml 200 mM PEGDGE in 0.25N NaOH, respectively, these solutions completely covering the metal capsules to be treated. The tubes are placed on an orbital shaker for 1 hour at room temperature. At the end of this time, the capsules are removed from the solution of crosslinking agent and placed in a heating chamber at 60° C. for 60 mins for E2 and 15 mins for E3 and E4. The metal tubes are then washed with distilled water on an orbital shaker for 15 mins at room temperature. This is followed by four successive washing baths. Finally, the capsules are immersed vertically in a beaker containing 80 ml of 0.2% (m/v) hyaluronic acid in distilled water. The beaker is stirred on an orbital shaker for 2 hours at room temperature. The crosslinking method can be repeated a second time. The capsules are immersed in a beaker containing 80 ml of 0.3% (m/v) (hyaluronic acid in distilled water. To evaluate the effect of the crosslinking agents, the inventors measured the stripping force. To do this, the inventors pushed a stent inside the treated capsule while measuring the force necessary to make it move forward. This is the stripping force. The results obtained for the different instances of crosslinking are shown inFIG.1. The following table 1 summarizes the results inFIG.1. CapsuleStripping force (N)El - non-crosslinked HA45.96E2 - HA crosslinked by TYZOR TE 200 mM26.90E3 - HA crosslinked by BDDE 200 mM44.64E4 - HA crosslinked by PEGDGE 200 mM51.58 From the data obtained, the capsule giving the best results is the E2 capsule, where only 26.9N is needed to move a stent. The E1 and E3 capsules gave slightly lower results than an untreated capsule (no covering; not shown): an average of 45.3N for these two capsules compared with 53.7N for an untreated capsule. The E4 capsule gives results equivalent to an untreated capsule (51.6N compared with 53.7N). The crosslinking agents are therefore not equivalent, and TYZOR TE is the best crosslinking agent and allows good surface lubrication. Example 2 In this example, capsules are covered as indicated in example 1, in the section “Hydrophobic surface covering.” Crosslinking Five capsules are covered with hyaluronic acid according to the above method. The hyaluronic acid layer is crosslinked by TYZOR TE at different concentrations:Capsule 1 (E1a): by TYZOR TE 50 mM,Capsule 2 (E2a): by TYZOR TE 100 mM,Capsule 3 (E3a): by TYZOR TE 200 mM,Capsule 4 (E4a): by TYZOR TE 400 mM, andCapsule 5 (E5a): by TYZOR TE 800 mM. The five metal capsules E1a, E2a, E3a, E4a and E5a are immersed vertically in tubes containing 8 ml TYZOR TE 50, 100, 200, 400 and 800 mM, respectively, in distilled water, these solutions completely covering the metal capsules to be treated. The tubes are placed on an orbital shaker for 1 hour at room temperature. At the end of this time, the capsules are removed from the solution of crosslinking agent and placed in a heating chamber at 60° C. for 60 mins. The metal tubes are then washed with distilled water on an orbital shaker for 15 mins at room temperature. This is followed by four successive washing baths. Finally, the capsules are immersed vertically in a beaker containing 80 ml of 0.2% (m/s′) hyaluronic acid in distilled water. The beaker is stirred on an orbital shaker for 2 hours at room temperature. The crosslinking method can be repeated a second time. In this case, the capsules are immersed in a beaker containing 80 ml of 0.3% (m/v) hyaluronic acid in distilled water. Results To evaluate the effect of the crosslinking agents, the inventors measured the stripping force. To do this, the inventors pushed a stent inside the treated capsule while measuring the force necessary to make it move forward. This is the stripping force. The results obtained for the different instances of crosslinking are shown inFIG.2. The following table 2 summarizes the results in said figure. CapsuleStripping force (N)El a - HA crosslinked by TYZOR TE 50 mM41.3E2a - HA crosslinked by TYZOR TE 100 mM33.0E3a - HA crosslinked by TYZOR TE 200 mM26.0E4a - HA crosslinked by TYZOR TE 400 mM24.5E5a - HA crosslinked by TYZOR TE 800 mM23.6 The efficiency of the sliding is dose-dependent on the concentration of the crosslinking agent (TYZOR TE). The more crosslinking agent is present, the more the sliding makes it possible to retain the layer of non-crosslinked hyaluronic acid. Example 3 Hydrophobic Polymer Surface Covering Polyethylene probes are washed beforehand by being vertically immersed in a beaker containing 95% ethanol. The beaker containing the probes is subjected to ultrasound for 2 min, then the beaker is left in a water bath at 60° C. for 1 hour. The probes are removed from the washing solution and allowed to air dry. The probes are then immersed vertically in a beaker containing a solution of 0.1% (m/v) stearylamine in dimethylformamide. The beaker containing the probes is placed in a thermostatically controlled heating chamber at 27° C. on an orbital shaker for 1 hour. At the end of this time, the probes are removed from the beaker and they are immersed in 3 successive baths of distilled water for washing. Finally, the probes are immersed vertically in a beaker containing a solution of 0.2% (m/v) hyaluronic acid in distilled water. The beaker is stirred on an orbital shaker for 2 hours at room temperature. Finally, the probes are removed and allowed to air dry for 24 hours. The probes are covered with hyaluronic acid according to the method described above. The probes are divided into 4 batches. The hyaluronic acid layer is crosslinked by TYZOR TE at different concentrations:Batch 1: non-crosslinked,Batch 2: crosslinked by TYZOR TE 50 mM,Batch 3: crosslinked by TYZOR TE 200 mM, andBatch 4: crosslinked by TYZOR TE 800 mM. The probes of batches 2, 3 and 4 are immersed vertically in tubes containing a solution of TYZOR TE 50 mM, 200 mM, and 800 mM, respectively, in distilled water; these solutions completely cover the polyethylene probes to be treated. The tubes are placed on an orbital shaker for 1 hour at room temperature. At the end of this time, the probes are removed from the solution of crosslinking agent and placed in a heating chamber at 60° C. for 60 mins. The probes are then washed with distilled water on an orbital shaker for 15 mins at room temperature. This is followed by four successive washing baths. Finally, the probes are immersed vertically in a beaker containing a solution of 0.2% (mlv) hyaluronic acid in distilled water. The beaker is stirred on an orbital shaker for 2 hours at room temperature. The crosslinking method is repeated a second time. Finally, the probes of batch 1 (non-crosslinked), and batch 2, 3 and 4 (crosslinked) are immersed in a beaker containing a solution of 0.3% (m/v) hyaluronic acid in distilled water. To evaluate the effect of the crosslinking agents, the inventors carried out sliding and/or resistance tests with a pass through 50 g jaws over 8 cm of probes hydrated by immersion in distilled water just before the measurement. The sliding coefficients of friction (sliding CoF) are estimated by a mean of the coefficients of the first pass through the jaws. The resistance coefficients of friction (resistance CoF) correspond to the mean of 5 passes of the same probe. The results are shown inFIG.3, and in the following table: StandardStandardSliding CoFdeviationResistance CoFdeviationBatch 10.0946II0.25770.1418Batch 20.0363II0.04010.0037Batch 30.0307II0.03090.0021Batch 40.0281II0.03040.0017 The results show that the crosslinking of the layer of hyaluronic acid significantly improves the sliding and very significantly improves the resistance of the covering even after several friction passes, compared with the control probe. The invention is not limited to the embodiments presented here and other embodiments will become clearly apparent to a person skilled in the art. | 9,576 |
11857703 | DETAILED DESCRIPTION The solution according to the invention consists in using a fully mechanical energy system for creating a delivery quality of a level similar to electrical devices, but using no external electrical energy source, and fixing the olfactory molecules in a polymer-type substrate. Fixing of the Olfactory Molecules to the Substrate The substrate elements are solid. They are made at least in part of a polymer material. Polymers include elastomers, for example a bi-polymer of the polyamide and polyether block amide type. Depending on the used polymer material and the fragrance, the beads naturally deliver the fragrance molecules for 6 to 18 months only in a hardly perceptible way. An example of such a material is Pebax® (trade name). As they are, the substrate elements spontaneously diffuse small quantities of the fragrance molecules they contain by natural evaporation, or more particularly by a phenomenon of desorption. On the other hand, when the substrate is subjected to airflow, mechanical interactions significantly increase the rate of release of olfactory molecules by up to 500 times. The substrate elements6may take the form of spheroids, rhombohedral or rectangular parallelepipeds, or prismatoids. In a preferred embodiment, the substrate elements are spheroid beads of polymer material and the fragrance molecules are adsorbed throughout the volume of each bead. As an example, beads made of polymer material each have, before adsorption of the fragrance, a smaller dimension equal to 3 mm and a larger dimension equal to 4 mm, and, after adsorption of the fragrance, a smaller dimension equal to 4 mm and a larger dimension equal to 6 mm. The weight of fragrance adsorbed in each bead corresponds approximately to the weight of a bead before the fragrance is adsorbed. The fragrance is encapsulated in polymer beads with fairly strong electrostatic bonds between the molecules making up the fragrance and the polymer beads. Without forced ventilation, the movement of the air does not have enough force to tear off the fragrance molecules and the electrostatic bond prevails. In this configuration, the delivery of fragrance requires about 18 months between the moment when the fragrance capsule is placed in the open air while being completely full of fragrance and the moment when all the available fragrance has been delivered; the delivery is linear way over time. A fragrance capsule containing an average of 2 g of fragrance concentrate means that the amount of fragrance released in a day is: 3.7×10−3g/day, i.e., 1.5×10−4g/hr. The polymer beads used are a bi-component polymer comprising apolar and polar portions which allows a relatively strong electrostatic interaction with the different molecules composing the fragrance concentrate which are themselves either polar or apolar. It should also be noted that even when temperature is high (for example in a car passenger compartment, a train or a plane cockpit left in direct sunlight), the quantity of fragrance released is very low: this means that the passenger compartment is not perfumed too strongly when the car is at rest, even in the heat. In forced ventilation, the kinetic energy brought by the movement of the air is sufficient to tear off the fragrance molecules and in this context, the entire fragrance concentrate is delivered into the air in approximately 24 hrs. The quantity of fragrance released into the air is thus of the order of 2 g/day, i.e. 0.08 g/hr. By way of comparison, a person who uses 100 ml eau de toilette containing 10% fragrance concentrate by spraying 3 times on him/her, will have put 0.06 g of concentrate on him/her (a 100 ml bottle allows on average 500 sprays), i.e., a quantity of fragrance equivalent to that released by the capsule. Thus at rest, the olfactory intensity released into the air is about 1000 times less than that released by a person who wears a fragrance, and the olfactory intensity in forced ventilation will be of the same order of magnitude as a person wearing a fragrance. The general principle implemented by the systems according to the invention consists in using the kinetic energy of a mobile base supported by an unstable linkage, which can take different configurations:a flexible rod connecting a cartridge holder containing one or more cartridge(s) to a mounting base fixed to a solid surface, for example the dashboard or ceiling of a vehicle such as a car or a train. During acceleration and deceleration of the vehicle both along the longitudinal and transverse axis (during changes of direction) or vertically (passing over uneven surfaces of a motor vehicle or turbulence for an aircraft), the cartridge holder is subjected to oscillating movements about an equilibrium position.A pivot about which the cartridge holder containing one or more cartridge(s) is hinged. This pivot can be horizontal, with the cartridge holder suspended to allow a swinging movement around an equilibrium position. This pivot can be vertical, with the cartridge holder rotating freely to allow a swinging movement around an equilibrium position. For the purposes of this patent, “oscillating movement” shall also be mean a rotation of several revolutions around the pivot. The movement will be favoured by the presence of an unbalance on the holder. The oscillating movements of the cartridge holder cause the cartridge to move relative to the surrounding air, which promotes the controlled release of odour substances. The cartridge is preferably supported—and not suspended—by the linkage element to the mounting holder, and is therefore placed above the holder. This configuration provides more “nervousness” to the device, which enters into oscillation as soon as the cartridge is subjected to a movement, resulting for example from the instability of the flexible rod and an acceleration transmitted to the holder. The movement of the cartridge amplifies the flexible deformation of the rod, unlike a solution where the cartridge is suspended from a flexible linkage where the movement will tend to compensate for the amplitude of the oscillating movement. Mechanical recovery, for the operation of the device, usually results in intermittent operation. This intermittent mode of operation prevents users from getting used to the odours released and losing the perception of these fragrances. Intermittence allows to regularly reactivate the perception of the odour according to the movements and action of the device. This inconsistency, beyond imposing an irregular operation, rather proposes an experience linked to the activity of the product. The principle of the solutions presented as non-limiting examples is based on the use of a dry fragrance capsule, as described in patent WO2013021114. This solution ensures that the invention operates safely and conveniently for the user. In particular, the invention aims to promote the extraction of the fragrance by setting the fragrance capsule in motion instead of the generation of the air flow by a third element, such as a fan. From a technical point of view, the performance of the delivery is linked to the agitation of the air molecules around the fragrance beads contained in the capsule. The airflow and air pressure around the beads promote desorption of the fragrance from the beads, and the airflow improves the distribution of the fragrance in the air. Description of a First Embodiment According to this first exemplary embodiment, the delivery system consists of a cartridge1, a base2and a flexible rod3. The cartridge1consists of a shell4the main faces of which are formed by grids5. This shell contains solid beads6made of a substrate material capable of allowing the penetration or fixation of fragrance molecules at least at their periphery. This cartridge1is fixed to a flexible rod3, for example a steel piano wire, the other end of which is fixed to a base2having for example on its lower surface a suction cup for fixing to a surface such as a vehicle dashboard. Optionally, the rod3is provided with a counterweight7on its upper portion. The counterweight is set in motion by all external movements such as vehicle movements and vibrations and/or manual agitation. The flexibility of the rod, its length and the mass of the counterweight determine the quality of the delivery. For example in cars, good results have been obtained with a 0.8 to 1.5 mm thick steel rod, about 10 cm long and a weight of about 50 to 80 g. Description of a Second Embodiment In this second embodiment, the cartridge1is supported by a vertical pivot8fixed on a first oscillating frame9. This first oscillating frame9is positioned inside a second frame10via two horizontal axes11,12. The two frames9,10together form a cardan joint, which is pivotably mounted to the base2by means of a vertical pivot13. The first frame9optionally has a counterweight7so that the pivot axis8of the pendulum is always perpendicular to the direction of acceleration. Thus, regardless of the direction of acceleration variations, the pivot disc will align and the pendulum will be able to pivot freely on its axis. Description of a Third Embodiment According to this third variant, the cartridge1is mounted on a disc15by means of a rod14, which can optionally be elastic or rigid. This disc15is pivotally mounted with respect to a first frame16by means of two pivots17,18oriented in a first direction. This frame is itself pivotally mounted with respect to a second frame19by means of two pivots20,21oriented perpendicularly to the first direction. Description of a Fourth Embodiment According to this other variant, the cartridge1is supported by a flywheel consisting of a disc plate21, e.g., a metal flywheel with a large mass is rotated manually by the user. Guided in rotation by elements with low coefficients of friction, once the maximum speed has been reached, the inertia will allow the rotating mass to maintain its movement for a long time. The cartridges1are positioned radially in a direction normal to the axis of rotation, so as to correctly take up the relative wind created by the opposition of air to the rotational movement. In order to function properly, this device must have a high ‘Rotational Mass/(Capsule Mass*Friction)’ ratio, so that it can rotate long enough at the desired speed. The assembly is pivoted on a fixed base with a ball bearing system and is equipped with a counterweight to add significant unbalance. One or more capsule(s) fixed on the periphery of the disc plate is/are thus animated by the change of orientation of the device. This device has proved effective on the dashboard of a vehicle, but seems to be suitable for integration into a vehicle with regular speed and direction variations such as a bus, a train, a tram or a metro. Optionally, the platform21is equipped with weights22to26, in an unbalanced manner to help set it in motion by the vehicle accelerations transmitted through the base. | 10,980 |
11857704 | DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS Various fragrance dispensers and related methods are described. Certain embodiments of the fragrance dispensers are described in the context of a fragrance dispenser with a replaceable cartridge having fragrant material in a substantially solid form and/or embedded in a substantially solid substrate, due to particular utility in that context. However, the embodiments and inventions disclosed herein can also be applied to other types of dispensers and other types of dispensed materials, such as fragrance dispensers that include fragrant material in a liquid, gel, or gaseous form, dispensers with non-replaceable cartridges, non-fragrance dispensers (e.g., humidifiers), or otherwise. No features, structure, or step disclosed herein is essential or indispensable. I. Overview FIG.1schematically illustrates a fragrance dispenser10(also called a dispenser). The dispenser10can be configured to dispense fragrance into a space in which the dispenser10is located, such as a bathroom, kitchen, or otherwise. The dispenser10can include housing that receives a replaceable fragrance unit12(also called a refill or a cartridge) that includes the fragrance reservoir14. The fragrance unit12can comprise a material that is odorizing or deodorizing. In some embodiments, the fragrance is embedded in a substrate, such as a polymer, carbohydrate (e.g., polysaccharide) or otherwise. The fragrance reservoir14can be substantially solid, such as being a highly viscous gel. The fragrance reservoir14can be solid enough to hold a shape. The fragrance reservoir14can be shaped as an impeller or other airflow-enhancing shape. The fragrance unit12can be positioned in an outer casing, which can protect the reservoir14and/or reduce the chance of a user touching the reservoir14. The fragrance unit12can be removable from the rest of the dispenser, such as when the fragrant material has become exhausted, thereby allowing a new fragrance unit12to be installed in the dispenser10. The dispenser10can include a connection unit16that is configured to connect with the fragrance unit12. In some embodiments, the connection unit16is configured to removably couple with the fragrance unit12. For example, the connection unit16can comprise a bayonet mount. The connection unit16can be configured to automatically release (e.g., partially or completely eject) the fragrance unit12, such as when the fragrance unit12is due for replacement. The dispenser10can include a control unit18that directs certain operations of the dispenser10. For example, the control unit18can be configured to control dispensation of the fragrance from the reservoir14and/or release of the fragrance unit12from the connection unit16. The control unit18can include a controller20, such as an electronic microprocessor and a memory. The control unit18can include a motor22, such as an AC or DC electric motor, which can be controlled by the controller20. The motor22can be configured to spin a fan, such as an impeller. The motor22can be configured to release the fragrance unit12from the connection unit16, such as by rotating the fragrance unit12relative to the connection unit16. The control unit18can include one or more sensors24, such as proximity sensors or switches, which can communicate with the controller20. The sensors24can detect, for example, a position of the fragrance unit12. The controller20, motor22, and/or sensors24and motor can receive electric energy from a power supply, such batteries, a plug or hardwired electrical connection, or otherwise. The dispenser10can be configured to indicate a status to an observer, such as maintenance personnel. The status can be, for example, that the fragrance unit12is due for replacement. In certain implementations, the change in status is indicated by a change in the position of the fragrance unit12within the dispenser10. For example, when due for replacement, the fragrance unit12can be released from the connection unit16, which causes the fragrance unit12to drop downward. As illustrated, a portion of the fragrance unit12can protrude from a bottom of the dispenser10. In certain implementations, the fragrance unit12moves from a non-protruding position to a protruding position, or increases the amount by which the fragrance unit12protrudes out of the housing. In some variants, the fragrance unit12is moved by force of gravity and/or by a biasing force, such as from a spring. An observer can easily see that fragrance unit12has changed position and thus readily identify the status of the dispenser10. For example, the observer can readily see whether the fragrance unit12is due for replacement. II. Dispenser110 FIGS.2-12Hillustrate another embodiment of a dispenser110. The dispenser110resembles and/or can include any of the features of the dispenser10. Reference numerals used to identify like features are incremented by a factor of one hundred. This numbering convention generally applies throughout this disclosure. Any component or step disclosed in any embodiment in this specification can be used in other embodiments. As illustrated inFIG.2, the dispenser110includes a housing H, such as a hard plastic or metal outer casing or other protective cover. The dispenser110can be configured to mount on a wall. The dispenser110can have an upper end125A and a lower end125B. The dispenser110can include one or more vents V, which can facilitate airflow into and/or out of the dispenser110. The dispenser110can have an indicator unit127, such as lights. As shown in the exploded view ofFIG.3, and the cross-sectional view ofFIG.4, the dispenser110can include a core unit111and a cartridge112. The cartridge112can be received in the housing H. For example, the cartridge112can be inserted into a chamber in the lower end125B (e.g., bottom) of the dispenser110. In certain implementations, the housing H is configured to interact with the cartridge112. For example, the housing H can have a catch128that engages with the cartridge112when the cartridge112disengages from (e.g., drops from) the core unit111, as discussed below. The catch128can retain the cartridge112in a disengaged position. In some embodiments, the catch128comprises an arm or a flange. The dispenser110can include a motor122, such as an electric motor. The motor122can drive an impeller126of the cartridge112. The motor122can be positioned above the cartridge112. The motor122can be a direct drive or indirect drive (e.g., with a transmission device, such as a belt, geartrain, etc.). The motor122and other components of the dispenser10can receive electric power from a power supply P. As shown, the power supply P can comprise one or more single-use or rechargeable batteries. In some variants, the power supply P comprises a wall outlet plug, solar cell, capacitor, or otherwise. The housing H can have a door D, which can provide access to the power supply, such as to enable replacement of the batteries. In some implementations, the housing H has features that orient the cartridge112relative to the connection unit116. For example, the housing H and cartridge112can be keyed such that the cartridge112can be inserted into the housing H in only certain orientations. This can aid in co-locating mating features of the cartridge112and core unit111, which are discussed below. In various embodiments, the dispenser110is configured to automatically indicate a status of the cartridge112. For example, the cartridge112can move from an engaged position (seeFIG.5A) to a disengaged position (seeFIG.5B) in response to the cartridge112being ready for replacement. As illustrated, in the disengaged position, the cartridge112can protrude, or can increase the amount of the cartridge112that protrudes, from a bottom of the housing H. This can be readily seen by an outside observer, such as a maintenance person, and thus communicate to the observer whether the cartridge112is ready for replacement. The indication can occur without the observer needing to physically contact the dispenser110(e.g., without opening a door on the dispenser) and/or with the observer being remote from the dispenser (e.g., on an opposite side of a room that the dispenser110is located in). II.A. Core Unit FIGS.2-11illustrate an example of the core unit111(coupled or associated with the cartridge112in certain figures). The core unit111can be positioned in the housing H. For example, the core unit11can be permanently mounted in the housing H. The core unit111can include a connection unit116and a control unit118. The connection unit116can removably couple with the cartridge112. The connection unit116can be biased to disengage from the cartridge112. The control unit118can control various operations of the dispenser110. II.A.1. Connection Unit The connection unit116can include a support element129and an engagement element130. As discussed in more detail below, in certain embodiments, the support element129is configured to be stationary relative to the housing H and/or the engagement element130is configured to move (e.g., slide) relative to the support element129. For example, the engagement element130can be configured to push the cartridge112away from the support element129. The support element129can comprise a rigid plate, disk, or other shape of material. The support element129can be adapted to couple to and/or secure the cartridge112. In some embodiments, the support element129has one or more first securing features131A, such as hooks, arms, male elements, or otherwise. The first securing features131A can project downward from the support element129. The support element129can include one or more tracks132, such as channels. The support element129can include one or more first positioning features135A. In some embodiments, the first positioning features135A comprise slots (e.g., elongate through holes), female elements, or otherwise. The illustrated embodiment has four first securing features131A and four first positioning features135A, but other numbers are contemplated, such as one, two, three, five, six, or more. In some embodiments, the number of first securing features131A is equal to the number of first positioning features135A. In certain variants, the number of first securing features131A is different from the number of first positioning features135A. As illustrated, in certain embodiments, the first securing features131A and first positioning features135A are interspersed in an alternating manner in a circumferential direction. In some implementations, the first securing features131A of the support element129are configured to engage with second securing features131B of the cartridge112, such as apertures, female elements, etc. (seeFIG.3). For example, the first securing features131A can engage (e.g., be received in) the second securing features131B. In some embodiments, the first and second securing features131A,131B comprise a bayonet connection mechanism. After the securing features131A,131B have engaged, the cartridge112can be rotated relative to the support element129. This can move a portion of the first securing features131A (e.g., hooks) out of alignment with the second securing features131B, thereby providing a physical interference between the first securing features131A and the cartridge112. In some embodiments, force from one or more biasing members134is applied to the cartridge112, but the cartridge112is maintained in position by the first securing features131A (e.g., the hooks engaged with a lid of the cartridge112). The cartridge112can thus be coupled and/or secured to the support element129. In certain implementations, the first positioning features135A of the support element129are configured to engage with second positioning features135B of the cartridge112, such as posts, male elements, etc. (seeFIG.3). For example, the first positioning features135A can engage (e.g., receive) the second positioning features135B of the cartridge112. In some embodiments, the first and second positioning features135A,135B comprise a slot and pin. In some embodiments, the pin can be configured to slide in the slot as the cartridge112is rotated relative to the support element129. In some implementations, the support element129includes a torque transmission element, such as a shaft136. As illustrated, the shaft136can project downward, such as generally vertically downward. The shaft136can be centrally located on the support element129. The torque transmission element can operably connect to the cartridge112to transmit motive force to the cartridge112. For example, the shaft136can be configured to be received in a corresponding cavity137in the cartridge112. In some embodiments, the shaft136includes one or more alignment features, such as flanges138. In some embodiments, the flanges138comprise radially extending wings. In some embodiments, the flanges138can taper outward, such as at an upper end, as illustrated. The flanges138can facilitate aligning and/or centering the cartridge112onto the shaft136. For example, the flanges138can aid in positioning the cartridge112such that an axis of rotation of the impeller126of the cartridge112is substantially collinear with an axis of rotation of the shaft136. The shaft136can couple to the impeller126. In some embodiments, the shaft136includes a first connecting element139A, such as a magnet. The first connecting element139A can be positioned on a bottom and/or free end of the shaft136. The first connecting element139A can be removably coupled with a second connecting element139B (e.g., a metal washer) of the cartridge112. The shaft136can couple to the motor122. For example, an output drive shaft of the motor122can be received in an upper end of the shaft136such that rotational motion from the motor122is transferred into the shaft136. In some implementations, the motor122can rotate the output drive shaft in clockwise and counterclockwise directions. The shaft136and motor122can be coupled with a one-way connection140, such as a one-way clutch, bearing, bushing, or other one-way torque transmission device. The one-way connection140can activate in only one rotational direction. This can permit rotation from the motor122to be transferred to the shaft136in one rotational direction (e.g., counterclockwise) but not in the other direction (e.g., clockwise). In several implementations, rotation of the motor122in a first direction spins the impeller126and/or rotation of the motor122in a second direction disengages the cartridge112from the connection unit116. In some embodiments, the shaft136is connected to a gear141(e.g., a spur gear) or other torque transfer element, such as via the one-way connection140. The gear141can be connected to one or more control gears142. As shown inFIG.9, the control gear142can include a smaller body portion143that includes the axis of rotation of the control gear142and a larger toothed portion144. The toothed portion144can engage with the gear141. In some implementations, the toothed portion144extends only around a portion of the periphery of the control gear142, such as at least about: 90°, 120°, 150°, or more. The control gear142can include one or more cartridge interface features, such as holes145(e.g., through holes). In certain implementations, when the first and second positioning features135A,135B are engaged (e.g., the posts protrude through the slots), the second positioning features135B of the cartridge112extends into the holes145of the control gears142. The position of the cartridge112can thus be affected by the position of the control gear142. For example, in an embodiment in which the first and second positioning features135A,135B comprise a slot and pin, rotating the control gear142in a first direction (e.g., counterclockwise) to a first rotational position can move the pin to one end of the slot and/or rotating the control gear142in a second direction (e.g., clockwise) to a second rotational position can move the pin to the other end of the slot. The control gear142can include a position indicator146, such as a peg. Movement of the control gear142can be limited by stops147on the support element129. The engagement element130can be positioned below the support element129. In certain implementations, the engagement element130comprises an annular member, such as a ring. As illustrated, in some embodiments, the engagement element130is radially outward and/or surrounds the first securing features131A and/or the first positioning features135A. When the cartridge112is not installed in the housing H and/or when the cartridge112has been dropped to the disengaged position, which may indicate that the cartridge112is due for replacement, the engagement element130can be visible through the vent V. For example, as shown inFIG.5B, the engagement element130can be generally horizontally positioned in and/or aligned with at least one of the vents V. The engagement element130can be brightly colored (e.g., yellow, orange, red, etc.) or otherwise provide a visual signal that the cartridge112is not present or is in the disengaged position. The engagement element130can include guides133, such as arms, which can project upwardly. The guides133can be received in a corresponding one of the tracks132. One or multiple biasing members134, such as springs, can be positioned between the support element129and an engagement element130. For example, the biasing members134can be positioned over a respective one of the guides133and/or in a respective one of the tracks132. The biasing member134can bias the engagement element130away from the support element129. The engagement element130can be adapted to engage with an upper portion of the cartridge112. For example, when the cartridge112is inserted into the dispenser110, the cartridge112can abut against the engagement element130. With continued upward force on the cartridge112, the cartridge112and engagement element130can be moved against the bias of the biasing member134. This can energize the biasing member134. In some embodiments, the cartridge112is pushed upward until the engagement element130is stopped by the support element129. In certain variants, an upper stop on the housing H limits upward travel of the engagement element130. A lower stop on the support element129or housing H can limit downward travel of the engagement element130. II.A.2 Control Unit As mentioned above, the core unit111can include the control unit118. The control unit118can be positioned above the connection unit116. In some embodiments, the motor122protrudes through the control unit118, such as through a central portion of the control unit118as illustrated. The control unit118can include a base150that couples to and supports the motor122. The base150can be rigid, such as made of metal or hard plastic. The base150can include recesses that receive the tracks132. In some embodiments, the control unit118includes an electronic controller, such as a processor and memory. The controller can be positioned on a printed circuit board (PCB)151. The control unit118can include a cover152, which can protect and/or cover a top portion of the PCB151. For example, when the door D is opened, the cover152can protect the PCB151. The cover152can be made of metal, hard plastic, or another rigid material. A power switch153or other user interface can extend through the cover152. The control unit118can include one or more sensors124. The sensors124can be, for example, switches, proximity sensors, or otherwise. In some embodiments, the control unit118includes an installation sensor that detects whether the housing H is installed on a wall or other structure. The dispenser110can be configured to not operate when not installed. In certain implementations, the control unit118has an occupancy sensor, such as a photosensor, motion sensor, or otherwise. This can enable the dispenser110to determine whether the space in which the dispenser110is located is occupied. For example, in an embodiment in which the occupancy sensor comprises a photosensor, detecting that the space is dark can indicate that the space is likely unoccupied. The dispenser110can be configured to change operation in response to information from the occupancy sensor. For example, the dispenser110can cease or slow spinning of the impeller126in response to determination that the space is unoccupied (e.g., dark). In some embodiments, the control unit118has a cartridge present sensor124A. The cartridge present sensor124A can detect whether the cartridge112has been pushed up into engagement with the connection unit116. In some embodiments, the cartridge present sensor124A comprises a switch that is depressed by an upper portion of the cartridge112, as shown inFIG.4. In certain embodiments, the control unit118has a cartridge secured sensor124B. The cartridge secured sensor124B can detect that the cartridge112has been secured to the connection unit116, such as by being rotated relative to the support element129and/or by the first and second securing members131A,131B being mated to inhibit or prevent removal of the cartridge112. In some embodiments, the cartridge secured sensor124B comprises a switch that is depressed by the position indicator146and/or the second positioning element135B, such as at or near an end of the pin sliding in the slot as the cartridge112is rotated relative to the support element129. The control unit118can include various conductors C, such as wires, traces, or otherwise. The conductors C can connect various electric elements of the dispenser110, for example, the conductors C can connect the controller to the power supply P, motor122, sensors124, controller, and otherwise. The control unit118can include an indicator unit127, such as a plurality of lights. In some embodiments, the indicator unit127includes a power status light that indicates (e.g., illuminates) when the dispenser110has electric power. The power status light can indicate, such as by flashing, when the power supply is low (e.g., when the batteries are due for replacement). The indicator unit127can include a cartridge present light, which can indicate (e.g., illuminate) when the cartridge112is pushed up into engagement with the connection unit116. The indicator unit127can include a cartridge secured light, which can indicate (e.g., illuminate) when the cartridge112is secured with the connection unit116. In certain implementations, the cartridge present light and cartridge secured light are the same light, but with different colors to indicate the different statuses. Some implementations include a cartridge disengaged light, such as a light that illuminates in response to the dispenser110disengaging the cartridge112from the connection unit116and/or dropping the cartridge112to the disengaged position. This can signify to a maintenance or other person that the cartridge112is due for replacement. II.B Cartridge FIGS.12A-12Hillustrate an example of the cartridge112. The cartridge112includes a fragrance reservoir114(also called a fragrance composition), which can include a fragrance liquid, such as a fragrance oil. The fragrance liquid can be suitable for use with plastics with sustained release and/or evaporation rate-vapor pressure. The cartridge112can be configured to reduce the chance of a person touching the fragrance reservoir114, which could cause damage to the reservoir114or apply the fragrance liquid directly to the person. For example, the fragrance reservoir114can be enclosed in the cartridge112. The fragrance reservoir114can include a substrate (also called a support structure) that the fragrance liquid is contained or embedded in or on. In some embodiments, the substrate comprises a lattice. The substrate can comprise a plurality of cells or chambers, such as interstitial spaces. The chambers can be in fluid communication. The chambers can receive the fragrance liquid. The substrate can be configured to facilitate movement of the fragrance liquid through the chambers. For example, the fragrance liquid can move from inner chambers to outer chambers in the substrate, thereby enabling the fragrance liquid to migrate to a location to escape the substrate (e.g., due to evaporation) to provide fragrance to a surrounding environment. The substrate can have a yielding, porous, and/or fibrous skeleton or framework. For example, the substrate can have a spongy texture and/or resiliency. In some embodiments, the substrate comprises thermoplastic elastomer (TPE) and/or ethylene-vinyl acetate (EVA) resin. In certain implementations, the substrate comprises a thermoplastic elastomer composition comprising a blend of hydrogenated styrenic block copolymer and a plasticizer (e.g., parafinic or naphthenic) that is compatible with the mid-blocks of the hydrogenated styrenic block copolymer. The hydrogenated styrenic block copolymer can comprise a polyolefin. In some variants, the TPE comprises olefinic block copolymers, thermoplastic urethane, coplysters, and coplyamides. In certain implementations, the substrate is comprised of gums (e.g., cellulose gum), gellers or thickeners (e.g., carrageenan), polymers, or other materials. In some embodiments, the framework is hydrophilic. In certain variants, the framework is hydrophobic. In some embodiments, the fragrance reservoir114includes hydrophilic and/or diffusion agents. For example, the fragrance reservoir114can include a powdered or beaded blend of amorphous silicon dioxide (e.g., silica and fumed silica) with optimal surface area and alumino silicate (e.g., zeolite) and/or inorganic fillers and/or EVA polymer binder. In certain implementations, using a TPE or EVA resin as a base, fillers are added to create a porous hydrophilic or resin. In some cases, a hydrophobic cell structure may be desirable. Various proportions of the substrate to other components (e.g., the combination of the liquid fragrance, a foamer, and/or a hydrophilic agent) are contemplated. In some implementations, the other components comprise 15% or greater by weight and/or the base resin comprises 85% or less by weight. In some implementations, the other components comprise 30% or greater by weight and/or the base resin comprises 70% or less by weight. In certain embodiments, the substrate comprises at least about 80% by weight of the fragrance reservoir114. In some variants, the substrate comprises less than or equal to about 80% by weight of the fragrance reservoir114. In some implementations, the substrate comprises a material that has been foamed. For example, the substrate can be formed by adding a foamer to a base resin (such as the materials described above). The foamer can comprise chemical foaming agents that include, for example, blends or individual chemicals of isocyanate and water, azodicarbonamide, hydrazine, and sodium bicarbonate. The action of the foamer can create the chambers in the substrate. In certain embodiments, the foamer comprises azobisisobutyronitrile (AIBN). The fragrance reservoir114can be contained in a casing, such as a hard plastic case. The casing can include a shell160and a lid161. The shell160can comprise a taper such that an upper portion is wider than a lower portion. A lower end (e.g., bottom) of the shell160can include a grip G, such as ribs, knurling, a handle, etc. When the cartridge112is in the disengaged position, the grip can protrude out of the housing H. The grip can provide a convenient location to grasp the cartridge112, such as during installation and/or removal from the housing H. The shell160can have a lower opening O. In some embodiments, the lid161includes the vents V. The lid161can be configured to engage (e.g., abut) the engagement element130. The lid161can be configured to receive the engagement element130. For example, the lid161can include a groove that the engagement element130fits into when the cartridge112is connected with the support element129. The groove and/or the engagement element130can be rounded or chamfered to facilitate guiding the engagement element130into the groove. The lid161can have windows W. The windows W align with and/or be in fluid communication with the vents V. In some embodiments, air can enter the opening O, pass over and/or around the fragrance reservoir114, and exit through the windows W and vents V. In some variants, air can enter the vents V and windows W, pass over and/or around the fragrance reservoir114, and exit through the opening O. The shell160can have one or more struts162, such as ribs. The struts162can protrude into the opening O. The struts can include a stop163, such as at the intersection of the struts163. The stop163can limit downward travel of the impeller126relative to the shell160. SeeFIG.11. The fragrance reservoir114can include the impeller126. For example, some or all of the fragrance reservoir114can be molded or otherwise formed into an impeller shape. The impeller126can include a plurality of blades. The blades can be configured to facilitate airflow over the fragrance reservoir114, thereby dispensing some of the fragrance to the air. As mentioned above, the impeller126can include the cavity137, which can be configured to receive the shaft136. In some embodiments, the cavity137extends at least about half of the height of the impeller126. In some embodiments, the impeller126is hollow though some, most, or all of its axial height. The impeller126can be floating in the casing. For example, in certain variants, the impeller126can move within and relative to the casing, such as in the axial direction. In several embodiments, the impeller126is configured to rotate around an axis or rotation and slide along the axis of rotation. The impeller126can include the second connecting element139B, such as a metal washer. As illustrated, in some embodiments, the second connecting element139B is positioned in a bottom end of the cavity137. The impeller126can include a step or other feature that supports the second connecting element139B. II.C Operation In use, the cartridge112can be positioned under the housing H. The cartridge112can be moved upward into the housing H. For example, the cartridge112can be passed through an opening in the bottom of the housing H. As mentioned above, the housing H can have features that orient the cartridge112relative to the connection unit116. For example, the housing H and cartridge112can be keyed such that the cartridge112can be inserted into the housing H in only certain orientations. This can aid in co-locating mating features of the cartridge112and core unit111, such as the securing features131A,131B and/or the positioning features135A,135B. In some embodiments, the shaft136is received in the cavity137of the cartridge112. The shaft136can interface with walls of the cavity137, thereby aligning the cartridge112with the shaft136and/or other portions of the core unit111. For example, an axial centerline of the impeller126can be substantially aligned with (e.g., substantially collinear with) an axial centerline of the shaft136. The shaft136can be configured to engage with the walls of the cavity137in such a manner that rotation of the shaft136is transferred to the impeller126. For example, the shaft136can be received in the cavity137with an interference fit. In some implementations, the shaft136is resilient and/or configured to compress within the walls of the cavity137. The cartridge112can be engaged with the engagement element130. For example, the cartridge112can be pressed against the engagement element130. The cartridge112and engagement element130can be moved upward as a unit. This can compress or otherwise energize the biasing member134. In certain variants, the engagement element130is moved to abut against the support element129or a stop on the housing H. In some embodiments, the positioning features135A,135B interface. For example, the first positioning features135A (e.g., slots) of the support element129can receive the second positioning features135B (e.g., posts) of the cartridge112. The posts135B can be positioned at an end of the slots. The positioning features135A,135B can aid in properly orienting the cartridge112relative to the support element129. In certain embodiments, the second positioning features135B are received in the respective holes145in the control gears142. For example, the posts on the cartridge112can protrude through the slots in the support element129and extend into the holes145of the control gears142. The control gears142can be in a first position. The first position of the control gears142can be called an “unsecured position” because, in this position, the cartridge112is not secured to the connection unit116(e.g., if released by the user the cartridge112can be pushed away from the support element129by the biasing member134). In some implementations, the impeller126moves axially relative to the casing of the cartridge112. For example, in response to the shaft136being inserted into the cavity137, and/or the cartridge112being engaged with the connection unit116, an attractive force between the first and second connecting elements139A,139B can move (e.g., pull) the impeller126upward. As shown inFIG.10, the impeller126can be spaced apart from (e.g., suspended above) the stop163. This can reduce friction on the impeller126or otherwise facilitate rotation of the impeller126in the casing. In some embodiments, the connection between the connecting elements139A,139B transfers torque between the shaft136and the impeller126. In certain implementations, the movement of the impeller126occurs concurrent with or after the interfacing of the positioning features135A,135B. In certain implementations, the securing features131A,131B can enter a first stage of engagement. For example, in the first stage of engagement, the first securing features131A (e.g., hooks) of the connection unit116can be received in the second features131B (e.g., apertures) of the cartridge112. In certain implementations, the first stage of engagement of the securing features131A,131B occurs concurrent with or after the interfacing of the positioning features135A,135B. In some embodiments, when the securing features131A,131B are in the first stage of engagement, the cartridge112can be readily separated from the connection unit116. The cartridge112can secured to the support element129. This can comprise moving the securing features131A,131B into a second stage of engagement. For example, in some embodiments, the cartridge112is rotated relative to the support element129and/or the engagement element130. The securing features131A,131B can move relative to each other. For example, in the illustrated embodiment, the hooks can slide within the apertures131B. This can move an end portion of the hooks out of alignment with the apertures131B, thereby providing a physical interference between the first securing features131A and the support element129in the axial direction. In some embodiments, when the securing features131A,131B are in the second stage of engagement, the cartridge112is inhibited or prevented from being separated from the connection unit116. For example, the physical interference can stop the biasing member134from moving the cartridge112out of position (e.g., downward). In certain implementations, the rotation of the cartridge112causes the positioning features135A,135B to move relative to each other. For example, in the illustrated embodiment, the posts of the cartridge112can slide in the slots of the support element129, such as to an opposite end of the slots. In certain embodiments, because the posts are received in the respective holes145in the control gears142, the movement of the posts causes the control gears142to rotate, such as to a second position. The second position of the control gears142can be called a “secured position” because, in this position, the cartridge112is secured to the support element129, as discussed above. In some embodiments, rotation of the control gears142causes rotation of the gear141. In some embodiments, the controller can determine that the cartridge112has been properly installed, such as using information from one or more of the sensors124A,124B. At least partly in response, the controller can instruct the motor122to operate. For example, after detecting that the cartridge112is present and secure, the dispenser110can commence spinning the impeller126. The motor can spin the shaft136, which is transferred to the impeller126. This can cause air to flow over the impeller126and then exit the dispenser110, thereby providing fragrance to the ambient environment. In some embodiments, the dispenser110dispenses fragrance at least partly based on the occupancy sensor detecting that the space is occupied and/or has recently been occupied (e.g., within the at least about the last 10 minutes). The control unit118can be configured to control various operations of the dispenser110. For example, the control unit118can control operation of the motor122, such as rotational speed, “on time,” and/or activation frequency. The control unit118can be configured to balance fragrance distribution over the life of the cartridge112. In some embodiments, the control unit118activates the motor122such that the impeller126rotates at a rotational speed for a period, stops for a period, and then repeats. In certain implementations, the amount of fragrance released is controlled at least in part by factors such as: the rate of impeller rotation, the period of impeller rotation, the frequency of impeller rotation (e.g., the time between periods), the type of fragrant material, and/or other factors. The control unit118can account for of these factors in directing operation of the dispenser110. The dispenser110can be configured to maintain a substantially constant level of fragrance in the environment. In some embodiments, the length of time that the motor122is operated (the run time) is a function of the age of the cartridge112(e.g., the length of time that the cartridge122has been installed in the dispenser110). For example, the longer the cartridge112has been in the dispenser110the longer the motor122can be operated and/or the shorter the cartridge112has been in the dispenser110the shorter the motor122can be operated. This can compensate, for example, for the fragrance reservoir114becoming less full and/or less portent over time and/or with use. In some implementations, the run time for a dispensation cycle is directly tied to the age of the cartridge112. The run time can be affected by other factors. For example, the run time can be affected by the type of fragrant material, as certain materials are more potent than others. In some implementations, the dispenser110is configured to provide a desired service life. For example, the dispenser110can be configured to dispense scent, operate the motor122, and/or perform other operations achieve a service life of about: 3 months, 6 months, 1 year, or otherwise. In some variants, the dispenser110is configured to receive (e.g., via an input device) or to determine an amount of available power or fragrance, such as in the battery or fragrance reservoir114. The dispenser110can be configured to adjust operation based at least partly on the amount of available power or fragrance, such as to ration the power and/or fragrance to achieve a desired service time. In some embodiments, the cartridge112is configured to communicate a service life to the control unit118. For example, the cartridge112can communicate via RFID or otherwise. In some implementations, the dispenser110is configured to vary operation based at least partly on the size of the room that the dispenser110is installed in. In some embodiments, the dispenser110is configured to receive an input, such as via a switch on the control unit118, regarding the size of the room. For example, the dispenser110can receive an input of whether the room is small or large. According to some embodiments, for a small room, the motor122is operated for less than or equal to about 15 seconds every cycle period (e.g., greater than or equal to about 30 minutes). In certain variants, for a large room, the motor122is operated for greater than or equal to about 25 seconds every cycle period (e.g., less than or equal to about 30 minutes). The dispenser110can be adapted to disengage the cartridge112from the support element129. This can occur, for example, in response to a period of use of the cartridge112, number of uses of the cartridge112, or other criteria. In various embodiments, the cartridge112can be disengaged when (e.g., in response to) a determination is made (e.g., by the controller) that the cartridge112has reached a depleted state. In some embodiments, the dispenser110determines that the cartridge112is depleted based on time. For example, based on the number of days or months since the cartridge112was engaged with (e.g., installed in) the connection unit116. In certain implementations, the time is at least: 30 days, 60 days, 90 days, 180 days, or otherwise. In some implementations, a component of the dispenser110, such as the controller, has a software-controlled timer that resets and/or activates when the cartridge112is inserted. The timer can be based at least partly on a “term” of the cartridge112. The term can be programmed in the controller, such as being retained in non-transitory memory. The term can be based on, for example, the size and/or life of the cartridge that determines its useful life. The dispenser110can eject the cartridge112when the term is reached and/or the cartridge112is otherwise considered depleted. In some variants, the dispenser110determines that the cartridge112is depleted based on the length of time that the motor122has been on since the cartridge112was installed. In some embodiments, during a disengagement operation, the motor122changes direction. As discussed above, during normal operation, the motor122spins the output drive shaft in a first rotational direction, and such rotation can be transferred to the shaft136and impeller126. Because of the one-way connection140, such rotation is not transferred to the gear141. In some implementations, during the disengagement operation, the motor122reverses to spin the output drive shaft in the opposite rotational direction. This causes the one-way connection140(e.g., one-way clutch) to activate and thus transfer the motion to the gear141. In turn, the gear141can cause the control gears142to rotate from the secured position toward the unsecured position. In certain implementations, when the motor122spins the output drive shaft in the opposite rotational direction, torque from the motor122is not transferred to the impeller126and/or the impeller126does not rotate. Because the second positioning features135B of the cartridge112(e.g., the posts) are located in the holes145of the control gears142, the movement of the control gears142cause movement of the posts too. For example, the posts135B of the cartridge112can slide in the slots135A of the support element129. This causes the cartridge112to rotate relative to the support element129and/or to slide along the engagement element130. As the cartridge112rotates, the securing features131B (e.g., hooks) can rotate too, which can remove the physical interference holding the cartridge112in place. For example, the ends of the hooks can rotate back into the slots. Because the physical interference has been removed, the cartridge112is released and/or is no longer supported. The cartridge112can thus can be ejected from the support element129and/or can fall downward, such as by force of gravity. As is shown inFIG.11, in the disengaged position, the cartridge112can be separated from the support element129. The separation of the cartridge112from the support element129can occur because of and/or be furthered by the biasing members134, which apply a downward force on cartridge112(e.g., via the engagement element130). In certain embodiments, in the disengaged position, the cartridge112is spaced apart from the engagement element130. In some variants, the cartridge112remains in contact with the engagement element130in the disengaged position. The connection between the impeller126can the shaft136can detach during release of the cartridge112. In some embodiments, the force of the biasing members134and/or the weight of the cartridge112can overcome the attractive force of the connecting elements139A,139B and/or the frictional force between the shaft136and walls of the cavity137. Thus, as shown in the example ofFIG.11, the impeller126moves downward relative to (e.g., disengages at least partly from) the shaft136and/or the elements139A,139B separate from each other. In some embodiments, the impeller126can drop within the casing. For example, the impeller126can fall into contact with the stop163. SeeFIG.11. In various embodiments, the cartridge112can fall to the disengaged position (seeFIG.5B). The cartridge112can be caught and/or inhibited from further downward movement by the catch128. In some embodiments, the cartridge112drops at least about: 12 mm, 19 mm, 25 mm, or otherwise. The cartridge112can be maintained in the housing H even after the cartridge112has dropped. An observer can readily see the changed position of the cartridge112and recognize that replacement is needed. III. Dispenser210 FIGS.13A-13CIllustrate Another Embodiment of a Dispenser210. The dispenser210resembles and/or can include any of the features of the dispenser10,110. For example, as illustrated inFIG.13A, the dispenser210can include a housing H with vents V. A front portion of the housing H can be removable, such as by sliding the front portion off a rear portion of the housing H. As shown inFIGS.13B and13C, the dispenser210can include a core unit211. The core unit211can include a connection unit216and a control unit218. The connection unit216can include an impeller226. Some embodiments do not include the impeller226. The control unit218can include a controller and indicator unit, such as lights227. The dispenser210can include a cartridge212. The cartridge212can be inserted into the housing H, such as through a lower opening O. In some embodiments, the cartridge212is inserted generally vertically and then rotated to secure it with a locking mechanism of the housing H, such as a bayonet connection mechanism. In certain variants, the cartridge212is rotated at least about: 45°, 60°, 90°, or more. The cartridge212can include a fragrance reservoir214. The fragrance reservoir214can include a plurality of fins. The cartridge212can include a base270(also called an adapter). The base270can be configured to mate in a corresponding recess271in the housing H. In some embodiments, the base272is fixedly attached to the housing H. The cartridge212can include a rotation element272, such as a bearing or bushing. The rotation element272can enable the fragrance reservoir214to rotate relative to the base270. The rotatable portion of the cartridge212can be a fan and/or may be combined with a fan. In some implementations, the rotatable portion of the cartridge212may be produced using a fragrance infused TPE. The cartridge212can include a coupling region, such as a hub273. In some embodiments, the hub273comprises a recessed portion. The hub273can be configured to mate with a corresponding coupling region of the connection unit216, such as a shaft236. The shaft236can be part of or mechanically connected to the motor222. In some embodiments, the hub273is configured to receive rotational motion from the shaft236. For example, an end of the shaft236can have one or more ribs or flutes that are received in corresponding grooves or notches in the hub273, or vice versa. In some embodiments, the shaft236is part of and/or rigidly connected to the impeller226. The dispenser210can include a motor222. In some embodiments, the motor222spins the shaft236, which spins the fragrance reservoir214. In certain implementations, the motor222spins the impeller226. The motor222can comprise an electric motor. The motor222can be positioned above the cartridge212. The control unit218can be configured to control the motor222, such as the rotational speed, “on time,” and/or activation frequency. The controller can balance fragrance distribution over the life of the cartridge212. In some embodiments, the controller activates the motor222such that the fragrance reservoir214rotates at a certain rotational speed, during an amount of time, stops for an amount of time and then repeats. In certain implementations, the amount of fragrance released is controlled by: the speed at which the fragrance reservoir214rotates, the length of time during which the fragrance reservoir214rotates, how often the fragrance reservoir214is activated (e.g., the time between intervals), and/or the type of fragrance reservoir214. The time, speed, and intervals can be automatically adjusted as the fragrance in the fragrance is depleted, such as to maintain a similar (e.g., generally uniform) level of scent distribution. In some implementations, when new, the fragrance reservoir214will rotate slower, for less time, and/or will have longer intervals in between uses. In some implementations, nearing the end of life, the fragrance reservoir214will rotate faster, for longer period of time, and/or with shorter intervals in between uses. IV. Dispenser310 FIGS.14A and14Billustrate another embodiment of a dispenser310. The dispenser310resembles and/or can include any of the features of the dispenser10,110,210. As illustrated, the dispenser210can include a housing H with vents V, a first door D1, and a second door D2. The first door D1can be on a top of the dispenser310. The first door D1can provide access to portions of a core unit311, such as a controller318(e.g., PCB), motor322, and/or power supply. In some embodiments, the power supply comprises batteries. The second door D2can be on a bottom of the dispenser310. The second door D2can provide access to a cartridge312. For example, a user can open the second door D2to install or remove the cartridge312. Air can access the cartridge312through the vents V and a bottom opening O. The cartridge312can include a fragrance reservoir314in an outer casing, such as a shell160. In some implementations, the fragrance reservoir314is enclosed in the cartridge312. In some variants, the cartridge312is open, such as on the top, and/or does not include a lid. The fragrance reservoir314can comprise an impeller326, such fan blades. In some embodiments, the impeller326is rotatable about a central axle380, such as a post projecting upward from a bottom of the cartridge312. The impeller326can have a cavity337that is configured to receive a shaft336of the core unit311. The shaft336can be rotatable by the motor322. In some embodiments, the motor322is a direct drive motor. The cavity337and shaft336can couple such that rotational motion can be transferred from the shaft336to the impeller326. For example, in some implementations, the shaft336is received in the cavity337with an interference fit, such as an interference in a radial direction. In some variants, the shaft336and impeller326are connected with attractive magnetic elements, such as a magnet on an end of the shaft336and a metal element (e.g., a washer) in the cavity337. The motor322can drive the shaft336to drive the impeller326, thereby dispensing fragrance. V. Certain Terminology Terms of orientation used herein, such as “top,” “bottom,” “horizontal,” “vertical,” “longitudinal,” “lateral,” and “end” are used in the context of the illustrated embodiment. However, the present disclosure should not be limited to the illustrated orientation. Indeed, other orientations are possible and are within the scope of this disclosure. Terms relating to circular shapes as used herein, such as diameter or radius, should be understood not to require perfect circular structures, but rather should be applied to any suitable structure with a cross-sectional region that can be measured from side-to-side. Terms relating to shapes generally, such as “circular” or “cylindrical” or “semi-circular” or “semi-cylindrical” or any related or similar terms, are not required to conform strictly to the mathematical definitions of circles or cylinders or other structures, but can encompass structures that are reasonably close approximations. Conditional language, such as “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain embodiments include or do not include, certain features, elements, and/or steps. Thus, such conditional language is not generally intended to imply that features, elements, and/or steps are in any way required for one or more embodiments. Conjunctive language, such as the phrase “at least one of X, Y, and Z,” unless specifically stated otherwise, is otherwise understood with the context as used in general to convey that an item, term, etc. may be either X, Y, or Z. Thus, such conjunctive language is not generally intended to imply that certain embodiments require the presence of at least one of X, at least one of Y, and at least one of Z. The terms “approximately,” “about,” and “substantially” as used herein represent an amount close to the stated amount that still performs a desired function or achieves a desired result. For example, in some embodiments, as the context may dictate, the terms “approximately”, “about”, and “substantially” may refer to an amount that is within less than or equal to 10% of the stated amount. The term “generally” as used herein represents a value, amount, or characteristic that predominantly includes or tends toward a particular value, amount, or characteristic. As an example, in certain embodiments, as the context may dictate, the term “generally parallel” can refer to something that departs from exactly parallel by less than or equal to 20 degrees and the term “generally perpendicular” can refer to something that departs from exactly perpendicular by less than or equal to 20 degrees. Unless otherwise explicitly stated, articles such as “a” or “an” should generally be interpreted to include one or more described items. Accordingly, phrases such as “a device configured to” are intended to include one or more recited devices. Such one or more recited devices can also be collectively configured to carry out the stated recitations. For example, “a processor configured to carry out recitations A, B, and C” can include a first processor configured to carry out recitation A working in conjunction with a second processor configured to carry out recitations B and C. The terms “comprising,” “including,” “having,” and the like are synonymous and are used inclusively, in an open-ended fashion, and do not exclude additional elements, features, acts, operations, and so forth. Likewise, the terms “some,” “certain,” and the like are synonymous and are used in an open-ended fashion. Also, the term “or” is used in its inclusive sense (and not in its exclusive sense) so that when used, for example, to connect a list of elements, the term “or” means one, some, or all of the elements in the list. Overall, the language of the claims is to be interpreted broadly based on the language employed in the claims. The language of the claims is not to be limited to the non-exclusive embodiments and examples that are illustrated and described in this disclosure, or that are discussed during the prosecution of the application. VI. Summary The technology of the present disclosure has been discussed in the context of certain embodiments and examples. The technology extends beyond the specifically disclosed embodiments to other alternative embodiments and/or uses of the embodiments and certain modifications and equivalents thereof. For example, although certain embodiments are disclosed in the context of a dispenser with a fan, the technology can be applied to dispensers without fans too. As another example, while some embodiments have been described in which the cartridge is replaced, in some variants the cartridge is configured for reuse, such as having a refillable fragrance reservoir. The fragrance dispensers can include any feature from any of U.S. Pat. Nos. 8,573,447, 8,860,347, 8,889,082, and 8,931,713, which are incorporated by reference herein in their entirety, but shall not be used for construing the claims herein. Any two or more of the components of the dispenser system can be made from a single monolithic piece or from separate pieces connected together. Various features and aspects of the disclosed embodiments can be combined with or substituted for one another in order to form varying modes of the invention. The scope of this disclosure should not be limited by the particular disclosed embodiments described herein. Certain features that are described in this disclosure in the context of separate implementations can also be implemented in combination in a single implementation. Conversely, various features that are described in the context of a single implementation can also be implemented in multiple implementations separately or in any suitable subcombination. Although features may be described above as acting in certain combinations, one or more features from a claimed combination can, in some cases, be excised from the combination, and the combination may be claimed as any subcombination or variation of any subcombination. Moreover, while operations may be depicted in the drawings or described in the specification in a particular order, such operations need not be performed in the particular order shown or in sequential order, and all operations need not be performed, to achieve the desirable results. Other operations that are not depicted or described can be incorporated in the example methods and processes. For example, one or more additional operations can be performed before, after, simultaneously, or between any of the described operations. Further, the operations may be rearranged or reordered in other implementations. Also, the separation of various system components in the implementations described above should not be understood as requiring such separation in all implementations, and it should be understood that the described components and systems can generally be integrated together in a single product or packaged into multiple products. Additionally, other implementations are within the scope of this disclosure. Some embodiments have been described in connection with the accompanying drawings. The figures are drawn to scale, but such scale is not limiting, since dimensions and proportions other than what are shown are contemplated and are within the scope of the disclosed invention. Distances, angles, etc. are merely illustrative and do not necessarily bear an exact relationship to actual dimensions and layout of the devices illustrated. Components can be added, removed, and/or rearranged. Further, the disclosure herein of any particular feature, aspect, method, property, characteristic, quality, attribute, element, or the like in connection with various embodiments can be used in all other embodiments set forth herein. Additionally, any methods described herein may be practiced using any device suitable for performing the recited steps. In summary, various embodiments and examples of fragrance dispensers and related processes have been disclosed. Although the dispensers and processes have been disclosed in the context of those embodiments and examples, the technology of this disclosure extends beyond the specifically disclosed embodiments to other alternative embodiments and/or other uses of the embodiments, as well as to certain modifications and equivalents thereof. This disclosure expressly contemplates that various features and aspects of the disclosed embodiments can be combined with, or substituted for, one another. Thus, the scope of this disclosure should not be limited by the particular disclosed embodiments described above, but should be determined only by a fair reading of the claims that follow. | 60,199 |
11857705 | DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT InFIG.1, an air treatment unit, according to the present invention, is shown in schematic form at10. The air treatment unit10is preferably configured to be attached to a wall12, which is most preferably a ceiling wall, but could be a peripheral side wall surrounding an occupiable space. The air treatment system10has a frame14that is mounted to the wall12. The frame14supports a light source16, characterized herein as a “UV light source”, which is intended to encompass all different forms of light known to those skilled in the art capable of deactivating molds, spores, germs, etc., that are entrained in air, to thereby effect disinfecting of that air. The frame14further supports an air moving assembly18that causes air within a space to be directed into a frame volume20that has UV rays from the source16therein capable of disinfecting air. By mounting the frame14to the wall12, the frame14and UV light source16are maintained in an operative position within a space22in which air is to be disinfected. The air moving assembly18causes room air to be directed into the volume20, wherein it is treated by the UV light source and thereafter reintroduced to the space22. The frame14is also configured to allow air expelled from a duct24on a forced air source26to be directed into the volume20for treatment by the UV rays from the light source16. FIGS.2and3show alternative setups for the air treatment unit10within the space22. In these Figures, additional details of the air treatment unit10are also shown. InFIG.2, a primary treatment volume28is shown on the frame14with direct exposure to the operatively positioned UV light source16. In the primary treatment volume28there is an active germicidal energy field. An air guidance assembly30has at least one opening32, preferably with an elongate configuration, through which air from the primary treatment volume28passes to be distributed to the space22with the frame14operatively positioned on the wall12. Preferably, the opening(s)32has/have a louver arrangement wherein UV light from the source16creates a kill zone within the volume of the openings32wherein the air is further disinfected before dispersing into the space22. Immediately outside of the frame14there exists a passive external germicidal energy field that treats the room air. That is, UV rays are directed through the louver volumes/openings32to the region immediately outside of the frame14and have sufficient intensity in this region to effect a significant level of passive treatment. The air moving assembly18forces air from the space22into the primary treatment volume28to avoid room air stagnation. The system10inFIG.3has the same basic construction for the frame14, and similar components thereon, including the UV light source16, the primary treatment volume28, the air guidance assembly30, and the air moving assembly18. Additionally, the frame14is configured so that the aforementioned duct24on the wall12forces air, typically conditioned through an HVAC system, directly into the primary treatment volume28. When the forced air source26and air moving assembly18are operating at the same time, air from the duct24and air moving assembly18is caused to mix within the primary treatment volume28, wherein it is treated by the UV radiation from the source16. The schematic representation of components inFIGS.1-3is intended to encompass the components, as shown in specific embodiments described hereinbelow, and virtually an unlimited number of variations of those components and their interaction. The preferred embodiments described herein are exemplary in nature only and represent specific forms of the invention as generically defined inFIGS.1-3. One exemplary form of the air treatment unit10is shown inFIGS.4and5. The frame14has a main frame portion34and a subframe portion36. The subframe portion34is used to effect mounting of the frame14to the wall12. In this embodiment, the subframe portion36has a mounting portion38that spans between, and is supported upon, T-bar components40on a ceiling grid T-bar system so that with the frame14in the operative position ofFIG.4, the main frame portion34depends from the downwardly facing ceiling surface42. In this embodiment, the length L and width W of the frame14are the same, with one preferred length and width dimension being 24 inches. Making the length L and width W the same is not a requirement, nor is a squared shape. Room geometry may dictate a different optimal shape. The components inFIGS.4and5are shown substantially to scale based upon the length and width L, W each being twenty four inches. The primary treatment volume28has a square shape as viewed along a vertical central axis44. The air guidance assembly30extends around and effectively frames the primary treatment volume28, as viewed from below inFIG.5. The air guidance assembly30consists of a series of slats46, each with a square frame shape. The slats46are mounted through a plurality of rods48depending from the subframe portion36. The slats46are flat, radially overlap, and are mounted in a close vertically spaced relationship to define louver volumes corresponding to the aforementioned elongate opening(s)32. The louvers/openings32define the aforementioned kill zone as air distributes radially outwardly relative the central axis44from the primary treatment volume28and funnels into the volume between the inner edges50of the slats46and the perimeter outer edges52thereof. This kill zone region is identified by the width dimension KZ inFIG.5. Air is forced to travel controllably in a confined path and in a radial direction through the volume of the louvers/openings32over the distance KZ and, in its overall path within the treatment energy field, between the primary treatment volume28and a region of the space22outside of the primary treatment volume. With this arrangement, air within the primary treatment volume28distributes through the louvers/openings32radially in a pattern substantially 360° around the central axis44. This flow pattern is identified generally by the arrows54. Air flow into the primary treatment volume28in a downward direction is blocked by a bottom wall56on the frame14, which defines the lower boundary of the primary treatment volume28. The bottom wall56supports the air moving assembly18, which is a conventional-type fan that draws air from the space22generally axially upwardly into the primary treatment volume28, as indicated by the arrows58. The bottom wall56and air moving assembly18can be constructed to move as one piece and are supported together on hanging rods60depending from the subframe portion36. A wingnut62is shown for securing the bottom wall56on the bottom of one of the hanger rods60in the operative position ofFIG.4, wherein the bottom wall56blocks the primary treatment volume28and provides a decorative cover for the unit10, including over the downwardly facing surface64of the bottommost slat46. With this arrangement, by removing the wingnuts62, the bottom wall56and air moving assembly18thereon can be lowered to better access the air moving assembly18and to also access the primary treatment volume28and the plurality of lamps66, together making up the UV light source16. In this embodiment, four lamps66are mounted to the frame14at equal distances from the central axis44. The lamps66are arranged at regular angular intervals around the axis44. In this embodiment, the lamps66cooperatively produce a square shape that is complementary to the shape of the primary treatment volume28. As viewed along the axis44, four radial lines spaced at 90° to each other are capable of passing, one each, through a different lamp66. As depicted, each lamp66includes a pair of bulbs68. Precise construction of the lamps66and their placement may vary considerably. One skilled in the art could readily come up with different arrangements to maximize exposure of air to the UV radiation generated by the lamps66within the primary treatment volume28, the kill zone region in the louvers/openings32, as well as in the passive treatment region outside of the frame14. The ability to separate the bottom wall56facilitates placement and maintenance of the lamps66, as to change bulbs68, and also permits cleaning of the slats46which may accumulate dust over time which contrasts with the preferred black coloration of the exposed slat surfaces. The subframe portion36is constructed so that the duct24can be connected thereto or positioned in relationship therewith, so that a discharge region70expels air from the forced air source26preferably downwardly, as indicated by the arrow72, directly into the primary treatment volume28. The forced air source26may be any type of structure that produces pressurized air and is typically one that delivers heated or cooled air under pressure to and through the duct24into the space22. While not required, in the depicted embodiment, the central axis44coincides with the downwardly moving path of air from the duct24and the upwardly moving path of air generated by the air moving assembly/fan18. As depicted, the axis44is at the center of both paths, which are substantially parallel to each other. The upwardly and downwardly directed air paths at least partially coincide so that air in the separate paths is caused to mix within the primary treatment volume28and is thereafter diverted in a non-vertical direction through the louvers/openings32into a region of the space outside of the primary treatment volume28. Commonly, the air moving assembly18will be running constantly with the air treatment unit10in an “on” state. Thus, air is continuously drawn from the space22upwardly into the primary treatment volume28, exposed to the radiation field generated by the UV light source16therein, and further treated in the kill zone within the louvers/openings32from where it is dispersed back into the space22, and there passively treated in a region immediately outside of the frame14. When the forced air source26is operated, the incoming flow of air from the duct24becomes exposed to the radiation within the primary treatment volume28as it is mixed with the flow generated by the air moving assembly/fan18. Thus, the incoming air is disinfected by the air treatment unit10as it is introduced into the space22. The pressure from the duct air causes a higher pressure distribution of air radially outwardly from the air treatment unit10relative to the axis44. It should be understood that the invention also contemplates a more passive introduction of duct air as contemplated in theFIG.2embodiment. Further, the description of the structure inFIGS.4and5, and others hereinbelow, relative to a ceiling mount is intended to be exemplary as one particular operative position for the air treatment unit10. The air treatment unit10could be mounted other than on a ceiling. Thus, the reference to vertical and horizontal should not be limited to a ceiling mount, and these references are arbitrary in the event that the air treatment unit is mounted in another orientation. For example, by changing the orientation of the air treatment unit10, the basic principles of operation are similar, even if not preferred. While the axis orientation may be changed to an extent to become horizontal, for purposes of simplicity in the claims and description herein, “vertical”, in characterizing the axis orientation, is an arbitrary reference that is not limited to any specific orientation. Also, while not necessary, for purposes of uniformity of air treatment, the frame24is symmetrical on diametrically opposite sides of a reference plane containing the vertically extending axis44. In this embodiment, the frame is symmetrical about orthogonal reference planes RP1, RP2extending through the central axis44. Some variations in the air treatment unit10, as described above, will now be described. Again, it is should be emphasized that these different versions are intended only to be exemplary in nature, showing other potential operating features and mounting options. InFIGS.6and7, a treatment unit10′ is shown that is similar to the treatment unit10with a primary difference being that the subframe portion36′ is modified from the subframe36. In this embodiment, the subframe portion36′ has a squared housing74with an upper, outwardly projecting flange76that is supported on T-bar components40on a drop ceiling to maintain the frame14′ in its operative position. The lamps66′ are mounted on a downwardly facing surface78on the housing74within a primary treatment volume28′. The lamps66′ are arranged so that the bulbs68′ are in side-by-side relationship as opposed to in vertically spaced relationship, as shown for the bulbs68inFIGS.4and5. An air moving assembly/fan18′ is mounted on a bottom wall56′ to draw in room air in a direction of the arrows IA′, with treated air directed into the room space in a pattern indicated by the arrows OA′. The air treatment unit10′ otherwise generally functions in the same manner as the air treatment unit10, as described above. The top wall80of the subframe portion36′ may have an opening as large as a discharge opening on the duct24, or may simply allow passage of one or more wires82associated with electrical components84on the frame14′ and required to operate the lamps66′, air moving assembly/fan18′, and any other electrical components. A like, or identical, unit10′ can be flush mounted to a surface86, as shown inFIGS.8-10. Mounting may be effected with the bottom wall56′ separated, as shown inFIG.9, to facilitate access to a top wall80through the primary treatment volume28′. This also facilitates the connection of the wires82within a junction box88on the wall90defining the mounting surface86. Conventional fasteners92can be used to secure the flange76against the surface86to maintain the unit10′ in its operative position, as shown inFIG.10. Air flow pattern is identical to that shown inFIG.7, as indicated by the arrows IA′, OA′. InFIGS.11-14, a modified form of air treatment unit is shown at10″, including sequence drawings showing how the same is installed with respect to ceiling T-bar components40on a drop ceiling. The air treatment unit10″ is substantially the same as the air treatment unit10′, with the main difference being that the air moving assembly/fan18″ is mounted to depend from a downwardly facing surface94on the bottom wall56″. FIG.11also shows the initial step for placing the air treatment unit10″ in its operative position ofFIG.14. As shown, the entire air treatment unit is placed at an angle α to horizontal. In this orientation, a leading end96of the flange76″ is situated so that it can be directed over a horizontal leg98on the T-bar component40. By then being shifted in the direction of the arrow100, the trailing end102of the flange76″ can be tipped upwardly and will clear a leg104of the T-bar component40shown on the right side in FIG.11. The entire air treatment unit10″ can then be shifted to the right inFIG.11so that the flange76″ bridges, and is supported cooperatively by, the legs98,104. The wires82can be electrically connected at the junction box88. By separating the wingnuts62″, the bottom wall56″ and air moving assembly/fan18″ can be lowered as a unit, as shown inFIG.13, to assist assembly, maintenance, cleaning, etc. The bottom wall56″ can then be re-secured to assume theFIG.14state. InFIG.15, an air treatment unit is shown at10″′ that is substantially the same as the air treatment unit10′ with the exception that the frame14″ has a plurality of mounting eyelets106fixed thereto. The eyelets106accommodate cables108which connect between the eyelets106and separate eyelets110fixed to a wall112at which the frame14″′ is operatively positioned. The eyelets106,110and cables108cooperatively make up a suspension assembly at114through which the frame14″′ is spaced from a downwardly facing surface116on a wall118with the frame14′″ operatively positioned. Of course, virtually any type of a conventional structure might be used to make up the suspension assembly to establish the relationship between the air treatment unit10″′ and the associated wall118. Wires82can be extended from the frame14′″ to the junction box88to electrically connect operating components. With all embodiments, the main frame portions and subframe portions may be configured to define spaces for electrical components and wiring needed to power the lamps, air moving assemblies, etc. It is not necessary to get into all of the details of the electrical components and their connection, as one skilled in the art would be able to readily devise different component arrangements to achieve the objectives set forth herein. As noted above, the inventive air treatment unit can be used to replace a supply vent conventionally used to distribute air in an occupied space. Alternatively, a more passive interaction between the air treatment unit and an existing duct outlet is effected. The air treatment unit can be operated to disinfect with air movement induced through the duct24and/or by the air moving assembly18. That is, the forced air source26and air moving assembly18may be separately operated or operated together, in the latter case causing a synergistic effect. Many different variations of the above-described structure are contemplated. Several such variations are described hereinbelow using the same basic components and concepts described above, with it being understood that all like functioning components are interchangeable between the different embodiments. In one form, the basic air treatment unit10may be made without its own, or any, air moving assembly, identified at18inFIGS.1-3. With the dotted line showing of the air moving assembly18inFIGS.1-3, the schematic representations depict the air treatment unit10in alternative forms both with and without an air moving assembly18being a part thereof. In other words, the invention contemplates that air flow is somehow induced into the volume20/primary treatment volume28and therefrom in a radial direction relative to a reference axis for the volume20/preliminary treatment volume28to produce the radially outwardly moving air pattern that ultimately results in disinfected air being distributed into the space22. This air flow can be induced by an air moving assembly18that is part of the air treatment unit10, an air moving assembly spaced from the frame14and dedicated to operation of the air treatment unit10, or another structure, such as one causing air to be delivered through an outlet200on a duct24, as shown inFIGS.1and3, from the source26to condition the space22, as by cooling, heating, moisturizing, dehumidifying, etc. Alternatively, conditions in a room may cause natural convection which more passively causes the air to move guidingly into the volume20/primary treatment volume28, and in a radially outwardly moving pattern, during which movement the air is disinfected by the light rays from the UV light source16. In further explaining variations of the above embodiments, description is made with reference to an axis, generally identified at202inFIG.16. The axis202extends through the volume20/primary treatment volume28and generally represents the location away from which air flow is directed from within the volume20/primary treatment volume28in a “radial” direction, as indicated by the arrows204. In the specific embodiments illustrated inFIGS.4-15, and described hereinabove, the air travels in a radially outwardly moving pattern substantially fully around the reference axis, which corresponds to what is depicted schematically inFIG.16. It should be understood that within the description of a full 360° pattern around a reference axis, it is contemplated that there might be certain frame structures or other structures that block some of the radial flow. However, even with such discrete blockage, the overall pattern is considered to be substantially a full 360°. The basic concepts and structures described above can also be adapted to deliver disinfected air in a radial outward pattern that is dictated by the geometry of the region at which the air treatment unit10is placed. For example, a modified air treatment unit10amight be placed at an inside corner location at206. From the reference axis202a, the angular dimension θa for the radially outwardly moving pattern of disinfected air, indicated by the arrows204a, is on the order of 90°. Another form of air treatment unit10bmay be matched to an outside corner region at208whereby the angle θb around the axis202b, corresponding to the angle θa, is on the order of 270°. The arrows204bshow the direction of the radially outwardly moving air pattern. As shown inFIG.19, an air treatment unit10cmay be placed against a vertical wall surface210whereby the flow pattern angle θc around the axis202c, indicated by the arrows204c, is on the order of 180°. It should also be emphasized that heretofore, the axis44, corresponding to the axis202, has been generally designated as vertical, which is a preferred orientation for the air treatment unit, whether suspended from a ceiling or wall mounted. The arrangements shown inFIGS.17-19can be ceiling and/or wall mounted. However, the reference axis may be horizontal and at any angle between horizontal and vertical. In all embodiments, whether the axis identified generically or as “vertical”, the intent herein throughout the Detailed Description and claims is that the axis orientation is not limited by its orientation, with “vertical” being adopted to provide a simple frame of reference throughout the description and claims. Starting with the generic descriptions above, and using components in the exemplary embodiments, numerous different variations of the air treatment unit, with and without an air moving assembly, can be produced, representative ones of which are shown schematically inFIGS.20-26, below. As shown inFIG.20, the air moving assembly10aeffectively is a combination of: a) a fan18aon a frame14a, which fan18amoves air parallel to the axis202a′ upwardly into the primary treatment volume28a; and b) a forced air source26adelivering air axially downwardly through a duct24athat causes flow mixing, resulting in untreated air being drawn axially upwardly by the fan18aand disinfected air being discharged radially from the primary treatment volume28aas respectively indicated by the arrows DA (disinfected air flow) and UA (untreated air flow). As in the prior embodiments, UV rays may effect further air treatment radially outside the frame14a, as potentially occurs with the other embodiments inFIGS.21-30, described below. FIG.21discloses an air treatment unit10b, with a frame14b, similar to the air treatment unit10ainFIG.20, with an air inputting duct24bbut without any fan corresponding to the fan18a. The direction of disinfected air is, as shown by the arrows DA, similar to that inFIG.20, without the effects of turbulence resulting from the colliding air inputs. Provision may be made to circulate room air back into the primary treatment volume28b. InFIG.22, an air treatment unit10cis depicted wherein a fan18con a frame14cis incorporated as inFIG.20but with a duct24cdrawing air so as to cause it to move oppositely to how air moves in the duct24a, thereby producing a low pressure region within the primary treatment volume28c. The result of this construction is that untreated air flows axially inwardly as indicated by the arrows UA, with disinfected air flowing radially outwardly as indicated by the arrows DA. The air treatment unit10dinFIG.23is similar to that inFIG.22, but does not use a fan, corresponding to the fan18c, on its frame14d. Air flows in the duct24din the same direction as the air flows in the duct24cinFIG.22, thereby to produce a low pressure volume with a resulting radial and/or axial inflow to the primary treatment volume28dof untreated air, as indicated by the arrows UA, and outflow of disinfected air, as indicated by the arrows DA. InFIG.24, an air treatment unit10ecorresponds to the unit10ainFIG.20, without any axial delivery of air through any duct corresponding to the duct24a. A fan18e, on a frame14e, moves air axially into the primary treatment volume28e, thereby causing radial delivery of disinfected air, as indicated by the arrows DA. FIG.25depicts an air treatment unit10f, corresponding in construction to the air treatment unit10e, with the exception that a fan18fon a frame14fmoves the air axially from the primary treatment volume28f. This produces a low pressure at the lower region of the primary treatment volume28f, thereby potentially allowing a certain volume of untreated air to be delivered radially to the primary treatment volume28ffrom the space, as indicated by the arrows UA, and disinfected air to be expelled radially from the primary treatment volume28fin the direction of the arrows indicated by DA. FIG.26discloses an air treatment unit10gwith a frame14gand which has no air moving assembly—fan or forced air—and thus relies upon natural convection to cause untreated air to migrate into the primary treatment volume28g, with disinfected air discharged in the direction of the arrows DA. The various configurations above are exemplary but do not make up all potential different layouts that might be devised, according to the invention, to cause different air movement to thereby induce flow of air into and from within the primary treatment volume in the radially outwardly moving pattern. Further, in theFIG.26embodiment, the convection may be altered by other dedicated or non-dedicated structure(s). For example, temperature differences may cause air to move in paths that induce a flow of untreated air into the primary treatment volumes and expulsion of disinfected air therefrom. Natural flow of air caused by doors, vents, windows, etc. may facilitate this air flow pattern development. As shown generically inFIG.27, UV lamps16a,16b,16c,16dare preferably strategically placed in spaced relationship to the axis202in a surrounding arrangement whereby air is caused to be substantially uniformly exposed to UV rays generated by the lamps16a-16din operation. While four such lamps16a-16dare shown, less than four or greater than four might be utilized depending upon the particular shape and size of the frame on the air treatment unit. Further, while straight UV lamp configurations are depicted above, the lamp shapes are not limited. For example, a curved shape might be integrated into the design, as could be a full ring-shaped lamp. The UV lamps16a-16dare selected to optimize air treatment. As noted above, there are different zones of treatment resulting from the basic design described above. That is, the air is preferably exposed within the primary treatment volume to a relatively uniform density of ultraviolet rays. Between the aforementioned slats, the louver volume is exposed to ultraviolet rays, which is identified above as the “kill zone”. A more passive exposure of the air to the UV rays occurs as the air is expelled radially from the louver volume between slats. Thus, the overall system is designed to coordinate the exposure in these three zones to optimize the progressive disinfecting of the air, starting within the primary treatment volume and continuing to where the air resides outside of the frame and within the particular space in which treated air is desired. FIG.28depicts a generic form of cooperating slats212a,212b,212c,212d, corresponding to the slats46, described above. As depicted, each of the slats212a-212dis of generally flat shape and resides effectively within a plane Pa, Pb, Pc, Pd, successively. Representative slats212a,212bhave flat surfaces214,216, respectively, which face each other and bound a louver volume218, making up a portion of the aforementioned “kill zone”. The other slat pairs212b,212c;212c,212dcooperate in the same fashion. As depicted, the slats212a-212dhave the same shape and locations, as viewed from an axial perspective. While this is not required, a certain level of radial overlap, identified from the axial perspective, is preferred to create “kill” volumes in which air flow is effectively confined and guided. The planes thereof (Pa-Pd) are substantially orthogonal to the axis202. There is no requirement that the slats have the same construction or that the spacing therebetween be identical. In the depicted form, the slats212a-212dhave the same configuration, spacing, and orientation. While the frame perimeter from the axial perspective in the above-described embodiments is square or rectangular, this shape is not critical. For example, as shown inFIG.29, the frame14hcould have a round shape, or any other shape best matched to its particular location, with an axis202. As further noted above, the ceiling mount is the most common location with a full 360° coverage. However, the same type of unit could be used on a vertical wall so that the axis202is horizontal, or assume another orientation, and still function effectively. As depicted in the prior embodiments, multiple UV lamps are situated at substantially the same axial location. The lamps could be axially stacked or in a staggered relationship. As depicted, the UV lamps are preferably at least partially radially inside of the slats212and the louver volumes218wherein air guidingly moving therethrough continues to be disinfected. The invention is further directed to a method of treating air in a space, as shown in flow diagram form inFIG.30. As shown at block220, an air treatment unit is obtained having a frame configured to define a primary treatment volume with an axis, together with a source of UV light. As shown at block222, the frame is placed in an operative position relative to a space in which air is to be treated. As shown at block224, air within the space is caused to be moved into the primary treatment volume and disinfected by being exposed to UV rays generated by the source of UV light and the disinfected air is controllably guided through the frame in a radially outwardly moving pattern extending through at least 90° around the axis. Another generic form of treatment unit, according to the invention, is shown inFIGS.31and32at104′. The treatment unit104′has a frame144′with a volume204′/284′within which air is treated by a UV light source164′and caused to be dispersed away from the frame144′. The treatment unit104′has different operating states, as described below. The frame144′is operatively mounted with respect to a wall12that may be a ceiling, vertical wall, etc. The frame144′has an associated wall250with at least one opening252therein to allow UV light rays to pass therethrough into a volume of space within which the air treatment unit resides with the treatment unit104′in at least one of its operating states. The at least one opening252has an “effective area” through which the UV light rays pass to contact any surface within a space in direct line with the light generating portions of the UV light source164′with the treatment unit104′in at least one of its operating states. At least one part254is provided that has different relationships with the at least one opening252. In one relationship, the at least one part254is situated so that the at least one opening252has a first effective area, mentioned above. In a second relationship, the at least one part254at least partially blocks the at least one opening252so that the effective area thereof is less than the first effective area. The at least one part254may effectively fully block the at least one opening252. With this arrangement, the air treatment unit104′is changeable between first and second states. In the first state, the at least one part254is situated relative to the at least one opening252whereby a predetermined part of the volume of space within which the air treatment unit resides is strategically blocked from direct exposure to UV light rays generated by the UV light source. In other words, at least part of the area defined by the at least one opening252is blocked so as not to allow passage thereinto of UV light rays from the UV light source164′. In a second state, the relationship of the at least one part254to the at least one opening252is such that at least a portion of the aforementioned predetermined part of the volume of space within which the air treatment unit resides becomes directly exposed to UV light rays from the UV light source164′. The change between the first and second states is characterized as changing the effective area of the at least one opening252. The area is considered to be effectively changed even though the at least one part254may be simply blocking a certain pathway for UV light rays which will be considered herein as an effective reduction in area of the at least one opening252. As noted above, each of the volumes204′,284′is considered to have an axis from which disinfected air distributes at least radially in a dispersion path. While the wall250in a preferred form is at a location where it blocks principally axial light ray transmission, this particular construction is not required. The wall250can be provided at any location with the at least one part254having a changed relationship with the at least one opening252, as the treatment unit is changed between the first and second states, such that there is surface treatment over one area with the treatment unit in the second state and a reduction in area or blocking of the surface treatment in the first state. By strategically constructing the treatment unit104′, including the construction and cooperation between the wall opening(s)252and associated part(s)254, the treatment unit104′can be changed selectively between states wherein it is used within a space primarily for surface treatment and one wherein it is used primarily to circulate disinfected air with controlled UV light ray projection, thereby to avoid direct contact with humans and animals within the space. The strategic construction of the components inFIG.32, with many potential different configurations, potentially also affords the ability to simultaneously carry on both surface and circulating air treatment without potentially dangerous exposure of occupants of the space to UV light rays from the UV light source164′. It should also be reemphasized that the description of orientation of axes, reference to top and bottom, etc., concerns relative terms which are not intended to be limiting. For example, the treatment unit104′with substantially the same construction may be attached to a ceiling wall so that the axis of the primary treatment volume extends vertically or attached to a vertically extending wall so that the same axis extends substantially horizontally. In the latter case, the axially spaced regions are still considered to be top and bottom locations herein. What is preferred with the construction inFIGS.31and32is that changing of state allows selection of primarily surface or air treatment or a combination thereof with controlling of direct exposure to UV light rays from the UV light source164′. The schematic showing of the treatment unit104′is intended to encompass all basic structures described hereinabove, as well as those described below, with the ability to change between the first and second states. Without limitation, the wall250may be any wall structure, whether or not described above. A modification of the bottom wall54will be used in examples, described below, but should not be viewed as limiting. InFIGS.33and34, a treatment unit is shown at104′with a frame144′having a volume204′/284′for air which is treated by a UV light source164′. The volume204′/284′has an axis2024′, with disinfected air guided by the frame144′generally radially outwardly in the direction of the arrow DA through a dispersion angle, preferably at least 90° and potentially through a full 360°. The frame144′has a bottom wall2504′with a substantially square opening2524′in communication with the volume204′/284′. In this embodiment, the part2544′is releasably connectable to the frame144′, as shown inFIGS.33and34, wherein the part2544′fully blocks the opening2524′. In this configuration, the treatment unit104′is in the first state as a result of which the treatment unit104′serves primarily as a circulating air treatment unit. At least one connector256is provided on the frame144′that cooperates with at least one connector258on the part2544′to releasably maintain the part2544′in the connected relationship with the frame144′, as shown inFIGS.33and34. The connectors256,258may be capable of cooperating with or without the use of separate fasteners. Multiple different arrangements could be devised by one skilled in the art to allow releasable connection of the part2544′. Once the part2544′is repositioned/separated to expose the full area of the opening2524′, the air treatment unit104′is in the second state, whereupon the UV light rays from the UV light source164′project in a diverging, generally conical volume axially downwardly from the frame144′. As depicted, the volume of space blocked by the part2544′is directly below the air treatment unit104′. However, as noted above, this is not required. While not specifically shown inFIGS.31-34, it is intended that the air guidance assemblies, as described with respect to the embodiments above, as well as variations thereof, could be used with the treatment unit104′as well as all additional embodiments described below. InFIG.35, a treatment unit is shown at105′with a frame145′generally corresponding to the frame144′. In this embodiment, there are two parts254a5′,254b5′that are translatable relative to the frame145′, between the solid line and dotted line positions for each, along lines as indicated by the double-headed arrows260. In the solid line positions, the parts254a5′,254b5′cooperatively fully block the opening2525′in the wall2505′. With the parts254a5′,254b5′in the solid line positions, the treatment unit105′is in the first state therefor, in this case fully blocking downward projection of UV light rays. In the dotted line positions, the treatment unit105′is in the second state. In this case, the area at the opening2525′is fully exposed for surface treatment. The parts254a5′,254b5′may be maintained in an intermediate position whereby the pattern of downwardly projecting UV light rays is changed. InFIG.36, another form of treatment unit is shown at106′wherein the parts254a6′,254b6′are pivotable relative to a frame146′between solid and broken line positions, with the latter representing the first state for the treatment unit106′and the latter representing the second state for the treatment unit106′. In the second state, UV light rays from the UV light source166′project in a diverging volume, indicated by the arrows A from the wall opening2526′. FIG.37represents another variation of wall2507′with an opening2527′having an effective area that is variable as by using parts2547′typical of those used on a camera shutter associated with a lens. The above are just examples of specific forms contemplated within the generic showing inFIGS.31and32. The generic showing is intended to encompass not only these versions but virtually an unlimited number of variations of the components and their interaction that would be obvious to one skilled in the art with the present teachings in hand. As shown inFIG.38, another form of treatment unit108′may incorporate a delayed start timer262which can be set to at least one of: a) cause the treatment108′to change from its “off” state into its “on” state; and b) cause the treatment unit to change between the first and second states, after a predetermined time interval. It is anticipated that the delayed start timer262might be incorporated into any of the embodiments hereinabove described. In a further modification, a separate timer264, as shown inFIG.39, might be incorporated into the treatment unit109′, intended to represent all treatment units herein, as well as others. The timer264is operable to cause the treatment unit109′to be one of: a) maintained in the “on” state; and b) operated in the second state, for a predetermined time interval. As shown inFIG.40, in one form, a treatment unit1010′, representative of all treatment units herein, and others, has a disabling feature266that causes the treatment unit1010′to be changed from one of: a) its “on” state into its “off” state; and b) its second state into its first state upon a predetermined triggering event occurring at a location spaced from the treatment unit. In one form, as shown inFIG.41, the disabling feature26610′incorporates a motion sensor, on or separate from the treatment unit1010′, that detects motion, in a space generally or in the vicinity of the treatment unit1010′. Thus, the system might be programmed so that with the treatment unit1010′on and in the second state, a user's movement in the vicinity of the treatment unit1010′may cause the treatment unit1010′to be turned off, or its state changed, to protect a human or animal from being directly exposed to UV light rays. In an alternative form, as shown inFIG.42, a treatment unit1011′may have an associated disabling switch268that is operable by an entry door270movable between open and closed positions. The disabling switch268and entry door270define the disabling feature26611′. By using an opening at which the entry door270is located to enter and leave a space within which the treatment unit1011′is located, a changing of the entry door270from its closed position into its open position activates the disabling switch268, thereby causing the treatment unit1011′to be changed from one of: a) its “on” state into its “off” state; and b) its second state into its first state so as to thereby protect persons or animals within the space from being directly exposed to UV light rays generated by the treatment unit1011′. In each embodiment, the repositionable part254may be manually moved as by direct engagement thereof. For example, one or more of the parts254a5′,254b5′inFIG.35might be engaged and manually translated. Alternatively, the part(s)254might be repositioned through an operable drive272, as shown inFIG.32. The drive272may be controlled by an actuator274that might be on the frame144′as indicated by dotted lines, or remotely situated therefrom. In the latter case, the actuator274might be operated from externally of a room to avoid inadvertent exposure of a user or animals to UV light. The actuator274may use any type of connection, such as Bluetooth, or otherwise. It is contemplated that a controller276, as shown inFIG.43, remote from the treatment unit1012′, can be used to control all functions associated with the treatment unit1012′—notably, but not exclusively: a) turning the entire treatment unit off; b) turning off the UV light source; c) turning off a moving assembly; d) changing between first and second states; etc. The controller276could use a wired connection, and may be located internally or externally of a room in which the treatment unit1012′is placed or may be a wireless controller276, such as a smartphone, tablet, etc., using wireless, such as Bluetooth, technology. The foregoing disclosure of specific embodiments is intended to be illustrative of the broad concepts comprehended by the invention. | 43,414 |
11857706 | DETAILED DESCRIPTION InFIGS.2to4, a display apparatus1for a domestic appliance100is shown, at least one air treatment apparatus2being integrated in the display apparatus1, the at least one air treatment apparatus2comprising a first radiation source device3by means of which a fluid, in particular air, passing through a passage channel5can be treated. FIG.1shows a domestic appliance100comprising at least one display apparatus1. The domestic appliance100can be a refrigerator, a freezer, a dishwasher, a washing machine or the like. The domestic appliance100comprises a housing101and a container device102provided therein. The display apparatus1can be arranged on or in the housing101of the domestic appliance100. At least one air flow device6is provided, by means of which an air flow7into and/or out of the air treatment apparatus2can be generated, the air flow7passing through the passage channel5. Furthermore, an air flow7from and/or into the container device102can be generated by means of the at least one air flow device6. Accordingly, the air in the container device102can be treated, cleaned or disinfected. The display apparatus1having the integrated air treatment apparatus2comprises a housing12which extends along a height axis Z, a longitudinal axis X and a width axis Y. This can be seen clearly inFIG.2. At least one air inlet opening13and at least one air outlet opening14are provided on the housing12. The housing12preferably consists of a plastics material or a metal. The air flow7flows into the housing12through the at least one air inlet opening13and out of the housing12through the at least one air outlet opening14. Accordingly, the air flow7flows from the container device102into the at least one air inlet opening13and from the at least one air outlet opening14into the container device102. Within the air treatment apparatus2, the air flow7flows through the passage channel5and subsequently to the at least one air outlet opening14. The air flow3entering the container device102is thus cleaned or processed. The at least one air flow device6generates a negative pressure at the at least one air inlet opening13, by means of which the air flow7into the at least one air inlet opening13can be generated. Correspondingly, an overpressure is generated at the at least one air outlet opening14. Furthermore, a closure device15can be provided, by means of which the air treatment apparatus2can be closed or separated from the container device102in a sealing manner. Thus, during the washing cycle of the domestic appliance, the interior of the air treatment apparatus2is protected from the washing liquid. The closure device15comprises at least one closure element15awhich, in a closed position, closes the at least one air inlet opening13and/or the at least one air outlet opening14in a sealing manner. At least one closure element15acan be moved from a closed position to an open position, and vice versa. In the closed position, the at least one air inlet opening13and the at least one air outlet opening14are closed in a sealing manner. The closure device15comprises at least one drive device which drives the at least one closure element15a(not shown). The drive device can, for example, be an electric motor which moves the closure element15avia at least one force transmission means, for example a transmission. The air treatment apparatus2extends along a height axis Z, a width axis Y and a longitudinal axis X. The air treatment apparatus2comprises a passage channel5for the air flow7, a first radiation source device3. According to one embodiment, the air treatment apparatus2further comprises a photocatalysis device8. The first radiation source device3emits electromagnetic radiation. The photocatalysis device8can be exposed to at least part of the electromagnetic radiation in order to produce a photocatalytic reaction. The photocatalysis device8comprises a photocatalytic surface8awhich comprises at least one photocatalytic material. The photocatalytic material is a semiconductor, preferably titanium(IV) oxide, TiO2. The photocatalytic surface8acomprises regions8bhaving the photocatalytic material. However, other configurations of the photocatalytic surface8aare also conceivable. When using titanium dioxide, it is advantageous that the first radiation source device3emits electromagnetic radiation with a wavelength of less than 400 nm, preferably in a range from 380 nm to 315 nm. The radiation source device3comprises at least one radiation source3a, the at least one radiation source3abeing a light-emitting diode (LED) or a UV LED. The radiation source device3comprises a large number of radiation sources3awith a total number Ntot of radiation sources3a. The at least one radiation source3ais arranged on the first side11aof a support device11. The support device11has a substantially plate-like design. The first side11a of the support device11is arranged substantially opposite the photocatalysis device8. The passage channel5for the air flow7is provided between the support device11and the photocatalysis device8. According to a further embodiment, a photocatalysis device8is not provided. The passage channel5is therefore defined by a delimiting surface16and the support device11, the first side11aof the support device11being arranged substantially opposite the one delimiting surface16. In this embodiment, the first radiation source device3comprises at least one radiation source3a, the at least one radiation source3abeing a light-emitting diode (LED). The first radiation source device3emits electromagnetic radiation with a wavelength in a range between 280 nm and 100 nm. The display device1comprises a second radiation source device4. The second radiation source device4emits electromagnetic radiation which is used or serves to display information. The second radiation source device4comprises at least one radiation source4a, which is advantageously designed as a light-emitting diode (LED). The second radiation source device4preferably emits electromagnetic radiation in a wavelength range between 400 nm and 700 nm. The first radiation source device3and the second radiation source device4are arranged on opposite sides11a,11bof the support device11. The first radiation source device3is arranged substantially opposite the photocatalysis device8or the delimiting surface16, the passage channel5for the air flow7being provided between the support device11and the photocatalysis device8or the delimiting surface16. At least one display element9is provided, which is irradiated with the electromagnetic radiation emitted by the second radiation source device4. At least one radiation conduction device10is provided in this case, by means of which the electromagnetic radiation emitted by the second radiation source device4can be conducted to the at least one display element9. Such a radiation conduction device10is preferably a light conductor into which at least part of the electromagnetic radiation emitted by the second radiation source4is coupled. This can be seen inFIGS.3and4. The support device11is arranged in a first portion12aof the housing12, which can be connected to the second housing portion12bby means of a force and/or a form-fitting connection, preferably by means of a snap connection. This is shown inFIG.3. The coupling of the electromagnetic radiation into the radiation conduction device10is provided in the first portion12aof the housing12. The at least one display element9can have regions which are lettering, a logo, a symbol, or the like. It would also be conceivable that part of the electromagnetic radiation emitted by the second radiation source4serves as background lighting of a component of the domestic appliance100. Such a component can be, for example, a door104or an interior lining. The second radiation source device4preferably comprises a plurality of radiation sources4a. The plurality of radiation sources4acan preferably be divided into at least two subsets4b,4c. These subsets and radiation sources4,4a,4b,4ccan be designed in such a way that they emit electromagnetic radiation with different wavelengths or colours. A plurality of radiation conduction devices10,10a,10bcan be provided, into which the emitted electromagnetic radiation is coupled in each case. InFIG.4, for example, an embodiment having subsets4b,4cis shown, the electromagnetic radiation of the first subset4bbeing coupled into the first radiation conduction device10,10aand the electromagnetic radiation of the second subset4cbeing coupled into the second radiation conduction device10,10b. The plurality of radiation conduction devices10,10a,10bcan advantageously open into different display elements9. Alternatively, the radiation conduction devices10,10a,10bcan advantageously open into only one display element9. Preferably, a radiation control device17is provided, by means of which the radiation from specific radiation conduction devices10,10a,10bcan be blocked or diverted. Thus, the beam path of the electromagnetic radiation can preferably be switched between different display devices9. Likewise, a subset of radiation sources4,4a,4b,4ccould illuminate a single display device9, while the radiation from the further subset of radiation sources4,4a,4b,4cis blocked. A domestic appliance100is shown inFIG.1. The housing101of the domestic appliance100can comprise a closure apparatus104, for example a door, by means of which the container device102can be closed. At least one display apparatus1having an integrated air treatment apparatus2can be arranged in or on the closure apparatus104. The domestic appliance100can have a substantially cubic or cuboid shape and comprise two lateral side walls105and a rear side wall105or also a rear wall, which is preferably opposite the closure apparatus104. Finally, the housing may comprise a front side wall105. The closure apparatus104can be designed, for example, as a door which is integrated in the front side wall105or is provided instead of a front side wall105. Operating elements can optionally be provided for the user on the front side wall and/or on the closure apparatus104. Operating elements of this type are, for example, program selection switches in a dishwasher. The at least one display apparatus1having an integrated air treatment apparatus2can be arranged in or on a side wall105of the housing101. The air treatment apparatus1can thus be arranged in or on a lateral side wall105or a rear side wall105. FIG.5shows a basic circuit diagram for a domestic appliance100having at least one display apparatus1having an integrated air treatment apparatus2. Accordingly, a control device103is provided which can be assigned to the domestic appliance100or the display apparatus1. The control device103is connected by signals to the air treatment apparatus2or to the first radiation source device3, the air flow device2, and optionally the drive device for the closure element13. A first status signal relating to the first status of the display apparatus1can be received or generated by means of the control device103. Furthermore, a second status signal relating to the second status of the display apparatus1can be received or generated by means of the control device103. Furthermore, a third status signal relating to the third status of the display apparatus1can be received or generated by means of the control device103, a fourth status signal relating to the fourth status of the display apparatus1being able to be received or generated by means of the control device (103). In the first status of the display apparatus1, the air treatment apparatus2is activated. In the one second status of the display apparatus1, the air treatment apparatus2is deactivated. In a third status of the display apparatus1, the components relating to the display4,4a,4b,4c,17are activated. In a fourth status of the display apparatus1, the components relating to the display4,4a,4b,4c,17are deactivated. The defined first and second statuses are independent of the defined third and fourth statuses. The display apparatus1can accordingly be in the first and third status or in the first and fourth status. In other words, the components relating to the display4,4a,4b,4c,17can be activated and deactivated independently of the air treatment apparatus2. Likewise, the air treatment apparatus2can be activated or deactivated independently of the components relating to the display4,4a,4b,4c,17. The third or fourth status or the activation or deactivation can also be initiated independently of one another for specific subsets of radiation sources4,4a,4b,4cor radiation control devices17. Accordingly, the lighting can be activated, deactivated or changed (changing the lighting from one subset to another subset) for specific display elements9. In the second status, the display device1having an integrated air treatment apparatus2can optionally be closed in a sealing manner with respect to the container device102by means of the closure device15. In the second status, the at least one closure element15ais in the closed position. Likewise, in the second status, the air flow device6can be deactivated by means of the control device103. In one embodiment of the domestic appliance100in the form of a dishwasher, a washing machine or the like, the washing liquid is introduced into the container device102or into the tub in the second status. Due to the sealing closure of the display device1having an integrated air treatment apparatus2with respect to the container device102, the washing liquid cannot penetrate into the air treatment apparatus1. The control device103is connected by signals to at least one input device106, by means of which the status signals can be generated. The input device106sends the status signals to the at least one control device103, as a result of which the corresponding statuses are initiated. The input device106can preferably be operated manually. Accordingly, the input device106can comprise, for example, buttons and/or switches and/or a touch screen. The input device106can preferably receive the first status signal and/or the second status signal from an external communication appliance200of a user. The connection between the external communication appliance and the input device is preferably a wireless connection201. An external communication appliance200can be, for example, a smartphone, a tablet computer, a laptop or a similar appliance. A corresponding wireless connection201can be, for example, an RFID (radio-frequency identification) connection, an NFC (near-field communication) connection, a WLAN connection or a cellular connection. Of course, further wireless connections or wired connections can also be used. However, the display apparatus1having an integrated air treatment apparatus2can also be activated or deactivated automatically. For this purpose, the control device103itself preferably generates the status signal in each case. The status signals are subsequently processed by means of the control device103in such a way that the corresponding status is initiated. The at least one control device103preferably generates the status signals on the basis of sensor data from a sensor device107. The sensor device107preferably comprises at least one sensor107awhich detects the loading status in the container device. Such a sensor107acan, for example, be a weight sensor which detects the weight of the articles introduced. A sensor107ain the form of a camera system, which can recognise a load status, for example by image recognition, would also be conceivable. The first status could thus be triggered or the air treatment apparatus2could be activated when a load is detected, for example in the case of a dishwasher in the form of dishes to be cleaned. Alternatively or cumulatively, the sensor device107preferably comprises at least one sensor107awhich detects specific gases in the air in the container device102. Gases of this type can be, for example, those which cause an unpleasant odour. When such a gas is detected, the first status could preferably be triggered or the air treatment apparatus2could be activated. After the removal of the gas, the second status could subsequently be triggered, or the air treatment apparatus2could be deactivated. Furthermore, the sensor device107could advantageously comprise at least one sensor107a, which detects an opening of the closure apparatus104or the door of the domestic appliance100. Thus, when opening the closure apparatus104, the second status could advantageously be triggered, or the air treatment apparatus2could be deactivated. After closing the closure apparatus104, the first status could be triggered, or the air treatment apparatus2could be activated. It would be conceivable that the at least one display element9is arranged on an inner wall of the closure apparatus102. Thus, when opening the closure apparatus102, the third status could be initiated or the components for the display4,4a,4b,4c,17could be activated. Accordingly, when closing the closure apparatus104, the fourth status could be initiated, or the components for the display4,4a,4b,4c,17could be deactivated. Furthermore, it is conceivable that the sensor device107advantageously comprises at least one sensor107awhich detects the ambient light conditions. The third status could thus be initiated when the ambient light falls below a predetermined limit value. A status signal can preferably also be generated or received when a specific program of the domestic appliance is started, for example when a washing program is started. This can take place by means of the control device103or also by means of a further control device. The display apparatus1can advantageously be used to display specific statuses of the domestic appliance100. For example, a load status, a specific operating program or a specific error in a status of the domestic appliance can be displayed by changing the lighting of the at least one display element9. According to a further embodiment, a timer device108is provided. Such a timer device108can preferably be integrated in the control device103or also be provided as a further device in the domestic appliance100. The status signals can advantageously be generated on the basis of a predetermined point in time or a predetermined time interval. The point in time of the activation of the statuses can thus advantageously be predetermined. The control device103advantageously comprises a memory device109in which specific sequence programs are stored. Sequence programs of this type can comprise the sequential control of specific devices, such as the first radiation source device3, the second radiation source device4, a radiation control device17, the air flow device6, etc. Likewise, the intensity of the activation of these devices can advantageously be provided in such a sequence program. The photocatalytic reaction, for example, can be controlled by advantageously controlling the operating current of the first radiation source device3. Likewise, the air flow speed can be controlled by an advantageous control of the air flow device6. The applicant reserves the right to claim all the features disclosed in the application documents as substantial to the invention, provided that these are novel individually or in combination over the prior art. It is further pointed out that features have also been described in the individual drawings, which in themselves can be advantageous. A person skilled in the art will immediately recognise that a specific feature described in one drawing can also be advantageous without adopting further features from said drawing. A person skilled in the art will further recognise that advantages can also result from a combination of a plurality of features shown in individual or in different drawings. LIST OF REFERENCE SIGNS 1Display apparatus2Air treatment apparatus3First radiation source device3aRadiation source4Second radiation source device4aRadiation source4bFirst subset of radiation sources4cSecond subset of radiation sources5Passage channel6Air flow device7Air flow8Photocatalysis device8aPhotocatalytic surface8bRegions of the photocatalytic surface having the photocatalytic material9Display element10Radiation conduction device11Support device11aFirst side of the support device11bSecond side of the support device12Housing of the air treatment apparatus12aFirst portion of the housing12bSecond portion of the housing13Air inlet opening14Air outlet opening15Closure device15aClosure element16Delimiting surface17Radiation control device100Domestic appliance101Housing102Container device103Control device104Closure apparatus105Side wall106Input device107Sensor device107aSensor108Timer device109Memory device200Communication appliance201Wireless connectionX Longitudinal axis of the display apparatusY Width axis of the display apparatusZ Height axis of the display apparatus | 20,922 |
11857707 | DETAILED DESCRIPTION Various embodiments are described more fully below with reference to the accompanying drawings, which form a part hereof, and which show specific exemplary embodiments. However, the concepts of the present disclosure may be implemented in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided as part of a thorough and complete disclosure, to fully convey the scope of the concepts, techniques, and implementations of the present disclosure to those skilled in the art. Embodiments may be practiced as methods, systems, or devices. The following detailed description is, therefore, not to be taken in a limiting sense. Reference in the specification to “one embodiment” or to “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiments is included in at least one example implementation or technique in accordance with the present disclosure. The appearances of the phrase “in one embodiment” in various places in the specification are not necessarily all referring to the same embodiment. In addition, the language used in the specification has been principally selected for readability and instructional purposes and may not have been selected to delineate or circumscribe the disclosed subject matter. Accordingly, the present disclosure is intended to be illustrative, and not limiting, of the scope of the concepts discussed herein. Acronyms Used AC—Alternating current AI—Artificial intelligence CDC—Centers for Disease Control and Prevention (US Government Agency) COVID-19—Coronavirus 2019 (SARS-CoV-2) DC—Direct current HVAC—Heating, ventilation, and air conditioning HV PSU—High voltage power supply unit LED—Light-emitting diode ML—Machine Learning N95—Particulate respirator meeting the N95 NIOSH air filtration rating NAI—Negative air ions PPA—Personal protection augmentation PPE—Personal protective equipment PPM—Parts per million UV—Ultraviolet (light, wavelength≤400 nm) Embodiments Some embodiments of the present invention are directed to a system configured to create a laminar curtain of negatively ionized air across a doorway or portal. An air ionizer uses high-voltage electricity to ionize air molecules. Ionizing air molecules comprises imparting either a positive or a negative charge to air molecules. The ionized air molecules, herein referred to as ions, tend to attract other airborne particles, including viruses and bacteria, and transfer their charge to said particles. Ionized air has been shown to inactivate virus particles and bacteria. Additionally, ionized particles tend to be attracted to earth ground (in the electrical sense). Such attraction causes ionized particles to precipitate out of the air and onto the floor or other surfaces, as well as intentionally grounded or charged plates. Whether or not such individual microbe particles are inactivated, they cease to be airborne, reducing the likelihood of person-to-person transmission. Multiple studies have shown that air ionizers are effective at reducing the spread of airborne contagions and preventing the spread of the influenza virus between lab animals held in close proximity. In countries previously affected by the SARS virus (a strain of coronavirus), manufacturers have added ionizers to many consumer products, including household appliances. Properly designed air ionizers do not produce harmful byproducts, require no consumables, are energy-efficient, and can be scaled up or down to suit a wide range of applications. Because ionized air does not cause any known negative effects to humans, it is considered safe for ionizers to be active in close proximity to people. Air ionizers function by passing air through one or more electrodes held at high (positive or negative) voltage—typically on the order of at least several kilovolts. Air molecules passing near the electrodes pick up a charge—they are ionized. Because their charge is the same polarity as the electrode(s), the ions are repelled away from the electrodes. As a result, some ionizers do not use a fan to create airflow—the ions themselves cause positive airflow out and away from the ionizer. Other ionizers may use fans to enhance airflow or direct the airflow in a particular direction; typically, net air ion production (e.g., ions per second) increases with air velocity over the electrodes. In the present context, air ionizers are able to continuously neutralize and precipitate aerosolized, airborne virus particles out of the air independent of ventilation. Strategically placed ionizers can effectively isolate rooms with respect to airborne pathogens from hallways and other rooms without physical barriers. This may be of particular interest in medical facilities wherein patients may be separated only by vertical partitions, such as curtains. In some embodiments, the laminar curtain may work similar to existing air curtains, with the addition of an anode system configured to create a negatively ionized air stream. An example of such an embodiment is shown inFIG.1. Embodiments create a protection from airborne pathogens, dust, smoke, or other airborne matter that is susceptible to ionization. When installed above a doorway, the system may be configured to create a downward flow of ionized air, forming a virtual partition between areas. In some embodiments, a high concentration of NAI is maintained for a significant distance within the laminar output. For example, in some embodiments, the NAI concentration four feet from the manifold may be over 1 million ions per cubic centimeter of air. For example, in some embodiments, the NAI concentration directly out of the manifold may be over 40 million or 50 million ions per cubic centimeter of air. Returning toFIG.1, a horizontal laminar curtain of negatively ionized air105is discharged from the bottom of the partition system100and directed downward. In some embodiments, the system is configured to discharge a horizontal laminar curtain of negatively ionized air105from the top of the partition system100and directed upward. In some embodiments, the system is configured to discharge a vertical laminar curtain of negatively ionized air (not shown) from one side to another side of a portal, perpendicular to the direction shown inFIG.1. Some embodiments of the system100may include a laminarizer or output manifold145. In some embodiments, in anion-only generation mode, the ozone production of the partition system100may be between zero and 0.01 PPM. In some embodiments, increasing anode potential with respect to ground or changing the geometry or positioning of components proximate to the anodes (not shown) within the partition system100may cause predictable concentrations of ozone to be produced. In some embodiments, such mechanism or circuitry may be used by the system100, via its control system110, to inhibit, enable, or regulate the production of ozone. In some embodiments, the manifold145is designed such that the airflow exiting the manifold145is laminar and of a prescribed geometry. For example, the airflow exiting the manifold145may have a net cross-sectional shape of at least one of a polygon, circle, ellipse, or oval. In some embodiments, this geometry is designed such that the laminar curtain of negatively ionized air105is at least as wide as the door160over which the system is affixed and extends downward for at least four feet. In some embodiments, the laminar curtain of negatively ionized air105is configured to reduce at least one of the transfer of contaminants or the concentration of viable contagions between a first air mass112and a second air mass114. In some embodiments, the term contaminant may also include contagions and contagions may also refer to contaminants. Contagions and contaminants may be polluting substances that render an environment less safe or impure, and may comprise bacteria, viruses, fungi, dust, particles, poisons, pesticides, and drugs. In some embodiments, it is possible to adjust the angle of the manifold145with respect to the system100to control the direction of airflow. In some embodiments, the width of the air105exiting the manifold145may be adjustable to cover a wider or smaller area. In some embodiments, the manifold145can be reconfigured or adjusted electromechanically, manually, and/or by the installation of one or more accessories, such that the otherwise laminar air105output of the system is diffused or diffuse. In some embodiments, this manifold configuration may be used to facilitate more effective mixing of anions with room air during non-partition operations or time periods. FIG.2illustrates an embodiment of a germicidal partition system200having a squirrel cage fan (also known as a tangential fan)215, motor220, and a power source225, such as a high voltage power supply unit or other negative high-voltage source, in accordance with one embodiment. In some embodiments, the system200may include a line of anodes230below the squirrel cage fan215and may blow air around, over, or past the anodes230to create a curtain of negatively ionized air205. Anodes, as referred to herein, are electrodes held at a large negative potential. The anodes230, combined with the power source225and at least one high voltage conductor (e.g., such as the one shown inFIG.8), comprise a negative ion generator, sometimes referred to as an ionizer. Some embodiments of the system200may include an output manifold or laminarizer (shown inFIG.1). In some embodiments, a fan215, powered by a fan motor220, draws air through the system200, with said air exiting through the manifold. In some embodiments, the anodes230impart negative charge to air flowing through the system200and air exiting the system200in the curtain of negatively ionized air205contains a prescribed concentration of anions. For example, in some embodiments, the air outputted through the manifold in the curtain of negatively ionized air205comprises at least 40 million negative air ions per cubic centimeter of air. In some embodiments, the air outputted through the manifold in the curtain of negatively ionized air205comprises at least 20 million negative air ions per cubic centimeter of air. In some embodiments, the air outputted through the manifold in the curtain of negatively ionized air205comprises at least 1 million negative air ions per cubic centimeter of air. In some embodiments, the motor220may be an electric motor such as a universal motor, brushless DC motor, or an induction motor. Electric motors harness electromagnetism to generate motion. The motor220is coupled to the fan215in some embodiments. In some embodiments, the torque produced by the motor220is transferred to the fan215, causing rotation. In some embodiments, the negative ion generator and the fan215are powered by the at least one power source225and controlled by the control system250. In some embodiments, the power source225may be a battery and charger system or may be a plug-in power supply. In some embodiments, the system200may be battery powered or may use mains electricity. In some embodiments, mains electricity may simplify and reduce the cost of the negative ion generator. Some embodiments may use modular HV PSU's (one for DC or battery and one for mains) or may use a hybrid system optimized for both battery and mains. In some embodiments where both a battery and mains power sources225are present, the system200is able to automatically switch to using the battery power source225in the event of a blackout or loss of mains power. Some embodiments may have mode flexibility, such as passive quiescent ion generation, constant or periodic fan activation. In some embodiments, the system200may be permanently integrated into a building and hard-wired into a building or facility's electrical system. In some embodiments, the power source225is at least one primary or rechargeable battery contained within or attachable to the housing. In some embodiments, the system200may further comprise a mechanism whereby an installed battery can be charged while the system200is connected to mains power. In some embodiments, the power source225is external to the system and is connected to the device by a plurality of conductors (e.g., a cable). In some embodiments, the power source225is an AC-to-DC converter. The design and construction of the high, negative voltage power supplies for negative ion generators (“negative ion generator power supplies”) varies significantly depending on the power source. In some embodiments, mains-AC-powered negative ion generator power supplies may use a variant of a Cockcroft-Walton voltage multiplier circuit (comprising primarily diodes and capacitors). In some embodiments, negative ion generators powered by lower-voltage DC sources, such as batteries, may employ switch-mode inverters that use high-voltage step-up transformers. In some embodiments, the system200may use a USB-C power supply. Some embodiments comprise a low-voltage (less than 48 V) DC-powered negative ion generator power supply as the power source225. In some embodiments, when operating from a battery power source, the DC battery powers the negative ion generator power supply directly. In some embodiments, when operating from a mains AC power source, an AC-to-DC converter is used to convert and step down the mains voltage to the DC supply voltage required by the DC-powered negative ion generator power supply. Some embodiments comprise a mains-AC-powered negative ion generator power supply as the power source225. In some embodiments, when operating from a mains AC power source, the negative ion generator power supply is powered directly from the mains. In some embodiments, when operating from a battery power source, a DC-to-AC inverter is used to convert and step up the battery voltage to mains AC voltage and frequency and the negative ion generator power supply is powered by said inverter. While the DC-to-AC inverter does contain a step-up transformer, said transformer is usually of simpler, more economical construction than the high-voltage step-up transformer typically used in DC-only negative ion generator power supplies. In some embodiments, the resulting negative ion generator power supply is simpler, smaller, and more economical than two separate negative ion generator power supplies while affording the flexibility to run on battery or mains AC within the same unit. Some embodiments comprise a first low-voltage DC-powered negative ion generator power supply and a second mains-AC-powered negative ion generator power supply as the power source225. In some embodiments, when operating from a battery power source, the first negative ion generator power supply is used. In some embodiments, when operating from mains AC, the second negative ion generator power supply is used. In some embodiments, the negative ion generator power supply is a modular, separable component of the device, allowing one of the first or second negative ion generator power supplies to be fitted to the unit for battery or mains power source operation, respectively. Some embodiments may exclusively use a battery power source. In some embodiments where a power source225is one or more batteries, the device further comprises one or more annunciators255. In some embodiments, the annunciator(s)255activate when a power source225level falls below a certain threshold and may indicate the approximate number of disinfection cycles remaining for the given level of the power source225. In some embodiments, an annunciator255is audible, comprising, e.g., a buzzer, beeper, speaker, etc. In some embodiments, an annunciator255is visual, comprising, e.g., a lamp, light, blinking indicator, etc. In some embodiments where the control system250is able to communicate with other digital or electromechanical systems, annunciation may be by means of message(s) or electrical signal(s) sent to or exchanged with one or more external systems. In some embodiments, the control system250may use sensor data to adjust fan speed, ionizer power, or other parameters based on, for example, relative humidity, air temperature, detected contaminant levels, or the user's movement. In some embodiments, the control system250is electromechanical, digital, or a combination of electromechanical and digital. In some embodiments, the control system250responds to a motion activation or audio triggering event by activating the fan215and the negative ion generator for a prescribed period of time. In some embodiments, the duration of activation may be extended if the control system250detects continued motion or the proximity of a person or persons within a prescribed area, or due to other conditions detected by the sensors. In some embodiments, the duration of activation may be extended if the control system250detects that a door or other portal remains open, either partially or fully. In some embodiments, the duration of activation may be further extended depending on how long the door or other portal remains open or how many times the door was opened and closed during the present activation period. In some embodiments, after the prescribed or extended period of time elapses, the control system250deactivates the fan215and negative ion generator. In some embodiments, upon motion activation or audio triggering, the fan215may run at a higher-than-typical speed for a short period of time. For example, the short period of time may be five seconds, ten seconds, thirty seconds, one minute, or two minutes. In some embodiments, the higher speed may provide a positive audible indication to the user that the device is active and may help ensure that any dust or debris that may have collected on the device while it was idle is cleared out before the user passes through the curtain of negatively ionized air205. In some embodiments, after this initial period, the fan speed may reduce to a prescribed or configurable speed to minimize fan and airflow noise while providing a prescribed level of germicidal partition protection. In some embodiments, acoustic noise produced by the system200during operation is less than 55 dBA. In some embodiments, the system200may comprise switches, buttons, or other mechanisms273to allow the user to turn the curtain of negatively ionized air205on and off, adjust the fan speed, check the battery charge level, or perform other operations. In some embodiments, the system200can be configured or operated in a mode wherein the negative ion generator is energized while the fan215is turned off In some embodiments, airflow through the system200is induced electrostatically by the negative ion generator, providing a continuous, low-velocity flow of ionized air when the fan215is turned off after the air passes over the anodes230. When air molecules or other particles become negatively charged, they are repelled from the one or more anodes230, which are also at a negative potential. Effectively, air is electrostatically “pumped” through the system200. In some embodiments, the system200can be configured to operate periodically or continuously to provide ongoing air quality improvement and germicidal action in an area. In some embodiments, the system200varies the concentration of anions injected into the negatively ionized air205via its control system250. In some embodiments, the anion concentration variation is controlled by adjusting at least one of the input or output voltage of the power source225, e.g., through pulse-width modulation or pulse-density modulation of the negative ion generator's input voltage. In some embodiments, at least one parameter comprising the anion concentration, anode voltage, fan speed, and/or device activation duration may be adjusted as a function of parameters including, but not limited to, air temperature, relative or absolute humidity, barometric pressure, or air quality index (measured locally or communicated to the device via one or more communications modules). In some embodiments, the system200may adjust any of the parameters based on the presence of infections in persons known to be proximate to the system200, local outbreaks of airborne infectious diseases, and/or configuration. FIG.3depicts an embodiment of a germicidal partition system300secured above a portal360in accordance with one embodiment. A portal360may refer to a door, doorway, opening, or other equivalent recognized by a person having ordinary skill in the art. In some embodiments, the air curtain may be outputted behind or in front of a portal360. In some embodiments, the air curtain may replace a solid portal360, such as a door, completely. In some embodiments, the system300may comprise at least one of a motion sensor365, a control panel325, at least one annunciator355, a user interface370, and an intake375. In some embodiments, the intake375may be a front intake (not shown). In some embodiments, the intake375may be a top intake375. In some embodiments, the intake375may be a bottom intake (not shown). The at least one motion sensor365may be pyroelectric (or passive) infrared sensors in some embodiments. In some embodiments, the width of the germicidal partition system300may be between 30 and 36 inches. In some embodiments, the height of the germicidal partition system300may be between 4 and 6 inches. In some embodiments, the depth or projection of the germicidal partition system300may be between 4 and 8 inches. In some embodiments, users may mount the system300with at least one mounting system380. Mounting may include hanging, suspending, directly affixing, or other means of permanently or temporarily coupling the system to another object. In some embodiments, the mounting system380may comprise a simple, no-tools-required system such as a non-permanent adhesive on at least one side of the unit. In some embodiments, the mounting system380may include a screw system wherein the system screws into above-door framing. In some embodiments, the system300may hang from screws and/or studs or is configured to attach to mounting bracket. In some embodiments, the mounting system380may include L-brackets or another attachment system for transom windows. In some embodiments, a mounting system380comprises the hook or loop side of a hook-and-loop attachment system. In some embodiments, a mounting system380comprises one or more adhesive strips or sheets that adhere the device to a wall, transom window, door frame, or other surface proximate to the portal. In some embodiments, a mounting system380comprises a plurality of holes, slots, hooks, grooves, or other features in the device housing which engage with a corresponding plurality of mating protrusions, such as nails, screws, hooks, brackets, etc. affixed to mounting points on a wall, door frame, or other surface proximate to the portal. In some embodiments, retention of the system300relies on the force of gravity to maintain engagement between the corresponding features of the system housing385and the mating protrusions. In some embodiments, a mounting system380comprises one or more magnets, with the external mounting point being a ferrous/magnetic material, such as steel or iron. In some embodiments, a mounting system380further comprises one or more elastomeric, rubber, foam, or other compliant or spring elements to dampen vibrations and/or reduce mechanical coupling of vibrations from the system380into the mounting surface. In some embodiments, the user may use the control panel325to adjust fan speed in the system300to avoid or mitigate vibration or vibration coupling between the device and the mounting point(s)) due to resonance(s). In some embodiments, a mounting system380further comprises an external component. In some embodiments, the external component and part of the system300are designed such that they mate together, providing retention of the system300in or by the external component; the external component is mechanically attached to a mounting point proximate to the portal360. In some embodiments, the external component contains or can be fitted with one or more strain reliefs for electrical wiring for permanent, hard-wired installations. In some embodiments, the germicidal partition system300may couple to existing forced air supplies, such as HVAC vents, HVAC units, portable fans, or existing air purifiers. In some embodiments, the mounting system380may include a plenum for air intake, such that the fan intake is not blocked by the wall, portal360, or other surface. In some embodiments, the mounting system380may include an accessory configured to allow the germicidal partition system300to be temporarily attached to a pole or rod, such as is found in tents and temporary shelters, via an adjustable clamp mechanism. Some embodiments may be installed horizontally, across the top of a portal opening, and air may be expelled from top to bottom of the portal360. In some embodiments, the system300may be installed to output a vertical air curtain on one or both sides of the portal360. Horizontal installation integrated on the floor may be the most effective in thermodynamic terms but in some embodiments but may be problematic where public pedestrian traffic crosses the doorway. In some embodiments, the mounting system380facilitates installation of the system300on a ceiling or other overhead surface with the top of the device parallel and proximate to or in contact with the ceiling or other overhead surface. In some embodiments, the mounting system380facilitates suspension of the system from a ceiling or other overhead surface. Some embodiments may be deployed or installed to leverage the system's capabilities away from or absent a portal360. For example, in some embodiments, a system300may be installed in a hallway, at the junction of hallways, or as an invisible room partition, such as between beds in a medical ward or between tellers and customers in a bank. In some embodiments, the system300further comprises at least one motion sensor390to detect motion or movement proximate to the system300. Common examples of motion sensors390include, non-exhaustively, active or passive infrared sensors, RADAR, time-of-flight sensors, imaging sensors, digital cameras, ultrasonic sensors, proximity sensors, electro-optical, magnetic, inductive, capacitive, or audio/sound sensors. In some embodiments, motion sensor data is fed to and/or read by the control system. In some embodiments, motion sensor data is used by the control system to trigger activation of the device according to prescribed or configurable parameters (“motion activation”). In some embodiments, the parameters may include, but are not limited to, motion sensor sensitivity, motion sensor range, fan speed, negative ion generator power level, and the duration of activation. In some embodiments, the control system will trigger device activation in response to sensor data indicative of a person or persons approaching the portal. Motion activation may apply to motion on the device-side of the portal and may also apply to motion on the opposite side of the portal. For example, motion activation may apply to a person approaching an open door or a portal without a door). In some embodiments, the control system may trigger device activation in response to sensor data indicative of the portal360opening or beginning to open. In some embodiments, such a door or portal-opening motion activation capability does not require modifications to the door, door frame, or other surrounding features of a portal360. In some embodiments, the system300further comprises at least one audio sensor395. In some embodiments, the at least one audio sensor395may be a microphone. In some embodiments, the control system is able to use audio sensor data to trigger device activation based on prescribed, configurable, programmable, and/or learned sound/audible indications (“audio triggering”). In some embodiments, audio triggering may be performed in response to detection of a doorbell, door chime, door knocker, or other knocking on the door. In some embodiments, audio triggering may be performed in response to detection of the sound of a key being inserted into a lock, actuation of a lock, turning of a door handle, etc. In some embodiments where the system300comprises at least one audio sensor395, the system300may provide a means for the user to disable or disconnect all audio sensors395from the control system with the control panel325. In some embodiments, a user may disable or connect an audio sensor395for reasons of privacy, policy, or other restrictions. In some embodiments, the system300further comprises one or more visual indicators or annunciators355that indicate when the audio sensors395are enabled. In some embodiments, the means of positive disablement of audio sensors395is an electromechanical switch367that disconnects the audio sensors395from the control system, disconnects power from the audio sensors395, or equivalent. In some embodiments where the system300comprises at least one motion sensor365or audio sensor395, the control system may use at least one of adaptive or intelligent algorithms, such as AI or ML to refine the set of conditions that should trigger system activation or that should not trigger system activation. Said algorithms may also consider other data available to the control system, such as time-of-day, ambient lighting, the states of other devices with which it is able to communicate and user preferences. In some embodiments, the system300may not activate or trigger due to the movement of pets or small children proximate to a portal360. In some embodiments, the system300may distinguish between the sound of the owner's actual doorbell and the sound of a doorbell on a television or other recorded program, a neighbor's doorbell, etc. The system300may include a controller and some form of user interface, such as a control panel325to allow the user to control power, adjust parameters such as fan speed, and set the system300to run for a fixed or customizable time duration. In some embodiments, the control system is able to detect with at least one sensor365,395or communication with other devices that the fan(s) of a forced-air heating or cooling system are active. In some embodiments, upon such detection, the control system may activate the negative ion generator and fan within the system300such that the negatively ionized air is able to circulate and mix more effectively over a larger area/volume due to the increased air circulation due to the forced-air system. In some embodiments, the system300may remain running for a prescribed or configurable period of time or it may automatically deactivate when it detects that the forced-air system's fans have turned off In some embodiments where the system300comprises one or more controls on the control panel325or otherwise, one or more controls may include magnetic switches, magnetic sensors, magnetometers, reed relays, inductive sensors, or any equivalent recognized by a person having ordinary skill in the art (“magnetic controls”). In some embodiments, a user may actuate the one or more magnetic controls using a permanent magnet, electromagnet, iron, steel, or other mass of magnetic or ferromagnetic material attached to, installed in or on, embedded in, or integral to a rod, pole, stick, or equivalent. In some embodiments, the user's height does not limit the user's ability to actuate the device's controls which, due to the height of the portal360, may otherwise be beyond the user's reach. In some embodiments, the method of actuation avoids direct contact with the system300and, thus, the spread of pathogens by surface contact. Some embodiments may have different control mechanisms and user interfaces. In some embodiments, the system300could be configured such that the control panel325is on the left side and some such that the control panel325is on the right side. In some embodiments, the system300may be configured such that the control panel325is accessible for those with a disability. In some embodiments, the control panel325may be visible at all times. In some embodiments, the control panel325may be hidden from view. In some embodiments, control may be wireless or integrated into a smart home. Some embodiments incorporate one or more interlocks352, such as electro-mechanical switches, that disable or deenergize at least one of the negative ion generator power supply, fan motor, or other components if the housing385is opened or disassembled or certain removable parts of the housing385are not fitted or installed. In some embodiments, the control panel325comprises one or means of temporarily disabling or locking the controls to prevent inadvertent adjustments. In some embodiments, one or more of the controls is designed to be “child-proof”, “child-resistant”, “child-safe”, or any equivalent thereof. In some embodiments, the control is difficult or impossible for a baby or child to actuate. In some embodiments, the controls are locked or unlocked by actuating multiple controls simultaneously or by maintaining actuation of one or more controls for a prescribed time duration. In some embodiments, the system300comprises one or more communications modules348permitting the system300to be wirelessly monitored and/or controlled from or with an external device. In some embodiments, a communications module348communicates via at least one of BLUETOOTH, WIFI (IEEE 802.11) wireless networking, a mobile or cellular network (e.g., GSM, LTE, 5G, etc.), power line networking (a data network superimposed on a buildings mains supply wiring), or an equivalent recognized by a person having ordinary skill in the art. In some embodiments, a communications module348communicates with or permits integration with other wireless products, such as baby monitors, home security systems, home monitoring systems, etc. or sensors, such as video cameras, surveillance equipment, etc. In some embodiments, the control system, via a communications module348, is able to communicate with home automation systems, smart home systems or devices, networked security systems, etc. In some embodiments, the system300can be controlled, monitored, triggered, or inhibited from triggering, and/or configured via one or more of said systems and/or may integrate with one or more of said systems. For example, in some embodiments, the system300could be configured to run when informed by a “smart” thermostat that a forced-air fan system is active. In some embodiments, the forced-air fan system is a proximate forced-air fan system. In some embodiments, the control system of a first system300is able to communicate with the control system of another device. In some embodiments, such communication may be peer-to-peer between the system300and another device or may be facilitated or governed by another system that communicates with the system300and the device. In some embodiments, the activation of the device may be triggered or influenced by the activation or non-activation of the system300. For example, in some embodiments, if a person walks past the system300in a direction that is likely to lead the person to another device, the other device may activate early, in anticipation of the person's arrival, to pre-disinfect the area. In some embodiments, the system300may be located above a door or other portal360to a room or area known to contain contagious individuals. In some embodiments, the act of opening this portal360may trigger a second device—providing protection for a nearby room or area—to further-inhibit the transfer of airborne pathogens between the respective areas. In some embodiments, coordination between the system300and another device may comprise intelligent, adaptive, and/or learning algorithms, such as those of artificial intelligence, machine learning, deterministic algorithms, control theory, or heuristics. In some embodiments, such coordination may use as inputs contemporaneous or historical sensor data from at least one of the system300or other device, sensor or other data from external sources, user input, or configuration. In some embodiments, the germicidal partition system300may include an efficiently grounded plate333held at an electrical potential opposite from that of the system's output or at ground potential with respect to the system. In some embodiments, the plate333may attract and retain pathogen particles or other airborne contaminants in the environment and may be used to assay pathogen or contaminant presence and/or concentration in an area. In some embodiments, the plate333may be within the housing385. In some embodiments, the plate333may be external to the system300and may be, for example, an electrostatically dissipative or electrically conductive floor title. In some embodiments, the plate333may be covered by a rug or mat, such that the rug or mat can be removed and cleaned to remove pathogen particles. In some embodiments, the plate300may be wiped down with cleaner or water to remove pathogen particles. FIG.4depicts a bottom view of an embodiment of a germicidal partition system400in accordance with one embodiment. In some embodiments, the system400further comprises one or more visual annunciators455, such as indicator lights, light-emitting diodes (LEDs), etc. In some embodiments, a visual annunciator455may be used to indicate at least one of the system's400power status (on, off, standby, etc.), mode, or battery capacity. In some embodiments, the system455further comprises one or more light sources466, such as white LEDs, that provide convenience lighting at or near the portal460. In some embodiments, the light sources466are controlled by the control system450and may be activated in concert with or independent of the negative ion generator and/or fan. In some embodiments, the system400may use convenience down-lighting. In some embodiments, the system400may be integrated into a smart home system, such as running the ionizer and fan when home HVAC fan is running, unit starts up when someone approaches the door or as user drives up to dwelling, adjust duty cycle based on local air quality index, etc. FIG.5depicts a side view of an embodiment of a germicidal partition system500mounted on a wall542above a portal560in accordance with one embodiment. In some embodiments, the germicidal partition system500may use a fan515and a motor520inside a housing585, connected to a laminarizer or manifold545, to output a laminar air curtain505. In some embodiments, the germicidal partition system500includes at least one anode530, such that the germicidal partition system500is configured to output a laminar air curtain505with a prescribed concentration of negative air ions. Some embodiments may use a fan515to propel and circulate the negative ions. In some embodiments, the fan515may run for a certain number of seconds after a motion sensor or other trigger565is activated. In some embodiments, the fan515may run periodically using a configurative or adaptive control. In some embodiments, the fan515may be user-configurable and may run continuously. In some embodiments, the fan515may be a multi-speed fan. In some embodiments, the fan speed may be adaptive, may have a learning mode, and/or may be user configurable. In some embodiments, the fan515may have a passive mode, comprising at least one of the fan515being off and/or electrostatic self-pumping. In some embodiments, the fan515may be direct or belt driven. In some embodiments, the fan515may use at least one of centrifugal, axial and crossflow to propel air through an ionizer and out through the manifold545. In some embodiments, the manifold545may be adjustable to increase the performance of the outputted air curtain505according to each situation. Some embodiments may be non-recirculating germicidal partition systems500. Some embodiments may be recirculating. A non-recirculating system500may be configured to discharge the air to the environment. A recirculating system500may be configured to collect and return the air from the discharged air. Recirculating air curtains may be more energy efficient in some embodiments. In some embodiments, the housing585and manifold545are designed such that internal energized or moving parts cannot be accessed or touched from outside the device. In some embodiments, the openings in at least one of the manifold545or air intake537are typically small enough to prevent insertion of a body part. In some embodiments, the system500further comprises one or more adjustable/repositionable components. In some embodiments, these components may be part of the manifold545or may be separate, substantially independent parts of the manifold545. In some embodiments, changing the position of the one or more adjustable/repositionable components, possibly in conjunction with adjusting anode potential, inhibits ozone production or controls the production of ozone. In some embodiments, the system500is capable of producing germicidal/antimicrobial concentrations of ozone. In some embodiments, the one or more adjustable/repositionable components are actuated electromechanically under the control of and pursuant to the programming or configuration of the system's control system. In some embodiments, the system500further comprises a mechanism525or circuitry that enables adjustment of the one or more adjustable and/or repositionable components' potential and/or impedance with respect to electrical/earth ground. In some embodiments, one or more anodes530are embedded in the structure of the manifold545. For example, in some embodiments, the manifold545or manifold may be injection molded, 3D-printed, thermoset, etc. such that the one or more anodes530are retained or partially contained within the structure of the manifold545. When air is passed over the anodes530, some fraction of the air molecules themselves and other airborne particles acquire a negative electrical charge; such negatively charged molecules or particles are referred to as anions and the resulting air mass is referred to as negatively ionized air. First, charges transferred to microbes (from the anodes or from charged air molecules) cause damage to the microbes and kill or deactivate the microbes—rendering them essentially harmless to humans. Anion-rich air also tends to cause other air contaminants, such as pollen, dust, allergens, smoke, and odor molecules, to precipitate out of suspension—again, improving air quality. Some embodiments described herein produce a laminar flow of negatively ionized air505downward across doorways or portals560. In some embodiments, the airflow itself reduces air exchange across the portal and the anions' germicidal effects reduce the concentration of live and/or active microbe aerosols that do cross the portal560. In addition, anions may be injected into the spaces on both sides512,514of the portal560, providing further germicidal and air-purifying benefits in some embodiments. In some embodiments, the system500may further comprise one or more air filtration components547within the intake537, in the housing585, or external to the housing585. In some embodiments, the system's air intake537is fed, in whole or in part, by an external air filtration, air treatment, germicidal treatment, or other purification or disinfection system. In some embodiments, the system500may further comprise one or more other germicidal or antimicrobial air treatment components, such as treating air passing through the device with germicidal ultraviolet irradiation. In some embodiments, the air entering through an inlet grille as the intake537, sometimes with filter functions547and sometimes without filter functions547, is compressed by at least one internal fan515and forced though an air outlet (shown as manifold545), which is directed at an open doorway560. In some embodiments, the filter547protects the interior components, such as a heat exchanger or coil567, fans515, or electronics, from dust and particles. In some embodiments, the air curtain505may be heated. Heated air curtains505may have a coil567(electric, hot/chilled water, steam, indirect or direct gas, direct expansion, etc.) to heat or cool the jet. Heating may be used to avoid people feeling a cold jet of air when crossing the doorway560and also to heat the volume of air coming in at the entrance. FIG.6shows a portable ion generator system, herein referred to as an ionizer600, in accordance with one embodiment. In some embodiments, the ionizer600may be an air ionizer designed to decontaminate or disinfect a prescribed area in a prescribed time. For example, in some embodiments, the ionizer may be configured to disinfect an area of 250-500 ft2in 30-60 minutes. In some embodiments, the ionizer600may be placed in a patient room or screened area after the patient leaves or after a procedure that is likely to generate pathogen-containing aerosols. The ionizer600may run for a fixed time duration, after which time the room or area may be safe for the next patient or safe for further cleaning without requiring the use of rated PPE. In some embodiments, the ionizer600may be mounted in the cargo hold of delivery vehicles or a car trunk. In some embodiments, assuming some minimum transit time, the ionizer600may provide a measure of protection against transmission via contaminated surfaces on goods or containers. In some embodiments, the ionizer600may be temporarily placed or permanently installed in vehicles, such as taxis, police cars, or private vehicles, to provide continuous disinfection of the vehicle cabin. In some embodiments, the ionizer600may perform “hands-off” disinfection of an area, wherein the ionizer600completely or nearly eliminates airborne and surface pathogens. This disinfection may be sufficient on its own for some purposes or may be followed up by further, traditional cleaning and disinfection procedures. Treating the area with the ionizer600should mitigate the need for cleaning staff to have to don rated PPE in order to safely clean or prepare the room/area. In some embodiments, the ionizer600may have an integrated high-voltage power supply625for the ionizer600. In some embodiments, external power supply625may be obtained via at least one of a mains power supply or a rechargeable battery pack636. In some embodiments, the unit may run off of a USB-C-connected power supply, battery pack, power bank, or an equivalent recognized by a person having ordinary skill in the art. In some embodiments, the ionizer600may further comprise a battery pack636or connections for an external battery power source. In some embodiments, battery-powered systems may be operated without connections to mains power. In some embodiments, battery-powered systems may be portable, such that the entire ionizer600may be moved and positioned manually. In some embodiments, battery packs636may be changed in the field. In some embodiments, the system may be powered by batteries, mains power, or both. In some embodiments, the system may further comprise a mechanism (not shown) whereby an installed battery pack636can be charged while the unit is connected to mains power. In one embodiment, the system further comprises at least one indicator627to inform the user of the battery charge level and may indicate the approximate number of disinfection cycles remaining for the given battery charge level. In some embodiments, the ionizer600may be coupled to a purpose-built fan unit615that is powered from the same power supply625as the ionizer600. In some embodiments, the fan unit615may incorporate a rotating base to enhance circulation. In some embodiments, the fan unit615and/or rotating base may be integrated with the ionizer600. Used with the purpose-built fan unit615, the ionizer600may be set on a table or other horizontal surface. In some embodiments, the ionizer600may include a controller and a user interface650configured to allow the user to control at least one of power, parameters such as fan speed and ionization, and run time duration. For example, in some embodiments, a user may set the ionizer600or fan unit615to run for a fixed or customizable time duration. In some embodiments, the ionizer600may comprise a removable metal plate633held at an electrical potential opposite from that of the ionizer's output or at ground potential with respect to the ionizer. In some embodiments, the plate633may attract and retain pathogen particles in the environment and may be used to assay pathogen presence and/or concentration in an area. In some embodiments, the removable metal plate may be within the ionizer600(not shown). In some embodiments, the removable metal plate633may be external to the ionizer600. Some embodiments may have at least one motion or proximity sensor665. In some embodiments, when the sensor665is activated, the sensor665may activate, deactivate, or adjust at least one of the fan speed or the ionizer output based on detected area occupancy or activity levels. In some embodiments, the at least one sensor665may be used to extend the battery life of battery-powered portable units. In some embodiments, the at least one sensor665may be used to automatically activate disinfection cycles whenever someone enters or leaves a room or area. In some embodiments, the at least one sensor665may be used to automatically activate disinfection cycles whenever a door opens or closes. In some embodiments, the sensor665may be used to automatically restart the disinfection cycle should someone enter the room (and thus possibly re-contaminate the area). Some embodiments may use at least one sensor665to activate the ionizer600when an external forced air source is active. For example, a sensor may activate the ionizer600when the HVAC's circulation fan is running. In some embodiments, the portable ionizer600may be compatible with a wide range of cleaning and disinfection methods. For example, to disinfect the ionizer600, a user may wipe-down the ionizer600with a disinfectant, use UV irradiation, or clean the ionizer600under running water. FIG.7shows an air ionizer PPA system700in accordance with one embodiment. In some embodiments, the system700may include a fan715, an ionizer730, a battery pack736, a laminar output manifold745, and a control system750. In some embodiments, the fan715is configured to push air704through the ionizer730and out the laminar output manifold745to produce laminar air flow705. In some embodiments, the fan715and the ionizer730may be powered by the battery pack736and controlled by the control system750. In some embodiments, the system700may be worn on the head799or otherwise attached to a user's body or a garment on a user's body. For example, the system700may be attached to a headband789, harness, visor, hat, helmet, or face shield, such that the fan715is configured to draw in air704in from above the user and direct the ionized output air705down and away from the user's face. The action of the fan715and the laminar output manifold745creates a sheet of ionized air705flowing down and away from the user's face. In some embodiments, the air705outputted through the laminar output manifold745comprises at least 1 million negative air ions per cubic centimeter of air. In some embodiments, the air705outputted through the laminar output manifold745comprises at least 10 million negative air ions per cubic centimeter of air. In some embodiments, the air705outputted through the laminar output manifold745comprises at least 20 million negative air ions per cubic centimeter of air. In some embodiments, the air705outputted through the laminar output manifold745comprises at least 40 million negative air ions per cubic centimeter of air. In some embodiments, the PPA system700provides protection to both the user and others proximate to the user. In some embodiments, aerosolized pathogen particles may be blown down and away from the user's face and be inactivated by the ionized air705. In some embodiments, this action provides protection from airborne pathogens to the user and others proximate to the user. In some embodiments, when aerosolized pathogen particles are expelled by the user, such as when breathing, speaking, sneezing, or coughing, the particles will likewise be both inactivated by the ionized air705and blown down and away from the user and below the faces of others. In some embodiments, the air705passing in front of the user's face has been drawn from above the user's head799and is less likely to contain aerosolized pathogen particles than air being drawn at the user's eye level or below. In some embodiments, the PPA system700has no consumables, is essentially infinitely reusable, and provides significant protection to the user, particularly if the user does not have access to a rated respirator. In some embodiments, the PPA system700enhances the protection provided by face masks or unrated respirators. In some embodiments, the PPA system700may reduce loading of other PPE that the user might be wearing, such as respirators. In some embodiments, the ionized air705will act to inactivate virus particles that may collect on such PPE or the user's body, thereby attenuating other transmission vectors. In some embodiments, the orientation of the laminar output manifold745is adjustable. In some embodiments, a user may adjust the angle of the manifold745to control the direction of airflow. In some embodiments, a user may adjust the width of the stream of air705exiting the manifold745to cover a wider or smaller area. In some embodiments, the battery pack736may comprise a rechargeable battery and may be interchangeable without removing the PPA system700from the head. In some embodiments, the PPA system700may comprise a removable metal plate (not shown) held at an electrical potential opposite from that of the ionizer's output or at ground potential with respect to the ionizer. In some embodiments, this plate may attract and retain pathogen particles that the user encounters and may be used to assay whether the user may have been exposed to the pathogen. In some embodiments, the metal plate may be used to assay to what extent the user may have been exposed to a pathogen. In some embodiments, this is akin to radiation dosimeters worn in radiology labs. In some embodiments, the PPA system700may have a control system750comprising switches, buttons, or other mechanisms to allow the user to turn the PPA system700on and off, adjust the fan speed, and check the battery charge level. In some embodiments, the control system750may further comprise one or more sensors765and use sensor data to adjust fan speed, ionizer power, or other parameters based on, for example, relative humidity, wind speed, air temperature, detected contaminant levels, or the user's movement. In some embodiments, the control system750is designed to adjust at least one of the fan speed, the ionizer, or the duty cycle such that the expected anion concentration at one or more prescribed locations downstream of the manifold745is at or above a prescribed value. Some embodiments may further incorporate one or more light sources777such as high-intensity LEDs, such that the PPA system700can also serve as a headlamp. Some embodiments may be designed to be powered from standard military personal power sources in addition to or instead of the battery pack736of the PPA system700. In some embodiments, the PPA system700may be compatible with a wide range of cleaning and disinfection methods. For example, to disinfect the PPA system, a user may wipe-down the ionizer with a disinfectant, use UV irradiation, or clean the ionizer under running water. The PPA system may be used to provide augmented protection for airborne pathogens, dust, smoke, or other airborne matter that is susceptible to ionization. Portable systems700may also be used for infant protection in strollers, infant seats/carriers, baby carriers worn by a parent or caregiver, or in a crib or playpen. Reducing the concentration of active aerosolized pathogens in the area proximate to the infant provides a prophylactic value similar to or better than the protection provided by a typical face mask without disrupting play or creating a choking hazard. Instead of affixing a portable system700to a head799of a user, some embodiments may affix a portable system to the top, bottom, or side of a baby carriage or playpen, such that a laminar stream of air705may exit the manifold745to create a partition between the air inside of the carriage and the air outside of the carriage. In some embodiments, the ionizer730in the system700is configured to provide a germicidal screen, implemented by flowing ionized air705, in a compact form-factor that can be readily mounted proximate to a person, including an infant or small child. In some embodiments, the ionizer730is configured to output a laminar ionized air curtain configured to create at least a partial barrier between the wearer and external air. In some embodiments, the ionizer730may comprise at least one mounting systems, including a headband789or strap configured to allow the device to be non-permanently attached to an external mounting point. In some embodiments, the system700may comprise a portable power source, such as a battery pack736. In some embodiments where a power source is one or more batteries, the system700further comprises at least one annunciator755. In some embodiments, when the battery charge or capacity falls below a prescribed threshold, the annunciator755will alert the user with at least one of an audible or visual indicator. In some embodiments, an audible annunciator755comprises a buzzer, beeper, or speaker. In some embodiments, a visual annunciator755comprises a lamp, light, or a blinking indicator. In some embodiments, the system700may comprise a mounting system such as a spring clip or clamp able to securely attach the device to a mounting point such as a strap, fabric, or panel. In some embodiments, the mounting system may comprise a pin or tack that can be inserted through fabric, webbing, or other materials in like manner to a pin-on nametag or button. In some embodiments, a mounting system comprises the hook or loop side of a hook-and-loop attachment system. In some embodiments, a mounting system comprises at least one of a strap, cord, harness, loop, or lanyard that can be placed or fastened to or around an external mounting point, such as a bar, tube, rail, etc. In some embodiments, a mounting system comprises at least one magnet, with the external mounting point being a ferrous/magnetic material, such as steel or iron. In some embodiments comprising one or more controls, the device further comprises one or means of temporarily disabling or locking the controls to prevent inadvertent adjustments. In come embodiments, one or more of the controls is designed to be “child-proof”, “child-resistant”, “child-safe”, or equivalent, such that the control is difficult or impossible for a baby or child to actuate. In some embodiments, the device's controls are locked or unlocked by actuating multiple controls simultaneously or by maintaining actuation of one or more controls for a prescribed time duration. In some embodiments, the system700can be configured or operated in a mode wherein the ionizer730is energized while the fan715is turned off. In this condition, airflow704through the device is induced electrostatically by the ionizer730, providing a continuous, low-velocity flow of ionized air. When air molecules (or other particles) become negatively charged, they are repelled from the one or more anodes in the ionizer730, which are also at a negative potential. Effectively, air is electrostatically “pumped” through the device. In some embodiments, the system700further comprises one or more communications modules784permitting the system700to be at least one of wirelessly monitored or controlled from or with an external device. In some embodiments, a communications module communicates with or permits integration with other household wireless products, such as baby monitors, home security systems, and home monitoring systems. FIG.8depicts a bottom view of a germicidal partition system800with anodes830′,830″,830″′ (collectively830) in accordance with one embodiment. In some embodiments, the germicidal partition system800comprises a fan815configured to direct air over at least one negative ion generator comprising at least one anode830, at least one high voltage conductor856, and at least one high voltage source. The negatively ionized air may then travel through the manifold845in some embodiments. In some embodiments, the air may travel through the manifold845before being directed over at least one anode830. In some embodiments, the anodes830are pointed. In some embodiments, pins are used to direct the air through the manifold845. In some embodiments, the airflow, as indicated, is perpendicular to the anodes830. In some embodiments, the anodes830may be parallel to the airflow. The anodes830may be located (in the air stream) before the manifold845, after the manifold845, inside the manifold845, or any combination thereof. In some embodiments, the anodes830are connected to a high voltage conductor856such that, when connected to a high voltage source (not shown), the air blowing through the manifold845comprises at least 1 million negative air ions per cubic centimeter of air. In some embodiments, the direction of the air is controlled by a laminarizer or other airflow shaping mechanism866. In some embodiments, a user may be able to adjust at least one of the output of negative air ions, the fan strength, or the direction of the airflow by manually adjusting the system800through the control panel850. In some embodiments, when a sensor receives stimulation, the sensor will adjust at least one of the output of negative air ions, the fan strength, or the direction of the airflow out of the manifold845. In some embodiments, the at least one manifold845may be removably attached to the system800, such that the manifold845can be removed with the at least one anode830from the system800and cleaned or exchanged with at least one replacement manifold845and at least one replacement anode830. In some embodiments, the anodes830are not integral to the manifold845and/or the manifold845may not be intended to be replaceable as a unit. FIG.9illustrates a method900of building a germicidal partition system in accordance with one embodiment. In some embodiments, the method comprises electrically connecting at least one high-voltage conductor to at least one negative high-voltage source and at least one anode905. In some embodiments, the at least one high-voltage conductor, the at least one negative high-voltage source, and the at least one anode comprise a negative ion generator. The method900further comprises connecting the negative ion generator to a fan configured to draw air into the system and output air from the system910. In some embodiments, the fan is further configured to direct air over at least one anode of the germicidal partition system and output the air through at least one manifold. In some embodiments, the air outputted through the at least one manifold is configured to create a barrier between a first air mass and a second air mass915, such that the outputted air reduces at least one of the transfer of contaminants or the concentration of viable contagions between the first air mass and the second air mass. The methods, systems, and devices discussed above are examples. Various configurations may omit, substitute, or add various procedures or components as appropriate. For instance, in alternative configurations, the methods may be performed in an order different from that described, and that various steps may be added, omitted, or combined. Also, features described with respect to certain configurations may be combined in various other configurations. Different aspects and elements of the configurations may be combined in a similar manner. Also, technology evolves and, thus, many of the elements are examples and do not limit the scope of the disclosure or claims. Embodiments of the present disclosure, for example, are described above with reference to block diagrams and/or operational illustrations of methods, systems, and computer program products according to embodiments of the present disclosure. The functions/acts noted in the blocks may occur out of the order as shown in any flowchart. For example, two blocks shown in succession may in fact be executed substantially concurrent or the blocks may sometimes be executed in the reverse order, depending upon the functionality/acts involved. Additionally, or alternatively, not all of the blocks shown in any flowchart need to be performed and/or executed. For example, if a given flowchart has five blocks containing functions/acts, it may be the case that only three of the five blocks are performed and/or executed. In this example, any of the three of the five blocks may be performed and/or executed. A statement that a value exceeds (or is more than) a first threshold value is equivalent to a statement that the value meets or exceeds a second threshold value that is slightly greater than the first threshold value, e.g., the second threshold value being one value higher than the first threshold value in the resolution of a relevant system. A statement that a value is less than (or is within) a first threshold value is equivalent to a statement that the value is less than or equal to a second threshold value that is slightly lower than the first threshold value, e.g., the second threshold value being one value lower than the first threshold value in the resolution of the relevant system. Specific details are given in the description to provide a thorough understanding of example configurations (including implementations). However, configurations may be practiced without these specific details. For example, well-known circuits, processes, algorithms, structures, and techniques have been shown without unnecessary detail in order to avoid obscuring the configurations. This description provides example configurations only, and does not limit the scope, applicability, or configurations of the claims. Rather, the preceding description of the configurations will provide those skilled in the art with an enabling description for implementing described techniques. Various changes may be made in the function and arrangement of elements without departing from the spirit or scope of the disclosure. | 66,681 |
11857708 | DETAILED DESCRIPTION In the following, embodiments of the present disclosure will be described with reference to an auto-injector. The present disclosure is however not limited to such application and may equally well be deployed with injection devices that eject other medicaments, or with other types of drug delivery devices, such as syringes, pre-filled syringes, needleless injectors and inhalers. An injection device10according to embodiments will now be described with reference toFIGS.1A and1B. In some embodiments, the injection device10is a single use auto-injector10. The auto-injector10has a proximal end P and a distal end D. The proximal end P is directed towards the injection site of a patient during an injection while the distal end D is directed away from the injection site. The auto-injector10comprises a body9and a cap12(also referred to herein as the outer needle cap or ONC12). The body9comprises an outer housing11. The outer housing11is an elongate tube. The outer housing11includes a cartridge holder or syringe holder (not shown) which supports a cartridge or syringe18containing liquid medicament16. Hereafter the description shall refer to a cartridge18, which is supported by a cartridge holder (not shown). The cartridge18is shown in broken lines inFIG.1B. The outer housing11also houses a dispense mechanism (not shown) for causing dispensing of the medicament16during injection. A hollow needle17communicates with an interior volume of the cartridge18and serves as a conduit for liquid medicament16during injection. The needle17and the cartridge18are in a fixed position relative to each other and to the body9. A stopper, plunger, piston or bung14is moveable within the cartridge18to as to expel medicament contained within the cartridge18through the needle17under action of the dispense mechanism. The dispense mechanism is mechanically coupled to the piston14of cartridge18. The dispense mechanism is configured to move the piston axially along the cartridge18in a proximal direction to dispense medicament16through the needle17. The dispense mechanism includes components that cooperate to apply a force to the piston14in response to an actuation input provided by a user. Here, the actuation input that triggers application of a force to the piston14is received by way of a dose dispense button13that is located at the distal end of the auto-injector10. The dispense mechanism is mechanically coupled to the dispense button13. The body9further comprises a dosage selector23at the distal end of the outer housing11. The dosage selector23allows to manually select a dosage to be injected by rotating it clockwise. An internal mechanism (not shown) is mechanically coupled to the dispense mechanism in order to adjust it for injection of a selected dosage. The body9also comprises a cap support19at the proximal end of the outer housing11. The cap support is concentric with the outer housing11and may have a smaller diameter. The cap support19extends from the proximal end of the housing11. The ONC12is received over the cap support19to close the proximal end of the body9and to cover the needle17. The ONC12comprises a cylindrical wall21and an end wall22. With the ONC12located on the body9, as shown inFIG.1A, an internal surface of the cylindrical wall21abuts an external surface of the cap support19in tightly abutting relation so that the ONC12is retained thereon in an attached position. Before injecting the medicament16, the user select via the dosage selector23the dose to be injected. To inject the medicament16, the ONC12is removed from the device10by the user, resulting in the arrangement shown inFIG.1B. Next, the proximal end of the auto-injector10is placed against an injection site of a patient, which may be the user or another person. The user then actuates the dispense button13. This causes the dispense mechanism to force the piston14to expel medicament from the cartridge18through the needle17into the injection site of the patient. The cartridge18is transparent and a window15is provided in the housing11coincident with the cartridge18so that the medicament16contained within the cartridge18is visible. A user of the auto-injector this is able by inspection to determine whether the entire quantity of medicament16has been ejected from the cartridge18during the injection. A label is provided on the housing11. The label includes information100about the medicament included within the injection device10, including information identifying the medicament. The information100identifying the medicament may be in the form of text. The information100identifying the medicament may also be in the form of a color. The information100identifying the medicament may also be encoded into a barcode, QR code or the like. The information100identifying the medicament may also be in the form of a black and white pattern, a color pattern or shading. FIG.2is a schematic illustration of an embodiment of a supplementary device50to be releasably attached to injection device10ofFIG.1. Supplementary device50comprises a carrier interface51configured to mechanically couple to the dosage selector23of injection device10ofFIG.1, particularly to be clamped on the dosage selector23so that a rotation of the interface51is transferred to the dosage selector23. Supplementary device50further comprises a dial knob52for dosage selection. Dial knob52overlaps carrier interface51at least partly. FIG.3is a cutaway illustration of the first embodiment of the supplementary device50showing the inner mechanism for dosage selection. The carrier interface51is clamped on the dosage selector23of the injection device. A metal spring53is mounted on a printed circuit board (PCB)54, which comprises electronics and a sensor, for torque transmission and definition of a resetting position of the dial knob52. A battery55for supplying the electronics of the PCB54is arranged between the PCB54and the inner side of the dial knob52. Two guidance56,57are comprised in/on the outer side of the carrier interface51, as can be seen in the view A. The guidance56,57are provided for the dial knob52, which serves two functions, namely dosage selection by turning it around the axis of the body9and injection by pressing it down to the release button13of the injection device. The guidance57prevents a damage of the sensor and/or the spring53when the device end stop is reached, and defines the resetting position of the dial knob52. The guidance56prevents an overwinding of the dial knob52. A further spring58is arranged between the carrier interface51and the dial knob52such that it pushes the dial knob52in the resetting position. FIG.4shows perspective illustrations of an implementation with two springs53,53′ and their arrangement on the PCB54. Both springs53,53′ are welded on one end53″ to the PCB54. The other ends of the springs53,53′ are freely movable arranged over sensor elements59on the PCB54. End stops53′″ restrict the movement of the freely movable spring ends in a respective direction. When a user turns the dial knob52to select a dosage (clockwise) or to unselect or correct a selected dosage (counter-clockwise), a dialing force is exerted on the springs53,53′ via cams51′,51″ (FIG.5) provided within the dial knob52, which results in a movement of the freely movable spring ends over the sensor elements59. A rotation of the PCB54is prevented by anti-rotation locks54′. The movements of the spring ends are restricted by the end stops53′″ arranged at the sensor elements59. Movements of the spring ends over the sensor elements59may cause sensor signals, which may be detected by an electronics of the PCB54and processed to determine a selected dosage, as will be explained with reference toFIG.16later. FIG.6is a perspective illustration of another implementation with one spring53″″ and its arrangement on the PCB54. The two ends of the spring53″″ are both welded near opposing edges of the PCB54. The spring53″″ contacts two sensor elements59′, which are welded on one of their sides on the PCB54. One sensor element is provided for detecting a left-hand turn of the dial knob52(for example, when unselecting a dose), and the other sensor is provided for detecting a right-hand turn of the dial knob52(for example, when selecting a dose). Both sensor elements59′ are arranged on different sides of the spring53″″. FIG.7shows two cutaway illustrations of the first embodiment with the dosage selection or dial knob52in two different statuses. The above illustration shows the status of unused or dialing or selecting a dosage with no pressure exerted on the dial knob52. The below illustration shows the status of an injection, when the dial knob52is pushed down. Before continuing with the description of further embodiments, the determination of a selected dosage and of an injection by the electronics of the PCB55is explained with regard to the diagram ofFIG.16, which shows an example course of the signal of a sensor generated during dialing or selecting a dosage and an injection of the selected dosage with the supplementary device50. The usage of the supplementary device50with an injection device10begins with mounting the supplementary device50on the injection device button23, which is provided for dosage selection. The supplementary device50may automatically detect a mounting, for example by a micro-switch arranged in the carrier interface51and activated upon mounting. This detection may trigger a power supply55of the electronics of the PCB54. Then, the user may confirm an initial unit position in order to set an absolute value, particularly a “0” dosage selection. The supplementary device50is thereafter ready to use. The user may now select or dial a desired dosage to be injected by the injection device10by turning the dial knob52for example clockwise. The clockwise turning causes—as described above—sensor signals corresponding to sensor measurements of for example the movement of the free ends of the springs53,53′ of the supplementary device50. The measurements typically comprise peaks, for example voltage peaks of a measurement voltage, which correspond to clicks caused by the dosage selection of the user, as illustrated in the diagram ofFIG.16. By counting these peak measurements, the electronics can determine the selected dosage. When the user then pushes the dial knob52down, the springs53,53′ are moved forward to the release button13and are pressed on the release button13such that the latter is activated for an injection. At the same time, the freely movable ends of the springs53,53′ are pressed by the pushing of the dial knob52on the sensor elements59, which may detect this pressure and generate a strong signal larger than the peaks, which may be again detected by the electronics as the begin of an injection. The correct end of the injection position or time can be detected by the resetting force (resetting progress) measurable by the sensor elements59. FIG.8is a perspective illustration of a second embodiment of a supplementary device60to be releasably attached to injection device10ofFIG.1. Supplementary device60comprises a carrier interface61configured to be mechanically coupled to the dosage selector23of injection device10ofFIG.1, particularly to be clamped on the dosage selector23so that a rotation of the interface61is transferred to the dosage selector23. Supplementary device60further comprises a dial knob62for dosage selection and an injection button63. Within device60, a PCB64and a battery65as power supply for the electronics of the PCB64are arranged (dashed lines inFIG.8). A sensor66is made from a quantum tunnelling composite (QTC) material. FIG.9is a perspective illustration of the PCB64with QTC component used as sensor66. The QTC component66comprises two blades66′″ arranged opposite to each other. A blade66″″ may comprise electrical connection points66′,66″ for connection with the electronics of the PCB64. The surface resistance of the QTC component between the connection points66′,66″ is influenced by pressure exerted on the blade66′″. The pressure is exerted by the dial knob62, which is turned by a user for dosage selection. The knob62transmits a torque change to the sensor66, particularly on the blades66′″. The change of the resistance between the connection points66′,66″ can be detected in order to determine the selected dosage, for example processed by a circuitry as shown inFIG.10: a microcontroller can be configured to detect the voltage U divided by the voltage divider circuit comprising a reference resistor Rref and the QTC component resistor between points66′,66″. FIG.11is a perspective illustration of an alternative implementation of the second embodiment, wherein the PCB with the electronics can be arranged in an angle of about 90° to the direction of a forcer67. The dial knob62′, which is illustrated partly transparent in order to show the distal end of the injection device with the release button13and the dosage selector23, is shaped to directly force a pressure in the QTC sensor66upon rotation when a user selects or dials a dosage. The forcer67transfers a pressure exerted in the axis of the body9on the release button13to start an injection. The QTC sensor66may comprise several surface resistors as represented by the plurality of electrical connection points. All resistors may be for example connected by the electronics of the PCB in parallel so that the lowest surface resistor has a relatively large impact on the total resistance of the parallel connection. FIG.12shows two cutaway illustrations of the embodiment fromFIG.8with the injection button63in two different positions. The above illustration shows the status of unused or dialing or selecting a dosage with no pressure exerted on the injection button63. The below illustration shows the status of an injection, when the injection button63is pushed down. In this status, the pressure exerted on the injection button63is transferred via the battery65, the PCB64, the QTC sensor66, and the forcer67to the release button13of the injection device. FIG.13is a cutaway illustration of a third embodiment of a supplementary device70to be releasably attached to injection device10ofFIG.1. Supplementary device70comprises a carrier interface77configured to be mechanically coupled to the dosage selector23of injection device10ofFIG.1, particularly to be clamped on the dosage selector23so that a rotation of the interface77is transferred to the dosage selector23. Supplementary device70further comprises a dial knob71for dosage selection. Within device70, a PCB72and a battery73as power supply for the electronics of the PCB72are arranged. An injection torque pin74is provided for transferring a pressure exerted on the dial knob71along the axis76to the release button13for an injection. The injection torque pin74extends through a clutch coupling plate being part of the carrier interface77and a sensor wheel75arranged within the clutch coupling plate. The sensor wheel75and the clutch coupling plate of the carrier interface77are shown in detail inFIG.14. The wheel75has at least two spokes79and a central bearing78through which the injection torque pin74may extend. The central bearing78comprises anti-rotation locks78′ for preventing a rotation of the pin74within the bearing and ensure that a torque exerted on the pin74via the dial knob71is transferred to the spokes79and the wheel75. The outer contour of the wheel75comprises teeth's75′ matching with corresponding teeth's at the inner side of the carrier interface77. The teeth's may be implemented for a permanent (play free) interface to the dosage selector23(more or less teeth's may be necessary). With at least one of the spokes79, a sensor element may be implemented. An implemented sensor element detects a bending of the spoke79. A sensor element may be implemented in various combinations of different sensor techniques and different sensor wheel materials. Combinations may be for example a QTC material combined with a rubber wheel; a force sensing resistor material combined with a plastic wheel; a strain gauge sensor material combined with a plastic or metal wheel. Depending on the combination of the sensor technique and the sensor wheel material, the design of the wheel with implement sensor elements may be different. The spokes of the wheel75are flexible and are bend upon exertion of a torque on the wheel75when a rotation of the wheel75is prevented. A wheel75with specially designed spokes79′ is shown inFIG.15. The spokes79′ comprise recesses in which sensor elements R1, R2are located. The tapering of the spokes79′ caused by the recesses allows a more extensive bending of the spokes79′ as can be seen in the left illustration inFIG.15. When a dose is dialled, for example when a user selects a dose by clockwise rotating the dial knob71or when the user corrects a selected dose by counter-clockwise rotating the dial knob71, a torque is transferred from the dial knob71via the injection torque pin74to the wheel75, which causes the bending of the spokes79′ as shown in the left and right illustration left inFIG.15. When no torque is exerted on the wheel75, it is in a free state and the spokes79′ are not bent, as shown in the middle illustration left. A bending of the spokes79′ activates the sensor elements R1, R2, which can be measured by the electronics of the PCB72. The resetting force of the wheel75(back to the free state) depends on several parameters such as the wheel material, design, particularly of the spokes79′, and the device counterforce. An injection device may be at least partially retained within the supplementary device as disclosed herein, but may be nevertheless removable from the supplementary device, for instance when injection device is empty and has to be replaced. The injection device and supplementary device may comprise co-operating alignment features to ensure that the supplementary device is correctly orientated and positioned with respect to the injection device. For example, the injection device and supplementary device may be releasably secured together using a bayonet fitting where the injection device has a protrusion on the housing and the supplementary device has a corresponding groove for receiving the protrusion. FIG.17is a block diagram of an electronics100of the supplementary device. The electronics100comprises a processor101and a memory102storing an operating system for the processor101and a software104for processing sensor signals and to determine the selected dosage from the processed sensor signals as well as data transmission and receipt. The processor101controls a communication circuitry106, particularly a wireless unit, which is configured to transmit and/or receive information to/from another device in a wireless fashion. Such transmission may for instance be based on radio transmission or optical transmission. In some embodiments, the wireless unit is a Bluetooth transceiver. Alternatively, wireless unit may be substituted or complemented by a wired unit configured to transmit and/or receive information to/from another device in a wire-bound fashion, for instance via a cable or fibre connection. When data is transmitted, the units of the data (values) transferred may be explicitly or implicitly defined. For instance, in case of an insulin dose, International Units (IU) may be used, or otherwise, the used unit may be transferred explicitly, for instance in coded form. The transmitted data may also include a time stamp associated with an injection. A battery105powers the processor101and other components by way of a power supply103. The attachment of the supplementary device to an injection device can be detected by a sensor or micro-switch being automatically activated, and this can be used as a wake-up or switch on trigger. Thus, the supplementary device may automatically turn on and begin operate when it is attached to an injection device. Similarly, when the supplementary device is detached from an injection device, it may automatically power off, thus saving battery power. In operation, the processor101is configured by the software104to receive and process signals output by the one or more sensors108of the supplementary device, such as shown inFIG.16. The processor101may count peaks of the sensor signals and derive from the counted peaks a dosage selected by the user. For example, the processor101may multiply the number of the counted peaks with a dose unit, which corresponds to one click when the user turns the dial knob of the supplementary device. The processor101may be also configured to detect the start and end of an injection from the sensor signals. As mentioned above with reference toFIG.16, when the injection button is pushed, the output sensor signals may clearly indicate the beginning of an injection, for example by a large peak measurement. If the processor101detects such a signal, it may generate a time stamp and store it together with the determined selected dosage in the memory102. Also, the end of the injection may be detected by the processor101, and a time stamp may be stored in memory102. After an injection, the processor101may be configured to transmit the stored information related to a selected dosage of a medicament and/or use of an injection device via the communication circuitry106to an external electronic device, for example a smartphone or a computer. This information can be also displayed on a display107for use by the user of the injection device. The information may be either processed by supplementary device itself, or may at least partially be provided to another device (e.g., a blood glucose monitoring system or a computing device). The processor101may be further configured to record a user's injection history. While the injection device may be a single use auto-injector, the supplementary device is reusable, and is configured to be removed from a used injector and attached to a new injector. The processor101of the supplementary device may have an internal clock in order to create time stamps associated with the injection events. The clock may be a relative clock or an absolute clock. The supplementary device may be configured to communicate with an external device through wireless unit106and the external device may provide an absolute time. The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders. As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated. The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more drugs. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20° C.), or refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some instances, the drug container may be or may include a dual-chamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and/or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body. The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and/or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (anti-diabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition. Examples of APIs for the treatment and/or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and/or exchanging at least one amino acid residue occurring in the naturally occurring peptide and/or by adding at least one amino acid residue. The added and/or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as “insulin receptor ligands”. In particular, the term “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and/or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide. Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin. Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N-tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N—(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N—(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin. Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide/HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN and Glucagon-Xten. An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia. Examples of DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine. Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin. Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g., a poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate. The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab′)2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and/or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV). The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and/or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full-length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present disclosure include, for example, Fab fragments, F(ab′)2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art. The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen. Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab). Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Those of skill in the art will understand that modifications (additions and/or removals) of various components of the APIs, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present disclosure, which encompass such modifications and any and all equivalents thereof. | 34,818 |
11857709 | DETAILED DESCRIPTION An illustrative embodiment of the present invention relates to a medical airway passage device suitable for maintaining an airway for a patient. The medical airway passage, or supraglottic airway, device includes a novel coupler device designed to prevent undesired or unintentional un-coupling, contamination, infection, and unwanted discharge of patient fluids and solids during usage. The coupler includes a locking mechanism configured to lock the coupler to a breathing tube, and thus, prevent undesired or unintentional un-coupling of the coupler from the breathing tube. The locking mechanism includes one or more detents configured to form an interference fit between the coupler device and a breathing tube. The interference fit prevents the coupler device from unintentionally becoming dislodged from the breathing tube during use. The coupler also includes a side port including a self-closing seal configured to receive a suction device for removing patient discharges from the breathing tube and/or coupler. The side port is configured such that the coupler does not need to be removed from the breathing tube to perform the suction operation. The coupler further includes a filter for enabling the free flowing passage of airflow while preventing the flow of patient fluid discharges. FIG.1depicts an example illustration of a conventional endotracheal tube100. The conventional endotracheal tube100includes a connector or coupler device102, a breathing tube104, a vocal cord level indicator106and other demarcations, a cuff108, a beveled opening110, a pilot balloon112, and a self-sealing valve114. As depicted inFIG.1, the coupler device102is attached to one end of the breathing tube104. Traditionally, the coupler102is coupled to the breathing tube104via a friction fit by inserting the coupler102into the open end of the breathing tube104. At the opposing end of the breathing tube104is the beveled opening110. Additionally, the cuff108and vocal cord level indicator106located proximal to the beveled opening110. The cuff108is an inflatable element which is inflated to form a seal against a tracheal wall of a patient. The seal created by an inflated cuff108prevents gases from leaking past the cuff108and allows positive pressure ventilation. As would be appreciated by one skilled in the art, not all conventional endotracheal tube100designs include each of the elements provided inFIG.1. For example, a conventional endotracheal tube100can be an un-cuffed design and not include the cuff108. The conventional endotracheal tube100can also include the pilot balloon112and self-sealing valve114located proximal to a mid-section of the conventional endotracheal tube100, as depicted inFIG.1. The pilot balloon112is connected to the cuff108by a thin tube. In practice, the conventional endotracheal tube100can be inserted into the trachea202of a patient200, starting with the beveled end110, to assist the patient in exchanging oxygen and carbon dioxide, as depicted inFIG.2. When the conventional endotracheal tube100is inserted in the trachea202of the patient200, the coupler device102, the pilot balloon112, and the self-sealing valve114are located outside of the patient200for access by a medical professional. A syringe can be inserted into the self-sealing valve114and as the syringe supplies pressurized air, the pilot balloon112and cuff inflate108. Once the cuff108is inflated the syringe is removed. Air does not leak out as there is a one way valve at the pilot balloon112. Additionally, when feeling the pilot balloon112, a medical professional can estimate an amount of pressure in the cuff108. For example, if the cuff108is leaking, the pilot balloon112will collapse. FIGS.3through5H, wherein like parts are designated by like reference numerals throughout, illustrate a first example embodiment of an improved medical airway device or supraglottic airway device, particularly an endotracheal tube device, according to the present invention. Although the present invention will be described with reference to the example embodiment or embodiments illustrated in the figures, it should be understood that many alternative forms can embody the present invention. One of skill in the art will additionally appreciate different ways to alter the parameters of the embodiment(s) disclosed, such as the size, shape, or type of elements or materials, in a manner still in keeping with the spirit and scope of the present invention. FIG.3depicts a supraglottic airway device in accordance with the present invention. In particular,FIG.3depicts an endotracheal tube device300embodiment, including an elongate breathing tube304having a first open end304aand a second open end304b. The endotracheal tube device300also includes a removable and replaceable coupler302disposed at and coupled to the first open end304aof the breathing tube304. The replaceable coupler302of the present invention includes a combination of novel elements not found in traditional couplers (e.g., coupler102) for airway devices, as discussed in greater detail with respect toFIGS.4-5H. The device300may also include a breathing valve400to enable introduction of air to the patient, and a pressure relief port500to enable relief of buildup content in the breathing tube304. The pressure relief port500may be used to removably engage a pressure application apparatus as needed. The endotracheal tube device300, as depicted inFIG.3, also includes other traditional elements of a conventional endotracheal tube100. For example, the endotracheal tube device300includes a vocal cord level indicator306and other traditional line demarcations disposed on the breathing tube304, an inflatable cuff308(disposed proximal the second open end of the breathing tube), a beveled opening310located at the second end304bof the breathing tube304, a pilot balloon312, and a self-sealing valve314. As would be appreciated by one skilled in the art, the endotracheal tube device300of the present invention can alternatively not include a cuff308and related elements without departing from the scope of the present invention. The breathing tube304, the cuff308, the beveled opening310located at the second end304bof the breathing tube304, the pilot balloon112corresponding to that ofFIG.1, and the self-sealing valve114corresponding to that ofFIG.2, of the endotracheal tube device300share the same functionality known in the art and as discussed with respect toFIGS.1and2. As would be appreciated by one skilled in the art, the novel elements of the present invention are not intended to be limited to an endotracheal tube but can be implemented for use with any applicable medical airway device known in the art. For example, the present invention can be adapted for use as any combination of airway devices utilizing a breathing tube304and a coupler302including but not limited to a supraglottic airway device or a supraglottic airway device; such as: The King, Combi-tube, LMA and any other non-invasive (blind-insertion) tubes utilized to protect/ventilate the airway of a patient. Additionally, all sizes of medical airway devices will be accounted for, and implementations will be incorporated on all adult sizes with the possibility of implementation to infant/child size breathing tubes. FIGS.4A-4Ddepict example illustrations of the coupler302of the present invention. In particular,FIG.4Adepicts a representative illustration of the coupler302andFIG.4Bdepicts an exploded view of the coupler302.FIG.4Cdepicts a two-dimensional/flattened view of the coupler302, andFIG.4Ddepicts the locking mechanics of the coupler302to the tube304. In accordance with an example embodiment of the present invention, the coupler302is a male-to-male coupler, as depicted inFIGS.4A-4D. More specifically, the coupler302includes a first cylindrical male end302aand a second cylindrical male end302bopposite the first cylindrical male end302a. The first cylindrical male end302ais adapted to couple (in a locked-in position) with a breathing tube304when positioned within the first open end304aof the breathing tube304. In particular, the first cylindrical male end302ais configured in a locked-in position with the breathing tube304via an interference fit created between a tube-engaging side surface318of the coupler302and an inner wall of the breathing tube304. A ring component331to enable attachment of the tube304to the patient provides a smooth engagement mechanism for doing so for trained medical provider usage. In accordance with an example embodiment of the present invention, the interference fit is further enhanced by use of a first detent322disposed on the tube-engaging side surface318of the first cylindrical male end302aengaging with a recess304adisposed in the inner wall of the breathing tube304. In particular, the detent322on the tube-engaging side surface318of the first cylindrical male end302aengages with a first recess disposed in the inner wall of the breathing tube304, which is sized, dimensioned, and positioned in such a way that the first recess engages with the first detent of the coupler302. The first recess is not shown in the figure but it would be readily understood by those of skill in the art that the recess would be a notch, groove, or the like that engages with the detent322. Additionally, the first recess can be a singular location, multiple locations, or can be in the form of a ring shaped groove around an entire circumference of the breathing tube304. When the detent322of the coupler302is disposed within the indent of the breathing tube304, the coupler302is in the locked-in position within the first open end304aof the breathing tube304by engaging with the first recess. In accordance with an example embodiment of the present invention, the interference fit is established by the relative size of the coupler302to the breathing tube304. As shown inFIG.5A, for example, the breathing tube304stretches to fit over the coupler302, thereby creating a tight interference fit between the tube-engaging side surface318of the coupler302and the inner wall of the breathing tube304. One of skill in the art would appreciate the specific dimensions of the coupler302must be sized to engage with the specific dimensioned breathing tube in any instance to create the described stretching of the breathing tube304and resulting interference fit. As would be appreciated by one skilled in the art, the coupler302can include any number of detents322(and corresponding indentations or holes) configured to engage with the breathing tube304. For example, the coupler302can include a second detent disposed on the tube-engaging side surface318of the first cylindrical male end302aof the coupler302. The combination of the one or more detents322with the recess304aand the interference fit of the coupler302with the inner wall of the breathing tube304, create a substantially improved removable coupling between the breathing tube304and the coupler302, which prevents the undesired or unintentional un-coupling of the breathing tube304from the coupler302that is evident in the prior conventional devices. The coupler device302includes a housing that contains the self-closable suction port316, a pressure port341and a ventilation port351.FIGS.5B-511depict different angles and components, as well as interior and exterior views of the device as shown inFIG.5A. In accordance with an example embodiment of the present invention, the coupler302is removably but securely coupled with the breathing tube304as described above. Alternatively, the coupler302can be fixedly or permanently attached to the breathing tube304through any combination of non-toxic glues, heat sealing, mold manufacturing process, etc. The fixedly attached implementation of the coupler302and the breathing tube304would form a single piece airway device. In accordance with an example embodiment of the present invention, a closable suction port316is disposed in and passing through the tube-engaging side318of the first cylindrical male end302aof the coupler302, as depicted inFIGS.3-6. In accordance with this example embodiment, the breathing tube304will include a hole at a location lining up with the suction port316of the coupler302when the coupler302is locked into place. In other words, there is a hole disposed in and passing through the breathing tube304and having a central axis in alignment with a central axis of the suction port316of the coupler302when the coupler302is in the locked-in position. The hole in the breathing tube304will enable liquid discharged from the patient to pass from the breathing tube304through the self-closable suction port316in the coupler302(e.g., via a suction device). In an alternative embodiment, the coupler302includes the self-closable suction port316disposed in and passing through the tube as depicted inFIGS.4A and4C. Regardless of the placement of the suction port316, the opening in the breathing tube304and the opening of the suction port316are intended to align and match up substantially in shape and substantially in dimension. Regardless of placement, the suction port316includes a self-closing seal316adisposed in the suction port316. The self-closing seal316aof the suction port316can be closed to prevent discharge (e.g., mucous, blood, vomit, other bodily fluids, etc.) from the patient from exiting the endotracheal tube device300or the suction port316can be opened such that a suction device can be inserted therein to remove solid and fluid discharge from the patient. Additionally, the suction port316is configured such that a suctioning tube (not depicted) can be left in place connected to the coupler302(and breathing tube304) without having to risk another sterile piece of equipment becoming unsterile by the same means the coupler302can become contaminated (e.g., unintentional removal). This feature allows the medical provider to always know where the suction tubing is, and have the capability of turning on/off suction immediately, when needed. As would be appreciated by one skilled in the art, any self-closing design known in the art for the seal can be utilized for the suction port316, depending on the desired opening and closing of the self-closing seal316aof the suction port316. For example, a gasket with pie shaped slits can be utilized as the self-closing seal316aof the suction port316, as depicted inFIG.4D. In accordance with an example embodiment of the present invention, the second cylindrical male end302bis sized, dimensioned, and configured for coupling with traditional medical devices in a similar fashion as traditional couplers (e.g., coupler102). For example, the second cylindrical male end302bof the coupler302is configured for engagement with a ventilator, a bag-valve mask, a catheter mount, etc., as would be readily appreciated by those of skill in the art. FIG.5Bdepicts a close up view of the coupler302disposed at and coupled to the first open end304aof the breathing tube304to result in the endotracheal tube device300of the present invention. In particular,FIG.5Bdepicts the coupler302removably locked into place with the breathing tube304(e.g., via the detent322and the interference fit of the tube-engaging side surface318of the coupler302engaged with the inner wall of the breathing tube304) and the suction port316including the self-closing seal316ais provided through the side of coupler302and the breathing tube304. Continuing withFIGS.4A-4D, in accordance with an example embodiment of the present invention, the coupler302further includes a contaminant blocking air pass filter320disposed therein. In particular, the filter320allows air to flow freely there through, but minimizes or inhibits liquid/solid content diffusion through the filter320and through the second cylindrical male end302bof the coupler302. Therefore, the filter320will allow air to enter and exit the breathing tube304while preventing secretions/fluids from exiting through the second cylindrical male end302bof the coupler302. As would be appreciated by one skilled in the art, the filter320can include any material known in the art to perform such filtering. In accordance with an example embodiment of the present invention, as depicted inFIGS.3-5H, the filter320is disposed within the second cylindrical male end302bof the coupler302after the suction port316. In an alternative embodiment of the present invention, the filter320is disposed within the first cylindrical male end302aof the coupler302prior to the suction port316, as depicted inFIGS.6A and6B. Regardless of the placement of the suction port316within the coupler302, which primary purpose is provided for suction of materials from the tube, the suction port316will always be placed before the filter320.FIGS.6A and6Bfurther depict an alternative ergonomic embodiment of the coupler302where the ventilation port351is angled/beveled so as not to interfere with the anterior area of the patient (not having the BVM or ventilator tubing resting on the patient's face). The device ofFIGS.6A and6Boptionally also includes the pressure relief port500. In operation, the design and elements of the coupler302are configured to reduce exposure of patient discharges, expelled forcefully and non-forcefully from a breathing tube304, to a medical professional while utilizing an airway breathing apparatus (such as an endotracheal tube device300). The reduction of such exposure is provided through the combination of improvements to the coupler302. In particular, the tube-engaging side surface318of the coupler302securely locks the coupler302in place at the end of the breathing tube304using a combination of an interference fit and a detent engaging with a recess as described herein. The locking mechanism provided by the tube-engaging side surface318of the coupler302also prevents the coupler302from decoupling from the breathing tube304and contaminating the coupler302and/or the breathing tube304. As would be appreciated by one skilled in the art, the coupler302and the breathing tube304should remain sterile to ensure the best medical care to the patient while reducing risks of infection and other issues. The best way to keep the coupler302and breathing tube304sterile is to maintain the coupling between the two pieces. Additionally, the inclusion of the suction port316enables improved suction operation (e.g., via a suction device of tube inserted into the endotracheal tube device300) such that the coupler302does not need to be intentionally removed for such operations. In other words, although the coupler302can optionally be de-coupled from the breathing tube304, the present invention eliminates any such reason to because of the self-closing seal316adisposed within the suction port316of the coupler302(and optionally through the breathing tube304). The self-closing seal316aallows suction tubing (e.g., French catheter tubing) to be inserted into the suction port316without having to remove the coupler302from the breathing tube304. As would be appreciated by one skilled in the art, any removal of the coupler302intentional (e.g., suction) or otherwise increases the chances of the coupler302and the breathing tube304becoming unsterile and/or lost. In addition, the inclusion of the filter320of the coupler302prevents low and high concentrations of patient discharges to expel directly out of the endotracheal tube device300or other airway device. In particular, the filter302provides the medical provider with an extra barrier of cross-contamination/exposure which is common in the field. By reducing a volume of discharges, the filter302reduces tension experienced by a medical professional when ventilating a patient which can reduce forceful ventilation and hyperventilation, which can harm the patient. Additionally, the filter302provides a passive benefit by restricting the medical provider's (bag squeeze) to overly/forcefully ventilate the patient with a bag valve mask. Moreover, the filter302will produce a semi-trap so all the content of the discharges contained within the coupler302and breathing tube304can be suctioned out with ease (e.g., via the suction port316). As would be appreciated by one skilled in the art, discharges in and around the breathing tubes that re-enter the patient's anatomy increases chance of infections, pneumonia, etc. As would be appreciated by one skilled in the art, the coupler302can include each of the elements316,318,320or some combination of those features. Overall, the features of the present invention are designed to increase positive outcomes in cardiac/respiratory arrest patients and patients that are in need of advanced airways by reducing infection overall. The patient benefits from the features of the present invention, and the medical provider assisting the patient's airway has a lower risk of exposure from patient contents. These benefits are achieved through the reduction in chances of pieces of the airway device losing sterility, a reduction of aspiration and ventilation pneumonia, easy-access suctioning, prevention of medical provider exposure to bodily fluids, and a reduction in hyperventilation. FIG.7depicts a method700for operating a supraglottic airway device. At step702a user inserts a first cylindrical male end of a removable and replaceable male-to-male coupler into a first open end of an elongate breathing tube forming an interference fit between a tube-engaging side surface of the coupler and an inner wall of the breathing tube. At step704the user aligns a first detent disposed on the tube-engaging side surface of the first cylindrical male end of the coupler with a first recess disposed in the inner wall of the breathing tube, sized, dimensioned, and positioned in such a way that the first recess engages with the first detent of the coupler. At step706the user aligns a side port disposed in and passing through the tube-engaging side of the first cylindrical male end. Upon completion of steps702-706of the method700the supraglottic airway device is ready for utilization on a patient. As utilized herein, the terms “comprises” and “comprising” are intended to be construed as being inclusive, not exclusive. As utilized herein, the terms “exemplary”, “example”, and “illustrative”, are intended to mean “serving as an example, instance, or illustration” and should not be construed as indicating, or not indicating, a preferred or advantageous configuration relative to other configurations. As utilized herein, the terms “about”, “generally”, and “approximately” are intended to cover variations that may exist in the upper and lower limits of the ranges of subjective or objective values, such as variations in properties, parameters, sizes, and dimensions. In one non-limiting example, the terms “about”, “generally”, and “approximately” mean at, or plus 10 percent or less, or minus 10 percent or less. In one non-limiting example, the terms “about”, “generally”, and “approximately” mean sufficiently close to be deemed by one of skill in the art in the relevant field to be included. As utilized herein, the term “substantially” refers to the complete or nearly complete extend or degree of an action, characteristic, property, state, structure, item, or result, as would be appreciated by one of skill in the art. For example, an object that is “substantially” circular would mean that the object is either completely a circle to mathematically determinable limits, or nearly a circle as would be recognized or understood by one of skill in the art. The exact allowable degree of deviation from absolute completeness may in some instances depend on the specific context. However, in general, the nearness of completion will be so as to have the same overall result as if absolute and total completion were achieved or obtained. The use of “substantially” is equally applicable when utilized in a negative connotation to refer to the complete or near complete lack of an action, characteristic, property, state, structure, item, or result, as would be appreciated by one of skill in the art. Numerous modifications and alternative embodiments of the present invention will be apparent to those skilled in the art in view of the foregoing description. Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the best mode for carrying out the present invention. Details of the structure may vary substantially without departing from the spirit of the present invention, and exclusive use of all modifications that come within the scope of the appended claims is reserved. Within this specification embodiments have been described in a way which enables a clear and concise specification to be written, but it is intended and will be appreciated that embodiments may be variously combined or separated without parting from the invention. It is intended that the present invention be limited only to the extent required by the appended claims and the applicable rules of law. It is also to be understood that the following claims are to cover all generic and specific features of the invention described herein, and all statements of the scope of the invention which, as a matter of language, might be said to fall therebetween. | 25,290 |
11857710 | DETAILED DESCRIPTION The disclosed ventilation mask incorporates features to deliver oxygen or other gases to a patient with an open mask structure. The ventilation mask can utilize fluid dynamics to provide high concentrations of oxygen or other gases to the patient despite the open mask structure. Further, the ventilation mask can utilize fluid dynamics to measure or sample gases exhaled by the patient. The detailed description set forth below is intended as a description of various configurations of the subject technology and is not intended to represent the only configurations in which the subject technology may be practiced. The detailed description includes specific details for the purpose of providing a thorough understanding of the subject technology. However, it will be apparent to those skilled in the art that the subject technology may be practiced without these specific details. In some instances, well-known structures and components are shown in block diagram form in order to avoid obscuring the concepts of the subject technology. Like components are labeled with identical element numbers for ease of understanding. Reference numbers may have letter suffixes appended to indicate separate instances of a common element while being referred to generically by the same number without a suffix letter. While the following description is directed to the administration of supplemental gas to a patient by a medical practitioner using the disclosed ventilation mask, it is to be understood that this description is only an example of usage and does not limit the scope of the claims. Various aspects of the disclosed ventilation mask may be used in any application where it is desirable to administer and/or sample gases. The disclosed ventilation mask overcomes several challenges discovered with respect to certain ventilation masks. One challenge with certain conventional ventilation masks is that high concentrations of oxygen or other gases cannot be administered to a patient using an open mask structure. Because delivery of high concentrations of oxygen or other gases may be required, the use of conventional ventilation masks is undesirable. Another challenge with certain conventional ventilation masks is that gases exhaled by a patient may be difficult to sample and/or measure when using an open mask structure. Because sampling or measurement of exhaled gases may be required during the administration of gases, the use of conventional ventilation masks is undesirable. Therefore, in accordance with the present disclosure, it is advantageous to provide a ventilation mask as described herein that allows for administration of high concentrations of oxygen or other gases while permitting an open mask structure. The disclosed ventilation mask provides gas ports and/or gas fences to direct gas flow toward a patient and away from vent openings in the ventilation mask. Further, it is advantageous to provide a ventilation mask as described herein that allows for the sampling of exhaled gases while permitting an open mask structure. The disclosed ventilation mask provides gas flow that directs exhaled gases toward sampling ports within the ventilation mask. An example of a ventilation mask that permits high concentrations of oxygen or other gases and/or sampling of exhaled gases while retaining an open mask structure is now described. FIG.1is a front perspective view of a ventilation mask100, in accordance with various aspects of the present disclosure. In the depicted example, the ventilation mask100can be utilized to administer oxygen or other supplemental gases to a patient. The ventilation mask100can direct a supplemental gas, such as oxygen, via the supply tubing102to the ventilation mask100via the supply gas port114. As described herein, a gas manifold can distribute the supplemental gas through the mask body110to the patient. As illustrated, the ventilation mask100can be worn by the patient over the patient's mouth and nose. The ventilation mask100can be attached to the patient by a strap104worn over the head of the patient. The strap104can be coupled to the mask body110at strap openings112formed in the mask body110. In the depicted example, the ventilation mask100can have a generally open mask structure. As illustrated, the mask body110includes one or more vent openings120a,120b,120cformed therethrough. The vent openings120a,120b,120ccan allow for access or fluid communication with the patient cavity defined by the mask body110. In some embodiments, the mask body110includes three vent openings120a,120b,120c. The upper vent openings120a,120bcan be positioned to be adjacent to a patient's nose when the ventilation mask100is worn. Further, the upper vent openings120a,120bcan be laterally spaced apart on either side of the patient's nose when the ventilation mask100is worn. The lower vent opening120ccan be positioned to be adjacent to a patient's mouth when the ventilation mask100is worn. Advantageously, by utilizing one or more vent openings120a,120b,120c, the ventilation mask100can allow for exhaled gases such as carbon dioxide to be cleared from the patient cavity of the ventilation mask, reducing the incidence of carbon dioxide rebreathing. Further, the vent openings120a,120b,120ccan permit various tasks to be performed without removing the ventilation mask100. Tasks can include, but are not limited to, medical procedures, eating, drinking, hygiene procedures, and/or talking. For example, the vent openings120a,120b,120ccan allow for nasal and/or oral bronchoscopy procedures, administering medications, and access for mouthpieces and/or nebulizers. Further, the open structure of the ventilation mask100can increase patient comfort by accommodating various facial features and reducing patient claustrophobia. FIG.2is a rear elevation view of a mask body110of the ventilation mask100ofFIG.1, in accordance with various aspects of the present disclosure. In some applications, the mask body110is configured to be worn over the mouth and nose of a patient to permit supplemental gases to be administered to the patient. The patient opening116of the mask body110can engage against the patient's face. Optionally, the patient opening116can be in sealing engagement with the patient. In the depicted example, the mask body110defines a patient cavity118over the patient's mouth and nose. As described herein, supplemental gases can be introduced and directed within the patient cavity118. Further, the vent openings120a,120b,120cmay be in fluid communication with the patient cavity118. In some embodiments, the mask body110can be formed from a soft material, such as a polymer. The mask body110can be compliant to permit the mask body110to accommodate a wide variety of facial features. In the depicted example, supplemental gases can be introduced into the patient cavity118via one or more gas ports132a,132b. The gas ports132a,132bcan be formed in a gas manifold130disposed within the patient cavity118of the mask body110. In some applications, the gas ports132a,132bcan administer high concentrations of supplemental gas to the patient cavity118and ultimately to the patient, notwithstanding the vent openings120a,120b,120cin fluid communication with the patient cavity118. As illustrated, the gas jets or ports132a,132bcreate and direct gas flows and/or flow paths towards the nose and/or mouth of the patient and away from the vent openings120a,120b,120c. In the depicted example, the gas ports132a,132bare vectored to direct the gas flow in a desired direction. During operation, the gas ports132a,132bcan utilize fluid dynamic characteristics to generate “curtain effect” gas flow (e.g., a distributed flow) or a gas curtain that directs gas flow towards the patient's mouth and nose while acting as a barrier or boundary to environmental gases entering the patient cavity118via the vent openings120a,120b,120c. In some embodiments, the boundary formed by the gas curtain can be disposed between or adjacent to the vent openings120a,120b,120cand the patient's breathing anatomy, such as the patient's mouth and nose. During operation, the boundary formed by the gas flow can create a protected volume of supplemental gas while reducing mixing with ambient or environmental gases. As shown, the gas ports132a,132bcan include various geometric features to direct the gas flow as desired. For example, the gas ports132acan have an elongated slot geometry, cross-section, or profile. Optionally, the gas ports132acan further include rounded edges. In some embodiments, the gas ports132acan be tapered to direct gas flow therethrough. For example, the gas ports132acan be axially tapered towards the patient. Further, the gas ports132bcan have a circular geometry, cross-section, or profile. In some embodiments, the gas ports132bcan be tapered to direct gas flow therethrough. For example, the gas ports132bcan be axially tapered towards the patient. Additionally, in some embodiments, the gas ports132a,132bcan be arranged to promote curtain effect gas flow and high concentrations of supplemental gas. For example, the gas ports132acan be disposed on the gas manifold130generally circumferentially around an upper edge of the vent opening120c. Further, the gas ports132bcan be clustered together on the gas manifold130at an upper edge of the vent opening120c. In some embodiments of the present disclosure, any of the gas ports132aand gas ports132bcan positioned between the vent openings120a,120b,120c. In some embodiments, the gas ports132bcan be positioned between or flanked by the gas ports132a. Optionally, the gas ports132a,132bcan be configured to follow the shape of a patient's upper lip region to the corners of the patient's mouth. Advantageously, the arrangement and geometric features of the gas ports132a,132bcan provide the curtain effect gas flow described herein. By utilizing the directed gas flow provided by the gas ports132a,132b, supplemental gas can be directed to patients with varying facial features and without the use of a snorkel or other structure that extends into the patient cavity, proximal to the patient when the ventilation mask100is worn. The gas ports132bcan have a diameter of between approximately 0.01 inches to 0.1 inches. In some embodiments, the gas ports132bcomprise a diameter of approximately 0.062 inches. In some embodiments, adjacent gas ports132bare spaced apart between approximately 0.1 inches to 0.75 inches. In some embodiments, adjacent gas ports132bare spaced apart in a first direction approximately 0.1 inches, and adjacent gas ports132bare spaced apart in a second direction, different than the first direction, approximately 0.2 inches. In some embodiments elongate gas ports132acomprise a length of between approximately 0.13 to 0.75 inches, and a width of between approximately 0.01 to 0.15 inches. In some embodiments, a first gas port132ahas a length of approximately 0.26 inches and a second gas port has a length of approximately 0.3 inches. Optionally, the mask body110can include one or more breath indicators111a,111b,111cto provide a visual indication if a patient is breathing. For example, the breath indicators111a,111b,111ccan provide a visual indication in response to exhaled carbon dioxide. In some embodiments, the breath indicators111a,111b,111care strips or patches of color changing or colorimetric media. For example, the breath indicators111a,111b,111ccan comprise a color changing media paper. During operation, the breath indicators111a,111b,111ccan undergo a reaction in the presence of carbon dioxide, which causes a change color in the breath indicators111a,111b,111c. In some embodiments, the breath indicators111a,111b,111ccan present a blue color in the absence of carbon dioxide and present a yellow color in the presence of carbon dioxide. Advantageously, the breath indicators111a,111b,111ccan rapidly respond to the presence of carbon dioxide to allow the breath indicators111a,111b,111cto change color on a breath by breath basis (e.g. cycle between blue to yellow with each breath, or cycle between transparent and opaque with each breath). Further, by changing color in response to a patient's breath, the breath indicators111a,111b,111ccan visually indicate if a patient is breathing or carbon dioxide buildup within the patient cavity118from a distance. In some embodiments, the breath indicators111a,111b,111care disposed about the mask body110at regions that are exposed to the exhaled breath of the patient. As illustrated, the breath indicators111a,111b,111ccan receive the exhaled breath of the patient from the patient's nose and/or mouth. For example, a breath indicator111acan be disposed close to a patient's nose between gas fences140a,140b. Further, in some embodiments, breath indicators111b,111ccan be disposed on gas fences140a,140brespectively. Advantageously, embodiments of the ventilation mask described herein allow for the breath indicators111a,111b,111cto signal a patient's breathing at supplemental gas flow rates ranging from 0 to 1, 2, 3, 4, 5, 8, 10, 12, 14, 16, 18, or 20 liters per minute. Optionally, the breath indicators111a,111b,111ccan comprise a paper-based indicator. The breath indicators111a,111b,111ccan be affixed or coupled to the mask body110with a secondary structure. In some embodiments, the breath indicators111a,111b,111ccan be bonded to an interior surface of the mask body110. Optionally, the breath indicators111a,111b,111ccan be over-molded into the mask body110. In some embodiments, the breath indicators111a,111b,111ccan be seen through the mask body110by a caretaker or clinician. Advantageously, by providing breath indicators111a,111b,111c, caregivers and clinicians can readily determine if a patient is breathing, as chest wall motion may be insufficient and other indicators, such as pulse oximetry, may be lagging indicators. In some applications, breath indicators111a,111b,111ccan provide clinicians timely warnings of respiratory conditions. FIG.3is a perspective view of the mask body110ofFIG.2, in accordance with various aspects of the present disclosure. With reference toFIGS.2and3, the gas fences140a,140b,140cextending from the mask body110and/or the gas manifold130can help control and/or direct supplemental gas flow from the gas ports132a,132b. Further, the gas fences140a,140b,140ccan promote the curtain effect gas flow of the supplemental gas as well as prevent entrainment of environmental air into the patient cavity118. In the depicted example, the gas fences140a,140b,140ccan extend axially within the patient cavity118toward the patient opening116or the patient generally. The gas fences140a,140b,140ccan extend axially while maintaining space for a patient's facial features and for patient comfort. Further, the edges of the gas fences140a,140b,140ccan be rounded for patient comfort. The gas fences140a,140b,140ccan be disposed generally between the gas ports132a,132band the vent openings120a,120b,120c. In the depicted example, the gas fences140a,140b,140care disposed proximal to the gas ports132a,132b. In some applications, the relative location of the gas fences140a,140b,140cwith respect to the gas ports132a,132bcreates a barrier to promote maintaining the gas curtain near the nose and mouth of the patient. Further, relative location the gas fences140a,140b,140crelative to the vent openings120a,120b,120ccreates a barrier to prevent the entrainment of environmental gases into the supplemental gas flow and into the patient cavity118generally. As illustrated, the gas fences140a,140b,140ccan be curved to follow the profile of the vent openings120a,120b,120c, respectively. The gas fences140a,140b,140ccan follow along an outer edge of the vent openings120a,120b,120c. In some embodiments, the gas fences140a,140b,140ccan extend along a portion of the vent openings120a,120b,120cto provide an open mask structure to the mask body110. For example, the gas fences140a,140b,140ccan extend at least partially circumferentially along an edge of the vent openings120a,120b,120c. In some embodiments, the gas fences140a,140b,140ccan be positioned between the vent openings120a,120b,120c. In some applications, the gas fences140a,140bcan be disposed on either side of the patient's nose and the gas fence140ccan be disposed below the patient's nose to promote curtain effect gas flow and to maintain supplemental gas concentration in the area adjacent to the patient's nose and mouth while preventing or limiting the entrainment of environmental gases from the vent openings120a,120b,120c. Further, in some embodiments, the lower gas fence140ccan promote curtain effect gas flow around the lower vent opening120cto promote supplemental gas concentration in the area adjacent to the patient's mouth. FIG.4is a cross-sectional view of the mask body110ofFIG.2taken along section line4-4, in accordance with various aspects of the present disclosure. As illustrated, the supplemental gas channel150directs supplemental gas from the supply gas port114to the gas ports132a,132bformed through the gas manifold130. In some embodiments, the supplemental gas channel150directs supplemental gas from the supply gas port114around the lower vent opening120c. Optionally, the supplemental gas channel150can be circumferentially disposed around the lower vent opening120c. In the depicted embodiment, the supplemental gas channel150is defined by the gas manifold130disposed against the mask body110. For example, an inner edge134and an outer edge136of the gas manifold130can engage with an inner lip152and an outer lip154of the mask body110to define the supplemental gas channel150. In particular, the inner edge134of the gas manifold130can engage with the inner lip152of the mask body110and the outer edge136of the gas manifold130can engage with the outer lip154of the mask body110. Further, a manifold surface138of the gas manifold130and a mask surface156of the mask body110can cooperate and be spaced apart to define the walls of the supplemental gas channel150. FIG.5is an exploded view of the gas manifold130and the mask body110ofFIG.2, in accordance with various aspects of the present disclosure. As described herein, the gas manifold130and the mask body110can cooperatively define the supplemental gas channel150. In the depicted embodiment, the mask body110can include features that are complimentary to the features of the gas manifold130to receive and engage the gas manifold130to the mask body110and define the supplemental gas channel150therein. For example, the inner lip152and the outer lip154of the mask body110can define an engagement profile for the gas manifold130. The inner edge134and the outer edge136of the gas manifold130can be located with the engagement profile formed by the inner lip152and the outer lip154. In some embodiments, the engagement profile of the mask body110can allow the gas manifold130to be aligned with the mask body110to allow the supplemental gas channel150to be formed. In some embodiments, the mask body110and/or the gas manifold130can include alignment posts, holes, or other features to align the gas manifold130with the mask body110. In the depicted example, the gas manifold130can have a complimentary shape to nest within the mask body110. In some embodiments, the gas manifold130is disposed with the inner portion of the mask body110. Optionally, the gas manifold130can be disposed along an outer portion of the mask body110to define a supplemental gas channel150along an outer surface of the mask body110. In some embodiments, the gas manifold130can be resiliently or elastically engaged to the mask body110, wherein portions of the mask body110and/or the gas manifold130resiliently deform to couple the gas manifold130to the mask body110. Upon engagement, the gas manifold130can be sealingly engaged with the mask body110to prevent leakage of the supplemental gas flow through the supplemental gas channel150. In some embodiments, the gas manifold130can be bonded to the mask body110with any suitable adhesive (e.g. solvent bonding, adhesive bonding). In some embodiments, the gas manifold130can be welded to the mask body110, such as by laser or RF welding using high frequency electromagnetic energy to fuse the materials. In some embodiments, the gas manifold130and the mask body110are mechanically coupled, such as by using a latch, an interference fit, or heat staking. The gas manifold130and the mask body110can be formed from similar materials or different materials. FIG.6is a front elevation view of the gas manifold130ofFIG.2, in accordance with various aspects of the present disclosure. In the depicted embodiment, the gas manifold130defines the inner portion of the supplemental gas channel150(as shown inFIG.4). As illustrated, the gas manifold130can have a generally modified toroidal shape. Further, the manifold surface138can define the inner wall of the supplemental gas channel150. As illustrated, the gas ports132a,132bcan be formed through the manifold surface138to allow fluid communication with the supplemental gas channel150. The manifold surface138can extend between the inner edge134and the outer edge136of the gas manifold130. As illustrated, the inner edge134of the gas manifold130can be formed around a lower vent opening120cof the mask body110. FIG.7is a rear elevation view of the mask body110ofFIG.2, in accordance with various aspects of the present disclosure. In the depicted embodiment, the mask body110defines the outer portion of the supplemental gas channel150(as shown inFIG.4). As illustrated, the mask body110can have a generally modified conical shape or any other anatomically suitable shape. As illustrated, the mask surface156can define the outer wall of the supplemental gas channel150. In some embodiments, the supply gas port114can be formed through the mask surface156to allow fluid communication with the supplemental gas channel150. The mask surface156can be defined between the spaced apart inner lip152and the outer lip154of the mask body110. Optionally, the inner lip152and the outer lip154can extend axially toward the patient or the gas manifold130to provide engagement features for the gas manifold130to engage with. As illustrated, the inner lip152can be circumferentially formed around the lower vent opening120cof the mask body110. As described herein, embodiments of the ventilation mask allow for effective and efficient delivery and administration of supplemental gases to the patient while retaining an open mask structure. Advantageously, embodiments of the present disclosure do not require gas delivery or sampling structures that protrude through the patient cavity of the mask to a position near the patient's nose or mouth. The absence of gas delivery or sampling structures near the patient's nose or mouth can prevent unintended contact between the mask and the patient, provide increased volume in the mask for facial features, and can provide consistent performance for a variety of patient facial structures and breathing types (e.g., mouth and/or nose breathing). Further, features of the embodiment of the ventilation mask described herein prevent the loss of supplemental gas to the environment and prevent the entrainment of environmental gases into the supplemental gas flow. FIG.8is a chart depicting a fraction of inspired oxygen compared to an oxygen flow rate for a ventilation mask in accordance with various aspects of the present disclosure. Embodiments of the ventilation mask have been tested using a breathing simulator with a tidal volume of 500 mL per inspiration and a respiratory rate of 15 breaths per minute. During simulation, breathing through a combination of the nose and mouth was simulated.FIG.9is a chart depicting a fraction of inspired oxygen compared to an oxygen flow rate for a ventilation mask in accordance with various aspects of the present disclosure. During simulation, breathing through the mouth was simulated.FIG.10is a chart depicting a fraction of inspired oxygen compared to an oxygen flow rate for a ventilation mask in accordance with various aspects of the present disclosure. During simulation, breathing through the nose was simulated. With reference toFIGS.8-10, accordingly, embodiments of the ventilation mask described herein allow for an open mask structure while providing higher concentrations of oxygen or other supplemental gases at various flow rates compared to conventional ventilation masks with an open mask structure. In some applications, the fraction of inspired oxygen provided by some embodiments of the ventilation mask described herein can range from approximately 30% to 80%. Further, as shown, at higher flow rates, embodiments of the ventilation mask described herein provide significantly higher concentrations of oxygen compared to conventional ventilation masks. For example, embodiments of the ventilation mask may effectively provide fraction of inspired oxygen rates greater than 40%, 45%, 50%, 60%, 70%, 75%, or 80%. Advantageously, as embodiments of the ventilation mask described herein are able to deliver supplemental gas more effectively compared to conventional ventilation masks, embodiments of the ventilation mask may waste less supplemental gas during operation. For example, in some applications embodiments of the ventilation mask may waste 0% to 10%, 20%, 30%, 40%, or 50% less supplemental gas during delivery compared to conventional ventilation masks. FIG.11is perspective view of a ventilation mask200, in accordance with various aspects of the present disclosure. In the depicted example, various features of the ventilation mask200may be similar to features described with respect to ventilation mask100. Accordingly, similar reference numerals may be utilized to reference various features of ventilation mask200that may be similar to features of ventilation mask100. In the depicted example, the ventilation mask200can be utilized to administer supplemental gases to a patient and/or sample exhaled gases from a patient for measurement or analysis. Accordingly, in addition to directing a supplemental gas to the ventilation mask200via the supply gas port214a, the ventilation mask200can direct exhaled gases from a patient to a monitor via a sensing port214b. In some embodiments, multiple monitors can be connected to the sensing port214bvia pigtail connections or other suitable connections to monitor multiple parameters or for redundancy. In some applications, capnography methods can be used with sampled exhaled gases from the ventilation mask200to monitor carbon dioxide levels. For example, sampled exhaled gases can be analyzed to monitor for a percentage of carbon dioxide in an exhaled breath or monitor a partial pressure of carbon dioxide in an exhaled breath. Optionally, values can be shown as a breath by breath waveform. In some embodiments, the sensing port214bcan be coupled to a negative pressure source to draw in exhaled gases from the patient cavity of the ventilation mask200. FIG.12is a rear elevation view of a mask body210of the ventilation mask ofFIG.11, in accordance with various aspects of the present disclosure. In some applications, the mask body210is configured to be worn over the mouth and nose of a patient to permit supplemental gases to be administered to a patient and to permit exhaled gases to be sampled. In the depicted example, supplemental gases can be introduced into the patient cavity218via one or more gas ports232a,232b. In some applications, the gas ports232a,232bcan administer high concentrations of supplemental gas to the patient cavity218and ultimately to the patient, notwithstanding the vent openings220a,220b,220cin fluid communication with the patient cavity218. Optionally, exhaled gases can be sampled from the patient cavity218via one or more sampling portals262a,262b,262c. The sampling portals262a,262b,262ccan be formed in a sampling cover260disposed within the patient cavity218of the mask body210. In some embodiments, the sampling cover260is coupled to the gas manifold230. In some applications, the sampling portals262a,262b,262ccan intake exhaled gases from the patient cavity218and ultimately from the patient, notwithstanding the vent openings220a,220b,220cin fluid communication with the patient cavity218and the gas ports232a,232bintroducing supplemental gas flow into the patient cavity218. As illustrated, the sampling portals262a,262b,262ccan be configured to be circumferentially disposed or otherwise adjacent to a patient's mouth when the mask body210is worn. In the depicted embodiment, the sampling portals262a,262b,262care circumferentially disposed around the lower vent opening220c. For example, the sampling portals262a,262b,262ccan be disposed circumferentially around the lower vent opening220cat approximately 0 degrees, 60 degrees, 180 degrees, and 300 degrees from a top center portion of the vent opening220c. As can be appreciated, the sampling portals262a,262b,262ccan be disposed at any circumferential position such as 0 degrees, 15 degrees, 30 degrees, 45 degrees, 60 degrees, 90 degrees, 120 degrees, 180 degrees, 210 degrees, 225 degrees, 240 degrees, 270 degrees, 300 degrees, 330 degrees, or 345 degrees. Optionally, the sampling portals262a,262b,262ccan be spaced apart at approximately 10 degrees, 20 degrees, 30 degrees, 45 degrees, 60 degrees, 90 degrees, 120 degrees, 135 degrees, 160 degrees, or 180 degrees. In some embodiments of the present disclosure, the sampling portals262a,262b,262ccan be disposed between the gas ports232a,232band the vent opening220c. The shape and position of sampling portals262a,262b,262cand/or the gas ports232a,232bprovide for improved gas delivery and gas sampling for a variety of breathing characteristics. For example, the shape and position of sampling portals262a,262b,262cand/or the gas ports232a,232bare configured to provide improved gas delivery and gas sampling for patients who may breathe solely or primarily from their mouth and/or nose, as well as for patients with different face morphologies and patient positions. Additionally, the shape and position of sampling portals262a,262b,262cand/or the gas ports232a,232bare configured to facilitate providing higher fractions of inspired oxygen relative to conventional ventilation masks. In some embodiments, the sampling portals262a,262b,262ccan be circular openings. Optionally, the sampling portals262a,262b,262ccan be any other suitable shape. The sampling portals262a,262b,262ccan further includes features such as hoods, scoops, and/or shrouds to promote the intake of exhaled gases and prevent the intake of supplemental gas flow or environmental gases. In some embodiments, the sampling portals262a,262b,262ccan range in diameter from approximately 0.02 inches to 0.1 inches. For example, in some embodiments, sampling portals262a,262b,262ccan vary in size or diameter for improved functionality with patients with various breathing patterns (nose/mouth), facial features, and/or positions. Optionally, one or more sampling portals262a,262b,262ccan have a size or diameter that is different from other sampling portals262a,262b,262c. For example, the sampling portal262adisposed at the top center location may have a larger diameter ranging from approximately 0.04 inches to 0.07 inches, while the sampling portal262cdisposed at a bottom center location may have a smaller diameter ranging from approximately 0.02 inches to 0.04 inches. Further, in some embodiments, sampling portals262blocated at side locations may have intermediate diameters ranging from approximately 0.03 inches to 0.05 inches. During operation, in addition to providing supplemental gas flow, the gas ports232a,232bcan help direct exhaled gases from the patient toward the sampling portals262a,262b,262c. In some embodiments, the curtain effect gas flow or gas curtain created by the gas ports232a,232bcan create a flow path to direct the exhaled gases from the patient toward the sampling portals262a,262b,262c. Advantageously, by utilizing the gas flow from the gas ports232a,232b, supplemental gas flow can be introduced into the patient cavity218while permitting sampling of exhaled gases through the sampling portals262a,262b,262c, without any loss of sampling signal. In some embodiments, gas fences240a,240b,240cextending from the mask body210and/or the gas manifold230can help control and/or direct supplemental gas flow from the gas ports232a,232b. Further, gas fences240a,240b,240ccan further help control and/or direct exhaled gases toward the sampling portals262a,262b,262cand prevent or limit the entrainment of environmental air into the patient cavity218. For example, the upper gas fences240a,240bcan prevent or limit the entrainment of environmental gases into the patient cavity. Further, the lower gas fence240ccan be disposed generally between the gas ports232a,232band at least some of the sampling portals262a,262b,262c. In some applications, the relative location of the gas fence240cwith respect to the gas ports232a,232band the sampling portals262a,262b,262ccreates a barrier to prevent or limit supplemental gas flow from entering the sampling portals262a,262b,262cwhile promoting exhaled gases to enter the sampling portals262a,262b,262c. Optionally, the mask body210can include one or more breath indicators211a,211b,211cto provide a visual indication if a patient is breathing. FIG.13Ais a cross-sectional view of the mask body210ofFIG.12taken along section line13A-13A, in accordance with various aspects of the present disclosure. As illustrated, the supplemental gas channel250directs supplemental gas from the supply gas port to the gas ports232a,232bformed through the gas manifold230. Optionally, the opposite surface of the gas manifold230and the sampling cover260can form the sampling channel270. In some embodiments, the sampling channel270is disposed adjacent to the gas channel250. Optionally, the sampling channel270is disposed generally concentric with the gas channel250.FIG.13Bis a detail view of the mask body210ofFIG.13A, in accordance with various aspects of the present disclosure. With reference toFIGS.13A and13B, in some embodiments, the sampling channel270directs exhaled gases from the sampling portals262a,262b,262cto the sensing port conduit231a. In some embodiments, the sampling channel270directs exhaled gases from the sampling portals262a,262b,262caround the lower vent opening220c. Optionally, the sampling channel270can be circumferentially disposed around the lower vent opening220c. In the depicted example, the sensing port conduit231ain fluid communication with the sampling channel270extends from the gas manifold230through the gas channel250to direct exhaled gases out of the sampling channel270. As illustrated, the sensing port conduit231acan extend into and be at least partially disposed within the sensing port214b. In some embodiments, the sensing port conduit231aextends through the sensing port214b. In some embodiments, a portion of the sensing port conduit231acan be concentrically disposed within the sensing port214b. Optionally, the sensing port conduit231acan have an interference or friction fit with portions of the sensing port214b. In some embodiments, the sensing port214band/or the sensing port conduit231acan be configured to be disposed below a patient's chin when the ventilation mask200is worn. Further, in some embodiments, the sensing port214band/or the sensing port conduit231acan be configured to be disposed parallel to a patient's nose when the ventilation mask200is worn. In the depicted embodiment, the sampling channel270is defined by the sampling cover260disposed against the gas manifold230. For example, the inner edge264and the outer edge266of the sampling cover260can engage with an inner surface of the gas manifold230to define the sampling channel270. Further, a cover surface268and the inner surface of the gas manifold230can cooperate and be spaced apart to define the walls of the sampling channel270. FIG.14is an exploded view of the sampling cover260and the gas manifold230ofFIG.12, in accordance with various aspects of the present disclosure. As described herein, the sampling cover260and the gas manifold230can cooperatively define the sampling channel270therebetween. In the depicted embodiment, in addition to forming the sampling gas channel250, the gas manifold230can include features that are complimentary to the features of the sampling cover260to receive and engage the sampling cover260to the gas manifold230and define the sampling channel270therein. For example, the inner lip272and the outer lip274of the gas manifold230can define an engagement profile for the sampling cover260. The inner edge264and the outer edge266of the sampling cover260can be located with the engagement profile formed by the inner lip272and the outer lip274. In some embodiments, the engagement profile of the gas manifold230can allow the sampling cover260to be aligned with the gas manifold230to allow the sampling channel270to be formed. In some embodiments, the gas manifold230and/or the sampling cover260can include alignment posts, holes, or other features to align the sampling cover260with the gas manifold230. In the depicted example, the sampling cover260can have a complimentary shape to nest within the gas manifold230. In some embodiments, the sampling cover260is disposed along an inner surface of the gas manifold230. Optionally, the sampling cover260can be disposed along an outer surface of the gas manifold to define a sampling channel270along an outer surface of the gas manifold230or the mask body210. In some embodiments, the sampling cover260can be resiliently or elastically engaged to the gas manifold230, wherein portions of the gas manifold230and/or the sampling cover260resiliently deform to couple the sampling cover260to the gas manifold230. Upon engagement, the sampling cover260can be sealingly engaged with the gas manifold230to prevent leakage of the exhaled gases through the sampling channel270. In some embodiments, the sampling cover260can be bonded to the gas manifold230with any suitable adhesive (e.g. solvent bonding, adhesive bonding). In some embodiments, the sampling cover260can be welded to the gas manifold230, such as by laser or RF welding using high frequency electromagnetic energy to fuse the materials. In some embodiments, the sampling cover260and the gas manifold230are mechanically coupled, such as by using a latch, an interference fit, or heat staking. The sampling cover260and the gas manifold230can be formed from similar materials or different materials. FIG.15is a front elevation view of the sampling cover260ofFIG.12, in accordance with various aspects of the present disclosure. In the depicted embodiment, the sampling cover260defines the inner portion of the sampling channel270. As illustrated, the sampling cover260can have a generally modified toroidal shape. Further, the cover surface268can define the inner wall of the sampling channel270. As illustrated, the sampling portals262a,262b,262ccan be formed through the cover surface268to allow fluid communication with the sampling channel270. The cover surface268can extend between the inner edge264and the outer edge266of the sampling cover260. As illustrated, the inner edge264of the sampling cover260can be formed around a lower vent opening220cof the mask body210. FIG.16Ais a rear elevation view of the gas manifold230ofFIG.12, in accordance with various aspects of the present disclosure. In the depicted embodiment, the outer surface of the gas manifold230defines the outer portion of the sampling channel270. As illustrated, the groove formed between the inner lip272and the outer lip274defines the outer portion of the sampling channel270. In some embodiments, a conduit opening231bfor the sensing port conduit231acan be formed through the groove formed between the inner lip272and the outer lip274. The width of the groove can be defined between the spaced apart inner lip272and the outer lip274of the gas manifold230. Optionally, the inner lip272and the outer lip274can extend axially toward the patient or the sampling cover260to provide engagement features for the sampling cover260to engage with. As illustrated, the inner lip272can be circumferentially formed around the lower vent opening220cof the mask body210. FIG.16Bis a front perspective view of another embodiment of a gas manifold230′, in accordance with various aspects of the present disclosure.FIG.16Cis a front elevation view of the gas manifold230′ ofFIG.16B, in accordance with various aspects of the present disclosure. In the depicted example, the gas manifold230′ allows for flow through the supplemental gas channel to be balanced or otherwise evenly distributed. As described herein, the gas manifold230′ in conjunction with the mask body define a supplemental gas channel to direct supplemental gas from the supply gas port to the gas ports232a′,232b′. In some applications, the sensing portion conduit231a′ can extend through the supplemental gas channel250, creating a flow restriction or obstruction. In the depicted example, the gas manifold230′ includes a protrusion233′ extending at least partially into the supplemental gas channel to create a complimentary flow restriction or obstruction to balance the flow through the supplemental gas channel. As can be appreciated, the protrusion233′ can be disposed opposite to the sensing portion conduit231′. In some embodiments, the protrusion233′ can be any suitable shape to obstruct or restrict a desired portion of the supplemental gas channel. As described herein, embodiments of the ventilation mask described herein allow for effective sampling of a patient's exhaled gases while permitting administration of supplemental gases with an open mask structure. FIG.17is a chart depicting a measured carbon dioxide using capnography methods compared to an oxygen flow rate for a ventilation mask in accordance with various aspects of the present disclosure. Embodiments of the ventilation mask have been tested using a breathing simulator with a tidal volume of 500 mL per inspiration, 5% exhaled carbon dioxide and a respiratory rate of 15 breaths per minute. During simulation, breathing through a combination of the nose and mouth was simulated.FIG.18is a chart depicting a measured carbon dioxide using capnography methods compared to an oxygen flow rate for a ventilation mask in accordance with various aspects of the present disclosure. During simulation, breathing through the mouth was simulated.FIG.19is a chart depicting a measured carbon dioxide using capnography methods compared to an oxygen flow rate for a ventilation mask in accordance with various aspects of the present disclosure. During simulation, breathing through the nose was simulated. With reference toFIGS.17-19, accordingly, embodiments of the ventilation mask described herein allow for an open mask structure while more accurately and effectively sampling exhaled gases from a patient at various supplemental gas flow rates compared to conventional ventilation masks with an open mask structure. In some applications, the measured carbon dioxide percentage provided by some embodiments of the ventilation mask described herein can range from approximately 2% to 3.5%. Further, as shown, at higher supplemental gas flow rates, embodiments of the ventilation mask described herein provide significantly more accurate exhaled gas samples compared to conventional ventilation masks. For example, embodiments of the ventilation mask may accurately measure carbon dioxide percentages greater than 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.8%, 3.0%, 3.2%, 3.4%, or 3.5%. FIG.20Ais a rear perspective view of a ventilation mask300, in accordance with various aspects of the present disclosure. In the depicted example, the mask body310can include a contact seal380disposed along the edge of the mask body310to seal the mask body310against a patient's facial structure. The contact seal380can have a resilient construction to conform and seal against the patient's facial structure. As can be appreciated, the contact seal380can be configured to adapt to a wide demographic of facial structures. Advantageously, by utilizing the contact seal380, the ventilation mask300may be able to more effectively deliver supplemental gas flow and/or sample exhaled gases. FIG.20Bis a top cross-sectional view of a ventilation mask300b, in accordance with various aspects of the present disclosure. In the depicted example, the mask body310bincludes an inward-curling contact seal380b. As illustrated, the edges of the contact seal380bcurl inward toward the facial structure of the patient. As can be appreciated, the curled structure of the contact seal380bcan allow for the contact seal380bto conform to facial features of the patient. In some embodiments, the contact seal380bcan be formed from resilient materials such as thermoplastic elastomers. FIG.20Cis a top cross-sectional view of a ventilation mask300c, in accordance with various aspects of the present disclosure. In the depicted example, the mask body310cincludes an outward-curling contact seal380c. As illustrated, the edges of the contact seal380ccurl outward away from the facial structure of the patient. As can be appreciated, the curled structure of the contact seal380ccan allow for the contact seal380cto conform to the facial features of the patient. FIG.21is an elevation view of a ventilation mask400, in accordance with various aspects of the present disclosure. In the depicted example, the strap404can be split to improve patient comfort when the ventilation mask400is worn over the patient's mouth and nose. As illustrated, the mask portion405can separate into an upper portion406aand a lower portion406bat a separation area407. During operation, the upper portion406acan be worn over a patient's ears and the lower portion406bcan be worn below a patient's ears. Advantageously, the upper portion406aand the lower portion406bcan be separated to provide for patient comfort and proper fitting of the ventilation mask400. FIG.22is an elevation view of a ventilation mask500, in accordance with various aspects of the present disclosure. In the depicted example, the mask portion505of the strap504can be separated by a clinician to adjust the length of the mask portion505and the upper and lower portions506a,506bof the strap504. As illustrated, the mask portion505includes a perforated separation area507that allows the length of the upper and lower portions506a,506bto be extended as the mask portion505is separated. Illustration of Subject Technology as Clauses Various examples of aspects of the disclosure are described as numbered clauses (1, 2, 3, etc.) for convenience. These are provided as examples, and do not limit the subject technology. Identifications of the figures and reference numbers are provided below merely as examples and for illustrative purposes, and the clauses are not limited by those identifications. Clause 1. A ventilation mask, comprising: a mask body defining a patient cavity, the mask body comprising: a patient opening in fluid communication with the patient cavity; and at least one vent opening formed through the mask body, the at least one vent opening in fluid communication with the patient cavity, wherein the at least one vent opening is disposed generally opposite to the patient opening; and a gas manifold coupled to the mask body, the gas manifold defining a gas channel, the gas manifold comprising a plurality of vectored gas ports in fluid communication with the gas channel, wherein the plurality of vectored gas ports are configured to create a curtain effect gas flow within the patient cavity to form a gas curtain within the patient cavity and adjacent to the at least one vent opening. Clause 2. The ventilation mask of Clause 1, wherein at least one of the plurality of vectored gas ports comprises a tapered geometry. Clause 3. The ventilation mask of any of Clauses 1 and 2, wherein at least one of the plurality of vectored gas ports comprises a slot cross-section. Clause 4. The ventilation mask of any of Clauses 1-3, wherein at least one of the plurality of vectored gas ports comprises a circular cross-section. Clause 5. The ventilation mask of any of Clauses 1-4, the mask body further comprising at least one gas fence disposed adjacent to the at least one vent opening, the at least one gas fence extending axially toward the patient opening. Clause 6. The ventilation mask of Clause 5, wherein the at least one vent opening comprises a first and second vent openings spaced laterally apart and the at least one gas fence comprises a first gas fence adjacent to the first vent opening and a second gas fence adjacent to the second vent opening. Clause 7. The ventilation mask of Clause 6, wherein the first gas fence extends at least partially circumferentially around the first vent opening and the second gas fence extends at least partially circumferentially around the second vent opening. Clause 8. The ventilation mask of any of Clauses 1-4, the gas manifold further comprising at least one gas fence disposed adjacent to the at least one vent opening, the at least one gas fence extending axially toward the patient opening. Clause 9. The ventilation mask of any of Clauses 1-4, wherein the at least one vent opening comprises a lower vent opening surrounded by the gas manifold and at least one gas fence is disposed between the lower vent opening and the plurality of vectored gas ports. Clause 10. The ventilation mask of Clause 9, wherein the at least one gas fence extends at least partially circumferentially around the lower vent opening. Clause 11. The ventilation mask of any of Clauses 1-10, wherein the gas manifold is disposed within the patient cavity of the mask body. Clause 12. The ventilation mask of Clause 11, wherein the gas channel is cooperatively defined by the gas manifold and the mask body. Clause 13. The ventilation mask of Clause 12, wherein the gas manifold is sealingly engaged with an inner surface of the mask body to define the gas channel. Clause 14. The ventilation mask of Clause 13, wherein the inner surface of the mask body comprises a complimentary gas manifold engagement profile to engage the gas manifold and define the gas channel. Clause 15. The ventilation mask of any of Clauses 1-10, wherein the gas manifold is disposed on an outer surface of the mask body. Clause 16. The ventilation mask of any of Clauses 1-15, further comprising a sampling cover coupled to the gas manifold. Clause 17. The ventilation mask of Clause 16, wherein the sampling cover defines a sampling channel, the sampling cover comprising at least one sampling portal in fluid communication with the sampling channel and the curtain effect gas flow within the patient cavity directs a sample gas flow toward the sampling portal. Clause 18. The ventilation mask of Clause 17, wherein the at least one sampling portal is disposed adjacent to the at least one vent opening. Clause 19. The ventilation mask of Clause 18, wherein the at least one sampling portal comprises an oxygen sampling portal and a carbon dioxide sampling portal. Clause 20. The ventilation mask of Clause 18, wherein the at least one sampling portal comprises a hood, scoop, or shroud feature. Clause 21. The ventilation mask of Clause 17, wherein the gas manifold comprises a sensing port conduit in fluid communication with the sampling channel, and the sensing port conduit extends through the gas channel. Clause 22. The ventilation mask of Clause 21, wherein the gas manifold comprises a protrusion disposed opposite to the sensing port conduit and extending at least partially through the gas channel. Clause 23. The ventilation mask of Clause 16, wherein the sampling cover is welded to the gas manifold. Clause 24. The ventilation mask of any of Clauses 1-23, wherein the at least one vent opening comprises a lower vent opening and the gas manifold is disposed around the lower vent opening. Clause 25. The ventilation mask of any of Clauses 1-24, further comprising a color-changing indicator coupled to the mask body, wherein the color-changing indicator is configured to change color in response to exposure to carbon dioxide. Clause 26. The ventilation mask of Clause 25, wherein the color-changing indicator is configured to change color in response to absence of carbon dioxide. Clause 27. The ventilation mask of Clause 25, wherein the color-changing indicator comprises a paper-based indicator. Clause 28. The ventilation mask of Clause 25, wherein the color-changing indicator is bonded to an inner surface of the mask body or over-molded within the mask body. Clause 29. The ventilation mask of Clause 25, wherein the color-changing indicator is disposed on a gas fence disposed adjacent to the at least one vent opening, the at least one gas fence extending axially toward the patient opening. Clause 30. The ventilation mask of Clauses 1-29, wherein the gas manifold is welded to the mask body. Clause 31. The ventilation mask of Clauses 1-30, wherein the mask body comprises a contact seal disposed along an edge of the mask body. Clause 32. The ventilation mask of Clause 31, wherein the contact seal comprises an inward-curling portion or an outward-curling portion. Clause 33. The ventilation mask of Clauses 1-32, further comprising a strap coupled to the mask body, the strap comprising: a mask portion coupled to the mask body; and an upper and lower portion extending from the mask portion. Clause 34. The ventilation mask of Clause 33, wherein the mask portion of the strap comprises a perforated separation area configured to separate and extend a length of the upper and lower portion. Clause 35. A ventilation mask, comprising: a mask body defining a patient cavity, the mask body comprising: a patient opening in fluid communication with the patient cavity; and at least one vent opening formed through the mask body, the at least one vent opening in fluid communication with the patient cavity, wherein the at least one vent opening is disposed generally opposite to the patient opening; at least one gas fence disposed adjacent to the at least one vent opening, the at least one gas fence extending axially toward the patient opening; and a gas manifold coupled to the mask body, the gas manifold defining a gas channel, the gas manifold comprising a plurality of gas ports in fluid communication with the gas channel. Clause 36. The ventilation mask of Clause 35, wherein the plurality of gas ports and the at least one gas fence are configured to create a curtain effect gas flow within the patient cavity to form or retain an oxygen curtain within the patient cavity and adjacent to the at least one vent opening, the oxygen curtain comprising an oxygen concentration between 30%, 40%, 45%, 50%, 60%, 70%, 75%, or 80%. Clause 37. The ventilation mask of Clause 35, wherein the plurality of gas ports and the at least one gas fence are configured to create a curtain effect gas flow within the patient cavity to direct the curtain effect gas flow away from the at least one vent opening. Clause 38. The ventilation mask of any of Clauses 35-37, wherein the plurality of gas ports are configured for delivery of gas to a patient. Clause 39. The ventilation mask of any of Clauses 35-38, wherein the at least one vent opening comprises a first and second vent openings spaced laterally apart and the at least one gas fence comprises a first gas fence adjacent to the first vent opening and a second gas fence adjacent to the second vent opening. Clause 40. The ventilation mask of Clause 39, wherein the first gas fence extends at least partially circumferentially around the first vent opening and the second gas fence extends at least partially circumferentially around the second vent opening. Clause 41. The ventilation mask of any of Clauses 35-40, wherein the gas channel is cooperatively defined by the gas manifold and the mask body. Clause 42. The ventilation mask of any of Clauses 35-41, further comprising a sampling cover coupled to the gas manifold. Clause 43. The ventilation mask of Clause 42, wherein the sampling cover defines a sampling channel, the sampling cover comprising at least one sampling portal in fluid communication with the sampling channel. Clause 44. The ventilation mask of Clause 43, wherein the sampling channel receives a negative pressure to draw exhaled gases from the patient cavity through the at least one sampling portal. Clause 45. The ventilation mask of Clause 43, wherein the at least one sampling portal comprises a hood, scoop, or shroud feature. Clause 46. The ventilation mask of Clause 43, the gas manifold further comprising at least one manifold gas fence disposed adjacent to the at least one vent opening and the at least one sampling portal, the at least one manifold gas fence extending axially toward the patient opening. Clause 47. The ventilation mask of Clause 46, wherein the at least one vent opening comprises a lower vent opening surrounded by the sampling cover and the at least one manifold gas fence is disposed between the at least one sampling portal and the plurality of vectored gas ports. Clause 48. The ventilation mask of Clause 47, wherein the at least one manifold gas fence extends at least partially circumferentially around the lower vent opening. Clause 49. The ventilation mask of any of Clauses 35-48, wherein the at least one vent opening comprises a lower vent opening and the gas manifold is disposed around the lower vent opening. Clause 50. A method of introducing a gas into a ventilation mask, the method comprising: introducing the gas into a patient cavity of the ventilation mask via a plurality of gas ports; directing the gas via the plurality of gas ports to create a curtain effect gas flow; and forming a gas curtain within the patient cavity and adjacent to at least one vent opening of the ventilation mask. Clause 51. The method of Clause 50, further comprising: directing the curtain effect gas flow away from the at least one vent opening via a gas fence disposed adjacent to the at least one vent opening. Clause 52. The method of any of Clauses 50 and 51, further comprising: directing the gas to the plurality of gas ports via a gas channel cooperatively defined by a gas manifold and a mask body of the ventilation mask. Clause 53. The method of Clause 50, further comprising: receiving a sample gas flow from the patient cavity via a sampling portal. Clause 54. The method of Clause 53, further comprising: directing the sample gas flow toward the sampling portal via the curtain effect gas flow. Clause 55. The method of Clause 53, further comprising: directing the sample gas flow toward the sampling portal via a manifold gas fence disposed on a gas manifold. Clause 56. The method of Clause 55, further comprising: directing the curtain effect gas flow away from the sampling portal via the manifold gas fence. Clause 57. The method of Clause 53, further comprising: measuring the sample gas flow with a carbon dioxide percentage greater than 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.8%, 3.0%, 3.2%, 3.4%, or 3.5%. Clause 58. The method of Clause 50, further comprising: visually indicating exposure to carbon dioxide via a color-changing indicator coupled to the ventilation mask. Clause 59. The method of Clause 50, further comprising: providing the gas within the patient cavity with a fraction of inspired oxygen rates greater than 40%, 45%, 50%, 60%, 70%, 75%, or 80%. Clause 60. The method of Clause 50, further comprising: accessing the patient cavity through the at least one vent opening to perform a medical procedure. Clause 61. The method of Clause 60, further comprising: performing a bronchoscopy procedure through the at least one vent opening. Clause 62. A method of introducing a gas into a ventilation mask, the method comprising: introducing the gas into a patient cavity of the ventilation mask via a plurality of gas ports; receiving a sample gas flow from the patient cavity via a sampling portal; directing the gas via the plurality of gas ports to create a curtain effect gas flow; and directing the sample gas flow toward the sampling portal via the curtain effect gas flow. Clause 63. The method of Clause 62, further comprising: directing the curtain effect gas flow away from the sampling portal via a manifold gas fence. Clause 64. The method of Clauses 62-63, further comprising: directing the sample gas flow toward the sampling portal via a manifold gas fence disposed on a gas manifold. Clause 65. The method of Clauses 62-64, further comprising: measuring the sample gas flow with a carbon dioxide percentage greater than 2.0%. Clause 66. The method of Clauses 62-65, further comprising: visually indicating exposure to carbon dioxide via a color-changing indicator coupled to the ventilation mask. Clause 67. The method of Clauses 62-66, further comprising: providing the gas within the patient cavity with a fraction of inspired oxygen rates greater than 40%. FURTHER CONSIDERATIONS In some embodiments, any of the clauses herein may depend from any one of the independent clauses or any one of the dependent clauses. In one aspect, any of the clauses (e.g., dependent or independent clauses) may be combined with any other one or more clauses (e.g., dependent or independent clauses). In one aspect, a claim may include some or all of the words (e.g., steps, operations, means or components) recited in a clause, a sentence, a phrase or a paragraph. In one aspect, a claim may include some or all of the words recited in one or more clauses, sentences, phrases or paragraphs. In one aspect, some of the words in each of the clauses, sentences, phrases or paragraphs may be removed. In one aspect, additional words or elements may be added to a clause, a sentence, a phrase or a paragraph. In one aspect, the subject technology may be implemented without utilizing some of the components, elements, functions or operations described herein. In one aspect, the subject technology may be implemented utilizing additional components, elements, functions or operations. The present disclosure is provided to enable any person skilled in the art to practice the various aspects described herein. The disclosure provides various examples of the subject technology, and the subject technology is not limited to these examples. Various modifications to these aspects will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other aspects. A reference to an element in the singular is not intended to mean “one and only one” unless specifically so stated, but rather “one or more.” Unless specifically stated otherwise, the term “some” refers to one or more. Pronouns in the masculine (e.g., his) include the feminine and neuter gender (e.g., her and its) and vice versa. Headings and subheadings, if any, are used for convenience only and do not limit the invention. The word “exemplary” is used herein to mean “serving as an example or illustration.” Any aspect or design described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other aspects or designs. In one aspect, various alternative configurations and operations described herein may be considered to be at least equivalent. A phrase such as an “aspect” does not imply that such aspect is essential to the subject technology or that such aspect applies to all configurations of the subject technology. A disclosure relating to an aspect may apply to all configurations, or one or more configurations. An aspect may provide one or more examples. A phrase such as an aspect may refer to one or more aspects and vice versa. A phrase such as an “embodiment” does not imply that such embodiment is essential to the subject technology or that such embodiment applies to all configurations of the subject technology. A disclosure relating to an embodiment may apply to all embodiments, or one or more embodiments. An embodiment may provide one or more examples. A phrase such an embodiment may refer to one or more embodiments and vice versa. A phrase such as a “configuration” does not imply that such configuration is essential to the subject technology or that such configuration applies to all configurations of the subject technology. A disclosure relating to a configuration may apply to all configurations, or one or more configurations. A configuration may provide one or more examples. A phrase such a configuration may refer to one or more configurations and vice versa. In one aspect, unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, including in the claims that follow, are approximate, not exact. In one aspect, they are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain. In one aspect, the term “coupled” or the like may refer to being directly coupled. In another aspect, the term “coupled” or the like may refer to being indirectly coupled. Terms such as “top,” “bottom,” “front,” “rear” and the like if used in this disclosure should be understood as referring to an arbitrary frame of reference, rather than to the ordinary gravitational frame of reference. Thus, a top surface, a bottom surface, a front surface, and a rear surface may extend upwardly, downwardly, diagonally, or horizontally in a gravitational frame of reference. Various items may be arranged differently (e.g., arranged in a different order, or partitioned in a different way) all without departing from the scope of the subject technology. All structural and functional equivalents to the elements of the various aspects described throughout this disclosure that are known or later come to be known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be encompassed by the claims. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims. No claim element is to be construed under the provisions of 35 U.S.C. § 112, sixth paragraph, unless the element is expressly recited using the phrase “means for” or, in the case of a method claim, the element is recited using the phrase “step for.” Furthermore, to the extent that the term “include,” “have,” or the like is used, such term is intended to be inclusive in a manner similar to the term “comprise” as “comprise” is interpreted when employed as a transitional word in a claim. The Title, Background, Summary, Brief Description of the Drawings and Abstract of the disclosure are hereby incorporated into the disclosure and are provided as illustrative examples of the disclosure, not as restrictive descriptions. It is submitted with the understanding that they will not be used to limit the scope or meaning of the claims. In addition, in the Detailed Description, it can be seen that the description provides illustrative examples and the various features are grouped together in various embodiments for the purpose of streamlining the disclosure. This method of disclosure is not to be interpreted as reflecting an intention that the claimed subject matter requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed configuration or operation. The following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separately claimed subject matter. The claims are not intended to be limited to the aspects described herein, but is to be accorded the full scope consistent with the language claims and to encompass all legal equivalents. Notwithstanding, none of the claims are intended to embrace subject matter that fails to satisfy the requirement of 35 U.S.C. § 101, 102, or 103, nor should they be interpreted in such a way. | 68,361 |
11857711 | DETAILED DESCRIPTION OF THE FIGURES FIG.1shows a greatly simplified illustration of a blood treatment apparatus1000, connected to an extracorporeal blood circuit3000and to an only roughly indicated discharge hose system having an optional effluent bag4000. The extracorporeal blood circuit3000comprises a first line3010, herein in the form of an arterial line section. The first line3010is in fluid communication with a blood treatment device, herein a blood filter or dialyzer3030by way of example. The blood filter3030comprises a dialysis liquid chamber3030aand a blood chamber3030b, which are separated from each other by a mostly semi-permeable membrane3030c. The extracorporeal blood circuit3000further comprises at least a second line3050, herein in the form of a venous line section or a return line. Both the first line3010and the second line3050may serve for connection to the vascular system of the patient who is not illustrated. The first line3010is optionally connected to a (first) hose clamp3020for blocking or closing the line3010. The second line3050is optionally connected to a (second) hose clamp3060for blocking or closing the line3050. The blood treatment apparatus1000which is represented, only by some of its devices and merely schematically, inFIG.1, comprises a blood pump1010. During the patient's treatment the blood pump1010conveys blood through sections of the extracorporeal blood circuit3000and towards the blood filter or dialyzer3030. This is indicated by the small arrow tips, which are used inFIG.1to generally illustrate the direction of flow Fresh dialysis liquid is pumped from a source2000along the dialysis liquid inlet line1040into the dialysis liquid chamber3030a, by a pump1210for dialysis liquid, which may be designed as a roller pump or as an otherwise occluding pump. The dialysis liquid leaves the dialysis liquid chamber3030ain the direction of the basin6000, as dialysate possibly enriched by filtrate, and is herein referred to as effluent. The source2000may be, for example a bag or a container. Further, the source2000may also be a fluid line from which the online and/or continuously generated or mixed liquid is provided, for example a hydraulic outlet or connection of the blood treatment apparatus1000. A further source2010with substituate may be optionally provided. It may correspond to the source2000or be a separate source. At the bottom right ofFIG.1is indicated where the discharge hose system with the effluent bag4000is connected to the blood treatment apparatus1000. In addition to the aforementioned blood pump1010, the arrangement inFIG.1further comprises purely optionally a series of further pumps, in each case optional, namely the pump1110for substituate, the pump1210for dialysis liquid and the pump1310for the effluent. The pump1210is provided to supply dialysis liquid, from a source2000, for example a bag, via an optional existing bag heater with a bag H2to the blood filter3030, via a dialysis liquid inlet line1040. The thus supplied dialysis liquid exits from the blood filter3030via a dialysate outlet line1020, supported by the pump1310, and may be discarded. Upstream of blood pump1010an optional arterial sensor PS1is provided. During the patient's treatment it measures the pressure in the arterial line. Downstream of the blood pump1010, but upstream of the blood filter3030and if provided, upstream of a coupling site25for heparin, a further optional pressure sensor PS2is provided. It measures the pressure upstream of the blood filter3030(“pre-hemofilter”). Another further pressure sensor may be provided as PS4downstream of the blood filter3030, however preferably upstream of the pump1310, in the dialysate outlet line1020to measure the filtrate pressure of the blood filter3030. Blood, which leaves the blood filter3030, passes through an optional venous blood chamber29, which may comprise a deaeration device31and which may be in fluid communication with a further pressure sensor PS3. A control device or a closed-loop control device1500for controlling or regulating the blood treatment apparatus1000may be provided and may be in signal communication and/or control communication with all the a.m. components of the blood treatment apparatus1000. Furthermore, an input device100, a reading device150and a storage device160are connected to the blood treatment apparatus1000in signal communication and/or control communication. FIG.2shows a treatment result d (in [ml/kg*h]) over the time t (in [h]) upon completion of a common blood treatment session set for 24 hours for the acute treatment of the patient with two interruptions starting after 6 hours respectively after 17 hours. The interruptions can each be recognized by the drop of Qdia. Qdiacorresponds to the flow of the dialysis pump1210. Other pump flows, for instance QBfor the blood pump1010, QUFfor the ultrafiltration pump or flows of the effluent pump may as well be affected by the interruptions. The treatment result is also affected by both interruptions: d decreases further upon and during each interruption. This would require a regulating mechanism in order to achieve the desired treatment result dtargof 25 ml/kg*h until the completion or the end of the predetermined 24 hours. As can be seen inFIG.2, the set treatment target dtargis not reached after 24 hours due to both interruptions, because the actual achieved treatment result dactis less than dtarg. FIG.3shows the course of a blood treatment session with the same interruptions like inFIG.2, herein however by using an exemplary embodiment of the method. The treatment target was automatically corrected upwards already before the beginning of the treatment session, i.e. at t less than or equal to 0, by a correction factor (here exemplarily by 20%). Pump flows and/or other machine parameters were raised to the new, higher, corrected treatment target dkorr. Based thereon, the set, initial treatment target is achieved after 24 hours; dtarg=dactapplies. FIG.4shows the course of an exemplary embodiment of the method in a flow diagram. In this, S1describes the input of the correction factor fkorror the reading out thereof from the storage device160. The step S2describes the setting of the initial value dkorrtaking into consideration the correction factor fkorr, added to the treatment target dtarg. Step S3represents the running treatment over 24 hours, with interruptions of the treatment session. Step S4represents achieving the treatment target dtargat the end of the 24-hour treatment session, wherein preferably dact=dtargis achieved. LIST OF REFERENCE NUMERALS 25addition site for heparin (optional)29venous blood chamber31deaeration device100input device150reading device160storage device1000blood treatment apparatus1010blood pump1020dialysate outlet line, effluent inlet line1040dialysis liquid inlet line1110pump for substituate1210dialysis liquid pump1310pump for dialysate or effluent1500control device or closed-loop control device2000dialysis liquid source2010substituate source, optional3000extracorporeal blood circuit3010first line (arterial line section)3020(first) hose clamp3030blood filter or dialyzer3030adialysis liquid chamber3030bblood chamber3030csemi-permeable membrane3050second line (venous line section)3060(second) hose clamp4000effluent bag6000basinH2bag heating with bag (dialysis liquid)H1bag heating with bag (substituate)PS1, PS2arterial pressure sensor (optional)PS3venous pressure sensor (optional)PS4pressure sensor for measuring the filtrate pressuredactactually reached treatment resultdtargset treatment targetdkorrcorrected treatment targetfkorrcorrection factor, predetermined correction factorQdiadialysis liquid pump flowQBblood pump flowQUFultrafiltration pump flow | 7,776 |
11857712 | Like reference numbering between FIG.'s represents like features and elements. DETAILED DESCRIPTION Definitions Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the relevant art. The definitions provided herein should not be rigidly construed without taking into account the context and other ascribed meanings provided, or by their use, in other parts of the specification, claims, and drawings. The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. The term “substantially” refers to an extent of similarity between any two given values that is at least 75 percent, 80 percent, 85 percent, 90 percent, 95 percent, or 99.9 percent, the given values optionally including values in weight, height, length, area, temperature, angle dimensions, among others. The term “acid or base equivalents” refers to an equivalent acid or base donating or accepting an equal number of moles of hydrogen or hydronium ions per mole of the acid to which the equivalent acid is being equated, or mole of hydroxide ions to which the equivalent base is being equated. The term “cation infusate pump” historically known as an “acid concentrate pump” in dialysis systems refers to a pump that serves the function to move or control the flow of a fluid to and/or from a reservoir having a substance that contains at least one cation species, such as calcium, magnesium and potassium ions. In the present invention, the historically used term of “acid concentrate pump” is used. The term “acid feed” refers a state of fluid communication that enables an acid solution to be obtained from an acid source and connected or feed into a receiving source or flow path. An “acid” can be either an Arrhenius acid, a Brønsted-Lowry acid, or a Lewis acid. The Arrhenius acids are substances or fluids which increase the concentration of hydronium ions (H3O+) in solution. The Brønsted-Lowry acid is a substance which can act as a proton donor. Lewis acids are electron-pair acceptors. The term “activated carbon” may refer to a porous carbon material having a surface area greater than 500 m2per gram. Activated carbon can be capable of absorbing several species including heavy metals such as lead, mercury, arsenic, cadmium, chromium and thallium among others, oxidants such as chlorine and chloramines, fluoride ions, and waste species such as phosphate and certain nitrogen-containing waste species such as creatinine and uric acid. The terms “administering,” “administer,” “delivering,” “deliver,” “introducing,” and “introduce” can be used, in context, interchangeably to indicate the introduction of water or a dialysate having an altered concentration of at least one component, including electrolytes and alkali and/or alkali earth ions, to a patient in need thereof, and can further mean the introduction of water, any agent or alkali and/or alkali earth ions to a dialysate or dialysis circuit where such water, agent or alkali and/or alkali earth ion will enter the blood of the patient by diffusion, transversal of a diffusion membrane or other means. The term “air trap” refers to a structure for separating a gas from a mixture of a gas and a liquid or any other separation means known in the art. An air trap can include a hydrophobic membrane for allowing gases to pass and for preventing the passage of water. The term “albumin sieving coefficient” can be used to describe the amount of albumin that will cross a membrane. The terms “ammonia sensing module” and “ammonia detector” refer to a unit that performs all or part of the function to detect a predetermined level of, or measure a concentration of, ammonia and/or ammonium ions in a fluid. The term “anion exchange membrane” refers to a positively charged membrane, which allows negatively charged ions (anions) to pass through. The term “anticoagulant” is a substance that prevents or delays the clotting of blood, such as heparin, Fragmin®, and sodium citrate. The term “atmospheric pressure” refers to the local pressure of air in the environment in proximity to the system at the time that the system is operating. The term “base concentrate pump” refers to a device that performs work on a fluid solution to cause fluid flow to control the volume transfer of a basic or alkaline solution into a circuit. The term “base concentrate reservoir” refers to a vessel or container, optionally accessible by a pump that contains a variable amount of a basic or alkaline fluid solution. The term “base module” refers to a basic unit of an apparatus for hemodialysis, hemodiafiltration, or hemofiltration that incorporates one or more fluid pathways. Exemplary, non-limiting components that can be included in the base module include conduits, valves, pumps, fluid connection ports, sensing devices, a controller and a user interface. The base module can be configured to interface with reusable or disposable modules of the apparatus for hemodialysis, hemodiafiltration, or hemofiltration to form at least one complete fluid circuit, such as a dialysis, cleaning, disinfection, priming or blood rinse back circuit. A “base” can be either a substance that can accept hydrogen cations (protons) or more generally, donate a pair of valence electrons. A soluble base is referred to as an alkali if it contains and releases hydroxide ions (OH—) quantitatively. The Brønsted-Lowry theory defines bases as proton (hydrogen ion) acceptors, while the more general Lewis theory defines bases as electron pair donors, allowing other Lewis acids than protons to be included. The Arrhenius bases act as hydroxide anions, which is strictly applicable only to alkali. The term “base feed” refers a state of fluid communication that enables a base solution to be obtained from a base source and connected or feed into a receiving source or flow path. The term “bicarbonate buffer component” refers to any composition contain bicarbonate (HCO3−) ion or a conjugate acid of bicarbonate ion in any amount, proportion or pH of the composition. The bicarbonate buffering system is an important buffer system in the acid-base homeostasis of living things, including humans. As a buffer, it tends to maintain a relatively constant plasma pH and counteract any force that would alter it. In this system, carbon dioxide (CO2) combines with water to form carbonic acid (H2CO3), which in turn rapidly dissociates to form hydrogen ions and bicarbonate (HCO3−) as shown in the reactions below. The carbon dioxide—carbonic acid equilibrium is catalyzed by the enzyme carbonic anhydrase; the carbonic acid—bicarbonate equilibrium is simple proton dissociation/association and needs no catalyst. CO2+H2O⇄H2CO3⇄HCO3−+H+ Any disturbance of the system will be compensated by a shift in the chemical equilibrium according to Le Chatelier's principle. For example, if one attempted to acidify the blood by dumping in an excess of hydrogen ions (acidemia), some of those hydrogen ions will associate with bicarbonate, forming carbonic acid, resulting in a smaller net increase of acidity than otherwise. The term “bicarbonate buffer concentrate” refers to a bicarbonate (HCO3−) buffer component composition at a higher concentration than found at normal physiological levels that can be used to for instants to readjusted the pH of the dialysate (see also definition of bicarbonate buffer component relating to its use). The term “bicarbonate cartridge” refers to a container that can be a stand-alone container or alternatively can be integrally formed with an apparatus for hemodialysis, hemodiafiltration, or hemofiltration. The bicarbonate cartridge can store a source of buffering material, such as sodium bicarbonate, and can be configured to interface with at least one other functional module found in systems for hemodialysis, hemodiafiltration, or hemofiltration. For example, the bicarbonate cartridge can contain at least one fluid pathway and include components such as conduits, valves, filters or fluid connection ports. The bicarbonate cartridge can be disposable or be consumable wherein the cartridge is recharged upon depletion. Specifically, the term “bicarbonate consumables container” refers to an object or apparatus having or holding a material in solid and/or solution form that is a source of bicarbonate, such as sodium bicarbonate, that is depleted during operation of the system. The object or apparatus may be single use, or may be replenished and used multiple times, for example, by refilling the object to replace the consumed material. The term “bicarbonate feed” refers to fluid solution introduced into part of the dialysis or ultrafiltrate system. For example a “bicarbonate feed” is a conduit that contains a bicarbonate buffer concentrate that is used to readjust the pH of the dialysate. The term “bidirectional pump” refers to a device configured to perform work on a fluid to cause the fluid to flow alternatively in either of two opposing directions. A “biocompatible material” is a material that has the ability to interface with living biological tissues with an acceptable host response in any of specific medical systems, methods of treatment or delivery contemplated herein. The biocompatible material can consist of synthetic, natural or modified natural polymers intended to contact or interact with the biological systems during application of any of the inventions contained herein. The term “bipolar electrodialysis system” refers to an electrochemical separation process in which ions are selectively transferred through a bipolar membrane. The term “bipolar membrane” refers to a membrane formed by bonding an anion exchange and a cation exchange membrane together wherein the membranes result in the dissociation of water into hydrogen ions. The anion- and cation-exchange membranes can either be bound together physically or chemically such that the bipolar membrane has a thin interface where water diffuses into the membrane from outside aqueous salt solutions. The term “blood access connection” refers to a junction or aperture through which the blood of a subject is conveyed to or from an extracorporeal circuit. Commonly, the blood access connection is made between a terminal end of a conduit of an extracorporeal circuit and the terminal end of a catheter or fistula needle that is distal to the subject receiving therapy. A subject may have more than one blood access connection when receiving therapy. In the case of two blood access connections they can be referred to as an arterial blood access connection and a venous blood access connection. The term “blood solute” refers to a substance dissolved, suspended, or present in blood or dialysate. The term “bolus” refers to an increase (or at times a decrease) of limited duration in an amount or concentration of one or more solutes, for example sodium, glucose and potassium, or a solvent, for example water, such that the concentration of a solution is changed. The term “bolus” includes delivery of solute and/or solvent to the dialysate fluid path such that it is delivered to the blood of a subject via diffusion and/or convection across a dialysis membrane such that the amount or concentration in the subject is increased or decreased. A “bolus” may also be delivered directly to the extracorporeal flow path or the blood of a subject without first passing through the dialysis membrane. The term “bottled water” refers to water that may be filtered or purified and has been packaged in a container. Bottled water can include water that has been packaged and provided to a consumer as drinking water. The term “breakthrough capacity” refers to the amount of solute a sorbent material can remove until breakthrough occurs. Breakthrough occurs when the concentration of a certain solute exiting a regeneration module becomes non-zero. The terms “bubble detector”, “bubble sensor”, “gas detector” and “air detector” refer to a device that can detect the presence of a void, void space, or gas bubble in a liquid. The term “buffer conduit flow path” refers to a fluid flow path in fluid communication with a stored source of a buffering material, such as bicarbonate. The term “buffer source” refers to a stored material, such as bicarbonate, acetate or lactate that provides buffering. The terms “buffer source container” and “buffer source cartridge” refer to objects that have or hold one or more materials, in solid and/or solution form, that are a source of buffering, for example a bicarbonate, a lactate, or acetate; and the object further having at least one port or opening to allow at least a portion of the buffering material to be released from the object during operation of the system. The term “blood based solute monitoring system” refers to a system for monitoring a substance dissolved or suspended or present in blood or dialysate. The term “blood rinse back” refers to returning the blood from a dialyzer and/or extracorporeal circuit to a subject, normally at conclusion of a therapy session and prior to disconnecting or removing the subject's blood access connection or connections. The procedure can include conveying a physiologically compatible solution through the extracorporeal circuit to push or flush the blood from the extracorporeal circuit to the subject via the subject's blood access connection or connections. The terms “bypass circuit” “bypass conduit,” “bypass flow path,” “bypass conduit flow path” and “bypass” refer to a component or collection of components configured or operable to create an alternate fluid pathway to convey a fluid around one or more other components of a fluid circuit such that at least a portion of the fluid does not contact or pass through the one or more other components. At times the term “shunt” may be used interchangeable with the term “bypass.” When any of the above “bypass” terms listed in this paragraph are used in context as being part of a controlled compliant system, then the relevant referenced “bypass” has the proper characteristics as to operate within a controlled compliant system as defined herein. The term “bypass regulator” refers to a component such as valve that can determine the amount of fluid that can pass through a by-pass portion of a fluid circuit. The term “capacitive deionization” refers to a process for directly removing salts from solution by applying an electric field between two electrodes. The term “cartridge” refers to a compartment or collection of compartments that contains at least one material used for operation of the system of the present invention. The term “cassette” refers to a grouping of components that are arranged together for attachment to, or use with the device, apparatus, or system. One or more components in a cassette can be any combination of single use, disposable, consumable, replaceable, or durable items or materials. The term “cation exchange membrane” refers to a negatively charged membrane, which allows positively charged ions (cations) to pass. By convention, electrical current flows from the anode to the cathode when a potential is applied to an electrodialysis cell. Negatively charged anions such as chloride ions are drawn towards the anode, and positively charged cations such as sodium ions are drawn towards the cathode. The term “cation infusate source” refers to a source from which cations can be obtained. Examples of cations include, but are not limited to, calcium, magnesium and potassium. The source can be a solution containing cations or a dry composition that is hydrated by the system. The cation infusate source is not limited to cations and may optionally include other substances to be infused into a dialysate or replacement fluid, non-limiting examples can be glucose, dextrose, acetic acid and citric acid. The term “cation concentrate reservoir” refers to an object having or holding a substance that is comprised of at least one cation, for example calcium, magnesium, or potassium ions. The terms “communicate” and “communication” include, but are not limited to, the connection of system electrical elements, either directly or remotely, for data transmission among and between said elements. The terms also include, but are not limited, to the connection of system fluid elements enabling fluid interface among and between said elements. The terms “conduit”, “conduit” or “flow path” refer to a vessel or passageway having a void volume through which a fluid can travel or move. A conduit can have a dimension parallel to the direction of travel of the fluid that is significantly longer than a dimension orthogonal to the direction of travel of the fluid. The term “central axis” refers to (a) a straight line about which a body or a geometric figure rotates or may be supposed to rotate; (b) a straight line with respect to which a body or figure is symmetrical—called also axis of symmetry; (c) a straight line that bisects at right angles a system of parallel chords of a curve and divides the curve into two symmetrical parts; or (d): one of the reference lines of a coordinate system. The term “chelating resins” refers to a class of resins that interacts and selectively binds with selected ions and ligands (the process is referred to as chelation). According to IUPAC, the formation or presence of two or more separate coordinate bonds. The term “chronic kidney disease” (CKD) refers to a condition characterized by the slow loss of kidney function over time. The most common causes of CKD are high blood pressure, diabetes, heart disease, and diseases that cause inflammation in the kidneys. CKD can also be caused by infections or urinary blockages. If CKD progresses, it can lead to end-stage renal disease (ESRD), where the kidneys fail to function at a sufficient level. The term “citric acid” refers to an organic acid having the chemical formula C6H8O7, and may include anhydrous and hydrous forms of the molecule, and aqueous solutions containing the molecule. The term “cleaning and/or disinfection concentrate” refers to a dry substance, or concentrated solutions containing at least one material for use in cleaning and/or disinfection of an apparatus. The term “cleaning and/or disinfection solution” refers to a fluid that is used for the purpose of removing, destroying or impairing at least a portion of at least one contaminant. The contaminant may be organic, inorganic or an organism. The fluid may accomplish the purpose by transmission of thermal energy, by chemical means, flow friction or any combination thereof. The terms “cleaning manifold” and “cleaning and disinfection manifold” refer to an apparatus that has fluid connection ports and one or more fluid pathways, or fluid port jumpers, that, when connected to jumpered ports of a base module, create one or more pathways for fluid to be conveyed between the jumpered ports of the base module. A cleaning manifold may be further comprised of additional elements, for example valves and reservoirs. The term “container” as used herein is a receptacle that may be flexible or in-flexible for holding fluid or solid, such as for example a spent dialysate fluid, or a sodium chloride or sodium bicarbonate solution or solid. The terms “common container,” “common cartridge,” or “common reservoir,” and the like refer to an object or apparatus that can hold more than one material; however, the time of holding more than one material may or may not necessarily be at the same time. The material(s) may be in solid and/or solution forms and may be held in separate compartments within the object or apparatus. The term “common fluid inlet port” refers to an opening or aperture through which all fluid first passes to enter an object, apparatus or assembly. The term “common fluid outlet port” refers to an opening or aperture through which all fluid passes to exit an object, apparatus or assembly. The terms “communicate” and “communication” include, but are not limited to, the connection of system electrical elements, either directly or remotely, for data transmission among and between said elements. The terms also include, but are not limited, to the connection of system fluid elements enabling fluid interface among and between said elements. The terms “component” and “components” refer to a part or element of a larger set or system. As used herein, a component may be an individual element, or it may itself be a grouping of components that are configured as a set, for example, as a cassette or a cleaning and/or disinfection manifold. The term “comprising” includes, but is not limited to, whatever follows the word “comprising.” Thus, use of the term indicates that the listed elements are required or mandatory but that other elements are optional and may or may not be present. The term “concentrate pump” refers to a device that can perform work on a fluid solution to cause the fluid flow and can actively control the transfer of fluid volume such as an infusate or an acid concentrate, base concentrate, or buffer concentrate into a circuit. The terms “concentrate flow channel,” “concentrate flow loop,” “concentrate stream,” refer to a fluid line in which ion concentration is increased during electrodialysis. The terms “conditioning conduit flow path” and “conditioning flow path” refer to a fluid pathway, circuit or flow loop that incorporates a source of a conditioning material, for example a sodium salt or bicarbonate. The term “conditioning flow path inlet” refers to a location on a conditioning flow path where fluid enters the conditioning flow path. The term “conditioning flow path outlet” refers to a location on a conditioning flow path where fluid exits the conditioning flow path. The terms “conductivity meter,” “conductivity sensor,” “conductivity detector”, conductivity electrode or the like, refer, in context, to a device for measuring the electrical conductance of a solution and/or the ion, such as a sodium ion, concentration of a solution. In specific examples, the conductivity sensor, meter, or conductor can be directed to a specific ion such as sodium and be referred to as a “sodium electrode,” “sodium sensor,” “sodium detector,” or “sodium meter.” The term “conductive species” refers to a material's ability to conduct an electric current. Electrolytes are an example of a conductive species in dialysate fluids, such as, but not limited to the presence sodium, potassium, magnesium, phosphate, and chloride ions. A fluid's ability to conduct an electrical current is due in large part to the ions present in the solution. A fluid's ability to conduct an electrical current is due in large part to the ions present in the solution. The terms “conduit”, “circuit”, and “flow path” refer to a vessel or passageway having a void volume through which a fluid can travel or move. A conduit can have a dimension parallel to the direction of travel of the fluid that is significantly longer than a dimension orthogonal to the direction of travel of the fluid. The term “connectable” refers to being able to be joined together for purposes including but not limited to maintaining a position, allowing a flow of fluid, performing a measurement, transmitting power, and transmitting electrical signals. The term “connectable” can refer to being able to be joined together temporarily or permanently. The term “consisting of” includes and is limited to whatever follows the phrase “consisting of.” Thus, the phrase indicates that the limited elements are required or mandatory and that no other elements may be present. The term “consisting essentially of” includes whatever follows the term “consisting essentially of” and additional elements, structures, acts or features that do not affect the basic operation of the apparatus, structure or method described. The term “consumables” refers to components that are dissipated, wasted, spent or used up during the performance of any function in the present invention. Examples include a quantity of sodium, bicarbonate, electrolytes, infusates, sorbents, cleaning and disinfecting ingredients, anticoagulants, and components for one or more concentrate solutions. The terms “consumables cartridge” and “consumables container” refer to an object or apparatus having or holding one or more materials that are depleted during operation of the system. The one or more materials may be in solid and/or solution form and can be in separate compartments of the object or apparatus. The object or apparatus may be single use, or may be replenished and used multiple times, for example, by refilling the object to replace the consumed material. The terms “contact”, “contacted”, and “contacting” refers, in context, to (1) a coming together or touching of objects, fluids, or surfaces; (2) the state or condition of touching or of immediate proximity; (3) connection or interaction. For example, in reference to a “dialysate contacting a sorbent material” refers to dialysate that has come together, has touched, or is in immediate proximity to connect or interact with any material or material layer of a sorbent container, system or cartridge. The term “container” as used herein is a receptacle that may be flexible or in-flexible for holding fluid or solid, such as for example a spent dialysate fluid, or a sodium chloride or sodium bicarbonate solution or solid, or the like. The term “contaminant” refers to an undesirable or unwanted substance or organism that may cause impairment of the health of a subject receiving a treatment or of the operation of the system. The term “control pump,” such as for example an “ultrafiltrate pump,” refers to a pump that is operable to pump fluid bi-directionally to actively control the transfer of fluid volume into or out of a compartment or circuit. The terms “control reservoir,” “ultrafiltrate reservoir,” “solution reservoir,” “therapy solution reservoir,” and “waste reservoir”, as the case may be, refers, in context, to a vessel or container, optionally accessible by a control pump that contains a variable amount of fluid, including fluid that can be referred to as an ultrafiltrate. These reservoirs can function as a common reservoir to store fluid volume from multiple sources in a system. Other fluids that can be contained by these reservoirs include, for example, water, priming fluids, waste fluids, dialysate, including spent dialysate, and mixtures thereof. In certain embodiments, the reservoirs can be substantially inflexible, or non-flexible. In other embodiments, the reservoirs can be flexible containers such as a polymer bag. The term “control signals” refers to energy that is provided from one element of a system to another element of a system to convey information from one element to another or to cause an action. For example, a control signal can energize a valve actuator to cause a valve to open or close. In another example a switch on a valve can convey the open or close state of a valve to a controller. A “control system” consists of combinations of components that act together to maintain a system to a desired set of performance specifications. The control system can use processors, memory and computer components configured to interoperate to maintain the desired performance specifications. It can also include fluid control components, and solute control components as known within the art to maintain the performance specifications. The terms “control valve” and “valve” refer to a device that can be operated to regulate the flow of fluid through a conduit or flow path by selectively permitting fluid flow, preventing fluid flow, modifying the rate of fluid flow, or selectively guiding a fluid flow to pass from one conduit or flow path to one or more other conduits or flow paths. The terms “controlled compliant flow path”, “controlled compliant dialysate flow path” and “controlled compliant solution flow path” refer to flow paths operating within a controlled compliant system having the characteristic of controlled compliance, or of being controlled compliant as defined herein. A “controller,” “control unit,” “processor,” or “microprocessor” is a device which monitors and affects the operational conditions of a given system. The operational conditions are typically referred to as output variables of the system wherein the output variables can be affected by adjusting certain input variables. The terms “controlled compliance” and “controlled compliant” describe the ability to actively control the transfer of fluid volume into or out of a compartment, flow path or circuit. In certain embodiments, the variable volume of fluid in a dialysate circuit or controlled compliant flow path expands and contracts via the control of one or more pumps in conjunction with one or more reservoirs. The volume of fluid in the system is generally constant (unless additional fluids are added to a reservoir from outside of the system) once the system is in operation if the patient fluid volume(s), flow paths, and reservoirs are considered part of the total volume of the system (each individual volume may sometimes be referred to as a fluid compartment). The attached reservoirs allow the system to adjust the patient fluid volume by withdrawing fluid and storing the desired amount in an attached control reservoir and/or by providing purified and/or rebalanced fluids to the patient and optionally removing waste products. The terms “controlled compliance” and “controlled compliant” are not to be confused with the term “non-compliant volume,” which simply refers to a vessel, conduit, container, flow path, conditioning flow path or cartridge that resists the introduction of a volume of fluid after air has been removed from a defined space such as a vessel, conduit, container, flow path, conditioning flow path or cartridge. In one embodiment, and as discussed herein and shown in the drawings is that the controlled compliant system can move fluids bi-directionally. In certain cases, the bi-directional fluid movement is across a semi-permeable membrane either inside or outside a dialyzer. The bi-directional fluid flow can also occur across, through, or between vessels, conduits, containers, flow paths, conditioning flow paths or cartridges of the invention in selected modes of operation. The term “moving fluid bi-directionally” as used in connection with a barrier, such as a semi-permeable membrane, refers to the ability to move a fluid across the barrier in either direction. “Moving fluid bi-directionally” also can apply to the ability to move fluid in both directions in the flow path or between a flow path and reservoir in a controlled compliant system. The terms “controlled compliant flow path”, “controlled compliant dialysate flow path” and “controlled compliant solution flow path” refer to flow paths operating within a controlled compliant system having the characteristic of controlled compliance, or of being controlled compliant as defined herein. The term “convective clearance” refers to the movement of solute molecules or ions across a semi-permeable barrier due to force created by solvent molecules moving across the semi-permeable barrier. The terms “controller,” “control unit,” “processor,” and “microprocessor” refers, in context, to a device which monitors and affects the operational conditions of a given system. The operational conditions are typically referred to as output variables of the system wherein the output variables can be affected by adjusting certain input variables. The terms “coordinately operates” and “coordinately operating” refer to controlling the function of two or more elements or devices so that the combined functioning of the two or more elements or devices accomplishes a desired result. The term does not exclusively imply that all such elements or devices are simultaneously energized. The term “deaeration” refers to removing some or all of the air contained in a liquid including both dissolved and non-dissolved air contained in the liquid. The terms “de-aeration flow path” and “de-aeration flow path” refer to a set of elements that are configured in fluid communication along a fluid flow pathway such that a liquid can be passed through the fluid flow pathway to accomplish removal of some or all of the air or gas contained in the liquid, including removal of air or gas that is dissolved in the liquid. The terms “degas module” and “degassing module” refer to a component that separates and removes any portion of one or more dissolved or undissolved gas from a liquid. A degas module can include a hydrophobic membrane for allowing ingress or egress of gases through a surface of the module while preventing the passage of liquid through that surface of the module. The term “deionization resin” refers to any type of resin or material that can exchange one type of ion for another. In one specific case, the term can refer to the removal of ions such as potassium, magnesium, sodium and calcium in exchange for hydrogen and/or hydroxide ions. The term “detachable” refers to a characteristic of an object or apparatus that permits it to be removed and/or disconnected from another object or apparatus. The term “dialysate” describes a fluid into or out of which solutes from a fluid to be dialyzed diffuse through a membrane. A dialysate typically contains electrolytes that are close in concentration to the physiological concentration of electrolytes found in blood. A common sodium level for dialysate is approximately 140 mEq/L. Normal blood sodium levels range from approximately 135 mEq/L to 145 mEq/L. The REDY system typically uses dialysate ranging from 120 mEq/L to 160 mEq/L. In certain embodiment, a “predetermined limit” or “predetermined concentration” of sodium values can be based off the common sodium levels for dialysate and normal blood sodium levels. “Normal” saline at 0/9% by weight and commonly used for priming dialyzers and extracorporeal circuits is 154 mEq/L. The terms “dialysate flow loop”, “dialysate flow path”, and “dialysate conduit flow path” refers, in context, to a fluid pathway that conveys a dialysate and is configured to form at least part of a fluid circuit for hemodialysis, hemofiltration, hemodiafiltration or ultrafiltration. The terms “dialysate regeneration unit” and “dialysate regeneration system” refer to a system for removing certain electrolytes and waste species including urea from a dialysate after contact with a dialyzer. In certain instances, the component contained within the “dialysate regeneration unit” or “dialysate regeneration system” can decrease the concentration or conductivity of at least one ionic species, or release and/or absorb at least one solute from a dialysate. “Dialysis” is a type of filtration, or a process of selective diffusion through a membrane. Dialysis removes solutes of a specific range of molecular weights via diffusion through a membrane from a fluid to be dialyzed into a dialysate. During dialysis, a fluid to be dialyzed is passed over a filter membrane, while dialysate is passed over the other side of that membrane. Dissolved solutes are transported across the filter membrane by diffusion between the fluids. The dialysate is used to remove solutes from the fluid to be dialyzed. The dialysate can also provide enrichment to the other fluid. The terms “dialysis membrane,” “hemodialysis membrane,” “hemofiltration membrane,” “hemodiafiltration membrane,” “ultrafiltration membrane,” and generally “membrane,” refer, in context, to a semi-permeable barrier selective to allow diffusion and convection of solutes of a specific range of molecular weights through the barrier that separates blood and dialysate, or blood and filtrate, while allowing diffusive and/or convective transfer between the blood on one side of the membrane and the dialysate or filtrate circuit on the other side of the membrane. The term “dialyzer” refers to a cartridge or container with two flow paths separated by semi-permeable membranes. One flow path is for blood and one flow path is for dialysate. The membranes can be in the form of hollow fibers, flat sheets, or spiral wound or other conventional forms known to those of skill in the art. Membranes can be selected from the following materials of polysulfone, polyethersulfone, poly(methyl methacrylate), modified cellulose, or other materials known to those skilled in the art. “Diffusive permeability” is a property of a membrane describing permeation by diffusion. Diffusion is the process of solutes moving from an area of higher concentration to an area of lower concentration. The terms “diluate flow channel,” “feed stream,” “diluate stream,” and the like, refer, in context, to a fluid line of solution entering an electrodialysis cell or electrodialysis unit wherein the ion concentration in the fluid solution is changed. The terms “diluent” and “diluate” refer to a fluid having a concentration of a specific species less than a fluid to which the diluent is added. A “disc electrode” consists of an electrode with an electrode head in the shape of a disc. A “rod electrode” refers to an electrode in the shape of a rod or cylinder, with one end functioning as an electrode head. A “sheet electrode” refers to an electrode with an electrode head in the shape of a sheet. The sheet can be square, rectangular, circular or other solid planar geometries. A “mesh electrode” refers to an electrode with an electrode head consisting of a mesh, where a mesh is the same as that described for a mesh electrode. An “antenna electrode” refers to an electrode with an electrode head in the shape of an antenna, where antenna shape refers to a serpentine structure of conductive wires or strips. A “pin electrode refers” to a rod electrode with a small diameter. Other electrode and electrode head geometries can be considered. The term “disinfection fluid” refers to a solution for use in cleaning and disinfecting an apparatus for hemodialysis, hemodiafiltration or hemofiltration. The disinfection fluid may act thermally, chemically, and combinations thereof to inhibit growth of or to destroy microorganisms. The “disinfection fluid” may further act to remove, at least in part, a buildup of microorganisms on a surface of a fluid flow path, such buildups of microorganisms may be commonly referred to as a biofilm. The terms “diverted sample stream” and “diverting a sample stream” refer redirecting part of a fluid from the main flow path to accomplish another purpose, such as to measure a fluid characteristic, remove a portion of the fluid stream in order to take a sample. More that one sample stream may be diverted, such as a “first sample stream, “second sample stream”, “third sample stream”, “fourth sample stream”, and the like. The term “dry” as applied to a solid or a powder contained in a cartridge means not visibly wet, and may refer interchangeably to anhydrous and also to partially hydrated forms of those materials, for example, monohydrates and dihydrates. The term “downstream” refers to a direction in which a moving dialysate or other fluid moves within a conduit or flow path. The term “downstream conductivity” refers to the conductivity of a fluid solution as measured at a location of a fluid flow path in the direction of the normal fluid flow from a reference point. The term “drain connection” refers to being joined in fluid communication with a conduit or vessel that can accept fluid egress from the system. The term “dry composition” refers to a compound that does not contain a substantial quantity of water and can include anhydrous forms as well as hydrates for example, monohydrates and dihydrates. The term “effluent dialysate,” as used herein describes the discharge or outflow after the dialysate has been used for dialysis. The term “electrode” as used herein describes an electrical conductor used to make contact with a part of a fluid, a solid or solution. For example, electrical conductors can be used as electrodes to contact any fluid (e.g. dialysate) to measure the conductivity of the fluid or deliver or receive charge to the fluid. A “disc electrode” consists of an electrode with an electrode head in the shape of a disc. A “rod electrode” refers to an electrode in the shape of a rod or cylinder, with one end functioning as an electrode head. A “sheet electrode” refers to an electrode with an electrode head in the shape of a sheet. The sheet can be square, rectangular, circular or other solid planar geometries. A “mesh electrode” refers to an electrode with an electrode head consisting of a mesh, where a mesh is the same as that described for a mesh electrode. An “antenna electrode” refers to an electrode with an electrode head in the shape of an antenna, where antenna shape refers to a serpentine structure of conductive wires or strips. A “pin electrode” refers to a rod electrode with a small diameter. Other electrode and electrode head geometries can be considered. The term “electrode array” refers to an array of one or more electrodes contained in an insulator substrate. The insulator substrate can be rigid or flexible and acts to isolate the electrodes from each other. A non-limiting example of an “electrode array” is a flex-circuit, which is a flexible circuit board containing electrodes. The term “electrode head” refers to the portion of an electrode that is in physical contact with a fluid, that conductivity is to be measured from. The terms “electrode rinse” and “electrode rinse solution” refer to any suitable solution such as sodium sulfate solution that prevents undesirable oxidation and flushes reactants from an electrode surface. The terms “electrode rinse flow channel,” “electrode rinse stream,” and the like refer to a fluid line of an electrode rinse or “electrode rinse solution.” The term “electrode rinse reservoir” refers to a vessel or container for holding the electrode rinse or electrode rinse solution. The reservoir may have an inflexible or flexible volume capacity. The term “electrodialysis” refers to an electrically driven membrane separation process capable of separating, purifying, and concentrating desired ions from aqueous solutions or solvents. The term “electrodialysis cell” refers to an apparatus having alternating anion- and cation-exchange membranes that can perform electrodialysis using an electrical driving force between an anode and cathode housed at opposite ends of the cell. The cell consists of a diluate compartment fed by a diluate stream and a concentrate compartment fed by a concentrate stream. One or more electrodialysis cells can be multiply arranged to form an “electrodialysis stack.” The term “electrolyte” refers to an ion or ions dissolved in an aqueous medium, including but not limited to sodium, potassium, calcium, magnesium, acetate, bicarbonate, and chloride. The terms “electrolyte source” and “electrolyte source” refer to a stored substance that provides one or more electrolytes. The terms “equilibrated,” “equilibrate,” “to equilibrate,” and the like, refer to a state where a concentration of a solute in a first fluid has become approximately equal to the concentration of that solute in the second fluid. However, the term equilibrated as used herein does not imply that the concentration of the solute in the first fluid and the second fluid have become equal. The term can also be used in reference to the process of one or more gases coming into equilibrium where the gases have equal pressures or between a liquid and a gas. The term “equilibrated to the solute species concentration” refers to more specifically where a concentration of a particular solute species in a first fluid has become approximately equal to the concentration of that solute species in the second fluid. The concentration need not be exact. The terms “evacuation volume”, “priming volume” and “void volume” refer to the internal volume of a component or collection of components comprising a fluid flow path and are the volume of fluid that can be removed from the fluid flow path to empty the fluid flow path if it has been filled with fluid. The term “extracorporeal,” as used herein generally means situated or occurring outside the body. The term “extracorporeal circuit” refers to a fluid pathway incorporating one or more components such as, but not limited to, conduits, valves, pumps, fluid connection ports or sensing devices configured therein such that the pathway conveys blood from a subject to an apparatus for hemodialysis, hemofiltration, hemodiafiltration or ultrafiltration and back to the subject. The terms “extracorporeal flow path pump” and “blood pump” refer to a device to move or convey fluid through an extracorporeal circuit. The pump may be of any type suitable for pumping blood, including those known to persons of skill in the art, for example peristaltic pumps, tubing pumps, diaphragm pumps, centrifugal pumps, and shuttle pumps. The term “feed solution” refers to a dialysate or ultrafiltrate fluid solution introduced into part of the dialysis or ultrafiltrate system. For example a “feed solution” can refer to a dialysate or ultrafiltrate fluid solution introduced to an electrodialysis cell. The term “filtering media” refers to a material that can allow a fluid to pass through, but which inhibits passage of non-fluid substances that are larger than a predetermined size. The terms “filtrate regeneration unit” and “filtrate regeneration system” refer to a system for removing certain electrolytes and waste species including urea from a filtrate produced using filtration. The terms “filtrate regeneration circuit”, “filtrate regeneration loop”, and the like, refer to a flow path containing fluid resulting from filtration; for the removal of certain electrolytes and waste species including urea. The term “filtration” refers to a process of separating solutes from a fluid, by passing the fluid through a filter medium across which certain solutes or suspensions cannot pass. Filtration is driven by the pressure difference across the membrane. The term “first terminal end” of a flow path refers to one end of the flow path and “second terminal end” refers to another end of the flow path. Neither the “first terminal end” nor the “second terminal end” has any limitation on placement on an arterial or venous side. The term “first terminal valve” refers to a valve substantially located at one end of a first fluid conduit without any requirement that the valve be place on an arterial or venous side. Similarly, the term “second terminal valve” refers to a valve substantially located at one end of a second fluid conduit and so on without any limitation on placement on an arterial or venous side. The term “flow loop” refers to a grouping of components that may guide the movement of a fluid, convey the fluid, exchange energy with the fluid, modify the composition of the fluid, measure a characteristic of the fluid and/or detect the fluid. A flow loop comprises a route or a collection of routes for a fluid to move within. Within a flow loop there may be more than one route that a volume of fluid can follow to move from one position to another position. A fluid volume may move through a flow loop such that it recirculates, or passes the same position more than once as it moves through a flow loop. A flow loop may operate to cause fluid volume ingress to and fluid volume egress from the flow loop. The term “flow loop” and “flow path” often may be used interchangeably. The term “flow path” refers to a route or a collection of routes for a fluid to move within. Within a flow path there may be more than one route that a fluid can follow to move from a first position to a second position. A fluid may move through a flow path such that it recirculates, or passes the same position more than once as it moves through a flow path. A flow path may be a single element such as a tube, or a flow path may be a grouping of components of any type that guide the movement of a fluid. The term “flow loop” and “flow path” often may be used interchangeably. Further types of flow paths may be further defined; for example, (1) a recirculation flow path, would be a flow path whose function is in whole or part is to recirculate fluid through the defined flow path; (2) a dialyzer recirculation flow path would be a flow path whose function is in whole or part is to recirculate fluid through the defined flow path having a dialyzer' (3) a controlled compliant flow path would be a flow path would be a flow path that is controlled compliant as defined herein. Any of the defined flow paths may be referred to numerically, as a first flow path, second, third flow path, or fourth flow path, and the like flow paths. The terms “flow restriction”, “flow restriction device” and “flow restrictor” refer to an element or grouping of elements that resist the flow of fluid through the element or grouping of elements such that the fluid pressure within a flow stream that passes through the element or grouping of elements is greater upstream of the element or grouping of elements than downstream of the element or grouping of elements. A flow restrictor may be an active or passive device. Non-limiting examples of passive flow restriction devices are orifices, venturis, a narrowing, or a simple length of tubing with flow cross section that produces the desired pressure drop when the fluid flows through it, such tubing being essentially rigid or compliant. Non-limiting examples of active flow restrictors are pinch valves, gate valves and variable orifice valves. The term “flow stream” refers to fluid moving along a flow path The term “fluid balance control pump” refers to where a control pump is used to adjust the concentration or amount of a solute or fluid in the system. For example, a fluid balance control pump is used for selectively metering in or selectively metering out a designated fluid wherein the concentration or amount of a solute or fluid is adjusted. The term “fluid characteristic” refers to any chemical or biological components that make up or can be found dissolved or suspended in the fluid or gas properties associated with the fluid; or to any physical property of the fluid including, but not limited to temperature, pressure, general or specific conductivities associated with the fluid or related gases. The term “fluid communication” refers to the ability of fluid to move from one component or compartment to another within a system or the state of being connected, such that fluid can move by pressure differences from one portion that is connected to another portion. The term “fluid port” refers to an aperture through which a liquid or gas can be conveyed. The term “fluid port cap or plug” refers to a device that can be connected to a fluid port to prevent fluid from passing through the fluid port. A fluid cap or plug may be configured into an apparatus having multiple caps or plugs to prevent fluid from passing through multiple fluid ports when the apparatus is connected to the multiple fluid ports. The term “flush reservoir” is used to describe a container that can accept or store fluid that is removed from the system during rinsing or cleaning of fluid pathways of the system, including draining the system after cleaning and/or disinfection has been completed. The term “forward osmosis” refers to a filtration method using an osmotic pressure gradient wherein a permeate side of a membrane contains a “draw” solution which has a higher osmotic potential than a feed solution on the other side of the membrane. That higher osmotic potential in the “draw” solution drives the filtration process wherein fluid moves through the membrane and is filtered in the process to dilute the higher solute concentration fluid on the permeate side. The term “gas port” refers to an aperture through which any gaseous form of matter can be conveyed. “Gas phase pressure”, also known as “vapor”, is the equilibrium pressure from a liquid or a solid at a specific temperature. If the vapor is in contact with a liquid or solid phase, the two phases will be in a state of equilibrium. “Hemodiafiltration” is a therapy that combines hemofiltration and hemodialysis. “Hemofiltration” is a therapy in which blood is filtered across a semi-permeable membrane. Water and solutes are removed from the blood via pressure-driven convection across the membrane. The sieving properties of the membrane exclude certain solutes above a certain threshold from crossing the membrane. One common sieving property is “albumin sieving.” In most situations it is not desirable to remove albumin during renal replacement therapy, as lower blood serum albumin is associated with increased mortality rates. In hemofiltration, solutes small enough to pass through the membrane in proportion to their plasma concentration are removed. The driving force is a pressure gradient rather than a concentration gradient. A positive hydrostatic pressure drives water and solutes across the filter membrane from the blood compartment to the filtrate compartment, from which it is drained. Solutes, both small and large, get dragged through the membrane at a similar rate by the flow of water that has been engineered by the hydrostatic pressure. Hence, convection overcomes the reduced removal rate of larger solutes (due to their slow speed of diffusion) observed in hemodialysis. The rate of solute removal is proportional to the amount of fluid removed from the blood circuit, which can be adjusted to meet the needs of a clinical situation. In general, the removal of large amounts of plasma water from the patient requires volume substitution. Substitution fluid, typically a buffered solution close to the plasma water composition a patient needs, can be administered pre or post filter (pre-dilution mode, post-dilution mode). “Hemodialysis” is a technique where blood and a “cleansing fluid” called dialysate are exposed to each other separated by a semi-permeable membrane. Solutes within the permeability range of the membrane pass while diffusing along existing concentration gradients. Water and solutes are also transferred by convection across a pressure gradient that may exist across the dialysis membrane. The dialysate employed during hemodialysis has soluble ions such as sodium, calcium and potassium ions and is not pure water. The sieving properties of the membrane exclude certain solutes above a certain threshold from crossing the membrane. One common sieving property is “albumin sieving.” In most situations it is not desirable to remove albumin during renal replacement therapy, as lower blood serum albumin is associated with increased mortality rates. The term “hemofilter” refers to a apparatus (or may refer to a filter) used in hemofiltration. A hemofilter apparatus can be connected to an extracorporeal circuit and configured to operate with a semipermeable membrane that separates at least a portion of the fluid volume from blood to produce a filtrate fluid. The term “horizontal to a central axis” refers to a relative position of components such as sensors that can be placed in a plane having portions generally horizontal to the central axis. The term “hydrophobic membrane” refers to a semipermeable porous material that may allow gas phases of matter to pass through, but which substantially resists the flow of water through the material due to the surface interaction between the water and the hydrophobic material. The terms “hydrophobic vent” and “hydrophobic vent membrane” refer to a porous material layer or covering that can resist the passage of a liquid such as water through the pores while allowing the passage of a gas. The pores may also be of a sufficiently small size to substantially prevent the passage of microorganisms. “Hemodiafiltration” is a therapy that combines hemofiltration and hemodialysis. The term “perpendicular to a central axis” refers to the position of components, e.g. sensors that can be placed in a plane having portions generally perpendicular to the central axis. The term “in contact” as referred to herein denotes (a) a coming together or touching, as of objects or surfaces; or (b) the state or condition of touching or of being in immediate proximity. “In contact” also includes fluids that are “in fluid communication with” with a solid, such as for example, a fluid, like a dialysate, in contact with a material layer of a sorbent cartridge, or a fluid in contact with a sensor. The term “impedance meter” refers to a device for measuring the opposition of an object or structure to an alternating current. The term “impurity species” refers to solutes in the blood that are in too high of a concentration in the blood from standard ranges known in the art or that are solutes that have resulted from metabolism to generate a non-healthy component now residing in the blood. An “impurity species” is one which is also regarded as a “waste species,” or “waste products”. The term “ion selective electrode” refers to electrodes coated with a material that only allows certain ions to pass through. An “ion selective electrode” (ISE), also known as a specific ion electrode (SIE), is a transducer (or sensor) that converts the activity of a specific ion dissolved in a solution into an electrical potential, which can be measured by a voltmeter or pH meter. The voltage is theoretically dependent on the logarithm of the ionic activity, according to the Nernst equation. The sensing part of the electrode is usually made as an ion-specific membrane, along with a reference electrode. The terms “infusate container” and “infusate reservoir” refer to a vessel, which can be substantially inflexible or non-flexible for holding a solution of one or more salts for the adjustment of the composition of a dialysate. The term “infusate solution” refers to a solution of one or more salts for the adjustment of the composition of a dialysate, such as salts of calcium, magnesium, potassium, and glucose. The term “infusate system” refers to a system that incorporates at least one fluid pathway including components such as conduits, valves, pumps or fluid connection ports, an infusate container or a controller configured to add an infusate solution to the dialysate. The term “interchangeable bicarbonate cartridge” refers to a bicarbonate cartridge that can be configured for removal and replacement with a like bicarbonate cartridge. Interchangeable bicarbonate cartridges can be single use disposable, or re-fillable, re-usable containers. The term “interchangeable sodium chloride cartridge” refers to a sodium chloride cartridge that can be configured for removal and replacement with a like sodium chloride cartridge. Interchangeable sodium chloride cartridges can be single use disposable, or re-fillable, re-usable containers. The terms “introduce” and “introducing” refer to causing a substance to become present where it was not present, or to cause the amount or concentration of a substance to be increased. The term “ion-exchange material” refers to any type of resin or material that can exchange one type of ion for another. The “ion-exchange material” can include anion and cation exchange materials. In one specific case, the term can refer to the removal of ions such as potassium, magnesium, sodium, phosphate and calcium in exchange for other ions such as potassium, sodium, acetate, hydrogen and/or hydroxide. An “ion-exchange resin” or “ion-exchange polymer” is an insoluble matrix (or support structure) that can be in the form of small (1-2 mm diameter) beads, fabricated from an organic polymer substrate. The material has a developed structure of pores on the surface of which are sites with easily trapped and released ions. The trapping of ions takes place only with simultaneous releasing of other ions; thus the process is called ion-exchange. There are multiple different types of ion-exchange resin which are fabricated to selectively prefer one or several different types of ions. In one specific case, the term can refer to the removal of ions such as potassium, magnesium, sodium, phosphate and calcium in exchange for other ions such as potassium, sodium, acetate, hydrogen and/or hydroxide. The term “junction” refers to a common point of connection between two or more flow paths or conduits that allows a liquid and/or a gas to move from one pathway or conduit to another. A junction may be a reversible connection that can be separated when transfer of a liquid and/or gas between the flow paths or conduits is not needed. The term “kidney replacement therapy” as used herein describes the use of a provided system to replace, supplement, or augment the function of a patient with impaired kidney function, such as would occur for a patient with Chronic Kidney Disease. Examples of kidney replacement therapy would include dialysis, hemofiltration, hemodialysis, hemodiafiltration, peritoneal dialysis, and the like. The terms “luer connector” and “luer adapter” refer to adapters or connectors conforming to International Standards Organization (ISO) standards 594-2. The term “manifold” refers to a collection of one or more fluid pathways that are formed within a single unit or subassembly. Many types of manifolds can be used, e.g. a cleaning and/or disinfecting manifold is used to clean or disinfect the defined flow loop when the flow loop is connected to the cleaning and/or disinfecting manifold. The term “material layer” refers to the layers of materials found in a sorbent cartridge. The material layers in a sorbent cartridge may have one or more layers selected from a urease-containing material, alumina, zirconium phosphate, zirconium oxide, and activated carbon. The term “memory” refers to a device for recording digital information that can be accessed by a microprocessor, such as RAM, Dynamic RAM, microprocessor cache, FLASH memory, or memory card. The term “mesh electrode” refers to an electrode in the shape of a mesh, where a mesh consists of a planar structure with openings. The mesh can be made from; overlapping wires or strips, a sheet machined or manufactured to contain holes or openings, or a sheet with a permeable, porous structure. In all cases the mesh is manufactured from materials that result in electrodes, such as titanium, platinum, stainless steel, and iridium. In the case of an electrode mesh consisting of overlapping wires or strips, certain wires or strips can be isolated from other wires or strips with an insulator material in order to apply one polarity to certain wires or strips and the opposite polarity to other wires or strips. The term “metabolic waste species,” as used herein describes organic and inorganic components generated by a patient. They can be metabolic products such as urea, uric acid, creatinine, chlorides, inorganic sulfates and phosphate, or excess electrolytes such as sodium, potassium, etc. It will be understood that the specific “metabolic waste species” can vary between individuals depending on diet and environmental factors. Hence, the term is intended to encompass any waste component that is normally removed by a kidney or by dialysis without restriction on the specific type of waste substance. The term “mid-weight uremic wastes” refers to uremic wastes that can pass through a dialysis membrane and have a molecular weight less than about 66,000 g/mol and greater than about 1000 g/mol. An example of a middle molecule is beta-2 microglobulin. The term “mixing chamber” refers to a chamber or vessel, with one or more inlet and outlet fluid streams, that provides mixing between the fluid streams entering the chamber. The term “moving fluid bi-directionally” as used in connection with a barrier, such as a semi-permeable membrane, refers to the ability to move a fluid across the barrier in either direction. “Moving fluid bi-directionally” also can apply to the ability to move fluid in both directions in the flow loop in a controlled compliant system. A multiplexer” or “mux” is an electronic device that selects one of several analog or digital input signals and forwards the selected input into a single line. The term “nitrogenous waste” refers to any non-polymeric nitrogen-containing organic compound originating from the blood of a patient. Nitrogenous waste includes urea and creatinine, which are both “waste species.” The term “one-way valve” refers to a device that allows flow to pass in one direction through the valve, but prevents or substantially resists flow through the valve in the opposite direction. Such devices can include devices commonly referred to as check valves “Osmolarity” is defined as the number of osmoles of a solute per liter of solution. Thus, a “hyperosmolar solution” represents a solution with an increase in osmolarity compared to physiologic solutions. Certain compounds, such as mannitol, may have an effect on the osmotic properties of a solution as described herein. The term “parallel or wound hollow fiber assembly” refers to any device that incorporates a porous or non-porous hollow fiber material that allows a gas to pass through the material wall of the hollow fibers, but resists the passage of a liquid through the material wall and is configured as multiple strands aligned in parallel or wrapped around a core. The liquid to be degassed may be conveyed through either the inside of the hollow fibers or around the outside of the hollow fibers. Optionally, a gas may be conveyed on the side of the material wall that is opposite the liquid to be degassed. Optionally, a vacuum may be applied on the side of the material wall that is opposite the liquid to be degassed. A “patient” or “subject” is a member of any animal species, preferably a mammalian species, optionally a human. The subject can be an apparently healthy individual, an individual suffering from a disease, or an individual being treated for a disease. The term “parallel to a central axis” refers to the position of components, e.g. sensors that can be placed in a plane having portions generally parallel to the central axis. The terms “pathway,” “conveyance pathway” and “flow path” refer to the route through which a fluid, such as dialysate or blood travels. The term “patient fluid balance” refers to the amount or volume of fluid added to or removed from a subject undergoing a treatment. The term “peristaltic pump” refers to a pump that operates by compression of a flexible conduit or tube through which the fluid to be pumped passes. The term “perpendicular to a central axis” refers to the position of components, e.g. sensors that can be placed in a plane having portions generally perpendicular to the central axis. “Peritoneal dialysis” is a therapy wherein a dialysate is infused into the peritoneal cavity, which serves as a natural dialyzer. In general, waste components diffuse from a patient's bloodstream across a peritoneal membrane into the dialysis solution via a concentration gradient. In general, excess fluid in the form of plasma water flows from a patient's bloodstream across a peritoneal membrane into the dialysis solution via an osmotic gradient. The term “pH-buffer modifying solution” refers to a solution that can reduce the acidity (pH) of the working dialysate solution when added to the dialysate The term “pH-buffer sensor” refers to a device for measuring the acidity or basicity (pH) and the buffer concentration of the dialysate solution. The term “pH-buffer management system” refers to a system managing the pH and buffer concentration of a dialysate by adding, removing or generating a fluid to the dialysate such that the dialysate is modified by the pH-buffer management system to have a different pH and buffer concentration. The term “pH-buffer measurement system” refers to a system measuring the pH and/or buffer concentration of a dialysate or fluid within the system. The terms “portable system” and “wearable system” refers to a system in whole or in part having a mass and dimension to allow for transport by a single individual by carrying the system or wearing the system on the individual's body. The terms are to be interpreted broadly without any limitation as to size, weight, length of time carried, comfort, ease of use, and specific use by any person whether man, woman or child. The term is to be used in a general sense wherein one of ordinary skill will understand that portability as contemplated by the invention encompasses a wide range of weights, geometries, configurations and size. The term “potable water” refers to drinking water or water that is generally safe for human consumption with low risk of immediate or long term harm. The level of safety for human consumption can depend on a particular geography where water safe for human consumption may be different from water considered safe in another jurisdiction. The term does not necessarily include water that is completely free of impurities, contaminants, pathogens or toxins. Other types of water suitable for use in the present invention can include purified, deionized, distilled, bottled drinking water, or other pre-processed water that would be understood by those of ordinary skill in the art as being suitable for use in dialysis. The term “potassium-modified fluid” refers to fluid having a different conductivity or potassium concentration compared to a second fluid to which the potassium-modified fluid is added to modify the conductivity or potassium concentration of the second fluid. The terms “physiologically compatible fluid” and “physiological compatible solution” refer to a fluid that can be safely introduced into the bloodstream of a living subject. The term “plumbing,” as used herein generally describes any system of valves, conduits, channels, and lines for supplying any of the fluids used in the invention. The term “porosity,” as used herein describes the fraction of open pore volume of a membrane. The terms “pressure differential” and “pressure drop” refer to the difference in pressure measurements of a fluid between two points of measurement. The terms “pressure meter” and “pressure sensor” refer to a device for measuring the pressure of a gas or liquid in a vessel or container. The terms “priming process” and “priming” refer to the process of conveying a liquid into the void volume of a fluid pathway to fill the pathway with liquid. The term “priming volume” refers to the volume of priming fluid required to fill the void volume of the subject pathway, device, or component, as the particular case may be. The term “priming overflow reservoir” refers to a reservoir which during priming is used to collect the overflow of fluid during the priming process. The terms “processor,” “computer processor,” and “microprocessor” as used herein are broad terms and are to be given their ordinary and customary meaning to a person of ordinary skill in the art. The terms refer without limitation to a computer system, state machine, processor, or the like designed to perform arithmetic or logic operations using logic circuitry that responds to and processes the basic instructions that drive a computer. In some embodiments, the terms can include ROM (“read-only memory”) and/or RAM (“random-access memory”) associated therewith. The term “programmable” as used herein refers to a device using computer hardware architecture with a stored program and being capable of carrying out a set of commands, automatically that can be changed or replaced. The term “pump” refers to any device that causes the movement of fluids or gases by the application of suction or pressure. The term “pulsatile pump” refers to a pump where the pumped fluid undergoes periodic variation in velocity and/or pressure. The terms “pump rate” and “volumetric pumping rate” refer to the volume of fluid that a pump conveys per unit of time. The term “purified water” refers to water that has been physically processed to remove at least a portion of at least one impurity from the water. The term “outlet stream” refers to a fluid stream exiting a chamber, vessel or cartridge. The terms “reconstitute” and “reconstituting” refer to creating a solution by addition of a liquid to a dry material or to a solution of higher concentration to change the concentration level of the solution. A “reconstitution system” in one use, is a system that rebalances the dialysate in the system to ensure it contains the appropriate amount of electrolytes and buffer. The term “refilled” refers to having replenished or restored a substance that has been consumed or degraded. The terms “sorbent regeneration”, “sorbent regeneration system”, “sorbent system, and the like, refer, in context, to devices that are part of a sorbent regenerated dialysate delivery system for hemodialysis, functioning as an artificial kidney system for the treatment of patients with renal failure or toxemic conditions, and that consists of a sorbent cartridge and the means to circulate dialysate through this cartridge and the dialysate compartment of the dialyzer. The device is used with the extracorporeal blood system and the dialyzer of the hemodialysis system and accessories. The device may include the means to maintain the temperature, conductivity, electrolyte balance, flow rate and pressure of the dialysate, and alarms to indicate abnormal dialysate conditions. The sorbent cartridge may include absorbent, ion exchange and catalytics. The term “shunt,” as most often used herein describes a passage between channels, in the described filtration and purification systems, wherein the shunt diverts or permits flow from one pathway or region to another. An alternate meaning of “shunt” can refer to a pathway or passage by which a bodily fluid (such as blood) is diverted from one channel, circulatory path, or part to another. The term “bypass” can often be used interchangeably with the term “shunt.” The term “sodium-concentrate solution” refers to a solution having a high concentration of sodium ions relative to another solution or fluid. The terms “sodium chloride cartridge” and “sodium chloride container” refer to an object that can be a stand-alone enclosure or alternatively can be integrally formed with an apparatus for hemodialysis, hemodiafiltration, or hemofiltration. The object can store a source of sodium, such as sodium chloride in solid and/or solution form, and can be configured to interface with at least one other functional module found in systems for hemodialysis, hemodiafiltration, or hemofiltration. For example, the sodium chloride cartridge or container can contain at least one fluid pathway and include components such as conduits, valves, filters or fluid connection ports. The term “regenerative capacity of the sorbent” refers to the remaining capacity for the sorbent cartridge or a particular material layer of the sorbent cartridge to perform its intended function. The term “regenerative substance” refers to a sorbent material contained in a “regeneration module.” The term “first chosen regenerative substance,” as used in the present invention refers to a particular regenerative substance, identified as “first chosen regenerative substance.” The term “second chosen regenerative substance” refers to a particular regenerative substance, identified as “second chosen regenerative substance.” The term “regeneration module” refers to an enclosure having one or more sorbent materials for removing specific solutes from solution, such as urea. In certain embodiments, the term “regeneration module” refers to one or more regeneration cartridge or regeneration unit. In certain embodiments, the term “regeneration module” includes configurations where at least some of the materials contained in the module do not act by mechanisms of adsorption or absorption. The terms “remnant volume” and “residual volume” refer to the volume of fluid remaining in a fluid flow path after the fluid flow path has been partially emptied or evacuated. The terms “replacement fluid” and “substitution fluid” refer to fluid that is delivered to the blood of a subject undergoing convective renal replacement therapies such as hemofiltration or hemodiafiltration in order to replace at least a portion of the fluid volume that is removed from the subject's blood when the blood is passed through a hemofilter or a dialyzer. The term “reserve for bolus infusion” refers to an amount of solution available, if needed, for the purpose of administering fluid to a subject receiving therapy, for example, to treat an episode of intradialytic hypotension. The term “reusable” refers to an item that is used more than once. Reusable does not imply infinitely durable. A reusable item may be replaced or discarded after one or more use. The term “reverse osmosis” refers to a filtration method of forcing a solvent from a region of high solute concentration through a semi-permeable membrane to a region of low solute concentration by applying a pressure in excess of osmotic pressure. To be “selective,” this membrane should not allow large molecules or ions through the pores (holes), but should allow smaller components of the solution (such as the solvent) to pass freely. The term “reverse osmosis rejection fraction” refers to the resulting solute that is retained on the pressurized side of the membrane and the pure solvent is allowed to pass to the other side in a reverse osmosis system. The term “reversible connections” refers to any type of detachable, permanent or non-permanent connection configured for multiple uses. The term “salination pump” refers to a pump configured to move fluid and/or control movement of fluid through a conditioning flow path, such as through or from a source of a conditioning material such as sodium chloride or sodium bicarbonate. The term “salination valve” refers to a valve configured to control the flow of fluid in a conditioning flow path, such as through or from a source of a conditioning material such as sodium chloride or sodium bicarbonate. The term “segment” refers to a portion of the whole, such as a portion of a fluid flow path or a portion of a fluid circuit. A segment is not limited to a tube or conduit, and includes any grouping of elements that are described for a particular segment. Use of the term “segment,” by itself, does not imply reversible or detachable connection to another segment. In any embodiment, a segment may be permanently connected to one or more other segments or removably or detachably connected to one or more segments. The terms “selectively meter fluid in” and “selectively meter fluid out” generally refer to a process for controllably transferring fluids from one fluid compartment (e.g. a selected patient fluid volume, flow path, or reservoir) to another fluid compartment. One non-limiting example is where a control pump may transfer a defined fluid volume container, reservoirs, flow paths, conduit of the controlled compliant system. When fluid is moved from a reservoir into another part of the system, the process is referred to as “selectively metering fluid in” as related to that part of the system. Similarly, one non-limiting example of removing a defined volume of dialysate from a dialysate flow path in a controlled compliant system and storing the spent dialysate in a control reservoir, can be referred to as “selectively metering-out” the fluid from the dialysate flow path. The terms “semi-permeable membrane”, “selectively permeable membrane”, “partially permeable membrane”, and “differentially permeable membrane”, refer to a membrane that will allow certain molecules or ions to pass through it by diffusion and occasionally specialized “facilitated diffusion”. The rate of passage depends on the pressure, concentration, and temperature of the molecules or solutes on either side, as well as the permeability of the membrane to each solute. The term “semi-permeable membrane” can also refer to a material that inhibits the passage of larger molecular weight components of a solution while allowing passage of other components of a solution having a smaller molecular weight. For example, Dialyzer membranes come with different pore sizes. Those with smaller pore size are called “low-flux” and those with larger pore sizes are called “high-flux.” Some larger molecules, such as beta-2-microglobulin, are not effectively removed with low-flux dialyzers. Because beta-2-microglobulin is a large molecule, with a molecular weight of about 11,600 daltons, it does not pass effectively through low-flux dialysis membranes. The term “sensor,” which can also be referred to as a “detector” in certain instances, as used herein can be a converter that measures a physical quantity of a matter in a solution, liquid or gas, and can convert it into a signal which can be read by an electronic instrument. The term “sensor element” refers to a device or component of a system that detects or measures a physical property. The terms “sodium management system” and “sodium management” broadly refer to a system or process that can maintain the sodium ion concentration of a fluid in a desired range. In certain instances, the desired range can be within a physiologically-compatible range. The sodium ion concentration of an input solution can be modified by any means including application of an electrical field. The term “sodium-modified fluid” refers to fluid having a different conductivity or sodium concentration compared to a second fluid to which the sodium-modified fluid is added to modify the conductivity or sodium concentration of the second fluid. The term “sodium conduit flow path” refers to a flow path in fluid communication with a sodium chloride cartridge which then can pump saturated sodium solution into the dialysate by pumping and metering action of a salination pump. The term “sodium source” refers to a source from which sodium can be obtained. For example, the sodium source can be a solution containing sodium chloride or a dry sodium chloride composition that is hydrated by the system. The term “solid potassium” refers to a solid composition containing a salt of potassium such as potassium chloride at any purity level. In general, the solid potassium will be easily soluble in water to form a solution. The term “solid sodium” refers to a solid composition containing a salt of sodium such as sodium chloride at any purity level. In general, the solid potassium will be easily soluble in water to form a solution and of high purity. The term “solid bicarbonate” refers to a composition containing a salt of bicarbonate such as sodium bicarbonate at any purity level. In general, the solid bicarbonate will be easily soluble in water to form a solution. The term “solute” refers to a substance dissolved, suspended, or present in another substance, usually the component of a solution present in the lesser amount. The terms “sorbent cartridge” and “sorbent container” refer to a cartridge containing one or more sorbent materials for removing specific solutes from solution, such as urea. The term “sorbent cartridge” does not necessarily require the contents in the cartridge be sorbent based. In this connection, the sorbent cartridge may include any suitable amount of one or more sorbent materials. In certain instances, the term “sorbent cartridge” refers to a regeneration cartridge which may include one or more sorbent materials in addition to one or more other regeneration materials. “Sorbent cartridge” includes configurations where at least some of the materials contained in the cartridge do not act by mechanisms of adsorption or absorption. The term “source of cations” refers a source from which cations can be obtained. Examples of cations include, but are not limited to, calcium, magnesium and potassium. The source can be a solution containing cations or a dry composition that is hydrated by the system. The cation infusate source is not limited to cations and may optionally include other substances to be infused into a dialysate or replacement fluid. Non-limiting examples include glucose, dextrose, acetic acid and citric acid. The term “specified gas membrane permeability” refers to a determined rate at which a gas membrane will allow a gas to pass through the membrane from a first surface to a second surface, the rate being proportional to the difference in absolute pressure of the gas in proximity to the first side of the membrane and in proximity to the second side of the membrane. The term “spent dialysate” refers to a dialysate that has been contacted with blood through a dialysis membrane and contains one or more impurity, or waste species, or waste substance, such as urea. The term “static mixer” refers to a device that mixes two or more component materials in a fluid solution without requiring the use of moving parts. The term “substantially inflexible volume” refers to a three-dimensional space within a vessel or container that can accommodate a maximum amount of non-compressible fluid and resists the addition of any volume of fluid above the maximum amount. The presence of a volume of fluid less than the maximum amount will fail to completely fill the vessel or container. Once a substantially inflexible volume has been filled with a fluid, removal of fluid from that volume will create a negative pressure that resists fluid removal unless fluid is added and removed simultaneously at substantially equal rates. Those skilled in the art will recognize that a minimal amount of expansion or contraction of the vessel or container can occur in a substantially inflexible volume; however, the addition or subtraction of a significant volume of fluid over a maximum or minimum will be resisted. The term “tap water” refers to water, as defined herein, from a piped supply. The term “temperature sensor” refers to a device that detects or measures the degree or intensity of heat present in a substance, object, or fluid. A “therapy solution reservoir” refers to any container or reservoir that holds a physiological compatible fluid. The term “total bicarbonate buffer concentration” refers to the total concentration of bicarbonate (HCO3−) ion and a conjugate acid of bicarbonate in a solution or composition. A “therapy solution reservoir” refers to any container or reservoir that holds a physiological compatible fluid. The terms “treating” and “treatment” refer to the management and care of a patient having a pathology or condition by administration of one or more therapy contemplated by the present invention. Treating also includes administering one or more methods of the present invention or using any of the systems, devices or compositions of the present invention in the treatment of a patient. As used herein, “treatment” or “therapy” refers to both therapeutic treatment and prophylactic or preventative measures. “Treating” or “treatment” does not require complete alleviation of signs or symptoms, does not require a cure, and includes protocols having only a marginal or incomplete effect on a patient. The term “uremic wastes” refers to a milieu of substances found in patients with end-stage renal disease, including urea, creatinine, beta-2-microglobulin. The term “ultrafiltrate” refers to fluid that is removed from a subject by convection through a permeable membrane during hemodialysis, hemofiltration, hemodiafiltration, or peritoneal dialysis. The term “ultrafiltrate,” as used herein, can also refer to the fluid in a reservoir that collects fluid volume removed from the patient, but such a reservoir may also include fluids or collections of fluids that do not originate from the subject. The term “ultrafiltration” refers to subjecting a fluid to filtration, where the filtered material is very small; typically, the fluid comprises colloidal, dissolved solutes or very fine solid materials, and the filter is a microporous, nanoporous, or semi-permeable medium. A typical medium is a membrane. During ultrafiltration, a “filtrate” or “ultrafiltrate” that passes through the filter medium is separated from a feed fluid. In general, when transport across a membrane is predominantly diffusive as a result of a concentration driving force, the process is described herein as dialysis. When transport is primarily convective as a result of bulk flow across the membrane induced by a pressure driving force, the process is ultrafiltration or hemofiltration depending on the need for substitution solution as the membrane passes small solutes but rejects macromolecules. The term “ultrafiltration” can also refer to the fluid removal from blood during a dialysis or a hemofiltration process. That is, ultrafiltration refers to the process of passing fluid through a selective membrane, such as a dialysis or hemofiltration membrane, in either a dialysis, a hemodiafiltration, or a filtration process. The terms “unbuffered sodium bicarbonate” and “solution of unbuffered sodium bicarbonate” refer to a sodium bicarbonate composition that is not buffered with a conjugate acid or base in any amount, proportion or pH adjusted. The term “upstream” refers to a direction opposite to the direction of travel of a moving dialysate or other fluid within a conduit or flow path. The term “Urea Reduction Ratio” or “URR” refers to a ratio defined by the formula below: URR=Upre-UpostUpre×100% Where: Upreis the pre-dialysis urea level Upostis the post-dialysis urea level Whereas the URR is formally defined as the urea reduction “ratio”, in practice it is informally multiplied by 100% as shown in the formula above, and expressed as a percent. The term “urea sensor” refers to a device for measuring or allowing for the calculation of urea content of a solution. The “urea sensor” can include devices measuring urease breakdown of urea and measurement of the resulting ammonium concentration. The sensing methods can be based on any one of conductimetric, potentiometric, thermometric, magnetoinductic, optical methods, combinations thereof and other methods known to those of skill in the art. The term “vacuum” refers to an action that results from application of a pressure that is less than atmospheric pressure, or negative to the reference fluid or gas. The term “vent” as referred to in relationship to a gas, refers to permitting the escape of a gas from a defined portion of the system, such as, for example, as would be found in the degassing module. The term “void volume” refers to a specific volume that can be occupied by a fluid in a defined space such as a dialysate circuit of the invention including all components contained therein. The terms “waste species,” “waste products” and “impurity species” refers to any molecular or ionic species originating from the patient or subject, including metabolic wastes, molecular or ionic species including nitrogen or sulfur atoms, mid-weight uremic wastes and nitrogenous waste. Waste species are kept within a specific homeostasis range by individuals with a healthy renal system. The term “waste fluid” refers to any fluid that does not have a present use in the operation of the system. Non-limiting examples of waste fluids include ultrafiltrate, or fluid volume that has been removed from a subject undergoing a treatment, and fluids that are drained or flushed from a reservoir, conduit or component of the system. The term “water feed” refers to a source of water that is added to a dialysate flow path by means of a pump or other delivery system. The term “water source” refers to a source from which potable or unpotable water can be obtained. The term “water source connection” or “water feed” refers to a state of fluid communication that enables water to be obtained from a water source and connected or feed into a receiving source or flow path. The term “within” when used in reference to a sensor or electrode located “within” the sorbent cartridge refers to all, or part of the sensor or electrode is located inside, or encased by, at least part of the inner chamber formed from the sorbent cartridge wall. The term “working dialysate solution” refers to a dialysate solution that is undergoing active circulation or movement through a system including conduits, pathways, dialyzers and cartridges. Measuring Dialysis End stage renal disease (ESRD) results in a clinical condition called uremia, a toxic state resulting from accumulation in blood and tissues of solutes that are normally excreted by the kidneys. An important function of hemodialysis is to treat uremia by blood purification that removes the toxic solutes directly from the blood and indirectly from other tissues. Diffusive removal of small solutes across a semipermeable membrane by concentration gradient between blood and dialysate is the technique responsible for much of the blood purification that occurs during hemodialysis. The proportion of accumulated toxins removed from the blood and tissue by hemodialysis therapy can be used to quantify the dialysis dose. There are many solutes that accumulate at different rates in association with uremia. Medical science has not fully evaluated all of the solutes nor determined acceptable blood and tissue concentrations for each solute. Given this situation, clearance of a marker solute, urea, is commonly utilized to quantify the general dialysis dose given. Further, clearance of the marker solute, urea, has been correlated to morbidity and mortality of ESRD patients being treated by dialysis The principal waste species removed during treatment of a patient is urea that accumulates in the blood of individuals based on various degrees of kidney disease or impairment. Since urea is an electrically neutral species, a dialysate regeneration unit can convert urea to a charged ammonium species that can then be removed from the circulating dialysate within the dialysate flow loop. However, in order to maintain electrical neutrality, the removal of charged ammonium species has to be matched by exchange with another charged species, which is sodium ion in certain embodiments. As such, the concentration of sodium ions can increase over time through use of the sorbent materials and can be specifically monitored by the conductivity monitoring system. Loss of renal function also can result in loss of the ability to balance the intake and elimination of calcium, magnesium, potassium and phosphorus that is necessary to maintain homeostasis within the tight range necessary for health. Regulation of calcium and magnesium within these tight ranges is critical to physiologic function. Altered mineral metabolism, including calcium and magnesium, contributes to bone disease, cardiovascular disease, and other clinical problems in patients with end-stage renal disease. Disorders of mineral metabolism are independently associated with mortality and morbidity associated with cardiovascular disease and fracture in hemodialysis patients, and increased serum calcium concentration is associated with increased risk of death in hemodialysis patients. Hypermagnesemia can be manifested by hypocalcaemia, hypotension, bradycardia, osteodystrophy and bone pain, impaired cardiac contractility and intradialytic hemodynamic instability, atherosclerosis and vascular calcification, and has been demonstrated as a significant determinant, inversely correlated to serum parathyroid concentration, independent of calcium and phosphorus. Calcium and magnesium exist in the blood in free ionized and bound forms, but it is the serum ionized form that is biologically active and integrated into the body's regulatory systems that maintain homeostasis. Although ionized serum calcium is most important, total serum calcium is typically measured for hemodialysis patients, due to the lower cost and ready availability of the test for total calcium, as opposed to serum ionized calcium. Total serum calcium measurements do not assess hypocalcaemia and hypercalcaemia as accurately as ionized serum calcium measurements and, further, methods to determine adjusted serum calcium are no more accurate than total serum calcium measurements in predicting hypo and hypercalcaemia. Further, while an individual's diet and medications may cause calcium and magnesium levels to fluctuate daily, for reasons of cost and convenience, the blood tests are typically performed only monthly. The United States National Kidney Foundation Dialysis Outcome Quality Initiative (DOQI) has approved three measures for monitoring delivered hemodialysis dose for thrice-weekly treatment: urea reduction ratio (URR), Kt/V by urea kinetic modeling (UKM), and Kt/V by the second generation Daugirdas formula. Each measurement method utilizes, at a minimum, pre- and post-dialysis blood urea (BUN) measurements. It will be understood by those of skill in the art that URR is a relatively simple method to quantify dialysis dose as proposed by Lowrie et al. (Lowrie E G, Lew N L. “The urea reduction ratio (URR): A simple method for evaluating hemodialysis treatment.” Contemp Dial Nephrol. 1991; 12:11-20). URR is the ratio of urea removed to starting urea, calculated: URR=(BUNpre-BUNpost)BUNpre(Equation1)where,BUNpre—blood urea concentration at start of dialysis sessionBUNpost—blood urea concentration at end of dialysis session Kt/V is a dimensionless expression of the fractional clearance of urea, where,K—dialyzer clearance rate of urea (mL/min)t—dialysis time (min)V—volume of distribution of urea, approximately equal to patient's total body water (mL) It will be understood by those of skill in the art that Urea Kinetic Modeling (UKM) is a complex, computer-based method of estimating urea clearance developed by Gotch and Sargent to quantify dialysis dose based on data from a National Cooperative Dialysis Study (Gotch F A, Sargent J A “A mechanistic analysis of the National Cooperative Dialysis Study (NCDS)”.Kidney int.1985; 28:526-34). UKM includes factors for estimated dialyzer clearance, dialysis session time, and the patient's urea distribution volume, urea generation rate, pre and post-dialysis BUN, ultrafiltration volume, interdialytic weight gain, interdialytic interval, and clearance by residual renal function. Urea distribution volume is equal to the total volume in a patient where urea is present, and is approximately equal to the volume of water in a patient. A computer is used in UKM to iteratively solve two equations until the solution converges. A second generation Daugirdas formula calculates Kt/V from pre and post-dialysis BUN, dialysis session time, ultrafiltration volume, and post-dialysis weight (Daugirdas J T. “Second generation logarithmic estimates of single-pool variable volume Kt/V: and analysis of error.” J Am Soc Nephrol. 1993; 4:1205-13). It will be appreciated by those of skill in the art that each of the three methods approved by the United States National Kidney Foundation Dialysis Outcome Quality Initiative (DOQI) for measuring delivered hemodialysis dose require, at minimum, two measurement of the patient's blood urea concentration. Conductivity Monitor The present invention provides for the determination of urea content (amount or concentration) in a spent dialysate in real-time for determination of adequacy or efficiency of dialysis therapy including but not limited to hemodialysis and hemodiafiltration, and also ultrafiltration. In particular, the invention is directed toward a conductivity monitor that can operate with a dialysate regeneration unit to perform dialysis with a limited volume of dialysate. In any embodiment, a working dialysate fluid can be circulated in a dialysis flow loop between a dialyzer and a dialysate regeneration unit, certain embodiments of which include a dialysate regeneration cartridge. Spent dialysate containing at least one waste species elutes from an outlet of the dialyzer during treatment where the spent dialysate is passed through the dialysate regeneration unit where waste species including urea are removed from the dialysate. Using the dialysate regeneration unit, the working dialysate can be regenerated for recirculation through the dialyzer by the removal of waste species and the re-addition and/or re-constitution of species needed for a biocompatible dialysate, such as buffers, calcium ions, potassium ions, magnesium ions and other components typically employed for dialysate solutions. The conductivity monitor operating with systems and methods can also provide inputs for the monitoring of sodium ion concentration and/or conductivity of the dialysate and operate with a means to add a sodium-modified fluid or other infusates to the dialysate flow loop when needed to adjust conductivity or electrolyte concentration. Blood circulating through a dialyzer via an extracorporeal circuit exchanges waste components with dialysate circulating through the dialyzer and dialysate flow loop. Waste species including ions and uremic toxins, such as uric acid, creatinine, and β2-microglobin, and urea diffuse from the blood to the dialysate within the dialyzer via a semipermeable membrane contained therein. As such, the limited volume of dialysate within the dialysate flow loop can reach equilibrium with the content of waste species in the blood without ongoing removal of waste species from the dialysate to maintain a concentration gradient of waste species between the blood and the dialysate within the dialysate flow loop. During treatment employing the dialysate regeneration unit, the urea content of the spent dialysate will normally be less than the actual urea content of the blood due to on-going removal of urea from the dialysate as part of dialysate regeneration. The urea concentration difference between the blood and the dialysate depends on several factors (e.g. point in treatment, flow rates, dialyzer efficiency, etc.) such that urea content of the blood cannot be readily determined solely through measurement of real-time concentration of urea in the dialysate. The sensing components, systems and methods of the invention can provide real-time information regarding cleared solutes within the dialysate stream that can be applied to detect and measure these factors so that corrective action can be taken within the dialysis session or between dialysis sessions to ensure that the dialysis session clearance goals are met. Dialysis standards of care are used to establish specific session clearance goals (Kt/V) that are to be achieved by hemodialysis treatment. The invention can also demonstrate and document that a prescribed clearance, Kt/V, has been achieved by the dialysis therapy provided. The present invention can also provide for urea Kt to be measured directly such that clearance is documented in the medical record. Similarly, measurements of urea reduction ratio (URR) and equilibrated Kt/V (eKt/V) are also documented. Many factors can compromise the effective clearance achieved during a dialysis session such that clearance, Kt/V, differs from what would be predicted by the configuration of the dialyzer, dialysis and blood flow rates, etc. Factors include blood access recirculation, access connection errors, dialyzer clotting, blood flow errors, dialysis session interruptions, and dialyzer variability. However, in any embodiment, the sensing methods of the present invention can provide real-time information regarding cleared solutes within the dialysate stream that can be applied to detect and measure these factors so that corrective action can be taken within the dialysis session or between dialysis sessions to ensure that the dialysis session clearance goals are met. In any embodiment, a dialysate regeneration cartridge, such as a sorbent cartridge, can contain several materials and/or sorbents that are capable of removing solutes from the dialysate including: urea, phosphate, calcium, magnesium, potassium, creatinine, uric acid, beta-2-microglobulin and sulfate. The regeneration cartridge can also contain components or materials that release or bind sodium during the process of removing solutes from the dialysate. For example, the dialysate regeneration cartridge can be a sorbent cartridge containing activated carbon, urease, zirconium phosphate and hydrous zirconium oxides. In particular, a urease-containing material can convert neutral urea to an ammonium salt that affects the conductivity of the dialysate and allows for ammonium, and hence nitrogen, to be removed by cation exchange with other sorbent materials. In certain embodiments, the urease-material and sorbent materials can be contained in a single housing. In other embodiments, the urease-material and sorbent materials can be contained in multiple housings including two or more housings. In some embodiments, a conductivity monitoring system is provided for measuring the conductivity change in the dialysate affected by specific sorbent and/or urease-containing materials individually or in combination. For example, the conductivity monitoring system can measure the change in conductivity of spent dialysate prior to contact with the urease-containing material and after completing contact with the urease-containing materials. As such, the change in conductivity caused by the conversion of urea to ammonium salts can be determined prior to downstream contact with other materials that may further affect conductivity. In other embodiments, the conductivity monitoring system can measure the change in conductivity affected by non-urease containing materials to evaluate the effectiveness and performance of sorbent materials. Regeneration of the dialysate within the dialysate flow loop can be achieved through contacting the dialysate with sorbents contained within the dialysate generation unit. Examples of useful sorbent materials include the REDY sorbent system and U.S. Pat. Nos. 3,669,880; 3,989,622; 4,581,141; 4,460,555; 4,650,587; 3,850,835; 6,627,164; 6,818,196; and 7,566,432 and U.S. Patent Publications 2010/007838; 2010/0084330; and 2010/0078381 and International Patent Publication WO 2009/157877 A1, which are incorporated herein by reference. In some embodiments, the dialysate regeneration unit with one or more sorbent cartridges can contain one or more materials selected from the group consisting of: 1) a urease-containing material, where urease is an enzyme that catalyzes the conversion of urea to ammonium ions and carbon dioxide; 2) a zirconium phosphate (ZrP) material that has the capacity to act as a cation exchanger by absorbing a large quantity of ammonium ions in exchange for sodium and hydrogen ions; 3) a zirconium oxide material (ZrO), which acts as an anion exchanger by exchanging phosphate for acetate; and 4) an activated carbon material that has a surface area for adsorption of wide range of impurities including metal ions and uremic toxins, such as uric acid, creatinine, and β2-microglobin. The term zirconium oxide is used interchangeably with the term hydrous zirconium oxide. In some embodiments, the zirconium phosphate material can be replaced with a magnesium phosphate material. In some embodiments, the urease and/or sorbent materials used for dialysate regeneration include a layer of urease and alumina that converts urea in spent dialysate into ammonium, which changes the conductivity of the dialysate fluid as the fluid flows through a dialysate regeneration unit. The difference in conductivity measured in the dialysate pre- and post-contact with a urease-containing material is correlated to the amount of urea removed during hemodialysis therapy. The methods disclosed make use of solution conductivity increase that occurs as a result of the ionic byproducts of catalytic hydrolysis of urea by the enzyme urease according to In some embodiments, a single conductivity meter or detector can measure multiple flow streams, where each flow stream represents the spent dialysate contacted with a different combination of urease-containing materials and/or sorbents, or the spent dialysate prior to any contact with urease-containing materials and/or sorbents. As such, calibration, temperature, electronic drift and other errors between separate conductivity meters can be reduced or eliminated. The ability to monitor conductivity changes affected by different combinations of urease-containing materials and/or sorbents allows for the performance or efficiency of various system components to be evaluated as well as the determination of the amount of urease in the dialysate. In certain embodiments, the urease-containing material and additional sorbent materials are interdispersed within the same housing. The performance of conversion of urea to ammonia can be monitored and determined by intermittently providing a bolus of a sodium chloride solution to the dialysate regeneration cartridge such that the urea content of spent dialysate entering the regeneration cartridge can be determined. In certain embodiments, an equilibration bypass is provided to allow for the dialysate within the dialysate flow loop to come into equilibration with the urea concentration of the blood in contact with the dialyzer. After equilibration, the conductivity monitoring system can determine the urea content of the equilibrated dialysate, which reflects the urea content of the blood. In certain embodiments, the components of the dialysate flow loop can have a controlled compliant volume. As such, fluid is in passive equilibrium and does not provide for net flow from the extracorporeal circuit to the dialysate flow loop due to the controlled compliant volume of the dialysate loop. The net balance of fluid is prevented from passively flowing between the flow loop to the extracorporeal circuit via the dialyzer since such a movement of fluid will leave a vacuum in the flow loop or require the flow loop to expand. Since the dialyzer can be a high-flux type that readily allows for the passage of water, there is some fluid flux back and forth across the dialyzer membrane due to the pressure differential on the blood and dialysate sides of the membrane. This is a localized phenomenon due to the low pressure required to move solution across the membrane and is called backfiltration; however, this results in no net fluid gain or loss by the patient. The components forming the dialysate flow loop of the invention can have a controlled compliant volume wherein the dialysate flow loop further incorporates a control or ultrafiltration pump that can be operated bi-directionally to cause the net movement of fluid from an extracorporeal side of the dialyzer into the dialysis flow loop or to cause net movement of fluid from the dialysate flow loop into the extracorporeal side of the dialyzer. In particular, a control or ultrafiltration pump is operated in the efflux direction to cause the movement of fluid from the extracorporeal side of the dialyzer into the dialysis flow loop and in the influx direction to cause the movement of fluid from the dialysis flow loop into the extracorporeal side of the dialyzer. The action of typical pumps contemplated by the invention function by expanding or contracting a space wherein any suitable type of pump can be used in the present invention. In certain embodiments, operation of the control or ultrafiltration pump in the influx direction can be substituted with operation of the infusate pump to drive liquid from the infusate reservoir into the dialysis flow loop and subsequently cause movement of fluid from the dialysis flow loop to the extracorporeal side of the dialyzer. The control or ultrafiltration pump can also be used for the movement of fluid in the opposite direction across the dialyzer into the dialysis flow loop. It is noted that the infusate reservoir or ultrafiltrate reservoir can allow the system to adjust the patient fluid volume by withdrawing fluid and storing the desired amount in the respective reservoir and/or by providing rebalanced fluids to the patient and removing waste products. For example, the fluid stored in a control reservoir attached to the dialysate circuit can be used to store a volume of fluid equal to the ultrafiltrate volume removed from the patient during ultrafiltration (UF). Alternatively, the fluid stored in the control reservoir can be an infusate delivered to the patient. In certain embodiments, the delivered fluid can contain a therapeutic component deliverable across the dialyzer and into the patient's bloodstream. Additionally, the volume of the dialysate flow loop can be actively controlled by the user or a programmed controller. The control or ultrafiltration pump allows for fluid to move from the dialysate flow loop to the extracorporeal side without creating a vacuum, wherein the operation of the control pump is controlled as described herein. Likewise, the control pump allows for fluid to move from the extracorporeal side, and hence the patient's body via the action of the control pump. Movement of fluid between the extracorporeal side of the dialyzer and the dialysate flow loop can be accurately controlled and metered using the removed fluid in certain embodiments. In other embodiments, the removed fluid can be transferred back to the patient through the dialysate flow loop using the ultrafiltrate stored in ultrafiltration reservoir. In some embodiments, the ultrafiltration reservoir can be prefilled with water, dialysate or other fluid for addition to the dialysate flow loop and/or for use or treatment within the sodium control system. As such, some embodiments have a controlled compliant dialysate flow loop that can be accurately controlled to precisely remove or add fluid to the extracorporeal side of the dialyzer. Due to the substantially inflexible void volume of the conduits, the dialysate regeneration unit and other components of the dialysate flow loop, the net movement of fluid over any time interval across the dialysate membrane within the dialyzer can be accurately controlled by creating a means to accurately introduce or remove fluid from the patient. This capability can further be used to enhance the convective clearance of the system for uremic impurities while controlling the net fluid removed from the patient, for example, creating periods of fluid movement across the membrane with occasional reversal of direction. In certain embodiments, an ultrafiltrate can be used as described herein. However, the present invention is not limited to a controlled compliant flow path. As such, the dialysate flow loop in certain embodiments is not a controlled compliant flow path and may include one or more open reservoir for storing or accumulating dialysate. In certain embodiments, a control pump can be a peristaltic pump, a volumetric metering pump, diaphragm pump, or a syringe style pump. Hence, the dialysate flow loop has a substantially inflexible volume except for controlled changes in volume modulated by the control or ultrafiltration pump, the infusion pump and optionally any other pumps that add fluid to the dialysate flow loop. The contents of U.S. patent application Ser. No. 13/565,733 filed on Aug. 2, 2012 are incorporated herein by references in their totality. In certain embodiments, the dialysate flow loop has a void volume from about 0.15 L to about 0.5 L. In other embodiments, the dialysate flow loop has a void volume from about 0.2 L to about 0.4 L or from 0.2 L to about 0.35 L. Other volumes can be envisioned by those of ordinary skill in the art depending on parameters such as patient weight, size, and health condition. The system can be designed to be a portable system, a desktop system or a large system suitable for heavy use in a clinical setting. Hence, both large volumes greater than 0.5 L to about 5 L, and micro-volumes from as small as 0.1 L to about 0.5 L such as 0.1 L to 0.2 L, 0.1 L to 0.3 L, 0.1 L to 0.4 L, 0.2 L to 0.3 L, 0.3 L to 0.4 L, or 0.3 L to 0.5 L are contemplated by the invention. Exemplary dialysate flow loops are described in more detail below including in relation toFIGS.7,8and11. A dialysate flow loop has a dialysate flow path320and post-dialyzer flow path310for transporting a dialysate between a dialyzer318and a dialysate regeneration cartridge or system100. A bypass loop308can be present to allow for the diversion of a portion of the dialysate around the dialyzer318to rejoin the flow path in the post-dialyzer310flow path. One or more infusates can be added by an infusate injector313, which can be present to add an infusate to either the dialysate flow path320or post-dialyzer310flow paths. Similarly, a buffer pump or source solution311can be present for addition to the dialysate flow loop and/or a pump or source for adding fresh water/dialysate323. Fresh water/dialysate323can be added to the dialysate flow loop as a diluent to decrease the conductivity or sodium chloride content of the circulating dialysate. An ultrafiltration or control pump can also be present to add or remove volume from the dialysate flow loop (not shown). Where dilution of the sodium concentration or conductivity of the dialysate is needed, water from fresh water or dialysate source323can be added to the dialysate flow loop and dialysate removed from the dialysate flow loop using the control pump. The control pump can also be used to affect ultrafiltration of the blood by drawing fluid out of the blood through the membrane of the dialyzer318and/or the control pump can be used to add volume to the dialysate flow loop to counter hemoconcentration within the dialyzer318. The systems and methods disclosed herein can be broadly applied to dialysis equipment and be used in a blood based solute monitoring system. A critical principle utilized by the blood based solute monitoring system is that a small volume of dialysate can be recirculated through the dialyzer multiple times in a short period of time to equilibrate a dialysate solute concentration to a blood solute concentration on the blood side of a dialyzer in order to obtain certain measurements of patient blood solute concentration. In some embodiments a small void volume dialysate loop with sorbent based regeneration and fluid circulating in a closed loop can take advantage of this critical principle. However, a sorbent is not necessarily required as part of the present system where dialysate is recirculated. In other embodiments, addition of a small volume recirculating dialysate loop to a sorbent regenerative dialysis system having an open reservoir, such as a REDY system, can make these systems capable of utilizing this principle. In certain embodiments, a small recirculating loop and a miniature sorbent column can be added to a standard single pass dialysate system to enable this type of system to be able to utilize the measurement principles disclosed. In any embodiment, the dialysate flow rate can be increased or the volume of the dialysate loop decreased to reduce the equilibration time. In certain embodiments, a measurement can be taken by the present blood based solute monitoring system without a second flow path that is not equilibrated with blood on the blood side of a dialyzer. In other embodiments, the present blood based solute monitoring system can be in fluid communication with a sorbent regenerated dialysate loop, or a controlled compliant loop. In still further configurations, a small volume recirculation loop with a control valve could be installed in a traditional single pass system to take advantage of the principles discussed herein. For example, the small volume recirculation loop can be installed and in fluid communication with a REDY type system or a REDY open reservoir type system. One of ordinary skill will understand that many systems known within the art can advantageously employ a small recirculating volume to equilibrate the solute concentration quickly across a dialyzer. Because the circulating volume in a recirculating flow path is sufficiently small, the system can pump in a short period of time the necessary volume of fluid to recirculate the fluid through the dialyzer a sufficient number of times to equilibrate the concentration of solutes in the dialysate to the concentration of solutes in the blood. One or more pumps can be configured in the system to reduce equilibration times or to cause fluid flows through specific fluid paths. In certain embodiments, the small recirculating volume can be configured into a controlled compliant flow path as described herein to reduce equilibration time and/or be configured to be in fluid communication with a dialysate flow path that is also controlled compliant. However, it will be understood that the present recirculating loop having small, quickly equilibriated volumes can be configured to be in fluid communication with any dialysis machine or therapy device using combinations of tubing, one or more valves, and one or more sensors. A theoretical minimum volume for use in the blood based solute monitoring system can be a priming volume of the dialysate compartment of the dialyzer. Various sensor types can be used to detect the chemical changes occurring as the dialysate flows through the various sorbent layers. Chemical sensing that operates by fluid conductivity measurement with a conductivity meter can be used. In any embodiment, ion selective membranes can be applied to the conductivity electrodes by techniques that are known in the art and commercially available, in order to measure pH, or other ion species such as sodium and potassium. In some embodiments, additional sensors for measuring pH, temperature, and pressure can be added to one or more flow paths containing the conductivity meter to enhance the measurement accuracy and specificity. The blood based solute monitoring system requires at least one measurement. For example, an ion selective sensor such as a potassium sensor can be used wherein only a single sensor is required and a single measurement is taken to determine the equilibrated dialysate concentration, and thus the blood concentration. Similarly, a single sensor reading from an ammonium ion sensor located post-urease can be used to measure BUN. For determining both conductivity and/or a pH-based measurement, at least 2 sensors or 2 fluid samples both before and after fluid has passed urease are required to obtain BUN. In certain embodiments, the blood based solute monitoring system need not rely solely on equilibration but can utilize an electrolyte bolus to perform the measurement of the blood solute concentration. For example, a bolus is provided between the dialyzer outlet and the sorbent inlet. As shown in the non-limiting, embodiment ofFIG.8, three sample points and a bolus injector are located between the outlet of the sorbent and the inlet of the dialyzer. In any embodiment, the conductivity monitor of the present invention can be used to measure urea concentration in the dialysate, further enabling the determination of blood urea concentration, for example at the beginning and at the end of a dialysis session, at intermediate time points during a dialysis session, at a specific time after the end of a dialysis session (to measure rebound of urea, or other solutes, to determine equilibrated clearance, or eKt), or for determination of protein catabolic rate (PCR), a nutritional marker derived from interdialytic urea accumulation that can be important in determining the dialysis prescription. In any embodiment, measurement of the urea concentration in the dialysate can further be used to monitor the time course of urea concentration decrease, effective dialysance, for deviations that may indicate deficiencies related to blood access recirculation, access connection errors, blood flow inaccuracy, or dialyzer clotting that requires intervention within the dialysis session to ensure therapy targets are met. In some embodiments, measurement of the urea concentration in the dialysate can further be used to determine total urea mass clearance for a dialysis session by multiplying urea concentration by dialysate flow rate and integrating over dialysis session time to obtain the urea Kt. FIG.1shows a dialysate regeneration cartridge100in accordance with certain embodiments of the invention. The dialysate regeneration cartridge100can include a urease material segment or layer in sequence with one or more sorbent materials. For example, the sorbent cartridge100illustrated inFIG.1includes a segment or layer containing the enzyme urease and alumina102, a zirconium phosphate segment or layer103, a zirconium oxide segment or layer104, and an activated carbon segment or layer105. In any embodiment, the urease material102can also include alumina. Spent dialysate containing blood impurities, such as urea, enters the sorbent cartridge100through inlet stream301, passes through the urease material102and the sorbent materials, and regenerated or partially regenerated dialysate exits the sorbent cartridge100through outlet stream302. The sorbent materials remove the impurities from the dialysate, and the dialysate returns to the dialyzer through the sorbent outlet stream302. Urea can be converted to ammonium carbonate as the dialysate passes through the urease layer102, according to Scheme 1 as described herein. As the solution passes through the urease layer102, ammonium and bicarbonate ions produced by this reaction can result in an increase in dialysate solution conductivity proportional to the concentration of urea in the dialysate stream entering the regeneration cartridge100through inlet stream301. The dialysate regeneration cartridge100ofFIG.1can be associated with a pre-urease conductivity measurement point201upstream from the urease material102in the dialysate flow loop between a dialyzer outlet and the sorbent inlet stream301, and an integral post-urease conductivity measurement point202downstream of the urease material102. A measurement point refers to a position in a flow path or sorbent cartridge that is in fluid communication with a sensor. The sensor can be in fluid communication at a particular position, or measurement point, by being physically located at the position of interest, or located away from the position of interest and have a fluid stream from the position of interest conveyed to the sensor. Conveyance of the fluid stream can occur via flow paths. In any embodiment, the post-urease measurement point can be located downstream from the sorbent outlet stream302between any stage or stages of the regeneration cartridge100and a dialyzer inlet. In any embodiment, a controller, such as a digital processor, can monitor the conductivity measurements taken at the conductivity measurement points201and202. The controller can further perform calculations using the conductivity measurements and/or additional measurements, such as the dialysis flow rate taken at the dialysate flow sensor203, for example, to determine the amount of urea removed by the urease material102over time. The difference between the conductivity measurements at conductivity measurement points202and201can be used to determine the urea concentration of the spent dialysate entering the sorbent cartridge101through the inlet stream301. The urea concentration can further be multiplied by the dialysate flow rate as measured by flow sensor203to determine the urea mass flow rate cleared by the dialyzer. FIG.2shows a dialysate regeneration unit that can include a urease housing101that contains the urease material102and a separate sorbent housing106that can contain one or more sorbent material segments or layers, for example, the zirconium phosphate segment or layer103, the zirconium oxide segment or layer104, and the activated carbon segment or layer105. Spent dialysate enters the urease housing101through the sorbent cartridge inlet stream301, passes through the urease material102and exits the urease housing101through the urease housing outlet stream303, then enters the sorbent housing106through the sorbent housing inlet stream304and passes through the sorbent materials103,104,105before exiting the sorbent housing106by way of the sorbent cartridge outlet stream302as regenerated or partially regenerated dialysate. The dialysate regeneration unit ofFIG.2can be further associated with a pre-urease conductivity measurement point201upstream of the urease housing101and a post-urease conductivity measurement point202downstream of the urease housing101and upstream of the sorbent housing106. In some embodiments, conductivity measurement point202is external to the urease housing101and the sorbent housing106, which can have advantages in certain applications. For example, having the conductivity measurement point external to the sorbent cartridge can simplify placement of a conductivity sensor directly at the measurement point or simplify incorporation of a flow path used to convey a fluid stream to a sensor positioned at a location different than the measurement point. In some embodiments, sorbent housing106can include multiple layers of individual sorbent materials. In other embodiments, sorbent housing106can contain multiple sorbent materials that are blended together to form a single, uniformly mixed layer. Additional embodiments can include multiple sorbent cartridge housings that each contain an individual sorbent material. As described inFIG.1, a controller can monitor the conductivity measurements taken from the conductivity measurement points201and202, and in any embodiment the dialysate flow sensor203can measure the flow rate of the dialysate, which can be used in further computations. FIGS.1and2show exemplary embodiments of dialysate regeneration units and are not exclusive. Other types of sorbent materials and other sequences of materials can be provided. Conductivity Monitoring System FIG.3shows a dialysate regeneration unit or device that can include a urease housing101containing, for example, a urease material102and a sorbent housing106containing, for example, one or more sorbent materials or other regenerative materials107to remove waste species from the dialysate, such as the sorbent cartridge shown inFIG.2. In some embodiments, the urease housing101and the sorbent housing106can be integral to a single unit, such as an interchangeable sorbent cartridge, whereas in other embodiments the urease housing101and the sorbent housing106can be separate and independent units. Post-dialyzer dialysate, or spent dialysate, can enter the urease housing101through the sorbent cartridge inlet stream301, pass through the urease material102and exit the urease housing101through urease housing outlet stream303before entering the sorbent housing106through sorbent housing inlet stream304, passing through one or more layers of sorbents and/or other regenerative materials107in sorbent housing106and exiting the sorbent housing106through the sorbent cartridge outlet stream302. Within the sorbent housing, there may be multiple sub-layers of materials of different sorbent compositions, such as illustrated and described forFIGS.1and2. The dialysate regeneration unit or device can further include a conductivity monitoring system having a single conductivity meter204and a sampling valve401, such as a three-way valve shown inFIG.3, capable of selecting between two separate sample streams306or307that are drawn from the junction points501or503, respectively. The single conductivity meter204may alternatively be referred to as “single conductivity sensor204”, “common conductivity meter204”, or “common conductivity sensor204.” The junction points501and503allow dialysate fluid to flow towards conductivity meter204, depending on the position of sampling valve401. The junction points501and503could consist of a 3-way tee-connector. One of ordinary skill in the art will recognize that junction points501and503can also include two-way valves, which could replace the three-way valve and provide equivalent functionality for any of the sampling valves described herein. In some embodiments the sample streams306and307can convey a continuous flow of dialysate from the selected flow streams306or307, while in other embodiments the sample streams306and307can convey an intermittent flow of dialysate. In any embodiment of the invention, sampling can be accomplished using tubing or a flow conduit external to or integral to the urease housing101and sorbent housing106. The first sample stream306can be drawn from the post-dialyzer dialysate flow stream310upstream of the sorbent cartridge inlet stream301before the urease has hydrolyzed the urea into ionic byproducts, and the second sample stream307can be drawn from the dialysate flow downstream of the urease housing outlet303. In some embodiments, each sample stream can convey a small fraction of the main dialysate flow stream. The sampling valve401can be placed in a closed position to inhibit flow through both sample streams306and307and allow dialysate to flow through the urease and sorbent housings101and106without any sampling. In order to measure the reduction in the urea concentration of the dialysate when it passes through the urease102using the conductivity monitoring system, the sampling valve401can be intermittently toggled between a first intake position and a second intake position. When sampling valve401is placed in the first intake position, sample stream306delivers dialysate to the sampling valve401prior to entering the urease housing101and/or contacting the urease layer102; the first sample stream306conveys post-dialyzer dialysate from junction point501, which contains urea that has not yet been converted into ammonium ion species. Dialysate in sample stream306can be passed through the sampling valve401to a conductivity meter204and a first conductivity measurement is obtained from the post-dialyzer dialysate before urea is hydrolyzed into ionic by-products. When first sampling valve401is placed in the second intake position, sample stream307is delivered to the sampling valve401and subsequently to the conductivity meter204. The second sample stream307can be drawn from the dialysate flow after the dialysate has contacted the urease layer102but before the dialysate has contacted any downstream layers within the sorbent housing106. More specifically, the second sample stream307is sampled from junction point503after contact with the urease layer102has been completed and the conversion from urea to ammonium salt is substantially complete. In some embodiments, sample stream307can be taken from a position at the interior of an integral sorbent cartridge. For example, sample stream307may result from a tube inserted part-way into the sorbent cartridge and in fluid communication with the dialysate flowing through the sorbent cartridge at a point near the urease housing outlet stream303. In certain embodiments sample stream307can be drawn from a junction point between separate and independent urease and sorbent housings101and106. A second conductivity measurement can be taken by conductivity meter204using the second sample stream307. Dialysate in sample stream307can be passed through the sampling valve401to a conductivity meter204and a second conductivity measurement can be obtained for the dialysate after some or all of the urea has been hydrolyzed into ionic byproducts. In any embodiment, sampling valve401can be periodically alternated between the first sample flow stream306and the second sample flow stream307and alternating conductivity measurements can be taken by the conductivity meter204corresponding to the two sample streams306and307to measure the reduction in the urea concentration of the dialysate affected by the urease material102. The period of time for performing the conductivity readings in various, non-limiting embodiments can be less than 5 minutes, less than 3 minutes, less than 1 minute, less than 45 seconds, less than 30 seconds or less than 15 seconds depending on each separate conductivity measurement. However, it will be understood that any period of time is contemplated by the present invention. In certain embodiments, the sampling valve401can remain in a fixed position until a conductivity reading taken by the conductivity meter204stabilizes to an acceptable level of drift, rather than remaining in a certain position for a fixed period of time. The reduction in the concentration of urea in the dialysate resulting from the removal of urea as the dialysate passes through the urease material102can be determined by comparing the conductivity reading from sample stream307and the conductivity reading from sample stream306. The monitoring of urea concentration or amount in the dialysate can be monitored in a real-time manner during the period where the sampling valve401is actively toggled between sample stream306and307. Alternatively, the sampling valve401can periodically be placed in the closed position and conductivity measurements can be intermittently taken to determine the urea content of the dialysate on an intermittent basis. In addition, any embodiment of the invention can include a dialysate flow sensor203to measure the rate of flow of the dialysate passing through the dialysate regeneration unit or device. In certain embodiments, the dialysate flow sensor203can be located along flow stream310to measure the flow rate of dialysate through the dialysate regeneration cartridge100or urease housing101. The measured flow rate of dialysate through the regeneration cartridge100or urease housing101can be used to calculate additional data, for example, in combination with the conductivity readings to quantify the amount of urea removed from the dialysate by the dialysate regeneration cartridge100or urease housing101during a specified period of time. After a conductivity reading is taken at conductivity meter204, the sample stream exiting conductivity meter204can be diverted to the bypass loop308and rejoined with the working dialysate solution in the dialysate flow loop at a position downstream from the dialyzer and upstream from the dialysate regeneration unit or device. Since a single conductivity meter204is used to measure the conductivity of both the first and the second sample streams306and307, offset slope and drift errors that may occur when comparing measurements taken by two separate sensors can be eliminated. Further, in certain embodiments thermal differences between the first and second sample streams306and307can be minimized by co-routing and/or insulating the corresponding conduits. In any embodiment, the conductivity meter204can be fluid temperature compensated by having a thermocouple contained in the conductivity meter, or in close proximity. In the embodiment shown inFIG.3, the conductivity meter204is configured to take a conductivity measurement from two separate sample flow streams, where each flow stream represents a stream having a different degree of contact or modification by the dialysate regeneration unit or device. InFIG.4, a dialysate regeneration device is shown that is capable of measuring three different flow streams306,307and302using one shared conductivity meter204. As described inFIG.3, the first sample stream306consists of dialysate prior to contact with the urease-containing layer102contained in the urease housing101. The second sample stream307consists of dialysate after contact with the urease-containing layer102contained in the urease housing101.FIG.4shows an additional embodiment where a conductivity measurement can be taken from the sorbent housing outlet flow stream302consisting of dialysate that has passed through all layers of the dialysate regeneration unit, including the urease-containing layer102and the other sorbent materials107contained in sorbent housing106. In any embodiment an optional sample return buffer reservoir109as shown inFIGS.3-15can temporarily store the sample fluid before it is returned to the main dialysate flow loop via bypass loop308, in order to prevent returned sample fluid from modifying the composition of fluid in the main dialysate flow loop while a conductivity reading is being taken. An optional buffer pump412can be operated in conjunction with sampling valve411to either transfer fluid exiting the conductivity meter204into the sample return buffer reservoir109, or to transfer fluid from the sample return buffer reservoir109to the main fluid loop via bypass loop308. In some embodiments, the buffer pump412can also function as an ultrafiltration or fluid balance control pump and the sample return buffer reservoir109can also serve as an ultrafiltrate or fluid balance control reservoir. As shown inFIG.4, the sampling valve401can be alternated between a closed position and first and second sampling positions to select the first306or second307flow stream, as described above. In the closed position, dialysate is prevented from entering the conduits forming the first306and second307flow paths. A common conductivity meter204can intermittently measure the conductivity from all three sample streams306,307and302, as such, errors that can result from calibration differences between separate conductivity meters are eliminated. In addition to measuring urea removal by comparing conductivity differences between pre- and post-urease sample streams306and307, the conductivity meter204can also monitor performance of the sorbents within sorbent housing106by comparing conductivity measurements of dialysate fluid from flow stream302exiting the sorbent housing106with conductivity measurements from the dialysate fluid taken through the second sampling conduit307before it has entered the sorbent housing106through sorbent housing inlet304. That is, conductivity of the second sample stream307can be compared to the conductivity of dialysate flow stream302to determine performance of the materials within the sorbent housing106. Further, the conductivity of the dialysate flow stream302can indicate the actual conductivity of the dialysate entering the dialysate flow loop via dialysate flow path320to determine if overall dialysate sodium ion concentration is within a predetermined level for the dialysis therapy session. In the embodiment shown inFIG.4, the urea content of the dialysate entering the dialysate regeneration unit can be measured in a real-time and/or continuous fashion as described inFIG.3. However, in some embodiments the conductivity of flow stream302is measured during the majority of the period of treatment, for example, 90% of the treatment time. To obtain a reading from the first sample flow306(pre-urease flow), the first sampling valve401can be switched to a first sampling position to allow flow into the bypass conduit306and the second sampling valve402can be switched to a position to block flow from the regeneration cartridge outlet302from reaching conductivity meter204. To measure the conductivity of the second sample stream307, sampling valve401can be switched to the second intake position to allow flow from the second sampling conduit307while the second sampling valve402remains switched to allow the sampling flow307to pass through conductivity meter204and the post-urease conductivity measurement is taken. As described above with reference toFIG.3, the dialysate flow sensor203can take dialysate flow rate measurements that can be used to calculate additional data. FIG.5illustrates a dialysate regeneration unit or device in which the urease material102and the regenerative material(s)107can be contained in sequential layers within a single housing of the sorbent cartridge100. In this example, either the pre-urease sample stream306or a post-urease sample stream307can be intermittently directed to the single conductivity sensor204by way of sampling valve401for conductivity measurement. InFIG.5, the post-urease sample stream307is conveyed directly from the interior of the sorbent cartridge100at the interface505between the urease material layer102and the sorbent material(s) layer107. Sample stream307is conveyed to the exterior of the regeneration cartridge100by way of a dedicated sampling bypass duct326. The inlet305to the sampling bypass duct326is positioned immediately below the interface505between the urease material layer102and the sorbent material(s) layer107, to ensure sample stream307has contacted a majority of the urease material layer102, but has not contacted the sorbent material(s) layer107, which could adversely affect the conductivity measurement. In various embodiments, the sorbent material(s)107can consist of a single material, multiple layers of individual materials, or multiple intermixed materials. In any embodiment in accordance withFIG.5, the sampling bypass duct326can consist of a segment of metallic, polymeric or composite tubing that extends between the urease material102and the sorbent material(s)107to the exterior of the sorbent cartridge100. In various embodiments, the sampling bypass duct326can be a compatible rigid-wall, flexible or pliable material known in the art. The inlet305to the sampling bypass duct326could also contain a mesh or filter material to prevent urease material102from leaving the sorbent cartridge100. Thus, the chemical reactions and adsorption occurring in individual sorbent material layers can be monitored independently without necessitating the insertion of a sensor into the cartridge or packaging of the sorbent layers in separate containers joined by connecting fluid conduits. In various embodiments, the sensor can measure differential conductivity, pH, and/or use optical detection to analyze the dialysate. In any embodiment in accordance withFIG.5, the operation of sampling valve401is equivalent to that described above with reference toFIG.3. Thus, conductivity measurements can be taken for the pre-urease sample stream306and the post-urease sample stream307and compared to determine the performance of the urease material102in removing urea from the spent dialysate. As described above with reference toFIG.3, the dialysate flow sensor203can take dialysate flow rate measurements that can be used to calculate additional data. FIG.6depicts a dialysate regeneration unit or device in which the urease material102and the sorbent material(s)107can be comingled or intermixed in the sorbent cartridge100. Any embodiment in accordance withFIG.6can intermittently divert a post-dialyzer (pre-urease) sample stream306via junction point501upstream of the dialysate regeneration sorbent cartridge100and a post-regeneration sample stream309via junction point507downstream of the regeneration cartridge100by way of sampling valve413to conductivity sensor204. The operation of the sampling valve413can be equivalent to that described above with reference toFIG.3, except that in embodiments in accordance withFIG.6the difference between the measured conductivity of the post-urease sample stream309and that of the pre-urease sample stream306can determine the differential conductivity across the entire sorbent cartridge100. For example, the differential conductivity across the sorbent cartridge100can be used to monitor the sodium ion concentration and/or conductivity of the dialysate, which can be used to determine an appropriate amount of a diluent to be added to the dialysate flow loop to maintain a relatively constant biocompatible saline solution. Ionic dialysance is a method known in the art to effectively quantify effective clearance for a dialysis session (Steil et al., Int'l Journ Artif Organs, 1993, In Vivo Verification of an Automatic Noninvasive System for Real Time Kt Evaluation, ASAIO J., 1993, 39:M348-52, which is incorporated herein by reference). Periodic sodium ion boluses can be directed through the dialysate regeneration sorbent cartridge100to calculate the effective ionic clearance based upon the changes in pre- and post-dialyzer conductivity measurements during the bolus. The measurements can be taken multiple times during a hemodialysis session and integrated to measure session “Kt”. By this method, errors due to factors that change the clearance rate (clearance variability between dialyzers, blood access recirculation, blood flow rate errors, dialyzer clogging, access connection reversal, dialysis session interruptions) can be eliminated. Because sodium and urea have nearly identical clearances, a conductive dialysance measurement with sodium boluses has been demonstrated to be a surrogate for urea clearance. The general method for measuring effective dialysance by means of a bolus and conductivity measurements is as follows, with reference toFIG.7and any other figures with like component numbers:1. Measure initial conductivity at dialyzer inlet314(Cdi1).2. Measure initial conductivity at dialyzer outlet315(Cdo1).3. Introduce electrolyte concentrate or diluent to the dialysate stream in order to create a bolus shift in the electrolyte concentration and corresponding conductivity level.4. Measure bolus conductivity at dialyzer inlet314(Cdi2).5. Measure bolus conductivity at dialyzer outlet315(Cdo2).6. Calculate effective clearance (Keff). The effective clearance is calculated according to Equation 2. Keff=Qd*(Cdi1-Cdo1)-(Cdi2-Cdo2)(Cdi1-Cdi2)(Equation2) K can be calculated using Equation 3 below using dialysate flow rate (Qd), concentration in the dialysate entering the dialyzer (Cdi) and the concentration in the dialysate exiting the dialyzer (Cdo) and concentration in the blood entering the dialyzer (Cbi). K=Qd*Cdo-CdiCbi-Cdi(Equation3) Since the concentration of urea entering the dialyzer is zero, this relationship can be reduced to K=Qd*CdoCbi(Equation4) or rearranged as Equation 5 Cbi=Qd*CdoK.(Equation5) The dialysate flow rate is readily measured by means such as a flow meter203shown in various figures. The effective clearance can be determined as described above and with equation 2, by ionic dialysance measurements. The effective clearance determined with ionic dialysance is essentially equal to the clearance (K) for urea. Therefore, by determining the dialysate flow rate (Qd) and the urea concentration of the dialysate exiting the dialyzer (Cdo) the blood concentration of urea entering the dialyzer (Cbi) can be determined. The urea concentration of the dialysate exiting from the dialyzer outlet can be measured by comparison of the conductivity of sample streams306and307, shown in various figures and described above. FIG.7shows a dialysate regeneration unit or device in which the urease material102and the sorbent material(s)107can be contained in sequential layers within the regeneration cartridge100, similar to the configuration described above with reference toFIG.5. However, in embodiments in accordance withFIG.7, four different sample streams306,307,309,312can be diverted from various points in the dialysate flow path to the single conductivity sensor204by way of the sampling valves401,414and404for intermittent conductivity measurement. The first sample stream306can be diverted from the post-dialyzer (pre-urease) sample stream310via junction501and intermittently directed to the conductivity sensor204by way of sampling valves401and404for conductivity measurement. The second sample stream307, which consists of dialysate that has passed through the urease material layer102can be collected as described above through the sampling bypass duct326and intermittently directed to the conductivity sensor204by way of sampling valves401and404for conductivity measurement. The third sample stream309, which consists of dialysate that has passed through sorbent cartridge100can be collected through junction511and intermittently directed to the single conductivity sensor204by way of sampling valves414and404for conductivity measurement. The fourth sample stream312, which consists of dialysate exiting the dialyzer318can be collected through junction513and intermittently directed to the single conductivity sensor204by way of sampling valves414and404for conductivity measurement. In this respect, in any embodiment in accordance withFIG.7sampling valve401can be configured to close off flow from sample stream307and allow flow from sample stream306, or vice versa. Also, sampling valve404can be configured to close off flow from stream521and allow flow from stream519, or vice versa. Finally, sampling valve414can be configured to close off flow from sample stream312and allow flow from sample stream309, or vice versa. Similarly, with reference toFIG.7, the second, post-urease, sample stream307can be diverted from the urease material102near the interface505between the urease material102and the sorbent material(s)107and intermittently directed to the single conductivity sensor204by way of the sampling bypass duct326, sampling valve401and sampling valve404for conductivity measurement. In this case, sampling valve401can be configured to close off flow from sample stream306and allow flow from sample stream307, while sampling valve404simultaneously is configured to close off flow from stream519and allow flow from stream521to the single conductivity sensor204. With further reference toFIG.7the pre-urease conductivity (Cpre-U) can be obtained by switching valves401and404to permit the first sample stream306to flow through the conductivity meter204. Post-urease conductivity (Cpost-U) can be obtained by switching valve401to allow the second sample stream307to flow through the conductivity meter204to measure the conductivity of fluid exiting the urease material102. The post sorbent cartridge sample stream302ofFIG.7can be diverted downstream of the sorbent cartridge100via junction511and intermittently directed to the conductivity sensor204by way of sampling valve414and sampling valve404for measurement of the dialysate or bolus conductivity at the dialyzer inlet314. In order to accomplish this, sampling valve414can be configured to close off flow from sample stream312at the dialyzer outlet315and allow flow from sample stream309, while sampling valve404simultaneously is configured to close off flow from sampling valve401and allow flow from sampling valve414to the conductivity sensor204. In addition, any embodiment can incorporate an infusate injector313, downstream of the dialyzer and upstream of the sorbent cartridge100that can add one or more infusates to the dialysate, such as a buffering agent or other components typically employed to compose a dialysate solution. The infusate injector313can consist of a reservoir containing an infusate and a pump to deliver the infusate to the dialysate flow loop via junction515. Alternatively, the infusate injector313may be located in other locations on the dialysate flow loop. In order to facilitate the determination of the conductivity change contributed by the infusate from the infusate injector313, a sample stream312can be diverted downstream of the dialyzer318and upstream of the infusate injector313and intermittently directed to the conductivity sensor204by way of sampling valve414and sampling valve404. In order to accomplish the conductivity measurement of sample stream312, sampling valve414can be configured to close off flow from sample stream309and allow flow from sample stream312, while sampling valve404simultaneously is configured to close off flow from sampling valve401and allow flow from sampling valve414to the conductivity sensor204. Conductivity measurements taken from sample stream312can then be compared to those of sample stream306, which can be taken as described above, to determine the conductivity change resulting from the addition of the infusates to the spent dialysate. Likewise, conductivity measurements taken from sample stream312can also be compared to those of sample stream309, which can be taken as described above, to determine the performance or efficiency of the dialyzer318with respect to the removal of impurities and waste products from the bloodstream entering inlet stream316and exiting outlet stream317of the dialyzer318. As described above, measurements of the dialysate flow rate taken at flow rate sensor203can be used to calculate the total amount of infusates added to the dialysate or the total amount of impurities and waste products removed from the bloodstream over time. Further, the embodiment ofFIG.7can be advantageously applied to ionic dialysance measurements as describe above in connection toFIG.6. As describe above, the system described inFIG.7can be used to alternately measure four different sample streams using single conductivity sensor204, which can be summarized as follows: pre-urease or first sample stream306, post-urease or second sample stream307, pre-dialyzer or third sample stream309and post-dialyzer or fourth sample stream312. Ionic dialysance measurements can be accomplished by selectively modifying the rate of introduction of an infusate by infusate injector313. Initial conductivity (Cdi1) at the dialyzer inlet314can be obtained by switching valves414and404to permit the third sample stream309to flow through the conductivity meter204to indicate conductivity at the dialyzer inlet314prior to introduction of an electrolyte bolus or diluent. The initial conductivity (Cdo1) at the dialyzer outlet315can be obtained by switching valve414and404to permit the fourth sample stream312to flow through the conductivity meter204to indicate conductivity of the stream at the dialyzer outlet315prior to introduction of an infusate from the infusate injector313. With reference toFIG.7, conductivity measurements for ionic dialysance can be obtained through the following operations. Additional conductivity measurements can then be obtained by initiating an electrolyte bolus (or diluent bolus) from the infusate injector313to allow an altered conductivity at the dialyzer inlet314and outlet315of the dialyzer to be obtained. A bolus can be initiated by switching valves414and404to allow for the third sample stream309to flow through the conductivity meter204and an infusate is introduced by infusate injector313to either raise or lower the electrolyte concentration in dialysate stream310. Bolus conductivity (Cdi2) at the dialyzer inlet can then be obtained by continuing to measure conductivity with valves414and404set to allow the third sample stream309to flow into the conductivity senor204until a minimum or maximum conductivity is detected in response to the bolus introduced by infusate injector313. After a minimum or maximum conductivity for Cdi2is detected in response to the bolus, valve414is switched to allow the fourth sample stream312to be directed toward conductivity meter204and the bolus conductivity at the dialyzer outlet (Cdo2) is obtained when a minimum or maximum conductivity is observed. Upon obtaining conductivity values Cdi1, Cdo1, Cdi2, and Cdi2, effective clearance can be calculated using Equation 2 above. The dialysate flow rate (Qd) can be obtained from flow sensor203. One skilled in the art will understand that pre-(Cpre-U) and post-urease (Cpost-U) are not needed for the calculation of effective clearance (Keff). As such, the dialysate regeneration unit can contain intermixed sorbent and/or urease materials as shown inFIG.6while allowing for ionic dialysance measurements to be taken. Further, blood urea concentration can be calculated using Equation 5 upon calculating the value of urea in the dialysate exiting the dialyzer (Cdo) using the pre- and post-urease conductivity measurements. As shown inFIG.8, any embodiment can incorporate an infusate injector311downstream of the sorbent cartridge100and upstream of the dialyzer318that can add one or more infusates to the dialysate, such as potassium ion, calcium ions, magnesium ions or other components typically employed to compose a dialysate solution. In order to facilitate the determination of the overall conductivity change resulting from the removal of impurities and waste products by the sorbent materials107in the sorbent cartridge100and the addition of the infusates by infusate injector311, the sample stream319can be diverted downstream of the sorbent cartridge100and infusate injector311and upstream of the dialyzer318with junction527and intermittently directed to the single conductivity sensor204by way of sampling valve405. Infusate injector311is the same as infusate injector313, shown inFIG.7, except for its position along the dialysate flow loop. In order to accomplish the conductivity measurement of sample stream319, sampling valve405can be configured to close off flow from sampling valve401and allow flow from sample stream319to the single conductivity sensor204. Conductivity measurements from sample stream319can be compared to those from sample stream306or sample stream307, taken as described above with reference toFIG.7in order to determine the overall conductivity change resulting from the removal of impurities and waste products by the sorbent materials107in the sorbent cartridge100and the addition of the infusates by infusate injector311. Similarly, conductivity measurements from sample stream319can be compared to those from sample stream307, also taken as described above with reference toFIG.7in order to determine the overall conductivity change resulting from the removal of impurities and waste products by both the urea material102and the sorbent materials107as well as from the addition of the infusates by infusate injector311. Urea content can be determined by comparing the conductivity of sample streams306and307as described forFIG.3. As inFIG.7, the embodiment shown inFIG.8can be used to obtain ionic dialysance measurements for use in conjunction with Equations 2-5. Initial conductivity (Cdi1) at the dialyzer inlet314can be obtained by switching valve405to permit the third sample stream319to flow through the conductivity meter204. Initial conductivity (Cdo1) at the dialyzer outlet315can be obtained by switching valves401and405to permit the first sample stream306to flow through the conductivity meter204. Since the infusate injector311is not located between the dialyzer outlet315and the inlet301of the sorbent cartridge100, the first sample stream306indicates the conductivity of the spent dialysate exiting the dialyzer. A bolus can be initiated by switching valves401and405to allow for the third sample stream319to flow through the single conductivity sensor204and an infusate (bolus) is introduced by infusate injector311to either raise or lower the electrolyte concentration in the dialysate flow path320. Bolus conductivity (Cdi2) at the dialyzer inlet314can then be obtained by continuing to measure conductivity of the third sample stream319until a minimum or maximum conductivity is detected in response to the bolus introduced by infusate injector311. After a minimum or maximum conductivity (Cdi2) at the dialyzer inlet314is detected in response to the bolus, valves401and405are switched to allow the first sample stream306to be directed toward the single conductivity sensor204and the bolus conductivity (Cdo2) at the dialyzer outlet315is obtained when a minimum or maximum conductivity is observed. Upon obtaining conductivity values for Cdi1, Cdo1, Cdi2, and Cdi2, effective clearance can be calculated using Equation 2 above. The dialysate flow rate (Qd) can be obtained from flow sensor203. As explained above, all of the values indicated by Equations 2-5 can be calculated from the obtained conductivity data. Further, any embodiment can incorporate a modified sorbent cartridge110that includes one or more sorbent materials108, such as a highly-selective ion exchange resin, for example, selective for calcium ions and/or magnesium ions, upstream of the urease material102and an additional one or more sorbent materials107as shown inFIG.9. In layer108, the selective resin releases hydrogen ions (H+) in exchange for calcium (Ca2+) and magnesium (Mg2+), which acts to acidify the solution and promotes the conversion of ammonia to ammonium after enzymatic urea breakdown occurs in the urease material102. The sorbent cartridge110can include a post-urease sampling bypass duct326, equivalent to that described above with reference toFIG.5, as well as an additional dedicated sampling bypass duct321, similar in construction to sampling bypass duct326, but downstream of the sorbent material(s)108and upstream of the urease material102. A sample stream322can be conducted from sampling bypass duct321with inlet531positioned immediately below the interface533between the urease material layer102and the sorbent material(s) layer108, to ensure sample stream322has contacted a majority of the sorbent material layer108, but has not contacted the urease material(s) layer102, which could adversely affect the conductivity measurement. In order to measure the conductivity of sample stream322inFIG.9, sampling valve406can be configured to close off flow from sample stream307and allow flow from sample stream322to the single conductivity sensor204. Conductivity measurements from sample stream307, taken as described above with reference toFIG.5with the substitution of sampling valve406directing the flows from sample stream322and sample stream307in place of sampling valve401directing the flows from sample stream306and sampling stream307in order to determine the conductivity change resulting from the removal of impurities and waste products by the urease material102in the modified sorbent cartridge110. As will be understood by one of ordinary skill in the art, the modified sorbent cartridge110described inFIG.9can be combined with any of the additional sampling configurations external to the sorbent cartridge100described herein, to configure additional embodiments of the invention. Any embodiment of the invention can include a sorbent cartridge bypass flow path330as shown inFIG.10. The sorbent cartridge bypass flow path330can be diverted from the upstream dialysate flow path310and rejoin at the dialysate flow path320downstream of the sorbent cartridge100. The sorbent cartridge bypass flow path330can incorporate a bypass valve407, which, for example, may be a three-way valve, as depicted inFIG.10, or a combination of two-way valves. One skilled in the art will appreciate that the bypass valve407can be placed as shown inFIG.10, as well as at an intermediate point within the sorbent cartridge bypass flow path330or at the downstream junction535. Thus, the sorbent cartridge bypass flow path330can inhibit the flow of dialysate through the sorbent cartridge100while continuing to circulate dialysate flow through the dialyzer. For example, the bypass flow path330can be utilized to facilitate equilibration of the dialysate concentration of urea and other impurities and waste products with the concentration of these components in the blood passing through the dialyzer. As described in connection withFIG.3, measurement of the urea concentration of the dialysate in the post-dialyzer segment310of the dialysate flow loop can be used to calculate and monitor clearance Kt. However, an indication of the urea content of the fluid within the dialyzer is not directly provided. During active dialysis, a concentration gradient between the dialysate and the blood is maintained to establish hemodialysis treatment. The size of the gradient depends on several factors, as such, measurement of dialysate urea content does not allow for a direct measurement to be made of the urea content of the blood. When bypass flow330is operated, hemodialysis treatment is suspended as the dialysate comes into equilibrium with the blood and the concentration gradient of urea and other solutes between the blood and the dialysate approaches zero. After several passes of the dialysate through the bypass flow330, the dialysate urea concentration will reflect the blood urea concentration. When valve307is operated to re-establish dialysate flow through the sorbent cartridge100, the single conductivity sensor204can be used to determine the performance of the urease-containing material as well as other sorbents to evaluate the content of the dialysate, which is in temporary equilibrium with the blood. As such, the system can be used to periodically determine the urea content of the blood followed by a return to hemodialysis treatment. Blood urea concentration or BUN and dialyzer clearance (K) can be measured as follows using the embodiment shown inFIG.10. Pre-urease conductivity (Cpre-U1) can be measured by switching valve401to permit the first sample stream306to flow to the single conductivity sensor204while valve407directs the dialysate stream301through junction501and through the sorbent cartridge100. Initial post-urease conductivity (Cpost-U1) is measured by switching valve401to allow the second sample stream307to flow through the conductivity meter204and a conductivity measurement is obtained as described above forFIG.5. Dialysate urea concentration exiting the dialyzer (Cdo) is determined by the conductivity difference between measurements Cdpre-U1and Cdpost-U1. Dialysate flow sensor203can be used to obtain the dialysate flow rate (Qd). Dialysate urea concentration is then equilibrated to blood urea concentration by switching valve407inFIG.10to divert the dialysate flow through sorbent bypass loop330to cause the dialysate to start the recirculating and equilibration process for a predetermined number of recirculation passes. Alternatively, conductivity of first sample stream306can be observed at conductivity meter204until it stabilizes, which will indicate that equilibration has occurred between blood and dialysate. With urea equilibrated between blood and dialysate, pre-urease conductivity (Cpre-U2) is measured by switching valve401to direct the first sample stream306through conductivity meter204and the conductivity measurement of the equilibrated dialysate stream310is recorded. The conductivity measurement can be recorded by means well known to those skilled in the art such as with a computer. With urea equilibrated between blood and dialysate, post-urease conductivity (Cpost-U2) is measured by switching valve407to stop the bypass re-circulation and direct the flow of urea-equilibrated dialysate through sorbent cartridge100. At the same time, valve401is switched to direct the second sample stream307to conductivity meter204and the conductivity measurement is recorded. To calculate the patient's blood urea concentration (Cbi), the conductivity difference between Cpre-U2and Cpost-U2can be correlated to urea concentration as indicated in Scheme 1. Clearance can be calculated according Equation 4 by using the blood urea concentration as Cbidetermined in the preceding step and using the difference between the conductivity readings (Cdpost-U1-Cdpre-U1) to determine dialyzer outlet urea concentration Cdo. It should be noted that individual conductivity measurements such as the equilibrated urea concentration can be performed differently and can be optionally measured before any dialysis has altered the patient's BUN. The examples ofFIGS.3-10show how the sorbent cartridge100or110can be used for urea sensing in conjunction with a hemodialysis fluid circuit. Further, in certain embodiments the fluid circuit may be configured for hemofiltration, hemodiafiltration, or peritoneal dialysis. For example,FIG.11shows how the sorbent cartridge100can be utilized in a hemofiltration circuit to measure approximate blood urea concentration, dialysate urea concentration, and urea removal. The sorbent cartridge100includes a urease material102and a sorbent material107. The sorbent cartridge outlet302is directed to a replacement fluid flow path328. A single conductivity sensor204is used to measure the conductivity of the dialyzer effluent flow path327via the sampling streams306and307before and after the dialysate passes through the urease layer102. Since ultrafiltrate has approximately the same urea concentration as whole blood, the subject's approximate BUN can be determined by measuring the conductivity change of the filtrate across the urease material102. The urea concentration of the filtrate stream310can be measured and multiplied by the filtration rate measured by the flow sensor203to determine the urea removal rate. The measurement method described can be repeated through the course of a therapy session and integrated to calculate the total urea removed during therapy. FIG.12shows how the sorbent cartridge100can be utilized in a hemodiafiltration circuit to measure blood urea concentration, dialysate urea concentration, and urea removal. The sorbent cartridge100includes a urease material102optionally configured as a layer and a sorbent material107optionally configured as a layer. The control pump415can be operated to transfer a fluid bolus from the replacement fluid reservoir328into the dialysate flow path320or to transfer dialysate from the dialysate flow path320to the replacement fluid reservoir537. The common conductivity meter204measures the conductivity of the dialyzer effluent flow path327via the sampling streams306,307before and after the dialysate passes through the urease layer102as described inFIG.10. The effluent flow rate is measured at the flow sensor203, and blood urea concentration or BUN can be calculated at the start of the therapy session, or at any time during the therapy session as described inFIG.10. FIG.13shows a configuration for using the sorbent cartridge100to measure the patient's urea concentration, spent dialysate urea concentration, and total urea removal in a peritoneal dialysis circuit. The sorbent cartridge100includes a urease material102and a sorbent material107. A common conductivity meter204measures conductivity of the dialysate stream310before and after passing through the urease containing layer102. In various embodiments, the dialysate flow sensor203or the speed of pump417can measure the flow rate of the effluent. The injection pump416can be operated to transfer dialysate from the dialysate reservoir111into the peritoneal cavity500of a subject and the extraction pump417can be operated to transfer dialysate from the peritoneal cavity500into the main dialysate flow path310for return to the sorbent cartridge100. The dialysate reservoir111can be an expandable reservoir that temporarily stores the purified dialysate exiting sorbent cartridge100downstream of the sorbent outlet flow path302. In any embodiment, the purified dialysate can be rebalanced with prescribed concentrations of electrolytes either before or after reservoir111. If the dialysate dwell time in the peritoneal cavity500is sufficiently long, the dialysate can equilibrate to the subject blood urea concentration and the blood urea concentration or BUN can be determined by measuring the conductivity change of the dialysate across the urease containing layer102as described forFIG.10. The urea concentration of the main filtrate flow path310can be measured and multiplied by the dialysate flow rate measured by flow sensor203to determine the urea removal rate. Multiple such measurements can be repeated through the course of a therapy session and integrated to measure total urea removed. FIG.14shows an embodiment employing a sorbent cartridge110similar to that shown inFIG.9having a sorbent layer108containing an ion exchange resin highly selective to Ca2+and Mg2+and releasing H+in exchange. Valves408and409alternate the first sample stream306, second sample stream322, and third sample stream307through a single or common conductivity meter204to obtain a precise conductivity difference between the fluid passing through the three sample streams, as follows: first sample stream306(post-dialyzer); second sample stream322(pre-urease); and third sample stream307(post-urease). Also, the flow diagram shown inFIG.14includes a sorbent cartridge bypass flow path330as described above forFIGS.10and12. In addition to BUN, total blood concentration of calcium and magnesium ions can also be determined. The first sorbent layer108contains a cation exchange resin highly selective for removal of the divalent Ca2+and Mg2+ions from the dialysate stream, such that substantially all Ca2+and Mg2+ions are removed, but only an insignificant proportion of the other cations such as potassium and sodium are removed by layer108. An example of such a material is a chelating cation exchange resin. An example of a commercially available chelating cation exchange resin is Chelex® 100 from Bio-Rad Laboratories, Hercules, Calif. This cation exchange can be expressed according to the following Scheme 2. The electrolytic conductivity of a single H+ion is approximately three-times greater than the electrolytic conductivity of individual Ca2+and Mg2+ions being removed by sorbent layer108. Further, since two H+ions are released for each Ca2+or Mg2+ion removed, the electrolytic conductivity of the ions exchanged is on the order of six-times greater at the outlet of sorbent layer108than at the inlet to sorbent layer108. This creates a readily measured conductivity increase that is proportional to the total amount of the total combined divalent Ca2+and Mg2+ions in the dialysate stream in the post dialyzer dialysate flow. Measurement of the total combined blood concentration of Calcium and Magnesium and also the BUN are performed as follows. Dialysate solute concentration is equilibrated to blood solute concentration by switching valve409to divert the dialysate flow through sorbent bypass loop330to cause the dialysate to start the recirculating and equilibration process and continues to recirculate for a predetermined number of recirculation passes. Alternatively, valves408and409can be positioned to pass the first sample stream306to conductivity meter204and the conductivity reading observed until it stabilizes, which will indicate that equilibration has occurred between blood and dialysate. With solutes now equilibrated between blood and dialysate, post-dialyzer conductivity (Cpost-dialyzer) is measured by switching valves408and409to direct the first sample stream306through conductivity meter204and the conductivity measurement of the equilibrated dialysate stream310is recorded. With solutes equilibrated between blood and dialysate, pre-urease conductivity (Cpre-U) is measured by switching valve409to stop the bypass re-circulation and to direct the flow of urea-equilibrated dialysate to enter dialysate regeneration unit110through inlet301. At the same time, valve408is switched to direct the second sample stream322to conductivity meter204and the pre-urease conductivity measurement is recorded. With solutes equilibrated between blood and dialysate, post-urease conductivity (Cpost-u) is measured by switching valve409to direct the sample stream307through conductivity meter204and the post-urease conductivity measurement is recorded. Because the dialysate and blood solutes are equilibrated, the patient's total combined blood concentration of calcium and magnesium is now determined by the conductivity increase between observations Cpost-dialyzerand Cpre-U. Because the dialysate and blood urea are equilibrated, the patient's blood urea concentration can be determined by the conductivity increase between observations Cpre-Uand Cpost-Uaccording to Scheme 1. The effective clearance, Keff, of either the urea or calcium/magnesium can be further calculated by taking a second set of conductivity readings from each sample stream in the non-equilibrated state and then using the ionic dialysance method of Equation 2 to calculate Kefffor urea as explained in relation toFIG.9. If the infusates containing calcium and magnesium ions are stopped when the second set of readings are taken, then Equation 2 can also be used to determine Kefffor calcium and magnesium. If the infusates containing calcium and magnesium were not turned off during the second set of conductivity readings, but instead being infused at a known concentration by a sufficiently accurate metering system, then equation 3 can be used to determine the Kefffor calcium and magnesium. The Kefffor urea and calcium and magnesium can be measured periodically throughout a therapy session and changes in the Keffcan be used to determine issues with the therapy. For example, declines in Keffcould indicate the occurrence of access recirculation and/or poor blood flow from the access and/or clotting or clogging of the dialyzer and/or dialysate flow error and/or blood flow error. Some methods for determining the underlying cause of a decrease in Keffcan include increasing the patient's anticoagulant dose to reduce clotting of the dialyzer. Also, the blood and/or dialysate flow could be increased to determine their effect on Keffand if necessary maintained at higher flow rates in order to achieve a desired Keff. As shown inFIG.14, It will be understood that the number of conductivity measurements can depend upon the number of material layers used in the sorbent system. Hence, a fourth measurement can be taken to obtain the concentration of a third solute, a fifth measurement to obtain the concentration of a fourth solute, and so on until all material layers and sensor types in the sorbent system have been measured. Conductivity measurement across additional sorbent layers will require additional sampling bypass ducts similar to sampling bypass duct321and326at the new material interfaces (not shown). Also, additional sampling valves, similar to408and409will be required (not shown) to divert the new sample streams to the conductivity sensor204. As shown inFIG.15, any embodiment of the invention can combine various concepts described herein with a fresh water/dialysate source323to dilute the dialysate. The fresh water/dialysate source323can consist of a reservoir containing water and a pump to deliver water to the dialysate flow loop. Non-limiting types of water that can be used include tap water, potable water, bottled water, deionized water and distilled water. For example, the fresh water/dialysate source323can enter the dialysate at a junction point537downstream of the dialyzer318and the infusate injector313and upstream of the sorbent cartridge100, as depicted inFIG.15. One skilled in the art will recognize that additional configurations can be used in certain embodiments of the invention, for example, the fresh water/dialysate source323can enter the dialysate at a junction point downstream of the dialyzer318and upstream of the infusate injector313. In combination with the fresh water/dialysate source323, a pre-water source sample stream324and a post-water source sample stream325can be incorporated into the dialysate flow path310and directed to the conductivity sensor204by way of a sampling valve421, such as the three-way valve shown inFIG.15. The flow from sampling valve421can be further directed to the conductivity sensor204by way of sampling valve418and sampling valve419, facilitating conductivity measurement from at least five junction points along the dialysate flow path310and320. Of course, one skilled in the art will recognize that conductivity measurements can be taken from any number of sample streams along the dialysate flow path using a single conductivity sensor204by configuring additional sampling valves in a similar manner. As further shown inFIG.15, any embodiment of the invention can combine various concepts described herein with a buffer source311to change the buffer concentration of the dialysate. The buffer source311can consist of a reservoir containing a buffer solution and a pump to deliver the buffer source to the dialysate flow loop. Non-limiting types of buffer source that can be used include aqueous solutions of bicarbonate, lactate and acetate. For example, the buffer source311can enter the dialysate at a junction point539upstream of the dialyzer318and downstream of the sorbent cartridge100, as depicted inFIG.15. One skilled in the art will recognize that additional configurations can be used in certain embodiments of the invention, for example, the buffer source311can enter the dialysate at a junction point downstream of the dialyzer318and upstream of the fresh water/dialysate source323. In combination with the buffer source311, a pre-buffer source sample stream309and a post-buffer source sample stream319can be incorporated into the dialysate flow path320and directed to the single conductivity sensor204by way of sampling valves418,419, and420. Thus, conductivity measurements can be taken from sample streams309,319,312by configuring the corresponding sampling valves418,419,420as described above with reference toFIG.7, with the substitution of the sampling valves418,419,420for the sampling valves401,414,404, respectively. In addition, conductivity measurements can be taken from sample stream324by configuring sampling valve421to close off flow from sample stream325and allow flow from sample stream324, while configuring the downstream sampling valves418and419to close off flow from sample streams309and319and allow flow from sampling valve421to the conductivity sensor204. Conductivity measurements from sample in dialysate conductivity resulting from dilution of the dialysate with water from the fresh water/dialysate source323. FIG.16is a simplified flow diagram for a controlled compliant recirculating dialysate loop utilizing a sorbent cartridge725for dialysate regeneration and a sorbent cartridge bypass loop723for achieving equilibration between the dialysate and blood. Sorbent cartridge725can include sorbent materials and function as described for sorbent cartridges100and110shown in various FIG.'s. In general, the sorbent cartridge725is designed to remove certain species from the dialysate, such as but not limited to urea, creatinine, phosphate, sulfate, calcium, magnesium, potassium and beta-2-microglobulin. Blood from a patient is directed along flow path737with pump735and enters a dialyzer709through a blood inlet flow path701and exits the dialyzer709through a blood outlet flow path703and is returned to the patient. Dialysate is recirculated and regenerated in the dialysate flow loop717. Dialysate exits the dialyzer709through the dialysate outlet flow path705and a portion of the dialysate is removed from the dialysate flow loop717with a control pump713and is collected in a reservoir711. Dialysate is recirculated through the dialysate flow loop with the dialysate pump715and continues to flow towards a sorbent cartridge725and a sorbent cartridge bypass loop723. The position of valves719,721and739determine if the dialysate flows through the sorbent cartridge725or through the sorbent cartridge bypass loop723. Other valve positions and valve types are possible to achieve flow through either the sorbent cartridge725or the sorbent cartridge bypass loop723and are well known to those skilled in the art. Next, dialysate flows to pass a sensor system727. Sensor system727may include a single sensor or multiple sensors. The specific sensors making up sensor system727may include one or several of the following, but is not limited to, a conductivity sensor, ion-selective sensor, osmotic pressure sensor, pH sensor, urea sensor, and creatinine sensor. After the sensor system727the dialysate flows to pass a reconstitution system733which acts to change the composition of the dialysate before the dialysate re-enters the dialyzer through the dialysate inlet flow path707. The reconstitution system733also functions to replace certain species that are removed by the sorbent cartridge725such as calcium, magnesium and potassium. The reconstitution system733as shown inFIG.16includes a reconstitution pump729and a reconstitution reservoir731. The reconstitution reservoir can contain, but is not limited to, electrolyte solutions such as salts of calcium, magnesium, potassium, acetate, chloride and sodium, which will be added to the dialysate via pump729in order to change the chemical composition of the dialysate. The reconstitution system may also include multiple pumps and reservoirs (not shown), each containing a different solution for delivery to the dialysate flow loop717. Other examples of chemical species that can be delivered with the reconstitution system733include bicarbonate, glucose, and lactate. The reconstitution system733can also include a reservoir containing water that will act to dilute the concentration of species in the dialysate. In certain embodiments the sorbent cartridge725can consist of ion-exchange materials that will remove certain waste species in exchange for sodium. Therefore, in order to maintain a certain dialysate sodium concentration it may become necessary to remove sodium from the dialysate by direct removal of the sodium, or by dilution of the sodium concentration by adding water to the dialysate loop717. In certain embodiments for the system illustrated inFIG.16the volume of the dialysate flow loop717can be less than 1 liter and as small as 0.5 liters. The combination of using a controlled compliant flow path, along with a sorbent cartridge725for dialysate regeneration, water feed from the reconstitution system733for sodium management, and a control pump713for the removal of a certain volume of dialysate from the dialysate flow loop717, allows the dialysate flow loop to have a small volume. In certain embodiments the dialysate flow loop volume717can be 0.5 liters or less. FIG.17shows a flow diagram similar to the one inFIG.16, except it includes a sorbent cartridge recirculation loop751. The sorbent cartridge recirculation loop751includes a recirculating pump741that recirculates the dialysate remaining in the sorbent cartridge725while the dialysate from the dialysate flow loop717is directed through the sorbent cartridge bypass loop723. The open or closed status of the two-way valves719,739and721and operation of recirculating pump741determine if dialysate will be recirculated through the sorbent cartridge recirculation loop751, flow through the sorbent cartridge bypass loop723or flow through the sorbent cartridge725. For example, by closing valves719and739and opening valve721and operating pump741the dialysate contained in the sorbent cartridge725will be recirculated through the sorbent cartridge recirculation loop751and the remaining dialysate in the dialysate flow loop717will flow through the sorbent cartridge bypass loop723. It will be apparent to those skilled in the art that other valve positions and valve types, such as three-way valves, can be utilized to achieve the same outcomes. In certain embodiments, where the sorbent cartridge725is configured, as described above, to direct various flow paths to a conductivity sensor in order to measure urea and/or calcium and magnesium concentration, it can be beneficial to recirculate the dialysate remaining in the sorbent cartridge725in order to remove certain species still present in the dialysate contained in the sorbent cartridge725. Removal of any residual species present in the dialysate contained in the sorbent cartridge725, by recirculation through the sorbent cartridge recirculation loop751may improve the accuracy of concentration measurements after dialysate equilibration with the blood has occurred. In certain embodiments the sorbent cartridge725can be of a size that can contain several hundred milliliters of dialysate, for example 100 to 1000 milliters. Therefore, any remaining volume of dialysate contained in the sorbent cartridge725will contain a certain concentration of species, for example urea, that has not been removed yet, and this urea, for example, will affect the concentration reading obtained using the sorbent cartridge sensor systems described above after dialysate equilibration has occurred with the blood. Continual recirculation of the dialysate with the sorbent cartridge recirculation loop751helps ensure complete removal of any residual species present in the dialysate contained in the sorbent cartridge725during equilibration of the dialysate with the blood. FIG.18shows a flow diagram similar to the one shown inFIG.16, except it includes a dialyzer bypass flow path767. The dialyzer bypass flow path767can be used to circulate dialysate through the sorbent cartridge725without having the dialysate pass through the dialyzer709. Two-way valves747,745and743determine where the dialysate will flow. For example, by closing valves745and743and opening valve747, the dialysate will flow through the dialyzer bypass flow path767and will not flow through the dialyzer709. It will be apparent to those skilled in the art that other valve positions and valve types, such as three-way valves, can be utilized to achieve the same flow outcomes. Recirculating the dialysate through the sorbent cartridge725without passing the dialysate through the dialyzer will completely remove certain species from the dialysate. After the complete removal of certain species from the dialysate, such as urea, the dialysate flow can be directed back through the dialyzer and concentration changes over time of certain species in the dialysate can be measured with sensor system727and used to determine the performance of the dialyzer throughout the therapy and/or the decrease in concentration of certain species in the blood throughout the therapy. FIG.19shows a flow diagram for a single-pass hemodialysis system utilizing a bypass flow loop759to achieve periodic equilibration between the dialysate and blood. Prepared dialysate enters the system through flow path753by operation of dialysate pump757and continues to pass sensor system727. The dialysate continues through the dialyzer709as described before forFIG.16. After exiting the dialyzer709through the dialysate outlet flow path705the dialysate exits the system through flow path765. By closing valves755and763and opening valve761the dialysate will be directed through the dialysate recirculation loop759and will eventually equilibrate with the blood flowing through the dialyzer709, thereby allowing the determination of blood concentration levels for certain species by utilization of sensor system727. The dialysate recirculation loop759can be prepared to have a small volume, around 500 milliliters or less to minimize the time required to reach equilibration between the dialysate and blood. FIGS.20through23illustrate the effect of various parameters on equilibration time between dialysate and blood. The governing equations used to generate the graphs are derived from a total and differential mass balance on a species between the dialysate and blood. Equation 6 shows the total mass balance for an arbitrary species at any given time during equilibration: VD·CD+VB·CB=VB·CBo[Eq. 6] where VDis dialysate volume in liters, CDis dialysate concentration at time tin mg/dL, VBis the patient volume for a particular species in liters. For urea VBwould be equal to the urea distribution volume described above. CBis the blood concentration in mg/dL at time t and CBois the blood concentration at a time defined as zero in mg/dL. Equation 7 shows the differential mass balance for the dialysate: VD·(dCD/dt)=K(CB−CD) [Eq. 7] where dCD/dt is the differential change in dialysate concentration with time and K is the dialyzer clearance for an arbitrary species as described above. The use of equations 6 and 7 assumes instantaneous transfer of species between the blood compartment of the body and extra-vascular compartments and assumes the generation of species is negligible and removal of species by means other than dialysis are also negligible. Equations 6 and 7 also assume no filtration is occurring across the dialyzer and that the dialyzer clearance K does not depend on the concentration of blood or dialysate. Equations 6 and 7 can be solved, assuming the initial dialysate concentration is zero to yield the following non-linear equation 8: CD=CBo[(1/VD)/(1/VB+1/VD)][1−e{circumflex over ( )}[−Kt(1/VB+1/VD)]] [Eq. 8] Also, the concentration of blood during equilibration can be determined by rearrangement of Eq. 8 and the total mass balance equation 6. FIG.20is generated using the equations described above to illustrate the change in dialysate and blood concentration of urea during equilibration. The results are shown for a 6 liter dialysate volume, a dialyzer clearance of 290 milliliters/minute and a starting blood urea, BUN concentration of 70 mg/dL. The dialyzer clearance of 290 milliliters/minute is used based on a blood flow of 400 ml/min and a dialysate flow of 400 milliliters/minute and a dialyzer size of 1.5 meters squared. Likewise,FIG.21shows the change in dialysate concentration and blood over time for urea during equilibrium with the same conditions as forFIG.20, except with a dialysate volume of 0.5 liters. The time to reach equilibration between blood and dialysate with 6 liters of dialysate takes over 30 minutes compared to less than 5 minutes if the dialysate volume is 0.5 liters, illustrating the significant advantage to having a small dialysate volume in terms of minimizing equilibration time.FIGS.20and21also show the blood concentration of urea over time during equilibration. As shown inFIG.21the blood concentration does not change by a significant amount during equilibration resulting in an accurate determination of the actual blood concentration. However,FIG.20shows a significant decline in blood concentration during equilibration, which will result in an inaccurate determination of blood concentration at the time point of interest.FIG.22also illustrates the effect of dialysate volume on the change in dialysate concentration of urea over time during equilibration with blood. The data shown inFIG.22is generated under the same conditions as the data inFIGS.20and21, except dialysate volumes of 1 liter and 3 liters are also shown.FIG.22also illustrates the significant effect dialysate volume has on equilibration time, even at volumes as low as 1 liter. Therefore, there is significant advantage to having a dialysate flow path with a small volume of 0.5 liters or less, as described in various embodiments of the invention. FIG.23shows the effect of dialysate flow rate on the change in dialysate concentration over time during equilibration with blood. The data is generated assuming a starting blood urea BUN concentration of 70 mg/dL, a blood flow rate of 400 ml/min, a 1.5 meter square dialyzer and a dialysate volume of 0.5 liters. The dialyzer clearance at dialysate flow rates of 50, 100, 200 and 400 ml/min are assumed to be 50, 100, 190 and 290 ml/min, respectively.FIG.23illustrates the significant effect dialysate flow rate has on equilibration time. For example, a dialysate flow rate of 100 ml/min requires 15 minutes for equilibration, compared to only 5 minutes required for a dialysate flow rate of 400 ml/min. Therefore, increasing the dialysate flow rate during equilibration will reduce the time to reach equilibrium. For example, if a dialysis therapy requires a dialysate flow rate of 100 ml/min, due to capacity and flow limitations of the sorbent cartridge, during equilibration the dialysate flow rate can be increased above 100 ml/min without affecting the sorbent cartridge because the dialysate flow will not flow through the sorbent cartridge. Likewise, the blood flow can also be increased during equilibration, which will increase the dialyzer clearance, K, and thereby decrease the equilibration time. In some cases it may beneficial to increase the blood and dialysate flow, in order to minimize the equilibration time. The filtration rate across the dialyzer will also decrease the time to reach equilibration. Therefore, continuing to perform ultrafiltration on the patient during the equilibration period will help decrease the equilibration time. InFIGS.16,17and18the control pump713can be used to provide ultrafiltration across the dialyzer. In certain embodiments the ultrafiltration rate can be increased during equilibration to achieve a further reduction in equilibration time. Another feature of the systems described forFIGS.16,17and18, is the use of a conductivity sensor as part of the sensor system727. A conductivity sensor can be used in several ways. First, the conductivity of the dialysate can be monitored during equilibration to determine when equilibration is reached. In general the conductivity of the dialysate is a measure of the sodium concentration because it is the major conductive species present. If the blood sodium concentration differs from the dialysate sodium concentration, the conductivity of the dialysate can be monitored until a plateau is reached, which would indicate that the sodium concentration of the blood has equilibrated with the sodium concentration of the dialysate. Because sodium and urea occupy approximately the same volume in a patient and transfer across the dialyzer at similar rates, equilibration of sodium will also indicate equilibration with urea. The same is also true for calcium, magnesium, potassium and chloride with respect to sodium and urea. In certain cases the dialysate sodium concentration and blood sodium concentration will be close to the same value, which would lead to a negligible change in dialysate conductivity during equilibration. In such cases the dialysate sodium concentration can be temporarily increased by adding a sodium bolus to the dialysate with the reconstitution system733described above forFIGS.16,17and18. Likewise the reconstitution system733can also temporarily decrease the sodium concentration of the dialysate by adding water to dilute the dialysate. The temporary change in sodium concentration of the dialysate will result in a sodium concentration difference between the blood and dialysate and ultimately a conductivity difference that can be monitored during equilibration to determine when equilibration is complete. Another advantage of the equilibration method is the ability to determine a patient's pre-dialysis blood sodium concentration. In some cases it is beneficial to the patient if their blood sodium concentration before and after a dialysis session remains the same, which can result in less fluid gain between dialysis sessions. By utilizing the equilibration method at the start of a dialysis session, a patient's initial blood conductivity can be determined. However, as shown, accurate determination of the patient's blood conductivity requires minimization of the equilibration time between the blood and dialysate, which can be achieved utilizing several of the methods described for certain embodiments including low volume dialysate, increased dialysate and blood flow rates, and continuation of ultrafiltration during the equilibration. As stated before the conductivity of the blood and dialysate is approximately equal to the sodium concentration of the blood and dialysate. Therefore, the conductivity of the blood at the start and end of a dialysis session can be determined using the equilibration techniques described. The therapy can then be adjusted by changing the delivery of solutions with the reconstitution system733in order to ensure the blood conductivity at the end of the session matches the conductivity at the beginning of the session, as determined with the equilibration method. The sensor system727can also include a sodium sensor for measuring sodium directly, such as an ion-selective electrode for sodium. The patient's initial pre-dialysis sodium concentration, pH, conductivity values, ammonium ion or urea concentrations, can also be used to set target values for any one of conductivity, pH, sodium concentration, ammonium ion, or urea values for the dialysate to be used during the dialysis session. In some cases the dialysate conductivity can be controlled with a closed-loop system between the conductivity sensor and the reconstitution system733. Sensor types, such as ion-selective electrodes and pH can be used in a similar manner as described herein for closed-loop control and to make measurements by calculating a difference based on any one of pH, sodium and urea concentrations, and ammonium ion concentrations. FIG.24shows a diagram for a sorbent cartridge design that includes built-in conductivity electrodes603and605. The sorbent cartridge601is similar to sorbent cartridge100described forFIG.1, except for the addition of conductivity electrodes603and605. Dialysate enters the sorbent cartridge601through the inlet flow path301and exits through the outlet flow path302after passing through multiple sorbent material layers102,103,104, and105as described forFIG.1. However, the number of sorbent materials contained in the sorbent cartridge can be varied and the position of the sorbent materials can be changed. As shown inFIG.24the sorbent materials are in discrete layers separated by interfaces625,627and629. The interface625represents where the first sorbent material102ends and the second sorbent material103begins. Likewise, interface627represents where the second sorbent material103ends and the third sorbent material104begins. Also, interface629represents where the third sorbent material104ends and the fourth sorbent material105begins. Four or more sorbent layers and the required number of interface layers are contemplated by the present invention. A central axis606is shown which represents a straight line, parallel to the direction of flow through the sorbent cartridge601, to which the sorbent cartridge601is symmetrical. The electrode pair,603and605, include one conductivity sensor that is built into the sorbent cartridge601. The electrodes603and605can be fastened through the wall of the sorbent cartridge601. Various means for fastening the electrodes603and605can be envisioned and are well known to those of skill in the art. Non-limiting examples of fastening methods may include welding and adhesive bonding, and mechanical fixation among others. The electrodes may also be fastened at each end of the sorbent cartridge as opposed to the sides, which is the configuration shown inFIG.24. The electrodes603and605have an active electrode head631and633, respectively. An electrical conductivity measurement occurs when a potential is applied across the electrode heads631and633and the current is measured. The conductivity can then be calculated with Ohm's law (V=IR), where V is the applied potential, I is the measured current and R is the resistivity, which is equal to the inverse of the conductivity. The electrode heads631and633can be made from various materials known to those with skill in the art including, but not limited to platinum, platinum-iridium, titanium, gold-plated nickel, and graphite and can be positioned at any varying radii from the central axis606. For example, electrode heads631and633can be positioned near or at a perimeter, periphery or circumference of a sorbent layer, or near or on the central axis606. In embodiments where the sorbent layer has a circumference as measured from the central axis606, the electrode heads can be positioned at any one of 7r/8, 3r/4, r/2, r/3, r/4, r/5, r/8, r/16, r/32, and r/64 where r is the radius measured from the central axis606. The portion of the electrodes603and605leading out of the sorbent cartridge601can be made from the same material as the electrode head, or other conductive materials and can serve to both stabilize the electrode heads631and633within the sorbent cartridge601and provide a path to apply the potential and measure the current across the electrode heads631and633. The potential can be applied by various sources and methods well known to those of skill in the art, including with an external power supply. The resulting current can be measured by various ways well known to those of skill in the art, including with an ammeter. It is also possible to determine the conductivity by applying a current across the electrode heads631and633and measuring the resulting potential. The electrode heads631and633shown inFIG.24can be placed in various positions within the sorbent cartridge601. As shown inFIG.24both electrode heads631and633are positioned close to the central axis606as shown in the side-view and end-view ofFIG.24. The electrode heads as positioned inFIG.24, will measure conductivity across a distance perpendicular to the central axis606. The electrode heads631and633are also located in sorbent material102near interface625. However, other positions for the electrode heads631and633are considered. For example, the electrode heads631and633can be placed in any sorbent material layer and at any distance away from the interface. Also, the electrode heads631and633can be located any position from the central axis. The distance between the electrode heads631and633can also be varied. In some cases it is beneficial to have a minimum distance between the electrode heads631and633in order to avoid local conductivity measurements that may be high or low, compared to other locations within the sorbent cartridge. In certain embodiments, the electrode heads631and633are positioned in the same sorbent material layer. Finally, multiple electrodes may be placed throughout the sorbent cartridge601in order to measure multiple conductivities at multiple positions within the sorbent cartridge601. In the case of multiple electrodes present in the sorbent cartridge601a multiplexer can be used. FIG.25shows a sorbent cartridge601with electrodes603and605similar to the ones shown inFIG.24, except the electrode heads631and633are positioned to measure conductivity across a distance parallel to the central axis606. The electrode heads631and633can also be placed in the various positions described above with reference toFIG.24, for example, at different material layers in the sorbent cartridge The positioning of the electrode heads640and641farther apart allows the conductivity to be measured across a distance parallel to the direction of flow through the sorbent cartridge and can be used to determine changes in capacity of a particular sorbent material and cumulative removal of species from the dialysate. FIG.26is similar toFIG.25except the distance between the electrode heads640and641is farther apart. The electrode heads640and641can also be placed in the various positions described above with reference toFIG.24. FIG.27is similar toFIG.26, except several electrodes609A,609B,609C,611A and611B are shown. This configuration allows multiple electrode pairs to be selected resulting in multiple conductivity measurements. For example, a potential can be applied across electrodes609A and609B and the conductivity measured or a potential can be applied across electrodes609A and611A. Other combination of electrodes can be envisioned to gather specific measurements as may be required between the various material layers in the sorbent. FIG.28is similar toFIG.27, except the electrodes are made out of mesh and function to not only measure conductivity as described forFIG.27, but also function to provide flow redistribution as dialysate flows through the sorbent cartridge608and provide separation between the sorbent layers. The mesh electrodes can have a mesh size of 1 to 100 microns and the mesh opening can be configured in various geometries, such as squares (as shown inFIG.28side-view), circles or rectangles (not shown). FIG.29shows different electrode designs that can be used in embodiments described above with reference toFIGS.24,25,26and27. It will be obvious to those skilled in the art that other electrode designs can be used. Disc electrodes603A and605A have an electrode head649and650in the shape of a disc. Rod electrodes603B and605B refer to electrodes in the shape of a rod or cylinder, with one end functioning as an electrode head651and652. Sheet electrodes603C and605C refer to an electrode with an electrode head653and654in the shape of a sheet. The sheets can be square, rectangular, circular or other solid planar geometries. The mesh electrodes603D and605D refer to an electrode with an electrode head655and656consisting of a mesh, where a mesh is the same as that described for a mesh electrode. Antenna electrodes603E and605E refer to an electrode with an electrode head657and658in the shape of an antenna, where the antenna shape refers to a serpentine structure of conductive wires or strips. Pin electrodes603F and605F refer to a rod electrode with a small diameter and an electrode head659and660. Other electrodes and electrode head geometries known within the art are contemplated and can be used in the present invention. FIG.30shows a sorbent cartridge610with electrode strips621and622built into the wall of the sorbent cartridge610. The electrode strips621and622contain active electrode areas617,618,619and620that can be used in various pair configurations to measure conductivity. The electrode strips621and622can be built into the wall of the sorbent cartridge by bonding, welding or other methods well known to those of skill in the art. The electrode strips can also include flex circuits. The sorbent cartridge could also contain a single electrode strip that wraps around the whole perimeter of the sorbent cartridge wall. The use of electrode strips built into the wall of a sorbent cartridge simplifies the construction and incorporation of electrodes into a sorbent cartridge. The electrode strips can be connected external to the sorbent cartridge in order to apply a potential and measure current across active electrode areas. The FIG.'s and specific examples provided herein illustrate a possible embodiment of the invention and are non-limiting with respect to the specific physical geometries of the various components depicted in the illustrations. It will be apparent to one skilled in the art that various combinations and/or modifications can be made in the systems and methods described herein depending upon the specific needs for operation. Moreover, features illustrated or described as being part of one embodiment may be used on another embodiment to yield a still further embodiment. | 214,187 |
11857713 | DETAILED DESCRIPTION Referring now to the drawings and in particular toFIG.1, a schematic view of peritoneal dialysis (“PD”) system10having an automated peritoneal dialysis (“APD”) machine104is illustrated. System10provides and uses an improved peritoneal equilibration test (“PET”)12, which samples and employs multiple data points for determining the patient's ultrafiltration (“UF”) curve over the course of treatment. PET12improves UF prediction used to characterize an individual's response to PD therapies and helps the clinician to generate optimized prescriptions for patients. In one embodiment, PET12is performed as a fixed therapy using the APD machine104at home. PET12also requires lab testing and analysis as set forth below. System10also performs automated regimen generation14. Known regimen generation is performed manually by a physician110or clinician120using a hit or miss type strategy, which is time consuming and relies on scientific guessing by the nurse or physician. Automated regimen generation feature14uses the results of PET12, therapy input parameters and inputted therapy target parameters to generate regimens for the physician110or clinician120, which saves time and increases the likelihood that one or more regimen is generated that meets the therapy targets for clearance and UF, minimizes glucose exposure, and meets lifestyle needs. System10further includes a prescription filtering module16, which reduces the many regimens generated by automated regimen generation feature14to a manageable number of prescriptions, which are then selected by the patient and doctor/clinician to provide a set of approved prescriptions that are loaded onto the patient's APD machine104at home. In one embodiment, the APD machine104supports up to five prescriptions that are transferred to the APD machine104via a data card, the internet or other type of data communication. The different prescriptions can include for example: two primary (or standard) prescriptions, one volume depleted (low UF) prescription, and two fluid overloaded (high UF) prescriptions, totaling five. Not all of the prescriptions have to be enabled by the physician. However, once enabled by physician, the multiple prescriptions provide flexibility to the patient and allow the APD machine104and therapy to better fit the patient's life style needs, while providing a proper therapy. Prescription filtering16naturally leads to an inventory tracking feature or module18. Different prescriptions can require the patient to store different types of PD solutions at home. For example, one type of solution may be used for nighttime exchanges, while a second type of solution is used for a last fill or day exchange. Also, the same type of solution can be provided in different dextrose quantities. System10determines what types and varieties of type of solutions are needed, quantities of such types and varieties, and what related disposable components are needed to carry out the enabled prescriptions. The APD machine104tracks how many of which type and variety of solutions are used over the course of a delivery cycle and communicates the usage to the clinician's server. The clinician's server then determines how much of which supplies need to be delivered to the patient for the next delivery cycle. When the delivery person arrives at the patient's house, he or she can scan the patient's actual remaining inventory to compare against the clinician server's expected remaining inventory. The patient's delivery can be adjusted if needed. Here, the patient's post delivery inventory is known and sent to the clinician's server. Communication is performed using a communications module discussed below. System10as mentioned includes a prescription download and therapy data upload communications module20that transfers data between the APD software and doctor/clinician's software, e.g., via any one or more of the internet, modem and cell phone. The dialysis center could use communications module20for example to send updated prescriptions to the patient's APD machine. Therapy data, logs, and trending data can be uploaded to the doctor/clinician's data center, so that the physician or clinician can access patient information at any time and from anywhere. System10also includes an automated, e.g., twenty-four hour UF, blood pressure and body weight data collection feature22. The APD machine determines patient twenty-four hour UF, and obtains blood pressure and body weight daily and automatically in one embodiment. A remote exchange system (“RES”) collects the patient's mid-day exchange data and feeds such data to the APD machine daily, e.g., via bluetooth or other wireless communication. Blood pressure and body weight devices can also communicate the patient's blood pressure and body weight to the APD machine, e.g., daily and wirelessly. Data collection feature22also includes the collection and input of therapy ranges and target information, e.g., into regimen generation feature14. System10further includes a trending and alert generation feature24. The APD machine provides, for example, up to ninety days of trending of twenty-four hour UF, blood pressure, heart rate, body weight and prescription used. The patient, clinician, and/or doctor can view these curves on the display of the APD machine, the clinician's computer, or the doctor's computer. The APD machine obtains the data necessary for the trends, sends the data to a server computer, which in turn generates and monitors the trends. The APD machine and/or clinical software monitors the patient therapy trending data and generates alerts when any of the vital parameters falls outside a physician's preset range (or outside of the range in combination with other alert filtering criteria described herein). System10further includes a prescription recall and modification feature26. Based on the data the from trend feature24, patient102, doctor110and/or dialysis center120may recall one approved prescription for daily use over another. For example, if the patient's UF results for the past few days have been less than expected, the patient102, doctor110and/or dialysis center120may decide to use a higher UF prescription as opposed to a standard UF prescription. System10for example can store three or five different prescriptions, which have all been doctor approved. The five prescriptions may include, for example, (i) low UF, (ii) standard UF with shorter duration and higher dextrose, (iii) standard UF with longer duration and lower dextrose, (iv) high UF with shorter duration and higher dextrose, and (v) high UF with longer duration and lower dextrose. If the patient102, doctor110and/or dialysis center120knows that the patient has gained weight of late, a lower dextrose prescription may be selected to reduce the caloric input from the treatment. Otherwise the patient may wish to run a shorter therapy or one without a mid-day exchange for life style reasons. System10can be configured such that the patient chooses which prescription to run on a given day. Alternatively, the dialysis instrument104runs a prescription downloaded from the dialysis center120. Further alternatively, the dialysis instrument104runs a prescription downloaded from the doctor110. System10can run a hybrid control, which for example allows the patient to choose which prescription to run on a given day as long as the patient is making responsible choices, and if the patient does not make responsible choices, system10switches so that the prescription to run is set by the machine for the patient. Alternatively, if the patient does not make responsible choices, system10can, e.g., remove less aggressive options from the list of possible prescriptions but still allow the patient to choose from the remaining prescriptions. Many PD patients lose residual renal function (“RRF”) over time, so that the PD therapy needs to remove more UF. Also, the patient's transport characteristics may diminish due to a loss of RRF. When trending function24indicates that the patient's UF is underperforming no matter which prescription the patient runs, the patient is gaining too much weight, the patient's blood pressure is too high, or a combination of these conditions occurs, system10according to module26will automatically alert that the patient's prescriptions likely need to be modified. Discussed herein are a number of measures taken so that system10is not oversensitive and allows for natural fluctuations in patient UF, due for example to instrument error and residual volume of fluid left in the patient's peritoneum. However, when the patient shows a pattern of underperformance sufficient to indicate that it is not a result of normal fluctuation, system10institutes a number of procedures to improve the patient's PD performance. For example, system10can call for a new PET to be performed, new regimens to be generated accordingly, and new prescriptions to be filtered from the regimens generated. Or, perhaps as an initial attempt, system10calls for a new set of filtering criteria (e.g., more stringent therapy criteria) to be applied to the previously generated regimens to filter out a new set of prescriptions. The new prescriptions are downloaded to the patient's dialysis instrument104via either a data memory card or via an internet link from the doctor's office110or the dialysis clinic120. Peritoneal Equilibration Test (“PET”) Referring now toFIG.2A, a cross-section from a peritoneal blood vessel illustrates the three-pores of the vessel. The three-pores each have their own toxin and UF clearance, leading to one kinetic model called the three-pore model. The three-pore model is a mathematical model that describes, correlates and predicts relationships among the time-course of solution removal, fluid transfer, treatment variables and physiological properties. The three-pore model is a predictive model that can be used for different types of dialysate, such as Dianeal®, Physioneal®, Nutrineal®, and Extraneal® dialysates marketed by the assignee of the present disclosure. The three-pore model is based on an algorithm, which is described as follows: dVDdt=JVC+JVS+JVL-L in which: VDis the peritoneal fluid volume; JVCis the flow of fluid through transcellular pores or aquaporins shown inFIG.2A; JVSis the flow of fluid through small pores shown inFIG.2A; JVLis the flow of fluid through large pores shown inFIG.2A; and L is the peritoneal lymph flow. Research has shown the three-pore model and a modified two-pool model are essentially equivalent in terms of UF and small solute clearance. The modified two-pool model is easier to implement than the three-pore model because it requires less computation, and thus less computer time. Research also has shown that the correlation between predicted results derived from the prediction software versus actual results measured from actual therapies have, for the most part, good correlation. Table 1 below shows results of one study (E. Vonesh et al., 1999). Correlations (rc) are accurate for urea removed, weekly urea clearance (pKt/V), total urea clearance (Kt/V), creatinine removed, weekly creatinnine clearance (pCCr), total creatinine clearance (CCr), glucose absorption and total effluent (drain volume). The UF correlation however is not as accurate due possibly to: APD device UF volumetric accuracy, residual solution volume in the patient, variation of patient's transport characteristics, and limited input points for estimating key kinetic parameters. TABLE 1Correlation Between Kinetic SoftwareModel And Actual Measured ResultsThree-Pore Model(PD Adequest 2.0 with APD, n = 63)MeasuredPredictedOutcome measureMeanSDMeanSDrcUrea removed (g/day)5.331.865.351.880.93Kt/V2.250.442.230.490.83pKt/V1.930.561.940.590.89Creatinine removed (g/day)0.720.310.720.310.93CCr (L/week/1.73 m2)62.8916.1161.6416.260.87pCCr (L/week/1.73 m2)47.3815.5647.3215.030.86Glucose absorption (g/day)103.161.57105.954.050.9Total effluent (L/day)14.474.8314.570.5090.98Net ultrafiltration (L/day)0.9830.6721.090.7840.23 It has been found that the certain APD devices can measure fill and drain fluid volumes very accurately. For example, the HomeChoice®/HomeChoicePRO® APD machine provided by the assignee of the present disclosure has a reported total fill and drain volume accuracy of 1% or +/−10 mL. An APD machine employing multiple exchange cycles increases the data points needed to estimate key kinetic parameters, and at the same time, reduces the possibility of introducing errors due to the residual solution volume in the patient. A new PET is accordingly proposed to improve the UF prediction accuracy, while maintaining or improving the current good prediction of small solutes (or toxins). FIG.2Billustrates an alternative (two-pool PD) kinetic model that system10can use for PET12. The two-pool PD kinetic model ofFIG.2B, like that ofFIG.2A, is used to predict fluid and solute removal in PD to: (i) aid clinicians in the care and management of patients; (ii) assist clinicians in the understanding of the physiological mechanisms that govern peritoneal transport; and (iii) simulate a therapy outcome. A set of differential equations that collectively describe both diffusive and convective mass transport in both the body and dialysate compartments for an “equivalent” membrane core are as follows: Body Compartment d(VBCB)/dt=g−KPA(CB−CD)−QUsC−KRCB Dialysate Compartment d(VDCD)/dt=KPA(CB−CD)+QUsC The diffusive mass transfer rate is the product of the mass transfer area coefficient, KPA, and the concentrate gradient, (CB-CD). KPAis in turn equal to the product of the solute membrane permeability (p) and transfer area (A). The convective mass transfer rate is the product of the net water removal (UF) rate, QU, the solute sieving coefficient, s, and the mean membrane solute concentration,C. KRis the renal residual function coefficient. Using an approximation to the above equations, an analytical solution was obtained for the ultrafiltration rate, Qu, which in turn was solved analytically for the dialysis volume, VD, at time t as follows: Dialysate Volume VD=VD1{1+1.5LPA′∑i=1mKi*-1(1-si)(CD,i1-CB,i1)(e-Ki*t/VD1)}2/3e-QL0t/VD1 in which (i) VD1is the dialysate volume immediately after infusion (mL); (ii) LPA′ is the hydraulic permeability transport rate (mL/min/mmol/L); (iii) Ki* is the ith solute's value of mass transfer area coefficient (mL/min) minus 1.5 QL0; (iv) si is the ith solute's sieving coefficient; (v) CD,i1is the ith solutes dialysate concentration immediately after infusion (mmol/L); (vi) CB,i1is the ith solutes blood concentration immediately after infusion (mmol/L); (vii) t is the time (min); and (viii) QL0is the lymphatic absorption (ml/min). UF can accordingly be calculated from the above equation knowing infusion volume, solution concentration and dwell time. The above equations were all based initially on the Pyle-Popovich two-pool model (Vonesh et al, 1991) and were later modified by Vonesh et al (1999) to incorporate key aspects of the three-pore model resulting in a modified two-pool model which is also referred to as a modified three-pore model (Vonesh et al, 1999). All subsequent references to a two-pool model or three-pore model refer to the modified model described by Vonesh et al (1999). To estimate hydraulic permeability (LPA, mL/min/mmol/L) and lymphatic flow rate, (QL, mL/min) for the modified version of the above equation, two VDvalues at corresponding dwell time t1, and t2 are needed. The VD(fill volume+UF) value is difficult to measure due to the incomplete drain (cycler) and resulting UF measurement errors. PET12as shown inFIG.3uses multiple, e.g., five, dwell volume (VD) measurements at multiple (five) different corresponding dwell times, e.g., overnight, four-hour, two-hour, one-hour and half-hour, to improve the accuracy of LPAand QLestimation and thus improve the UF prediction accuracy. In one embodiment, the PET12of the present disclosure begins with a UF versus dwell time evaluation performed over the course of two treatments (e.g., two evenings or back to back) by directly estimating the patient's fluid transport parameters and correlating the measured parameters with other PET results. UF removed for a particular type of dialysate is measured by filling the patient with fresh dialysate, allowing the solution to dwell within the patient's peritoneum for a prescribed time, draining the patient, and subtracting the fill volume from the drain volume to determine a UF volume for that particular dwell time. In one implementation, on a first night, using a standard dialysate, such as a 2.5% dextrose Dianeal® dialysate, the APD machine runs four separate two liter fill/drain cycles: a first cycle at a thirty minute dwell; second cycle at a sixty minute (one hour) dwell; third cycle at a 120 minute (two hour) dwell; and a fourth cycle at a 240 minute (four hour) dwell. Total of all dwell times is about seven hours, thirty minutes, which including the time needed for filling and draining consumes about a typical nine and one-half hour total therapy time. The APD machine records fill volume, drain volume and actual dwell time for each cycle. The fill volume may be slightly less or more than two liters depending for example on how much fresh dialysate is actually existing initially in the bag and how empty the APD machine is able to make the bag. In any case, the fill and drain volumes are recorded accurately so that the resulting calculated UF is also accurate. In an alternative embodiment, to increase accuracy the patient weighs the dialysate bag before fill and after drain. The weight values can be sent wirelessly from the scale to the APD machine (as discussed in detail below). The patient alternatively enters weight data manually. The APD machine subtracts the pre-fill weight from the post-drain weight to accurately determine a UF value, which is matched with the actual dwell time. The dwell time can be: (i) the time between the end of a fill and the beginning of the corresponding drain; (ii) the time between the beginning of a fill and the end of the corresponding drain; and (iii) in one preferred embodiment the time between the end of a fill and the end of the corresponding drain. In any of the scenarios, the actual dwell time will likely be slightly more or less than the prescribed dwell time. For example, in scenarios (ii) and (iii), a kinked line during drain will lengthen drain time and thus recorded dwell time. In scenario (ii) a kinked line during fill will lengthen fill time and thus recorded dwell time. The APD machine records the actual dwell times for use as shown below. The actual, not the prescribed times, are used so that any difference between actual and prescribed dwell times does not introduce error into the UF predictive model. On the next or second night, using the standard (e.g., 2.5% dextrose Dianeal®) dialysate, the APD machine patient runs a single fill volume with a 480 minute or eight hour dwell. The APD machine records actual dwell time (according to any of the scenarios (i) to (iii) above) and matches the actual dwell time with the actual UF recorded (e.g., via the APD or weigh scale) in the APD machine. At the end of two days, the APD machine has recorded five UF/dwell time data points (more or less data points could be achieved, however, the above five dwell times are acceptable and achievable over two standard eight hour therapies). In one embodiment, the APD machine sends the UF/dwell time data points to a server computer located at a dialysis clinic120or doctor's office110(FIGS.15A,15B,16A and16B) at which the remainder of the PET12is performed. Various embodiments for linking the APD machine to a server computer are shown herein, for example, an electronic mail link can be used to transport data. In another embodiment, the APD machine records the five (or other number) data points onto a patient data card that the patient inserts into the APD machine. The patient then brings the data card and accompanying data to the dialysis center120or doctor's office110to complete PET12. The patient then travels to the dialysis center or doctor's office, e.g., the next day. The patient is filled an additional time and drained typically after four hours. Blood and dialysate samples are taken for example at two hours and four hours. A second four-hour dwell UF data point can be taken and compared to the first four-hour dwell UF data point for additional accuracy. Alternatively, the second blood sample is taken at four hours but the patient is drained at, e.g., five hours, providing an additional UF dwell data point. FIG.3illustrates a plot of the UF data points for the different actual dwell times. The server computer, or other clinical software computer is programmed to fit a curve30to the five data points. Curve30fills the gaps between the different recorded dwell periods (e.g., at 0.5 hour, one hour, two hours, four hours and eight hours) and thus predicts the UF that will be removed for any dwell period within the eight hour range and beyond, and for the particular dialysate and dextrose level used. The osmotic gradient created by the dextrose in the dialysis solution decreases with time as dextrose is absorbed by the body. The patient's ultrafiltration rate accordingly begins at a high level and decreases over time to a point at which the rate actually becomes negative, such that the patient's body begins to reabsorb fluid. Thus UF volume as shown in the graph can actually decrease after a certain dwell time. One of the goals of the present disclosure is to learn the patient's optimal UF dwell time, which may be dextrose level dependent, and incorporate the optimal dwell time(s) into the prescriptions discussed in detail below. In the illustrated embodiment, curve30predicts UF removed for 2.5 percent dextrose. Once the curve is fitted for a particular patient, the curve can then be calculated using the kinetic model to predict UF/dwell time values for other dialysates and other dextrose levels, e.g., for 1.5 percent and 4.25 percent dextrose levels. As shown inFIG.3, for 2.5 percent dextrose, curve30has a maximum UF removed dwell time of about three hundred minutes or five hours. Five hours is likely too long a dwell time, however, UF for a dwell time of two hours or 2.5 hours comes fairly close to the maximum UF dwell time. A dwell time of two hours comes much closer to the maximum for 1.5 percent dextrose. 4.25 percent dextrose lends itself to longer dwells as seen inFIG.3. For example, a single day exchange is a good application for 4.25 percent dextrose. Besides predicting optimal UF, the five or six UF data points, blood testing and dialysate testing data are taken using a particular dialysate, such as 2.5 percent dextrose Dianeal® dialysate. Each of the UF, blood and dialysate the data are used to generate mass transfer area coefficient (“MTAC”) data and hydraulic permeability data to classify the patient's transport and UF characteristics. The MTAC data and hydraulic permeability data can then also be applied physiologically to other types of dialysates, such as 1.5 or 4.5 percent dextrose solutions and for different formulations, such as Extraneal® and Nutrineal® dialysates provided by the assignee of the present disclosure. That is, curve30is shown for one concentration. However, once the kinetic model and LPAand QL(from PET test results) are known, system10could calculate the VDaccording to the algorithm above, for each the solution type, dextrose concentration, dwell time, and fill volume. An LPAvalue of 1.0 (mL/min/mmol/L) and a QLvalue of 0.8 ml/min were used in the simulation for curve30(2.5% dextrose) and the curves for 1.5% dextrose and 4.25% dextrose inFIG.3. A kinetic modeling simulation was conducted using the above algorithm for dialysate volume VD, and the following data shown in Table 2 was generated, which shows a comparison of UF estimation and associated error using a known PET and PET12. Data showed that the PET12improved the UF prediction accuracy significantly compared with a known PET. TABLE 2UF Prediction Accuracy Using PET 12True UF withUF PredictionUF PredictionUF PredictionUF PredictionDwell TimeDextrose of 2.5%Using Known PETError UsingUsing PET 12Error Using(min)(mL)(mL)Known PET(mL)PET 123086.73158.8183.1%111.4828.5%60158.74281.5277.3%201.2826.8%90217.88374.3771.8%272.4925.1%120265.71442.2166.4%327.6823.3%150303.61488.9261.0%368.9821.5%180332.76517.7055.6%398.2519.7%210354.20531.2450.0%417.0417.7%240368.86531.7944.2%426.7215.7%270377.54521.2838.1%428.4813.5%300380.95501.3531.6%423.3511.1%330379.73473.4424.7%412.238.6%360374.42438.7917.2%395.925.7%390365.53398.449.0%375.112.6%420353.49353.340.0%350.42−0.9%450338.69304.29−10.2%322.39−4.8%480321.48252.00−21.6%291.49−9.3%510302.16197.07−34.8%258.15−14.6%540281.00140.03−50.2%222.73−20.7% Automated Regimen Generation As seen inFIG.1, present system10includes a therapy regimen generation module14. Regimen generation module14includes a plurality of prediction algorithms. The prediction algorithms use the above calculated patient transport and UF characteristics from PET12, target information and other therapy input information to generate the regimens. Regimen generation module14in one embodiment generates all of the possible therapy regimens that meet entered target requirements using the therapy input information and calculated patient transport and UF characteristics. The regimens generated are many as shown below. The prescription generation module16then filters the regimens generated at module14to yield a finite number of optimized prescriptions that can be performed on the APD machine for the particular patient. FIG.4Ashows one data entry screen for regimen generation module14. Data entered into the screen ofFIG.4Ais obtained from PET12.FIG.4Aprovides PET12data inputs for the dialysis center clinical nurse. The data includes the dialysate UF measurement, dialysate lab test results (urea, creatinine and glucose), and blood test results (serum urea, creatinine and glucose). Specifically, an “Overnight Exchange” module ofFIG.4Aprovides overnight exchange data input, including: (i) % dextrose, (ii) solution type, (iii) volume of solution infused, (iv) volume of solution drained, (v) dwell time(s), (vi) dialysate urea concentration (lab test result from drained dialysate), and (vii) dialysate creatinine concentration (lab test results from drained dialysate). A “Four-Hour Equilibration” module ofFIG.4Aprovides four-hour exchange data input, which is normally obtained from a patient blood sample taken in a clinic, the data including: (i) % dextrose, (ii) solution type, (iii) volume of solution infused, (iv) volume of solution drained, (v) infusion time, and (vi) drain time. A “Data” module ofFIG.4Aprovides four-hour exchange data input, including: (i) serum #1 sample time (normally 120 minutes after infusion of the dialysate), urea, creatinine, and glucose concentration, which are the clinician's inputs, “Corrected Crt” is a corrected creatinine concentration that the software algorithm calculates; (ii), (iii) and (iv) for dialysate #1, #2 and #3, sample time, urea, creatinine, and glucose concentration, which are clinician's inputs, “Corrected Crt” and “CRT D/P” (dialysate creatinine/plasma creatinine) which are calculated by software. InFIG.4B, the “serum concentration” module involves a blood test that is typically performed after the regular APD therapy, preferably in the morning, leading to result sent to the lab for analysis of creatinine, urea, glucose, and albumin. Serum concentration (sometimes called plasma concentration) is the lab test results of blood urea, creatinine and glucose concentration. A patient with end-stage kidney disease has blood urea and creatinine levels that are much higher than for people with functioning kidneys. The glucose concentration is important because it measures how much glucose the patient's body absorbs when using a dextrose-based solution. The “24-hour dialysate and urine collection” module ofFIG.4Bshows that the patient has no residual renal function, thus produces no urine. The overnight collection data is used for patient residual renal function (“RRF”) calculation, APD therapy results (fill, drain and lab test results), and for measuring the patient height and weight to calculate the patient's body surface area (“BSA”). As seen in the example for the second day of PET12, (eight hour dwell), 8000 milliliters of dialysate was infused into the patient, 8950 milliliters of dialysate was removed from the patient, yielding a net UF volume of 950 milliliters. The dialysate is sent to the lab for analysis of urea, creatinine, and glucose. A “weekly clearances” module calculates the weekly Urea Kt/V and weekly creatinine clearance (“CCL”), which are parameters that doctors use to analyze if patient has adequate clearance. FIG.4Cof regimen generation feature14shows a sample screen in which system10calculates mass transfer coefficients (“MTAC's”) and water transport parameters using the data of screens4A and4B and stored algorithms. RenalSoft™ software provided by the assignee of the present invention is one known software for calculating the data shown inFIG.4Cfrom the input data ofFIGS.4A and4B. Some of the data calculated and shown inFIG.4Cis used in an algorithm for regimen generation feature14. Specifically, the regimen generation algorithm uses the MTAC's for urea, creatinine and glucose, and the hydraulic permeability to generate the regimens FIG.4Dof regimen generation feature14shows the clinician or doctor the predicted drain volumes determined based on the hydraulic permeability ofFIG.4Cversus the actual UF measured from PET12. The results are shown for an overnight exchange (e.g., night one or night two of PET12) and the four-hour dwell test performed at the dialysis center120or doctor's office110. The difference between actual drain volume UF and predicted drain volume is calculated so that the clinician or doctor can view the accuracy of PET12and the prediction routines ofFIGS.4A to4Dfor drain volume and UF. To generate the predicted drain volumes, the operator enters a fluid absorption index. The machine also calculates a fluid absorption value used in the prediction of drain volume. As seen inFIG.4D, the software of system10has calculated the fluid absorption rate to be 0.1 ml/min based on values entered from the patient's PET. As seen at the top ofFIG.4D, the actual versus predicted drain volume for the overnight exchange was 2200 ml versus 2184 ml. The four hour (day) predicted drain versus the actual drain was 2179 ml versus 2186 ml. The bottom ofFIG.4Dshows the actual versus predicted drain values for a more common fluid absorption rate of 1.0 ml/min, which are not as close to one another as those for the 0.1 ml/min fluid absorption rate. The system can then ask the clinician to enter a fluid absorption rate that he/she would like to use for this patient when predicting UF, which is normally somewhere between and including 0.1 ml/min and 1.0 ml/min. FIG.5illustrates one possible regimen calculation input table for regimen generation feature14. The regimen calculation input table inputs Clinical Targets data including (a) minimum urea clearance, (b) minimum urea Kt/V, (c) minimum creatinine clearance, (d) maximum glucose absorption, and (e) target UF (e.g., over twenty-four hours). The table ofFIG.5also inputs Night Therapy Parameters data, such as (i) therapy time, (ii) total therapy volume, (iii) fill volume, (iv) percent dextrose for the chosen solution type, and possibly (v) solution type. Here, dwell times and number of exchanges are calculated from (ii) and (iii). Dwell time can alternatively be set according to the results of PET12as discussed above, which can be used in combination with at least one other input, such as, total time, total volume and fill volume to calculate the remainder of total time, total volume and fill volume inputs. For example, if dwell time, total volume and total time are set, system10can calculate the fill volume per exchange and the number of exchanges. The Night Therapy Parameters input also includes last fill inputs, such as (i) dwell time, (ii) last fill volume, and (iii) percent dextrose for the chosen solution type. The table ofFIG.5also inputs Day Therapy Parameters data, such as (i) therapy time, (ii) day fill volume, (iii) number of cycles, (iv) percent dextrose for the chosen solution type, and possibly (v) solution type. Day exchanges may or may not be performed. Solution type for the night and day therapies is chosen from a Solutions portion of the input table ofFIG.5, which inputs available dextrose levels, solution formulation (e.g., Dianeal®, Physioneal®, Nutrineal®, and Extraneal® dialysates marketed by the assignee of the present disclosure) and bag size. Bag size can be a weight concern especially for elderly patients. Smaller bags may be needed for regimens that use a different last fill and/or day exchange solution or dextrose level. Smaller bags may also be needed for regimens that call for a dextrose level that requires a mix from two or more bags of standard dextrose level (e.g., dextrose level of 2.0%, 2.88%, 3.38%, or 3.81%) listed under the Solutions portion of the table ofFIG.5. Mixing to produce customized dextrose level is discussed below in connection withFIG.14. Solution bag inventory management is also discussed below in connection withFIGS.10to13. The regimen calculation input table ofFIG.5also illustrates that many of the inputs have ranges, such as plus/minus ranges for the Clinical Targets data and minimum/maximum/increment ranges for certain Night Therapy Parameters data and Day Therapy Parameters data. Once the clinician or doctor starts to complete the table ofFIG.5, system10automatically places suggested values in many of the other cells, minimizing the amount of entries. For example, the solutions available under Solutions data can be filled automatically based upon the solutions that have been indicated as available by the dialysis center, which is further based the available solution portfolio approved for a specific country. In another example, system10can adjust the fill volume increments for Night Therapy Parameters data automatically to use all of the available solutions (e.g., when a twelve liter therapy is being evaluated, the number of cycles and the fill volumes can range as follows: four-3000 mL fills, five-2400 mL fills, six-2000 mL fills, and seven-1710 mL fills). System10allows the operator to change any of the suggested values if desired. The software of system10calculates the predicted outcomes for all of the possible combinations of parameters based upon the ranges that are entered for each parameter. As seen inFIG.5, some regimens will have “adequate” predicted outcomes for urea clearance, creatinine clearance and UF that meet or exceed the minimum criteria selected by the clinician. Others will not. Selecting “Only Display Adequate Regimens” speeds the regimen generation process. Some patients may have hundreds of regimens that are adequate. Others may have only few, or possibly even none. When none are adequate, it may be necessary to display all regimens so that the regimens that are close to meeting the target requirements can be identified for filtering. Filtering when starting with all regimens displayed provides the clinician/doctor the most flexibility when trying to find the best prescription for the patient. System10feeds all of the therapy combinations into outcome prediction software and tabulates the results in a table that system10can then filter through as shown below in connection with prescription filtering module16. One suitable software is RenalSoft™ software provided by the assignee of the present disclosure. The combinations take into account the different ranges entered above in the regimen calculation input table ofFIG.5. Table 3 below shows the first ten results (of a total of 270 results) for one set of data inputted into system software. Here, a 1.5% night dextrose solution is chosen. No day exchange is allowed. Results are shown generated for a standard PD therapy but could alternatively or additionally be generated for other types of PD therapies, such as a tidal therapy.FIG.5has check boxes that allow either one or both of continuous cycling peritoneal dialysis (“CCPD”) or tidal therapies (both APD therapies) to be included in the regimen generation process. TABLE 3APD TherapyNightNightNightNightNumberLast FillLast FillLast FillNumber ofDay FillDay FillDay FillDexTher TimeTher VolumeFill Volumeof Night ExchVolumeSolutionDwell TimeDay ExchVolumeSolutionDwell Time11.57824000000021.5782.23000000031.5782.43000000041.5782.63000000051.5782.83000000061.57832000000071.57924000000081.5792.24000000091.5792.430000000101.5792.630000000 As stated, Table 3 illustrates ten of two-hundred seventy valid combinations possible with a 1.5% night dextrose level. The same two-hundred seventy combinations will also exist for 2% dextrose level, 2.5%, etc., night dextrose level. An equal number of valid combinations is created for each possible dextrose level when a day fill is added. Further, the last fill dwell time can be varied to create even more valid combinations. Prescription Filtering As shown above, system10allows the doctor/clinician to prescribe values for clinical targets and therapy inputs, such as patient fill volume, total therapy volume, total therapy time, etc., and generates a table, such as Table 3, containing all therapies that meet all of the clinical requirements. The table of therapies that meet all of the clinical requirements can then be automatically filtered and sorted based upon parameters such as total night therapy time, therapy solution cost, therapy weight, etc. The software uses one or more algorithm in combination with the therapy combinations (e.g., of Table 3) and the patient physiologic data generated via PET12as shown in connection withFIGS.4A to4Dto determine predicted therapy results. Therapy combinations (e.g., of Table 3) that meet the Clinical Targets ofFIG.5are filtered and presented to the clinician, nurse or doctor as candidates to become prescribed regimens. FIGS.6A and6Billustrate examples of filters that the doctor or clinician can use to eliminate regimens. InFIG.6A, minimum Urea Kt/V removal is increased from 1.5 inFIG.5to 1.7 inFIG.6A. In one embodiment, the range of +0 to −0.2 inFIG.5is applied automatically to the new minimum value set inFIG.6A. Alternatively, system10prompts the user to enter a new range or keep the same range. A Boolean “And” operator is applied to the new minimum Urea Kt/V to specify that the value must be met, subject to the applied range, in combination with the other clinical targets. InFIG.6B, minimum twenty-four hour UF removal is increased from 1.0 inFIG.5to 1.5 inFIG.6B. In one embodiment, the range of +0 to −0.2 inFIG.5is again applied automatically to the new minimum value set inFIG.6B. Alternatively, system10prompts the user to enter a new daily UF range or keep the same UF range. Again, a Boolean “And” operator is applied to the new minimum twenty-four hour UF to specify that the value must be met, subject to the applied range, in combination with the other clinical targets. The clinician and patient are free to impose additional, clinical and non clinical requirements, such as: solution cost, solution bag weight, glucose absorbed, night therapy time, day fill volume, night fill volume. Referring now toFIG.7A, the regimens that meet the Clinical Targets and other inputs ofFIG.5and the additional filtering ofFIGS.6A and6Bare shown. As seen, each of the regimens is predicted to remove at least 1.5 liters of UF per day and has a minimum Urea Kt/V removal of greater than 1.5. Regimen36is highlighted because it has the smallest day fill volume (patient comfort), the lowest solution weight (patient convenience), and the next to lowest glucose absorption value (least dietary impact). Thus, regimen36is chosen and prescribed by a doctor as a standard UF regimen. The patient, clinician and/or doctor can also pick one or more additional prescription for approval that also meets with a patient's lifestyle needs. Suppose for example that the patient is a member of a bowling team during the winter months that competes in a Saturday night league. He drinks a little more than normal while socializing. The patient and his doctor/clinician agree that a therapy regimen that removes about 20% more UF should therefore be performed on Saturday nights. Also, on bowling nights, the patient only has seven hours to perform therapy rather a standard eight hour therapy. Filtered potential prescription34highlighted inFIG.7Ais accordingly approved as a higher UF prescription, which uses a higher dextrose concentration to remove the extra UF and does so in the required seven hours. Further, suppose that the patient lives in a southern state and does yard work on the weekends during the summer months (no bowling league) and accordingly loses a substantial amount of body fluid due to perspiration. The doctor/clinician and patient agree that less than 1.5 liters of UF needs to be removed on such days. BecauseFIG.7Aonly shows regimens that remove at or over 1.5 liters of UF, further filtering is used to provide low UF regimens for possible selection as a low UF prescription. The doctor or clinician uses an additional filtering of the twenty-four hour UF screen ofFIG.6Cto restrict the prior range of daily UF that the regimes must meet. Here, the doctor/clinician looks for regimes having daily UF removals of greater than or equal to 1.1 liter and less than or equal to 1.3 liters. The Boolean “And” operator is selected such that the therapy meets all of the other clinical requirements ofFIGS.5and6A. Referring now toFIG.7B, the regimens that meet the Clinical Targets and other inputs ofFIG.5and the additional filtering ofFIGS.6A and6Care shown. As seen, each of the regimens is predicted to remove at or between 1.1 and 1.3 liters of UF per day, while meeting the minimum Urea Kt/V removal of greater than 1.5 and other clinical targets. The doctor/clinician and patient then decide on a tidal therapy regimen58(highlighted), which does not require a day exchange, and requires the shortest night therapy time. The doctor then prescribes the therapy. Referring now toFIGS.8A to8C, the three agreed-upon high UF, standard UF and low UF prescriptions are illustrated, respectively. The prescriptions are named (see upper-right corner), so that they are easily recognizable by the patient102, doctor110and clinician120. While three prescriptions are shown in this example, system10can store other suitable numbers of prescriptions as discussed herein. System10downloads the prescription parameters onto a data card in one embodiment, which is then inserted in the APD machine104, transferring the prescriptions to the non-volatile memory of the APD machine. Alternatively, the prescriptions are transferred to APD machine104via a wired data communications link, such as via the internet. In one embodiment, the patient is free to choose which prescription is performed on any given day. In an alternative embodiment, the data card or data link transfer of the prescriptions is entered into the memory of the dialysis instrument, such that the instrument runs a prescribed treatment each day automatically. These embodiments are discussed in detail below in connection with the prescription recall and adjustment module26. In any case, when the patient starts any of the therapies, system10provides instructions on which solution bags to connect to a disposable cassette for pumping since the therapies may use different solutions. FIGS.9A to9Eillustrate another filtering example for module16.FIG.9Aillustrates filtered settings on the left and corresponding results on the right, which yield223possible regimens. InFIG.9B, the clinician further filters to regimens by limiting the day fill volume (patient comfort) to 1.5 liters. Such filtering reduces the possible regimens to 59. InFIG.9C, the clinical software further filters the regimens by decreasing the regimens to 19. InFIG.9D, the clinical further filters the available regimens by reducing the glucose absorbed to 500 Kcal/day. Such action reduces the available regimens to three. FIG.9Eshows the three filtered regimens that can either be prescribed by the physician or discarded to enable another filtering exercise to be performed. The exercise ofFIGS.9A to9Dshows that prescription optimization is made convenient once the patient's physiological characteristics are known.FIGS.9A to9Dalso show suitable lists of possible filtering criteria. Inventory Tracking Referring now toFIGS.10to13, one embodiment for an inventory tracking subsystem or module18of system10is illustrated. As discussed herein, system10generates agreed-upon prescriptions, such as high UF, standard UF and low UF prescriptions as shown in connection withFIGS.8A to8C. The different prescriptions require different solutions as seen inFIG.10.FIG.10shows that the standard UF prescription uses twelve liters of 1.5% Dianeal® dialysate and two liters of Extraneal® dialysate. The high UF prescription uses fifteen to eighteen (depending on alternate dialysis used) liters of 1.5% Dianeal® dialysate and two liters of Extraneal® dialysate. The low UF prescription uses twelve liters of 1.5% Dianeal® dialysate and three liters of 2.5% Dianeal® dialysate. FIG.11shows an example screen that a server in a dialysis center120can display for a patient having the above three prescriptions. The screen ofFIG.11shows the minimum base supply inventory needed for the three prescriptions over a delivery cycle. The screen ofFIG.11shows that the patient is to be supplied the solutions needed to perform thirty-two standard UF prescription therapies. The patient is to be supplied the solutions needed to perform six high UF prescription therapies. The patient is also to be supplied the solutions needed to perform six low UF prescription therapies. The patient is further to be provided one “ultrabag” case (six 2.5 liter bags). The stem of a Y-shaped ultrabag tubing set can connect to the patient's transfer set. An empty bag is attached to the one leg of the Y and a full bag is pre-attached to the other leg of the Y. The ultrabag is used to perform CAPD exchanges if the APD machine breaks, if power is lost and the APD machine cannot operate, or if the patient is traveling and his/her supplies do not arrive on time. Additionally, the patient is also to be provided with forty-five disposable sets (one used for each treatment), which includes a disposable pumping cassette, bag line, patient line, drain line, heater bag and associated clamps and connectors. The patient is provided with low (1.5%), medium (2.5%) and high (4.25%) dextrose concentration dialysis solutions, so that the patient can remove more or less fluid by switching which dextrose level is used. Prescription flexibility (including mixing) could increase the total number of bags needed for a given month to about forty-five days worth of solutions. The patient is also to be provided forty-five caps or flexicaps, which are used to cap the patient's transfer set when the patient is not connected to the cycler. The flexicaps contain a small amount of povidone iodine to minimize the potential for bacterial growth due to touch contamination. FIG.12shows an example screen that the dialysis center120can display for a patient having the above three prescriptions. The screen ofFIG.12shows the expected actual patient inventory at the time a new delivery of inventory is to be made. That is, the screen ofFIG.12shows what inventory the server computer thinks will be at the patient's home when the delivery person arrives. In the example, the server computer expects that when the delivery person arrives at the patient's home, the patient will already have: (i) five cases (two bags per case) of 1.5% Dianeal® dialysate containing six liter bags, (ii) one case (four bags per case) of 2.5% Dianeal® dialysate containing three liter bags, (iii) one case (six bags per case) of Extraneal® dialysate containing two liter bags, (iv) twenty-four (out of a case of thirty) disposable sets, each including the apparatuses described above, (v) two 1.5%, 2.5 liter Ultrabags of dialysate (out of a case of 6), and six caps or flexicaps (out of a case of thirty). FIG.13shows an example screen that the server of dialysis center120can display for a patient having the above three prescriptions. The screen ofFIG.13shows the actual inventory that will be delivered to the patient. That is, the screen ofFIG.13shows the inventory difference between what the patient is supposed to have at the start of the inventory cycle and what the server computer thinks will be at the patient's home when the delivery person arrives. In the example, the patient needs: (i) eighty-eight, six liter bags of 1.5% Dianeal® dialysate, has ten at home, reducing the need to seventy-eight bags or thirty-nine cases (two bags per case); (ii) six, three liter bags of 2.5% Dianeal® dialysate, has four at home, reducing the need to two bags or one case (four bags per case, resulting in two extra delivered); (iii) thirty-eight, two liter bags of Extraneal® dialysate, has six at home, reducing the need to thirty-two bags or six cases (six bags per case, resulting in four extra delivered); (iv) forty-five disposable sets, has twenty-four at home, reducing the need to twenty-one or one case (thirty per case, resulting in nine extra disposable sets delivered); (v) six, 2.5 liter 1.5% Ultrabags, has two at home, reducing the need to four bags or one case (six bags per case, resulting in two extra ultrabags delivered); and (vi) forty-five flexicaps, has thirty-six at home, reducing the need to nine or one case (thirty-six per case, resulting in twenty-seven extra flexicaps delivered). In one embodiment, the dialysis center server database of the inventory tracking module18maintains and knows: (a) how much of each dialysate and other supplies the patient is supposed to have at the beginning of a delivery cycle; (b) the patient's different prescriptions, solutions used with each, and the number of times each prescription is to be used over the delivery cycle; and (c) accordingly how much of each dialysate the patient is supposed to use over a delivery cycle. Knowing the above, the inventory tracking server can calculate how much of each solution and other supplies needs to be delivered at the next delivery date. Chances are the patient has consumed more or less of one or more solution or other item than expected. For example, the patient may have punctured a solution bag, which then had to be discarded. The patient may misplace a solution bag or other item. Both instances result in more inventory being consumed than expected. On the other hand, the patient may skip one or more treatment over the course of the delivery cycle, resulting in less inventory being consumed than expected. In one embodiment, the inventory tracking module or subsystem18of system10expects that the estimated amount of solutions and other supplies is close to the actual amount needed. If too much inventory is delivered (patient used less than prescribed), the delivery person can deliver the extra inventory to the patient and scan or otherwise note the additional inventory, so that it can be saved into the inventory server memory. For the next cycle, system10updates (e.g., increases) (a) above, namely, how much of each dialysate and other supplies the patient is supposed to have at the beginning of a delivery cycle. Alternatively, the delivery person only delivers the needed amount of inventory, so as to make the patient's actual inventory at the beginning of the delivery cycle equal to the expected inventory at (a) above. If not enough inventory is scheduled for delivery (patient lost or damaged solution or related supplies for example), the delivery person brings extra inventory so as to make the patient's actual inventory at the beginning of the delivery cycle equal to the expected inventory at (a) above. The inventory subsystem18of system10in one embodiment maintains additional information such as the individual cost of the supplies, the weight of the supplies, alternatives for the required supplies if the patient depletes the required supplies during the delivery cycle. As shown above inFIGS.7A and7B, the regimen generation software in one embodiment uses or generates the weight and cost data as a factor or potential factor in determining which regimes to be selected as prescriptions. The server of the dialysis center120downloads (or transfers via data card) the alternative solution data to the patient's APD Cycler. In one implementation, when a patient starts a therapy, the patient is notified of the particular solution bag(s) needed for that day's particular prescription. If the patient runs outs of one type of solution, the system can provide an alternative based upon the solutions held in current inventory. Dextrose Mixing As shown above inFIG.5, system10contemplates using a plurality of different dextrose levels for each of the different brands or types of dialysates available, which increases the doctor/clinician's options in optimizing prescriptions for the patient. The tradeoff with dextrose is generally that higher levels of dextrose remove more UF but have higher caloric input, making weight control for the patient more difficult. The converse is also true. Dialysate (at least certain types) is provided in different standard dextrose levels including 0.5%, 1.5%, 2.5% and 4.25%. As seen inFIG.6, night dextrose, last fill dextrose and day dextrose can be chosen to have any of the above standard percentages or to have a blended dextrose level of 2.0%, 2.88%, 3.38% or 3.81%. System10uses the dialysis instrument104to mix the standard percentages to create the blended percentages. It is believed that since each of the standard dextrose level dialysates has been approved by the Federal Drug Administration (“FDA”) and that the blended dextrose levels are within approved levels, that such mixing would meet readily with FDA approval. TABLE 4Glucose-Based Solutions Mixing Ratios and Concentrations.AvailableDextroseSolutions ofDextroseMixingConcentration (%)DextroseConcentration (%)Ratioafter mixingConcentration (%)1.5 and 2.51 to 12.001.51.5 and 4.251 to 12.882.02.5 and 4.251 to 13.382.52.5 and 4.251 to 33.812.883.383.814.25 Using 1:1 or 1:3 mixing shown in Table 4 generates more dextrose solutions, providing more therapy options for clinicians. At the same time, these mixing ratios will use all the solution in a container, resulting in no waste. Referring now toFIG.14, dialysis instrument104illustrates one apparatus capable of producing the blended dextrose level dialysates. Dialysis instrument104is illustrated as being a HomeChoice® dialysis instrument, marketed by the assignee of the present dialysate. The operation of the HomeChoice® dialysis instrument is described in many patents including U.S. Pat. No. 5,350,357 (“the '357 patent”), the entire contents of which are incorporated herein by reference. Generally, the HomeChoice® dialysis instrument accepts a disposable fluid cassette50, which includes pump chambers, valve chambers and fluid flow pathways that interconnect and communicate fluidly with various tubes, such as a to/from heater bag tube52, a drain tube54, a patient tube56and dialysate supply tubes58aand58b. WhileFIG.14shows two supply tubes58aand58b, dialysis instrument104and cassette50can support three or more supply tubes and thus three or more supply bags. Further, as seen in the '357 Patent, one or both supply tubes58aand58bcan Y-connect to two supply bags if more supply bags are needed. In one embodiment, system10pumps fluid from a supply bag (not shown), through one of supply tubes58aor58b, cassette50, to a warmer bag (not shown) located on a heater tray of APD104. The warmer bag provides an area for the solutions to mix before being delivered to the patient. In such a case, the warmer bag can be fitted with one or more conductive strip, which allows a temperature compensated conductivity reading of the mixed solution to be taken to ensure that the solutions have been mixed properly. Alternatively, APD104uses inline heating in which case the mixing is done in the tubing and the patients peritoneum. To operate with cassette50, the cassette is compressed between a cassette actuation plate60and a door62. The '357 Patent describes a flow management system (“FMS”), in which the volume of fluid pumped from each pump chamber (cassette50includes two in one embodiment), after each pump stroke is calculated. The system adds the individual volumes determined via the FMS to calculate a total amount of fluid delivered to and removed from the patient. System10contemplates proportioning the pump strokes from different standard dextrose supplies using FMS to achieve a desired blended dextrose. As seen at Table 4 above, a 1.5% standard dextrose supply bag can be connected to supply line58a, while a 4.25% standard dextrose supply bag is connected to supply line58b. Dialysis machine104and cassette50pump dialysate from each supply bag in a 50/50 ratio using FMS to achieve the 2.88% blended dextrose ratio. In another example, a 2.5% standard dextrose supply bag is connected to supply line58a, while a 4.25% standard dextrose supply bag is connected to supply line58b. Dialysis machine104and cassette50pump dialysate from each supply bag in a 50/50 ratio using FMS to achieve the 3.38% blended dextrose ratio. In a further example, a 2.5% standard dextrose supply bag (e.g. 2 L bag) is connected to supply line58a, while a 4.25% standard dextrose supply bag (e.g. 6 L bag) is connected to supply line58b. Dialysis machine104and cassette50pump dialysate from each supply bag in a 25/75 (2.5% to 4.25%) ratio using FMS to achieve the 3.81% blended dextrose ratio. The first two examples can include a connection of a six liter bag of dialysate to each of lines58aand58b. In the third example, a three liter 2.5% standard dextrose supply bag is connected to supply line58a, while a three liter 4.25% supply bag is Y-connected to a six liter 4.25% supply bag, which are both in turn connected to supply line58b. Dialysis machine104and cassette50pump dialysate from each supply bag to a heater bag in one embodiment, which allows the two different dextrose dialysates to fully mix before being pumped from the heater bag to the patient. Accordingly, system10can achieve the blended dialysate ratios shown inFIG.6and others by pumping different standard dextrose levels at different ratios using FMS. Dialysis instrument104in one embodiment is configured to read bag identifiers to ensure that the patient connects the proper dialysates and proper amounts of the dialysate. Systems and methods for automatically identifying the type and quantity of dialysate in a supply bag are set forth in U.S. patent application Ser. No. 11/773,822, now U.S. Pat. No. 8,330,579, (“the '822 application”), entitled “Radio Frequency Auto-Identification System”, filed Jul. 5, 2007, assigned to the assignee of the present disclosure, the entire contents of which are incorporated herein by reference. The '822 application discloses one suitable system and method for ensuring that the proper supply bags are connected to the proper ports of cassette50. System10can alternatively use a barcode reader that reads a barcode placed on the bag or container for solution type/volume identification. In the case in which Y-connections are needed, APD machine104can prompt the patient to confirm that the Y-connection(s) to an additional bag(s) has been made. U.S. Pat. No. 6,814,547 (“the '547 patent”) assigned to the assignee of the present disclosure, discloses a pumping mechanism and volumetric control system in connection withFIGS.17A and17Band associated written description, incorporated herein by reference, which uses a combination of pneumatic and mechanical actuation. Here, volume control is based on precise control of a stepper motor actuator and a known volume pump chamber. It is contemplated to use this system instead of the FMS of the '357 Patent to achieve the above blended dextrose levels. Prescription Download And Therapy Data Upload Communication Module Referring now toFIG.15A, network100aillustrates one wireless network or communication module20(FIG.1) for communicating the PET, regimen generation, prescription filtering, inventory tracking, trending and prescription modification information (below) between patient102, doctor110and dialysis center120. Here, the patient102operates a dialysis instrument104, which communicates wirelessly with a router106a, which is in wired communication with a modem108a. The doctor110operates the doctor's (or nurse's) computer112a(which could also be connected to a doctor's network server), which communicates wirelessly with a router106b, which is in wired communication with a modem108b. The dialysis center120includes a plurality of clinician's computers112bto112d, which are connected to a clinician's network server114, which communicates wirelessly with a router106c, which is in wired communication with a modem108c. Modems108ato108ccommunicate with each other via an internet116, wide area network (“WAN”) or local area network (“LAN”). FIG.15Billustrates an alternative wired network100bor communication module20(FIG.1) for communicating the PET, regimen generation, prescription filtering, inventory tracking, trending and prescription modification information (below) between patient102, doctor110and dialysis center120. Here, the patient102includes a dialysis instrument104, which is in wired communication with modem108a. The doctor110operates the doctor's (or nurse's) computer112a(which could also be connected to a network server), which is in wired communication with a modem108b. The dialysis center120includes a plurality of clinician's computers112bto112d, which are in wired communication with a modem108c. Modems108ato108cagain communicate with each other via an internet116, WAN or LAN. In one embodiment, the data points for curve30ofFIG.3are generated at instrument104and sent to either the doctor110or the dialysis center120(most likely dialysis center102), which houses the software to fit curve30to the data points. The patient then travels to the dialysis center120to have the blood work performed and to complete the PET as discussed herein. The software configured to run the PET and regimen generation screens ofFIGS.4A,4B,5A,5B and6can be stored on clinician's server114(or individual computers112bto112d) of clinic120or computers112aof doctor110(most likely clinic120) of system100aor100b. Likewise, software configured to run the filtering and prescription optimization screens ofFIGS.6A to6C,7A,7B,8A to8C and9A to9Ecan be stored on server114(or individual computers112bto112d) of clinic120or computers112aof doctor110of system100aand100b. In one embodiment, dialysis center120runs the PET, generates the regimens and filters the prescriptions. Dialysis center120via network100(referring to either or both networks100aand100b) sends the prescriptions to doctor110. The filtering can be performed with input from the patient via either network100, telephone or personal visit. The doctor reviews the prescriptions to approve or disapprove. If the doctor disapproves, the doctor can send additional or alternative filtering criteria via network100back to dialysis center120to perform additional filtering to optimize a new set of prescriptions. Eventually, either dialysis center120or doctor110sends approved prescriptions to instrument104of patient102via network100. Alternatively, dialysis center120or doctor110stores the approved prescriptions and instrument104and on a given day queries dialysis center120or doctor110over network100to determine which prescription to run. The prescriptions can further alternatively be transferred via a data card. In an alternative embodiment, dialysis center120runs the PET and generates the regimens. Dialysis center120via network100sends the regimens to doctor110. The doctor reviews the regimens and filters same until arriving at a set of prescriptions to approve or disapprove. The filtering can again be performed with input from the patient via either network100, telephone or personal visit. If the doctor disapproves, the doctor can perform additional filtering to optimize a new set of prescriptions. Here, doctor110sends approved prescriptions to instrument104and of patient102via network100. Alternatively, doctor110stores the approved prescriptions and instrument104on a given day queries doctor110over network100to determine which prescription to run. Further alternatively, doctor110sends the approved prescriptions to dialysis center120over network100, the dialysis center stores the approved prescriptions, and instrument104on a given day queries dialysis center120over network100to determine which prescription to run. As discussed above, dialysis center120is likely in a better position to handle the inventory tracking module or software18than is doctor110. In one embodiment therefore, dialysis center120stores the software configured to run the inventory tracking screens ofFIGS.10to13. Dialysis center120communicates with dialysis instrument104and patient102via network100to control the inventory for the patient's approved prescriptions. Referring now toFIG.16A, network100cillustrates a further alternative network or communication module20(FIG.1). Network100calso illustrates the patient data collection module22ofFIG.1. It should be appreciated that the patient data collection principles discussed in connection with network100care also applicable to networks100aand100b. Network100cincludes a central clinical server118, which could be stored in one of the dialysis centers120, one of the doctor's offices110or at a separate location, such as at a facility run by the provider of system10. Each of patients102aand102b, doctors110aand110band dialysis centers120aand120bcommunicates with clinical server118, e.g., via internet116. Clinical server118stores and runs the software associated with any of the PET, regimen generation, prescription filtering, inventory tracking, trending and prescription modification (below) modules and facilitates communication between patients102a/102b, doctors110a/110band dialysis centers120a/120b. Clinical server118in one embodiment receives the PET data from one of the dialysis centers120(referring to either of centers120aor120b) and sends it to clinical server118. The UF data points ofFIG.3can be sent to clinical server118either directly from patient102(referring to either of patients102aor102b) or from dialysis center120via patient102. Clinical server118fits curve30(FIG.3) to the data points and generates the regimens and either (i) filters the regimens (perhaps with patient input) into optimized prescriptions for the doctor110(referring to either of doctors110aor110b) to approve or disapprove or (ii) sends the regimens to doctor110to filter into optimized prescriptions (perhaps with patient input). In either case, the approved prescriptions may or may not be sent to an associated dialysis center120. For example, if the associated dialysis center120runs inventory tracking module18of system10, the dialysis center120needs to know the prescriptions to know which solutions and supplies are needed. Also, if system10is operated such that the patient's dialysis instrument104(referring to either instrument104aor104b) queries the dialysis center120on a given day for which prescription to run, the dialysis center120needs to know the prescriptions. Alternatively, the patient's dialysis instrument104queries clinical server118daily for which prescription to run. It is also possible for clinical server118to run inventory tracking module18of system10, in which case the associated dialysis center120can be relegated to obtaining the PET data. Clinical server118can be a single server, e.g., a national server, which is a logical geographical boundary because different countries have different sets of approved dialysis solutions. If two or more countries have the same approved set of dialysis solutions and a common language, however, clinical server118could service the two or more countries. Clinical server118can be a single server or have spoke and hub links between multiple servers. Referring now toFIG.16B, network100dincludes a central clinical server118, which is housed at or close to one of the dialysis centers120. The dialysis center120houses a doctor's office110and a patient service area90, each including one or more computer112ato112d. Patient service area90includes a server computer114, which communicates with clinical server118in one embodiment via a local area network (“LAN”)92for the dialysis center120. Clinical server118in turn includes a clinical web server that communicates with internet116and LAN92, a clinical data server that communicates with LAN92and a clinical database that interfaces with the clinical data server. Each of patients102aand102bcommunicates with clinical server118, e.g., via internet116. Clinical server118stores and runs the software associated with any of the PET, regimen generation, prescription filtering, inventory tracking, trending and prescription modification (below) modules and facilitates communication between patients102a/102b, doctors110and dialysis centers120. Other dialysis centers120can communicate with center-based clinical server118with internet116. Any of systems100ato100dcan also communicate with an APD machine manufacturer's service center94, which can include for example a service database, a database server and a web server. Manufacturer's service center94tracks machine problems, delivers new equipment, and the like. Data Collection Feature PET module12, regimen generation module14and prescription optimization or filtering module16output data that networks100(referring now additionally to networks100cand100d) use to run dialysis therapies. In this regard, the networks114and118of system10use results from analysis that have already been performed. As seen with network100c, system10also generates real-time daily patient data, which is fed to a server114(of a center120) or118for tracking and analysis. This real-time data, along with therapy parameter inputs and therapy target inputs make up the data collection module22(FIG.1) of system10. Each dialysis machine104(referring to either or both machines104aand104b) includes a receiver122as illustrated inFIG.16A. Each receiver122is coded with an address and a personal identification number (“PIN”). The patient is equipped with a blood pressure monitor124and a weigh scale126. Blood pressure monitor124and weigh scale126are each provided with a transmitter, which sends patient blood pressure data and patient weight data, respectively, wirelessly to receiver122of dialysis machine104. The address and PIN ensure that the information from blood pressure monitor124and weigh scale126reaches the proper dialysis machine104. That is, if machines104aand104band associated blood pressure monitors124and weigh scales126are within range of each other, the addresses and PIN's ensure that the dialysis machine104areceives information from the blood pressure monitor124and weigh scale126associated with dialysis machine104a, while dialysis machine104breceives information from the blood pressure monitor124and weigh scale126associated with dialysis machine104b. The address and PIN also ensure that dialysis machines104do not receive extraneous data from unwanted sources. That is, if data from an unwanted source is somehow transmitted using the same frequency, data rate, and communication protocol of receiver122, but the data cannot supply the correct device address and/or PIN, receiver122will not accept the data. The wireless link between blood pressure monitor124, weigh scale126and dialysis machine104allows the devices to be located conveniently with respect to each other in the patient's room or house. That is, they are not tied to each other via cords or cables. Or, blood pressure and weight data are entered into instrument104manually. The wireless link however also ensures that the blood pressure data and weight data, when taken, are transferred automatically to the dialysis machine104. It is contemplated that the patient takes his/her blood pressure and weighs himself/herself before (during or directly after) each treatment to provide a blood pressure and weight data point for each treatment. Data collection module22is configured alternatively to have a wired connection between one or more of blood pressure monitor124and instrument104and weight scale126and instrument104. Another data point that is generated for each treatment is the amount of ultrafiltration (“UF”) removed from the patient. All three data points, blood pressure, patient weight and UF removed, for each treatment can be stored in the memory of the dialysis machine104, on a data card and/or be sent to a remote server114or118. The data points are used to produce performance trends as described next. Any one or combination of the processing and memory associated with any of the dialysis instrument104, doctor's (or nurse's) computer112, clinician's server114, clinical web server118or manufacturer's service center94may be termed a “logic implementer”. Trending And Alert Generation The trending analysis and statistics module24(FIG.1) of system10as seen herein calculates short term and long term moving averages of daily UF and other patient data shown below. Monitoring actual measured daily UF, only, produces too much noise due to residual volume and measurement error of the dialysis instrument104. The trending regimes of module or feature24therefore look at and trend daily data as well as data that is averaged over one or more period of time. Trending and Alert Generation Using Multiple Patient Parameters Trending module24in one embodiment uses the following equation to form the short term and long term moving averages: UFma(n)=1/k*(UF(n)+UF (n−1)+UF (n−2) . . . +UF (n−k)). For the short term moving average, typical values for k can be, e.g., three to fourteen days, such as seven days. For the long term moving average, typical values for k can be, e.g., fifteen to forty-five days, such as twenty-eight days. The difference between target UF and actual measured UF is set forth as: ΔUF=UFtarget−UFma. UFtargetis the physician prescribed UF, and UFmais the moving average value of actual daily UF measured (either daily measured value or two to three days for short term moving average). ΔUF can be either positive or negative. When the absolute value of ΔUF/UFtargetexceeds the alert threshold preset by physician, system10(either at the machine104level or via server114/118) alerts the patient and the physician110and/or clinician120, which can trigger prescription adjustment or other response as discussed below. The alert threshold can account for UF anomalies so as not to make system10false trigger or be oversensitive to daily UF fluctuations, which can inherently be significant (e.g., due to measurement error and residual volume). The following equation illustrates an example in which system10requires a number of days of a certain UF deviation: δ(alert generated)=|ΔUF/UFtarget|>X% forYdays. X % can be preset by the physician or clinician, and a typical value may be thirty to fifty percent. Y can also be preset by either the physician or clinician, and a typical value may be three to seven days. The next equation addresses the possibility of a patient skipping dialysis or the patient's UF being consistently much lower than the target UF: Ifδ=∑i=1qδi=∑i=1q❘"\[LeftBracketingBar]"ΔUF/UFtarget❘"\[RightBracketingBar]"〉P%forQdays P % can be preset by the physician or clinician, and a typical value may be 150% to 250%. Q can also be preset by the physician or clinician, and a typical value can be two to three days. The above equation calculates a difference between the daily measured UF and the target UF and expresses the difference as a percentage of the target UF to determine an error in the percentage. Then the error percentage is accumulated over several days, e.g., two to three (Q) days. If the accumulated errors exceeds the threshold (P %), system10will generate UF alerts. The following examples illustrate the above algorithm: Example #1 P=150%, Q=3 Days Day #1, patient skipped therapy, UF error=100%; Day #2, patient skipped therapy, UF error=100%; Day #3, patient performed therapy, UF error=10%; accumulated UF error=210%>150%, then it will generate alarm. Example #2 P=150%, Q=3 Days Day #1, patient skipped therapy, UF error=100%; Day #2, patient performed therapy, UF error=20%; Day #3, patient performed therapy, UF error=10%; accumulated UF error=130%<150%, no alarm will be generated. FIGS.17to21show trending screens128,132,134,136and138, respectively, which can be displayed to the patient on a display device130of the dialysis instrument104and/or on a computer monitor at doctor110or dialysis center120. It is contemplated to generate the trends at any of these locations as needed. The main trending screen128ofFIG.17allows the patient for example to select to see: (i) pulse and pressure trends; (ii) recent therapy statistics; (iii) UF trends; and (iv) weight trends. The patient can access any of the screens via a touch screen input, via a membrane or other type of switch associated with each selection, or via knob or other selector that allows one of the selections to be highlighted, after which the patient presses a “select” button. When the patient selects the pulse and pressure trends selection of the main trending screen128, display device130displays the pulse and pressure trends screen132ofFIG.18. Pulse (heart rate, line with •'s), systolic pressure (line with ▴'s), and diastolic pressure (line with ▪'s) are shown for a one month time period in units of mmHg. Selection options on the pulse and pressure trends screen132include (i) returning to the main trending screen128, (ii) seeing weekly trends for pulse, systolic pressure, and diastolic pressure instead and (iii) advancing to the next trending screen134. The one or more therapy performed during the trend period, namely, therapy number 1 (e.g., standard UF), is also shown. When the patient selects the next trending selection of the pulse and pressure trends screen132, display device130displays a recent therapy trends or statistics screen134as seen inFIG.19.FIG.19shows actual values for UF removed (in milliliters, including total UF and breakout UF's for day and night exchanges), cumulative dwell time (in hours, seconds, including total dwell and breakout dwells for day and night exchanges), drain volume (in milliliters, including total volume and breakout volumes for day and night exchanges), and filled volume (in milliliters, including total volume and breakout volumes for day and night exchanges). The recent therapy trends or statistics screen134as seen inFIG.19in one embodiment shows statistics from the previous therapy. Screen134alternatively includes a logs option that enables the patient to view the same information for prior therapies, e.g., therapies up to a month ago or since the download of the last set of prescriptions. Selection options displayed on the recent therapy trends or statistics screen134include (i) returning to the main trending screen128, (ii) returning to the previous trending screen132and (iii) advancing to the next trending screen136. When the patient selects the next trending selection of the recent therapy trends or statistics screen134, display device130displays a UF trends screen136as seen inFIG.20. UF trends screen136shows a target UF line and a measured UF line for a one month time period in units of milliliters. Selection options on the UF trend screen include (i) returning to the main trending screen128, (ii) seeing weekly trends for UF, monthly trends for UF or even three month trends for UF as long as the data is available, and (iii) advancing to the next trending screen138. The therapy performed during the UF trending period is also shown. When the patient selects the next trending selection of the recent UF trends screen136, display device130displays a patient weight trends screen138as seen inFIG.21. Patient weight trends screen138shows a measured body weight (“BW”) line for a one month time period in units of pounds. Selection options on the patient weight trend screen138include (i) returning to the main trending screen128and (ii) advancing to a next screen. The therapy performed during the BW trending period is also shown. Alternative trending charts ofFIGS.22and23display actual days on the x-axis. These trends could be reserved for the doctor110and/or dialysis center120or be accessible additionally by the patient, meaning that the alerts can be generated from the APD device104to the doctor and/or clinician or from a server computer to the doctor, clinician and/or patient. The trending charts ofFIGS.22and23show the expected UF value or UF target for the patient based upon the patient's last PET results. If the difference between expected PET UF and the actual UF increases beyond a value that the doctor or clinician determines is significant, the clinician can order a new PET with or without lab work. That is, the patient can perform the UF portion of the PET as described in connection withFIGS.2and3and bring the drain volumes to the dialysis center120. U.S. patent application Ser. No. 12/128,385, now U.S. Pat. No. 8,449,495, entitled “Dialysis System Having Automated Effluent Sampling And Peritoneal Equilibration Test”, filed May 28, 2008, the entire contents of which are incorporated herein by reference, discloses an automated PET, which results in effluent samples that the patient can bring to the dialysis center120so that the samples can be analyzed for urea clearance, creatinine clearance, etc. The trending charts ofFIGS.22and23also show which therapy prescription was used on a given day, as seen at the right side of the figures (assuming for example that therapy prescription Zero is low UF, therapy prescription One is standard UF and therapy prescription Two is high UF). As seen inFIGS.22and23, the standard UF prescription is performed on all but two days in which the high UF prescription is performed. InFIG.22, the thirty day moving average (line with •'s) in particular shows that, generally, the patient's treatment is meeting the UF goal. InFIG.23, the thirty day moving average (line with •'s) shows that after about Oct. 2, 2006, the patient's treatment started to not meet the UF goal and became progressively worse. Moreover, the entire thirty day trend line for October, 2006 slopes towards less and less UF removal. A skilled clinician here will see such trend as potentially being due to a loss of the patient's renal function and either (in conjunction with a doctor) order a new PET, provide new prescriptions or put the patient's UF performance on a close watch to see if the trend continues. The clinician/doctor could alternatively prescribe that the high UF prescription be performed more frequently in an attempt to reverse the negative-going UF trend. As alluded to above, the doctor or clinician likely does not want to be notified when a single day falls below the lower limit. The UF data therefore needs to be filtered. The filter for example considers all three of daily UF values, the seven day rolling average UF (line with ▾'s) and the thirty day rolling average (line with •'s) in an algorithm to determine if the patient's prescription needs to be modified. The filter can also consider which therapies are being performed. For example, alert notification can occur sooner if the patient runs a high percentage of High UF therapies and is still failing to meet standard therapy UF targets. One specific example of an alert algorithm is: the thirty day rolling average UF (line with •'s) has fallen by ten percent, and the actual UF (base line) has been below the lower limit for three of the past seven days while performing either the standard UF prescription or the high UF prescription. Another specific example of an alert algorithm is: the thirty day rolling average UF (line with •'s) has fallen by ten percent and the seven day rolling average UF (line with ▾'s) has fallen below the lower limit LCL, while performing either the standard UF of the high UF therapies. The alert algorithm can also take into account daily weight and blood pressure data. For example, when the UF deviation, daily blood pressure and body weight each exceed a respective safety threshold, an alert is triggered. In one specific example, system10alerts if (i) UF deviates from the target UF; and (ii) short term moving average (e.g., three to seven days) body weight (“BW”) is greater than a threshold; and (iii) short term moving average (e.g., three to seven days) systolic/diastolic blood pressure (“BP”) is greater than a threshold. BP and BW thresholds are preset by physician110. Further, body weight data alone can trigger an alarm when for example the patient is gaining weight at a certain rate or gains a certain amount of weight. Here, system10can notify the doctor110and/or clinician120, prompting a call or electronic mail to the patient asking for an explanation for the weight gain. If the weight gain is not due to diet, it could be due to an excessive amount of dextrose in the patient's prescription, such that a new lower dextrose prescription or set of such prescriptions may need to be prescribed. For example, clinician120can set the patient's target body weight, and if the daily measured body weight is off by Xw pounds for Yw days in a seven day period, body weight gain is considered excessive and an alert is triggered: ΔBW=BWm−BWtarget>XwforYwdays, where BWmis the measured daily body weight, BWtargetis the target body weight (set by doctor110or clinician120), Xw is a limit of body weight exceeding the target (set by doctor110or clinician120), and Yw is the number of days (set by doctor110or clinician120). Likewise, an increase in blood pressure alone could prompt a communication from the doctor110and/or clinician120for an explanation from the patient. It is further contemplated to trend the patient's daily bio-impedance, especially as such sensing comes of age. A bio-impedance sensor can for example be integrated into a blood pressure cuff (for wired or wireless communication with dialysis instrument104), so that such sensing does not inconvenience the patient. System10uses bio-impedance in one embodiment to monitor the dialysate patient hydration state by estimating the patient's intra and extra-cellular water. Such data aids the patient and clinician in selecting a therapy (e.g., high UF when patient is over hydrated and low UF patient is dehydrated). Bio-impedance can thereby help to control the patient's fluid balance and blood pressure. The clinician in the main is concerned about two factors: therapy effectiveness and patient compliance. Patients whose UF is below target because they are running a low UF therapy too often, or are skipping therapies, need to be told in a timely manner to change their behavior. Patients whose UF is below target but who are fully compliant and may even be performing high UF therapies to obtain their target UF may need to have their prescription(s) changed in a timely manner. The trends ofFIGS.22and23provide all such information to the clinician. System10knows accordingly if the lower than expected UF is due to compliance issues or potential therapy prescription issues. In an embodiment in which the patient chooses to pick which prescription to run on a given day, the dialysis instrument104can be programmed to provide a warning to the patient when the patient runs the low UF prescription too often (low UF prescription may be less demanding than standard UF prescription). The programming can be configured to escalate the warnings if the patient continues with this behavior, let the patient know that the dialysis center120is being notified, and notify the dialysis center accordingly. The instrument104can likewise be programmed to warn the patient if the patient skips too many treatments and notify the dialysis center120if the missed treatments continue. Here, the warning and notification can be made regardless of whether the patient picks the prescription to run or the machine104/clinic120chooses the prescriptions on a given day. FIG.24summarizes the options available for setting simple or complex alert generation logics. The parameters that could be monitored include (on the top row): (i) daily UF deviation limit, (ii) UF deviation accumulation limit, (iii) body weight target and (iv) blood pressure limit. The middle logic operators show that using one or more of (a) measured daily UF, (b) measured daily body weight, and (c) measured daily blood pressure, the limits of the top row can be combined in different combinations using “AND” logic “OR” Boolean logic to determine when to send an alert to the patient, doctor or clinician. The illustrated, alerts are based on (i) UF and BW or (ii) UF, BW and BP. An alert can be based on UF alone, however. Referring now toFIG.25, algorithm or action flow diagram140shows one alternative alert sequence for system10. Upon starting at oval142, system10collects daily UF, BP, and BW data at block144. At block146, deviation analysis is performed, e.g., based on doctor/clinician settings and rolling averages for UF, BP and BW. At diamond148, method or algorithm140of system10determines whether any of UF, BP, and BW is exceeding limits. If not, method or algorithm140waits for another day, as seen at block150, and then returns to the collection step of block144. If one or a combination of limits is exceeded at diamond148, an alert is sent to the patient, clinician and/or doctor, as seen at block152. Deviation and accumulated values are reset. A hold or watch period is then started at diamond154, e.g., for seven days, to see if the alert condition persists. During this period, it is contemplated that system10communicates between patient104, doctor110and/or clinician120daily or otherwise regularly until the low UF trend is reversed. The clinician may make suggestions during this period, e.g., to try the high UF prescription or modify the patient's diet. As discussed, dialysis center120also receives trending data for patient weight and blood pressure in addition to the UF trending data. The mean arterial pressure (“MAP”) may be the most appropriate value to trend relative to blood pressure. The clinicians evaluate the weight and MAP data concurrently during the low UF periods. If the alert condition persists for a period, e.g., seven days as seen at diamond154, method140and system10order a new PET and/or change the patient's prescription, as seen at block156. Afterwards, method140ends as seen at oval158. Patient Case Studies Patient A started peritoneal dialysis treatment just two months ago and still has residual renal function (“RRF”). His UF target is 800 mL/per day. The doctor set the alert watch to look at daily UF deviation, UF deviation accumulation and target body weight. Here, a deviation limit X was chosen to be 30%, for a period Y equal to four out of seven days. A three-day UF deviation accumulated error was chosen to be 150%. Target body weight was selected to be 240 pounds with a safety limit delta of +five pounds in seven days. The following table is an example of the measured daily twenty-four hour UF, BP and BW for a seven day period. TABLE 5Patient A measured parametersParametersSunMonTueWedThurFriSatDaily UF (mL)600650700600550750730Daily Systolic/Diastolic150/90148/95160/97153/88165/98170/95160/92Pressure (mmHg)Daily Body Weight242.5243.3243.5244.7243.1245.4245.8(LB)Daily UF Deviation25%19%13%25%31%6%9%From Target UFDaily UF Deviation——57%57%69%62%46%Accumulated ErrorDaily Body Weight2.53.33.54.73.15.45.8Deviation from Target(LB) In the week of therapy shown above for Patient A, only Thursday's daily UF falls below the 30% lower limit threshold. The three-day accumulated UF deviation does not exceed 150%. The patient's body weight stays under limit (+five pounds) in all but the last two days. Here, system10does not generate an alert. Patient B has been on PD for over two years. She is very compliant with her therapy and follows clinician's instructions strictly. She does not have any RRF and her daily UF target is 1.0 L. Here, the doctor110and/or clinician120set alert conditions as follows. A deviation limit X was chosen to be 20%, for a period Y equal to four out of seven days. A three-day UF deviation accumulated error was chosen to be 150%. Target body weight was selected to be 140 pounds with a safety limit delta of +five pounds in seven days. The following table is an example of the measured daily twenty-four hour UF, BP and BW for a seven day period TABLE 6Patient B measured parametersSunMonTueWedThurFriSatDaily UF (mL)880850920870910950930Daily Systolic/Diastolic150/93142/86147/92153/86155/90173/90166/87Pressure (mmHg)Daily Body Weight (LB)143.5144.3143.8144.3143.1144.6144.8Daily UF Deviation From12%15%8%13%9%5%7%Target UFDaily UF Deviation——35%36%30%27%21%Accumulated ErrorDaily Body Weight3.53.33.84.33.14.64.8Deviation from Target (LB) In the week of therapy shown above for Patient B, none of the daily 24-hour UF values falls below the 20% lower limit threshold. The 3-day accumulated UF deviation does not exceed 150% on any day. The patient's weight never exceeds the threshold of +five pounds. Accordingly, system10does not generate a trending alert this week. Patient C has been on PD for over a year. The patient sometimes over-eats/drinks and skips a therapy from time to time. He does not have any RRF and his daily UF target is 1.0 L. Here, the doctor110and/or clinician120set alert conditions as follows. A deviation limit X was chosen to be 25%, for a period Y equal to four out of seven days. A three-day UF deviation accumulated error was chosen to be 150%. Target body weight was selected to be 220 pounds with a safety limit delta of +five pounds in seven days. The following table is an example of his measured daily 24-hour UF, BP and WE for a seven day period. TABLE 7Patient C measured parametersSunMonTueWedThurFriSatDaily UF (mL)8807008409000700500Daily Systolic/Diastolic167/97156/88177/96163/96165/90166/90178/89Pressure (mmHg)Daily Body Weight (LB)223.5225.3223.8224.3225.1225.6225.8Daily UF Deviation From12%30%16%10%100%30%50%Target UFDaily UF Deviation——58%56%126%140%180%Accumulated ErrorDaily Body Weight3.55.33.84.35.15.65.8Deviation from Target(LB) In the week of therapy shown above for Patient C, the patient's daily UF fell below the 25% threshold on Monday, Thursday, Friday and Saturday, as highlighted. The three-day accumulated UF deviation exceeded the 150% limit after Saturday's therapy. The patient also exceeds his +five pound weight limit four times, namely, on Monday, Thursday, Friday and Saturday. System10accordingly sends a trending alert after this week. Trending and Alert Generation Using Statistical Process Control It is also contemplated to use statistical process control (“SPC”) to identify instability and unusual circumstances. Referring now toFIG.26, one example moving average or trend is shown, which shows a five-day average UF (dots) and an average UF for the previous thirty days (base middle line). A range is calculated to be the difference between the lowest and the highest UF values over the past thirty days. An upper control limit (“UCL”, line with X's through it) for a given day is calculated to be: UCL=(the moving average for the given day)+(a constant, e.g., 0.577,*the range for the given day) and the lower control limit (“LCL”, line with /'s through it) is calculated to be LCL=(the moving average for the given day)−(the constant, e.g., 0.577,*the range for the given day). FIG.26shows a UF trend created for a patient, e.g., from August 2003 through June 2004 using SPC. In December of 2003 and in April of 2004, the five day moving average UF (dots) fell below the LCL. System10could be configured to monitor the five day average and alert the patient, clinic and/or doctor when the five day moving average UF (dots) falls below the LCL (or falls below the LCL for a number of days in a row). The software configured to generate the trends can be located at the dialysis instrument104or at either server computer114or118. In various embodiments, any one or more or all of the patient102, dialysis center120or doctor110can access and view the trends. The trend data is generated whether or not the trend is actually viewed by anyone. The alerts are auto-generated in one embodiment, enabling system10to monitor patient102automatically for the dialysis center120and doctor110. FIG.27shows a second trend for the same patient after changes have been made to the patient's prescription (line with •'s). Here, the patient's daytime exchange has been changed from Nutrineal® dialysate to Extraneal® dialysate.FIG.27shows the difference a new prescription line with •'s) had on the patient's UF starting in September of 2004 and again in November of 2004 when the patient's residual renal function tapered off. The statistical process control alert algorithm can also take into account body weight (“BW”) and/or blood pressure (“BP”). If UF has a normal distribution having a mean value of μ and standard deviation of σ calculated based on time and population, and wherein C is an empirically determined constant. In most processes that are controlled using Statistical Process Control (SPC), at each time point, multiple measurements or observations are made (e.g. measure the room temperature multiple times at 8:00 AM), however in one embodiment of system10, the SPC only one measurement is made at each time point, e.g., one UF measurement, one pressure and weight reading per day. System10could then alert if: (i) short term moving average (e.g., three to seven days) UF is outside the upper control limit (UCLUF=UFtarget□+Cσ) or lower control limit (LCLUF=UFtarget□−Cσ); or (ii) short term moving average (three to seven days) body weight>BW threshold; and/or (iii) short term moving average (three to seven days) systolic/diastolic BP>BP threshold. FIG.27shows that the SPC trending charts can also display the expected UF value (line with ▴'s) for the patient based upon his/her last PET results. The thirty-day average line shows that actual UF, while lagging slightly behind expected UF (which is to be expected for a thirty day average) eventually aligns itself with the expected UF results. Here, the patient is not underperforming, he/she is able to meet target. The patient may be losing RRF, however, meaning the patient's prescription needs to be more aggressive for UF because the patient has increasing less ability to remove waste and excess water himself/herself. On the other hand, if the difference between expected UF and the actual UF increases beyond a value that the doctor/clinician determines is significant, e.g., below LCL for one or more day, the clinician/doctor can order a new PET as discussed above. Prescription Recall and Modification System10also includes a prescription recall and modification feature26shown and described above in connection withFIG.1. Referring now toFIG.28, prescription recall and adjustment feature or module26is illustrated in more detail. Prescription recall and adjustment feature or module26relies on and interfaces with other features of system10, such as the improved PET feature12, regimen generation feature14, prescription filtering feature16, and trending an alert generation feature24. As seen inFIG.28, one aspect of prescription recall and adjustment feature or module26is the selection of one of the approved prescriptions for treatment. Referring now toFIG.29, a screen160of display device130of dialysis machine104illustrates one patient selection screen that allows the patient to select one of the approved prescriptions (standard, high and low UF) for the day's treatment. The type of input can be via membrane keys or here via a touch screen overlay, for which areas162,164and166have been mapped into memory as standard UF prescription, high UF prescription and low UF prescription selections, respectively. System10in the illustrated embodiment allows the patient to select a prescription for each day's treatment. For example, if the patient has consumed more fluids than normal on a given day, the patient can run the high UF prescription. If the patient has worked out, been in the sun, or for whatever reason perspired a great deal during the day, the patient may choose to run the low UF prescription. If the patient viewing the therapy trend screens134and136above notices a drop in UF running the standard UF prescription, the patient may be empowered to choose to run the high UF prescription for a few days to see how the patient reacts to the prescription change. Presumably, daily UF will increase. But it should also be appreciated that the patient, clinician or doctor should check to see if the actual increased UF meets the increased expected UF due to the use of the high UF prescription. If the patient is underperforming for both prescriptions, it may be time for a new PET and possibly a new set of prescriptions. Allowing the patient to adjust his/her therapy as described above is likely done only when the doctor or clinician has a comfort level with the patient that the patient is compliant in terms of lifestyle and adherence to treatment. Also, the doctor/clinician may wish to make sure that the patient has enough experience with the treatment and the dialysis instrument104to be able to accurately gauge when the patient needs a high, versus a low, versus a standard UF treatment. Even though the patient is making the prescription decisions in this embodiment, the data for trending as shown above is being sent to the dialysis center120and/or doctor110, so that if the patient is making poor decisions as to which prescriptions to run, the dialysis center120and/or doctor110can detect the situation in short order and correct it. For example, system10enables the dialysis center120and/or doctor110to remove prescriptions from possible selection or to set the dialysis instrument104such that it automatically selects a prescription set at either machine104or a server computer114or118. It is believed, given the importance of a dialysis treatment, that most people will be responsible and that a conscientious and thoughtful patient will best be able to gauge when the patient may need a more aggressive or less aggressive prescription, knowing that even the less aggressive prescriptions have been approved and will remove a certain amount of UF. It is contemplated to provide more than three prescriptions. For example, the patient can have two high UF prescriptions, one that requires a longer night therapy and the other that requires a higher dextrose level. Assuming the patient knows that he/she needs to run a high UF prescription after a relatively large liquid intake day, the patient may choose the longer night therapy high UF prescription knowing that he/she has gained weight of late and is better off staying away from the higher caloric intake of the higher dextrose prescription. System10attempts to accommodate the patient's lifestyle, while ensuring that a proper therapy is performed, while also gathering therapy data over time to establish a thorough patient history that enables physiologic changes of the patient to be detected relatively quickly and accurately. In another embodiment, dialysis instrument104selects which prescription the patient is to run based on the patient's daily body weight and possibly the patient's blood pressure. The patient weighs himself/herself, a weight signal is transmitted, e.g., wirelessly to dialysis instrument104, which uses the weight signal to determine how much UF the patient has accumulated and accordingly which prescription to run. In one embodiment, the patient weighs himself/herself just prior to the last nighttime fill or just prior to a mid-day fill to establish a localized “dry weight”. The patient then weighs himself/herself at night, just after the last fill drain, to establish a localized “wet weight”. The difference between the localized “wet weight” and the localized “dry weight” determines a UF amount. The UF amount is fitted into one of a low UF range, standard UF range and high UF range. Dialysis instrument104then picks a corresponding low UF prescription, standard UF prescription or a high UF prescription to run. Alternatively, dialysis instrument104provides alternative prescriptions for a particular range, e.g., two high UF prescriptions, allowing the patient to pick one of the two high UF prescriptions. As discussed above, dialysis instrument104is configured in one embodiment to read bag identifiers to ensure that the patient connects the proper dialysate(s) and proper amount(s) of dialysate(s). In a further alternative embodiment, the doctor110or dialysis center120chooses or pre-approves the prescriptions to be run on a given day, such that the patient does not have the ability to run a different prescription. Here, fill, dwell, and/or drain times can be preset, and the dialysis instrument104can also be configured to read bag identifiers to ensure that the patient connects the proper dialysate(s) and proper amount(s) of dialysate(s). It is further contemplated to allow the patient to have input into which prescriptions are run, but wherein the doctor110or dialysis center120ultimately approves of a prescription selection or selection plan before the prescriptions are downloaded into dialysis instrument104. For example, it is contemplated that the dialysis center120send an auto-generated email to the patient102, e.g., each month one week prior to the start of the next month. The email includes a calendar, each day of the calendar shows all available prescriptions, e.g., (i) lowUF, (ii) midUFlowDEX, (iii) midUFhighDEX, (iv) highUFlowDEX and (v) highUFhighDEX. The patient clicks on one of the prescriptions for each day and sends the completed calendar to clinician120for approval. For example, the patient may choose to run one of the high UF prescriptions on the weekends and one of the middle or standard prescriptions during the week. Perhaps the patient attends physically demanding workout classes after work on Mondays and Wednesdays and selects the low UF prescription for those days. It is contemplated to allow the patient to type notes in the days to explain why a particular prescription has been proposed. For example, the patient could select the lowUF prescription and type “spin class” in that calendar day. Or the patient could select the highUFhighDEX prescription and type “birthday party, up early next day” in that calendar day. When the clinician receives the completed, proposed calendar from the patient, the clinician can either approve of the proposed calendar, call or email the patient with questions as to why one or more prescription was chosen for a particular day, forward the calendar to the doctor's office110if the clinician is concerned or has questions regarding the proposed calendar, or modify the selections in the calendar and send the modified calendar back to the patient. The clinician can review the patient's trend data when evaluating the proposed prescription calendar. For example, if the patient has been gaining weight and has selected the high dextrose standard UF for many or all of the days of the month, the clinician can call or email the patient and suggest switching to the low dextrose standard UF prescription in an attempt to control the patient's weight gain. Eventually, the clinician and the patient reach a consensus. The doctor may or may not need to be consulted. It is expected that the patient's calendars will look similar from month to month and may change naturally based on season, vacations, and holidays. When a more radical change is presented, e.g., the patient intends to start a vigorous workout or training routine and wants to introduce more low UF days, the clinician can seek doctor approval. In one embodiment, dialysis instrument104confirms that the patient wants to run a non-standard treatment on a particular day. The dialysis instrument104also enables the patient to switch to a standard therapy if the patient desires. For example, if the patient has Mondays and Wednesdays approved for a low UF prescription because the patient expects to have vigorous workouts those days, but the patient skips a workout, the patient can choose to run a standard UF prescription instead. Or, if the patient is slated to run a high UF prescription because he/she is supposed to attend a party on a given day, but misses the party, the patient can choose to run a standard UF prescription instead. Dialysis instrument104could also be configured to provide the patient with a limited amount of prescription changes from a standard UF prescription to a low or high UF prescription. For example, if the patient decides to workout Thursday instead of Wednesday, the patient could switch the prescription from standard UF to low UF on Thursday. System10could be configured to allow for one such standard to non-standard prescription change per week, for example. In another example, dialysis instrument104allows the patient to increase the UF removal at any time, that is, switch from low UF prescription to a standard or high UF prescription, or switch from a standard UF prescription to a high UF prescription at any time. If the patient chooses this option a certain number of times during the month, dialysis instrument104can be configured to send an alert to the doctor110or clinician120. The approved calendar in one embodiment is integrated with the inventory tracking feature18. The approved calendar tells the inventory tracking feature18what is needed for the next delivery cycle, which can be a month to month cycle. If the patient can plan and gain approval for multiple months, the delivery cycle can be for the multiple months. In any case, the patient can be delivered extra solution if needed to allow for switches from the planned prescriptions. In a further alternative embodiment, the patient and clinician and/or doctor agree that for each week the patient will run a certain number of standard, low and high prescriptions, e.g., five standard, one low and one high. The patient then chooses which days during the week to run the various prescriptions. The weekly allotment does not have to include any low UF or high UF allotments. The patient could have seven standard UF allotments with four low dextrose standard and three high dextrose standard prescriptions, for example. Here too, dialysis instrument104can be configured to let the patient change prescriptions in certain instances as described above. In still a further alternative embodiment, dialysis instrument104or one of the server computers114or118picks one of the approved prescriptions for the patient for each therapy. The pick can be based on any of the trending data above and/or based on a series of questions answered by the patient such as: (i) Was your fluid intake today low, moderate, average, high or very high? (ii) Was your food intake today low, moderate, average, high or very high? (iii) Was your carbohydrate intake today low, moderate, average, high or very high? (iv) Was your sugar intake today low, moderate, average, high or very high? (v) Was your activity level today low, moderate, average, high or very high? System10then picks one of the approved prescriptions for the patient. Inventory management for this embodiment can be based on average usages over the past X number of delivery cycles. In any of the above regimes, dialysis instrument104can also read bag identifiers to ensure that the patient connects the proper dialysate(s) and proper amount(s) of dialysate(s). As seen inFIG.28, the selected daily prescriptions are fed into a switch mechanism for prescription recall and modification feature26. The switch mechanism is activated when the applied alert generation algorithm of feature24computes an error that is greater than the threshold(s) of the applied alert generation algorithm. As seen inFIG.28, when the applied alert generation algorithm of feature24computes an error that is not greater than the threshold, feature26maintains the current set of prescriptions and whichever prescription recall regime is being employed. Accordingly, the switch mechanism does not switch to a new prescription or set of prescriptions. When a prescription is used for a treatment, the prescription carries with it a predicted UF, which is generated via regimen generation feature14and selected via prescription filtering feature16. Actual UF data is obtained from the short term and long term moving averages as discussed above in connection with trending and alert generation feature24, which are in turn developed from measured UF data generated at dialysis instrument104. Actual UF values area function of the patient's transport characteristics as has been described herein but also account for environmental factors, such as regimen deviation by the patient. Actual UF values are subtracted from the predicted UF values at difference generator66aand fed into the alert generation algorithm at diamond24. The actual UF values are also fed into a difference generator66b, which are used to adjust target UF values used to generate the regimens in connection with feature14. Other target values include target urea removal, target creatinine removal and target glucose absorption as discussed above. As seen at diamond24, once system10determines an alarm condition, system10triggers prescription adjustment switch mechanism. That does not necessarily mean that the patient's prescriptions will be adjusted. The doctor110ultimately makes the call based on the data of UF, patient daily weight, daily blood pressure, or estimated dry weight using a bio-impedance sensor. When it appears prescription adjustment is needed, system10via communications module20communicates with the patient, e.g., via wireless communication between APD system to modem through a router. Based on the received data, the nephrologist110at switch mechanism26could make following decisions: (i) continue with current prescriptions and come to office visit as previously planned; (ii) continue with current prescriptions but visit office sooner for possible prescription adjustment; (iii) switch to a different routine using current prescriptions, visit office soon, e.g., within two weeks, receive trending data on new routine; (iv) warn the patient that he/she is not being compliant with treatment and maintain current prescription(s); (v) warn the patient that he/she is running a low UF prescription(s) too often and maintain current prescription(s); (vi) continue with the current therapy and monitoring, but lower the UF target to A and lower the UF limit to B; and (vii) perform a new APD PET to evaluate the change of PD membrane transport characteristics and provide the center with updated therapy suggestions based upon this PET. If the patient is fully compliant and the low UF is as a result of transport characteristic changes as verified by the new PET, doctor110can order a new one or prescription be generated, including a change in one or more standard UF prescription. To do so, regimen generation module14and prescription filtering module16are used again to develop the new prescription(s). The doctor agrees to the new prescriptions and switch mechanism26changes to the new prescription(s) as seen inFIG.28. It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages. It is therefore intended that such changes and modifications be covered by the appended claims. | 116,843 |
11857714 | DETAILED DESCRIPTION There are several aspects of the present subject matter which may be embodied separately or together in the devices and systems described and claimed below. These aspects may be employed alone or in combination with other aspects of the subject matter described herein, and the description of these aspects together is not intended to preclude the use of these aspects separately or the claiming of such aspects separately or in different combinations as set forth in the claims appended hereto. Where existing therapies for treating one or more diseases may result in certain unintended side effects, additional treatment may be desired or required. One procedure which has been shown to be effective in the treatment of diseases and/or the side effects of existing therapies involving mononuclear cells is extracorporeal photopheresis or “ECP”. Extracorporeal photopheresis (also sometimes referred to as extracorporeal photochemotherapy) is a process that may include: (1) collection of mononuclear cells (MNC) from a blood source (e.g., patient, donor, blood-filled bag, etc.), (2) photoactivation treatment of the collected MNC cells, and (3) re-infusion of the treated cells (MNC) back to the blood source. More specifically, ECP involves the extracorporeal exposure of peripheral blood mononuclear cells combined with a photoactive compound, such as 8-methoxypsoralen or “8-MOP” which is then photoactivated by ultraviolet light, followed by the re-infusion of the treated mononuclear cells. The combination of 8-MOP and UV radiation may cause apoptosis or programmed cell death of ECP-treated T-cells. During ECP treatment, photoactivation is known to cause 8-MOP to irreversibly covalently bind to the DNA strands contained in the T-cell nucleus. When the photochemically damaged T-cells are reinfused, cytotoxic effects are induced. For example, a cytotoxic T-cell or “CD8+ cell” releases cytotoxins when exposed to infected or damaged cells or otherwise attacks cells carrying certain foreign or abnormal molecules on their surfaces. The cytotoxins target the damaged cell's membrane and enter the target cell, which eventually leads to apoptosis or programmed cell death of the targeted cell. In other words, after the treated mononuclear cells are returned to the body, the immune system recognizes the dying abnormal cells and begins to produce healthy lymphocytes (T-cells) to fight against those cells. ECP may result in an immune tolerant response in a patient. For example, in the case of graft versus-host disease, the infusion of apoptotic cells may stimulate regulatory T-cell generation, inhibit inflammatory cytokine production, cause the deletion of effective T-cells and result in other responses. See Peritt, “Potential Mechanisms of Photopheresis in Hematopoietic Stem Cell Transplantation,” Biology of Blood and Marrow Transplantation 12:7-12 (2006). FIG.1shows, in general, the mechanical components that make up an ECP system5and that may be used in one or more of the systems and methods described herein. The system5may include a separation component10and a treatment (i.e., irradiation) component20. Irradiation component20may be independent and housed separately from the separation component10, or components20and10may be integrated into a single device. In an embodiment in which components20and10are housed separately, the separation device10and irradiation device20may be located adjacent to each other, allowing an operator or clinician to have access to both devices during a particular treatment procedure. A blood source may be connected to a fluid circuit200as shown inFIGS.1,2,4that provides a sterile closed pathway between separation component10and irradiation component20and may be cooperatively mounted on the hardware of the separation device10. The separation device10may have one or more features of an apheresis device, such as a system marketed as the AMICUS® separator by Fenwal, Inc. of Lake Zurich, Illinois, as described in greater detail in U.S. Pat. No. 5,868,696, which is hereby incorporated herein by reference in its entirety, although any suitable separation device may be used. With reference toFIG.1, whole blood may be withdrawn from the blood source and introduced into the separation component10where the whole blood is separated to provide a target cell population. In one embodiment, the target cell population may be mononuclear cells (MNCs) or MNCs of a particular type (lymphocytes, monocytes, etc.). Other components separated from the whole blood, such as red blood cells (RBCs), plasma, and/or platelets may be returned to the blood source or collected in pre-attached containers of the blood processing set. The separated target cell population, e.g., mononuclear cells, may then be treated and irradiated in treatment component20. As discussed above, treatment of mononuclear cells may involve the photoactivation of a photoactive agent that has been combined with the mononuclear cells. Mononuclear cell collection, harvest, and transfer using a device such as the Amicus® are described in greater detail in U.S. Pat. No. 6,027,657, the contents of which are incorporated by reference herein in its entirety. Preferably, the apparatus used for the harvesting, collection and reinfusion of mononuclear cells may be a “multifunctional” automated apheresis device, as is the case with the Amicus® Separator. In other words, the separation component10may be a multifunctional automated apparatus that can perform various collection protocols and/or serve multiple purposes, as may be needed by a particular hospital or facility, such that it can be used not only in the systems and methods for performing photopheresis treatment of MNC as described herein, but can also be used for other purposes including the collection of blood and blood components including platelets, plasma, red blood cells, granulocytes and/or perform plasma/RBC exchange, among other functions required by the hospital or medical facility. FIGS.2-4depict a separator10with fluid circuit200mounted thereon (FIG.2), the fluid circuit (FIG.4) having a blood processing container14(FIG.3) defining a separation chamber12suitable for harvesting mononuclear cells (MNC) from whole blood. As shown inFIG.2, a disposable processing set or fluid circuit200(which includes container14) may be mounted on the front panel of separator10. The fluid circuit200may include a plurality of processing cassettes23L,23M and23R with tubing loops for association with peristaltic pumps on separator10. Fluid circuit200may also include a network of tubing and pre-connected containers for establishing flow communication with the blood source and for processing and collecting fluids and blood and blood components, as shown inFIG.4. As seen inFIGS.2and4, disposable processing set200may include a container60for supplying anticoagulant, a waste container62for collecting waste from one or more steps in the process for treating and washing mononuclear cells, a container64for holding saline or other wash or resuspension medium, a container66for collecting plasma, a container68for collecting the mononuclear cells and, optionally, container69for holding the photoactivation agent. Container68may also serve as the illumination container, and the illumination container68may be pre-attached to and integral with the disposable set200. Alternatively, container68may be attached to set200by known sterile connection techniques, such as sterile docking or the like. InFIG.2, container68is shown as suspended from device10. However, container68may be housed within an adjacent separately housed irradiation device20(as shown by broken lines inFIG.4), thereby eliminating the step of having the operator place container68into irradiation device20. The tubing leading to and/or from container68in fluid circuit200may be of a sufficient length to reach an irradiation device20that is adjacent to but housed separately from the separation device. With reference toFIG.4, fluid circuit200may include inlet line72, an anticoagulant (AC) line74for delivering AC from container60, an RBC line76for conveying red blood cells from chamber12of container14to container67, a platelet poor plasma (PPP) line78for conveying PPP to container66and line80for conveying mononuclear cells to and from blood processing container14and collection/illumination container68. The blood processing set may include one or more access devices (e.g., port, needle, cannula, adapter, connector, etc.) for accessing the blood source (e.g., circulatory system of a patient, blood-filled bag). As shown inFIG.4, fluid circuit200may include inlet access device70and return access device82. In an alternative embodiment, a single access device may serve as both the inlet and outlet access device. Fluid flow through fluid circuit200may be driven, controlled and adjusted by a microprocessor-based controller in cooperation with the valves, pumps, weight scales and sensors of device10and fluid circuit200, the details of which are described in the aforementioned U.S. Pat. No. 6,027,657, although any suitable controller may be used. In accordance with the present disclosure, the fluid circuit may be further adapted for association with the irradiation device20. One example of a suitable irradiation device is described in U.S. Pat. No. 7,433,030, which is incorporated by reference herein in its entirety, although any suitable irradiation device may be used. The irradiation device20may include a tray or other holder for receiving one or more containers during treatment. Referring toFIG.3, separation chamber12is defined by the walls of a flexible processing container14carried within an annular gap defined by a rotating spool element18and an outer bowl element (not shown). The blood processing container14may take the form of an elongated tube which is wrapped about the spool element18before use. The bowl and spool element18may be pivoted on a yoke between an upright position and a suspended position. In operation, the centrifuge10may rotate the suspended bowl and spool element18about an axis28, creating a centrifugal field within the processing container14. Details of the mechanism for causing relative movement of the spool18and bowl elements as described are disclosed in U.S. Pat. No. 5,360,542 entitled “Centrifuge with Separable Bowl and Spool Elements Providing Access to the Separation Chamber,” which is also incorporated herein by reference in its entirety, although any suitable separation mechanism may be used. FIG.5depicts one embodiment of an online method of treating mononuclear cells. An “online” photopheresis system includes both the blood separation device and the irradiation device in an integrated system. An online system provides for reinfusion of treated target cells back to the blood source. The fluid circuit200ofFIG.4may first be primed with a priming fluid, such as saline, albumin, and/or blood components (step30A). Whole blood may then be withdrawn from a blood source (step30B) through inlet access device70(FIG.4) and introduced into the separation chamber12of container14of processing set200, where the whole blood is subjected to a centrifugal field. The centrifugal field may separate the target cell population, e.g., mononuclear cells, from a red blood cell constituent and a platelet/plasma constituent (step32). A portion of the components of red blood cells and platelets/plasma may be returned to the blood source (steps32A and32B). Another portion of red blood cells and platelets/plasma may be diverted to other portions of the fluid circuit200(e.g., container67for RBCs, container66for plasma/platelets) for further utilization and/or processing (steps44A and44B). Collection of the mononuclear cells may proceed in one or more cycles comprising steps30B,32,32A,32B,33B,44A, and44B, with the number of processing cycles conducted in a given therapeutic procedure depending upon the total yield of MNCs to be collected. During collection of the MNCs over one or more cycles, anticoagulated whole blood may enter the separation chamber12continuously, at select intervals, and/or for a predetermined period of time. Once the desired number of cycles has taken place, the MNCs accumulated in the separation chamber12may be collected (step31). A photoactivation agent may be added to the collected MNCs (step34), and the MNCs may be irradiated (step36). The portion of red blood cells and platelets/plasma that were diverted to other portions of the fluid circuit200in steps44A and44B may be reinfused into the blood source (steps45A and45B) while the MNCs are being irradiated in step36, or they may be reinfused during reinfusion of the irradiated MNCs into the blood source (step37). AlthoughFIG.5depicts an online method of treating MNCs, offline methods are available as well. In offline methods, an apheresis device may be used to collect target cells. The collected target cells, typically contained in one or more collection containers, are severed or otherwise separated from the tubing set used during collection, where they are later treated in a separate irradiation or UVA light device followed by subsequent reinfusion of the treated cells to a blood source. During such offline methods, when the cells are transferred from the apheresis device to the irradiation device (which device may be located in another room or laboratory), communication with the blood source is severed and the cells detached from the blood source. Effective treatment of the MNCs with light may be facilitated by collecting mononuclear cells in a suspension having a suitable hematocrit, volume, and/or thickness. The hematocrit, volume, and/or thickness of the MNC suspension to be treated may affect the amount of UV light absorbed by the MNCs, given that the red blood cells in the MNC suspension block at least a portion the UV light from reaching the targeted MNCs. Control of hematocrit may be desirable in cases in which the light source of the irradiation device is configured to irradiate a set intensity of light, limited settings of light intensity values, and/or a set dose of irradiation, although hematocrit/thickness control may be desirable also in cases in which intensity, dose, and/or exposure settings may readily be adjusted according to hematocrit. It is common for a transmitter (e.g., bank of light bulbs) of an irradiation device to not be adjustable in terms of intensity of emission and therefore may emit a near-constant intensity of light. If the hematocrit of the suspended MNCs is too high (such that the red blood cells prevent the absorption of light by the MNCs), it may be desired to dilute the mononuclear cells with a diluting solution, such as plasma or saline, as shown in step33(FIG.5), to control the hematocrit, volume, and/or thickness so that a desired amount of UV light will reach the targeted MNC. The diluted mononuclear cells (in container68) may then be combined with the suitable photoactivation agent in step34. A procedure may often involve introducing fluids into the fluid circuit in excess of the optimal fluid volume to be reinfused into the blood source. For example, saline may be introduced into the fluid circuit200(FIG.4) at the initial priming stage (e.g., step30A ofFIG.5). Saline may also be added to the MNC suspension (e.g., steps33and/or33B). Anticoagulant may be added to source blood during the draw process (e.g., step30B ofFIG.5). Reinfusing treated cells and fluid remaining in the fluid circuit may result in a blood source's fluid balance at the end of the procedure being positive compared to the initial blood volume prior to the procedure. For certain blood sources for which even small total fluid volume changes (both positive and negative) are undesirable, e.g., lung transplant patients, products intended for lung transplant patients, low blood volume patients, products intended for low blood volume patients, etc., it may be desirable to monitor the final fluid balance and adjust the procedure to maintain a close to constant total blood volume before and after the procedure. Some embodiments may allow an operator to input a target fluid balance of a blood source (e.g., donor, patient, blood-filled container, etc.) and adjust a fluid procedure accordingly. Some embodiments may adjust a fluid procedure during the procedure based on a blood source becoming hypervolemic due to anticoagulation, saline boluses, prime fluid, saline drip, and/or reinfusion. Some embodiments may provide an estimate of the final fluid balance of a blood source (e.g., donor, patient, container, etc.) and make necessary procedural changes to keep the blood source at a desired fluid balance. Table 1 shows a number of inputs an operator may enter into the system5ofFIG.1that may be used by the controller to monitor fluid balance and adjust the procedure. The inputs may comprise default settings that may be optionally changed by an operator, settings that may be hard-coded into the system, and/or open settings intended to be manually inputted by an operator. TABLE 1Input nameDescriptionACD RatioConfigured ratio (e.g., in volume) of extracorporealunanticoagulated whole blood to anticoagulant duringstep 30B of FIG. 5. For example, a 10:1 ACD volumeratio is equal to 10 units in volume of extracorporealunanticoagulated whole blood processed to 1 unit ofanticoagulant.Citrate Infusion RateConfigured rate of citrate infusion into the system(CIR)during step 30B of FIG. 5 based on the citrateconcentration of the anticoagulant solution and athreshold determined by operator of mass of citrateper body weight per time. For example, it may bedetermined that a threshold CIR is 1.25 mg of citrateper kg of body weight per minute (1.25 mg/kg/min).Plasma Flush per CycleConfigured volume of plasma used in step 33B of FIG.5 to gather any remaining MNCs into container 68 ofFIG. 4Patient ParametersGender, height, weight, and hematocrit of the bloodsource prior to step 30B of FIG. 5. Hematocrit may beobtained, e.g., by historical patient information orsampling the whole blood prior to the procedure.WB to ProcessConfigured volume of total whole blood to process(WBP)during the procedure. Default value may be, e.g., 2liters. Operator may manually edit WB to process, e.g.,based on the total amount of MNCs desired.Custom PrimeIf custom prime is selected, the fluid circuit may be(Custom Prime HCT)primed with fluid in addition to saline during step 30A.For example, for low blood volume patients, anoperator may choose to prime the circuit first withsaline prior to connecting with the patient. Afterconnecting with the patient, albumin or bloodcomponents may be used to displace the saline in thefluid circuit while diverting the saline away from thepatient so that the patient receives blood as thepatient's own blood is being drawn out in step 30b ofFIG. 5. An operator may input the hematocrit of thecustom prime fluid. If custom prime is not selected,regular prime with saline without custom prime fluidmay be performed.Divert PrimeIf divert prime is selected, prime fluid leaving theseparation chamber 12 of FIG. 4 may be diverted to aseparate container, e.g., container 66 of FIG. 4, ratherthan returning to the blood source. If divert prime is notselected, prime fluid may return to the blood source,via step 32B of FIG. 5.ReinfusionAn operator may choose from a number of reinfusionoptions for steps 45A, 45B, and 37 of FIG. 5. Forexample, both treated cells and blood componentsremaining in the fluid circuit may be reinfused in steps45A, 45B, and 37. In another example, only treatedcells may be reinfused in step 37. In yet anotherexample, only blood components remaining in the fluidcircuit may be reinfused in steps 45A and 45B.Total Blood VolumeTotal blood volume of the blood source may be(TBV)manually inputted or may be calculated based on theother inputted information. Total blood volume may beupdated within the system throughout the procedure.MNC Transfer RateConfigured flow rate during step 31 of FIG. 5 of MNCsbeing directed from the separation chamber 12 of FIG.4 to container 68. The MNC transfer rate may be set ata default setting, e.g., 10 mL/min.PRP Flush RateConfigured flow rate during step 45B of FIG. 5 duringwhich platelet-rich plasma that has settled towards thebottom of container 66 of FIG. 4 may be returned tothe blood source via the separation chamber 12. ThePRP flush rate may be set at a default setting, e.g., 45mL/min.Plasma Flush VolumeConfigured volume during step 33B of FIG. 5 duringwhich a portion of platelet-poor plasma in container 66of FIG. 4 may be directed to container 68 to diluteMNCs. The plasma flush volume may be set at adefault setting.PRP RateCalculated flow rate during step 33B of FIG. 5 duringwhich the plasma flush volume in container 66 of FIG.4 is directed to container 68 to dilute MNCs. The PRPrate may be calculated based on patient parameters. Based on one or more of the inputted information in Table 1, an estimate of the final fluid balance of a blood source may be calculated. In an embodiment in which TBV is calculated based on patient parameters, the controller may be configured to calculate TBV according to Equations 1a and 1 b, where patient weight W is in kg and patient height H is in meters: TBVfemale=(0.3561H3+0.03308W+0.1833)×1000 {Eq. 1a} TBVmale=(0.3669H3+0.03219W+0.6041)×1000 {Eq. 1b} Based on the citrate infusion rate (CIR), the ACD Ratio, and the weight of the patient, the controller may be configured to calculate an acceptable whole blood flow rate for step30B ofFIG.5according to Equations 2a and 2b, where CIR is in mg/kg/min, weight W is in kg, and using an example in which the anticoagulant solution used has a citrate ion concentration of 21.4 mg/mL: EqQb=CIR×(ACDRatio+1)×W21.4mg/mL{Eq.2a} WBFlow Rate=max(min(EqQb,MaximumWBFlow Rate),10) {Eq. 2b} EqQb derived from equation 2a refers to how high the WB Flow Rate may be set to ensure that the CIR stays within the programmed limit (e.g., CIR set to 1.25 mg/kg/min). Equation 2b shows that WB Flow Rate may not exceed a maximum WB flow rate. WB Flow Rate may also not exceed EqQb, and the lower value between the maximum WB Flow Rate and the EqQb will be selected. A minimum WB Flow Rate may be utilized to maintain a certain level of accuracy around the volume pumped, and the system may be configured with a minimum WB Flow Rate of 10. In such a case, the controller may be configured to select as the WB Flow Rate the higher value between 10 m L/min and the lower value between EqQb and the maximum WB flow rate. In one embodiment, the system5may be configured to have a maximum WB flow rate of 80 m L/min. In the event the WB flow rate is less than ACD Ratio plus 1, the system may be configured to alert an operator that the ACD ratio is unachievable. Equations 2a and 2b may be used to determine flow rate at step30B except when MNCs are transferred to collection container68ofFIG.4in step31ofFIG.5. During step31, a different equation (equation 7a below) may be used to determine step30B. Based on WB Flow Rate calculated from Equation 2b and Whole Blood to Process (WBP) listed in Table 1, the controller may be configured to calculate Collection Time, which may be characterized as the time it takes to collect MNCs within separation chamber12ofFIG.4from the total whole blood to process, where WB to Process is in mL and WB Flow Rate is in mL/min: CollectionTime=WBtoProcessWBFlowRate{Eq.3} Based on WBP and the ACD Ratio in Table 1, the volume of anticoagulant solution required at step30B ofFIG.5during collection of MNCs in the separation chamber may be calculated. The anticoagulant solution volume required may be calculated by Equation 4, where WBP is in mL: ACVol.RequiredDuringCollection=WBtoProcessACDRatio+1{Eq.4} Based on the ACD Ratio, the blood source hematocrit expressed as a decimal, and the plasma flush per cycle (mL) from Table 1 and based on the AC Volume Required During Collection from Equation 4, the controller may calculate by Equation 5a below an estimated volume of AC that the blood source will receive by the end of the procedure, with the exception of the volume of AC contributed to the system during step31ofFIG.5of MNC transfer. The result of Equation 5a may be used in Equation 5b to estimate the actual citrate infusion rate the blood source will receive, with the exception of the CIR contributed to the system during step31of MNC transfer. Est.ACVol.toBloodSource=(Eq.4)-2×(PlasmaFlushperCycle)ACDRatio-(HCT)×(ACDRatio)2(ACDRatio)+1+1{Eq.5a} Est.ActualCIR=(Eq.5a)×21.4mg/mLWeight×CollectionTime{Eq.5b} Utilizing the previous equations, an estimate of the maximum extracorporeal volume of red blood cells at any given time during the procedure (Max RBC Out) may be calculated based on knowledge of the areas of the fluid circuit where the red blood cells are known to reside during the procedure. The procedure may be known to have the Max RBC Out during step44A ofFIG.5when a portion of red blood cells may be diverted to other portions of the fluid circuit200, e.g., into container67(FIG.4). The controller may be configured to display to an operator this estimate of the maximum extracorporeal volume of red blood cells. The Max RBC Out may be expressed as a percentage of a blood source's total RBCs in circulation within the system5(FIG.1), including the blood source. In one embodiment, the system may be configured to provide a response action when Max RBC Out is greater than 10-15%. Equation 6a may be used to determine the hematocrit of anticoagulated whole blood (Hct AC WB) prior to separation, using the ACD Ratio and the blood source hematocrit value expressed as a decimal. The Max RBC Out may be calculated using Equations 6b and 6c. Equation 6b may be used for an embodiment in which custom prime has not been selected, and Equation 6c may be used for an embodiment in which custom prime has been selected. HctACWB=HCT×ACDRatioACDRatio+1{Eq.6a} MaxRBCOut=(130.46×HctACWB)+0.85(45.89+RBCChamber)TBV×HctACWB{Eq.6b} MaxRBCOut=(130.46×HctACWB)+0.85(45.89+RBCChamber)(139.36×CustomPrimeHCT)+(TBV×HctACWB){Eq.6c} HCT ACWB in equation 6a refers to the hematocrit of anticoagulated whole blood within the whole blood fluid flow path of the fluid circuit200FIG.4. In one embodiment, the whole blood fluid flow path may comprise the path from the access device72to the left cassette23L to the separation chamber12. 130.46 mL in equation 6b represents the fluid volume capacity of the whole blood fluid flow path between the access device72and the separation chamber12, although a different number may be used in the equation for a different whole blood fluid flow path (e.g., different fluid circuit, different pathway configuration, etc.). RBC Chamber in equation 6b refers to the volume (in mL) of cells (primarily RBCs) pumped from the separation chamber12ofFIG.4during step44A ofFIG.5. RBC Chamber may be pre-configured as a default setting within the system or may be inputted by an operator. In one embodiment, the packed RBC flow path of the fluid circuit200may comprise the path from the separation chamber12to the middle cassette23M to the RBC container67. 45.89 mL in equation 6b represents the fluid volume capacity of the RBC fluid flow path, including the volume of RBCs disposed in container67. Equation 6b uses 0.85 as the estimate for the hematocrit of the packed RBCs disposed within the separation chamber12and the RBC fluid pathway. Equation 6c is similar to Equation 6b, except Equation 6b takes into account the custom prime fluid that has been placed into circulation within the fluid circuit. The RBCs contributed by the custom prime fluid may be described as the Custom Prime HCT (Table 1) (expressed as a decimal) multiplied by the fluid volume capacity (e.g., 139.36 mL) of the custom prime fluid flow path. In one embodiment, the custom prime fluid flow path may comprise the pathway from the access device72, into the left cassette23L, into the centrifuge, into the middle cassette23M, into the left cassette23L, and back to the blood source via access device82. As mentioned previously, equations 2a through5bdid not account for fluid volume contributions made during MNC transfer (step31ofFIG.5) during which MNCs collected within the separation chamber12ofFIG.4are transferred to the container68. During MNC transfer, the whole blood flow rate during step30B may be calculated by equation 7a as WB Flow Rate Transfer (WBFRT), which is a function of the ACD Ratio from Table 1 and the WB Flow Rate from equation 2b: WBFRT=max(min(ACDRatio+1,WBFlow Rate),10) {Eq. 7a} From the WBFRT, the volume of fluid used to push the MNCs out of the separation chamber12may be calculated by equation 7b. During step31ofFIG.5, RBC Chamber in equation 7b may comprise the same numerical value as RBC Chamber from equations 6b and 6c, but the volume for RBC Chamber in equation 7b may include both RBCs and MNCs. Additionally, 30 mL of RBCs from container67ofFIG.4may be used to push the MNCs within the volume represented by RBC Chamber and is included in equation 7b. Transfer Volume=30+RBCChamber {Eq. 7b} From the WBFRT of equation 7a, the Transfer Volume from equation 7b, and the MNC Transfer Rate, PRP Flush Rate, PRP Flush Volume, and the PRP Rate from Table 1, Equation 7c may be used to calculate the Whole Blood to Process during the transfer step of31ofFIG.5. WBPTransfer=WBFRT×(TransferVolumeMNCTransferRate+TransferVolumePRPFlushRate+PlasmaFlushVolumePRPRate){Eq.7c} From the WBP Transfer value from equation 7c and the ACD Ratio, equation 7d may be used to calculate the anticoagulant volume required during the transfer step of31ofFIG.5. ACRequiredTransfer=WBPTransferACDRatio+1{Eq.7d} Knowing the anticoagulant volume required during transfer from equation 7d and the anticoagulant required during collection from equation 4, the total anticoagulant required for the whole procedure may be calculated by equation 8. AC Required Transfer may be multiplied in equation 8 by the number of transfer cycles performed. In one embodiment, the number of transfer cycles may be set to 2. TotalACRequired=ACVol·Required During Collection+2(ACRequired Transfer) {Eq. 8} Once the Total AC Required is known, an estimated net change in volume by the end of the procedure may be calculated based on the inputs of Table 1 and equations 9a through 9c below. Equation 9a may be used for the net change in blood volume in an embodiment in which the blood components remaining in the fluid circuit may be reinfused to the blood source along with treated cells during step37. Δ Blood Volume=180 mL+TotalACRequired+160 mL {Eq. 9a} 180 mL in equation 9a refers to the volume of a diluting solution (e.g., saline) not originally from the blood source that may have been used in step33ofFIG.5to dilute the MNCs in container68ofFIG.4. If plasma from the blood source or other blood component from the blood source is used as the diluting solution, this volume may be removed from equation 9a. 160 mL in equation 9a refers to an example volume of saline that may have entered the fluid circuit in the course of the procedure, e.g., from container64ofFIG.4. Saline may have contributed to the 160 mL during the priming process, in the course of administering a saline drip (if the blood source is a patient that requires vein access to be open), etc. In an embodiment in which prime fluid leaving the separation chamber12ofFIG.4is diverted to a separate container instead of returning to the blood source as shown in step32B ofFIG.5, Equation 9b may be used for the net change in blood volume to exclude the diverted volume from the equation. Δ Blood Volume=180 mL-90 mL+TotalACRequired+160 mL {Eq. 9b} 90 mL in equation 9b represents an example volume of prime fluid diverted into the separate container. Equation 9c may be used for the net change in blood volume in an embodiment in which only the treated cells in container68ofFIG.4are reinfused to the blood source during step37without reinfusing the blood components remaining in the fluid circuit. Δ Blood Volume=180 mL+TotalACRequired+25 mL {Eq. 9c} 25 mL in equation 9a represents an example volume of fluid not originating from the blood source (e.g., saline) that may be used during reinfusion of the treated cells in container68ofFIG.4back to the blood source. For example, after most of the treated cells have been returned to the blood source, 25 mL of saline may be used to rinse and recover any remaining treated cells in the fluid flow path between container68and the blood source. In an embodiment in which prime fluid is diverted, the volume of prime fluid diverted may be subtracted from the result of equation 9c. Once the estimated net change in volume by the end of the procedure from equation 9a, 9b, or 9c is known, an estimated fluid balance expressed as a multiple of TBV (equation 1 a or 1b) may be determined according to equation 10. FluidBalance=1+ΔBloodVolumeTBV{Eq.10} The controller may be programmed with minimum and maximum limits for fluid balance. In one embodiment, the controller may be configured to have a permissible fluid balance in the range of 0.95 to 1.3. In the event the fluid balance is outside the programmed range, the controller may be configured to perform a response action, which may comprise allowing automatic or manual changes to procedure parameters that affect fluid balance. The system and controller may be programmed to allow an operator to make changes or implement automatic changes to a fluid procedure based on the estimated fluid balance derived from equation 10. One or more changes may be implemented in order to lower or raise the fluid balance to a desired value or range. In an embodiment in which the priming phase of step30A ofFIG.5has not yet reached completion, the change may comprise changing settings for the diversion of prime fluid (referring to equations 9a through 9c). If it desired to lower the fluid balance and prime fluid is not set to be diverted, prime fluid diversion may be selected. If it is desired to raise the fluid balance and prime fluid is set to be diverted, prime diversion may be turned off. In an embodiment in which the priming phase of step30A ofFIG.5has not begun, the change may comprise changing the anticoagulant solution to one having a different AC citrate concentration (referring to equation 2a). If it is desired to lower the fluid balance, an anticoagulant solution having an increased AC citrate concentration may be selected. If it is desired to raise the fluid balance, an anticoagulant solution having a decreased AC citrate concentration may be selected. In another embodiment, at any point in the procedure, the change may comprise changing the ACD ratio setting (primarily determined by equations 4 and 7d). If it is desired to lower the fluid balance, the ACD ratio may be raised. If it is desired to raise the fluid balance, the ACD ratio may be lowered. In another embodiment, at any point in the procedure, the change may comprise altering the value for WB to process (referring to equations 4 and 8). If it is desired to lower the fluid balance, the WBP may be lowered to decrease the amount of citrate returning to the blood source. If it is desired to raise the fluid balance, the WBP value may be raised to increase the amount of citrate returning to the blood source. In another embodiment, at any point in the procedure, the change may comprise altering settings for reinfusing treated cells and/or blood components remaining in the fluid circuit (referring to equations 9a and 9c). If it is desired to lower the fluid balance, an operator may elect to reinfuse back to the blood source the treated cells without returning blood components remaining in the fluid circuit (equation 9c). Otherwise, in some instances, an operator may elect to reinfuse back to the blood source blood components remaining in the fluid circuit without returning the treated cells. If it is desired to raise the fluid balance, an operator may elect to reinfuse back to the blood source both the treated cells and blood components remaining in the fluid circuit (equation 9a). In another embodiment, at any point in the procedure, the change may comprise altering the value for RBC Chamber (referring to equation 7b). If it is desired to lower the fluid balance, the RBC Chamber may be lowered to decrease the anticoagulant required during MNC Transfer (equation 7d). If it is desired to raise the fluid balance, the RBC Chamber may be raised to increase the anticoagulant required during MNC Transfer. In another embodiment, at any point in the procedure, the change may comprise concentrating the treated cells prior to returning to the blood source in step37ofFIG.5by directing the treated cells from container68ofFIG.4after treatment into the separation chamber12to separate the treated cells from the diluent (e.g., saline, plasma) before returning the concentrated treated cells to the blood source. In an embodiment in which the estimate of the maximum extracorporeal volume of red blood cells (Max RBC Out in equations 6b and 6c) is above a threshold, the system may be configured to automatically or manually lower the RBC Chamber value (equations 6b and 6c) until Max RBC Out reaches a threshold. The system may also be configured to switch priming fluid from saline during step30A ofFIG.5to prime fluid having a positive hematocrit (triggering equation 6c) so that the blood source receives blood as whole blood is being drawn out in step30B. Without limiting the foregoing description, in accordance with one aspect of the subject matter herein, there is provided a system for monitoring and controlling fluid balance during an extracorporeal photopheresis procedure. The system comprises a disposable fluid circuit comprising a product container configured to receive a target cell component. The system also comprises a separator configured to work in association with the disposable fluid circuit, the separator comprising a chamber configured to rotate about a rotational axis and convey whole blood from a blood source into an inlet region of the chamber for separation into a red blood cell component, a plasma component, and the target cell component. The system also comprises a microprocessor-based controller in communication with the separator. The controller is configured to estimate an end-of-procedure fluid balance by calculating a total volume of anticoagulant solution having a citrate concentration to be used for the procedure, wherein the end-of-procedure fluid balance is estimated based on manual or automatic inputs comprising an ACD ratio relating unanticoagulated extracorporeal whole blood to anticoagulant solution, an amount of whole blood to process, a citrate infusion threshold rate, a patient body weight associated with the blood source, and a total blood volume of the blood source. The controller is also configured to draw anticoagulated whole blood into the disposable fluid circuit and the chamber at a whole blood flow rate. The controller is also configured to separate the anticoagulated whole blood into the red blood cell component, the target cell component, and the plasma component. The controller is also configured to direct the target cell component to the product container, treat the product container comprising the target cell component to create a treated target cell component, and return to the blood source the treated target cell component, a portion of the red blood cell component remaining in the fluid circuit, and/or a portion of the plasma component remaining in the fluid circuit. The controller is also configured to provide a first response action if the end-of-procedure fluid balance estimated is above or below a programmed fluid balance range. In accordance with a second aspect which may be used or combined with the immediately preceding aspect, the controller is further configured to calculate the total volume of the blood source with information comprising a gender, height, and weight of the blood source. In accordance with a third aspect which may be used or combined with any of the preceding aspects, a maximum extracorporeal volume of red blood cells during the procedure is estimated based on the ACD ratio, a hematocrit of the blood source, a hematocrit of a priming fluid, and the total blood volume. A second response action is provided if the estimated maximum extracorporeal volume of red blood cells is above or below a programmed limit. In accordance with a fourth aspect which may be used or combined with any of the preceding aspects, the end-of-procedure fluid balance is further estimated based on a volume of fluid not returning to the blood source, and the first response action comprises at least one of altering the volume of fluid not returning to the blood source, changing the citrate concentration of the anticoagulant solution, changing the ACD ratio, changing the amount of whole blood to process, altering settings for components returned to the blood source, and concentrating the treated target cell component in the separator prior to returning the treated target cell component to the blood source. In accordance with a fifth aspect which may be used or combined with any of the preceding aspects, the controller is further configured to calculate the total volume of anticoagulant solution to be used for the procedure based on the whole blood flow rate calculated based on manual or automatic inputs comprising the ACD ratio, the citrate infusion threshold rate, and the patient body weight associated with the blood source. In accordance with a sixth aspect which may be used or combined with any of the preceding aspects, the target cell component comprises mononuclear cells, and the treated target cell component comprises mononuclear cells combined with a photoactivation agent and subjected to irradiation. In accordance with a seventh aspect which may be used or combined with any of the preceding aspects, the programmed fluid balance range is 0.95 to 1.30. In accordance with an eighth aspect which may be used or combined with the third aspect, the second response action comprises changing the priming fluid to a priming fluid having a higher hematocrit. In accordance with a ninth aspect which may be used or combined with any of the third or eighth aspects, the programmed limit is 10-15% of a total amount of red blood cells of the blood source. In accordance with a tenth aspect, there is provided a method for monitoring and controlling fluid volume balance during an extracorporeal photopheresis procedure, driven and adjusted by a microprocessor-based controller. The controller is configured manually or automatically with a first set of inputs comprising a hematocrit of a blood source, a total blood volume of the blood source, and an ACD ratio relating unanticoagulated extracorporeal whole blood to anticoagulant solution. A maximum extracorporeal red blood cell amount during the procedure is estimated based on the first set of inputs. A fluid circuit is primed with a priming fluid having a prime fluid hematocrit value inputted into the controller. Whole blood is drawn from the blood source into the fluid circuit and a separator. The whole blood is separated into a red blood cell component, a target cell component, and a plasma component. The target cell component is directed to a product container. The product container comprising the target cell component is treated to create a treated target cell component. The treated target cell component, a portion of the red blood cell component remaining in the fluid circuit, and/or a portion of the plasma component remaining in the fluid circuit is returned to the blood source. A first response action is provided if the maximum extracorporeal red blood cell amount estimated is above a programmed limit. In accordance with an eleventh aspect which may be used or combined with the tenth aspect, the total blood volume of the blood source is calculated with information comprising a gender, height, and weight of the blood source. In accordance with a twelfth aspect which may be used or combined with the any of the tenth or eleventh aspects, the prime fluid hematocrit value comprises a positive value, and the maximum extracorporeal red blood cell amount during the procedure is estimated based also on the positive value. In accordance with a thirteenth aspect which may be used or combined with any of the tenth through twelfth aspects, the first response action comprises changing the priming fluid to a priming fluid having a different prime fluid hematocrit value. In accordance with a fourteenth aspect which may be used or combined with any of the tenth through thirteenth aspects, the controller is configured manually or automatically with a second set of inputs comprising an amount of whole blood to process, a citrate infusion threshold rate, and a patient body weight associated with the blood source. An end-of-procedure fluid balance is estimated based on the second set of inputs and an input from the first set of inputs. A second response action is provided if the estimated end-of-procedure fluid balance is above or below a programmed fluid balance range. In accordance with a fifteenth aspect which may be used or combined with any of the tenth through fourteenth aspects, the target cell component comprises mononuclear cells. In accordance with a sixteenth aspect which may be used or combined with any of the tenth through fifteenth aspects, the treated target cell component comprises mononuclear cells combined with a photoactivation agent and subjected to irradiation. In accordance with a seventeenth aspect which may be used or combined with the fourteenth aspect, the programmed fluid balance range is 0.95 to 1.30. In accordance with an eighteenth aspect which may be used or combined with any of the tenth through seventeenth aspects, the programmed limit is 10-15% of a total amount of red blood cells of the blood source. In accordance with a nineteenth aspect, there is provided a method for monitoring and controlling fluid volume balance during an extracorporeal photopheresis procedure, driven and adjusted by a microprocessor-based controller. 1) The controller is configured manually or automatically with inputs comprising a hematocrit of a blood source, a total blood volume of the blood source, an ACD ratio relating unanticoagulated extracorporeal whole blood to anticoagulant solution, a citrate infusion threshold rate, a volume of whole blood to process, and a patient body weight associated with the blood source. 2) A fluid circuit is primed with a priming fluid. 3) None or some of the priming fluid is returned to the blood source. 4) Whole blood is withdrawn from the blood source into the fluid circuit at a first flow rate and anticoagulant solution is withdrawn at a second flow rate in accordance with the ACD ratio, the citrate infusion threshold rate, the volume of whole blood to process, and the patient body weight. 5) The whole blood is separated within a separation chamber into a red blood cell component, a mononuclear cell component, and a plasma component. 6) A first portion of the red blood cell component and a first portion of the plasma component are returned to the blood source. 7) A second portion of the red blood cell component and a second portion of the plasma component are retained within the fluid circuit. 8) The mononuclear cell component is collected in the separation chamber over a plurality of cycles comprising steps4through7, while anticoagulated whole blood enters the separation chamber continuously, at select intervals, and/or for a predetermined period of time. 9) A volume of fluid comprising the mononuclear cell component and a third portion of the red blood cell component is pumped from the separation chamber at an MNC transfer rate. 10) The mononuclear cell component is directed into a first container without the red blood cell component. 11) The mononuclear cell component is diluted with a volume of the second portion of the plasma component within the fluid circuit pumped into the first container at a PRP rate. 12) A photoactivation agent is added to the mononuclear cell component to create an agent-added mononuclear cell component. 13) The agent-added mononuclear cell component is irradiated to create a photoactivated mononuclear cell component. 14) The photoactivated mononuclear cell component, the second portion of the red blood cell component, and/or the second portion of the plasma component is returned. The controller is configured to estimate throughout the procedure an end-of-procedure fluid balance based on the inputs of step1, any priming fluid returned to the blood source in step3, the volume of fluid in step9, the MNC transfer rate in step9, the volume of the second portion of the plasma component within the fluid circuit in step11, and the PRP rate in step11. The controller is configured to provide a response action if the end-of-procedure fluid balance is above or below a programmed fluid balance range. In accordance with a twentieth aspect which may be used or combined with the immediately preceding aspect, the response action comprises at least one of altering an amount of priming fluid returned to the blood source in step3, changing a citrate concentration of the anticoagulant solution, changing the ACD ratio, changing the volume of whole blood to process, changing the volume of fluid in step9, altering settings for components returned in step14, and concentrating the photoactivated mononuclear cell component in the separation chamber prior to returning the photoactivated mononuclear cell component to the blood source. The embodiments disclosed herein are for the purpose of providing a description of the present subject matter, and it is understood that the subject matter may be embodied in various other forms and combinations not shown in detail. For example, the subject matter may be applied to any technology in which biological fluid is combined with another fluid (e.g., apheresis, dialysis, transfusion, diagnostics, cell washing, cell therapy, infusion, anesthesia, etc.). Therefore, specific embodiments and features disclosed herein are not to be interpreted as limiting the subject matter as defined in the accompanying claims. | 50,589 |
11857715 | DETAILED DESCRIPTION With reference to the appended drawings,FIG.1shows a schematic representation of an extracorporeal blood treatment apparatus1. The apparatus1comprises one blood treatment device2, for example a hemofilter, a hemodiafilter, a plasmafilter, a dialysis filter, a membrane oxygenator, an adsorption device or other unit suitable for processing the blood taken from a patient P. The blood treatment device2has a first compartment or blood chamber3and a second compartment or fluid chamber4separated from one another by a semipermeable membrane5. A blood withdrawal line6is connected to an inlet port3aof the blood chamber3and is configured, in an operative condition of connection to the patient P, to remove blood from a vascular access device inserted, for example in a fistula on the patient P. A blood return line7connected to an outlet port3bof the blood chamber3is configured to receive treated blood from the treatment unit2and to return the treated blood, e.g. to a further vascular access also connected to the fistula of the patient P. Note that various configurations for the vascular access device may be envisaged: for example, typical access devices include a needle or catheter inserted into a vascular access which may be a fistula, a graft or a central (e.g. jugular vein) or peripheral vein (femoral vein) and so on. The blood withdrawal line6and the blood return line7are part of an extracorporeal blood circuit of the apparatus1. The extracorporeal blood circuit6,7and the treatment unit2are usually disposable parts which are loaded onto a frame of a blood treatment machine, not shown. As shown inFIG.1, the apparatus1comprises at least a first actuator, in the present example a blood pump8, which is part of said machine and operates at the blood withdrawal line6, to cause movement of the blood removed from the patient P from a first end of the withdrawal line6connected to the patient P to the blood chamber3. The blood pump8is, for example, a peristaltic pump, as shown inFIG.1, which acts on a respective pump section6aof the withdrawal line6. When rotated, e.g., clockwise, the blood pump8causes a flow of blood along the blood withdrawal line6towards the blood chamber3(see the arrows inFIG.1indicative of the blood flow along the blood withdrawal line6). It should be noted that for the purposes of the present description and the appended claims, the terms “upstream” and “downstream” may be used with reference to the relative positions taken by components belonging to or operating on the extracorporeal blood circuit. These terms are to be understood with reference to a blood flow direction from the first end of the blood withdrawal line6connected to the patient P towards the blood chamber3and then from the blood chamber3towards a second end of the blood return line7connected to the vascular access of the patient P. The apparatus1further comprises an air trapping device9operating on the blood return line7(the air trapping device9is a venous deaeration chamber). The air trapping device9is placed online in the blood return line7. A first section of the blood return line7puts in fluid communication the outlet port3bof the blood chamber3with the air trap9and a second section of the blood return line7puts in fluid communication the air trap9with the patient P. The blood coming from the blood chamber3of the treatment device2enters and exits the air trap9before reaching the patient P. The apparatus1further comprises one fluid evacuation line11connected with an outlet port4bof the fluid chamber4such as to receive at least a filtered fluid through the semipermeable membrane5. The evacuation line11receives the waste fluid coming from the fluid chamber4of the treatment device2, for example, comprising used dialysis liquid and/or liquid ultra-filtered through the membrane5. The evacuation line11leads to a receiving element, not shown, for example having a collection bag or a drainage pipe for the waste fluid. One or more dialysate pumps, not shown, may operate on the evacuation line11. In the example ofFIG.1, a dialysis line10is also present, for supplying a fresh treatment fluid to an inlet port4aof the fluid chamber4. The presence of this dialysis line10is not strictly necessary since, in the absence of the dialysis line, the apparatus1is still able to perform treatments such as ultrafiltration, hemofiltration or plasma-filtration. In case the dialysis line10is present, a fluid flow intercept device may be used, not shown, to selectively allow or inhibit fluid passage through the dialysis line10, depending on whether or not a purification by diffusive effect is to be performed inside the treatment device2. The dialysis line10, if present, is typically equipped with a dialysis pump, not shown, and is able to receive a fresh fluid from a module, for example a bag or on-line preparation section of dialysis fluid, and to send such a fluid to the inlet port4aof the fluid chamber4. The fluid evacuation line11, the dialysis line10, and the fluid chamber4are part of a treatment fluid circuit. Finally, the apparatus1as shown comprises an infusion circuit comprising one or more infusion lines12,13of a replacement fluid: for example a pre-infusion line12may be connected to the blood withdrawal line6and/or a post-infusion line13may be connected to the blood return line7. Infusion pump or pumps, not shown, equips typically the infusion circuit. The pre- and/or post-infusion lines12,13may be supplied by fluid coming from bags or directly by infusion fluid prepared on-line. The post-infusion line13is connected to the blood return line7through the air trapping device9to supply fluid to the blood at said air trapping device9. According to a different embodiment, not shown, the post-infusion line13is connected to the blood return line7upstream the air trapping device9. Downstream of the air trapping device9, the blood return line7presents a heating zone14coupled or configured to be coupled to a blood warmer15. It follows that the post-infusion line13is connected to the blood return line7upstream of the heating zone14and that the air trapping device9is placed on the blood return line7upstream of the heating zone14. The blood warmer15is associated with the apparatus1to form an assembly which is structured to treat blood and keep blood within predetermined desired temperature boundaries. The blood warmer15may be an independent device (e.g. a standalone unit physically separated from the apparatus1) cooperating with the apparatus1and—in particular—warming the heating zone14. Alternatively, the blood warmer15may be a component of the apparatus1. In this case the blood warmer15is not an independent standalone unit, but rather part of the apparatus1. In both cases, the blood warmer15has a heating unit, not shown, configured for receiving and heating the heating zone of the blood return line7. For instance, the heating zone14of the blood return line7may be in the form of a substantially flat bag insertable in a heating seat provided in the heating unit of the blood warmer. The flat bag presents an inlet and an outlet connected to the extracorporeal blood circuit. Alternatively, the heating zone14may include a section of the tubing or a rigid cassette inserted into the heating unit of the blood warmer15, which heating unit for instance may comprise a heating sleeve or a heating coil wound around the heating zone14. In practice the heating unit has heating elements (e.g. electric impedances, infrared emitters or other types of heating elements) configured to heat the corresponding heating zone14of the blood return line7. In the embodiment shown inFIG.1, an air bubble detector16is placed downstream of the heating zone14, between a terminal end with access device of the blood return line7, connected to the patient P, and said heating zone14. In order to make possible troubleshooting of air bubble detector16alarms, the blood return line7may also include a puncture site, not shown, upstream the air bubble detector16and clamp for the air removal procedure. A return pressure sensor17is placed on the blood return line7, between the heating zone14and the air bubble detector16, to monitor pressure downstream of the blood warmer15. Pressure upstream the blood warmer15may be monitored in the air trapping device9through a pressure monitor17′ which is operatively active in said air trapping device9, by way of example through an air filled service line required for a level adjustment in the air trapping device9. The apparatus shown inFIG.1further comprises a withdrawal clamp18placed close to a terminal end of the blood withdrawal line6and a return clamp19placed close to the terminal end of the blood return line7. The air bubble detector16is connected to a control unit100of the apparatus1and sends to the control unit100signals for the control unit100to cause closure of the return clamp19in case one or more bubbles above predetermined safety thresholds are detected. The control unit100, during treatment, may be configured to control the blood pump8based, by way of example, on a set blood flow rate. The control unit100of the apparatus1may also be configured to control the flow rate of dialysis fluid through the dialysis line10, of evacuation fluid through the evacuation line11, of infusion fluid/s through pre-infusion line12and post-infusion line13. The control unit100of the apparatus1may also be configured to control the blood warmer15, during treatment, to keep blood within said desired temperature boundaries. The control unit100may comprise a digital processor (CPU) and memory (or memories), an analog circuit, or a combination thereof. In use, during patient P treatment, the blood coming from the extracorporeal blood treatment device2and the infusion fluid flowing in the post-infusion line13enter the air trapping device9before flowing through the heating zone14. This allows to prevent air intake at the blood warmer15inlet. In addition, the air trapping device9may have at least a low level liquid sensor, not shown in figures, alerting the operator for adjusting the chamber level of said air trapping device9before air bubbles are moved to the blood warmer and to the air bubble detector16. Alternatively, the circuit may include a second air bubble detector16′ (dashed line inFIG.1) located immediately downstream of the air trapping device9. The apparatus1ofFIG.1is fully robust to the presence of some air bubbles in the post-infusion fluid. With respect to the apparatus ofFIG.1, the apparatus1shown inFIG.2further comprises a secondary post-infusion line20. Said secondary post-infusion line20is connected to the post-infusion line13at a branching off point21located upstream of the air trapping device9. The post-infusion line13of the apparatus ofFIG.2has a line segment13′ comprised between the branching off point21and the air trapping device9. In another embodiment, not shown, the secondary post-infusion line20is connected to the air trapping device9(the branching off point21is located on the air trapping device9). Said secondary post-infusion line20is connected to the blood return line7at a connection point22placed downstream of the heating zone14and upstream of the air bubble detector16. In this way, the secondary post-infusion line20by-passes the heating zone14and the blood warmer15. A by-pass pump23is placed on the secondary post-infusion line20. The return pressure sensor17is placed on the secondary post-infusion line20too (instead of on the blood return line7like inFIG.1). A warmer clamp24is placed on the blood return line7between the air trapping device9and the heating zone14. The by-pass pump23and the warmer clamp24are connected to the control unit100, not shown inFIG.2. The by-pass pump23is a control device operatively active on the secondary post-infusion line20, for controlling a flow through said secondary post-infusion line20. In use, during patient P treatment (FIG.2) the warmer clamp24is open, the return clamp19is open and the heating zone14is placed in the blood warmer15. The blood coming from the extracorporeal blood treatment device2and all or part of the infusion fluid flowing in the post-infusion line13enter the air trapping device9before flowing through the heating zone14. This allows to prevent air intake at the blood warmer15inlet. Through the by-pass pump23, it is also possible to control the post-infusion flow which is split between the air trapping device and the return circuit downstream of the blood warmer15. The post-infusion flow rate may be in the range of 50 ml/h to 6000 ml/h. The by-pass pump23may operate in continuous or in periodic mode. The blood warmer15may slightly overheat blood as to balance for the cooling effect of the secondary post-infusion, depending on the flow rates. The presence of the secondary post-infusion line20during treatment may require additional means in case the post-infusion contains some air bubbles. As infusion of such air bubbles downstream the blood warmer15will create difficult troubleshooting situations, it may be of interest to prevent these events by: stopping temporarily flow in the secondary post-infusion line20when presence of air bubbles is suspected (e.g. after a bag change); adding an air detector on the post-infusion13upstream the post-infusion line split (an optical detection may be suitable for this purpose); having preventing means in the post-infusion13, such as a self-venting chamber using an hydrophobic membrane, and taking advantage of the positive pressure present in the post-infusion13upstream the air trapping device9. According to a method of the invention, the apparatus detailed above and shown inFIG.2allows to control the flow of a priming fluid through the heating zone14, through the infusion line13and through the secondary post-infusion line20when priming of the apparatus before patient P treatment is performed. To this aim, the extracorporeal blood circuit of the extracorporeal blood treatment apparatus1is loaded and filled with the priming fluid so that the priming fluid flows at least through the blood withdrawal line6, through the blood treatment device2and through the blood return line7towards the heating zone14of said blood return line7. FIG.11shows a flow chart of one example of the priming procedure. FIG.3shows the configuration of the apparatus1ofFIG.2during an initial time interval ΔT1of the priming procedure. The initial time interval ΔT1may last for about the time required to flow a priming fluid volume matching with the total blood circuit volume. Priming may be done using the prescribed solutions for the patient treatment. During said initial time interval ΔT1the warmer clamp24is closed, the return clamp19is open. The by-pass pump23rotates clockwise to pump fluid from the branching off point21towards the connection point22or the by-pass pump23is not present and not active on the secondary post-infusion line20(a pump segment of the secondary post-infusion line20is unloaded). The priming fluid coming from the blood treatment device2and flowing through the section of the blood return line7placed upstream of the warmer clamp24enters the air trapping device9but is prevented from entering the heating zone14. Therefore, the priming fluid coming from the blood treatment device2, once in the air trapping device9, is compelled to flow into the line segment13′ of the post-infusion line13(comprised between the air trapping device9and the branching off point21) and then into the secondary post-infusion line20. Also the priming fluid coming from a source of priming fluid and flowing in a section of the post-infusion line13upstream of the branching off point21flows into the secondary post-infusion line20. All the priming fluid by-passes the heating zone14and the blood warmer15and enters again the blood return line7at the connection point22. Downstream of the connection point22, the priming fluid flows towards the terminal end of the blood return line7. FIG.4shows the configuration of the apparatus1after the initial time interval ΔT1, during the remaining priming step. During said remaining priming step, the warmer clamp24is open, the return clamp19is open, the pump segment of the secondary post-infusion line20is loaded onto the by-pass pump23and the by-pass pump23rotates clockwise to pump fluid from the branching off point21towards the connection point22. The by-pass pump23is compatible with the priming by-pass phase with relatively high flow rates and air-water mixture. Such a by-pass pump23may be a peristaltic pump which pump segment is loaded after the by-pass phase (initial time interval ΔT1). A diaphragm pump or a finger pump may also be considered. The priming fluid coming from the blood treatment device2and flowing through the section of the blood return line7placed upstream of the warmer clamp24enters and exits the air trapping device9, flows through a section of the blood return line7comprised between the air trapping device9and the heating zone14, then through said heating zone14towards the connection point22. The priming fluid coming from the source of priming fluid and flowing in a section of the post-infusion line13upstream of the branching off point21is split into the line segment13′ (and then into the air trapping device9) and into the secondary post-infusion line20. Indeed, said priming fluid flows in part into the air trapping device9and then through the heating zone14and in part through the secondary post-infusion line20towards the connection point22. Downstream of the connection point22, all the priming fluid flows towards the terminal end of the blood return line7. FIG.5shows a variant of the apparatus ofFIG.2, in which the by-pass pump23is not present and a 3-way pinch valve25is placed between the post-infusion line13and the secondary post-infusion line20at the branching off point21. Said pinch valve25is a control device operatively active on the post-infusion line13and on the secondary post-infusion line20, for controlling a flow through the line segment13′ of said post-infusion line13and through said secondary post-infusion line20. In use, during patient P treatment the warmer clamp24is open. The pinch valve25is periodically switched between a first and a second position. In the first position, the pinch valve25closes the secondary post-infusion line20and let the infusion fluid to flow into the line segment13′ and into the air trapping device9. In the second position, the pinch valve25closes the post-infusion line13and let the infusion fluid to flow through the secondary post-infusion line20and into the blood return line7downstream of the blood warmer15. The pinch valve design shall be such that, when switching during patient P treatment, no direct communication is present between the air trapping device9and the blood return line7as to prevent blood flow by-pass through the secondary post-infusion line20. When priming, during (warmer clamp24closed) and after (warmer clamp24open) the initial time interval ΔT1, the pinch valve25is set in a neutral position so that the air trapping device9is in fluid communication with the secondary post-infusion line20. The variant ofFIG.6differs from the apparatus ofFIG.5in that the pinch valve25is substituted by a flow resistor26placed on the secondary post-infusion line20in combination with a post-infusion clamp27placed on the line segment13′ of the post-infusion line13downstream of the branching off point21. During treatment, this prevents blood flow in the secondary post-infusion line20when post-infusion is stopped. The flow resistor26may be designed in order to prevent blood flow by-pass in the secondary post-infusion line20as soon the post-infusion flow rate is large enough. The post-infusion clamp27on the line segment13′ of the post-infusion line13is required for preventing blood flow by-pass when post-infusion is stopped. The variant ofFIG.7differs from the apparatus ofFIG.5in that the pinch valve25is substituted by a secondary post-infusion clamp28placed on the secondary post-infusion line20in combination with a non-return valve29placed on the line segment13′ of the post-infusion line13downstream of the branching off point21 The variant ofFIG.8differs from the variant ofFIG.7in that the secondary post-infusion clamp28is substituted by a secondary flow resistor30. The embodiment ofFIG.9differs from the apparatus ofFIG.5in thatFIG.9further comprises another auxiliary air trapping device31and in that no warmer clamp24is present. Said auxiliary air trapping device31is placed on the blood return line7downstream of the heating zone14and of the blood warmer15. Downstream of the heating zone14, the secondary post-infusion line20is connected to the blood return line7at the auxiliary air trapping device31. Moreover, the return pressure sensor17is not on the secondary post-infusion clamp28but it is operatively active in the auxiliary air trapping device31. Optionally, fluid level is automatically monitored in the chambers of both the air trapping devices9,31. Other variants, not shown, of the embodiment ofFIG.9(in which air trapping devices9,31are present both upstream and downstream of the blood warmer15) may comprise the control devices (operatively active on the post-infusion lines) shown inFIGS.2-4(post-infusion pump23),6(post-infusion clamp27and flow resistor26),7(non-return valve29and secondary post-infusion clamp28),8(non-return valve29and secondary flow resistor30). In other variants, not shown, of the embodiment ofFIG.9(in which air trapping devices9,31are present both upstream and downstream of the blood warmer15) no post infusion in the auxiliary air trapping device31is present. In the case, like in the embodiment ofFIG.1, the blood warmer15has not to compensate for any post-infusion cooling effect. Furthermore, the air trapping device9and the auxiliary air trapping device31may be each other identical, as inFIG.9, or the auxiliary air trapping device31′ may be a filled air trap including a soft diaphragm for return pressure measurement. FIG.10shows the filled air trap31′ and an auxiliary blood line32with an auxiliary blood pump33connecting the top of the filled air trap31′ to the air trapping device9. The auxiliary blood pump33may be a peristaltic pump. Pump flow rate might be settled in a wide range from a few ml/min to 100 ml/min and more. This auxiliary blood pump33does not need to be stopped in case of alarm and system safe state with stop of the blood pump8and return clamp19closure. The main purpose of this blood circuit loop is to flow air bubbles back to the air trapping device9, which should provide for means to remove this air. In a variant ofFIG.10, not shown, the auxiliary blood pump33on the auxiliary blood line32is substituted by an additional clamp. This variant plays with the position of two air trapping chamber for making possible the transfer of air bubbles from the filled air trap31′ to the air trapping device9, when stopping the blood flow and opening the additional clamp. In another variant ofFIG.10, not shown, the auxiliary blood line32is not present. While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiment, it is to be understood that the invention is not to be limited to the disclosed embodiment, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and the scope of the appended claims. | 23,553 |
11857716 | DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT An automatic urine treatment system according to an embodiment of the present invention includes a receiver100, a main body200, and a first connecting hose610to a third connecting hose630. <Receiver (100)> The receiver100of the present invention contacts wearer's buttocks and receives wearer's excrement. The receiver100includes a first filter unit110, a urine storage unit130, and a urine detection sensor120. 1. First Filter Unit (110) The first filter unit110is disposed at a portion contacting the wearer's skin, filters solid components from the excrement, and transfers the excrement from which the solid components are removed to the urine storage unit130. The first filter unit110includes a first filter body made of a fiber of a water-permeable material formed with a mesh or pores. In addition, the first filter unit110may contain a plant-derived extract in the fiber of a water-permeable material to prevent skin disease of the wearer and remove odor of the excrement. The plant-derived extract has an advantage of not causing skin trouble unlike chemical components, while removing bacteria contained in the excrement and the odor. The plant-derived extract may contain at least one among grapefruit seed extract, kiwi fruit extract, camellia extract, chamomile extract, lavender extract, rosemary extract, coconut extract, and olive extract. The grapefruit seed extract exhibits very excellent antibacterial activity against gram-negative bacteria, gram-positive bacteria, and true fungi including fungi and yeast. The camellia tree extract has inflammation suppressing and inflammation killing functions and may prevent skin trouble of a wearer. The kiwi fruit extract has a strong antifungal effect against Candida bacteria that cause vaginitis of women and thus may prevent vaginitis of a female wearer. The camellia extract has inflammation suppressing and inflammation killing effects and may prevent skin trouble of a wearer. The chamomile extract has a high antibacterial activity effect and may remove bacteria contained in the excrement. The lavender extract and the rosemary extract have high antibacterial activity against gram-negative bacteria. The coconut extract and the olive extract may increase antibacterial activity and form a protective film on the skin to prevent skin trouble of a wearer. The total amount of the plant extract may be 1 to 10 parts by weight when the weight of the first filter body is 100. In addition, the plant extract may contain 1 to 5 parts by weight of grapefruit seed extract, 1 to 2 parts by weight of kiwi fruit extract, 0.5 to 2 parts by weight of camellia extract, 1 to 3 parts by weight of chamomile extract, 1 to 3 parts by weight of lavender extract, 1 to 3 parts by weight of rosemary extract, 1 to 2 parts by weight coconut extract, and 1 to 2 parts by weight of olive extract. Alternatively, the first filter unit110may include nano zinc polypeptide in the first filter body. The zinc polypeptide has an immediate and lasting antibacterial deodorant effect while being harmless to human bodies. In addition, even with a small amount of use, a sterilizing effect of converging the survival rate of gram-positive bacteria and gram-negative bacteria to zero is obtained, and more than 99.8% of various stink and odor components can be removed. 2. Urine Storage Unit (130) The urine storage unit130is disposed under the first filter unit110. As described above, the urine storage unit130may receive and store liquid, i.e., the excrement from which at least some of the solid component has been removed by filtering the solid component, from the first filter unit110. The urine storage unit130may be made of a fiber of a highly water-permeable material in the form of an absorption layer that absorbs and stores the excrement of liquid component. Alternatively, the urine storage unit130may be configured as a non-water permeability soft container having an open top surface to store the excrement of liquid component inside the container. Alternatively, the urine storage unit130may be configured in the form of a urinal-cup to store the excrement of liquid component in the cup. The urine storage unit130may include a urine drainage hole140through which the first connecting hose610passes. The urine drainage hole140may be connected to the first connecting hose610to transfer the stored excrement of liquid component toward the urine tank210. 3. Urine Detection Sensor (120) The urine detection sensor120may be disposed between the first filter unit110and the urine storage unit130. The urine detection sensor120is for detecting urine of a wearer, and may detect urine using a sensing method of detecting urine by sensing a change in impedance between electrodes, a sensing method of detecting urine by sensing a change in temperature, and a sensing method of detecting urine by sensing a chemical change. The urine detection sensor120generates a urine detection signal when urine is detected. The urine detection signal is directly transferred from the urine detection sensor120to the control unit230described below, or transferred from the urine detection sensor120to the terminal700described below. <Connecting Hose> According to an embodiment of the present invention, the connecting hose may include a first connecting hose610of which one end is connected to the urine drainage hole140and the other end is connected to the urine tank210, a second connecting hose620of which one end is connected to the urine tank210and the other end is connected to an auxiliary tank300, and a third connecting hose630of which one end is connected to the auxiliary tank300and the other end is connected to the vacuum pump240. The first connecting hose610has a channel formed therein to move urine and gas stored in the urine storage unit130to the urine tank210. A wire passage channel through which a sensor wire connecting the urine detection sensor120and the control unit230described below passes may be formed outside the first connecting hose610. Alternatively, the wire passage channel may be formed separately from the first connecting hose610and connected to the urine detection sensor120and the control unit230described below. Alternatively, the wire passage channel may be formed separately from the first connecting hose610and connected to the terminal700described below and the control unit230described below. A gas tank and a hole through which gas contained in excrement may pass may be formed on one side of at least one among the first connecting hose610to the third connecting hose630. In addition, a gas sensor unit400for sensing the gas component contained in the excrement is formed on one side of at least one among the first connecting hose610to the third connecting hose630where the gas tank and the hole are formed. As described below, according to an embodiment of the present invention, water vapor among the gas component flowing into the auxiliary tank300through the second connecting hose620flows in and is stored in the auxiliary tank300. Therefore, the gas sensor unit400is preferably installed on one side of the second connecting hose620. Hereinafter, although it is configured to install the gas sensor unit400in the second connecting hose620for convenience, the scope of the present invention is not limited thereto, and it may also be installed in the first connecting hose610or the third connecting hose630according to the situation. First Embodiment of Gas Sensor Unit (400) Referring toFIG.5, a gas sensor unit400according to a first embodiment of the present invention may include an accommodation case410, a third filter420, and a gas sensor430. The accommodation case410accommodates the third filter420and the gas sensor430. The accommodation case410may include a first surface at least partially opened to communicate with the gas tank and the hole, and attached in parallel to the second connecting hose620, a second surface disposed in parallel to the second connecting hose620, and facing the first surface, a third surface perpendicular to the second connecting hose620, and connecting the first surface and the second surface, and a fourth surface facing the third surface, perpendicular to the second connecting hose620, and connecting the first surface and the second surface. The third filter420is installed to be spaced apart from the first surface of the accommodation case410by a predetermined distance. A first side surface of the third filter420is attached to the third surface of the accommodation case410, and a second side surface of the third filter420facing the first side surface is attached to the fourth surface of the accommodation case410. The third filter420removes moisture from the gas that has passed through the gas tank and the hole, and transfers the gas to the gas sensor430. The gas sensor430is installed on the second surface of the accommodation case410, and a gas sensing signal sensed by the gas sensor430is transferred to the control unit230through wired or wireless communication. Since the gas sensor430is mounted outside the receiver100and the second connecting hose620and embedded in the separate accommodation case410, a large amount of gas may not flow into the gas sensor430, and corrosion of the gas sensor430by the excrement gas may be prevented. In addition, since the gas component from which moisture is removed by the third filter420flows into the gas sensor430, there is an advantage of preventing corrosion of the gas sensor430caused by the moisture, and enhancing sensing accuracy and extending the lifespan of the gas sensor430. Second Embodiment of Gas Sensor Unit (400) Referring toFIG.6, a gas sensor unit400according to a second embodiment of the present invention may include an accommodation case411, a third filter420, and a gas sensor430. In addition, the second connecting hose620includes a gas inlet connecting hose621for transferring gas to the accommodation case, and a gas discharge connecting hose622for receiving gas discharged from the accommodation case411. The accommodation case411may include a first communication hole441communicating with the gas inlet connecting hose621and a second communication hole442communicating with the gas discharge connecting hose622. The air inside the urine tank210is transferred inside the accommodation case411through the gas inlet connecting hose621and the first communication hole441in order. The air transferred into the accommodation case411reaches the third filter420and is transferred to the gas sensor430after moisture is removed. The third filter420and the gas sensor430may be installed to be attached to a first surface and a second surface perpendicular to the gas inlet connecting hose621. Like the first embodiment, the gas sensor430transfers the sensed gas sensing signal to the control unit230through wired or wireless communication. <Main Body (200)> The main body200according to an embodiment of the present invention may include a urine tank210for storing urine, a vacuum pump240, a second filter unit260, a control unit230, a communication unit220, and an auxiliary tank300. The urine tank210, the vacuum pump240, the control unit230, the communication unit220, and the auxiliary tank300are accommodated inside the main body200. The second filter unit260may be accommodated under the urine tank210or may be mounted on an outer bottom surface of the main body200. 1. Urine Tank (210) The urine tank210is formed to have an open top surface and may be provided with a urine tank cover211that covers and seals the opened portion of the urine tank210. A first urine suction unit212and a first gas transfer unit213are formed on the top surface of the urine tank cover211. The first urine suction unit212is connected to the first connecting hose610, and the first gas transfer unit213is connected to the second connecting hose620. The urine tank210transfers negative pressure to the urine storage unit130and receives urine and gas from the urine storage unit130through the first urine suction unit212connected to the first connecting hose610. The urine tank210receives negative pressure from the auxiliary tank300and transfers gas contained in excrement toward the auxiliary tank300through the first gas transfer unit213. A float sensor510for detecting the level of the urine stored in the urine tank210, generating a urine level signal indicating the level of the stored urine, and transferring the generated urine level signal to the control unit230may be installed on one side of the urine tank cover211. A mass sensor520for detecting the mass of the urine stored in the urine tank210, generating a urine mass signal indicating the detected mass of the urine, and transferring the generated urine mass signal to the control unit230may be installed on the outer surface of the urine tank210. Preferably, the mass sensor520may be installed under the bottom surface of the urine tank210. A foam detection sensor530installed on the outer surface of the urine tank210to detect foam of the urine and generate a foam detection signal when the foam of the urine reaches a preset range may be included on the outer surface of the urine tank210. The foam detection sensor530may be an infrared sensor. At least one among the urine level signal generated by the float sensor510, the urine mass signal generated by the mass sensor520, and the foam detection signal generated by the foam detection sensor530may be transferred to the control unit230through wired or wireless communication. When the received urine level value is out of a preset range, the received urine mass information is out of a preset range, or the foam detection signal is received, the control unit230may generate and transfer a driving stop control signal to the vacuum pump240to stop driving of the vacuum pump240. When the driving stop control signal is received, the vacuum pump240may stop driving to prevent flow of the urine into the urine tank210. According to an embodiment of the present invention, a strip800capable of monitoring the wearer's health condition through urine may be mounted inside the urine tank210. In the strip800, pads820containing a detection reagent may be attached to a strip support810made of a plastic or paper material. The pad820containing the detection reagent is referred to as a color change unit820in the present invention. The strip800may include a plurality of color change units820changing color when urine touches in order to analyze various components in the urine at once. Preferably, the color change unit820changes to another color according to a predetermined reaction table according to the presence or amount of urobilinogen, glucose, ketone, bilirubin, protein, nitrite, pH, blood, specific gravity, and white blood cells contained in the urine. According to a first embodiment of the present invention, the strip800may be mounted on the strip mounting unit900. The strip mounting unit900may include a first support unit910for supporting the strip support810in the longitudinal direction, a second support unit930perpendicular to the first support unit910and supporting a first surface of the strip support810, and a latch unit920for supporting a second surface of the strip support630and latching the strip mounting unit900on one side of the urine tank210. AlthoughFIG.4shows that the strip mounting unit900is mounted on the top surface of the urine tank210for convenience, the strip mounting unit900may be mounted on the side surface or the bottom surface of the urine tank210depending on circumstances. The first support unit910has a plurality of openings911through which the urine stored in the urine tank210may flow. The urine stored in the urine tank210may be transferred to the color change units820through the openings911. Referring toFIG.3, the first support unit910and the second support unit930are formed to be perpendicular to each other, so that the first support unit910may support the strip support810of the longitudinal direction, and the second support unit930may support the strip support810of a direction perpendicular to the longitudinal direction. Preferably, a second surface (the bottom surface in the drawing) of the first support unit910may be bent vertically to form the second support unit930. The latch unit920is formed to be perpendicular to the first support unit910to face the second support unit930. The latch unit920may be formed to be perpendicular to the first support unit910on a first surface of the first support unit910. The first and second surfaces of the first support unit910face each other. The length of the outer surface of the latch unit920is formed to be longer than the length of the inner surface as much as the horizontal length of the first support unit910. The latch unit920includes a cutout unit that is cut in a rectangular shape having a horizontal surface of a first length and a vertical surface of a second length. The first length is smaller than the length of the horizontal surface of the latch unit920, and the second length is smaller than the length of the vertical surface of the latch unit920. The inner surface of the latch unit920has a shape bent twice through the cutout unit. A first bent unit bent first is extended from the inner surface of the first support unit910in a direction perpendicular to the first support unit910as much as a third length, bent in a direction parallel to the first support portion910, and extended as much as a second length. Then, the bent second bent unit is connected to the end of the first bent unit extended as much as the second length, extended starting from a direction perpendicular to the first support unit910as much as the first length, bent in a direction parallel to the first support unit910, and then extended as much as the second length. Referring toFIG.3, the first bent unit is bent in a ‘┘’ shape, and the second bent unit is bent in a ‘┐’ shape. One side of the strip support810is seated in and supported by the first bent unit, and the second bent unit, which is a second bent portion, is seated on one surface of the urine tank210. Referring toFIG.3, the vertical portion of the first bent unit and the horizontal portion of the second bent unit are connected to each other. As the components of the urine stored in the urine tank210are detected by opening the urine tank cover211and latching the strip mounting unit900on one side of the urine tank210, there is an advantage in that the sealing force of the urine tank210is not weakened. In addition, it is also advantageous in that cleaning is easy when the urine tank210is cleaned since only the strip mounting unit900needs to be removed. As one side surface of the urine tank210on which the strip mounting unit900is mounted is formed of a transparent material, color change of the color change units820may be easily detected with naked eyes. In addition, at least one first optical sensor unit540may be disposed on the outer surface of the urine tank210in order to automatically detect color change of the strip800. As many first optical sensor units540as the number of the color change units820are installed at the locations corresponding to the positions of the color change units820. Preferably, the first optical sensor units540may be detachably installed at the locations corresponding to the positions of the color change units820. When the strip800includes six color change units820capable of detecting urobilinogen, glucose, ketone, bilirubin, protein, and nitrite contained in the urine, a total of six first optical sensor units540may be installed at the locations corresponding to the positions of the six color change units820, respectively. Alternatively, the first optical sensor unit540may include a single light source, a transmission unit for distributing light emitted from the single light source and outputting the light to each color change unit820, and a plurality of light receiving units for receiving light reflected from each color change unit820. Information on the strip color change sensed by the first optical sensor unit540may be transferred to the control unit230. A second optical sensor unit for sensing at least one among turbidity and color change of the urine stored in the urine tank210may be included on the side surface of the urine tank210. A light receiving unit552of the second optical sensor unit is installed on a first outer surface of the urine tank210, and a light emitting unit551of the second optical sensor unit is installed on a second outer surface of the urine tank210to sense least one among the turbidity and the color change of the urine stored in the tank210and transfer urine turbidity information and urine color information to the control unit230. 2. Auxiliary Tank (300) The auxiliary tank300is formed to have an open top surface and may be provided with a second urine tank cover311that covers and seals the opened portion of the auxiliary tank300. A second gas transfer unit312and a third gas transfer unit313are formed on the top surface of the second urine tank cover311. The second gas transfer unit312is connected to the second connecting hose620, and the third gas transfer unit313is connected to the third connecting hose630. The auxiliary tank300transfers negative pressure to the urine tank210through the second gas transfer unit312connected to the second connecting hose620, and receives gas contained in the excrement from the urine tank210. The auxiliary tank300receives the negative pressure from the vacuum pump240through the third gas transfer unit313and transfers the gas contained in the excrement toward the vacuum pump240. The auxiliary tank300receives the gas contained in the excrement from the urine tank210. This gas also includes water vapor vaporized from water. The auxiliary tank300may prevent transfer of moisture to the vacuum pump240by condensing and storing the received water vapor. The capacity of the auxiliary tank300may be 0.1 to 0.5 when the capacity of the urine tank210is set to 1. 3. Vacuum Pump (240) The vacuum pump240of the present invention is connected to the control unit230and operates according to a control signal generated by the control unit230. The urine sensor120may generate and transmit a urine detection signal to the terminal700mounted on the receiver100through wired or wireless communication. The terminal700may transfer the received urine detection signal to the control unit230through wireless or wired communication. When the urine detection signal is received, the control unit230may generate and transfer a driving start signal for driving the vacuum pump240to the vacuum pump240. The vacuum pump240operates when the driving start signal is received from the control unit230. When the vacuum pump240operates, a negative pressure is formed by sucking the air in the urine tank210. The negative pressure formed in this way is transferred to the auxiliary tank300through the third connecting hose630. The negative pressure applied to the auxiliary tank300is transferred to the urine tank210through the second connecting hose620. The negative pressure applied to the urine tank210is transferred to the urine drainage hole140of the receiver100through the first connecting hose610. The negative pressure is transferred to the urine storage unit130of the receiver100through the urine drainage hole140, and as the negative pressure is applied to the urine storage unit130, the urine and the gas stored in the urine storage unit130are transferred to the urine tank210through the urine drainage hole140via the first connecting hose610. In addition, the vacuum pump240may blow the gas transferred through the third connecting hose630toward the second filter unit260. 4. Control Unit (230) The control unit230may receive a urine detection signal from the terminal700or directly receive the urine detection signal from the urine detection sensor110through wired or wireless communication. When the urine detection signal is received, the control unit230generates and transfers a driving start signal that controls to drive the vacuum pump240to the vacuum pump240. When the driving start signal is received, the vacuum pump240is driven and generates a negative pressure. In addition, the control unit230may receive a urine level signal from the float sensor510through wired or wireless communication, a urine mass signal from the mass sensor520through wired or wireless communication, and a foam detection signal from the foam detection sensor530through wired or wireless communication. The control unit230may generate a first danger signal when the urine level is greater than or equal to a preset range based on the received urine level signal. In addition, the control unit230may generate a second danger signal when the mass of the urine is greater than or equal to a preset range based on the received urine mass signal. In addition, the control unit230may generate a third danger signal when a foam detection signal is received from the foam detection sensor530. In addition, the control unit230may generate and transfer a driving stop control signal for controlling to stop driving of the vacuum pump240to the vacuum pump240when at least one among the first to third danger signals is generated. The vacuum pump240may stop driving to prevent flow of moisture into the vacuum pump240when the driving stop control signal is received. In addition, the control unit230may receive gas sensing information from the gas sensor430and distinguish between feces and fart. The control unit230forms a graph using the horizontal axis as the time axis and the vertical axis as the gas level axis based on the gas sensing information, and when the peak of the gas level lasts for a predetermined time, it is determined as feces, and when it does not last for the predetermined time, it is determined as fart. When feces is detected based on the gas sensing information, the control unit230transfers a signal for replacing the receiver100to the communication unit220, and when the signal for replacing the receiver100is received, the communication unit220transfers the signal to the terminal10or20of the guardian or medical staff to replace the receiver100. The control unit230may receive strip color change information from the first optical sensor unit540through wired or wireless communication, and urine turbidity information and urine color information from the second optical sensor unit. The control unit230previously stores strip color change information according to health conditions, and compares the received strip color change information with the previously stored strip color change information. The strip color change information stored in the control unit230may include first strip color change information indicating a healthy state, second strip color change information indicating an abnormal health state, and a third strip color indicating a serious problem in the health state. When the received strip color change information matches the second strip color change information, the control unit230may generate a first health state abnormal signal indicating an abnormal health state, and transfers the first health state abnormal signal and the received strip color change information to the communication unit220. In addition, when the received strip color change information matches the third strip color change information, the control unit230may generate a second health state abnormal signal indicating a serious problem in the health state, and transfers the second health state abnormal signal and the received strip color change information to the communication unit220. In addition, when the second health state abnormal signal is generated, the control unit230may generate a first alarm device driving signal to trigger a visual or audible alarm through an alarm device (not shown) installed outside the main body200, and immediately inform that there is a serious problem in the health state of the wearer. When the alarm is generated in this way, the medical staff may directly see the color change of the strip800with naked eyes and detect early that the patient is in a dangerous condition. In addition, the control unit230stores urine turbidity information and urine color information according to the health conditions, and compares urine turbidity information and urine color information received from the second sensor unit through wired or wireless communication with the previously stored urine turbidity information and urine color information. The urine turbidity information and urine color information stored in the control unit230may include first urine information indicating a healthy state, second urine information indicating an abnormal health state, and third urine information indicating that there is a serious problem in the health state. When the received urine turbidity information and urine color information match the second urine information, a third health state abnormal signal indicating an abnormal health state is generated. The control unit may transfer the generated third health state abnormal signal and the received urine turbidity information and urine color information to the communication unit220. In addition, when the received urine turbidity information and urine color information match the third urine information, the control unit230may generate a fourth health state abnormal signal indicating that there is a serious problem in the health state, and transfer the fourth health state abnormal signal and the received urine turbidity information and urine color information to the communication unit220. In addition, when the fourth health state abnormal signal is generated, the control unit230may generate a second alarm device driving signal to trigger a visual or audible alarm through an alarm device (not shown) installed outside the main body200, and immediately inform that there is a serious problem in the health state of the wearer. When the alarm is generated in this way, the medical staff may directly see the stored urine turbidity and urine color with naked eyes and detect early that the patient is in a dangerous condition. In addition to those described above, the control unit230of the present invention may supply dry air to the receiver100or generate a control signal for driving the vacuum pump240depending on operating conditions according to various environments, such as transferring air to the second filter unit260described below. 5. Communication Unit (220) In addition, the communication unit220may transfer the first health state abnormal signal and the strip color change information from the control unit230to the guardian terminal10or the medical staff terminal20. In addition, the communication unit220may transfer the second health state abnormal signal and the strip color change information from the control unit230to the guardian terminal10or the medical staff terminal20. In addition, the communication unit220may transfer the third health state abnormal signal, the urine turbidity information, and the urine color information from the control unit230to the guardian terminal10or the medical staff terminal20. In addition, the communication unit220may transfer the fourth health state abnormal signal, the urine turbidity information, and the urine color information from the control unit230to the guardian terminal10or the medical staff terminal20. 6. Power Supply Unit (250) The power supply unit250according to an embodiment of the present invention may supply power to the vacuum pump240, the communication unit220, and the control unit230. In addition, the power supply unit250may be connected to the terminal700through a wire and supply power to the terminal700. The terminal700connected to the conventional receiver100is embedded with a battery. However, the terminal700embedded with a battery as described above has a disadvantage in that the vacuum pump240is not driven since the urine detection signal transmitted from the receiver100is not received when the battery is exhausted. In particular, in the case where the vacuum pump240does not operate properly during the late night when the healthcare assistants are absent for a long time, urine of the receiver100is not discharged, and this causes skin erosion of the wearer and indoor air pollution. 7. Second Filter Unit (260) The second filter unit260according to an embodiment of the present invention may receive the air flowing out from the urine tank210, filter the air, and discharge the air to the outside of the automatic urine treatment system. Although the air is sterilized through a UV lamp conventionally, skin rash or erythema occurs when the skin is excessively exposed to the UV lamp, and it is known that skin cancer is caused when the skin is overexposed. To solve this problem, in the present invention, the second filter unit260may be formed by mixing natural plant-derived powder with activated carbon having an excellent odor removal function, and hardening the mixture. The second filter unit260is generated through the process described below. The second filter unit260may be manufactured in the steps of crushing activated carbon, obtaining eucalyptus powder by vacuum-drying and crushing eucalyptus extract extracted using ethanol, obtaining lotus leaf powder by vacuum-drying and crushing lotus leaf extract extracted using ethanol, and forming a block by uniformly mixing the activated carbon crushed powder, the eucalyptus powder, the lotus leaf powder, and a resin binder and molding the mixture. Activated carbon is known to be the most excellent one in removing odor among natural substances. Eucalyptus terpenes oxidize in the air and generate ozone, and the ozone generated in this way has a strong sterilizing effect. Lotus leaves have excellent deodorizing and antibacterial effects. The solid block manufactured by mixing the activated carbon, the eucalyptus, and the lotus leaves is a natural plant-derived material harmless to the human body, while having excellent deodorizing, antibacterial, and sterilizing effects. Alternatively, the second filter unit260may be manufactured in the steps of crushing activated carbon, obtaining eucalyptus powder by vacuum-drying and crushing eucalyptus extract extracted using ethanol, obtaining lotus leaf powder by vacuum-drying and crushing lotus leaf extract extracted using ethanol, obtaining chlorine dioxide powder, and forming a block by uniformly mixing the activated carbon crushed powder, the eucalyptus powder, the lotus leaf powder, the chlorine dioxide powder, and a resin binder and molding the mixture. The present invention has an advantage of preventing failure of the vacuum tank by removing moisture transferred to the vacuum pump through the auxiliary tank. The present invention has an advantage of caring health of elderly or disabled people by mounting a strip for analyzing components of urine through a color change in the urine tank, analyzing the color change through a first optical sensor, and transferring a result thereof to the terminal of a guardian or a medical staff. In addition, the present invention has an advantage of preventing skin trouble of a wearer by including a substance having antibacterial, sterilizing, and deodorizing functions of natural plant-derived components in the first filter unit of the receiver contacting the wearer's skin. In addition, the present invention has an advantage of purifying the air of a room in which the urine tank is installed by including the second filter unit that removes germs or odor contained in the excrement flowing out from the urine tank. | 35,785 |
11857717 | FIGS.1and2show an aerosol-generating system10comprising an aerosol-generating device20and a cartridge100for use with the aerosol-generating device20. The aerosol-generating system further comprising a mouthpiece30configured to attach releasably to a proximal end24of the aerosol-generating device20. The aerosol-generating device20comprises a housing having a cavity22for receiving the cartridge100through an opening at the proximal end24of the housing. The aerosol-generating device20comprises an inductor coil28within the cavity22. The inductor coil is held within the internal walls the cavity22as shown inFIG.2. The aerosol-generating device20comprises an electrical energy supply40in the housing, in this example a rechargeable lithium ion battery. The device10further comprises a controller42connected to the battery30, the inductor coil28and a user interface (not shown). In this embodiment, the user interface comprises a mechanical button. Upon activating the user interface, the controller supplies the inductor coil28with a high frequency oscillating current, to produce an oscillating magnetic field. This causes one or more susceptors in the cartridge100to heat as a result of induced eddy currents and hysteresis losses. This heats the nicotine source and a lactic acid source contained within the cartridge, producing a nicotine vapour and a lactic acid vapour. As the user puffs on the mouthpiece30, a flow of air is drawn from an air inlet26through the cartridge to convey the vaporized nicotine and lactic acid towards the mouthpiece. The vaporized nicotine and lactic acid, each in a gas phase, then react and cool in the mouthpiece30to form an aerosol containing nicotine salt particles. During the puff, the user receives a volume of the aerosol through an exhaust outlet32. FIG.3is an exploded view of the cartridge100. The cartridge100has a length of about 15 millimetres, a width of about 7.1 millimetres and a height of about 6.75 millimetres. The cartridge100in this illustrated example comprises an elongate cartridge body102closed by an end cap130at either of its distal104and proximal ends106. The body102has a length of about 11 millimetres, a width of about 7.1 millimetres and a height of about 6.75 millimetres. The end cap130has a length of about 2 millimetres, a width of about 7.1 millimetres and a height of about 6.75 millimetres. The cartridge100comprises a nicotine source210contained in a first compartment110and a lactic acid source220contained in a second compartment120of the cartridge100. The first compartment110and the second compartment120each extend longitudinally within the cartridge body102. The first compartment110and the second compartment120are arranged to be closed by an end cap130at their respective distal end104and proximal end106. The first compartment110and the second compartment120are identical compartments each having a substantially rectangular cross-section with a depth of about 1 mm. The first compartment110and the second compartment120are arranged in a parallel configuration. The incoming air stream splits before entering the first compartment110and the second compartment120. The nicotine vapour and the lactic acid vapour are generated simultaneously in separate compartments. The distal end cap130comprises a plurality of air inlets132,134providing flow passages between an incoming air flow108and the first and second compartments110,120. The air inlets are identical apertures through the distal end cap. The plurality of air inlets132,134comprise first air inlets132in fluid communication with the first compartment110, and second air inlets134in fluid communication with the second compartment134. In the illustrated example, there are more second air inlets134than first air inlets132. This results in a larger cross-sectional flow area through the second air inlets134than through the first air inlets132. This enables a higher volumetric air flow through the second compartment120than the first compartment110. This causes more acid to vaporize in the second compartment120than would be the case if there were fewer second air inlets. The end cap130as shown inFIG.3is a distal end cap having air inlets132,134opened to the first and second compartments110,120. In this example, a proximal end cap, comprising air outlets (not shown) that mirror the air inlets132,134at the distal end cap, is provided at the proximal end106of the cartridge100. The air outlets at the proximal end cap are in fluid communication with the first and second compartments110,120, as well as the exhaust32at the mouthpiece30. The first compartment110and the second compartment120each extends from the distal end cap to the proximal end cap. That is, the first compartment110and the second compartment120both extend all the way through the length of the cartridge body102. The cartridge body102comprises a plurality of heater cavities140each extending along the longitudinal axis of the cartridge100. Each of the heater cavities has a depth of 0.4 millimetres. The heater cavities104are parallel to the first compartment110and the second compartment120. Each of the heater cavities140and its corresponding first compartment110or second compartment120are separated by 0.4 millimetres. Each of the plurality of heater cavities140is arranged to receive a susceptor. The plurality of heater cavities140are closed at both of the distal end104and the proximal end106by their respective distal end cap and proximal end cap. In the illustrated example, each of the first compartment110and the second compartment120is sandwiched between a pair of heater cavities140. In this embodiment, a plurality of identical susceptors are used, one placed in each heater cavity140. During use both the nicotine source210and the acid source220are heated to the same temperature. The first compartment110and the second compartment120each comprise a plurality of parallel ridges150extending longitudinally along the length of the cartridge100. The plurality of ridges150protrude from a sidewall of the first compartment110and a sidewall of the second compartment120. Once assembled, the nicotine source210and the lactic acid source220abut the plurality of ridges150of the cartridge. This is illustrated in the sectional view of the cartridge100inFIG.4. Once the nicotine source210and the lactic acid source220are assembled into the first compartment110and the second compartment120, they rest against the ridges150. The sources210,220are closed by the end caps130at either ends of the cartridge100and in fluid communication with their respective air inlets132,134and air outlets133,135. FIG.5is a different sectional view of the cartridge100, orthogonal to the section ofFIG.4, showing the flow path of air streams flowing through the interior of the cartridge100. The air streams enter the cartridge100through air inlets132,134and exit the cartridge100through air outlets133,135. Both the air inlets132,134and the air outlets133,135are provided in the end caps130. A plurality of air flow channels160are formed within the voids between the parallel ridges150, the nicotine/lactic acid source and the side walls of the cartridge100. As the air streams pass through the air flow channels160, they collects vaporized nicotine and lactic acid at the surface of the respective nicotine source210and lactic acid source220. In this example, the nicotine source210comprises a porous ceramic substrate impregnated with a nicotine liquid. The lactic acid source220comprises a porous ceramic impregnated with lactic acid. The nicotine liquid also comprises flavorings that are arranged to vaporize with the nicotine when the nicotine source is heated. Said flavorings are arranged to produce a desirable taste in the generated aerosol. More specifically, the nicotine source210comprises a porous ceramic substrate impregnated with about 10 milligrams of nicotine and about 4 milligrams of menthol, and the lactic acid source220comprises a porous ceramic substrate impregnated with about 20 milligrams of lactic acid. The porous ceramic is a relatively inert material that does not deteriorate when it is put in contact with either the nicotine liquid or the lactic acid. The rigidity of the porous ceramic ensures consistent external dimensions for both of the nicotine and lactic acid sources210,220over the lifetime of the cartridge. More specifically, the nicotine and lactic sources210,220do not expand or shrink dependent on the amount of liquid remaining. The cross sectional area of the air flow channels150remains unchanged during different stages of cartridge use, thus providing a consistent puffing experience for the user. In practice, the user puffs on the mouthpiece30to draw a volume of air flow through the air flow channels150. A portion of the air stream entering the first compartment110and the second compartment120may penetrate beneath the surface of the porous ceramic material, before emerging back to the air flow channels160. This aids the evacuation of vaporized nicotine and lactic acid as it is generated from within the pores of the ceramic. As shown inFIG.5, each of the end caps130comprises end cap ridges138which are complementary to the ridges150in the cartridge100. The inwardly facing side of the end cap130is shown in further detail in the perspective view ofFIG.6. The end cap130shown inFIG.6is a distal end cap configured to close the distal end104of the cartridge body102. The proximal end cap is of a similar design where the air inlets arrangement is mirrored for closing the proximal end106of the cartridge body102. The end cap130comprises fittings137for effecting a non-releasable coupling with the cartridge body102. This ensures the user cannot dismantle or tamper with the cartridge100. The end cap130comprises a plurality of end cap cavities131each complementary to the first compartment110and second compartment120in the cartridge body102. The end cap cavities131are arranged to open on an inwardly-facing surface and extend partially along the depth of the end cap130. The end cap cavities1371are configured to contain the ends of both the nicotine source210and the lactic acid source220when the end cap130is fitted onto the distal end104or the proximal end106of the cartridge body102. The plurality of end cap ridges138are complementary to the plurality of ridges150in the first compartment110and the second compartment120, and providing further support to the nicotine and lactic acid sources210,220. The end cap ridges138also serve as extension to the air flow channels160. By positioning the end cap cavities137over the nicotine and lactic acid sources210,220in the first and second compartments110,120, the end caps can be easily aligned and assembled onto the cartridge body102. The end cap130further comprises end cap heater cavities136complementary to the heater cavities140in the cartridge body102. Similar to the end cap cavities137, the end cap heater cavities136open at an inwardly-facing surface of the cartridge body102and extend partially along the depth of the end cap130. The end cap heater cavities136allow the susceptors as contained in the heater cavities to be further supported therein. In this particular embodiment, the end cap heater cavities136are configured to provide a snug fit to the susceptors. As a result, the susceptors are held firmly in place by the end caps. As discussed with reference toFIG.5, the parallel ridges150protruding from the cartridge wall serve several functions. They support and stabilize the nicotine and lactic acid sources when they are assembled into their respective first and second compartments110,120. The ridges150also form air channels160to allow air streams to pass over the surface of the nicotine and lactic acid sources110,120to evacuate vaporized nicotine and lactic acid effectively. Because the majority of the air stream does not flow through the nicotine or lactic acid sources, this arrangement significantly reduces the resistance to draw (RTD). The ridges150as shown inFIG.5define straight flow paths and therefore they allow vaporized nicotine and lactic acid to be promptly evacuated from their respective first and second compartments110,120. However in some cases, other types of protrusions may be used in place of the ridges150to provide other functions. For example, instead of straight ridges, ridges with a sinusoidal profile may be used to induce turbulence in the air streams. This improves convection within the air flow channels, as well as forcing a larger portion of the air stream to penetrate beneath the surface of the porous nicotine and lactic acid source. FIG.7ashows a sectional side view of an alternative cartridge design having a plurality of bosses152extending from the side walls of the compartments. In this embodiment, the bosses replace the parallel ridges150as shown inFIG.5. These bosses152support and stabilize the nicotine and lactic acid sources210,220once they are assembled into their respective compartments110,120. As illustrated inFIG.7a, the bosses result in tortuous flow paths in the air streams. This induces more turbulence in the air flow, and so increases the contact time and contact area of the air with the nicotine source and acid source. In an alternative embodiment, as shown inFIG.7b, the end cap130as shown inFIG.6is used for closing a cartridge body102cthat does not feature any ridge in either the first compartment110or the second compartment120. Therefore, a single air flow channel160cis formed in the void between the surface of the sources210,220and the sidewalls of the compartments110,120. In this embodiment, the nicotine source210and the lactic acid source220are retained in the respective first110and second120compartments solely by the end cap ridges138. In use, air streams entering the first and second compartments110,120may flow freely across the width of a single air flow channel160c. This encourages lateral convection across each of the compartments110,120. In an alternative embodiment, the airflow channels160do not extend all the way through the cartridge body102d. As shown inFIG.8, the channels between the ridges150gradually fill towards the air outlets133,135. This causes the cross-sectional area across each of the air flow channels160to progressively reduce in the direction of air flow. In the illustrated example, the air flow channels160do not open to the air outlets133,135at the proximal end106of the cartridge100d. Instead, the air streams in the air flow channels are forced to penetrate and flow through the nicotine and lactic acid sources210,220, before exiting the cartridge100dthrough the air outlets133,135. This means that the air streams in the air flow channels, already dosed with nicotine and lactic acid vapors, are exposed to more vaporized nicotine and lactic acid within the pores of the porous ceramic material. In another embodiment, the heater cavities140in the cartridge100are merged with their respective first compartment110and second compartment120. More specifically, the susceptors are no longer supported in separate heater cavities140. Instead they are held in place by the end cap heater cavities136. As a result, the susceptors no longer conduct heat through the sidewalls of the compartments110,120. Instead, the susceptors directly heat the nicotine source210and lactic source220in their respective compartments110,120. The susceptors in this case are mesh susceptors. The use of mesh susceptors permits unrestricted air flow within the compartments, and thus enhances heat convection therein. FIG.9shows a cartridge300according to an alternative embodiment. The cartridge300is closed by end caps330at either end of the cartridge300. In comparison with the cartridge100as shown inFIG.4, the cartridge300employs susceptors340that are put into direct contact with the nicotine and lactic acid sources210,220. The susceptors in cartridge300are ferrous meshes. The mesh susceptors are arranged to be positioned at the interfaces between ridges360and the nicotine or lactic acid sources210/220. More specifically, the mesh susceptors340are configured to partition each of the first compartment310and second compartment320such that the sources210,220and flow channels350formed between the ridges360are separated from each other. In this example, the heater cavities140in cartridge100ofFIG.4are not present. Due to the absence of such heater cavities, the end cap heater cavities136as featured in cartridge100ofFIG.4are also not present in end caps330. The absence of such cavities allows larger first and second compartments110,120in the cartridge300. As a result, thicker nicotine and lactic acid sources210,220, e.g. ones with larger storage capacities, may be used. In use, the inductor coil28induces eddy currents in the mesh susceptors, causing the mesh susceptors340to heat up. Because of its mesh construction, the mesh susceptors340permit vaporized nicotine and lactic acid at the surface of their respective sources210,220to escape into their respective air flow channels350. Since heating takes place at the surface of the nicotine and lactic acid sources210,220, vaporized nicotine and lactic acid no longer have to percolate through the depth of the sources to be extracted at their respective surfaces. Therefore, such arrangement allows a more efficient extraction of vaporized nicotine and lactic acid. The mesh susceptors340are supported by the ridges in the first and second compartments310,320. This allows the mesh susceptors340to be formed from materials with lower mechanical strength. In other words, the mesh susceptors may be formed from flexible materials and do not need to sustain their own weight. In yet another embodiment as shown inFIG.10, the inductor coil28in the aerosol-generating device20and the susceptors are replaced by a plurality of resistive heating elements29. In this embodiment the resistive heating elements are part of the aerosol-generating device20. During use, the controller42controls the power supply to the resistive heating elements29to heat the nicotine source210and lactic acid source220. The plurality of resistive heating elements29are elongate electric heaters positioned in the cavity22of the aerosol-generating device20. The elongate electric heaters extend along the longitudinal axis of the cavity22and are each arranged to fit into a corresponding heater cavity of the cartridge400. In comparison to the end cap130ofFIG.5, a modified distal end cap is provided for the cartridge400in this embodiment. The end cap heater cavities136inFIG.6are replaced by open heater slots extending through the depth of the distal end cap. Through these heater slots, the heater elements29of the aerosol-generating device20extend into the heater cavities of the cartridge body. In this particular embodiment, the heater slots are configured to provide a snug fit to the resistive heating elements29. Thus allowing the cartridge400to be supported by the heating elements29when it is inserted into the cavity22of the aerosol-generating device20. Prior to first use of the cartridge100, the air inlets132,134and the air outlets133,135are sealed by a removable peel-off foil seal (not shown) applied to the outwardly facing surface of the end caps130. This reduces loss of nicotine and lactic acid to the atmosphere, thus lengthening the shelf life of the cartridge. In addition, the foil seal prevents contamination of the nicotine source210and the lactic acid source220. The exemplary embodiments described above illustrate but are not limiting. In view of the above discussed exemplary embodiments, other embodiments consistent with the above exemplary embodiments will now be apparent to one of ordinary skill in the art. | 19,767 |
11857718 | When practical, similar reference numbers denote similar structures, features, or elements. DETAILED DESCRIPTION Implementations of the current subject matter include methods and devices relating to vaporizing of one or more materials for inhalation by a user. The term “vaporizer” is used generically in the following description and refers to a vaporizer device. Examples of vaporizers consistent with implementations of the current subject matter include electronic vaporizers, electronic cigarettes, e-cigarettes, or the like. In general, such vaporizers are often portable, frequently hand-held devices that heat a vaporizable material to provide an inhalable dose of the material. A vaporizer consistent with certain implementations of the current subject matter is a hand-held device that operates primarily by convection to provide efficient transfer of air being heated as well as rapid delivery of vaporizable material to a user. Vaporizers consistent with certain implementations of the current subject matter are configured to permit very rapid (e.g., within 3 seconds, within 2 seconds, within 1 second, etc.) heating of air drawn through an oven chamber to cause vaporizable material (e.g., loose leaf plant material, etc.) in the oven chamber to be heated to a target vaporization temperature. The oven chamber may be thermally conductive (to permit additional heating and vaporization of the material within the oven) or thermally insulating (to resist transfer of heat to the oven, so that heat is transferred just to the vaporizable material). The oven chamber may be present at the distal end of the device, opposite from a proximal mouthpiece. Alternatively, the oven chamber may be located adjacent or in close proximity to the mouthpiece, for example below or adjacent a mouthpiece portion of the device. The oven chamber may be connected near the distal end of the device (e.g., to a frame or skeleton of the vaporizer) though one or more contacts; however, some or a majority of the oven chamber may be surrounded by an air gap (or other thermal isolation means, for example insulating material) to reduce transfer of heat from the oven chamber to the rest of the apparatus. The oven chamber may include a lid. The oven chamber may be manufactured as a deep drawn oven, e.g., may have a depth, width, and breadth, wherein the depth (the distance from the inside of the lid to the bottom, e.g., screen) of the oven chamber, for example, may be between 0.3× and 2× the width of the oven; the breadth may be between 0.1× and 1× the width. Generally, the oven chamber may be sized for an intended use of the vaporizer device in which it is housed, and/or the oven chamber may be sized based on manufacturing considerations. The oven chamber may have solid walls, perforated walls, a basket-weave structure, or some other configurations of solid and open areas, or combinations of these, configured to reasonably contain the material to be vaporized. The oven chamber can be configured to accept a further inner vessel (not shown) which can contain vaporizable liquids or waxes or the like. The heater (e.g., resistive heating element) may be positioned in the air path and configured for rapidly heating air passing around and/or through the heater. The heater may include one or more openings, passages, channels, slots, slits, etc., for passage of air through and/or around the heater, one or more of which such air passages may have irregular, jagged, fractal, protruding edges or the like which, together and/or separately with the configuration of the heater may create increased turbulent airflow through or around the heater, increasing the transfer of heat to the air as it passes through/around the heater. In one embodiment, the heater may be an elongate tube extending in a long axis, the tube having one or more cut-out regions along its length therethrough to generate turbulence in air passing transversely across and/or along the long axis of tube. In some variations, the heater can include one or more thin layers or sheets of material having a plurality of slots, slits, or cut-out regions through which air passes; these sheets may be folded, crumpled, layered, or the like; alternatively, in some variations the sheet is flat. In other variations, the heater can be a coil or string of resistive material, which can have surface variations, bumps, vanes, or the like to increase surface area, and thereby improve heat transfer to the air flowing around and through the heater. In certain implementations of the current subject matter, the heater may be controlled by heater control circuitry that includes four-point inputs; a first pair of inputs may correspond to the heater power leads/inputs; the second pair of inputs/leads may be offset from the heater power inputs (and in some variations positioned between the heater power leads) and may be configured to sense the voltage drop across a region of the heating element. The four-point measurement control may be used to determine the temperature of the resistive heater with a relatively fine resolution (e.g., within +/−5° C., within +/−4° C., within +/−3° C., within +/−2° C., etc.). Alternatively, a two-point temperature sensing system can be used, where the same leads used for applying the heater power current also can apply a smaller current to measure a voltage drop across the leads, thereby measuring the heater temperatures at times different from when heater current is applied. In addition, a temperature sensor (e.g., thermocouple, infrared sensor, or similar) may be deployed within the air flow path downstream of the heater (e.g., between the heater and the oven chamber, within the oven chamber, etc.) to sense the temperature of air flowing into, through, or around the oven chamber and vaporizing the material within the oven chamber. In any of the variations described herein, the temperature control circuitry may receive input from the heater (e.g., the resistance and therefore temperature of the heater via two- or four-point measurement) and may also receive input from the downstream air flow temperature sensor(s) (e.g., one or more thermistors in the entry for heated airflow into the oven chamber). The temperature control circuitry may be configured to, upon sensing negative pressure due to a user drawing on the mouthpiece, immediately deliver an elevated power (current) to the heater at a first frequency/duty cycle. This elevated power may near-immediately increase the temperature of the heater (e.g., >500° C.), but may be limited by the control circuitry to remain below a safety limit (e.g., 700° C.) or within a useful temperature range. The control circuitry may further monitor the temperature of the heated air that has passed over the heater prior to entering the oven chamber (e.g., via the one or more thermistors) and may limit the temperature of the oven chamber (e.g., by modifying the power applied and/or the frequency/duty cycle of the power applied to the heater) as part of a control loop. Thus, the vaporization temperature, corresponding to the temperature of the air applied to vaporize the material within the oven chamber, may be kept at a desired target temperature, or within a desired or useful temperature range. The target temperature may be predetermined (e.g., preset on the device) and/or may be user selected or user modified. The target temperature may be a single temperature or a plurality of temperatures, including a temperature profile (e.g., a plurality of temperatures over time), or an acceptable temperature range. The user may input absolute temperatures (e.g., degrees Celsius or Fahrenheit) or may modulate predetermined temperatures (up or down). In general, the vaporizer devices consistent with some implementations of the current subject matter may be configured for use with a loose-leaf, or liquid or wax or other vaporizable material. Any of these devices may be configured to wirelessly connect to one or more devices, including user-controlled devices, to modify operation of the vaporizer device. For example, the devices described herein may wirelessly communicate with a user interface that allows dosing control (dose monitoring, dose setting, dose limiting, user tracking, etc.), locational information (e.g., location of other users, retailer/commercial venue locations, vaping locations, etc.), vaporizer personalization (e.g., naming the vaporizer, locking/password protecting the vaporizer, parental controls, associating the vaporizer with a user group, registering the vaporizer, etc.), and engaging in social activities (games, groups, etc.) with other users. A vaporizer device consistent with implementations of the current subject matter may include a stack-up arrangement of circuit board and battery and other components. The oven chamber may be comparatively large compared to the overall size of the vaporizer device, yet have a relatively small thermal mass, allowing it to heat rapidly (e.g., within 1 second or less) to the vaporization temperature of the material (e.g. for tobacco, between 100° C. and 300° C.). Thus the relative size/ratio of vaporization chamber can be greater when compared to other devices. Overall the device may be thin and small. Since the device may heat quickly (within 1 second or less) to vapor, and energy losses due to thermal mass around the convective heating path can be kept relatively low, a user applying a puff (or if the device is lip sense activated) (or, alternatively, a user turning on (e.g., selecting or depressing a button or the like)) may need only a three to four second puff to get a satisfying amount of vapor almost instantly, effectively duplicating the effect of conventional combustion-based cigarettes, cigars, pipes or the like, increasing user satisfaction. Consistent with some implementations of the current subject matter, a vaporizer may have a large, or even unlimited number of customizable temperature settings. A number of sessions per charge and a number of user puffs per charge, as well as a charge time of the vaporizer device, may be based on the size of battery that is used. With reference toFIGS.1A-1D, exterior features of an exemplary vaporizer device100consistent with implementations of the current subject matter are illustrated. As shown, the vaporizer device100may have an elongate or generally rectangular shape with two opposing end portions shorter in length than two opposing side portions. However, variations of the size and shape of a vaporizer consistent with implementations of the current subject matter are possible. For example, the vaporizer device100may have an essentially square, tubular, spherical, faceted, ovoid, or other shape, or combinations thereof. A vaporizer consistent with implementations of the current subject matter may be compact and sized to easily fit within a hand of a user, as shown inFIG.1B. The vaporizer device100has an outer housing114, a mouthpiece122at a top (or proximal) end120, and a lid110at a bottom (or distal) end130. As shown inFIG.1D, inlet air holes160are provided on and extend through the outer housing114. A universal serial bus (USB) charging port170is also provided extending through the outer housing114. FIG.2, via an exploded view, illustrates several of the features of the vaporizer device100. Internal to the outer housing114is a structural housing component212. One or more side air channels215(one shown inFIG.2) may be formed into one or more respective side surfaces of the structural housing component212. Consistent with some implementations of the current subject matter, the structural housing component212may be made from a ceramic material, other insulating material, or other material (such as metal) thermally insulated from the heater. A battery240and a printed circuit board (PCB)216are layered and contained within the structural housing component212. A portion of an oven chamber201with a housing213is also contained within the structural housing component212near end130of the vaporizer200. Electrical leads205are shown extending from within the housing213. The lid110covers an open portion of the oven chamber201. The mouthpiece122is at the end120of the vaporizer200. FIG.3, via a cross-sectional view, illustrates several features of a vaporizer device300. As shown inFIG.3, the vaporizer device300includes, near (e.g., nearly adjacent or adjacent) the bottom end330, an internal oven chamber301with a surrounding oven housing313. The lid310mates or otherwise attaches to the outer housing314at the bottom end330. The mouthpiece322mates or otherwise attaches to the outer housing314at the top end320. Internal to the outer housing314is a structural housing component312. One or more internal side slots or channels309are formed between and extend along the lengths of outer side walls of the structural housing component312and inner side walls of the outer housing314. The internal side channel309extends from the oven chamber301to the mouthpiece322, providing a cooling pathway for the vaporizable material to be inhaled by a user. Heater302is a flat-plated heater which may allow for fast heat-up and is capable of high watt density (e.g., ˜60 W/in2) and may have a high (˜700° C.) operating temp limit, driven by melting point of the dielectric. FIGS.4A-4Eillustrate various features of the exemplary vaporizer device ofFIG.3.FIG.4Aillustrates, via a cross-sectional view, features of an oven chamber301and heater302, andFIGS.4B and4Cillustrate airflow therethrough consistent with some implementations of the current subject matter. As shown, heated air flows up from heater302through the oven chamber301containing the vaporizable material, and back around over the edge of the oven chamber301. Lead305is shown connected to the heater302. In some implementations of the current subject matter, as shown inFIG.4A, a thermal conduction path is through a flange of the oven chamber301, which may have a multiply perforated bottom (e.g., screen315). The openings though the bottom may be arranged in a pattern to distribute the heated air evenly, e.g., having a hole density pattern that is greater on the outer region than the inner region, or other variations for equal or near equal heat distribution. An inlet air path may circulate around the outside of the oven301, to reclaim any heat from the oven301. The heater302may be mechanically captured between two bottoms of deep drawn parts (e.g., deep drawn oven, with another deep drawn part welded to it). The heater302may be welded and/or brazed to the oven chamber301, or possibly mechanically captured. In some implementations of the current subject matter, the heater302may include a “thick film heater” that is anchored only at coolest points. FIGS.4A-4Ealso illustrate some additional features of the oven chamber301and surrounding areas of the vaporizer device300, such as the outer housing314, the structural housing component312, and the lid310. Also shown are two leads305and inlet air holes360. With reference toFIGS.4B and4C, the screen315may be installed within the oven chamber301to prevent the vaporizable material from contacting the heater302. The heater302may be located˜1 mm (e.g., between 0.5 mm and 5 mm, between 0.5 mm and 3 mm, etc.) below the screen315. The screen315and heater302may be constrained by perimeter welds or other means.FIGS.4B and4Cillustrate air paths from air inlet into heater, circulating below, then through, then over the heater, and up into the oven chamber. The heater302may be a low-mass composite structure.FIG.4Dshows an enlarged view of an example heater structure, andFIG.4Eshows airflow paths. Substrate450of the heater302may be, e.g., 0.003″ 430 stainless steel. Each side of the heater substrate450may be coated with a thin layer, 0.002-0.003″, of glass dielectric452. The bottom layer of the heater302is the resistive heating element454which may be composed of a silver palladium alloy 0.001″ thick. A thin layer of glass dielectric (not shown) may also be applied over the resistive element to mitigate oxidative damage. These glass and resistive layers may be applied as, for example, pastes using a screen-printing process. In an embodiment, the heater302may include a stainless steel (SS) substrate with a glass dielectric layer, and a screen-printed resistive trace of ˜0.010″ total thickness. In operation of the vaporizer300illustrated inFIGS.3-4E, a user may remove the lid310, load the oven chamber302with material to be vaporized, place the lid310back on, and take a puff from the device300on the opposite side of the device from the oven, where a mouthpiece is located. As the user draws on the mouthpiece, ambient air enters the device through the inlets of the outer housing314, passes through the structural support housing312(e.g., skeleton) providing structural support for the oven chamber301and other internal components, enters the oven chamber301around cutouts332for leads305, creating a pressure drop within the device which can be measured by a pressure sensor (not shown). When this pressure drop is detected, the heater302is powered by passing an electric current through it via the leads305, causing the resistive element of the heater302to rapidly increase in temperature. The air being drawn into the oven chamber301will be heated as it passes under the heater302, through a central hole337in the heater302, and as it is deflected over the top of the heater by the non-porous region of the screen315. The rest of the screen315is perforated to allow the hot air to readily pass through the material in the oven chamber301before it exits the top of the oven chamber301and runs down the side channels309in the frame (skeleton) to the user. The increased air turbulence generated by the structure of the device, including the airflows across the lower portion of the heater302, through its central hole (or any number of other holes, then over its upper surface and then through oven screen315into the oven chamber301allows for efficient heat transfer from heater302to air to vaporizable material, increasing efficiency and time to vaporization. To minimize energy loss from the heater302, the oven may be very low mass (<0.25 mm walls), and may be thermally isolated. As shown inFIG.4A, there may be a small air gap304between the oven chamber301and the structural housing312that acts as thermal insulation, aiding in the prevention of thermal sink (transfer) into the outer housing314from the heater302. This way, much of the energy from the heater302in the form of heat will pass through the material to be vaporized rather than the body of the device300, or it will transfer to the oven chamber301itself, which will also aid in vaporization (by conductive heating). In the example ofFIGS.3-4E, a thermocouple is not shown, however one or more may be suspended within or over the central hole337in the heater302, or somewhere within oven chamber301. This may provide closed loop control of the air temperature. Although not necessary, a thermocouple would allow for faster vapor production since the heater302could be run at a higher temperature initially, and then be ramped down once the thermocouple indicates the desired vaporization air temperature. Vaporizers consistent with implementations of the current subject matter may include a resistive heating element (e.g., heater302) that is powered with an electric current through two terminals (e.g., leads305). A precision resistance measurement circuit may be used to track resistance of the heating element when not heating and when heating to control the temperature of the heater302based on changes in heater material resistance. In some implementations of the current subject matter, the vaporizer device has an “on”/active mode, but ideally the heater is fired only by triggering a pressure/flow sensor, by capacitive lip sensing, or by the user pressing a button for use, or the like. FIGS.5A-5Eillustrate, via various views, features of another exemplary vaporizer device500consistent with some implementations of the current subject matter.FIGS.5A and5Bshow a section through a front view of the vaporizer device500, showing the heater assembly and oven assembly which can replace the heater and oven assembly shown in the overall vaporizer embodiment shown inFIGS.1through4. The vaporizer device500, consistent with implementations of the current subject matter, is configured as an on-demand, convection-based vaporizer.FIG.5Cillustrates an exemplary heater502.FIG.5Dillustrates a top perspective view of the vaporizer device500, showing details of an oven chamber501.FIG.5Eillustrates airflow through the vaporizer device500. The vaporizer device500includes the oven chamber501that may hold a vaporizable material; this material may be packed or otherwise inserted into the oven chamber501. The oven chamber (or oven)501may be formed by a progressive forming process. The vaporizable material (including loose-leaf vaporizable material) may be stored in the oven chamber501for vaporization. The vaporizer device500may also include an oven lid510that may cover, enclose, and/or seal a loading side of the oven chamber501. The lid510may be attached over an accessible portion of the oven chamber501by various mechanisms, including a friction fit, a magnetic attachment, a mechanical attachment, some combination thereof, or the like. The vaporizer device500also includes a notched-tube heater502(e.g., heating assembly, convective heating assembly), which includes a heating element that may be placed directly or nearly adjacent (e.g., below inFIGS.5A and5B) the oven chamber501and may reside in an open chamber or cavity507within the elongate, flat body of the device500. The notched-tube heater502may be a tube made from a type of resistive metal alloy that is notched or slotted via a process such as laser etching. A notched555region may provide a higher electrical resistance than the rest of the tube so that air (e.g., drawn by the user) passes through the slots with relatively more turbulence before coming in contact with the vaporizable material. The notched-tube heater502may be held in the air path, and coupled to the inner chamber of the vaporizer device500by a small number of contact points, or thermally or electrically insulating couplings, insulating lining, or the like, to minimize thermal transfer. In operation, the vaporizer device500may be loaded with a vaporizable material by removing the oven lid510to load the oven chamber501with a desired vaporizable material. The user may then place the oven lid back on, and take a puff from the device500on the opposite side of the oven where a mouthpiece is located (e.g., mouthpiece122shown inFIG.2). As the user draws on the mouthpiece, ambient air enters the device500(through the same sort of air inlets160ofFIG.1and360ofFIG.4A) of the outer housing514, which may be a shell or other extrusion (including an aluminum extrusion), and may pass through the support housing (e.g., support fixture or skeleton)512within the outer housing514(which may provide structural support for the notched-tube heater502and oven chamber/heater housing517) entering into a cavity507and creating a pressure drop which is detected by a pressure sensor508. When this pressure drop is detected, the notched-tube heater502may be powered by passing an electric current through it via power leads505, causing the notched or slotted region of the heater502to rapidly increase in temperature. The air being drawn into the cavity507may flow into the tube of the heater502and increase in temperature as it passes by the tube extensions and notched region555. With the air passing through the notched region555of the heater502, it begins to flow up past a thermocouple sensor503that is suspended close to a screen515at the bottom of the oven chamber501. The screen515is perforated to allow the hot air to readily pass through the material in the oven chamber501before it exits the top of the oven and runs down side slots509formed by the housing512(e.g., support frame or skeleton) to the mouthpiece at the opposite end for inhalation by the user. To minimize energy loss from the notched-tube heater502, the heater502and the oven chamber501may be housed in a low thermally conductive material such as zirconia. The walls of the oven chamber/heater housing517may be relatively thin to reduce the amount of thermal mass associated with the material. As seen inFIG.5A, there are small air gaps504between the oven chamber501and the housing517that may act as insulation (or could comprise an insulating material), aiding in the prevention of thermal sink (conduction) into the housing517. This way, most of the energy, in the form of heat, will pass through the material to be vaporized as opposed to the body (e.g., the outer housing514) of the device500. The heater502may be a resistive heating element that is heated by electric current passing between two terminals505to which the heater502is attached. The heater502may be an elongate tube (having any appropriate cross-sectional shape, including round, oval, rectangular, square, etc.) that is hollow; the tube may be straight, curved, bent (including doubling back on itself) and may include one or more cuts or openings in the lateral sides of the elongate tube through which air may be drawn. The tube of the heater502may be arranged generally transverse to the air path of the device so that drawing air from the mouthpiece pulls air through the cuts or openings, both heating the air and resulting in a turbulent airflow through the heater502, which may mix the heated air to prevent local hotspots/cold spots. The device500may also include a precision resistance measurement circuit to track resistance of the heater502when not heating and/or when heating to control the temperature of the heater502based on changes in the element's resistance from room temperature to vaporization temperatures. This measurement circuit may be a multi-terminal (e.g., four-terminal) sensing system that uses, e.g., two smaller leads506to sense the voltage drop across a region of the heater502, e.g., across the notched region of the heating element, when a testing current (e.g., a small, but known, constant current) is applied through the testing leads506. This applied testing current may be different than the heating current used to heat the heater502through power leads505to high temperatures and may be applied to the heater502when taking measurements between heating. In the exemplary device500, the measurement circuit may be configured to provide a four-point resistive measurement, and this circuit may in certain cases give a more accurate resistance measurement than a two-terminal resistive sensing circuit. A four-point measurement circuit may bypass the change in resistance the power leads experience from thermal conduction (as the power leads are welded to the heater tubes) and electrical heating from the high currents. In some configurations, a two-terminal resistance measurement circuit may not accurately compensate for the change in resistance of the power leads causing skewed results for the calculated temperature. FIG.6illustrates features of a controller that may be adapted for regulating temperature in a vaporizer device consistent with implementations of the current subject matter. Block diagram600includes a measurement circuit620that can measure the resistance of the resistive heater (e.g., heater502) and provide an analog signal to a microcontroller610. A device temperature, which can be inputted into the microcontroller610from temperature sensor503and an input from a sensor (e.g., pressure sensor508, a button, or any other sensor) may be used by the microcontroller610to determine when the resistive heater502should be heated, e.g., when the user is drawing on the device or when the device is scheduled to be set at a warmer temperature (e.g., a standby temperature). InFIG.6, a signal from the measurement circuit620, an example of which is shown inFIG.7, goes directly to the microcontroller610. The example ofFIG.6consistent with implementations of the current subject matter provides for delivery of electrical energy from a power source, that may be part of the vaporizer500, to the heater502. Additionally, an additional input may be a desired temperature input630, determined and inputted by a user and used as described below by the microcontroller610. The desired temperature input, rather than inputted by a user, may be pre-established and inputted to the microcontroller610. FIG.7illustrates features of a control (e.g., measurement) circuit620for regulating temperature in a vaporizer device consistent with implementations of the current subject matter. To accurately control the temperature of the resistive element during heating, it may be helpful for the resolution for the resistance measurements to be relatively precise. Based on the temperature coefficient of resistance (TCR) of the metal alloy used for the heating element, a change of only a few milliohms (mΩ) can represent a change of over 100° C. To achieve high resolution measurement of such temperature changes, a scalable resistance measurement circuit (e.g., a four-point resistance measurement circuit) may be used.FIG.7illustrates one example of a circuit schematic for a resistance measurement circuit configured as a four-point resistance measurement circuit. As shown inFIG.7, power source720is provided. In operation, the circuit may enable MOSFET Q10704, which allows a small current from current source U2706to pass through the heating element702(which is separately connected to the circuit by the terminals HI+ and HI− via power leads505—FIG.5Afor providing the higher heating current), where a voltage drop across the heating element can be detected through the HV+708and HV−708′ leads (via leads506shown inFIGS.5A and5B). This low voltage drop (in the low tens of millivolts) is sensed through the first stage of the amplifier circuit (U12A)710, which can be configured as a differential amplifier with unity gain. Achieving the high resolution for resistance measurements comes from scaling the second stage of the amplifier circuit (U12B)712. Selectable scaling factors714can selectably switch (under microprocessor610control) a specific combination of the MOSFETs Q5-Q9to scale the input to the second stage amplifier, which can be set up as a non-inverting amplifier with a fixed gain, allowing for greater resolution of measurement of the heater's resistance. Scaling the second stage of the amplifier circuit as opposed to the first stage ensures that there will be little or no effect from the scaling resistors R10-R14on the differential amplifier's closed-loop gain. This is desirable since the differential stage should preferably remain symmetric to accurately measure the differential voltage on the heating element. Also, this circuit has the capability to measure the thermoelectric, or Seebeck, effect that occurs when two dissimilar metals are at different temperatures. This may allow the vaporizer to compensate for the Seebeck effect. For example, using a microcontroller's analog-to-digital converter (ADC), the output voltage of the second stage amplifier may be sampled and converted to a binary representation, which may be used in a lookup table to convert these readings to a resistance. The lookup table may be determined theoretically (e.g., from an analysis of the circuit); and may be corrected with the measurements taken for the Seebeck effect along with some fixed offset that arises from component tolerances. The vaporizers consistent with some implementations of the current subject matter may regulate and adjust the air temperature applied to the vaporizable material. In any of the variations described herein, the vaporizer devices may be configured to allow the user to choose (Desired Temperature Input630) different air temperatures for vaporizing the material of interest (e.g., by a button or other control input on the device, or wirelessly, e.g., through a user interface on a remote device such as a smartphone that is in communication with the vaporizer). The vaporizer control circuitry (e.g., the block diagram600ofFIG.6) may include one or more controllers to regulate overall temperature selection. In particular, the device controller610can regulate the temperature of the heating element502(resistive heater) using a first controller circuit (control law) to control and rapidly heat the resistive heater and estimate its temperature based on the TCR of the resistive heater; and a second controller circuit (control law) may further regulate the resistive heater based on the user-selected or predetermined vaporization temperature (e.g., between 200° C. and 500° C.), which may be sensed by one or more thermocouples503in the airflow path (e.g., downstream from the resistive heater and/or between the resistive heater and the oven chamber). These two controller circuits may cooperate together to adjust the heating temperature or rate of increase of heating by modulating the duty cycle of the energy applied to the heater. For example, a proportional-integral-derivative controller (PID controller) may be implemented on the microcontroller610that monitors the thermocouple sensor503above the heating element502and uses this as the feedback mechanism for the air temperature controller. Separately, another second PID controller may be used to regulate the temperature of the heating element502using the TCR of the metal alloy (of the resistive heater) to determine the target resistance set point of the heater so that it does not exceed a safe operating point. These two PID controllers may be run simultaneously, e.g., at 128 Hz, and control logic may be used to determine which PID controller (air temperature or heater temperature) output to use at any given point. The output for both of the PID controllers may be alternated in a duty cycle of the PWM signal input to the power MOSFET701(e.g., Q2in the schematic ofFIG.7), with only one output at a time used to control the transistor. When the device detects that the user has started a puff, which may be determined from a sensor such as a pressure sensor (see, e.g.,FIG.5A,508) (or from a button pressed by the user), the TCR-sensed heater temperature PID controller may be initiated first. This may ensure that the temperature of the heating element rapidly increases to its maximum operating temperature to heat the incoming air as quickly as possible. As mentioned, the temperature of the thermocouple503is monitored and when this crosses a predetermined threshold, the output of the air temperature PID controller is then applied. For example, if the user sets the vaporization temperature to 350° C. and proceeds to draw on the device (tripping the pressure sensor's threshold for the start of a puff), this causes the microcontroller to begin to pulse the power MOSFET using the duty cycle from the heater temperature PID controller to regulate the heating element's temperature to the maximum value allowed of 700° C. As the incoming air is heated, the air temperature PID controller then controls applied heater current once the air temperature detected crosses a set threshold value (e.g., corresponding to a temperature of, for example, 300° C.). The heating element is then controlled via the air temperature PID controller to regulate the air temperature to 350° C., but the heater temperature PID controller will not allow the temperature of the heating element to exceed the 700° C. cutoff. The system can alternate the two PID controllers if the airflow is low enough to allow the heating element to reach the maximum allowed safe operating temperature. That is, if the airflow is too high, the heater may not be able to reach its maximum temperature. Embodiments described above were tested, using an airflow of 4 L/min passing through the heating element and oven, while data from the thermocouple was recorded during the session. As seen in the graphs800and900ofFIGS.8and9, respectively, the thermocouple reaches vaporization temperatures in approximately one second (FIG.9shows a more detailed plot of between three and seven seconds fromFIG.8, showing the heat up time). The control law running on this device uses the resistance measurements of the heating element to ensure that the element never exceeds a safe operating temperature (e.g., 700° C.). The device continuously monitors the thermocouple and regulates the air temperature to a set value (350° C. in this example). There is an overshoot on the heat up, but this can be intentional, to get the vaporizable material up to vaporization temperatures as quickly as possible. The coarse resolution on the data below is due to the minimum sample time of the thermocouple monitor used in the device. However, it is enough to control the air temperature to within at least ±5° C. Finer grained control systems are also within the scope of the present subject matter. In some variations of the on-demand convection-based vaporizers described herein, the resistive heater (resistive heating element) may be formed of one or more different types of metal alloys, such as stainless steel 316, stainless steel 309, Nichrome, or any other resistive metal alloy. Alternatively or in addition, the housing for the resistive heating element and oven may be made from a metal or alloy, such as a thin piece of aluminum or stainless steel. The heating element may be insulated from the housing by a sleeve or bushing made from Teflon or similar material. In any of the variations described herein, the vaporizer may include a heat exchanger in thermal communication with the heater, which may achieve better efficiency. This may involve a circular type of metal baffling or disc that may be inserted into each side of the heating element's tube and mounted close to the notched region, such as the notched region555. Some of the heat that is being conducted down the tube away from the notched region may also be conducted into these heat exchangers. As the air is drawn in through the ends of the tube, these alternate proposed heat exchangers may utilize some of the lost heat being conducted down the ends of the tube and put this otherwise “lost” energy back into the drawn air. Another method similar to such discs or baffling would include raised portions of the heater tube, or fins, that protrude in towards the center of the tube. These fins can provide another style of heat exchanger to help add heat back into the air path. Consistent with some implementations of the current subject matter, a thermocouple may be built into the vaporizer rather than incorporating a thermocouple sensor503in the vaporizer500. In one example, as a surrogate for taking the air temperature measurement with a thermocouple, a temperature of the screen515can be measured. For example, if the screen515is electrically isolated from the oven chamber501, it can be used as a thermistor. By inclusion of a lead coming off of either end along the long axis via which the resistance can be measured. This approach allows the microcontroller610to calculate the average temperature of the screen515, which may be used as an alternative to an air temperature measurement as they should be highly correlated. As another example, if the screen515stays electrically connected to the oven chamber501, a single lead of a dissimilar material can be pulled off of the screen515, creating an ad hoc thermocouple. By measuring the voltage across the oven chamber/screen construction and the lead of dissimilar material, the temperature at the junction between the two materials can be calculated by the microcontroller610. Or, an infrared sensor within or near the oven chamber can similarly measure the temperature of the air vaporizing the material. Alternatively, the downstream air temperature sensor can be removed outright and an algorithm could be used to predict the downstream air temperature as a function of the heater temperature, flow rate, and/or time. Consistent with some implementations of the current subject matter, the oven chamber and the mouthpiece of a vaporizer are not required to be on opposing ends of the vaporizer. For example, the mouthpiece may be adjacent or near adjacent the oven chamber. In such a configuration, the one or more air paths from the oven chamber connected to the mouthpiece, through which the vapor travels, can be configured to allow for the vapor to sufficiently cool before being provided to a user via the mouthpiece. For example, a turbulent path for the air flow after the oven chamber may be provided to allow for sufficient cooling. Such a turbulent path may include a zig-zag path, a path with various bumps and/or projections, or other configurations or methods, to allow for the relatively quick exchange of heat away from the heated vapor. FIG.10shows another variation of a heater element1000, in which the heater is a flat-plate heater that has a thin serpentine design made from a resistive metal alloy, for example. This design may replace the heater302shown inFIGS.3-4E. In this design, the flat heating element may be placed directly in the air path below the oven chamber. Instead of the air path passing through a tube and then changing direction to exit the tube from a notched region, as described above in reference toFIGS.5A and5B, inFIG.10the air path may be much more direct. The air may enter the device from below the heater serpentine element1000and pass through slots1005in the heater1000before entering the oven chamber. A thermocouple may be mounted between the heater and the oven chamber, as inFIG.5A, to measure and control the air temperature before contacting or otherwise heating the vaporizable material. In some variations, the heater (resistive heating element) may be a thin-film resistive heating element that is coiled, bent, or otherwise arranged in a 3D structure having an appropriate number (e.g., 1, 2, 3, 5, etc.) of channels, slits, slots, etc. therethrough to allow air to flow over and through the resistive heater for rapid heating. In any of these variations, the resistive heater1000may be held in the air path, and coupled to the inner chamber of the device by a small number of contact points1010to minimize thermal transfer; alternatively the heater1000may be connected by thermally and/or electrically insulating couplings. In any of these variations, the channels, slits, etc. or surface area of the heater can have fractal, jagged, finned or other features to further increase heat transfer to the air. With reference toFIG.11, a process flow chart1100illustrates features of a method, which may optionally include some or all of the following. At1110, a draw on a mouthpiece by a user of a vaporizer is detected (or, alternatively, a button or other start indicator device can be selected by the user). This detection may be via a pressure sensor in an airflow path of ambient air entering a cavity of the vaporizer. At1120, energy is applied to a heater of the vaporizer, which begins the process of rapidly increasing the heater to a high or maximum operating temperature to quickly heat incoming ambient air. At1130, an air temperature of heated air from the heater is monitored. This monitoring may be through one or more thermocouple sensors between the heater and an over chamber of the vaporizer, to determine the temperature of air leaving the heater. At1140, an oven temperature of the oven chamber of the vaporizer is limited by modifying the energy applied to the heater. This may ensure that the heater does not exceed a predetermined threshold. At1150, a heater temperature of the heater is regulated to control the heater temperature in response to changes in resistance of the heater. As discussed above, implementations of the current subject matter include methods and apparatuses for vaporizing materials so that they may be inhaled by a user. The apparatuses described herein include vaporizer devices and systems including vaporizer devices. In particular, described herein are on-demand convection vaporizer apparatuses (devices and systems) that may be configured for user control and operation. The following descriptions of example implementations are provided for illustration of various features that may be part of the current subject matter. They are not intended to be limiting. For example, on-demand, hand-held convection vaporizer devices may include: an elongate body having a shell; a mouthpiece on the elongate body; a sensor to detect draw through the mouthpiece; an oven chamber within the elongate body, wherein the oven chamber's lateral walls are surrounded by an air gap; a convection heater within the elongate body, the convection heater having a plurality of slots and/or openings configured to pass air over the convection heater and generate a mixing turbulence as air is passed over and/or through the convection heater; a heater control circuit, the heater control circuit configured to heat the convection heater to a temperature of greater than 500° C. upon detection of draw through the mouthpiece; further wherein the heater control circuit limits the heater to maximum temperature; further wherein air flowing into the oven chamber from the heater is heated to a target vaporization temperature. An on-demand, hand-held convection vaporizer device may include: an elongate body having a shell; a mouthpiece at a proximal end of the elongate body; a sensor to detect draw through the mouthpiece; an oven chamber at a distal end of the elongate body, wherein greater than 80% of the oven chamber's lateral walls are surrounded by an air gap; a convection heater within the elongate body, the convection heater having a plurality of slots and/or openings configured to pass air over the convection heater and generate mixing turbulence as air is passed over and/or through the convection heater; a heater control circuit, the heater control circuit configured to heat the convection heater to a temperature of greater than 500° C. upon detection of draw through the mouthpiece; further wherein the heater control circuitry limits the heater to maximum temperature; wherein air flowing into the oven chamber from the heater is heated to a target vaporization temperature of greater than 200° C. within 4 seconds of detection of draw through the mouthpiece. Any of these vaporizers may use a tubular convection heater such as an elongate tube extending in a long axis, the tube having a plurality of cut-out regions along its length therethrough to generate turbulence in air passing therethrough. For example, described herein are on-demand, hand-held convection vaporizer devices that may include: an elongate body having a shell; a mouthpiece at a proximal end of the elongate body; a sensor to detect draw through the mouthpiece; an oven chamber at a distal end of the elongate body, wherein greater than 80% of the oven chamber's lateral walls are surrounded by an air gap; a convection heater including an elongate tube extending in a long axis, the tube having a plurality of cut-out regions along its length therethrough to generate turbulence in air passing therethrough; a heater control circuit, the heater control circuit configured to heat the convection heater to a temperature of greater than 500° C. upon detection of draw through the mouthpiece; further wherein the heater control circuitry limits the heater to maximum temperature; wherein air flowing into the oven chamber from the heater is heated to a target vaporization temperature of greater than 200°. Any of the vaporizers and/or methods according to implementations of the current subject matter may also include or make use of a heater control circuit including a four-point measurement circuit. For example, an on-demand, hand-held convection vaporizer device may include: an elongate body having a shell; a mouthpiece at a proximal end of the elongate body; a sensor to detect draw through the mouthpiece; an oven chamber at a distal end of the elongate body, wherein the oven chamber's lateral walls are surrounded by an air gap; a convection heater having a plurality of slots and/or openings along its length therethrough to generate turbulence in air passing therethrough; a heater control circuit, the heater control circuit including a four-point measurement circuit having four leads coupled to the convection heater, wherein two of the leads are configured to sense the voltage drop across a region of the heating element, further wherein the heater control circuit is configured to heat the convection heater to a temperature of greater than 500° C. upon detection of draw through the mouthpiece and to limit the heater to maximum temperature; wherein air flowing into the oven chamber from the convection heater is heated to a target vaporization temperature. Thus in general, when the device includes a four-point measurement circuit having four leads coupled to the convection heater, two of the leads may be configured to sense the voltage drop across a region of the heating element; these leads may be between two outer leads. The two outer leads may apply power to the convection heater. For example, a first lead and second lead of the four leads of the heater control circuitry may be configured to apply power to heat the convection heater. The two leads configured to sense the voltage drop may be spaced apart from the power-applying leads so that the temperature increase due to the high levels of power applied will not impact the resistance/conductivity of the voltage-sensing leads. Any of the vaporizers according to implementations of the current subject matter may include a temperature sensor between the convection heater and an inside of the oven chamber, wherein the temperature sensor provides air temperature input to the heater control circuitry. In general, the heater control circuitry may be configured to control the energy applied to the convection heater based on a temperature of the convection heater and based on a temperature of the air between the convection heater and the oven chamber. In any of these devices, the mouthpiece may be at a proximal end of the elongate body and the oven chamber may be within the distal end of the elongate body. The devices according to implementations of the current subject matter may be configured to immediately or near-instantaneously heat air to vaporize a material in the oven chamber. For example, air flowing into the oven chamber from the heater may be heated to a target vaporization temperature of greater than 200° C. within 4 seconds (e.g., within 3 second, within 2 seconds, within 1 second, etc.) of detection of draw through the mouthpiece. A chamber's lateral walls may be surrounded by an air gap such that the chamber's lateral (e.g., side walls, perpendicular to the bottom of the oven chamber) are at least 50% surrounded by the air gap (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 95% surrounded, etc.). Methods of operating any of the apparatuses described herein may include methods of vaporizing materials. For example, methods of operating an on-demand, hand-held convection vaporizer may include features such as: sensing a draw on a mouthpiece of the vaporizer; applying energy to a conductive heater of the vaporizer; adjusting the energy applied to the conductive heater based on a four-point measurement including a first pair of inputs corresponding to a first pair of leads connected to the conductive heater and a second pair of inputs corresponding to a second pair of leads connected to the conductive heater wherein the second pair of leads are offset from the first pair of leads; and vaporizing a vaporizable material within the oven chamber of the vaporizer. Applying energy to the conductive heater of the vaporizer may include increasing the temperature by more than 200 degrees within about one second, and/or applying energy from the first pair of leads. The second pair of leads may be positioned between the first pair of leads. Any of these methods may also include determining a temperature of the conductive heater from the four-point measurement. Adjusting the energy applied to the conductive heater based on the four-point measurement may include adjusting the frequency and/or duty cycle of the energy applied to the conductive heater. Any of these methods may also include adjusting the energy applied to the conductive heater based on a temperature of the air between the convection heater and an oven chamber of the vaporizer, and/or sensing the temperature of the air between the convection heater and the oven chamber of the vaporizer. Any of these methods may also include limiting the energy applied to the conductive heater so that the temperature of the conductive heater does not exceed a maximum threshold (e.g., 500° C., 550° C., 600° C., 650° C., 700° C., 750° C., etc.). For example, a method of operating an on-demand, hand-held convection vaporizer may include: sensing a draw on a mouthpiece of the vaporizer; applying energy to a conductive heater of the vaporizer from a first pair of leads to increase the temperature by more than 200 degrees within about one second; adjusting the energy applied to the conductive heater based on a four-point measurement including a first pair of inputs that corresponds to the first pair of leads and a second pair of inputs corresponding to a second pair of leads connected to the conductive heater wherein the second pair of leads that are positioned between the first pair of leads; adjusting the energy applied to the conductive heater based on a temperature of the air between the convection heater and an oven chamber of the vaporizer; and vaporizing a vaporizable material within the oven chamber of the vaporizer. When a feature or element is herein referred to as being “on” another feature or element, it can be directly on the other feature or element or intervening features and/or elements may also be present. In contrast, when a feature or element is referred to as being “directly on” another feature or element, there are no intervening features or elements present. It will also be understood that, when a feature or element is referred to as being “connected”, “attached” or “coupled” to another feature or element, it can be directly connected, attached or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being “directly connected”, “directly attached” or “directly coupled” to another feature or element, there are no intervening features or elements present. Although described or shown with respect to one embodiment, the features and elements so described or shown can apply to other embodiments. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature. Terminology used herein is for the purpose of describing particular embodiments and implementations only and is not intended to be limiting. For example, as used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or groups thereof. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as “/”. In the descriptions above and in the claims, phrases such as “at least one of” or “one or more of” may occur followed by a conjunctive list of elements or features. The term “and/or” may also occur in a list of two or more elements or features. Unless otherwise implicitly or explicitly contradicted by the context in which it used, such a phrase is intended to mean any of the listed elements or features individually or any of the recited elements or features in combination with any of the other recited elements or features. For example, the phrases “at least one of A and B;” “one or more of A and B;” and “A and/or B” are each intended to mean “A alone, B alone, or A and B together.” A similar interpretation is also intended for lists including three or more items. For example, the phrases “at least one of A, B, and C;” “one or more of A, B, and C;” and “A, B, and/or C” are each intended to mean “A alone, B alone, C alone, A and B together, A and C together, B and C together, or A and B and C together.” Use of the term “based on,” above and in the claims is intended to mean, “based at least in part on,” such that an unrecited feature or element is also permissible. Spatially relative terms, such as “under”, “below”, “lower”, “over”, “upper” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the exemplary term “under” can encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms “upwardly”, “downwardly”, “vertical”, “horizontal” and the like are used herein for the purpose of explanation only unless specifically indicated otherwise. Although the terms “first” and “second” may be used herein to describe various features/elements (including steps), these features/elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one feature/element from another feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and similarly, a second feature/element discussed below could be termed a first feature/element without departing from the teachings provided herein. As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word “about” or “approximately,” even if the term does not expressly appear. The phrase “about” or “approximately” may be used when describing magnitude and/or position to indicate that the value and/or position described is within a reasonable expected range of values and/or positions. For example, a numeric value may have a value that is +/−0.1% of the stated value (or range of values), +/−1% of the stated value (or range of values), +/−2% of the stated value (or range of values), +/−5% of the stated value (or range of values), +/−10% of the stated value (or range of values), etc. Any numerical values given herein should also be understood to include about or approximately that value, unless the context indicates otherwise. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein. It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value “X” is disclosed the “less than or equal to X” as well as “greater than or equal to X” (e.g., where X is a numerical value) is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point “15” are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed. Although various illustrative embodiments are described above, any of a number of changes may be made to various embodiments without departing from the teachings herein. For example, the order in which various described method steps are performed may often be changed in alternative embodiments, and in other alternative embodiments one or more method steps may be skipped altogether. Optional features of various device and system embodiments may be included in some embodiments and not in others. Therefore, the foregoing description is provided primarily for exemplary purposes and should not be interpreted to limit the scope of the claims. One or more aspects or features of the subject matter described herein can be realized in digital electronic circuitry, integrated circuitry, specially designed application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs) computer hardware, firmware, software, and/or combinations thereof. These various aspects or features can include implementation in one or more computer programs that are executable and/or interpretable on a programmable system including at least one programmable processor, which can be special or general purpose, coupled to receive data and instructions from, and to transmit data and instructions to, a storage system, at least one input device, and at least one output device. The programmable system or computing system may include clients and servers. A client and server are generally remote from each other and typically interact through a communication network. The relationship of client and server arises by virtue of computer programs running on the respective computers and having a client-server relationship to each other. These computer programs, which can also be referred to programs, software, software applications, applications, components, or code, include machine instructions for a programmable processor, and can be implemented in a high-level procedural language, an object-oriented programming language, a functional programming language, a logical programming language, and/or in assembly/machine language. As used herein, the term “machine-readable medium” refers to any computer program product, apparatus and/or device, such as for example magnetic discs, optical disks, memory, and Programmable Logic Devices (PLDs), used to provide machine instructions and/or data to a programmable processor, including a machine-readable medium that receives machine instructions as a machine-readable signal. The term “machine-readable signal” refers to any signal used to provide machine instructions and/or data to a programmable processor. The machine-readable medium can store such machine instructions non-transitorily, such as for example as would a non-transient solid-state memory or a magnetic hard drive or any equivalent storage medium. The machine-readable medium can alternatively or additionally store such machine instructions in a transient manner, such as for example as would a processor cache or other random access memory associated with one or more physical processor cores. To provide for interaction with a user, one or more aspects or features of the subject matter described herein can be implemented on a computer having a display device, such as for example a cathode ray tube (CRT) or a liquid crystal display (LCD) or a light emitting diode (LED) monitor for displaying information to the user and a keyboard and a pointing device, such as for example a mouse or a trackball, by which the user may provide input to the computer. Other kinds of devices can be used to provide for interaction with a user as well. For example, feedback provided to the user can be any form of sensory feedback, such as for example visual feedback, auditory feedback, or tactile feedback; and input from the user may be received in any form, including, but not limited to, acoustic, speech, or tactile input. Other possible input devices include, but are not limited to, touch screens or other touch-sensitive devices such as single or multi-point resistive or capacitive trackpads, voice recognition hardware and software, optical scanners, optical pointers, digital image capture devices and associated interpretation software, and the like The examples and illustrations included herein show, by way of illustration and not of limitation, specific embodiments in which the subject matter may be practiced. As mentioned, other embodiments may be utilized and derived there from, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to herein individually or collectively by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any single invention or inventive concept, if more than one is, in fact, disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description. | 66,379 |
11857719 | DETAILED DESCRIPTION In the following description, numerous specific details are set forth in order to provide a thorough understanding of the various principles of the present invention. However, those skilled in the art will appreciate that not all these details are necessarily always required for practicing the present invention. Although the principles of the present invention are largely described herein in relation to laparoscopy or open surgery procedures, this is an example selected for convenience of presentation, and is not limiting. The filter assemblies described herein may be used for any suitable medical procedure and in any suitable medical system comprising a gas delivery circuit, such as a gas delivery system for delivering respiratory gases. Reference is now made toFIG.1, which is a schematic view of an insufflation system comprising a filter assembly constructed and operative in accordance with an embodiment of the present invention. FIG.1illustrates an insufflation system100for delivering temperature- and humidity-controlled gas to a patient102, the insufflation system100having a humidification apparatus or humidifier104incorporating a humidifier control system106. The humidifier104is connected to a gas source108through an inlet conduit110. The humidifier104delivers humidified gas to the patient102through a patient conduit112. The conduits110,112may be made of flexible plastic tubing. The humidifier104receives, at an inlet114, gas from the gas source108through the inlet conduit110. The gas is humidified as it passes through a humidifying chamber116, which is effectively a water bath, or passover humidifier, and the gas flows out through a humidifier outlet118and into the patient conduit112. The gas may be filtered through a filter assembly140and delivered to the patient102through the patient conduit112, Luer connector111and the patient interface136. The patient interface136may be, for example, but not limited to, a trocar or cannula for laparoscopic surgery or a diffuser for open surgery. According to an embodiment, the system may be for delivering respiratory gases rather than insufflation gases, and in this embodiment the patient interface may be, for example, a nasal cannula, full-face mask, nasal mask, nasal pillows interface, tracheostomy interface or endotracheal tube. The humidifier104comprises a body124removably engageable with the humidification chamber116. The humidification chamber116has a metal base121and is adapted to hold a volume of water120, which can be heated by a heater plate122. The heater plate122may be in thermal contact with the metal base121of the humidification chamber116. Providing power to the heater plate122may cause heat to flow from the heater plate122to the water120through the metal base121. As the water120within the humidification chamber116is heated it may evaporate and the evaporated water can mix with gases flowing through the humidification chamber116from the gas source108. Accordingly, the humidified gases leave the humidification chamber116via outlet118and are passed to the patient102via the patient conduit112, the filter assembly140, the Luer connector111, the patient interface136and into the surgical site to, for example, insufflate the surgical site and/or expand body cavity. The humidifier104includes the humidifier control system106configured to control a temperature and/or humidity of the gas being delivered to the patient102. The humidifier control system106may be configured to regulate an amount of humidity supplied to the gases by controlling an electrical power supplied to the heater base122. The humidifier control system106may control operation of the humidification system104in accordance with instructions set in software and in response to system inputs. System inputs may include a heater plate sensor126, an outlet chamber temperature sensor128, and a chamber outlet flow sensor130. For example, the humidifier control system106may receive temperature information from the heater plate sensor126which it may use as an input to a control module used to control the power or temperature set point of the heater plate122. The humidifier control system106may be provided with inputs of temperature and/or flow rates of the gases. For example, the chamber outlet temperature sensor128may be provided to indicate to the humidifier control system106the temperature of the humidified gas as it leaves the outlet118of the humidification chamber116. The temperature of the gases exiting the chamber may be measured using any suitable temperature sensor128, such as a wire-based temperature sensor. The chamber outlet flow sensor130may be provided to indicate to the humidifier control system106the flow rate of the humidified gas. The flow rate of the gases through the chamber116may be measured using any suitable flow sensor130, such as a hot wire anemometer. In some embodiments, the temperature sensor128and flow sensor130are in the same sensor housing. The temperature sensor128and flow sensor130may be connected to the humidifier104via connector132. Additional sensors may be incorporated into the insufflation system100, for example, for sensing parameters at the patient end of the patient conduit112. The humidifier control system106may be in communication with the heater plate122such that the humidifier control system106may control a power delivered to the heater plate122and/or control a temperature set point of the heater plate122. The humidifier control system106may determine an amount of power to deliver to the heater plate122, or a heater plate set point, based at least in part on a flow condition, an operation mode, a flow reading, an outlet temperature reading, a heater plate sensor reading, or any combination of these or other factors. The insufflation system100may include a conduit heating wire134configured to provide heat to the gases traveling along the patient conduit112. Gases leaving the outlet118of the humidification chamber116may have a high relative humidity (e.g., about 100%). As the gases travel along the patient conduit112there is a chance that water vapor may condense on the conduit wall, reducing the water content of the gases. To reduce condensation of the gases within the conduit, the conduit heating wire134may be provided within, throughout, and/or around the patient conduit112. Power may be supplied to the conduit heating wire134from the humidifier104and may be controlled through the humidifier control system106. In some embodiments, the heating wire134is configured to maintain the temperature of the gas flowing through the patient conduit112. In some embodiments, the conduit heating wire134may be configured to provide additional heating of the gas to elevate the gases temperature to maintain the humidity generated by the heated water bath in the humidifier104. The filter assembly140may be configured to filter the humidified gases exiting the humidification chamber116so as to deliver filtered humidified gases to the patient102through the patient conduit112, the Luer connector111and the patient interface136. InFIG.1, the filter assembly140is shown as being positioned in a median zone of the patient conduit112between the Luer connector111/patient interface136and the humidifier104. Those skilled in the art will however appreciate that this configuration is provided as an example only and is not limiting. The filter assembly140may be positioned at any suitable position in the wet-side of the insufflation system100i.e. between the humidifier104and the patient interface136. For example, but not limited to, the filter assembly140may be positioned adjacent to the humidifier104, in the humidification chamber116, adjacent to and/or in the Luer connector111/patient interface136. The filter assembly140may comprise a housing, a filter medium and heating means. The housing may comprise an inlet and an outlet and be configured to receive the filter medium. The humidified gases may therefore enter the filter assembly by the housing inlet, pass through the filter medium and exit the filter assembly by the housing outlet. Non-limiting examples of filter medium includes a membrane, a glass-based or hydrophobic material, paper, pleated material (e.g. preferably linear parallel pleats), etc. The heating means may be any suitable means adapted to heat actively or passively the filter assembly140so as to prevent condensation clogging the filter medium. Active heating means may include, for example, but not limited to, a heated mesh on the filter medium, a heated conductive plastic housing, heater wires (e.g. in the gases flow path defined by the housing but spaced apart from the housing or attached and/or embedded in the housing), heating elements electrically or thermally coupled to the humidifier104, etc. Passive heating means may include, for example, but not limited to, designing the insufflation system100and the filter assembly140so that the heated gases flow is redirected and used to heat the filter assembly140before or after passing through the filter medium, using heat loss from the humidification chamber116to heat the filter assembly140, etc. Reference is now made toFIG.2, which is a schematic view of a filter assembly, constructed and operative in accordance with an embodiment of the present invention. FIG.2illustrates a filter assembly240positioned in use adjacent to the humidifier204of the insufflation system200between the humidification chamber and the patient conduit212. The filter assembly240may, for instance, be provided as part of a connector (e.g. elbow connector) configured to connect the outlet of the humidification chamber to the patient conduit212. This connector may be integral with the patient conduit212or provided as a component separate from the patient conduit212. In another example, the filter assembly240may be provided as a separate unit operative to be removably coupled to the humidification chamber. The filter assembly240may comprise a connecting portion arranged to be coupled to the cylindrical wall of the humidification chamber outlet. In a further example, the filter assembly240may be permanently coupled to the humidification chamber outlet by welding, overmoulding, using a snap-fit connection, etc. Further embodiments of the present invention comprising a filter assembly adjacent to the humidifier240will be described in relation toFIGS.3A to7B. The filter assembly240may also comprise heating means configured to reduce condensation on the filter medium and the filter housing. The heating means may be any suitable heating elements operative to maintain the gas temperature above the dew point temperature. The heat may be applied by the heating elements directly to the filter medium or to the filter housing as it will apparent hereinafter. Reference is now made toFIGS.3A to3C, which are views of the filter assembly ofFIG.2, constructed and operative in accordance with an embodiment of the present invention. FIG.3Ashows a filter assembly340comprising a housing341, a filter medium342and heating elements343,344. The housing341comprises an inlet operative to be coupled to an outlet of the humidification chamber and an outlet operative to be coupled to the patient conduit. The housing341further comprises a filter medium342disposed in use between the inlet and the outlet of the housing341so that humidified gases entering the housing341at the inlet pass through the filter medium342before exiting the housing341at the outlet. The filter assembly340also comprises a heating element343operative to be connected to a power supply. For example, the heating element343may be a thermoconductive plastic that may be heated by electrical wires connected to the power source of the humidifier heater base or any other suitable power source. As it is apparent fromFIGS.3B and3C, the heating element343may comprise holes filled with the filter medium342. When the heating element343is heated, the filled medium342is therefore heated so as to reduce condensation in the filter assembly340. Reference is now made toFIGS.4A and4B, which are views of the filter assembly ofFIG.2, constructed and operative in accordance with another embodiment of the present invention. FIG.4Aillustrates a filter assembly440similar to the filter assembly340ofFIG.3A. The filter assembly440also comprises a housing441, a filter medium442and heating elements443,444. In this exemplary embodiment of the present invention, however, the heating element443connected to the power supply is provided as a resistive wire mesh insert disposed in use on an external surface of the filter medium442. When the heating element443is heated, the filter medium442is therefore heated so as to reduce condensation in the filter assembly440. Reference is now made toFIG.5, which is a cross sectional view of the filter assembly ofFIG.2, constructed and operative in accordance with a further embodiment of the present invention. FIG.5illustrates a filter assembly540similar to the filter assemblies340and440described hereinabove. The filter assembly540, however, does not comprise a separate heating element. The housing541is preferably made of a thermoconductive plastic material that can be heated by any suitable power source. Therefore, the housing541is and/or acts as a heating element so as to heat the filter medium542and reduce condensation in the filter assembly540. Reference is now made toFIGS.6A and6B, which are views of the filter assembly ofFIG.2, constructed and operative in accordance with an embodiment of the present invention. FIG.6Ashows a filter assembly640positioned in use adjacent to the humidifier between the outlet of the humidification chamber616and the patient conduit612. The filter assembly640comprises a housing641, a filter medium642and heating elements643,644. The housing641comprises an inlet operative to be coupled to an outlet of the humidification chamber and an outlet operative to be coupled to the patient conduit612. The housing641further comprises a filter medium642disposed in use between the inlet and the outlet of the housing641so that humidified gases entering the housing641at the inlet pass through the filter medium642before exiting the housing641at the outlet. FIG.6Bis a cross sectional view of the filter assembly640and shows the heating elements643positioned in an upper region of the housing641but spaced apart from the inner top surface. The heating elements643are preferably the heater wires of the patient conduit612extending through the housing641so as to be connected to the power supply. When the heating elements643are heated, the filter medium642is therefore heated so as to reduce condensation in the filter assembly640. Reference is now made toFIGS.7A and7B, which are views of the filter assembly ofFIG.2, constructed and operative in accordance with another embodiment of the present invention. FIGS.7A and7Billustrate a filter assembly740similar to the filter assembly640ofFIGS.6A and6B. The filter assembly740also comprises a housing741, a filter medium742and a heating element743. In this exemplary embodiment, however, the heating element743, connected to the power supply744, is provided as a printed circuit board heater overmoulded into a top surface of the housing741. When the heating element743is heated, the filter medium742is therefore heated so as to reduce condensation in the filter assembly740. Reference is now made toFIG.8, which is a schematic view of a filter assembly, constructed and operative in accordance with another embodiment of the present invention. FIG.8illustrates a filter assembly840positioned in use within the humidifier804of the insufflation system800between the inlet and the outlet of the humidification chamber. The filter assembly840may, for instance, be provided as part of a medical taper that is configured to connect the outlet of the humidification chamber to the patient conduit812. In another example, the filter assembly840may be positioned within the humidification chamber. Further embodiments of the present invention comprising a filter assembly within the humidifier chamber will be described in relation toFIGS.9to11. The filter assembly840ofFIG.8may also comprise heating means configured to reduce condensation on the filter medium and the filter housing. The heating means may be any suitable heating elements operative to maintain the filter medium at a particular temperature (i.e. gas temperature being greater than the dew temperature) due to its location within the humidification chamber. Reference is now made toFIGS.9A and9B, which are cross sectional views of the filter assembly ofFIG.8, constructed and operative in accordance with embodiments of the present invention. FIG.9Ashows a filter assembly940comprising a housing941, a filter medium942and heating elements943. The housing941may be made of a plastic material and may correspond to a portion of a medical taper configured to push-fit into the outlet of the humidification chamber916to connect the humidification chamber916to the patient conduit912.FIG.9Aalso shows the filter medium942being provided as a push-fit insert that protrudes from the outlet of the humidification chamber916, such that the housing941attaches to the humidification chamber916by friction fit with the filter medium942. In use, humidified gases entering at an inlet of the housing941pass through the filter medium942before exiting the housing941at an outlet. The filter medium942may be heated by the heating element943corresponding to the heater wires of the patient conduit912and extending through an upper region of, but spaced apart from, the housing941. Additionally and/or alternatively, the heating element943may comprise the heater plate922of the humidifier which may be configured to heat the water present in the humidification chamber916. The heat may pervade the humidification chamber916to heat and/or maintain the filter medium942at a particular temperature so that condensation may be reduced in the filter assembly940. FIG.9Bshows a filter assembly940similar to the one described in relation toFIG.9A. The filter medium942is however provided as a push-fit insert that is fully inserted into the outlet of the humidification chamber916. In such embodiment of the present invention, the housing941may be connected to the outlet of the humidification chamber916by friction fit. Reference is now made toFIGS.10A and10B, which are cross sectional views of the filter assembly ofFIG.8, constructed and operative in accordance of other embodiments of the present invention. FIG.10Ashows a filter assembly1040similar to the filter assembly940ofFIG.9A. The filter assembly1040also comprises a housing1041, a filter medium1042and a heating element1043. In this exemplary embodiment, however, the humidification chamber1016may be at least partially overmoulded with a thermoconductive plastic element1017. In addition, a thermoconductive plastic element1045may also be provided around the filter medium1042. The filter medium1042may be heated by the heating element1043corresponding to the heater wires of the patient conduit1012and extending through an upper region of, but spaced apart from, the housing1041. Additionally and/or alternatively, the heating element of the filter assembly1040may comprise the heater plate1022, the thermoconductive plastic element1017of the humidification chamber1016, and the thermoconductive plastic element1045surrounding the filter medium1042. When the heater plate1022heats the water present in the humidification chamber1016, the heat is conducted to the housing1041via the thermoconductive plastic elements1017and1045to heat the filter medium1042so as to reduce condensation in the filter assembly1040. FIG.10Bshows a filter assembly similar to the ones shown inFIGS.9B and10A. In such exemplary embodiment, the filter medium1042and its surrounding thermoconductive plastic element1045is provided as a push-fit insert that is fully inserted into the outlet of the humidification chamber1016. Reference is now made toFIG.11, which is a cross sectional view of the filter assembly ofFIG.8, constructed and operative in accordance with a further embodiment of the present invention. FIG.11shows a humidification chamber1116connected to a patient conduit1112via a medical taper that push-fits into the humidification chamber outlet. The interior of the humidification chamber1116may be configured so as to permit a filter medium1142to be disposed in the flow path of humidified gases exiting the chamber. In such embodiment, the housing of the filter assembly1140may comprise a portion of the humidification chamber1116. In addition, the heater plate1122of the humidifier may serve as the heating element of the filter assembly1140so as to heat the filter medium1132and reduce condensation in the filter assembly1140. Reference is now made toFIG.12, which is a schematic view of a filter assembly, constructed and operative in accordance with an embodiment of the present invention. FIG.12illustrates a filter assembly1240positioned in use adjacent to the patient interface1236of the insufflation system1200. The filter assembly1240may, for instance, be provided as part of the Luer connector1211configured to connect the patient conduit1212to the patient interface1236. Alternatively, the filter assembly1240may be provided as a standalone unit positioned in use between the patient conduit1212or the Luer connector1211and the patient interface1236. In another example, the filter assembly1240may be integral with the patient interface1236and disposed in use inside the housing of the patient interface1236. Further exemplary embodiments of the present invention comprising a filter assembly adjacent to the patient interface1236will be described in relation toFIGS.13to18. The filter assembly1240ofFIG.12may comprise a housing, a filter medium and heating means. The heating means may be configured to reduce condensation on the filter medium and the filter housing. The heating means may be any suitable heating elements operative to maintain the gas temperature above the dew point temperature. Reference is now made toFIG.13, which is a cross sectional view of the filter assembly ofFIG.12, constructed and operative in accordance with an embodiment of the present invention. FIG.13shows a patient conduit1312and a Luer connector1311. The Luer connector1311is typically configured to connect the patient conduit1312to a patient interface (not shown). The tubing end of the Luer connector1311(i.e. the Luer connector end connecting to the patient conduit1312) may be an insert made of a plastic material. This plastic insert may be configured to receive the filter medium1342so as to act as the housing of the filter assembly1340. For example, the filter medium1342may be overmoulded onto or glued to the plastic insert. It will be apparent to those skilled in the art that the filter medium1342may be coupled to the Luer connector1311by any suitable means as long as humidified gases flowing though the patient conduit1312pass through the filter medium1342of the filter assembly1340before being delivered to the patient interface. The patient conduit1312may comprise heating elements such as, for example, but not limited to, heating wires1343. The heating wires1343incorporated into the tubing of the patient conduit1312may therefore heat the filter medium1342so that the gases are conditioned in a state that prevents condensation across the filter assembly1340. The gases leaving the patient conduit1312may be heated at a temperature higher than a dew point temperature so as to compensate for heat losses associated with the parts of the filter assembly1340/Luer connector1311and patient interface that are not heated. By heating the gases in the patient conduit1312to a temperature higher than the dew point, or to a temperature higher than the temperature desired at the patient, the gases have a relative humidity of less than 100% as they enter the filter assembly1340and are higher in temperature than is desired at the patient. The gases will then cool as they pass through the parts of the filter assembly1340/Luer connector1311and patient interface that are not heated, and will be delivered to the patient at optimal humidity and/or temperature. In another exemplary embodiment of the present invention, the insert of the Luer connector1311may be made of a thermoconductive plastic material and the heating wires of the patient conduit1312may be soldered to the insert. In such embodiment, the heat provided by the heating wires1343is conducted to the thermoconductive plastic insert which, in turn, heats directly the filter medium1342to reduce condensation in the filter assembly1340. Reference is now made toFIGS.14,15and16, which are cross sectional views of the filter assembly ofFIG.12, constructed and operative in accordance with other embodiments of the present invention. FIGS.14and15show different filter assemblies1440and1540similar to the one depicted inFIG.13. In the exemplary embodiment ofFIG.14however, the filter medium1442does not protrude from the Luer connector1411. In the exemplary embodiment ofFIG.15, the filter medium1542may be provided as part of the Luer connector1511and lies partially within the patient conduit1512. FIG.16illustrates a filter assembly1640in which the filter medium1642is attached at the humidifier end of the patient conduit1612and lies within the patient conduit1612. With such configuration, the gases flowing from the humidifier enter the filter medium1642and only pass through the lumen of the patient conduit1612by passing through the filter medium1642. Reference is now made toFIGS.17A to17C, which are different views of the filter assembly ofFIG.12, constructed and operative in accordance with a further embodiment of the present invention. FIGS.17A-17Cillustrate a filter assembly1740integrated within a patient interface1736.FIG.17Ashows a patient interface1736comprising a main body and a cover1741configured to fit into openings of the main body.FIG.17Bshows the same patient interface1736in a situation where the cover1741is coupled to the main body. In this exemplary embodiment, the cover1741may be configured to receive a filter medium1742. The patient interface1736may be connected to a patient conduit and/or Luer connector. In such embodiment, the patient conduit comprises heating elements (e.g. heater wires) configured to heat humidified gases. The humidified gases may be heated at a temperature higher than a dew point temperature. In other words, the humidified gases are conditioned in a state that compensates for heat losses associated with the parts of the Luer connector and patient interface that are not heated and therefore condensation in the filter assembly1740is prevented. Reference is now made toFIG.18, which is a cross sectional view of the filter assembly ofFIG.12, constructed and operative in accordance with an embodiment of the present invention. FIG.18illustrates a filter assembly1840similar to the one described in relation toFIGS.17A-17C. The patient interface1836may comprise a main body and a cover1841arranged to receive a filter medium1842. The patient interface1836may further comprise a patient interface fitting1837configured to be coupled to a patient conduit1812via a Luer connector1811. The patient conduit1812may comprise heating elements1843(e.g. heater wire) adapted to heat humidified gases flowing through the conduit from the humidifier and also provide radiant heat to the patient interface1836and the filter medium1842. In such embodiment, at least a portion of the main body and/or at least a portion of the cover1841may be made of a thermoconductive plastic material. Similarly, at least a portion of the Luer connector may be made of a thermoconductive material. The heating elements1843of the patient conduit1812may be arranged so that heat is conducted to the filter medium1842via the Luer connector1811and the patient interface1836so as to prevent and/or reduce condensation in the filter assembly1840. Reference is now made toFIG.19, which is a cross sectional view of a filter assembly, constructed and operative in accordance with another embodiment of the present invention. FIG.19shows a filter assembly1940comprising a housing1941and a humidifier1904provided as a single unit. Water enters through the gap1905and is spread using hydrophilic material positioned adjacent to the filter medium1942. The entire assembly (i.e. filter assembly1940and humidifier1904) may be heated using a thermally conductive plastic element1943surrounding the filter medium1942and hydrophilic material and connected to a heating power supply1944. Gaps in the thermally conductive plastic element1943allow gases to flow through the entire assembly and become conditioned in the process. This particular configuration of the filter assembly1940and humidifier1904is efficient in that little energy is used to heat a small layer of water on the hydrophilic material and little energy is lost by the conditioned gas as it passes through the filter assembly1940as the filter medium1943is heated by the thermoconductive plastic material element1943. Reference is now made toFIGS.20A and20B, which are different views of a filter assembly, constructed and operative in accordance with a further embodiment of the present invention. FIGS.20A and20Bshow a filter assembly2040provided as part of an elbow connector configured to couple a patient conduit2012to the outlet of a humidification chamber2016. This exemplary embodiment is similar to the one described in relation toFIGS.9and10. However, the filter medium2042is coupled to the elbow connector—so as to be within or protruding from the housing2041—and is configured to be inserted directly into the outlet of the humidification chamber2016. Reference is now made toFIG.21, which is a cross sectional view of a filter assembly, constructed and operative with an embodiment of the present invention. FIG.21shows a filter assembly2140disposed in use between a humidification chamber2116and a patient conduit2112. The filter assembly2140comprises a housing2141consisting of an air gap2147which surrounds the filter medium2142. The housing2141and/or the air gap2147is/are configured such that the humidified gases received from the humidifier chamber2116enter the air gap2147prior to the air gap2149where the filter medium2142is positioned. With such configuration, the air gap2149may be insulated by the humidified gases flowing through the air gap2147and therefore heat transfer may be in the direction of the filter medium2142. Reference is now made toFIGS.22A to22Cwhich are cross sectional views of filter assemblies including a sensor, constructed and operative in accordance with further embodiments of the present invention. FIGS.22A to22Cillustrate a filter assembly2240that may comprise a sensor2245. The sensor2245may be positioned in the gases flow path at any suitable location.FIG.22Ashows the filter assembly ofFIGS.7A-7Bwith the sensor2245positioned in the inlet port. Similarly,FIG.22Bshows the filter assembly ofFIG.5with the sensor2245being positioned in the inlet port. Lastly,FIG.22Cshows the filter assembly ofFIGS.17A-17Cwith the sensor2245positioned on a side surface of the cover. The sensor2245may be configured to measure one or more operating parameter related to the gases flow such as, for example, but not limited to, a temperature, a pressure, humidity and/or a flow rate of the gases. Alternatively, a plurality of sensors may be provided and disposed in the gases flow path and within the filter assembly2240. The sensor2245may be further configured to transmit the measured data to the humidifier for instance and/or to any other local or remote component of the insufflation system. The measured data may be transmitted by any suitable means such as, for example, but not limited to, a wire associated with the patient conduit (e.g. inside the inner tubing, between the inner and outer tubings, on the outside of the outer tubing, or embedded within either the inner or outer tubings), in a flying lead, or wirelessly using RFID (Radio-Frequency Identification) or Wi-Fi technologies, etc. Non-limiting examples of how the data may be used include: using the measured temperature and/or humidity data in closed loop control of the humidifier; using the measured flow rate and/or pressure data to display the actual pressure drop from the gases source to the patient interface; using the measured flow rate and/or pressure data in closed loop control of the gases source if such control input is available, etc. AlthoughFIGS.22A-22Cshow the filter assemblies depicted inFIGS.5,7A-7B and17A-17C, those skilled in the art will appreciate that sensor2245may be used with any of the filter assemblies described hereinabove in relation toFIGS.1-21. Reference is now made toFIGS.23A and23B, which are cross sectional views of a filter assembly, constructed and operative in accordance with an embodiment of the present invention. FIGS.23A and23Bshow a filter assembly2340comprising a filter assembly fitting2346on the housing2341. The filter assembly fitting2346may be configured to be coupled to a patient conduit2312. As it is apparent fromFIGS.23A-23B, a Luer connector2321may be provided to couple the filter assembly fitting2346to the patient conduit2312. Those skilled in the art will appreciate that such Luer connector may be used with any suitable filter assembly described hereinabove such as, for example, but not limited to, the filter assemblies shown inFIGS.1to7B. The Luer connector2321ofFIG.23Amay comprise a deformable end adjacent to the filter assembly2340. To connect the filter assembly2340to the patient conduit2312, the filter assembly fitting2346is press-fitted into the deformable end of the Luer connector2321. When the filter assembly fitting2346is inserted into the Luer connector2321, threads on an outer surface of the filter assembly fitting2346are configured to grip onto ridges provided in an inner surface of the deformable end of the Luer connector2321so as to secure and seal the connection between the Luer connector2321and the filter assembly2340. On the tubing end of the Luer connector2321, barb and boss connectors may be provided so as to couple the double tubing patient conduit2312to the Luer connector2321. FIG.23Bshows a filter assembly2340similar to the one depicted onFIG.23A. The Luer connector2321is different but is also operative to secure and seal the connection between the Luer connector2321and the filter assembly2340. On the tubing end of the Luer connector2321, the patient conduit2312may be coupled to the Luer connector2321by overmoulding for instance. Reference is now made toFIG.24, which is a cross sectional view of a filter assembly, constructed and operative with another embodiment of the present invention. The filter assembly2440ofFIG.24comprises a housing2441, a filter medium2442and heating elements2443. The housing2441comprises an inlet operative to be coupled to an outlet port2418of the humidification chamber2416. The filter assembly2440is configured so that humidified gases exiting the humidification chamber2416enter the filter assembly2440at the inlet, pass through the filter medium2442and exit the filter assembly2440at the outlet2446to enter into the patient conduit2412. As it is apparent fromFIG.24, the humidified gases change direction after the filter medium2442to exit the filter assembly2440at the outlet2446. The filter medium2442is positioned in use above the outlet port of the humidification chamber2416. Such configuration improves the reduction in condensation in the filter assembly2440as the condensate forming on a surface of the filter medium2442facing the humidification chamber2416can drain back into the humidification chamber2416. Additionally, such configuration minimizes the distance between the heating element2443and the surface of the liquid present in the humidification chamber2416(i.e. the portion of the system during which the humidified gases are not heated) and therefore minimizes condensation in the filter assembly2440. Reference is now made toFIG.25, which is a cross sectional view filter assembly including a water trap, constructed and operative in accordance with a further embodiment of the present invention. FIG.25shows a filter assembly2540similar to the one depicted inFIG.5. The filter assembly2540may further comprise a water trap2547. The water trap2647is positioned below the filter medium2542so that condensation forming on a surface of the filter medium2542can drain back to the water trap2547. Those skilled in the art will appreciate that the water trap2547may be positioned at any suitable location and/or may be coupled to any suitable element so that condensation forming on a surface of the filter medium2542can be received into the water trap2547. In addition, those skilled in the art will appreciate that water trap2547may be used with any suitable filter assembly described hereinabove in relation toFIGS.1-24. Reference is now made toFIG.26, which is a cross sectional view of a filter assembly, constructed and operative in accordance with an embodiment of the present invention. The filter assembly2640ofFIG.26may comprise two lumens. The housing2641of the filter assembly2640may comprises lumens, each of the lumens comprising an inlet port, an outlet port and a filter medium2642a,2642bpositioned in use in the gases flow path. Those skilled in the art will appreciate that filter assembly2640may comprise any suitable number of lumens and may be used with any suitable filter assembly described hereinabove in relation toFIGS.1-25. Reference is now made toFIGS.27and28, which are isometric and cross sectional views of a filter assembly, constructed and operative with another embodiment of the present invention.FIGS.27and28show a filter assembly2740,2840positioned in use adjacent to the humidifier between the outlet of the humidification chamber2816and the patient conduit2712,2812. The filter assembly2740,2840comprises a housing2741a,2741b,2841a,2841b, a filter medium2842and heating elements2843,2844. The housing may comprise upper2741a,2841aand lower2741b,2841bportions. The lower portion2741b,2841bmay comprise an inlet configured to be coupled to an outlet of the humidification chamber2816while the upper portion2741aand2841amay comprise an outlet2746,2846configured to be coupled to the patient conduit2712,2812. In addition, the filter medium2842may be disposed in use on the upper portion2741a,2841abetween the inlet and the outlet2746,2846so that humidified gases entering the lower portion2841a,2841bof the housing at the inlet pass through the filter medium2842before exiting the upper portion2741a,2841aof the housing at the outlet2746,2846. FIG.28shows the heating elements2843,2844in greater details. The heating elements may comprise a heater wire2843positioned in an upper region of the upper portion2841aof the housing but spaced apart from the inner top surface. The heater wire2843may be the heater wire of the patient conduit2812or a separate heater wire configured to extend through and provide additional heating to at least a portion of the patient conduit2812. In addition, the heater wire2843extends through the upper portion2841aof the housing and is configured to be coupled to an electrical connector2844providing power to the heater wire2843. When the heater wire2843is heated by receiving power from the electrical connector2844, the gases in the filter assembly2840and the patient conduit2812are therefore heated. As it is apparent fromFIG.28, the humidified gases change direction after the filter medium2842to exit the filter assembly2840at the outlet2846. The filter medium2842is positioned in use above the outlet port of the humidification chamber2816. Such configuration improves the reduction in condensation in the filter assembly2840as any condensate forming on a surface of the filter medium2842facing the humidification chamber2816can drain back into the humidification chamber2816. Additionally, such configuration minimizes the distance between the heater wire2843and the surface of the liquid present in the humidification chamber2816(i.e. the portion of the system during which the humidified gases are not heated) and therefore minimizes condensation in the filter assembly2840. FIGS.27and28show a patient conduit2712,2812being coupled, at one end, to the outlet2746,2846of the upper portion2741a,2841aof the filter assembly2740,2840and, at another end, to a Luer lock connector2711,2811. The Luer connector2711,2811and the outlet2746,2846of the filter assembly2740,2840may be attached to any suitable dual-tubing conduit or any suitable type of single tubing conduit such as, for example, but not limited to: a conduit having annular corrugations as disclosed in U.S. Patent Application No. 2013/0098360 (Fisher & Paykel Limited); a conduit having helical crested corrugations; a conduit having helical corrugations as disclosed in U.S. Patent Application No. 2013/0233318 (Fisher & Paykel Limited); a conduit having an helical bead and bubbles as disclosed in PCT Patent Application WO 2015/142192 (Fisher & Paykel Limited); and a conduit having an helical bead and a film as disclosed in PCT Patent Application WO 2016/048172 (Fisher & Paykel Limited). The patient conduit2712,2812may have an inner tubing, and an outer tubing. The inner tubing provides for a lumen or gases pathway, to allow for the passage of gases along and through the tube. The inner tubing may pneumatically seal with a barb portion provided on a first end of the Luer lock connector2711,2811and/or the outlet2746,2846of the upper portion2741a,2841aof the filter assembly270,2840. The seal between the inner tubing and the barb portion may be formed by one or more of: deformation of the inner tube around the barb portion, or an adhesive, or an overmould. The outer tubing is located outward or external to the inner tubing. The outer tubing may pneumatically seal with a boss portion provided on the first end of the Luer lock connector2711,2811and/or the outlet2746,2846of the upper portion2741a,2841aof the filter assembly270,2840. The seal between the outer tubing and the boss portion may be formed by one or more of: deformation of the inner tube around the barb portion, or an adhesive, or an overmould. In some embodiments, the barb portion may act as a stop or surface to engage with an end of the inner tubing to prevent over insertion of the barb portion within the inner tubing. Similarly, in some embodiments a part of the Luer lock connector2711,2811and/or a part of the outlet2746,2846of the upper portion2741a,2841aof the filter assembly270,2840may act as a stop for the outer tubing (for example a cuff at the end of the outer tubing). The inner tubing and outer tubing may provide for a space therebetween. The space may define an insulation layer. The insulation layer may comprise an air gap to insulate the inner tubing with respect to the surrounding environment. The patient conduit2712,2812may also include a heater wire configured to heat the gases in the conduit2712,2812. The heater wire may be located in the lumen of the inner tube (e.g. heater wire2843also configured to heat the filter medium2842of the filter assembly2841and/or a separate heater wire), and/or located in or on a wall of the inner tube. FIGS.27and28also show the patient conduit2712,2812being coupled to a Luer lock connector2711,2811. The Luer lock connector may comprise a body having an interior region defining a gases flow passageway allowing insufflation/humidified gases to flow through. The body can comprise a first end that removably connects to a fitting of a patient interface (e.g. patient interface136ofFIG.1) and a second end that permanently attaches to the tubing of the patient conduit2712,2812. It will be appreciated that the Luer lock connector2711,2811can be a high flow Luer lock connector providing particular sealing and retention features with less resistance to gases flow than traditional Luer connectors of the art. Embodiments of such high flow Luer lock connectors2711,2811are described, for example, in International Patent Application No. PCT/NZ2017/050149 (Fisher & Paykel Limited), which is incorporated by reference herein in its entirety. There have been described and illustrated herein several embodiments of a filter assembly. While particular embodiments of the invention have been described, it is not intended that the invention be limited thereto, as it is intended that the invention be as broad in scope as the art will allow and that the specification be read likewise. Thus, while particular types of housing, heating element and filter medium have been disclosed, it will be appreciated that any suitable combination of these may be used to provide a filter assembly. In addition, while particular types of materials, sensors, connectors, tubings, water traps and lumens have been disclosed, it will be understood that other types can be used. It will therefore be appreciated by those skilled in the art that yet other modifications could be made to the provided invention without deviating from its spirit and scope as claimed. | 45,383 |
11857720 | DETAILED DESCRIPTION Before any embodiments of the invention are explained in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. FIG.1Aillustrates an example of a device100for dispensing an inhaled medication such as the Advair Diskus® dry powder inhaler (DPI). The dispenser100includes a dispenser body101, a thumb grip103, and a dose counter105. A rotatable cover107is rotatably connected to the dispenser body101. To place the dispenser device100in the “open” position, a user places her thumb in the thumb grip103and rotates the dispenser body101relative to the dispenser cover107as indicated by the arrow. FIG.1Bshows the dispenser device100in the open position. Because the dispenser body101has been rotated relative to the cover107, the thumb grip103and the dose counter105are now shown on the opposite side of the device100. When in the open position, a priming lever109and a mouthpiece111of the device100are uncovered. To use the dispenser device shown inFIGS.1A and1B, a patient rotates the dispenser body101into the “open” position and moves the priming lever109as indicated by the arrow inFIG.1B. Moving the priming lever109causes a dose of medication to be removed from packaging stored within the device body101. In some constructions, moving the priming lever109both removes a medication from a packaging and crushes a pill-form medication into an inhalable powder. The patient then places their mouth on the mouthpiece111and inhales the medication from the dispenser100. FIG.2illustrates an attachment device200that monitors usage of the dispenser100. Data collected from the attachment device200can be used to track the time, date, and location of regular uses of a medicament dispenser, such as described in U.S. Pub. No. 2009/0194104, filed on Jan. 5, 2009 and entitled “DEVICE AND METHOD TO MONITOR, TRACK, MAP, AND ANALYZE USAGE OF METERED-DOSE INHALERS IN REAL-TIME.” Alternatively, the collected data can be analyzed to confirm that the medication is being taken appropriately. For example, the data can be analyzed to verify that the medication is being taken at the appropriate times as prescribed by the doctor. Furthermore, as described in further detail below, the audio signal recorded during usage can be analyzed to ensure that the medication is being properly inhaled and, in some cases, to confirm that the proper medication is being used. As shown inFIG.2, the attachment device200includes an upper body201with two leg portions203,205extending from the upper body201and reconnecting at a lower ring body207. A medication dispenser, such as dispenser100illustrated inFIGS.1A &1Bis selectively insertable into the cavity formed by the upper body201, the leg portions203,205, and the lower ring body207. The attachment device200is also water proof (or water resistant) to protect the electronics housed within. The attachment device200is constructed of a bio-compatible material that will not adversely affect the medication being dispensed and will not adversely affect the patient using the device200. The attachment device200is sized to receive the dispenser200and hold the dispenser in place by friction. In some constructions, all external surfaces of the attachment device200are constructed of a rigid plastic material. However, in some alternative constructions, the leg portions203,205are construction of a flexible and stretchable material to allow the attachment device to better conform to the dispenser and to increase friction between the attachment and the dispenser. The attachment device200is sized and shaped so that it does not interfere with the operation and actuation of the medication dispenser or with the dispensed medication. The priming lever109is able to move freely and access to the mouthpiece111is not obstructed. When there are no more medication doses remaining in the dispenser100, the dispenser100can be removed from the attachment device200and replaced with a new dispenser100. The opening in the lower ring body207provides access to the dispenser100, making it easier for the dispenser100to be removed. In some constructions, color coding is used to ensure that the correct dispenser is used and that the dispenser is properly inserted into the attachment device200. The attachment device200also includes a “cassette” portion209. The “cassette” portion209houses the electronics of the attachment device200as described below and can be removed from the upper body201of the attachment device200. The cassette portion209includes a protrusion211that extends from the upper body201when the cassette portion209is properly installed. The protrusion211positions various sensors—including a pair of infrared sensors that detect whether the dispenser100is in the open (FIG.1B) or closed position (FIG.1A). FIG.3illustrated the electronic components housed within the cassette portion209of the attachment device200. Although, in this example, the electronics can be removed from the attachment device200by removing the cassette portion209, in other constructions, the electronics can be permanently housed within the upper body201or elsewhere in the attachment device200. The cassette portion209includes a processor301which controls the operation of the attachment device200. In various constructions, the processor301can include a microcontroller, microprocessor, ASIC, or other circuitry. However, in this particular example, the processor301accesses software instructions stored on a memory303and executes the instructions to control the operation of the attachment device200. The memory303can include, for example, one or more transitory or non-transitory memory components such as random access memory (“RAM”), read-only memory (“ROM”), flash memory, and other magnetic memory media. In this example, the memory module303includes a non-volatile memory that retains stored data when power is lost (or intentionally removed). The processor301is connected to three sensor modules—an accelerometer305, an IR sensor module307, and a microphone309. The accelerometer305measures accelerations applied to the attachment device200caused by movements of the device. Furthermore, as described in detail below, the accelerometer305may be positioned and configured to detect an impulse caused by the movement of the priming lever209. The accelerometer305includes a low-power, 3-axis accelerometer that is being monitored at all times. Alternatively, the attachment device may include one or more capacitive sensors to detect when the device is being handled. The IR sensor module307includes a pair of infrared sensors positioned in the protrusion211of the attachment device200. The IR sensors are positioned to monitor movements of the device body201and to indicate whether the dispenser is in an open position or a closed position. In particular, the IR sensor module monitors the position of the air intake ridges of the dispenser or the location of the dose counter window (depending on how the dispenser is inserted into the attachment device). Although the examples described herein include an IR sensor module, some alternative constructions will include other sensor mechanisms to determine whether a dispenser is opened or closed. For example, a mechanical switch or magnetic detection can be used to detect rotation of the dispenser body. Alternatively, the attachment housing itself can be constructed of a metalized plastic material or with electrodes which would allow the entire body of the attachment device to operate as a capacitive sensor. Changes in capacitance could be monitored to indicate when the device is being handled—thereby also replacing the accelerometer. In addition, the electrodes can sense when the patient lips are near or contacting the mouthpiece. The microphone309captures audio of the patient inhaling the medication. This audio data is processed by the processor301or by an external computer system to ensure appropriate medication usage. Furthermore, the microphone system309is configured to identify, note, and segregate inhalation events from other background noise. The microphone system309eventually adapts to eliminate false positives by recognizing an audio signal that is associated with a user's unique inhalation. As the microphone system309is able to adapt based on “learned” data, the accuracy of the attachment device and its ability to correctly identify inhalation events is improved. The processor301is also connected to a wireless transceiver311that is configured to exchange data with an external device. In the example ofFIG.3, the wireless transceiver311communicates with a cellular telephone313carried by the patient. The cellular telephone313further relays information between the attachment device200and a remote computer server. The wireless transceiver in this example is a Bluetooth-type transceiver. However, other constructions may include any other type of wireless communication device including, for example, Wi-Fi, cellular, or RF transceivers. The example ofFIG.3shows the accelerometer205, IR sensor module307, microphone309, and wireless transceiver311all directly connected to the processor301. However, it is to be understood that the attachment device may include a controller area network (“CAN”) with a bus for relaying data between the various components of the attachment device200. Other configurations and communication mechanisms are also possible. Furthermore, although the example ofFIG.3shows communication with the computer server315through a wireless relay with a cell phone313carried by the user, other constructions may include other mechanisms for transferring data between the attachment device200and the computer server315. For example, the attachment device200may be equipped with a cellular communication module for directly communicating with the computer server315over a cellular telephone network. Alternatively, the attachment device200may include a Wi-Fi transceiver for communicating with the computer server315through the Internet or other computer network. Furthermore, wired communication mechanisms can also be utilized. In some constructions, the attachment device includes a wired data port. When the attachment device is directly connected to a personal computer through the wired data port, the controller is configured to communicate with the computer through the wired data port. The wired data port can also be used to provide software/firmware updates to the attachment device. FIG.4illustrates one example of a method of monitoring usage of the dispenser100using the attachment device200. The method ofFIG.4is stored as software instructions on the memory303and executed by the processor301. The attachment device begins in a low-power “sleep mode” where the acceleration sensor is being monitored, but the IR sensor module and the microphone are both disabled (step401). The controller continuously compares the measured acceleration to an acceleration threshold (step403). Once the threshold is exceeded-indicating excessive movement of the dispenser device, the controller provides power to the IR sensors (step405) and monitors the IR sensors to determine whether the dispenser is in an open position or closed position (step407). Once the IR sensors indicate that the dispenser is in the open position, the controller monitors the acceleration sensor for a motion impulse associated with activation of the priming lever (step409). When the priming impulse is detected (step411), the controller activates the microphone and begins recording audio data (step413). The audio data is amplified, low-pass filtered, and converted to digital data by a 12-bit analog-to-digital converter. The raw digital data is stored to the memory and analyzed (e.g., FFT, cepstral coefficients, zero-crossing rate, average amplitude vs. time, envelope, etc.) to create a compressed set of metadata associated with the recorded audio. The controller then wirelessly transmits the compressed audio data to a cellular phone (step415) which then sends the data to a computer server for further analysis and determination of whether a detected “usage event” was an actual dispense and inhalation of the medication. Alternatively, in some constructions, the raw, uncompressed audio data is sent to an external system where the audio processing and analysis is later performed. To provide for more robust operation, the controller in some constructions is programmed to operate in a number of “states” rather than executing a linear series of operations as illustrated inFIG.4.FIG.5illustrates one example of a state diagram for controlling the operation of the attachment device. The device begins in “Sleep Mode 1” (state501) where the controller believes that the device cover is closed. The accelerometer is turned on, but the IR sensor module and the microphone are both disabled. When the acceleration exceeds a threshold, the system moves into a “waiting to open” state (state503). In this state, the accelerometer and the IR sensor module are both turned on and the cover is closed. If the system times-out before movement of the cover is detected, it returns to “Sleep Mode 1” (state501). However, if the IR sensor module indicates that the cover is opened, the system moves to a “waiting for prime” state (state505). Again, a system timeout can send the device into a “Sleep Mode 2” (state507) where the IR sensor module is disabled to conserve power. Also, if the IR sensors indicate that the cover is closed at this stage, the system returns to “Sleep Mode 1” (state501). However, if the priming impulse is detected by the accelerometer, the system moves to a “Record Audio/Inhalation” state (state509) in which the microphone is also powered on. Audio recording is terminated when either the cover is closed (as indicated by the IR sensors) or when a timer expires. In either case, the system moves to the “Audio Data Processing” state (state511) where the microphone is powered off and the audio data is processed before being saved to memory. After the data processing is complete, the system attempts to initiate wireless communication (entering the “Initiate Wireless Comm” state) (state513). If communication fails, the system returns to either “Sleep Mode 1” (state501) or “Sleep Mode 2” (state503) depending on whether the IR sensor module indicates that the dispenser cover is open. However, if communication is successful, the system moves to a “Wireless Comm” state (state515) where data is wirelessly transmitted to a terminal device such as a cell phone carried by the user. Once data has been successfully transmitted, it is deleted from the internal memory of the attachment device. After the wireless communication is complete, the system returns to either “Sleep Mode 1” (state501) or “Sleep Mode 2” (state507)—again, depending on whether the IR sensor module indicates that the dispenser cover is open. Other constructions of the attachment may include additional sensors and functionality not illustrated or described above. Similarly, other constructions may include fewer sensors and few functional steps than those illustrated above. For example, in some constructions, steps409and411ofFIG.4are omitted. In such constructions, the attachment does not monitor separately for a priming impulse and, instead, assumes that medicament is dispensed based on either (1) the opening of the mouthpiece (as detected by the IR sensor305) or (2) the audible sound of the medicament being inhaled (as detected by the microphone309). Furthermore, in still other constructions, fewer sensors can be utilized. For example, in one construction, the IR sensor307is omitted, leaving only the accelerometer305and the microphone309. As a result, steps405and407ofFIG.4are omitted. The attachment monitors the accelerometer305to determine when the device is being handled and then activates the microphone309. The microphone309is then monitors for the audible sound of the medicament being inhaled. Alternatively (or in addition), the output of the microphone309can be monitored to determine a sound associated with the priming action of the dry powder inhaler (i.e., the sound of the pill being crushed or of the priming lever109being moved). Once the relevant sound is detected, the attachment determines that the medicament has been dispensed and transmits relevant information to the cell phone (or other device). In yet another construction, the microphone309is omitted and only the accelerometer305and the IR sensor307remain. In such embodiments, step413is omitted from the method ofFIG.4. The accelerometer305is used to detect handling of the device and to detect a priming impulse (i.e., movement of the priming lever109). The IR sensor307is used to determine whether the mouthpiece of the inhaler is opened. Alternatively, the IR sensor307can be used to visually detect movement of the priming lever109(i.e., a dispensing of the medicament is detected when the priming lever109breaks the IR beam emitted by the IR sensor307). In still another construction, the microphone309and the IR sensor307are both omitted leaving only the accelerometer305. In such embodiments, the accelerometer305is used to detect handling of the device (i.e., steps401&403) and is also used to detect the priming impulse of the dispenser (steps409&411). Steps405,407, and413are omitted. In another construction, the IR sensor is positioned to sense when the mouth of the patient is placed in proximity to the mouthpiece during medication use. In some constructions, the attachment device200may include additional sensors to monitor galvanic skin response, oxygen saturation, and heart rate. These sensors can be passively activated, and their measurements obtained, by the fingers either in the normal course of handling and using the inhaler, or by activating specific buttons on the surface of the housing. Once these biometric parameters (for example, heart rate) are determined, the processor stores the data to the memory and attempts to initiate a wireless communication link to send the data to the patient's cell phone. Once the biometric data is sent, it is deleted from the local memory. As described above, the wireless communication link is initiated whenever a usage event or heart rate event are concluded. The stored audio data and/or heart rate data is then uploaded to the computer server through a cell phone. However, in situations where a wireless link cannot be established, the data remains stored in the memory until the next wireless link is successfully established. Furthermore, in some constructions, the attachment device stores further information including, for example, a history of accelerometer readings that indicate movement of the dispenser device. In some constructions, this additional accelerometer data is also uploaded to the computer server whenever a wireless link is established (i.e., after a medication usage event or heart rate event). Although not illustrated in the examples above, some constructions of the attachment device include a user interface. The user interface can include one or more indicators (e.g., LED, OLED, audible signals, visual signals, etc.) that indicate information regarding the operation of the attachment device (e.g., low battery, wireless comm established, etc.). The user interface can also include various buttons that, for example, establish pairing between the attachment device and a particular cell phone or perform a factory reset of the device. Lastly, in some constructions, the attachment device includes a vibration component that vibrates to call the attention of the user. The vibration feature and other components of the user interface can be used in conjunction with an application running on the user's cell phone to help the user locate a lost dispenser. The user can initiate a signal from the cell phone that then causes the attachment device to vibrate, blink, or emit an audio signal. Some constructions also utilize the user interface to notify the user when the attachment device is out of range and cannot establish a wireless link with the user's cell phone. If the attachment device is unable to connect with the cell phone, an indicator—such as, for example, a light, vibration, or tone—is initiated by the attachment device. Similarly, an application can be run on the user's cell phone that provides an indication on the cell phone when a link with the attachment device cannot be established. Therefore, the attachment device notifies the user when the attachment device is being taken out of range of the cell phone and the cell phone can be configured to notify the user when they are leaving the house without their medication dispenser. In some constructions, the attachment device is further configured to determine whether the attachment device is coupled to a dispenser. For example, whenever the attachment device described above comes out of one of the “Sleep Modes,” the IR sensor module will indicate whether a dispenser is “opened,” “closed,” or “not attached.” In other constructions, the attachment device may include a mechanical switch or an ambient light sensor to detect whether the attachment device is properly coupled to a dispenser. The array of sensors described above can also be monitored to establish a “use profile.” In such constructions, the device will determine and store indications of whether the device was recently opened (based on the IR sensors), whether the device was recently primed/cocked (based on the accelerometer and microphone), whether a sound was recorded that could be an inhalation, and whether each of these events occurred within a temporal window that indicates a normal usage of the medication dispenser. FIG.6Aillustrates the exterior of another construction of an attachment600for use with a medicament dispensing device such as the Diskus dry-powder inhaler. The attachment again includes an upper body601and a lower body603connected by two side connection portions605and607. The external casing of the upper body601is generally circular with a cut-out portion609. The cut-out portion609provides greater access to the thumb grip103of the rotating dispenser body101(FIG.1A) as well as visual access to the dose counter105when the dispenser is in the closed position. When the dispenser is in the opened position, the cut-out portion609provides greater access to the mouthpiece111. The lower body603also includes a pair of screw holes611used to tighten pressure screws which are used to hold the attachment in place on the dispenser, as described in greater detail below. In some constructions, the upper body601or lower body605also includes a cut-out (not pictured) to ensure that a dose counter on the dispensing device is not covered by the attachment600. FIG.6Bprovides a top view of the attachment600. This view better illustrates the shape of the upper body601(including the cut-out portion609). It also illustrates the shape of the side connection portions605,607which join the upper body601to the lower body603. As shown inFIG.6B, the side connection portions605,607are generally formed to conform to the shape of the medicament dispenser. The two side connection portions605,607are separated by an opening613which can be used to push the dispenser out of the attachment600as necessary when the dispenser is being removed from the attachment600. FIG.6Cshows the attachment600from the bottom. As shown inFIG.6C, the upper body601extends beyond the lower body603. Furthermore, from the bottom, the pair of friction screws615,617can be seen. When the dispenser is inserted into the attachment, the friction screws615,617are tightened into screw holes611to increase the friction between the dispenser and the upper body601of the attachment thereby securing the attachment600to the dispenser. Although this discussion refers to screws615,617as “friction screws” that are used to secure the dispenser within the attachment, in other constructions, the size and material of the attachment600is configured to hold the dispenser device in place by a friction fit without the use of screws. In some such constructions, screws615,617may be used to secure an external cover of the attachment600to the body of the attachment600. FIGS.6D and6Eshow the attachment600from the left and the right sides. As shown inFIGS.6D and6E, the upper body601is thicker than the lower body603. The upper body601is shaped to provide sufficient internal space to hold the processor301, the wireless transceiver311, the memory303, and the various sensors employed to monitor the usage of the dispenser. As shown inFIG.6F, the arrangement of the upper body601, the lower body603, and the side connection portions605,607forms a large opening619for receiving the dispenser. To couple the attachment600to the dispenser, the cover107of the dispenser is inserted into the larger opening619and the friction screws615,617are tightened to hold the dispenser in place. As a result, the cover107is held stationary relative to the attachment600while the dispenser body101is allowed to rotate relative to the attachment600. As shown inFIG.6G, the opening613is positioned opposite the larger opening619. To decouple the attachment600from the dispenser, the friction screws615,617are loosened and the user inserts one or more fingers into the opening613to push the dispenser through the larger opening619on the opposite side, thereby disengaging the dispenser from the attachment600. Although the examples illustrated above discuss an attachment that is adapted to be coupled to a Diskus-type dry powder inhaler, the sensing functionality and arrangements described above can be applied to other types of medicament dispensers. For example, an accelerometer can be incorporated into an attachment for use with a canister-style metered dose inhaler such as the cap housing described in U.S. Pub. No. 2009/0194104. Such an accelerometer can be used to detect dispensing of the medicament from the canister and then provide power to additional electronic components within the attachment. FIG.7Aillustrates a construction of an attachment800configured for use with a medicament dispenser device such as the Respimat soft mist inhaler (SMI)700developed by Boehringer Inhelheim. The Respimat dispenser700includes a main body701with a cavity for receiving a medication canister703. A cover705is then placed over the canister703. Another cover707and a dispensing button709are positioned on the opposite end of the main body701. The cover707is opened to reveal a mouthpiece711underneath. To prime the Respimat dispenser700for use, the cover705is rotated relative to the main body701. This causes the medicament canister703to move out of the cavity of the main body701along axis “A.” When the cover707is opened and the button709is pressed, the medicament is dispensed through the mouthpiece711as the canister moves into the cavity of the main body701along axis “A.” The attachment800includes an external body801which is sized to fit around the exterior of the rotatable cover705of the Respimat dispenser device700. A printed circuit board803is positioned within the external body801and, in this example, includes a microphone805, an IR sensor807, and an accelerometer809. However, in other constructions, the attachment800may be fitted with additional sensors, alternative sensors, or fewer sensors. Similarly, the sensor may have different placement in other constructions. A pair of button-type batteries811is positioned at the distal end of the attachment and are electrically coupled to the circuit board803. A button813is also positioned on the external body801of the attachment800. A described above in reference toFIGS.4and5, the accelerometer809is used to bring the attachment out of a low-power “sleep mode” and to then apply electrical power from the batteries811to the microphone805and the IR sensor807. Once out of the sleep mode, the IR sensor807monitors for the movement of the medicament canister703through the transparent cover705of the Respimat dispenser device700. The attachment determines that the medicament has been dispensed when the canister703first moves to obstruct the IR sensor807and then moves again to a position that does not obstruct the IR sensor807. Once dispensing is detected, the microphone805is activated to detect and measure sounds associated with the inhaled medicament. For example, the output of the microphone805can be used to measure inhalation characteristics of the patient using the medication and, together with application software running on the user's smartphone, provide feedback to a doctor or the patient. Alternatively, in other constructions, the IR sensor807is omitted, leaving only the microphone805and the accelerometer809. In such constructions, the accelerometer is used to detect handling of the attachment800and the Respimat dispenser device700. Once handling is detected and power is applied to the microphone805, the output of the microphone805is monitored for a “click” sound associated with the priming of the Respimat dispenser device700(i.e., the rotation of the transparent canister cover705) Alternatively, the output of the microphone805can be monitored to detect when the button709of the dispenser device700is pressed indicating that medication has been dispensed. In still other constructions, the positioning of the IR sensor807can be moved such that the IR sensor detects compression and decompression of a spring in the transparent base of the dispenser device700(which indicates priming and movement of the medication canister). This can be in addition to or instead of the IR sensor807positioned to directly detect canister movement from the side of the transparent base. FIG.7Bshows an exploded view of the various components of the attachment800. The Respimat dispenser device700fits into an internal receiving body815of the attachment800. The internal receiving body815is sized and configured to be placed in close proximity with the external surfaces of the Respimat dispenser device700such that rotation of the attachment800(and, therefore, rotation of the internal receiving body815) causes rotation of the transparent canister cover portion705of the Respimat dispenser device700. A circuit board/logic portion803is formed to fit between the internal receiving body815of the dispenser and the external body801. The attachment800may be configured to attach to the housing of the dispenser device700without requiring adhesive material or excessive force and can be done in a single one-step on/off procedure. The attachment housing design may include clear material so no labeling of the dispensing device700is covered. When attached, the attachment800does not interfere with or restrict use of the dispensing device700. FIGS.8A-8Gillustrate another example of an attachment device901for use with a Respimat-type medicament dispenser. As shown inFIG.8A, the external surface of the attachment device901includes a substantially cylindrical sheath body903and a top surface905. As show inFIGS.8B and8C, the cylindrical sheath body903includes a slight beveled portion near the top surface905such that the diameter of the top surface905is slightly smaller than the diameter of an opening at the opposite end of the sheath body903. The sheath body903is also formed to include a protrusion907formed to receive a similarly shaped protrusion of the transparent cover705of the Respimat dispenser device700. Another similarly sized protrusion911is formed on the opposite side of the sheath body903(see,FIGS.8C,8D, and8E). A button909is positioned on the sheath body903near the top surface905. Thus, the invention provides, among other things, an attachment device for monitoring the usage of a medication dispenser. The attachment device come out of a low-powered “sleep mode” when it detects that the dispenser is being handled and then provides power to additional components that consume more power. The attachment device can be configured to fit with a variety of different dispenser devices including, for example, a canister-type metered dose inhaler, a Diskus-type dry powder inhaler, and a Respimat soft mist inhaler. Various features and advantages of the invention are set forth in the following claims. | 32,574 |
11857721 | DETAILED DESCRIPTION Aspects and features of certain examples and embodiments are discussed/described herein. Some aspects and features of certain examples and embodiments may be implemented conventionally and these are not discussed/described in detail in the interests of brevity. It will thus be appreciated that aspects and features of apparatus and methods discussed herein which are not described in detail may be implemented in accordance with any conventional techniques for implementing such aspects and features. As described above, the present disclosure relates to (but is not limited to) electronic aerosol or vapor provision systems, such as e-cigarettes. Throughout the following description the terms “e-cigarette” and “electronic cigarette” may sometimes be used; however, it will be appreciated these terms may be used interchangeably with aerosol (vapor) provision system or device. Similarly, “aerosol” may be used interchangeably with “vapor”. As used herein, the term “component” is used to refer to a part, section, unit, module, assembly or similar of an electronic cigarette that incorporates several smaller parts or elements, often within an exterior housing or wall. An electronic cigarette may be formed or built from one or more such components, and the components may be removably connectable to one another, or may be permanently joined together during manufacture to define the whole electronic cigarette. FIG.1is a highly schematic diagram (not to scale) of an example aerosol/vapor provision system such as an e-cigarette10. The e-cigarette10has a generally cylindrical shape, extending along a longitudinal axis indicated by a dashed line, and comprises two main components, namely a control or power component or section20and a cartridge assembly or section30(sometimes referred to as a cartomizer, clearomizer or atomizer) that operates as a vapor generating component. The cartridge assembly30includes a reservoir3containing a source liquid comprising a liquid formulation from which an aerosol is to be generated, for example containing nicotine. As an example, the source liquid may comprise around 1 to 3% nicotine and 50% glycerol, with the remainder comprising roughly equal measures of water and propylene glycol, and possibly also comprising other components, such as flavorings. The reservoir3has the form of a storage tank, being a container or receptacle in which source liquid can be stored such that the liquid is free to move and flow within the confines of the tank. Alternatively, the reservoir3may contain a quantity of absorbent material such as cotton wadding or glass fiber which holds the source liquid within a porous structure. The reservoir3may be sealed after filling during manufacture so as to be disposable after the source liquid is consumed, or may have an inlet port or other opening through which new source liquid can be added. The cartridge assembly30also comprises an electrical heating element or heater4located externally of the reservoir tank3for generating the aerosol by vaporization of the source liquid by heating. An arrangement such as a wick or other porous element6may be provided to deliver portions of source liquid from the reservoir3to the heater4. The wick6has one or more parts located inside the reservoir3so as to be able to absorb source liquid and transfer it by wicking or capillary action to other parts of the wick6that are in contact with the heater4. This liquid is thereby heated and vaporized, to be replaced by a new portion of liquid transferred to the heater4by the wick3. The wick therefore extends through a wall that defines the interior volume of the reservoir tank3, and might be thought of as a bridge or conduit between the reservoir3and the heater4. A heater and wick (or similar) combination is sometimes referred to as an atomizer, and the reservoir with its source liquid plus the atomizer may be collectively referred to as an aerosol source. Various designs are known, in which the parts may be differently arranged compared to the highly schematic representation ofFIG.1. For example, the wick6may be an entirely separate element from the heater4, or the heater4may be configured to be porous and able to perform the wicking function directly (a metallic mesh, for example). Regardless of the implementation, the parts will be configured to form a liquid flow path by which the source liquid is able to travel from the interior of the reservoir3to the vicinity and surface of the heater4for heating and vaporization. This is the intended fluid path, whereby liquid is delivered to the heater and should be successfully vaporized and thereby prevented from arriving at any unwanted location. The cartridge assembly30also includes a mouthpiece35having an opening or air outlet through which a user may inhale the aerosol generated by the heater4. The power component20includes a cell or battery5(referred to herein after as a battery, and which may be re-chargeable) to provide power for electrical components of the e-cigarette10, in particular the heater4. Additionally, there is a printed circuit board28and/or other electronics or circuitry for generally controlling the e-cigarette. The control electronics/circuitry connect the heater4to the battery5when vapor is required, for example in response to a signal from an air pressure sensor or air flow sensor (not shown) that detects an inhalation on the system10during which air enters through one or more air inlets26in the wall of the power component20. When the heating element4receives power from the battery5, the heating element4vaporizes source liquid delivered from the reservoir3by the wick6to generate the aerosol, and this is then inhaled by a user through the opening in the mouthpiece35. The aerosol is carried from the aerosol source to the mouthpiece35along an air channel (not shown) that connects the air inlet26to the aerosol source to the air outlet when a user inhales on the mouthpiece35. An air flow path through the electronic cigarette is hence defined, between the air inlet(s) (which may or may not be in the power component) to the atomizer and on to the air outlet at the mouthpiece. In use, the air flow direction along this air flow path is from the air inlet to the air outlet, so that the atomizer can be described as lying downstream of the air inlet and upstream of the air outlet. Herein, the term “electrical power supply” is used to refer to either or both of the battery and the control circuitry. In this particular example, the power section20and the cartridge assembly30are separate parts detachable from one another by separation in a direction parallel to the longitudinal axis, as indicated by the solid arrows inFIG.1. The components20,30are joined together when the device10is in use by cooperating engagement elements21,31(for example, a screw or bayonet fitting) which provide mechanical and electrical connectivity between the power section20and the cartridge assembly30. This is merely an example arrangement, however, and the various components may be differently distributed between the power section20and the cartridge assembly section30, and other components and elements may be included. The two sections may connect together end-to-end in a longitudinal configuration as inFIG.1, or in a different configuration such as a parallel, side-by-side arrangement. The system may or may not be generally cylindrical and/or have a generally longitudinal shape. Either or both sections may be intended to be disposed of and replaced when exhausted (the reservoir is empty or the battery is flat, for example), or be intended for multiple uses enabled by actions such as refilling the reservoir and recharging the battery. Alternatively, the e-cigarette10may be a unitary device (disposable or refillable/rechargeable) that cannot be separated into two parts, in which case all components are comprised within a single body or housing. Embodiments and examples of the present disclosure are applicable to any of these configurations and other configurations of which the skilled person will be aware. The example device inFIG.1is presented in a highly schematic format.FIGS.2and3show more detailed representations of aerosol sources according to examples, indicating relative positions of the tank, heater and wick. FIG.2shows a cross-sectional side view of an aerosol source. A reservoir tank3has an outer wall32and an inner wall34, each of which is generally cylindrical. The inner wall34is centrally disposed within the outer wall32to define an annular space between the two walls; this is the interior volume of the tank3intended to hold source liquid. The tank is closed at its lower end (in the orientation depicted) by a bottom wall33and at its top end by an upper wall36. The central space encompassed by the inner wall34is an airflow passage or channel37which at its lower end receives air drawn into the electronic cigarette (such as via air intakes26shown inFIG.1), and at its upper end delivers aerosol for inhalation (such as through the mouthpiece35inFIG.1). Disposed within the airflow channel37is an atomizer40comprising a heater4and a wick6. The wick6, an elongate porous element that may, for example, be rod-shaped and formed from fibers, is arranged across the airflow passage (shown as closer to the lower end of the tank3, but it may be positioned higher) so that its ends pass through apertures in the inner wall34and reach into the interior volume of the tank3to absorb source liquid therein. The apertures (not shown) may be sealed to minimize source liquid leakage from the tank3into the airflow channel37; nevertheless leakage may still arise. The heater4is an electrically powered heating element in the form of a wire coil wrapped around the wick6. Connecting leads4a,4bjoin the heater4to a circuit (not shown) for the provision of electrical power from a battery. The aerosol source will be disposed within the housing of a cartridge assembly section (cartomizer) of an electronic cigarette, with a mouthpiece arranged at its top end and a controller and battery arranged at its lower end (possibly in a separable component). Note that the outer wall32of the tank3may or may not also be a wall of the cartridge assembly housing. If these walls are shared, the cartridge assembly may be intended to be disposable when the source liquid has been consumed, to be replaced by a new cartridge assembly connectable to an existing battery/power section, or may be configured so that the reservoir tank3can be refilled with source liquid. If the tank wall and the housing wall are different, the tank3or the whole aerosol source may be replaceable within the housing when the source liquid is consumed, or may be removable from the housing for the purpose of refilling. These are merely example arrangements and are not intended to be limiting. In use, when the aerosol source within its assembly housing is joined to a battery section (separably or permanently depending on the e-cigarette design), and a user inhales through the mouthpiece, air drawn into the device through an inlet or inlets enters the airflow channel37. The heater4is activated to produce heat; this causes source liquid brought to the heater4by the wick6to be heated to vaporization. The vapor is carried by the flowing air further along the airflow channel37to the mouthpiece of the device to be inhaled by the user. The arrows A indicate the airflow and its direction along the air flow path through the device. FIG.3shows a cross-sectional side view of an alternative example aerosol source. As in theFIG.2example, the tank3is an annular space formed between an outer wall32and an inner wall34, with the interior space of the tubular inner wall34providing an airflow channel37. In this example, however, the rod-shaped wick and coiled heating element are replaced by an atomizer40in which a single entity provides both the wicking and heating functions. An electrically conductive mesh can be used for this, for example, where the conductive characteristic allows the atomizer to receive electrical power and heat up, while the mesh structure allows a wicking action. The atomizer40is again arranged across the airflow channel37with parts passing through the inner wall34into the interior volume of the tank3. However, in this example, the atomizer40has an elongate planar configuration and is arranged such that its long edges reach into the reservoir, and its short ends are at each end of the airflow passage37. These ends4a,4bare connected to a battery by appropriate arrangement of electrical conductors (not shown). Thus, a larger area of vaporizing surface is offered to air flowing through the airflow channel. Apertures where the edges of the atomizer extend into the atomizer may or may not be sealed to minimize leakage into the air flow channel37, but some leakage may occur nevertheless. FIGS.2and3are merely examples of aerosol sources to illustrate various alternatives available for achieving aerosol generation. Other configurations can achieve the same effect, and the invention is not limited in this regard. In particular, the reservoir may have other formats and the coupling between the reservoir and the atomizer may differ. Whichever configuration is adopted, in any design which includes a reservoir in the form of a tank, container, receptacle or similar volume for holding the source liquid will be potentially vulnerable to unwanted leakage of the source liquid from the reservoir, where such leakage may be along paths, routes and directions that do not take the source liquid to a location where it can be vaporized. The construction of the reservoir may produce potential leakage points, such as where sections of the reservoir wall are joined together, or where the reservoir is joined to adjacent parts. Also, seals which may be included at potential weak spots such as where the wick passes through the reservoir wall or where an access cap or lid is provided for refilling the reservoir might be imperfect. Furthermore, issues may arise from liquid which has begun its journey along the intended path for vaporization and arrived at or near the heater, but which is then not vaporized. This may happen if, for example, the wicking action draws liquid towards the heater at a faster rate than it can be vaporized by the heater when activated, or when wicking continues when the heater is not activated. Liquid can then accumulate in the atomizer beyond the amount which can be held in the porous structure and then be released as free liquid into the airflow channel, creating an unwanted escape or leak of liquid. A potential technique to address unwanted leakage is to minimize any weak points in the structure (by reducing the number of joints between components, for example), or to make any apertures at these weak points as small as possible, or to apply or provide some form of sealing material at or over such weak points. However, it is not desirable to provide a completely sealed reservoir. While such a structure would be watertight and therefore leak-proof, it would also be airtight or close to airtight, restricting air from entering the reservoir. An ingress of air is necessary to equalize the pressure inside the reservoir as the source liquid is consumed, and to allow the continued outward flow of source liquid to the atomizer. Also, it is necessary to maintain the openings through which the liquid leaves the reservoir to reach the atomizer, and capillary action will continue to draw liquid to the atomizer if the heater is activated for vaporization or not. Accordingly, an alternative approach is proposed to address the leakage problem. Rather than attempting to prevent leaks from the reservoir from occurring, it is proposed to allow/expect some leakage, and arrange for collection of the leaked liquid before it can produce any problems such as spillage or damage to other parts of the electronic cigarette. An element made from absorbent material is disposed within the electronic cigarette to collect and absorb liquid which may escape from the reservoir and find its way along a path or route that does not result in vaporization. Herein, the term “escaped” includes source liquid that has directly leaked from the reservoir or dripped from the wick or heater, and also source liquid has followed the intended path from reservoir to heater for vaporization but which has then condensed back to liquid rather than being delivered as a vapor for inhalation. These mechanisms can all result in source liquid which is free within the electronic cigarette externally from the reservoir and not able to be vaporized, presenting a potential problem if it reaches the electrical power supply. The proposed absorbent element can collect this stray source liquid. FIG.4shows a longitudinal cross-sectional view of a cartomizer component including an absorbent element according to a first example. The cartomizer component30houses a reservoir3for source liquid and an associated atomizer40with a wicking component (which may be a separate wick or a combined wick and heater, for example) that reaches into the interior of the reservoir and which is arranged to generate and deliver vapor into the air flow path37for consumption via the mouthpiece35. Opposite the mouthpiece35, the cartomizer30terminates in a connector31configured to make mechanical and electrical connection to a power component housing a battery and circuitry to provide electrical power from the battery to a heating element in the atomizer40. The connector31forms an end wall of the cartomizer30which in use abuts a corresponding end wall connector on a power component. In this example, the airflow path37extends through this end wall of the cartomizer30, so the connector31has a central aperture38forming an air inlet to let air enter the air flow path37. Other air inlet arrangements are possible, so there may be no air aperture in the end wall. The reservoir3has an annular shape as in theFIGS.2and3examples, so that its interior storage volume is defined between outer and inner walls32,34. Any source liquid that escapes through the outer wall34will enter the interior of the cartomizer (defined within an exterior cartomizer housing39), and may find its way to the connector31. Any source liquid that escapes through the inner wall34will enter the air flow path37, and may also find its way towards the connector31. Source liquid may enter the air flow path as a direct leak, or via dripping from a saturated wicking element, as described above. When the cartomizer30is separated from its power component, any liquid in the air flow path37can exit through the central aperture38of the connector31. Liquid inside the cartomizer housing39may also exit, via any openings or apertures formed where the connector joins the cartomizer housing or where electrical connections extend through the connector (to connect the heater in the atomizer40to a battery external to the cartomizer). Thus, source liquid may undesirably escape as spillage from the cartomizer30. When the cartomizer30is connected to a power component20by means of the connector31, this spilled liquid could enter the interior of the power component, and may penetrate to the control circuitry and/or the battery (shown inFIG.1) and cause the usual problems produced when electrical components are exposed to liquid. The electronic cigarette may thereby be rendered unsafe or inoperable. To address this, the cartomizer30additionally comprises an absorbent element50, having in this example the form of a flat pad of absorbent material disposed inside the cartomizer housing adjacent to the inner surface of the connector31. In particular the absorbent element50is positioned upstream of the atomizer, having regard to the direction of air flow along the air flow channel37through the electronic cigarette when a user inhales on the electronic cigarette. The atomizer40lies between the absorbent element50and the mouthpiece35, with respect to the flow direction along the airflow channel37. The pad50has a central aperture aligned with the central aperture38in the connector31, so that it forms part of the side wall of the air flow path37. Note that the central position of these apertures in this example is merely illustrative; the air flow path may be non-central and/or may comprise more than one air inlet aperture. When positioned in this way, the absorbent material can collect any escaped source liquid in the air flow path37before it reaches the air inlet38, and any escaped source liquid inside the cartomizer housing39before it reaches the connector31. Any collected liquid is absorbed by the absorbent element50, so that the escape of liquid out of the cartomizer is reduced, inhibited or prevented altogether. As an alternative, the absorbent element may be separated from the air flow path37by an intervening wall so that it collects escaped source liquid inside the cartomizer housing only. The absorbent element50should be shaped and positioned to accommodate the required electrical connection from the connector31to the heater. The electrical connection(s) may pass through or around the absorbent element50, for example. FIGS.5A-5Cshow some perspective views of parts of an example electronic cigarette cartomizer configured in a similar manner to theFIG.4example.FIG.5Ashows a wall of a reservoir3defining a space forming part of the air flow path and within which lies an atomizer (not shown, and in this example this is a combined wick-and-heater arrangement such as that described with respect toFIG.3). An air path tube41is joined at one end of the reservoir to define the air flow path from the atomizer to the mouthpiece35. The opposite end of the reservoir is coupled to a connector31which in this example can be considered as an end cap forming an end wall of the cartomizer. The end cap31is configured for mechanical attachment to a power component (not shown), and includes a pair of electrical contacts42to make electrical connection to a battery and control circuit in an attached power component. The parts shown inFIG.5Awould be arranged in an outer cartomizer housing (not shown). FIG.5Bshows a perspective end view of the end cap connector31fitted onto the end of the cartomizer. The circular cross-section of the cartomizer is apparent from this view. The electrical contacts42can be seen, arranged diametrically opposite each other, and spaced apart on either side of a central aperture38being the air inlet for the cartomizer's air flow path. FIG.5Cshows a further perspective view of the end cap connector31, separated from its cartomizer. The connector31is positioned so that its internal face, which in use faces into the interior of the cartomizer, is in view. The connector31comprises a flat circular wall, which forms the end wall of the cartomizer, and an upstanding peripheral wall43around the circular wall. The central aperture38can be seen, defined through the circular wall, and the absorbent element50(shown as a textured surface) can be seen in the base of the connector31against the circular wall. The peripheral wall has a number of protrusions on its outer surface by which the connector31engages with the cartomizer housing and/or reservoir walls. FIGS.6A and6Bshow cross-sectional views through an example end cap connector.FIG.6Ashows the connector31, which is similar to the connector ofFIGS.5A-C. The circular end wall has a central aperture38as an air inlet for the cartomizer. Two electrical contacts42are on the lower surface of the end wall; these may be actual contacts or may be apertures through which contact elements may pass. The annular peripheral wall43extends up from the circular wall (in the depicted orientation) to define a recess inside the end cap connector31. FIG.6Bshows the end cap connector31together with an absorbent element50ready for insertion into the recess inside the connector (as indicated by the arrow). The absorbent element has a disc shape, with a width greater than its thickness, and with a central opening51which aligns with the air inlet aperture in the end cap when the absorbent element50is received in the recess. The width of the absorbent element is substantially the same as the width of the recess so that the absorbent element extends fully across the recess and can capture most if not all incident liquid. The absorbent element50may be pushed fully into the recess so that it lies against the inner surface of the end wall, or may be inserted less far so that there is a gap between the absorbent element and the end wall, for example to allow room for expansion of the absorbent element when wet. The central opening51may be smaller than the air inlet aperture or may be absent altogether, if the absorbent element does not present any significant increase in the resistance to draw when a user inhales through the electronic cigarette. For example, it may be made from a material with a sufficiently open structure that air can pass through the absorbent element with little or no impediment to the inhalation air flow rate. FIGS.7A-7Cshow perspective views of another example end cap connector, absorbent element and cartomizer.FIG.7Ashows a perspective view of a connector31, having a central air inlet aperture38in its end wall as before. A pair of further openings42a(only one properly visible) are formed in the end wall, diametrically opposed about the central aperture38; these allow electrical contact into the cartomizer. FIG.7Bshows a perspective view of an absorbent element50, configured for insertion into the recess in the end cap connector ofFIG.7A. The absorbent element50is shaped as a disc, with a diameter around three times its thickness, and a thickness of about 2.5 mm. These are example dimensions only and other sizes and proportions may be selected according to implementation. A central aperture51aligns with the central aperture38in the connector31when the absorbent element50is inserted into the recess. Additionally, the absorbent element50has a pair of notches52cut into its rim; these are arranged diametrically in order to align with the electrical contact openings42ain the connector31. The notches52may be differently shaped from the approximately square cut-outs shown, and may alternatively comprise holes through the material of the absorbent element50in place of notches. FIG.7Cis a perspective end view of a cartomizer to which the end cap31has been fitted, containing the absorbent element (not visible in this view). Electrical contacts42are shown, aligned with the openings42a. These may be disposed on a separate end plate which covers the end face of the cartomizer, for example. The central air inlet aperture38can be seen. The peripheral side wall43of the end cap is held inside the side walls of the cartomizer30. Although these examples show the absorbent element positioned inside the cartomizer, against or near the inner surface of an end wall component of the cartomizer such as the connector cap, it may alternatively be located on the outer surface of the cartomizer end wall. For example, it may be stuck to the end wall with adhesive, or a peripheral wall may define a recess to receive and hold the absorbent element, perhaps by a friction fit, or one or more retaining latches or clips or other supports may hold the absorbent element in place so that it is not lost when the cartomizer is separated from its power component. Other positions downstream of the atomizer may also be employed. The examples thus far have included an absorbent element in the cartomizer component of an electronic cigarette, but an absorbent element may alternatively or additionally be comprised in a power component of an electronic cigarette. Suitably located, it can be arranged to collect and absorb any liquid that enters the power component via its connector (which is likely a vulnerable part of the power component as regards liquid ingress) before the liquid can reach any electronic or electrical parts. FIG.8shows a schematic representation of an example power component comprising an absorbent element. The power component20comprises an outer housing22which accommodates a battery or cell5(which might be recharged via a charging port52by which the power component can be connected to an external power supply), and control circuitry. This may comprise any or all of a printed circuit board, a microprocessor, a microcontroller, logic gates, switches, and similar hardware items, plus possibly software, configured for controlling the electronic cigarette. This control includes controlling the supply of electrical power from the battery to the heater in a connected cartomizer, plus other control functions depending on the complexity of the electronic cigarette. These electrical items are at risk of damage and/or malfunction if they come into contact with liquid, so the power component further comprises an absorbent element50. This is arranged between the end connector21, by which electrical and mechanical connections are made to a cartomizer, and the electrical items (which may be arranged differently from the depicted configuration, which is purely illustrative). Thus, any source liquid which may have escaped from the reservoir housed in a cartomizer to which the power component is connected, and penetrated the connected connectors31(FIGS.1and4) and21can be collected by the absorbent element and inhibited or prevented from reaching the battery and/or the control circuitry (control electronics). FIG.8does not depict any air flow path for alignment with a cartomizer air flow path (such as the path37inFIG.4), but the absorbent element50and the connector21may include suitable apertures for air flow if the primary air inlet for the electronic cigarette is in the power component (as in theFIG.1example). Also, appropriate openings (apertures, holes, notches) to enable electrical connections to be made may be present. Also, the absorbent element may be placed on the outer side of the connector21rather than adjacent its inner face (for example as discussed above with regard to the cartomizer having an absorbent element on the outer surface of the cartomizer end wall). The absorbent element may have a porous structure to enable it to absorb incident liquid. It may be formed from a soft, flexible, non-rigid or semi-rigid, and possibly resilient, material. These properties will allow a suitably shaped absorbent element to be conveniently tightly fitted into its intended space so that the space can be fully bridged and liquid may be prevented from readily flowing past the absorbent element. The element may be made from any absorbent material, possibly subject to any restrictions from regulatory requirements governing electronic cigarettes. Possible materials include paper, cardboard, cotton, wool, and other synthetic and natural fabric materials. These materials may all be readily formed into a required shape by cutting or stamping, and are readily available in a range of thicknesses. A further alternative is a sponge material. Natural (animal fiber) sponge or synthetic sponge may be used. Example materials for synthetic sponge include cellulose wood fiber and foamed plastic polymers. Low-density polyether, polyester, PVA (polyvinyl acetate), polyethylene and polypropylene may be used, for example. Sponge absorbent elements may be cut or molded into the required shape and size. Other absorbent materials are not excluded, however. Examples include cellulose acetate filter material, cotton wadding, polyester wadding, absorbent materials used in nappies and sanitary towels, rayon, polyurethane, cellulose sponge, and so-called “post office sponge” (a natural, open cell sponge rubber). A material of particular interest for the absorbent element is a porous synthetic fibrous material made from polyolefin fibers comprising a mixture of polypropylene and polyethylene. Any proportion of these two materials may be combined as desired, for example 5% polypropylene and 95% polyethylene; 10% polypropylene and 90% polyethylene; 15% polypropylene and 85% polyethylene; 20% polypropylene and 80% polyethylene; 25% polypropylene and 75% polyethylene; 30% polypropylene and 70% polyethylene; 35% polypropylene and 65% polyethylene; 40% polypropylene and 60% polyethylene; 45% polypropylene and 55% polyethylene; 50% polypropylene and 50% polyethylene; 55% polypropylene and 45% polyethylene; 60% polypropylene and 40% polyethylene; 65% polypropylene and 35% polyethylene; 70% polypropylene and 30% polyethylene; 75% polypropylene and 25% polyethylene; 80% polypropylene and 20% polyethylene; 85% polypropylene and 15% polyethylene; 90% polypropylene and 10% polyethylene; or 95% polypropylene and 5% polyethylene; or within ranges close to these values. This fibrous material has a semi-rigid structure that lends itself favorably to formation of the absorbent element by cutting or stamping to the correct size and shape, and also to drilling for the creation of through-holes such as airflow apertures and electrical contact apertures. Material comprising relatively equal proportions of polypropylene and polyethylene may be used. For example, the material may comprise polypropylene in the range of 40% to 60% and polyethylene in the range of 60% to 40%; or polypropylene in the range of 45% to 55% and polyethylene in the range of 55% to 45%; or polypropylene in the range of 48% to 52% and polyethylene in the range of 52% to 48%; or polypropylene in the range of 49% to 51% and polyethylene in the range of 51% to 49%. Substantially equal proportions of these two materials may be used, so that the material comprises substantially 50% polypropylene and substantially 50% polyethylene. Similar or equal proportions of the polypropylene and polyethylene produce a material which has good hydrophilic properties (it absorbs incident liquid rather than repelling it), and also does not exhibit excessive expansion when it gets wet (i.e. when it has absorbed liquid). Materials formed from less equal proportions of polypropylene and polyethylene are also useful, however. Also, the material may include one or more other materials in addition to polypropylene and polyethylene. These may include the various example absorbent materials discussed above, or may be materials which impart other characteristics to the material, such as a finishing additive comprising nonionic emulsifiers to provide antistatic properties. Such an additive might comprise around 1% of the absorbent material, for example. The material used for the absorbent element may have an absorbency which is sufficient to retain any leaked liquid until it naturally evaporates from the absorbent material, or may act instead to delay the escape to the external environment of any leaked liquid compared to no absorbent material being present. This will depend at least in part on the rate of any leaks compared to the amount and absorbency properties of the absorbent material used. An absorbent material which does not expand too much when wet is useful for the absorbent element. This characteristic means that little or no expansion room needs to be provided within the electronic cigarette to accommodate the absorbent element when wetted. Hence, the inclusion of an absorbent element need not significantly increase the size of the electronic cigarette, and/or a larger volume of absorbent material can be included for a given available space. For example, the absorbent element may be made from an absorbent material which expands when wet to increase its volume in the range of 0% to 50%; or 0% to 40%; or 0% to 30%; or 0% to 20%; or 0% to 10%; or 0% to 5% when fully saturated (i.e. when it cannot absorb any more incident liquid). For example, the substantially 50% polypropylene and 50% polyethylene fibrous material discussed above has been found in tests to expand by less than 3% when fully saturated. The absorbent element may have a flat planar shape, such a round or oval disk or a square or rectangle or other polygon or other regular or irregular shape, depending on the interior cross-section or bore of the part of the electronic cigarette to which it is fitted. As noted, it is useful for the absorbent element to fill the bore where it is installed (i.e. there are no gaps left between the sides of the element and the surrounding wall of the component or other part of the electronic cigarette) so that incident liquid cannot run past the absorbent element and avoid being absorbed. This is not essential however. The absorbent element may have a thickness in the range of 1 mm to 10 mm, for example, although smaller and large thicknesses are not excluded. The thickness chosen will depend on the amount of space available to accommodate the absorbent element, and the absorbency of the material used for the absorbent element; a highly absorbent material may be used with a smaller thickness than a lower absorbency material, for example. The absorbent material used for the absorbent element may have a density in the range of 0.5 g/cm3to 10 g/cm3, such as between 0.5 g/cm3to 2, 3, 4, or 5 g/cm3. For example, a fibrous polypropylene/polyethylene material may have a density of about 0.9 g/cm3. Low density materials minimize the mass added to an electronic cigarette by the inclusion of an absorbent element. The absorbent element may be incorporated as a permanent feature of the component which houses it, or the component may be configured to allow the absorbent element to be removed by the user. For example, the absorbent element might be held in an end cap of a cartomizer or power component (similar to the cap inFIGS.5to7) which is configured to be removable by the user so that the absorbent element can be extracted. This allows the absorbent element to be temporarily removed for drying if it has become saturated, or allows the absorbent element to be replaced. The position of the absorbent element is not limited to those depicted and described thus far. It may be installed in any position or location within the electronic cigarette where it can usefully intercept the passage of liquid leaking from the reservoir and/or atomizer and following a path that will not lead to vaporization in an activated atomizer (a leak flow path). This includes paths leading directly away from the atomizer, and paths that deliver liquid to the atomizer where it can then escape as leakage into the airflow path if not vaporized promptly. To this end, the absorbent element is not limited to the shape of a flat pad, such as the planar disc ofFIGS.6and7. It can be alternatively be installed in a non-flat shape (either by bending or wrapping of a flat but flexible material, or by use of a curved shape formed by molding, for example). This includes wrapping or overlaying a non-flat surface of a part within the electronic cigarette with a sheet of absorbent material. Also, the absorbent element might be formed with one or more depressions or recesses on a surface facing towards the atomizer (i.e. on the downstream side of the absorbent element) which will act as a dish or cup to aid in collecting liquid and holding it for absorption into the absorbent material.FIG.9shows a schematic representation of a cartomizer30in which an absorbent element50located adjacent the connector31has a dished surface50afacing towards the atomizer40. In other words, the absorbent element50is concave on its downstream face. Other positions for an absorbent element can be chosen as required. Absorbent elements in accordance with embodiments can be utilized with any configuration of electronic cigarette, not merely those of a generally elongate structure in which a cartomizer and power component connect end to end as in theFIG.1example. The electronic cigarette may be generally cylindrical or non-cylindrical, elongate or non-elongate, and components may be arranged linearly (end-to-end) or in parallel (side-by-side); other configurations are also included. Parts may be variously distributed between components of the electronic cigarette as desired, and the components may be separable from and reconnectable to one another or may be permanently joined or connected together. For example, the atomizer may be in the same component as the reservoir (as in theFIGS.4and9examples) or may be in a different component; or the control circuitry may be in a different component from the reservoir (as in theFIG.8example) or may be in the same component; or the battery may be in a different component from the reservoir (as in theFIG.8example) or may be in the same component. The absorbent element may usefully be located anywhere within the electronic cigarette or component of the electronic cigarette where it is able to intercept source liquid which is free from the reservoir and not able to be vaporized, and collect that liquid by absorption. For example, the absorbent element may be situated to protect the battery and/or the control electronics or circuitry (such as a PCB or microcontroller) from exposure to source liquid. An absorbent element placed between the atomizer (and/or the reservoir) and the relevant electrical parts can achieve this; in a separable electronic cigarette it may be incorporated into either the cartomizer component or the power component. In other examples, the absorbent element may be located to collect any escaped liquid that would otherwise be likely to flow out of the component in which the reservoir is housed; this includes a component in a connected state or an unconnected state. Hence, the absorbent element might be positioned to collect liquid in the vicinity of a connection joint for coupling the reservoir component to another component such as a power component, or to collect liquid that might leak from inlets and/or outlets of the air flow path. An electronic cigarette or component therefor may comprise a single absorbent element, or may comprise two or more absorbent elements to increase the level of protection from leaks. Multiple elements might be located at different places within the electronic cigarette, such as to intercept liquid on different leak flow paths, or might be stacked along the same leak flow path, either in contact or spaced apart. Absorbent elements made from different materials might be included in the same electronic cigarette. In an alternative, an absorbent element might be positioned downstream of the atomizer where it could collect escaped source liquid in the air flow path to stop the liquid from exiting through the mouthpiece; in which case, the absorbent element may be made from a porous synthetic sponge material made from a mixture of polypropylene and polyethylene in any of the relative proportions described above.FIG.9indicates a possible position for such an absorbent element60, shown in phantom. To this end, a component of an electronic vapor provision device, where the device has a reservoir for storing source liquid, an atomizer for vaporizing source liquid from the reservoir and delivering vapor into an air flow path through the device, and an electrical power supply for providing electrical power to the atomizer, may comprise an absorbent element located to collect source liquid escaped from the reservoir, the absorbent element made from an absorbent material made from a mixture of polypropylene and polyethylene. The absorbent element may be upstream or downstream of the atomizer with respect to the air flow direction along the air flow path. The various embodiments described herein are presented only to assist in understanding and teaching the claimed features. These embodiments are provided as a representative sample of embodiments only, and are not exhaustive and/or exclusive. It is to be understood that advantages, embodiments, examples, functions, features, structures, and/or other aspects described herein are not to be considered limitations on the scope of the invention as defined by the claims or limitations on equivalents to the claims, and that other embodiments may be utilized and modifications may be made without departing from the scope of the claimed invention. Various embodiments of the invention may suitably comprise, consist of, or consist essentially of, appropriate combinations of the disclosed elements, components, features, parts, steps, means, etc., other than those specifically described herein. In addition, this disclosure may include other inventions not presently claimed, but which may be claimed in future. | 44,646 |
11857722 | Throughout the figures, the same reference signs will be assigned to the same or similar components and features. DETAILED DESCRIPTION Various example embodiments will now be described more fully with reference to the accompanying drawings in which some example embodiments are shown. However, specific structural and functional details disclosed herein are merely representative for purposes of describing example embodiments. Thus, the embodiments may be embodied in many alternate forms and should not be construed as limited to only example embodiments set forth herein. Therefore, it should be understood that there is no intent to limit example embodiments to the particular forms disclosed, but on the contrary, example embodiments are to cover all modifications, equivalents, and alternatives falling within the scope. In the drawings, the thicknesses of layers and regions may be exaggerated for clarity, and like numbers refer to like elements throughout the description of the figures. Although the terms first, second, etc. may be used herein to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another. For example, a first element could be termed a second element, and, similarly, a second element could be termed a first element, without departing from the scope of example embodiments. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items. It will be understood that, if an element is referred to as being “connected” or “coupled” to another element, it can be directly connected, or coupled, to the other element or intervening elements may be present. In contrast, if an element is referred to as being “directly connected” or “directly coupled” to another element, there are no intervening elements present. Other words used to describe the relationship between elements should be interpreted in a like fashion (e.g., “between” versus “directly between,” “adjacent” versus “directly adjacent,” etc.). The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments. As used herein, the singular forms “a,” “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises,” “comprising,” “includes” and/or “including,” if used herein, specify the presence of stated features, integers, steps, operations, elements and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components and/or groups thereof. Spatially relative terms (e.g., “beneath,” “below,” “lower,” “above,” “upper” and the like) may be used herein for ease of description to describe one element or a relationship between a feature and another element or feature as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, for example, the term “below” can encompass both an orientation that is above, as well as, below. The device may be otherwise oriented (rotated 90 degrees or viewed or referenced at other orientations) and the spatially relative descriptors used herein should be interpreted accordingly. Example embodiments are described herein with reference to cross-sectional illustrations that are schematic illustrations of idealized embodiments (and intermediate structures). As such, variations from the shapes of the illustrations as a result, for example, of manufacturing techniques and/or tolerances, may be expected. Thus, example embodiments should not be construed as limited to the particular shapes of regions illustrated herein but may include deviations in shapes that result, for example, from manufacturing. For example, an implanted region illustrated as a rectangle may have rounded or curved features and/or a gradient (e.g., of implant concentration) at its edges rather than an abrupt change from an implanted region to a non-implanted region. Likewise, a buried region formed by implantation may result in some implantation in the region between the buried region and the surface through which the implantation may take place. Thus, the regions illustrated in the figures are schematic in nature and their shapes do not necessarily illustrate the actual shape of a region of a device and do not limit the scope. It should also be noted that in some alternative implementations, the functions/acts noted may occur out of the order noted in the figures. For example, two figures shown in succession may in fact be executed substantially concurrently or may sometimes be executed in the reverse order, depending upon the functionality/acts involved. Although corresponding plan views and/or perspective views of some cross-sectional view(s) may not be shown, the cross-sectional view(s) of device structures illustrated herein provide support for a plurality of device structures that extend along two different directions as would be illustrated in a plan view, and/or in three different directions as would be illustrated in a perspective view. The two different directions may or may not be orthogonal to each other. The three different directions may include a third direction that may be orthogonal to the two different directions. The plurality of device structures may be integrated in a same electronic device. For example, when a device structure (e.g., a memory cell structure or a transistor structure) is illustrated in a cross-sectional view, an electronic device may include a plurality of the device structures (e.g., memory cell structures or transistor structures), as would be illustrated by a plan view of the electronic device. The plurality of device structures may be arranged in an array and/or in a two-dimensional pattern. Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which example embodiments belong. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein. Unless specifically stated otherwise, or as is apparent from the discussion, terms such as “processing” or “computing” or “calculating” or “determining” or “displaying” or the like, refer to the action and processes of a computer system, or similar electronic computing device, that manipulates and transforms data represented as physical, electronic quantities within the computer system's registers and memories into other data similarly represented as physical quantities within the computer system memories or registers or other such information storage, transmission or display devices. As disclosed herein, the term “storage medium”, “computer readable storage medium” or “non-transitory computer readable storage medium,” may represent one or more devices for storing data, including read only memory (ROM), random access memory (RAM), magnetic RAM, core memory, magnetic disk storage mediums, optical storage mediums, flash memory devices and/or other tangible machine readable mediums for storing information. The term “computer-readable medium” may include, but is not limited to, portable or fixed storage devices, optical storage devices, and various other mediums capable of storing, containing or carrying instruction(s) and/or data. Furthermore, at least some portions of example embodiments may be implemented by hardware, software, firmware, middleware, microcode, hardware description languages, or any combination thereof. When implemented in software, firmware, middleware or microcode, the program code or code segments to perform the necessary tasks may be stored in a machine or computer readable medium such as a computer readable storage medium. When implemented in software, processor(s), processing circuit(s), or processing unit(s) may be programmed to perform the necessary tasks, thereby being transformed into special purpose processor(s) or computer(s). A code segment may represent a procedure, function, subprogram, program, routine, subroutine, module, software package, class, or any combination of instructions, data structures or program statements. A code segment may be coupled to another code segment or a hardware circuit by passing and/or receiving information, data, arguments, parameters or memory contents. Information, arguments, parameters, data, etc. may be passed, forwarded, or transmitted via any suitable means including memory sharing, message passing, token passing, network transmission, etc. In order to more specifically describe example embodiments, various features will be described in detail with reference to the attached drawings. However, example embodiments described are not limited thereto. In at least one example embodiment, a vaporizing assembly for an aerosol generating system comprises a sheet heating element and a delivery device configured to deliver a liquid aerosol-forming substrate from a liquid storing portion to the sheet heating element. The sheet heating element is spaced apart from the delivery device and is configured to heat the delivered liquid aerosol-forming substrate to a temperature sufficient to volatilize at least a part of the delivered liquid aerosol-forming substrate. The sheet heating element is fluid permeable and comprises a plurality of electrically conductive filaments. As used herein, a sheet heating element comprises a thin, substantially flat, electrically conductive material, such as a mesh of fibers, a conductive film, or an array of heating strips, suitable for receiving and heating an aerosol forming substrate for use in an aerosol generating system. As used herein, “thin” means about 8 micrometers to about 2 millimeters, about 8 micrometers to about 500 micrometers, or about 8 micrometers to about 100 micrometers. In the case of a mesh made up of filaments, the filaments may have a diameter of less than about 40 micrometers. As used herein, “substantially flat” means having a planar profile, such that it can be disposed in the vaporizing assembly spaced apart from the delivery device and receive a jet or spray from the device substantially uniformly across the heating element. However, in some example embodiments, the sheet heating element may be curved in order to optimize the delivery of the substrate, depending on the characteristics of the delivery distribution of the delivery device. Accordingly, the “substantially flat” characteristic of the sheet heating element pertains to the form of the element in its manufacture, but not necessarily to its arrangement in the vaporizing assembly. In at least one example embodiment, the sheet heating element is also in a substantially flat orientation in the vaporizing assembly, spaced and opposed from the delivery device. As used herein, “electrically conductive” means formed from a material having a resistivity of about 1×10−4ohm meters, or less. The sheet heating element comprises a plurality of openings. In at least one example embodiment, the sheet heating element may comprise a mesh of fibers with interstices between them. The sheet heating element may comprise a thin film or plate, optionally perforated with small holes. The sheet heating element may comprise an array of narrow heating strips connected in series. The sheet heating element has a surface area of less than or equal to about 100 square millimeters, allowing the sheet heating element to be incorporated in to a handheld system. The sheet heating element may, have a surface area of less than or equal to about 50 square millimeters. In at least one example embodiment, electrically conductive filaments are arranged in a mesh to form the sheet heating element, having a size ranging from about 160 Mesh US to about 600 Mesh US (+/−10%) (e.g., ranging from about 400 filaments per centimeter to about 1500 filaments per centimeter (+/−10%)). The width of the interstices ranges from about 10 micrometers to about 200 micrometers, or from about 25 micrometers to about 75 micrometers. The percentage of open area of the mesh, which is the ratio of the area of the interstices to the total area of the mesh, ranges from about 25 percent to about 56 percent. The mesh may be formed using different types of weave or lattice structures. In at least one example embodiment, the electrically conductive filaments consist of an array of filaments arranged parallel to one another. In at least one example embodiment, an electrically conductive film or plate may form the sheet heating element. The film or plate may be made of metal, conductive plastic, or other appropriate conductive material. In at least one example embodiment, the plate of film is perforated with holes that have a size on the order of interstices as described in the mesh embodiment above. In at least one example embodiment, narrow heating strips may be combined in an array to form the sheet heating element. The smaller the width of the heating strips in an array, the more heating strips may be connected in series in the sheet heating element of the present invention. When using smaller width heating strips that are connected in series, the electric resistance of their combination into the sheet heating element is increased. The delivery device comprises an inlet and an outlet. The delivery device is configured to receive a liquid aerosol forming substrate at an inlet and to output, at an outlet, an amount of the liquid aerosol forming substrate to be delivered to the sheet heating element. The sheet heating element is configured to heat the delivered liquid aerosol-forming substrate to a temperature sufficient to volatilize at least a part of the delivered liquid aerosol-forming substrate. The sheet heating element is spaced apart from the delivery device. As used herein, “spaced apart” means that the vaporizing assembly is configured to deliver the liquid aerosol-forming substrate from the delivery device via an air gap to the sheet heating element. Spaced apart also means that the delivery device and the sheet heating element are not coupled by a tubing segment for leading flow of the liquid aerosol forming substrate from the delivery device to the heating element. Spaced apart may also mean that the delivery device and the sheet heating element are provided as individual members separated from each other by an air gap. The term spaced apart includes an integral combination of the delivery device and the sheet heating element into a combined component as long as the liquid aerosol-forming substrate has to pass through an air gap within this combined component immediately before being heated by the sheet heating element. By providing the sheet heating element spaced apart from the delivery device, the amount of liquid aerosol forming substrate delivered to the heating element may be better controlled compared to a vaporizer having a tubing segment configured to lead flow of the liquid aerosol forming substrate from the delivery device to the heating element. Capillary actions due to use of a tubing segment may be avoided which might otherwise, for example, give rise to movement of liquid between the heating element and the delivery device. When passing the air gap the delivered amount of the liquid aerosol-forming substrate may be transformed into a jet of droplets before hitting the surface of the sheet heating element. Thus, a uniform distribution of the delivered amount of the liquid aerosol forming substrate on the sheet heating element may be enhanced, leading to better controllability and repeatability of generating an aerosol with a desired (or, alternatively predetermined) amount of vaporized aerosol forming substrate per inhalation cycle. The operating temperature of the sheet heating element may range from about 120 degrees Celsius to about 210 degrees Celsius, or from about 150 degrees Celsius to about 180 degrees Celsius. The sheet heating element comprises a plurality of electrically conductive filaments. In at least one example embodiment, the sheet heating element is a mesh heating element, comprising the plurality of electrically conductive filaments. The plurality of electrically conductive filaments forms a mesh of the mesh heating element. The mesh is heated by applying electric power to the plurality of electrically conductive filaments. The sheet heating element may comprise a plurality of filaments which can be made of a single type of fibers, such as resistive fibers, as well as a plurality of types of fibers, including capillary fibers and conductive fibers. The electrically conductive filaments may comprise any suitable electrically conductive material. Suitable materials include but are not limited to: semiconductors such as doped ceramics, electrically “conductive” ceramics (such as, for example, molybdenum disilicide), carbon, graphite, metals, metal alloys and composite materials made of a ceramic material and a metallic material. Such composite materials may comprise doped or undoped ceramics. Examples of suitable doped ceramics include doped silicon carbides. Examples of suitable metals include titanium, zirconium, tantalum and metals from the platinum group. Examples of suitable metal alloys include stainless steel, constantan, nickel-, cobalt-, chromium-, aluminium- titanium- zirconium-, hafnium-, niobium-, molybdenum-, tantalum-, tungsten-, tin-, gallium-, manganese- and iron-containing alloys, and super-alloys based on nickel, iron, cobalt, stainless steel, Timetal®, iron-aluminium based alloys and iron-manganese-aluminium based alloys. Timetal® is a registered trade mark of Titanium Metals Corporation. The filaments may be coated with one or more insulators. The electrically conductive filaments made be formed of 304, 316, 304L, and 316L stainless steel, and graphite. The electrical resistance of the plurality of electrically conductive filaments of the mesh heating element may range from about 0.3 Ohms to about 4 Ohms. In at least one example embodiment, the electrical resistance of the plurality of electrically conductive filaments ranges from about 0.5 Ohms to about 3 Ohms, or about 1 Ohm. The electrical resistance of the plurality of electrically conductive filaments is at least an order of magnitude, or at least two orders of magnitude, greater than the electrical resistance of electrical contact portions of the mesh heating element. This ensures that the heat generated by passing current through the mesh heating element is localized to the plurality of electrically conductive filaments. The electrically conductive filaments may define interstices between the filaments and the interstices may have a width ranging from about 10 micrometers to about 100 micrometers. In at least one example embodiment, the filaments give rise to capillary action in the interstices, so that liquid to be vaporized is drawn into the interstices thereby increasing the contact area between the heater assembly and the liquid. The mesh of electrically conductive filaments may also be characterized by its ability to retain liquid. In at least one example embodiment, the mesh heating element comprises at least one filament made from a first material and at least one filament made from a second material different from the first material. This may be beneficial for electrical or mechanical reasons. In at least one example embodiment, one or more of the filaments may be formed from a material having a resistance that varies significantly with temperature, such as an iron aluminum alloy. This allows a measure of resistance of the filaments to be used to determine temperature or changes in temperature. This can be used in a puff detection system and for controlling temperature of the heating element to keep it within a desired temperature range. The sheet heating element is fluid permeable. As used herein, fluid permeable in relation to a sheet heating element means that the aerosol forming substrate, in a gaseous phase and possibly in a liquid phase, can readily pass through the sheet heating element. Including a fluid permeable heater may enhance surface area and improve vaporization. In addition, a fluid permeable heater may also allow improved mixing of vaporized liquid aerosol forming substrate with an air flow. In at least one example embodiment, the sheet heating element is substantially flat. As used herein, substantially flat means formed in a single plane and not wrapped around or other conformed to fit a curved or other non-planar shape. A flat heating element can be easily handled during manufacture and provides for a robust construction. In at least one example embodiment, where the sheet heating element is a mesh heating element, the mesh heating element may comprise a plurality of mesh layers stacked in an intended direction of airflow through the mesh heating element. Each mesh layer can be easily handled during manufacture and provides for a robust construction. Moreover, the stacked mesh layers improve vaporization of the liquid aerosol forming substrate. In at least one example embodiment, the sheet heating element has a square geometry. The sheet heating element may have a heating area with a square geometry with dimensions of each side within a range of about 3 millimeters to about 7 millimeters, or from about 4 millimeters to about 5 millimeters. The sheet heating element may comprise a plurality of narrow heating strips arranged spaced apart from each other on a plane. The heating strips are in a rectangular shape and spatially arranged substantially parallel to each other. The heating strips may be electrically connected in series. By appropriate spacing of the heating strips, a more even heating may be obtained compared with for example where a sheet heating element having the same area is used. In at least one example embodiment, the delivery device is configured to deliver a desired (or, alternatively predetermined) amount of the liquid aerosol-forming substrate to the sheet heating element upon performing one activation cycle. The desired (or, alternatively predetermined) amount of the liquid aerosol-forming substrate is delivered via the air gap from the delivery device to the sheet heating element. By depositing the liquid aerosol-forming substrate onto the sheet heating element directly, the liquid aerosol-forming substrate may remain substantially in its liquid state until it reaches the sheet heating element, although small droplets near the element may aerosolize before contacting the sheet heating element. The desired (or, alternatively predetermined) amount of the liquid aerosol-forming substrate may be an amount equivalent to produce a desired volume of aerosol in the sheet heating element. In at least one example embodiment, the delivery device is configured to spray the liquid aerosol forming substrate onto the sheet heating element as a spraying jet with a size and shape appropriate to the geometry of the sheet heating element. The delivery device may be configured to spray the liquid aerosol forming substrate onto the sheet heating element to cover at least 90 percent or at least 95 percent, of an upstream surface of the sheet heating element facing the delivery device. The delivery device may comprise an atomizer spray nozzle, in which case a flow of air is supplied through the nozzle by the action of puffing, which creates a pressurized air flow that will mix and act with the liquid creating an atomized spray in the outlet of the nozzle. Several systems including nozzles that work with small volumes of liquid are available, in sizes that meet the requirements to fit in small portable devices. Another class of nozzle that may be used is an airless spray nozzle, sometimes referred to as a micro-spray nozzle. Such nozzles create micro spray cones in very small sizes. With this class of nozzles, the airflow management inside the device, namely inside the mouth piece, surrounds the nozzle and the heating element, flushing the heating element surface towards the outlet of the mouth piece, including a turbulent air flow pattern of the aerosol exiting the mouth piece. For either class of nozzle, the distance of the air gap between the delivery device and the sheet heating element facing the nozzle, is within a range of from about 2 millimeters to about 10 millimeters, or from about 3 millimeters to about 7 millimeters. Any type of available spraying nozzles may be used. Airless nozzle 062 Minstac from manufacturer “The Lee Company” is an example of a suitable spray nozzle. In at least one example embodiment, the delivery device comprises a micropump configured to pump the liquid aerosol-forming substrate from a liquid storage portion. By using the micropump instead of a capillary wick or any other passive medium to draw liquid, only the actually required amount of liquid aerosol-forming substrate may be transported to the sheet heating element. Liquid aerosol-forming substrate may only be pumped upon demand, for example in response to a puff. The micropump may allow on-demand delivery of liquid aerosol-forming substrate at a flow rate of about 0.7 microliters per second to about 4.0 microliters per second for intervals of variable or constant duration. A pumped volume of one activation cycle may be around 0.5 microliters in micropumps working within a pumping frequency ranging from about 8 hertz to about 15 hertz. In at least one example embodiment, the pump volume in each activation cycle, as a dose of liquid aerosol-forming substrate per puff, may be of 0.4 microliters to about 0.5 microliters. The micropump may be configured to pump liquid aerosol-forming substrates that have a relatively high viscosity as compared to water. The viscosity of a liquid aerosol-forming substrate may be in the range from about 15 millipascal seconds to about 500 millipascal seconds, or in the range from about 18 millipascal seconds to about 81 millipascal seconds. In some example embodiments, the delivery device may comprise a manually operated pump for pumping the liquid aerosol-forming substrate from a liquid storage portion. A manually operated pump reduces the number of electric and electronic components and thus, may simplify the design of the vaporizing assembly. In at least one example embodiment, a vaporizing assembly suitable for an aerosol generating system comprises a sheet heating element and a delivery device configured to deliver a liquid aerosol-forming substrate from a liquid storing portion to the sheet heating element. The sheet heating element is spaced apart from the delivery device and is configured to heat the delivered liquid aerosol-forming substrate to a temperature sufficient to volatilize at least a part of the delivered liquid aerosol-forming substrate. In at least one example embodiment, an aerosol generating system comprises the vaporizing assembly and an operation detection unit configure to detect an operation to initiate aerosol generation. The operation detection unit may include a puff detection system, e.g. a puff sensor. In at least one example embodiment, the operation detection unit may include an on-off button, e.g. an electrical switch. The on-off button may be configured to trigger activation of at least one of the micropump and the heating element when being pressed down. A duration of the on-off button being pressed down may determine the duration of activation of at least one of the micropump and the heating element, e.g. by constantly pressing down the on-off button during a puff. In at least one example embodiment, the aerosol generating system further comprises a control unit which is configured to activate the delivery device with a desired (or, alternatively predetermined) time delay after activating the heating element in response to a detected user operation. Upon activation, such as using the on-off button or the puff sensor, the control unit may activate the sheet heating element first, and then, after delay of about 0.3 seconds to about 1 seconds, or from 0.5 seconds to about 0.8 seconds, may activate the delivery device. The duration of activation may be fixed or may correspond to an action like pressing the on-off button or puffing as, for example, detected by the operation detection unit. In at least one example embodiment, the control unit may be configured to activate the sheet heating element and the delivery device simultaneously. In at least one example embodiment, the aerosol generating system may comprise a device portion and a replaceable liquid storage portion. The device portion may comprise a power supply and the control unit. The power supply may be any type of electric power supply, typically a battery. The power supply for the delivery device may be different from the power supply of the sheet heating element or may be the same. The aerosol generating system may further comprise electric circuitry connected to the vaporizing assembly and to the power supply which is an electrical power source. The electric circuitry may be configured to monitor the electrical resistance of the sheet heating element, and to control the supply of power to the sheet heating element dependent on the electrical resistance of the sheet heating element. The electric circuitry may comprise a controller with a microprocessor, which may be a programmable microprocessor. The electric circuitry may comprise further electronic components. The electric circuitry may be configured to regulate a supply of power to the vaporizing assembly. Power may be supplied to the vaporizing assembly continuously following activation of the system or may be supplied intermittently, such as on a puff-by-puff basis. The power may be supplied to the vaporizing assembly in the form of pulses of electrical current. The power supply may be a form of charge storage device such as a capacitor, a super-capacitor, or hyper-capacitor. The power supply may require recharging and may have a capacity that allows for the storage of enough energy; for example, the power supply may have sufficient capacity to allow for the continuous generation of aerosol for a period of around six minutes or for a period that is a multiple of six minutes. In at least one example embodiment the power supply may have sufficient capacity to allow for a desired (or, alternatively predetermined) number of puffs or discrete activations of the vaporizing assembly. For allowing air to enter the aerosol generating system, a wall of the housing of the aerosol generating system, such as a wall opposite the vaporizing assembly or a bottom wall, is provided with at least one semi-open inlet. The semi-open inlet allows air to enter the aerosol generating system, but does not allow air or liquid to leave the aerosol generating system through the semi-open inlet. A semi-open inlet may be a semi-permeable membrane, permeable in one direction only for air, but is air- and liquid-tight in the opposite direction. A semi-open inlet may also be a one-way valve. In at least one example embodiment, the semi-open inlets allow air to pass through the inlet only if specific conditions are met, for example a reduced and/or minimum depression in the aerosol generating system or a volume of air passing through the valve or membrane. The liquid aerosol-forming substrate is a substrate that releases volatile compounds that can form an aerosol. The volatile compounds may be released by heating the liquid aerosol-forming substrate. The liquid aerosol-forming substrate may comprise plant-based material. The liquid aerosol-forming substrate may comprise tobacco. The liquid aerosol-forming substrate may comprise a tobacco-containing material containing volatile tobacco flavor compounds, which are released from the liquid aerosol-forming substrate upon heating. The liquid aerosol-forming substrate may alternatively comprise a non-tobacco-containing material. The liquid aerosol-forming substrate may comprise homogenized plant-based material. The liquid aerosol-forming substrate may comprise homogenized tobacco material. The liquid aerosol-forming substrate may comprise at least one aerosol-former. The liquid aerosol-forming substrate may comprise other additives and ingredients, such as flavorants. The aerosol generating system may be an electrically operated system. In at least one example embodiment, the aerosol generating system is portable. The aerosol generating system may have a size comparable to a cigar or cigarette. The system may have a total length ranging from about 45 millimeters to about 160 millimeters. The system may have an external diameter ranging from about 7 millimeters to about 25 millimeters. At least one example embodiment relates to a method for generating an aerosol. The method comprises heating a sheet heating element; and delivering, by a delivery device spaced apart from the sheet heating element, a liquid aerosol-forming substrate to the sheet heating element. The delivered liquid aerosol-forming substrate is heated by the sheet heating element to a temperature sufficient to volatilize at least a part of the delivered liquid aerosol-forming substrate. Features described in relation to one aspect may equally be applied to other aspects of the invention. In at least one example embodiment, as shown inFIG.1, a vaporizing assembly1comprises a sheet heating element2and a delivery device3incorporated into a common housing10. The delivery device3includes a micropump6and a spray nozzle5connected by a tubing segment12. The micropump6is configured to receive, via the tubing segment11, a liquid aerosol forming substrate from a replaceable liquid storing portion8. The delivery device3is spaced apart from the mesh heater element2. The delivery device3and the mesh heater element2are separated by an air gap having a length D between an outlet5A of the spray nozzle5and the upstream surface2A of the sheet heating element2facing the spray nozzle5. The spray nozzle5is configured to receive an amount of the liquid aerosol forming substrate pumped from the micropump6via tubing segment12and to spray the amount of liquid aerosol forming substrate as a spraying jet4S onto the upstream surface2A of the sheet heating element2. The spray nozzle5is configured to generate the spraying jet4S such that the amount of liquid aerosol-forming substrate is completely received by the sheet heating element2and covers the entire upstream surface2A of the sheet heating element2. The housing10comprises an air inlet4allowing air15to pass from outside the housing10into the vaporizing assembly1towards the upstream surface2A of the sheet heating element2. The sheet heating element2is configured to allow the air15that enters from air inlet4to pass towards a downstream surface2B of the sheet heating element2opposite from the spray nozzle5. Having passed through the sheet heating element2, the air15combines with the aerosol forming substrate vaporized by the sheet heating element2to form an aerosol16. In at least one example embodiment, as shown inFIG.2, a spraying jet is generated by a vaporizing assembly. The spraying jet4S output from the outlet5A of the spray nozzle5of the vaporizing assembly illustrated inFIG.1has a size and shape fitted to the geometry of the upstream surface2A of the sheet heating element2. The upstream surface2A has a square shape. The spraying jet4S exhibits substantially the same square shape. The size of the spraying jet4S arriving at the upstream surface2A is the same as the size of the upstream surface2A. In at least one example embodiment, as shown inFIG.3, an aerosol generating system20comprises the vaporizing assembly1as illustrated inFIG.1and is configured to generate a spraying jet as shown inFIG.2. Moreover, the aerosol generating system20comprises a liquid storing portion embodied by a replaceable container8, an electronic control unit9, a battery unit13, wiring components14for electrically connecting the battery unit13, the electronic control unit9and the electrically driven components of the vaporizing assembly1, i.e. the sheet heating element2and the micropump6. A replaceable mouth piece17having an air flow outlet18is coupled to the housing10. Various modifications and variations of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are apparent to those skilled in the mechanical arts, electrical arts, and aerosol generating article manufacturing or related fields are intended to be within the scope of the following claims. | 37,610 |
11857723 | DETAILED DESCRIPTION Devices and methods for delivering air to patients are provided herein. In certain embodiments, these devices and methods provide improved delivery of oxygen to a patient in need of artificial ventilation. U.S. Pat. No. 10,124,136 describes certain devices for delivering air to a patient utilizing a dual impeller system. The present disclosure provides improved devices and methods for delivery of oxygen to patients. Both manual and electronic systems are provided herein. In one aspect, as shown inFIGS.1A-5B, a device100for delivering air to a patient in need of artificial ventilation is provided. The device100includes a first portion102and a second portion104. The first portion102has a first airflow inlet106and a sensor116that is configured to sense airflow provided to the first portion102. The first portion102defines a first airflow path, including at least the first airflow inlet106. In certain embodiments, the first airflow path further includes a first airflow outlet108. The second portion104has a second airflow inlet110, an impeller118, and a second airflow outlet112for communicating airflow to the patient. The second portion104defines a second airflow path, including at least the second airflow inlet110and the second airflow outlet112. The device100further includes means for coupling the first portion102and the second portion104, such that the sensor116sensing airflow in the first portion drives corresponding movement of the impeller118. The impeller118is configured to impel air through the second airflow inlet110and out of the second airflow outlet112to the patient, upon movement of the impeller118. In certain embodiments, the first and second airflow paths are substantially not in fluid communication. Thus, the device100is configured such that a user can exhale, or otherwise provide air, into the first airflow inlet106to effectuate movement of the impeller118that impels air from the surrounding atmosphere through the second portion104of the device and out through the second airflow outlet112to the patient. Moreover, because the airflow paths may not be in fluid communication (i.e., are not directly connected), the risk of contamination from the user to the patient is minimized, as the exhaled air is not provided directly to the patient. Instead, air from the atmosphere (which beneficially contains a higher volume of oxygen than exhaled air) is provided to the patient. The means for coupling the first portion102and the second portion104may be any suitable means that would be understood by one of ordinary skill in the art, including various mechanical and electronic couplings. As used herein, the term “couples” and “coupling” are used broadly and refers to components being directly or indirectly connected to one another via any suitable fastening, connection, or attachment mechanism. In some embodiments, as shown inFIGS.1A-5B, the means for coupling the first portion102and the second portion104includes a controller114(e.g., microcontroller) that receives input from the sensor116and directs operation of the impeller118, such as via a motor124. In certain embodiments the first and second portions102,104are contained within a single external housing120. The housing120may be configured such that the first and second airflow paths are not in fluid communication. In other embodiments, the first and second portions102,104may each include a separate housing that defines their respective airflow path, and the two housings may be coupled to one another. That is, the housings of the first and second portions102,104may share one or more common walls or may be wholly separate from one another. The housing120illustrated inFIGS.1-5integrally forms both the first and second portions102,104; however, it should be understood that any suitable configuration, size and shape of the housings may be employed. The airflow inlets and outlets may be formed integrally with or coupled to the housing(s) of the first and second portions. The airflow inlets and outlets may have any suitable size and shape. For example, the inlets and outlets may be provided in the form of spouts, tubes, openings, vents, channels, or other suitable configurations. Additionally, the inlets and outlets may optionally include threads, flanges, or other suitable attachment means for coupling the inlet or outlet to an external apparatus, such as an bag valve mask, a respiratory mask150(as shown inFIGS.5A-5B), and/or an oxygen tank connector. For example, the second airflow outlet112of the second portion104of the device100may be configured for coupling to a respiratory mask150or pocket ventilator that is configured to fit over a patient's mouth. For example, the first airflow inlet106of the first portion102of the device100may be configured for coupling to a mechanically driven air source, such as a bag valve. For example, the second airflow inlet110of the second portion104of the device100may be configured for coupling to an oxygen tank, such as via an oxygen tube. In other embodiments, the second airflow inlet110is open to the atmosphere. In some embodiments, the second portion104contains a filter configured to filter air impelled through the second airflow inlet110. For example, the filter may be a screen or mesh, or a porous material designed to trap entrained particulate matter, keeping it from being introduced into the patient's lungs. The sensor116may be any suitable sensor that is effective at sensing airflow of a rescuer's breath or other airflow traveling through the first airflow path. For example, the sensor116may be a sensor capable of sensing volumetric flow rate of the airflow, or a proxy therefor, traveling through the first airflow path. That is, the sensor may be configured to sense the intensity of the rescuer breath being delivered to the device. In certain embodiments, the sensor116is a pressure sensor, e.g., an air pressure sensor. The sensor may also include an anemometer or a switch that is triggered by a mechanical component that moves with airflow (e.g., an electromechanical, optical or magnetic switch). In certain embodiments, the device is configured such that the corresponding movement of the impeller118is determined by the volumetric flow rate of the airflow sensed by the sensor116. That is, the device may be configured such that the sensor senses the amount, intensity, timing and/or pattern of breath or other airflow provided to the first airflow path, and then generates a corresponding airflow in the second airflow path, to mimic the breathing in the first airflow path to the patient. Thus, a first responder or other medically trained personnel may provide rescue breathing to the first airflow path, such that corresponding airflow is delivered to the patient, without cross-contamination of the airflow paths. In certain embodiments, the device is configured such that the corresponding movement of the impeller is initiated within about 200 to about 500 milliseconds, or less, of the sensor sensing airflow in the first portion. For example, a controller (e.g., microcontroller) may provide essentially immediate action of the impeller in response to the sensor sensing the breath or airflow in the first airflow path. In certain embodiments, the device contains a motor124configured to drive the impeller in response to the sensor sensing airflow in the first portion. For example, the device may be configured such that the motor is stopped within about 200 to about 500 milliseconds, or less, of the sensor failing to sense airflow in the first portion, when the motor is running. For example, the controller and motor may have any suitable design and configuration. In some embodiments, the motor is a drum motor having a maximum rotational speed of about 30,000 rpm. In certain embodiments, the motor is designed to accelerate quickly enough to deliver sufficient air volume at a sufficient pressure to inflate the patient's lungs within 1 to 2 seconds and also to decelerate quickly enough to allow the elastic recoil of the patient's lungs to naturally exhaust the air. If the impeller were to keep moving, it would prevent the air in the patient's lungs from being exhaled before the delivery of the next breath. Therefore, the motor may be able to decelerate from max speed to zero rpm within about 1 second. The controller may be suitable to facilitate operation of the motor in response to the sensor sensing airflow in the first portion. The device may also include a power source, such as batteries, and a power switch122for turning the device on and off. Any suitable impeller (e.g., rotor) designs may be used in the present devices100. The impeller may be of any size, shape, and design suitable for providing the desired air intake through the second airflow inlet110and delivering the air out of the second airflow outlet112to the patient. Thus, in the second portion104, any suitable impeller118that is capable of pulling in or impelling air through the second airflow path upon rotation or other movement of the impeller118may be used. Impellers having various fin designs may be used in the presently described devices100. The fins of the impeller118may be angled or otherwise configured to achieve the desired inflow of air in response to movement of the second impeller118. In some embodiments, the impeller118has a squirrel cage fan design. While the device100is generally described with reference to impeller118throughout the disclosure, it should be understood that alternative air delivery mechanisms may be substituted for, or used in addition to, the impeller118. For example, a motor-driven piston or bellow could be used instead of the impeller. In certain embodiments, in addition to the above-described functionality utilizing a manual breathing or sensed-breathing/airflow mode, the device100also has an automatic mode, upon activation of which the device is configured to serially activate the impeller for a predetermined duration, to deliver a predetermined series of air pulses from the outlet to the patient. For example, the automatic mode may be programmed in accordance with recommending rescue breathing patterns. For example, the automatic mode may be configured to run the motor, and therefore provide a rescue breath to the patient, for a duration of 1 second, every 5 seconds. The automatic mode may provide these rescue breaths continuously until the mode is terminated or for a predetermined number of breaths. A single device may provide more than one programmed automatic modes, for various rescue breathing situations (e.g., child, adult, continuous). Thus, in use in the sensed-breathing mode, a rescuer may exhale air or squeeze a bag mask to propel air through the first airflow path of the first portion102of the device100. This exhaled air is measured by the sensor116, which translates into motion of the second impeller118. Motion of the second impeller results in air from the attached air source (e.g., atmosphere or another oxygen supply) being pulled into the second portion104and expelled from the outlet112, and into an attached mask or patient mouth. In another aspect, a second design of a device200for delivering air to a patient, is provided. As illustrated inFIGS.6and7, device200includes a housing220, a first portion202associated with the housing220and having a first airflow inlet206and an expandable bladder203(e.g., elastic bladder) configured to expand within the housing in response to airflow from the first airflow inlet206filling the expandable bladder203, the first portion202defining a first airflow path. The housing220may be formed of a suitable rigid material that is effective to maintain its inner volume, while the expandable bladder203may be formed of a suitable elastic or other material or design that allows for expansion and retraction of the bladder within the housing220. The device200also includes a second portion204associated with the housing220and having a second airflow inlet210, and an outlet212for communicating airflow to a patient, the second portion204defining a second airflow path within the housing220. The device200is configured such that upon expansion of the expandable bladder203within the housing220, air within the second airflow path is forced out of the outlet212to the patient, via displacement of the air within the second airflow path out of the outlet212. Air is replenished in the second airflow path via inlet210upon retraction of the expandable bladder203. In certain embodiments, the first and second airflow paths are substantially not in fluid communication. In certain embodiments, the second airflow inlet210is an aperture in a wall of the housing220. In some embodiments, as shown inFIG.6, the aperture has a one-way valve therein, to reduce airflow out of the housing via the aperture. In certain embodiments, the second portion204contains a filter configured to filter air that enters through the second airflow inlet210. In certain embodiments, as shown inFIG.6, the outlet212is configured for coupling to a respiratory mask250. In certain embodiments, the first airflow inlet206is configured for coupling to a removable mouthpiece. In certain embodiments, the first airflow inlet206is configured for coupling to a mechanically driven air source. Thus, this device200design may provide a mechanical alternative to the electronic design described-above, allowing for the provision of rescue breathing without cross-contamination in situations in which a powered device may not be suitable (e.g., remote or long term first aid kits). The components of the devices100,200described herein may be formed from any suitable materials or combination of materials. For example, the housings, impeller, and mechanical coupling may be formed from suitable materials such as plastics and metals. In certain embodiments, the device100,200is configured for one-time, disposable use. In other embodiments, the device100,200is configured to be reusable and can be sanitized without harming the device components. In other aspects, methods for delivering air to a patient are provided. For example, the methods may include providing air to the airflow inlet of a device100having any configuration described herein to be sensed by the sensor and cause movement of the impeller, such that air is impelled through the second airflow inlet and out of the outlet to the patient. For example, the air may be provided to the first airflow inlet of the device via rescue breathing or a mechanically driven air source coupled to the first airflow inlet of the first portion102. In certain embodiments, methods for delivering air to a patient involve providing a device100as described herein, including any combination of features described herein, and then providing air to the airflow inlet of the device to move the impeller, such that air is impelled through the second airflow inlet and out of the outlet to the patient. In other embodiments, methods for delivering air to a patient involve providing a device200as described herein, including any combination of features described herein, and then providing air to the airflow inlet of the device to expand the expandable bladder within the housing, such that air within the second airflow path is forced out of the outlet to the patient. In further aspects, kits are provided, including a device100,200having any configuration described herein and a respiratory mask150,250configured for attachment to the outlet of the second portion112,212of the device100,200and/or a removable mouthpiece configured for attachment to the first airflow inlet106,206. Thus, the presently described devices and methods beneficially provide air to a patient via a rescuer exhaling (or pumping a bag valve, etc.), while reducing the risk of contamination between the patient and rescuer, due to the exhaled air from the medical personnel being directed away from the patient, while clean air from the atmosphere or another oxygen supply is inhaled by the patient. Because the exhaled air from the rescuer contains increased carbon dioxide, as compared to atmospheric air, the patient receives more oxygen than as compared to during mouth-to-mouth resuscitation, at a time when oxygen intake is critical. Moreover, the barrier between the two portions of the device (i.e., the portion that the rescuer contacts and the portion that the patient contacts) limits the potential exposure of the rescuer to regurgitation from the patient. Further, the device of the present disclosure is compact and simple to use, such that it may be easily transported by medical personnel into the field and/or may be provided at first aid stations/kits at various locations, such as at emergency stations in workplaces. While the disclosure has been described with reference to a number of example embodiments, it will be understood by those skilled in the art that the disclosure is not limited to such disclosed embodiments. Rather, the disclosed embodiments can be modified to incorporate any number of variations, alterations, substitutions, or equivalent arrangements not described herein, but which are commensurate with the spirit and scope of the disclosure. | 17,249 |
11857724 | DETAILED DESCRIPTION Hereinafter, a CPAP apparatus according to an embodiment of the present disclosure will be described in detail with reference to the accompanying drawings. Note that in the drawings, the same reference signs indicate the same or corresponding portions. (Configuration of Apparatus) FIG.1is a schematic diagram for explaining a configuration of a CPAP apparatus10according to the embodiment of the present disclosure.FIG.2is a cross-sectional view for explaining the configuration of the CPAP apparatus10according to the embodiment of the present disclosure.FIG.1shows an overview when the CPAP apparatus10is used for a patient. When the CPAP apparatus10is used for a patient, a mask30to be worn by the patient and a hose20for delivering air from the CPAP apparatus10to the mask30are required. The hose20is attachable to and detachable from the CPAP apparatus10. As shown inFIG.1, the mask30is applied and fixed so as to cover the nose of the patient. Note that as the mask30, a mask having a shape or a structure suitable for the patient can be selected from among various types, and a shape and a structure shown inFIG.1are an example. The CPAP apparatus10is provided with a display unit11for displaying a state and an operation method of the apparatus, and the like, a plurality of operation buttons12, and a connection portion13for connecting the hose20. The connection portion13configures an exhaust outlet, and the hose20configures an air passage member whose one end communicates with the exhaust outlet. The display unit11is configured with, for example, an LCD, but may be a seven-segment LED, an organic EL display, or the like. Further, the operation buttons12may not necessarily be a switch having a physical shape as shown in the figure, and may be a touch panel or the like provided on a display surface of the LCD. The CPAP apparatus10further has a structure to deliver air to the mask30. Note that inFIG.2, for simplicity of explanation, the structure is simplified and a structure for delivering air is shown on a right side of the display unit11and the operation button12. Therefore, arrangement of the display unit11, the operation button12, and the structure for delivering air in the CPAP apparatus10is not limited to the arrangement shown inFIG.2. An air supply unit15is provided inside a housing14of the CPAP apparatus10in order to deliver air from the connection portion13to the hose20. A fan16is provided in the air supply unit15, and the fan16is driven by a motor17. The air supply unit15drives the fan16, so that air in the housing14is taken from a lower portion of the air supply unit15as indicated by the arrow inFIG.2, and is expelled from the connection portion13to the hose20. Also, the housing14is provided with an intake port18serving as an intake inlet, and air is taken into the housing14from the outside via the intake port18. The CPAP apparatus10may be provided with a silencer (not shown) in the air supply unit15. The silencer is mounted near an air flow outlet of the air supply unit15, and plays a role of reducing outflow noise of air flowing out from the air supply unit15and passing through the air flow outlet. Further, the silencer can utilize a space from the intake port18to an inlet of the fan16, so that a silencing effect can be exhibited. Furthermore, the CPAP apparatus10includes a control board19on which circuits for performing display control of the display unit11, reception of an operation of the operation buttons12, control of the motor17for rotating the fan16, and the like are mounted.FIG.3is a block diagram for explaining a configuration of the control board19of the CPAP apparatus10according to the embodiment of the present disclosure. The control board19includes a CPU191for executing a program, a ROM/RAM192, and a motor driving unit193as main constituent elements. The ROM/RAM192includes a ROM for storing data in a nonvolatile manner, and a RAM for storing data generated by execution of the program by the CPU191or data input by using the operation buttons12. The respective constituent elements of the control board19are connected to each other with a data bus. Processing in the CPU191is implemented by each piece of hardware and software executed by the CPU191. Such software is stored in advance in the ROM/RAM192. The display control of the display unit11, the reception of the operation of the operation buttons12, the control of the motor17for rotating the fan16, and the like are also implemented by the software. An AC adapter21for supplying electric power is connected to the control board19, and a pressure sensor22and a flow rate sensor23are also connected to the control board19. The pressure sensor22is a sensor for measuring a pressure of air expelled by the air supply unit15. In addition, the pressure sensor22measures a pressure in an air flow path (air passage) including the CPAP apparatus10and an air passage member (hose20) that communicates with an exhaust outlet (connection portion13), so that a pressure of air that varies depending on respiration of a patient can be measured. The flow rate sensor23is a sensor for measuring a flow rate of air between the CPAP apparatus10and another end of the air passage member (hose20). In addition, the flow rate sensor23can measure a flow rate of air that varies depending on respiration of a patient in order to measure a flow rate in the closed air flow path (including the patient wearing the mask30located at the other end of the hose20) including the CPAP apparatus10and the air passage member (hose20) that communicates with the exhaust outlet (connection portion13). In the CPAP apparatus10according to the present embodiment, by using a value measured by at least one of the pressure sensor22and the flow rate sensor23, a command value for controlling a rotation number of the fan16is corrected such that a pressure of air expelled by the air supply unit15becomes a target pressure. A rotation number of the fan16can be obtained by detecting a rotor position of the motor17for driving the fan16by a hall sensor24. Specifically, the CPU191measures a rotation number of the fan16based on a detection signal from the hall sensor24obtained through the motor driving unit193. (Control of Apparatus) Next, control of a rotation number of the fan16performed by the CPAP apparatus10such that a pressure of air expelled by the air supply unit15becomes the target pressure will be described. The control of a rotation number of the fan16is performed by a circuit provided on the control board19, and is performed by a control unit which will be described below.FIGS.4A and4Bare block diagrams for explaining a control unit50(e.g. a processor or the like) of the CPAP apparatus10according to the embodiment of the present disclosure. The control unit50includes a command generation unit51, a storage unit52, a command correction unit53, a rotation number compensation unit54, and a respiration disturbance compensation unit55. The command generation unit51receives an operation of the operation buttons12, and generates a command value of a rotation number of the fan16such that a pressure of air expelled by the air supply unit15becomes the target pressure. A pressure of air expelled by the air supply unit15has correlation characteristic with a flow rate of air between the CPAP apparatus10and the other end of the air passage member (hose20), and follows a P-Q curve (static pressure-flow rate curve) to be determined due to an internal shape of the housing14, performance inherent in the air supply unit15, and a rotation number (rotation speed) of the fan16. Here, the P-Q curve is correlation characteristic indicating a relationship between a pressure and a flow rate of air generated by the fan16.FIG.5is a graph showing examples of P-Q curves of the air supply unit15. InFIG.5, a flow rate Q is set in a horizontal axis and a static pressure P is set in a vertical axis. Note that the static pressure P is a pressure loss in the air flow path from the CPAP apparatus10through the mask30to the airway and lungs of a patient, and varies depending on respiration of the patient. For example, when a patient inhales (inhalation), the lungs expand and increase in volume to decrease the static pressure P, and when the patient exhales (exhalation), the lungs contract and decrease in volume to increase the static pressure P. A P-Q curve of the air supply unit15differs depending on a rotation number of the fan16as long as the same air supply unit15is used. For example, in the P-Q curves shown inFIG.5three curves are shown when the rotation numbers of the fan16are different. Specifically, the rotation numbers of the fan16are reduced in order of a curve A, a curve B, and a curve C. That is, as a rotation number of the fan16increases, the flow rate Q of the air supply unit15also increases, as long as the static pressure P is the same. Information of P-Q curves is stored in the storage unit52. A configuration is illustrated in which the storage unit52shown inFIG.4Ainputs the information of the P-Q curves to the command generation unit51, and the information of the P-Q curves is provided from the command generation unit51to the command correction unit53. On the other hand, a configuration is illustrated in which the storage unit52shown inFIG.4Bdirectly inputs the information of the P-Q curves to the respiration disturbance compensation unit55. Of course, the storage unit52may input the information of the P-Q curves to the command generation unit51and the respiration disturbance compensation unit55. Also, the storage unit52is configured so as to correspond to the ROM/RAM192shown inFIG.3, but may also be an external storage device (for example, an SSD, an HDD, or the like) connected to the CPU191, separately from the ROM/RAM192. Description will be given below based on assumption that the information of the P-Q curve is stored in the storage unit52for each different rotation number of the fan16, however, the information of the P-Q curves may be stored only for the main rotation numbers of the fan16or information of a generalized P-Q curve which does not depend on a rotation number of the fan16may be stored. When the information of the P-Q curves is stored in the storage unit52only for the main rotation numbers of the fan16, the CPU191performs a known interpolation operation on the stored information to calculate the information of the P-Q curve corresponding to the required rotation number of the fan16. When the information of the generalized P-Q curve that does not depend on a rotation number of the fan16is stored in the storage unit52, the CPU191calculates the required rotation number of the fan16based on the information of the generalized P-Q curve. The command correction unit53corrects a command value generated by the command generation unit51based on values measured by the pressure sensor22and the flow rate sensor23. The pressure sensor22measures a pressure of air expelled by the air supply unit15, and outputs the measured value to the rotation number compensation unit54. The rotation number compensation unit54calculates a pressure difference between the pressure value obtained by the pressure sensor22and the target pressure, and calculates a correction value for correcting the command value in response to the pressure difference. In other words, the rotation number compensation unit54performs feedback control such that the pressure difference between the pressure value obtained by the pressure sensor22and the target pressure becomes 0 (zero). However, in the rotation number compensation unit54, pressure fluctuation accompanying respiration of a patient is corrected by follow-up, so that the return to the target pressure is delayed. On the other hand, the flow rate sensor23measures a flow rate of air expelled by the air supply unit15, and outputs the measured value to the respiration disturbance compensation unit55. The respiration disturbance compensation unit55obtains the flow rate value from the flow rate sensor23, and calculates a correction value for correcting the command value such that a pressure of air to be delivered to the patient becomes the target pressure. Specifically, when the patient inhales (inhalation) or when the patient exhales (exhalation), the respiration disturbance compensation unit55derives a required correction value (rotation number) by referring to the P-Q curve generalized from the flow rate value obtained by the flow rate sensor23and the target pressure. That is, in the respiration disturbance compensation unit55, feed-forward control is performed such that the flow rate value obtained by the flow rate sensor23becomes the target pressure. Therefore, the respiration disturbance compensation unit55can quickly correct the pressure fluctuation caused by the respiration of the patient, and can perform control for maintaining the target pressure without necessarily causing a delay in correction as in the case of the rotation number compensation unit54. The correction value calculated by the rotation number compensation unit54and the correction value calculated by the respiration disturbance compensation unit55are output to the command correction unit53. The command correction unit53determines a command value to be output to the motor driving unit193in consideration of the correction values calculated by the rotation number compensation unit54and the respiration disturbance compensation unit55, with respect to the command value generated by the command generation unit51. Note that the command correction unit53may change a percentage of the correction values to be considered with respect to the command value generated by the command generation unit51. For example, the command value output to the motor driving unit193is determined by combining 80% of a command value generated by the command generation unit51and a correction value calculated by the respiration disturbance compensation unit55with 20% of a correction value of the rotation number compensation unit54. Moreover, when a correction value of the respiration disturbance compensation unit55is strongly taken into consideration with respect to a command value generated by the command generation unit51, the command correction unit53determines a command value to be output to the motor driving unit193by combining 70% of the generated command value, 10% of the correction value of the rotation number compensation unit54, and 20% of the correction value of the respiration disturbance compensation unit55. The motor driving unit193supplies a DC voltage to the motor17so as to reach the rotation number of the fan16based on the command value output from the command correction unit53. The motor17rotates the fan16according to the DC voltage supplied from the motor driving unit193. Air expelled from the fan16passes through the hose20to the mask30and reaches the airway and lungs of the patient. (Control Flowchart) The control of the air supply unit15in the control unit50shown inFIGS.4A and4Bwill be described with reference to a flowchart.FIG.6is a flowchart for explaining the control of the CPAP apparatus10according to the embodiment of the present disclosure. The control unit50of the CPAP apparatus10starts control such that a pressure of air to be expelled from the other end of the hose20becomes the target pressure when a patient presses the operation button12. First, the control unit50generates a command value corresponding to the target pressure (step S11). Specifically, the command generation unit51shown inFIGS.4A and4Bgenerate the command value corresponding to the target pressure based on a pressure setting value input in advance. Next, the control unit50obtains a flow rate value measured by the flow rate sensor23(step S12). The control unit50calculates a correction value based on the obtained flow rate value (step S13). Specifically, the respiration disturbance compensation unit55shown inFIGS.4A and4Bcalculates a correction value for correcting the command value such that a pressure of air to be delivered to the patient becomes the target pressure based on a flow rate value obtained by the flow rate sensor23and the P-Q curve. Next, the control unit50generates a command value to be output based on the command value generated in step S11and the correction value calculated in step S13(step S14). In other words, the control unit50generates the command value in consideration of the correction value calculated in step S13. The control unit50outputs the command value generated in step S14to the motor driving unit193, thereby driving the motor17so as to become a rotation number of the fan16instructed by the command value (step S15). Next, the control unit50obtains a pressure value measured by the pressure sensor22(step S16). The control unit50determines whether or not the obtained pressure value is the target pressure (step S17). When the pressure value is not the target pressure (step S17: NO), the control unit50calculates a correction value based on the obtained pressure value as feedback control (step S18). Specifically, the rotation number compensation unit54shown inFIGS.4A and4Bcalculates a pressure difference between the pressure value obtained by the pressure sensor22and the target pressure, and calculates a correction value for correcting the command value according to the pressure difference. After the processing in step S18, the processing returns to step S12, and the control unit50generates a command value to be output in consideration of the correction value calculated in step S13and the correction value calculated in step S18. On the other hand, when the pressure value is the target pressure (step S17: YES), the control unit50returns the processing to step S12. Thereafter, the control unit50repeats the processing of step S11to step S18until an operation end by the patient pressing the operation button12is received, or a period of time of the set timer elapses. (Control Result) Next, description will be given by comparing between control results of a case where the air supply unit15is controlled based on only a pressure value obtained by the pressure sensor22and a case where the air supply unit15is controlled based on a pressure value obtained by the pressure sensor22and a flow rate value obtained by the flow rate sensor23as described in the present embodiment.FIG.7is a diagram showing a control result by the CPAP apparatus based on only a pressure value obtained by the pressure sensor22.FIG.8is a diagram showing a control result by the CPAP apparatus10according to the embodiment of the present disclosure. In addition, it is assumed that in the control result shown inFIG.7, the target pressure is set to 400 Pa, and in the control result shown inFIG.8, the target pressure is also set to 400 Pa. Note that inFIG.7andFIG.8, a unit of time is expressed by [s] as second, a unit of flow rate is expressed by [LPM] as liter/min, and a unit of pressure is expressed by [Pa] as pascal. In the control result shown inFIG.7, the flow rate suddenly increases when the patient starts to inhale at around the time of 10.5 seconds, and the pressure rapidly decreases. Therefore, the control unit50of the CPAP apparatus10performs feedback control based on a pressure value obtained by the pressure sensor22, thereby increasing a rotation number of the fan in order to return the pressure to the target pressure. However, when the control unit50performs control of the air supply unit15only by the feedback control, since the rotation number of the fan is increased by follow-up based on the pressure value measured by the pressure sensor22, a delay in the control for returning the pressure to the target pressure occurs. Specifically, in the control result shown inFIG.7, the pressure is changed to increase at around the time of 11 seconds. When such control is performed, the pressure does not reach the target pressure even though the patient inhales, so that the CPAP apparatus10may not sufficiently open the airway of the patient. In addition, in the control result shown inFIG.7, due to the fact that the patient starts to exhale at around the time of 13.2 seconds, even though the flow rate is suddenly reduced, the pressure continues to rise up to about the time of 13.4 seconds because of the delay in the control of the control unit50. When such control is performed, even though the patient exhales, the pressure is higher than the target pressure, so that it becomes difficult for the patient to exhale. On the other hand, in the CPAP apparatus10according to the present embodiment, not only feedback control is performed based on a pressure value obtained by the pressure sensor22but also feed-forward control is performed based on a flow rate value obtained by the flow rate sensor23. In the control result shown inFIG.8, the flow rate is suddenly increased by the fact that the patient starts to inhale around the time of 13.5 seconds, but the feed-forward control is performed based on the flow rate value obtained by the flow rate sensor23, thereby rapidly increasing the rotation number of the fan16. Therefore, the control unit50maintains the pressure substantially at the target pressure regardless of the inhalation of the patient. When such control is performed, even when the patient inhales, the pressure is maintained at the target pressure, so that the CPAP apparatus10can open the airway of the patient and deliver air to the airway and the lungs. In addition, in the control result shown inFIG.8, the flow rate is rapidly decreased by the fact that the patient starts to exhale at around the time of 16.8 seconds, but the rotation number of the fan16is quickly reduced by the feed-forward control of the control unit50. Therefore, the control unit50maintains the pressure substantially at the target pressure regardless of the exhalation of the patient. When such control is performed, even when the patient exhales, the pressure is maintained at the target pressure, so that it is easy for the patient to exhale. As described above, the CPAP apparatus10according to the present embodiment includes the housing14having the intake port18and the connection portion13, the hose20whose one end communicates with the connection portion13, the fan16which expels air flowing in from the intake port18, from the other end of the hose20, the motor17and the motor driving unit193which rotationally drive the fan16, the control unit50which controls the motor driving unit193, and the flow rate sensor23. The control unit50includes the command generation unit51for generating a command value of a rotation number of the fan16such that a pressure for expelling air from the other end of the hose20becomes the target pressure, and the command correction unit53for correcting the command value based on a flow rate value obtained by the flow rate sensor23. Also, the command generation unit51generates a command value by a pressure of air generated by rotational driving of the fan16. Additionally, the command value is a signal that is output from the control unit50to be input to the motor driving unit193, and that is for setting a rotation number of the fan16to a designated value. Therefore, in the CPAP apparatus10, due to the correction based on a flow rate value obtained by the flow rate sensor23, a pressure of air to be expelled can be controlled to become the target pressure regardless of a flow rate of the inhalation or exhalation of the patient. The command correction unit53and the respiration disturbance compensation unit55calculate a change in a pressure of air to be delivered to the other end of the hose20from a change in a flow rate value obtained by the flow rate sensor23, and correct the command value such that the pressure of the air delivered to the other end of the hose20becomes the target pressure. Specifically, the respiration disturbance compensation unit55obtains a flow rate value from the flow rate sensor23, and calculates a correction value for correcting the command value such that the pressure of the air to be delivered to the patient becomes the target pressure. The command correction unit53corrects the command value in consideration of the correction value calculated by the respiration disturbance compensation unit55. Specifically, the command correction unit53derives a required correction value (rotation number) by referring to the P-Q curve generalized a flow rate value obtained by the flow rate sensor23and the corresponding target pressure. For example, during inhalation, the command correction unit53corrects the command value such that a rotation number of the fan16increases, because the rotation number of the fan16at the time of measuring the flow rate value is smaller than the designated rotation number of the fan16shown in the P-Q curve corresponding to the flow rate value obtained by the flow rate sensor23and the target pressure. Further, for example, during exhalation, the command correction unit53corrects the command value such that a rotation number of the fan16decreases, because the rotation number of the fan16at the time of measuring the flow rate value is larger than the designated rotation number of the fan16shown in the P-Q curve corresponding to the flow rate value obtained by the flow rate sensor23and the target pressure. The CPAP apparatus10according to the present embodiment further includes the pressure sensor22as shown inFIG.3. Therefore, the command correction unit53and the rotation number compensation unit54correct the command value generated by the command generation unit51based on a pressure value obtained by the pressure sensor22. Therefore, the CPAP apparatus10can be controlled more accurately such that a pressure of air to be expelled becomes the target pressure in comparison with a CPAP apparatus provided with only a flow rate sensor. The command correction unit53and the rotation number compensation unit54calculate a pressure difference between a pressure value obtained by the pressure sensor22and the target pressure, and correct the command value according to the pressure difference. Specifically, when a pressure value obtained by the pressure sensor22is smaller than the target pressure, the command correction unit53corrects the command value so as to increase a rotation number of the fan16. In addition, when a pressure value obtained by the pressure sensor22is larger than the target pressure, the command correction unit53corrects the command value so as to decrease a rotation number of the fan16. (Modifications) (1) The CPAP apparatus10according to the present embodiment includes not only a configuration for performing feed-forward control based on a flow rate value obtained by the flow rate sensor23but also a configuration for performing feedback control based on a pressure value obtained by the pressure sensor22. However, the present disclosure is not limited thereto, and the CPAP apparatus may include only a configuration for performing feed-forward control based on a flow rate value obtained by the flow rate sensor23. Moreover, in addition to the configuration for performing the feed-forward control based on a flow rate value obtained by the flow rate sensor23, the CPAP apparatus may include a configuration for performing another feed-forward control and a configuration for performing feedback control. (2) In the CPAP apparatus10according to the present embodiment, information of P-Q curves (information of correlation characteristics) representing a relationship between a pressure of air generated by the fan16and a flow rate is stored in the storage unit52. However, the storage unit52may store information of P-Q curves related to only main rotation numbers of the fan16, and may store information of the generalized P-Q curve which does not depend on a rotation number of the fan16. This makes it possible to reduce a storage capacity of the storage unit52. (3) In the CPAP apparatus10according to the present embodiment, it has been described that the target pressure is a constant value regardless of exhalation and inhalation of a patient. However, the present disclosure is not limited thereto, and in the CPAP apparatus, the target pressure may be set so as to vary depending on the exhalation or the inhalation of the patient. (4) In the CPAP apparatus10according to the present embodiment, the pressure sensor22and the flow rate sensor23are provided in a vicinity of the air flow outlet of the air supply unit15. However, the present disclosure is not limited thereto, and a pressure sensor or a flow rate sensor may be provided in or on the hose20or the mask30which is provided closer to the patient. The CPAP apparatus is not limited to a configuration in which one pressure sensor and one flow rate sensor are provided, and a plurality of pressure sensors and a plurality of flow rate sensors may be provided. (5) In the CPAP apparatus10according to the present embodiment, a configuration in which a signal from the respiration disturbance compensation unit55is directly input to the command correction unit53as shown inFIGS.4A and4Bhas been described. However, when a signal from the respiration disturbance compensation unit55is directly input to the command correction unit53, there is a possibility of oscillation, so that the signal from the respiration disturbance compensation unit55may be input to the command correction unit53via a filter.FIG.9is a block diagram for explaining a control unit50A of a CPAP apparatus according to a modification. The control unit50A includes the command generation unit51, the storage unit52, the command correction unit53, the rotation number compensation unit54, the respiration disturbance compensation unit55, and a compensation filter56. Note that in a configuration shown inFIG.9, the same constituent elements as those shown inFIGS.4A and4Bare denoted by the same reference signs, and detailed description thereof will be omitted. The compensation filter56is a filter circuit for blunting a waveform of a signal from the respiration disturbance compensation unit55, and is, for example, a low pass filter circuit. The compensation filter56may employ a band pass filter circuit, a high pass filter circuit, or the like according to a signal whose waveform is blunted. The command correction unit53suppresses occurrence of oscillation by inputting a waveform of a signal blunted by the compensation filter56from the respiration disturbance compensation unit55. (6) In the CPAP apparatus10according to the present embodiment, as shown inFIGS.4A and4B, the command generation unit51and the respiration disturbance compensation unit55are individually provided, and a command value is corrected in the command correction unit53based on operation results that are separately performed, and then the corrected command value is output to the motor driving unit193. However, the CPAP apparatus may have a configuration in which an amount of operations is reduced by integrating the command generation unit51and the respiration disturbance compensation unit55. Hereinafter, a configuration in which the command generation unit51and the respiration disturbance compensation unit55are integrated will be described. FIG.10is a block diagram for explaining operations in the command generation unit51and the respiration disturbance compensation unit55. The command generation unit51includes a first rotation number derivation unit51afor calculating a rotation number of the fan16required for a pressure to become the target pressure at a flow rate of zero, based on a pressure command for commanding the target pressure. Further, the command generation unit51includes an FF coefficient unit51bwhich multiplies a value calculated by the first rotation number derivation unit51aby an FF (feed-forward) coefficient of feed-forward control. The command generation unit51outputs the value multiplied by the FF coefficient in the FF coefficient unit51bas a rotation number command. The respiration disturbance compensation unit55includes a second rotation number derivation unit55afor calculating a rotation number of the fan16required for a pressure to become the target pressure at the measured flow rate, based on a pressure command for commanding the target pressure and the flow rate measured by the flow rate sensor23. Further, the respiration disturbance compensation unit55includes a first rotation number derivation unit55bfor calculating a rotation number of the fan16required for a pressure to become the target pressure at a flow rate of zero, based on a pressure command for commanding the target pressure. In the respiration disturbance compensation unit55, a difference between values output from the second rotation number derivation unit55aand the first rotation number derivation unit55bis derived in a difference derivation unit55c, and is output as a rotation number command. The command correction unit53outputs a rotation number command to the motor driving unit193by using the rotation number command output from the respiration disturbance compensation unit55and the rotation number command output from the command generation unit51. As can be seen fromFIG.10, the first rotation number derivation unit51ain the command generation unit51and the first rotation number derivation unit55bin the respiration disturbance compensation unit55perform the same operation, and the operation processes are duplicated. Therefore, by integrating the command generation unit51and the respiration disturbance compensation unit55, it is possible to reduce the duplicated operation processes. FIG.11is a block diagram for explaining an operation of a processing unit500in which the command generation unit51and the respiration disturbance compensation unit55are integrated. The processing unit500has only a configuration in which an operation in the first rotation number derivation unit51aand an operation in the first rotation number derivation unit55bcancel each other, and the second rotation number derivation unit55aand the FF coefficient unit51bare included. Therefore, the processing unit500can reduce the operation processing in comparison with a case where the command generation unit51and the respiration disturbance compensation unit55are not integrated. (7) Further, a CPAP apparatus may be configured in which the command generation unit51, the rotation number compensation unit54, and the respiration disturbance compensation unit55are integrated to reduce an amount of operations. Hereinafter, a configuration in which the command generation unit51, the rotation number compensation unit54, and the respiration disturbance compensation unit55are integrated will be described with reference to the drawings. FIG.12is a block diagram for explaining operations of the processing unit500in which the command generation unit51and the respiration disturbance compensation unit55are integrated, and the rotation number compensation unit54. The processing unit500includes the second rotation number derivation unit55aand the FF coefficient unit51b. That is, the processing unit500performs feed-forward control. The rotation number compensation unit54includes a pressure difference derivation unit54afor deriving a difference between a pressure command for commanding the target pressure and a pressure response measured by the pressure sensor22, and a feedback control unit54bfor calculating a correction value of a flow rate from a pressure difference value derived by the pressure difference derivation unit54a. Further, the rotation number compensation unit54includes a second rotation number derivation unit54cfor calculating the rotation number of the fan16required for a pressure to become the target pressure at a current flow rate based on a pressure command for commanding the target pressure and the correction value of the flow rate calculated in the feedback control unit54b. That is, the rotation number compensation unit54performs feedback control. The command correction unit53outputs a rotation number command to motor driving unit193by using the rotation number command output from the rotation number compensation unit54and the rotation number command output from the processing unit500. As can be seen fromFIG.12, the second rotation number derivation unit54cin the rotation number compensation unit54and the second rotation number derivation unit55ain the processing unit500perform the same operation, and the operation processes are duplicated. Therefore, the command generation unit51, the rotation number compensation unit54, and the respiration disturbance compensation unit55are integrated, thereby reducing the duplicated operation processes. FIG.13is a block diagram for explaining an operation of a processing unit510in which the command generation unit51, the rotation number compensation unit54, and the respiration disturbance compensation unit55are integrated. In the processing unit510, in a process of calculating a rotation number command from a flow rate, by integrating a process of feedback control of the rotation number compensation unit54and a process of feed-forward control of the processing unit500, so that the second rotation number derivation unit54cand the second rotation number derivation unit55awhose operation processes are duplicated are integrated. Operation processing of the processing unit510can be reduced by integrating the second rotation number derivation unit54cand the second rotation number derivation unit55awhose operation processes are duplicated. Note that, as for the second rotation number derivation unit55a, a correction value of a flow rate derived from a pressure difference in the feedback control unit54band a value obtained by multiplying a flow rate measured by the flow rate sensor23by the FF coefficient in the FF coefficient unit51bare regarded as a flow rate to be input. That is, a flow rate to be input to the second rotation number derivation unit55ais a flow rate for which the feed-forward control process and the feedback control process have already been executed. It should be understood that the embodiment disclosed herein is illustrative and is not limited in all respects. The scope of the present disclosure is indicated by the appended claims rather than by the above description and is intended to include all modifications within the meaning and scope equivalent to those of the appended claims. REFERENCE SIGNS LIST 10CPAP APPARATUS11DISPLAY UNIT12OPERATION BUTTON13CONNECTION PORTION14HOUSING15AIR SUPPLY UNIT16FAN17MOTOR18INTAKE PORT19CONTROL BOARD20HOSE21AC ADAPTER22PRESSURE SENSOR23FLOW RATE SENSOR24HALL SENSOR30MASK50CONTROL UNIT51COMMAND GENERATION UNIT52STORAGE UNIT53COMMAND CORRECTION UNIT54ROTATION NUMBER COMPENSATION UNIT55RESPIRATION DISTURBANCE COMPENSATION UNIT192ROM/RAM193MOTOR DRIVING UNIT | 38,916 |
11857725 | DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention consists of several separate pieces that are fitted together to form a system to ventilate and aspirate a patient3. The system comprises a tracheostomy or endotracheal connector1(hereinafter “patient connector1”) which in use attaches to the tracheostomy or endotracheal fitting2located in the neck or throat of a patient3. In the Figures the patient is only shown with tracheostomy not an endotracheal fitting and tube. An elbow connector6and catheter tube4are connected together to form a catheter mount. The elbow connector6is attached to the patient connector1. An aspirating assembly8is also provided that is attached to the elbow connector6. The catheter tube4is effectively a piece of tubing that connects the elbow connector6to the ventilator system that supplies gases to the patient's airways. In the preferred embodiment described, the patient has undergone surgery and has had a tracheostomy or endotracheal fitting2inserted into his or her tracheostomy in order to allow ventilation and aspiration. Referring toFIGS.1and2, a ventilation and humidifying system as might be used with the suction catheter tube connector of the present invention is shown. A patient3is receiving humidified and pressurised gases through the tracheostomy or endotracheal fitting2(hereinafter “patient fitting2”). The catheter tube4is connected to a humidified gases transportation pathway or inspiratory conduit7that in turn is connected to a humidifier25supplied with gases from a ventilator23. An expiratory conduit24transports gases from the patient back into the ventilator to assist the breathing of patient3. The ventilator23, humidifier25and conduit24that make up the ventilation and humidifying system are disclosed in the prior art, and may be of the type described in U.S. Pat. No. 5,640,951 to Fisher and Paykel Limited. The aspirating assembly8consists of a suction tube9, a collapsible and flexible plastic envelope10and at least two fittings at each end, in particular, a distal fitting11furthest from the patient, and a proximal connector12nearest to the patient3. The suction tube9is capable of being slid backwards and forwards through the proximal connector12, such that in use the envelope10collapses and expands back out lengthwise with movement of the suction tube9. The proximal connector12has a releasable connector mechanism allowing attachment to the elbow connector6and hence catheter tube4. The plastic envelope10contains any hazardous biological waste from the lungs of the patient3that may be deposited on the outside of the suction tube9. The distal fitting11is connected to a suction pump13. The suction from pump13is used to suck fluid from the lungs and airway passages of the patient3through the suction tube9. In order for the suction tube9to access the lungs and airways of the patient3, its length can be pushed through the proximal connector12, passing through the elbow connector6, the patient connector1and the patient fitting2and then into the lungs of the patient3. In order to prevent obstruction of the patient's airways the suction tube9is not left inside the patient3when not in use. Thus the suction tube9is substantially withdrawn back through the proximal connector12and into the plastic envelope10when not in use. The plastic envelope10is able to collapse around the suction tube9as there is a small aperture31(seeFIG.3that enables the venting of air and hence collapse and filling of the envelope with air. The proximal connector12releasably connects the aspirating assembly8to the elbow connector6. In the preferred embodiment shown inFIGS.3and4, the elbow connector6and catheter tube4are substantially T-shaped in cross-section. The upright of the T-section forms or is connected to the ventilation tube4. The end of the arm of the T-section forms or is connected to the patient connector1and the other end forms a passage15which receives the proximal connector12of the aspirating assembly8. A seal16is located at the outermost end of passage15and seals passage15. In the preferred embodiment this is an elastomeric material, such as a silicone rubber, and has a slit17formed in the centre of the seal. The slit17allows the seal16to be pierced, for example by a central protrusion20(described below) or the suction catheter tube9, but then to reseal once the object piercing the seal has been removed. In other forms of the elbow connector and catheter tube an L-shaped configuration may exist where the corner of the L has located within it an aperture in which an elastomeric seal is disposed. In this configuration the passage15would be shorter in length. Referring now toFIG.5, the proximal connector12consists of two nested cup-shaped fittings, an inner cup fitting18and an outer cup fitting19, extending around a central protrusion20. The central protrusion20preferably projects past the rim28of the outer cup fitting19, although it is not strictly necessary that the protrusion20does. The rim28of the outer cup fitting19projects past the rim27of the inner cup fitting18. The outer cup fitting19preferably has an internal diameter slightly larger than the outer diameter of the elbow connector6that forms the passage15. The inner cup fitting18has a diameter slightly smaller than the outer diameter of the crosspiece of the elbow connector6. The proximal connector12and the elbow connector6are brought together and connected so that the central protrusion20passes through the slit17in elastomeric seal16, and protrudes into the passage15. The rim of the inner cup fitting18abuts the end of the passage15. A dead space21is formed between the outside surface of the seal16, the inside of the inner cup fitting18and the outside surface of the protrusion20. It is not considered necessary for the seal16to be airtight and stop gases escaping to atmosphere when the elbow connector6and the aspirating assembly8are connected in this manner, as sealing occurs between the seal16and the end27of the inner cup fitting18. In any event, any possible leakage that may occur is contained in the dead space21formed on connection. The dead space21breaks the direct path between gases flowing through the seal16and atmosphere as the elbow connector6and aspirating assembly8are brought together. Once the rim27of the inner cup fitting18has been pushed against the seal16at the end of the passage15, the rim27of the inner cup fitting18and seal16form a seal that prevents any further leakage to atmosphere. As the inner cup fitting18abuts the seal16, part of the outer cup fitting19overlaps and wraps around the outer end portion29of the passage15. The passage15and the outer cup fitting19are fitted with a releasable lockable bayonet fitting22of the type well known in the prior art. The bayonet fitting22prevents inadvertent release of the proximal connector12from the elbow connector6. In the preferred embodiment, the central protrusion20is a hollow tube protruding from the proximal connector12. The catheter tube9fits snugly within the central protrusion20, and slides easily within it. This snug fit has the advantage that little or no gases escape through the seal16to pass between the catheter tube9and the central protrusion20. In the event that gases did escape an additional seal or washer30within the proximal connector12prevents gases entering the envelope10. The seal or washer30also performs a wiping action about the suction tube and prevents excessive mucus, contaminants and the like to enter the envelope10. In some forms of the present invention the envelope10may be formed of a breathable material, such as SYMPATEX™. In use, when the proximal connector12and the elbow connector6are mated, the protrusion20is pushed through the slit17in the seal16and the proximal connector12is locked to the elbow connector6using the bayonet fitting22. The end of the suction tube9may then be pushed through the hollow centre of the central protrusion20into the elbow connector6and then through into the patient connector1, the patient fitting2and into the lungs of the patient3. After suction operations have been completed, the suction tube9may be withdrawn back through the proximal connector12and any contaminants on the outside surface of the suction catheter tube9are contained safely within the plastic envelope10. Once the aspirating assembly8and the elbow connector6have been mated, there is little or no inadvertent forcing or twisting of the elbow connector and catheter tube4in order to push the suction catheter tube9through the seal16. The suction catheter tube9moves easily within the tube formed by the central protrusion20. There is therefore a decrease degree of patient trauma offered by the system of the present invention. The seal16and the features of the proximal connector12outlined above also ensure that any gas leakage through the seal16does not result in an excessive loss of PEEP. In the preferred embodiment of the present invention described and shown in the figures, the patient connector1is connected to, or can be an integral part of, the elbow connector6. This is a common embodiment for ventilation circuits of this type, although bifurcated y-shaped tracheostomy fittings5of the type shown inFIG.6that allow an elbow connector6and a catheter tube4to be separately connected are not unknown. A similar alternative system is shown inFIG.7where the aspirating assembly8is attached to a cross- or x-shaped catheter tube26. One branch of the catheter tube26forms the passage15and the opposing branch forms the patient connector2. In this embodiment one of the side branches forms the inspiratory conduit7and the opposed branch forms either a bleed-off exhalation conduit or expiratory conduit24leading back to the ventilator23(if being used in an assisted breathing configuration). Systems of both the types described above in the preferred embodiment and the alternative forms with the bifurcated y-shaped tracheostomy fitting5, or the x-shaped catheter tube26, have the advantage that they are modular, and the separate parts, such as the elbow connector6or the aspirating assembly8can be easily removed from the system and replaced if necessary. This is especially useful, as the aspirating assembly8will likely need to be removed and replaced much more frequently that the other parts. | 10,347 |
11857726 | 8 DETAILED DESCRIPTION OF EXAMPLES OF THE TECHNOLOGY Before the present technology is described in further detail, it is to be understood that the technology is not limited to the particular examples described herein, which may vary. It is also to be understood that the terminology used in this disclosure is for the purpose of describing only the particular examples discussed herein, and is not intended to be limiting. The following description is provided in relation to various examples which may share one or more common characteristics and/or features. It is to be understood that one or more features of any one example may be combinable with one or more features of another example or other examples. In addition, any single feature or combination of features in any of the examples may constitute a further example. 8.1 Treatment Systems In one form, the present technology comprises an apparatus or device for treating a respiratory disorder. The apparatus or device may comprise an RPT device40for supplying pressurised air to the patient10via an air circuit50to a patient interface100. FIG.1Ashows a system including a patient10wearing a patient interface100, in the form of nasal pillows, receives a supply of air at positive pressure from a RPT device40. Air from the RPT device is humidified in a humidifier60, and passes along an air circuit50to the patient10. A bed partner20is also shown. FIG.1Bshows a system including a patient10wearing a patient interface100, in the form of a nasal mask, receives supply air at positive pressure from an RPT device40. Air from the RPT device is humidified in a humidifier60, and passes along an air circuit50to the patient10. FIG.1Cshows a system including a patient10wearing a patient interface100, in the form of a full-face mask (FFM), receives a supply of air at positive pressure from a RPT device40. Air from the RPT device is humidified in a humidifier60, and passes along an air circuit50to the patient10. 8.2 Patient Interface FIG.2depicts a patient interface100in accordance with one aspect of the present technology comprises the following functional aspects: a seal-forming structure160, a plenum chamber120, a positioning and stabilising structure130, a vent140, a forehead support150, one form of connection port170for connection to air circuit50. In some forms a functional aspect may be provided by one or more physical components. In some forms, one physical component may provide one or more functional aspects. In use the seal-forming structure160is arranged to surround an entrance to the airways of the patient so as to facilitate the supply of air at positive pressure to the airways. 8.2.1 Seal-Forming Structure In one form of the present technology, a seal-forming structure160provides a seal-forming surface, and may additionally provide a cushioning function. A seal-forming structure160in accordance with the present technology may be constructed from a soft, flexible, resilient material such as silicone. In one form the seal-forming portion of the non-invasive patient interface100comprises a pair of nasal puffs, or nasal pillows, each nasal puff or nasal pillow being constructed and arranged to form a seal with a respective naris of the nose of a patient. Nasal pillows in accordance the present technology include: a frusto-cone, at least a portion of which forms a seal on an underside of the patient's nose, a stalk, a flexible region on the underside of the frusto-cone and connecting the frusto-cone to the stalk. In addition, the structure to which the nasal pillow of the present technology is connected includes a flexible region adjacent the base of the stalk. The flexible regions can act in concert to facilitate a universal joint structure that is accommodating of relative movement both displacement and angular of the frusto-cone and the structure to which the nasal pillow is connected. For example, the frusto-cone may be axially displaced towards the structure to which the stalk is connected. In one form, the non-invasive patient interface100comprises a seal-forming portion that forms a seal in use on an upper lip region (that is, the lip superior) of the patient's face. In one form the non-invasive patient interface100comprises a seal-forming portion that forms a seal in use on a chin-region of the patient's face. 8.2.2 Plenum Chamber Preferably the plenum chamber120has a perimeter that is shaped to be complementary to the surface contour of the face of an average person in the region where a seal will form in use. In use, a marginal edge of the plenum chamber120is positioned in close proximity to an adjacent surface of the face. Actual contact with the face is provided by the seal-forming structure160. The seal-forming structure160may extend in use about the entire perimeter of the plenum chamber120. 8.2.3 Positioning and Stabilising Structure Preferably the seal-forming structure160of the patient interface100of the present technology may be held in sealing position in use by the positioning and stabilising structure130. 8.2.4 Vent In one form, the patient interface100includes a vent140constructed and arranged to allow for the washout of exhaled carbon dioxide. One form of vent140in accordance with the present technology comprises a plurality of holes, for example, about 20 to about 80 holes, or about 40 to about 60 holes, or about 45 to about 55 holes. 8.2.5 Terms Used in Relation to a Patient Interface Plenum chamber: a mask plenum chamber will be taken to mean a portion of a patient interface having walls enclosing a volume of space, the volume having air therein pressurised above atmospheric pressure in use. A shell may form part of the walls of a mask plenum chamber. Seal: The noun form (“a seal”) will be taken to mean a structure or barrier that intentionally resists the flow of air through the interface of two surfaces. The verb form (“to seal”) will be taken to mean to resist a flow of air. 8.3 Anatomy of the Face FIG.3Ashows an anterior view of a human face including the endocanthion, nasal ala, nasolabial sulcus, lip superior and inferior, upper and lower vermillion, and chelion. Also shown are the mouth width, the sagittal plane dividing the head into left and right portions, and directional indicators. The directional indicators indicate radial inward/outward and superior/inferior directions. FIG.3Bshows a lateral view of a human face including the glabaella, sellion, nasal ridge, pronasale, subnasale, superior and inferior lip, supramenton, alar crest point, and otobasion superior and inferior. Also shown are directional indictors indicating superior/inferior and anterior/posterior directions. FIG.3Cshows a base view of a nose with several features identified including naso-labial sulcus, lip inferior, upper Vermilion, naris, subnasale, columella, pronasale, the major axis of a naris and the sagittal plane. 8.3.1 Terms Used in Relation to the Anatomy of the Face Ala: the external outer wall or “wing” of each nostril (plural: alar) Alare: The most lateral point on the nasal ala. Alar curvature (or alar crest) point: The most posterior point in the curved base line of each ala, found in the crease formed by the union of the ala with the cheek. Auricle: The whole external visible part of the ear. Columella: the strip of skin that separates the nares and which runs from the pronasale to the upper lip. Columella angle: The angle between the line drawn through the midpoint of the nostril aperture and a line drawn perpendicular to the Frankfurt horizontal while intersecting subnasale. Glabella: Located on the soft tissue, the most prominent point in the midsagittal plane of the forehead. Nares (Nostrils): Approximately ellipsoidal apertures forming the entrance to the nasal cavity. The singular form of nares is naris (nostril). The nares are separated by the nasal septum. Naso-labial sulcus or Naso-labial fold: The skin fold or groove that runs from each side of the nose to the corners of the mouth, separating the cheeks from the upper lip. Naso-labial angle: The angle between the columella and the upper lip, while intersecting subnasale. Otobasion inferior: The lowest point of attachment of the auricle to the skin of the face. Otobasion superior: The highest point of attachment of the auricle to the skin of the face. Pronasale: the most protruded point or tip of the nose, which can be identified in lateral view of the rest of the portion of the head. Philtrum: the midline groove that runs from lower border of the nasal septum to the top of the lip in the upper lip region. Pogonion: Located on the soft tissue, the most anterior midpoint of the chin. Ridge (nasal): The nasal ridge is the midline prominence of the nose, extending from the Sellion to the Pronasale. Sagittal plane: A vertical plane that passes from anterior (front) to posterior (rear) dividing the body into right and left halves. Sellion: Located on the soft tissue, the most concave point overlying the area of the frontonasal suture. Septal cartilage (nasal): The nasal septal cartilage forms part of the septum and divides the front part of the nasal cavity. Subalare: The point at the lower margin of the alar base, where the alar base joins with the skin of the superior (upper) lip. Subnasal point: Located on the soft tissue, the point at which the columella merges with the upper lip in the midsagittal plane. Supramenton: The point of greatest concavity in the midline of the lower lip between labrale inferius and soft tissue pogonion 8.4 Automatic Patient Interface Sizing 8.4.1 Overview Obtaining a patient interface allows a patient to engage in positive pressure therapy. Patients seeking their first patient interface or a new patient interface to replace an older interface, typically consult a DME to determine a recommended patient interface size based on measurements of the patient's facial anatomy, which are typically performed by the DME. This may be an inconvenience that prevents some patients from receiving a needed patient interface and from engaging in positive pressure therapy. The present technology allows patients to more quickly and conveniently obtain a patient interface. It may permit a more efficient method to quickly measure their facial anatomy and receive a recommendation for an appropriate patient interface size from the comfort of their own home using a computing device, such as a desktop computer, tablet, smart phone or other mobile device. In a beneficial embodiment, the present technology may employ an application downloadable from a manufacturer or third party server to a smartphone or tablet with an integrated camera. When launched, the application may provide visual and/or audio instructions. As instructed, the user (i.e. a patient) may stand in front of a mirror330, and press the camera button on a user interface. An activated process may then take a series of pictures of the user's face, and then, within a matter of seconds for example, recommend a patient interface size for the user (based on the processor analysing the pictures). This is a vast improvement over the traditional method of visiting a DME who takes a series of measurements with a calliper as it allows a user, anywhere in the world, to quickly and conveniently find a patient interface suitable for their needs. Thus, it can allow patients to begin treatment more rapidly. Moreover, in that the user has control over the process, the customer can repeat it if desired, unhurriedly and to their satisfaction, increasing the user's confidence and sense of responsibility. As described further below, the present technology allows a user/patient to capture an image or series of images of their facial structure. Instructions provided by an application stored on a computer-readable medium, such as when executed by a processor, detect various facial landmarks within the images, measure and scale the distance between such landmarks, compare these distances to a data record, and recommend an appropriate patient interface size. Thus, an automated device of a consumer may permit accurate patient interface selection, such as in the home, to permit customers to determine sizing without trained associates. 8.4.2 System FIG.4depicts an example system200that may be implemented for automatic facial feature measuring and patient interface sizing. System200may generally include one or more of servers210, a communication network220, and a computing device230. Server210and computing device230may communicate via communication network220, which may be a wired network222, wireless network224, or wired network with a wireless link226. In some versions, server210may communicate one-way with computing device230by providing information to computing device230, or vice versa. In other embodiments, server210and computing device230may share information and/or processing tasks. The system may be implemented, for example, to permit automated purchase of patient's interfaces (mask) where the process may include automatic sizing processes described in more detail herein. For example, a customer may order a mask online after running a mask selection process that automatically identifies a suitable mask size by image analysis of the customer's facial features. 8.4.2.1 Computing Device Computing device230can be a desktop or laptop computer232or a mobile device, such as a smartphone234or tablet236.FIG.5depicts the general architecture300of computing device230. Device230may include one or more processors310. Device230may also include a display interface320, user control/input interface331, sensor340and/or a sensor interface for one or more sensor(s), inertial measurement unit (IMU)342and non-volatile memory/data storage350. Sensor340may be one or more cameras (e.g., a CCD charge-coupled device or active pixel sensors) that are integrated into computing device230, such as those provided in a smartphone or in a laptop. Alternatively, where computing device230is a desktop computer, device230may include a sensor interface for coupling with an external camera, such as the webcam233depicted inFIG.4. Other exemplary sensors that could be used to assist in the methods described herein that may either be integral with or external to the computing device include stereoscopic cameras, for capturing three-dimensional images, or a light detector capable of detecting reflected light from a laser or strobing/structured light source. User control/input interface331allows the user to provide commands or respond to prompts or instructions provided to the user. This could be a touch panel, keyboard, mouse, microphone, and/or speaker, for example. Display interface320may include a monitor, LCD panel, or the like to display prompts, output information (such as facial measurements or interface size recommendations), and other information, such as a capture display, as described in further detail below. Memory/data storage350may be the computing device's internal memory, such as RAM, flash memory or ROM. In some embodiments, memory/data storage350may also be external memory linked to computing device230, such as an SD card, server, USB flash drive or optical disc, for example. In other embodiments, memory/data storage350can be a combination of external and internal memory. Memory/data storage350includes stored data354and processor control instructions352that instruct processor310to perform certain tasks. Stored data354can include data received by sensor340, such as a captured image, and other data that is provided as a component part of an application. Processor control instructions352can also be provided as a component part of an application. 8.4.2.2 Application for Facial Feature Measuring and Patient Interface Sizing One such application is an application for facial feature measuring and/or patient interface sizing360, which may be an application downloadable to a mobile device, such as smartphone234and/or tablet236. The application360, which may be stored on a computer-readable medium, such as memory/data storage350, includes programmed instructions for processor310to perform certain tasks related to facial feature measuring and/or patient interface sizing. The application also includes data that may be processed by the algorithm of the automated methodology. Such data may include a data record, reference feature, and correction factors, as explained in additional detail below. 8.4.3 Method for Automatic Measuring and Sizing As illustrated in the flow diagrams ofFIGS.6A-6D, one aspect of the present technology is a method for controlling a processor, such as processor310, to measure patient facial features using two-dimensional or three-dimensional images and to recommend or select an appropriate patient interface size, such as from a group of standard sizes, based on the resultant measurements. The method may generally be characterized as including three or four different phases: a pre-capture phase400, a capture phase500, a post-capture image processing phase600, and a comparison and output phase700. In some cases, the application for facial feature measuring and patient interface sizing may control a processor310to output a visual display that includes a reference feature on the display interface320. The user may position the feature adjacent to their facial features, such as by movement of the camera. The processor may then capture and store one or more images of the facial features in association with the reference feature when certain conditions, such as alignment conditions are satisfied. This may be done with the assistance of a mirror330. The mirror330reflects the displayed reference feature and the user's face to the camera. The application then controls the processor310to identify certain facial features within the images and measure distances therebetween. By image analysis processing a scaling factor may then be used to convert the facial feature measurements, which may be pixel counts, to standard mask measurement values based on the reference feature. Such values may be, for example, standardized unit of measure, such as a meter or an inch, and values expressed in such units suitable for mask sizing. Additional correction factors may be applied to the measurements. The facial feature measurements may be compared to data records that include measurement ranges corresponding to different patient interface sizes for particular patient interface forms, such as nasal masks and FFM's, for example. The recommended size may then be chosen and be output to the user/patient based on the comparison(s) as a recommendation. Such a process may be conveniently effected within the comfort of the user's own home, if the user so chooses. The application may perform this method within seconds. In one example, the application performs this method in real time. 8.4.3.1 Pre-Capture Phase400 In the pre-capture phase, which is represented by the flow diagram ofFIG.6A, processor310, among other things, assists the user in establishing the proper conditions for capturing one or more images for sizing processing. Some of these conditions include proper lighting and camera orientation and motion blur caused by an unsteady hand holding the computing device230, for example. In one version of the method, a user may conveniently download an application for performing the automatic measuring and sizing at computing device230from a server, such as a third party application-store server, onto their computing device230. When downloaded, such application may be stored on the computing device's internal non-volatile memory, such as RAM or flash memory. Computing device230is preferably a mobile device, such as smartphone234or tablet236. When the user launches the application, processor310may prompt the user via the computing device's display interface320to provide patient specific information, such as age, gender, weight, and height. However, processor310may prompt to the user to input this information at any time, such as after the user's facial features are measured. Processor310may also present a tutorial, which may be presented audibly and/or visually, as provided by the application to aid the user in understanding their role during the process. The prompts may also require information for patient interface type, e.g. nasal or full face, etc. and of the type of device for which the patient interface will be used. Also, in the pre-capture phase400, the application may extrapolate the patient specific information based on information already gathered by the user, such as after receiving captured images of the user's face, and based on machine learning techniques or through artificial intelligence. 8.4.3.1.1 Sensor Activation410 When the user is prepared to proceed, which may be indicated by a user input or response to a prompt via user control/input interface331, processor310activates sensor340as instructed by the application's processor control instructions352. Sensor340is preferably the mobile device's forward facing camera, which is located on the same side of the mobile device as display interface320. The camera is generally configured to capture two-dimensional images. Mobile device cameras that capture two-dimensional images are ubiquitous. The present technology takes advantage of this ubiquity to avoid burdening the user with the need to obtain specialized equipment. 8.4.3.1.2 Display420 Around the same time sensor/camera340is activated, processor310, as instructed by the application, presents a capture display on the display interface320.FIG.7Adepicts an example of a capture display322and of contents thereof, which may include a camera live action preview324, a reference feature326, a targeting box328, and one or more status indicators327or any combination thereof. In this example, the reference feature326is displayed centred on the display interface and has a width corresponding to the width of the display interface320. The vertical position of the reference feature326may be such that the top edge of reference feature326abuts the upper most edge of the display interface320or the bottom edge of reference feature326abuts the lower most edge of the display interface320. A portion of the display interface320will display the camera live action preview324, typically showing the user's facial features captured by sensor/camera340in real time if the user is in the correct position and orientation. Live action preview324is a stream of images/content seen/detected by the camera/sensor340in, for example, real time. Thus, if the user directs the front facing camera340toward the user's facial features, the user's facial features may be presented on display interface320. Similarly, if the user directs the front facing camera340toward a mirror330, the reflection in the mirror330, which would preferably include the display interface320and one or more of its contents including the reference feature326, is displayed on the display interface320as part of live action preview324. However, it should be understood that, while live action preview324can include the patient's facial features, it is not necessary to display such facial features on display interface320, as is illustrated byFIG.7A. Nevertheless, the sensor340does capture the facial features during this aspect of the process. Reference feature326is a feature that is known to computing device230(predetermined) and provides a frame of reference to processor310that allows processor310to scale captured images. The reference feature may preferably be a feature other than a facial or anatomical feature of the user. Thus, during the image processing phase600, it assists processor310in determining when certain alignment conditions are satisfied, such as during the pre-capture phase400. As shown inFIG.7A, reference feature326may be a quick response (QR) code or known exemplar or marker, which can provide processor310certain information, such as scaling information, orientation, and/or any other desired information which can optionally be determined from the structure of the QR code. The QR code may have a square or rectangular shape. When displayed on display interface320, reference feature326has predetermined dimensions, such as in units of millimeters or centimeters, the values of which may be coded into the application and communicated to processor310at the appropriate time. The actual dimensions of reference feature326may vary between various computing devices. In some versions, the application may be configured to be a computing device model-specific in which the dimensions of reference feature326, when displayed on the particular model, is already known. However, in other embodiments, the application may instruct processor310to obtain certain information from device230, such as display size and/or zoom characteristics that allow the processor310to compute the real world/actual dimensions of reference feature326as displayed on display interface320via scaling. Regardless, the actual dimensions of reference feature326as displayed on the display interfaces320of such computing devices are generally known prior to post-capture image processing. Along with reference feature326, targeting box328may be displayed on display interface320and overlie live action preview324. Targeting box328allows the user to align certain components within capture display322in targeting box328, which is desired for successful image capture. In one example illustrated byFIG.7A, the application may include a capture condition that reference feature326will be entirely within target box328prior to image capture. Alignment of reference feature326within targeting box328may improve detection during later processing and ensure good position and alignment of reference feature326within the captured image. Additionally, alignment within targeting box328may help to ensure display interface320alignment along a superior-inferior axis so as to avoid excessive radial inward or outward tilt and rotationally about the superior-inferior axis to maintain display interface320generally parallel with a mirror330, for example. The status indicator327provides information to the user regarding the status of the process. This helps ensure the user does not make major adjustments to the positioning of the sensor/camera prior to completion of image capture. Thus, in the embodiment depicted inFIG.7A, when the user holds display interface320parallel to the facial features to be measured and presents user display interface320to a mirror330or other reflective surface, reference feature326is prominently displayed and overlays the real-time images seen by camera/sensor340and as reflected by the mirror330. This reference feature326may be fixed near the top of display interface320. Reference feature326is prominently displayed in this manner at least partially so that sensor340can clearly see reference feature326so that processor310can easily identify feature326. In addition, reference feature326may overlay the live view of the user's face, which helps avoid user confusion. A moveable reference feature image329, which is a real-time live view reflection of reference feature326, is positionable within the alignment box by movement of the display device having the image sensor. Ultimately, when movable reference feature image329is positioned within targeting box328, alignment box and moveable reference feature image329will be positioned and aligned in an offset manner relative to reference feature326(e.g., directly below), which facilitates usability. Other features or information can be displayed by processor310on display interface320. For instance, the application may establish parameters that must be satisfied regarding lighting conditions. If lighting conditions are unsatisfactory, processor310may display a warning on the display interface or output an audible warning to the user and instruct the user on steps that can be taken that can help rectify the unsatisfactory lighting conditions. FIG.7Billustrates an alternative capture display embodiment320a, which similarly includes a targeting box328and a reference feature326. However, unlikeFIG.7A, live action preview324shows the user's face, which in this case is alternatively designated for placement within targeting box328, rather than being designated to contain reference feature326. Further, display320aalso includes detection points321and bounding boxes323generated by the processor310. Processor310, controlled by instructions from the application, may detect and identify certain facial features in live action preview324. These may be displayed for the user using detection points321and bounding boxes323. This may help the user know that certain conditions, such as lighting, are satisfactory for image capture as it indicates that processor310is identifying these facial features with detection points321and bounding them in bounding boxes323. 8.4.3.1.3 Planar Alignment and Reflected Image430 As depicted inFIG.7C, the user may position themselves or their face and computing device230in front of a mirror330such that the user's facial features and display interface320are reflected back to sensor340. The user may also be instructed by processor310, via display interface320, by audible instructions via a speaker of the computing device230, or be instructed ahead of time by the tutorial, to position display interface320in a plane of the facial features to be measured. For example, the user may instructed to position display interface320such that it is facing anteriorly and placed under, against, or adjacent to the user's chin in a plane aligned with certain facial features to be measured. For example, display interface320may be placed in planar alignment with the sellion and suprementon. As the images ultimately captured are two-dimensional, planar alignment430helps ensure that the scale of reference feature326is equally applicable to the facial feature measurements. In this regard, the distance between the mirror330and both of the user's facial features and the display will be approximately the same. 8.4.3.1.4 Detecting Reference Feature440 When the user is positioned in front of a mirror330and display interface320, which includes reference feature326, is roughly placed in planar alignment with the facial features to be measured, processor310checks for certain conditions to help ensure sufficient alignment. One exemplary condition that may be established by the application, as previously mentioned, is that the entirety of reference feature326must be detected within targeting box328in order to proceed. If processor310detects that reference feature326is not entirely positioned within targeting box328, processor may310prohibit or delay image capture. The user may then move their face along with display interface320to maintain planarity until reference feature326, as displayed in the live action preview, is located within targeting box328. This helps optimized alignment of the facial features and display interface320with respect to mirror330for image capture. 8.4.3.1.5 Reading IMU & Tilt Alignment450 When processor310detects the entirety of reference feature326within targeting box328, processor310may read the computing device's IMU342for detection of device tilt angle, provided that computing device230includes an IMU342. The IMU342may include an accelerometer or gyroscope, for example. Thus the processor310may evaluate device tilt such as by comparison against one or more thresholds to ensure it is in a suitable range. For example, if it is determined that computing device230, and consequently display interface320and user's facial features, is tilted in any direction within about +/−5 degrees, the process may proceed to the capture phase500. In other embodiments, the tilt angle for continuing may be within about +/−10 degrees, +/−7 degrees, +/−3 degrees, or +/−1 degree. If excessive tilt is detected a warning message may be displayed or sounded to correct the undesired tilt. This is particularly useful for assisting the user to help prohibit or reduce excessive tilt, particularly in the anterior-posterior direction, which if not corrected, could pose as a source of measuring error as the captive reference image will not have a proper aspect ratio. 8.4.3.2 Capture Phase500 8.4.3.2.1 Capture Initiation510 When alignment has been determined by processor310as controlled by the application, processor310proceeds into the capture phase500. This phase500preferably occurs automatically once the alignment parameters and any other conditions precedent are satisfied. However, in some embodiments, the user may initiate the capture in response to a prompt to do so. 8.4.3.2.2 Capture “n” Images520 When image capture is initiated, the processor310via sensor340captures a number n of images, which is preferably more than one image. For example, the processor310via sensor340may capture about 5 to 20 images, 10 to 20 images, or 10 to 15 images, etc. The quantity of images captured may be time-based. In other words, the number of images that are captured may be based on the number of images of a predetermined resolution that can be captured by sensor340during a predetermined time interval. For example, if the number of images sensor340can capture at the predetermined resolution in 1 second is 40 images and the predetermined time interval for capture is 1 second, sensor340will capture 40 images for processing with processor310. The quantity of images may be user-defined, determined by server210based on artificial intelligence or machine learning of environmental conditions detected, or based on an intended accuracy target. For example, if high accuracy is required then more captured images may be required. Although, it is preferable to capture multiple images for processing, one image is contemplated and may be successful for use in obtaining accurate measurements. However, more than one image allows average measurements to be obtained. This may reduce error/inconsistencies and increase accuracy. The images may be placed by processor310in stored data354of memory/data storage350for post-capture processing. 8.4.3.3 Post-Capture Image Processing Phase600 Once the images are captured, the images are processed by processor310to detect or identify facial features/landmarks and measure distances therebetween. The resultant measurements may be used to recommend an appropriate patient interface size. This processing may alternatively be performed by server210receiving the transmitted captured images and/or on the user's computing device (e.g., smart phone). Processing may also be undertaken by a combination of the processor310and server210. In one example, the recommended patient interface size may be predominantly based on the user's nose width. In other examples, the recommended patient interface size may be based on the user's mouth and/or nose dimensions. 8.4.3.3.1 Read Images and Detect Facial Features610&620 Processor310, as controlled by the application, retrieves one or more captured images from stored data354. The image is then extracted by processor310to identify each pixel comprising the two-dimensional captured image. Processor310then detects certain pre-designated facial features within the pixel formation. Detection may be performed by processor310using edge detection, such as Canny, Prewitt, Sobel, or Robert's edge detection, for example. These edge detection techniques/algorithms help identify the location of certain facial features within the pixel formation, which correspond to the patient's actual facial features as presented for image capture. For example, the edge detection techniques can first identify the user's face within the image and also identify pixel locations within the image corresponding to specific facial features, such as each eye and borders thereof, the mouth and corners thereof, left and right alares, sellion, supramenton, glabella and left and right nasolabial sulci, etc. Processor310may then mark, tag or store the particular pixel location(s) of each of these facial features. Alternatively, or if such detection by processor310/server210is unsuccessful, the pre-designated facial features may be manually detected and marked, tagged or stored by a human operator with viewing access to the captured images through a user interface of the processor310/server210. 8.4.3.3.2 Measure Distance Between Facial Features630 Once the pixel coordinates for these facial features are identified, the application controls processor310to measure the pixel distance between certain of the identified features. For example, the distance may generally be determined by the number of pixels for each feature and may include scaling. For example, measurements between the left and right alares may be taken to determine pixel width of the nose and/or between the sellion and supramenton to determine the pixel height of the user's face. Other examples include pixel distance between each eye, between mouth corners, and between left and right nasolabial sulci to obtain additional measurement data of particular structures like the mouth. Further distances between facial features can be measured. 8.4.3.3.3 Apply Anthropometric Correction Factor640 Once the pixel measurements of the pre-designated facial features are obtained, an anthropometric correction factor(s) may be applied to the measurements. It should be understood that this correction factor can be applied before or after applying a scaling factor, as described below. The anthropometric correction factor can correct for errors that may occur in the automated process, which may be observed to occur consistently from patient to patient. In other words, without the correction factor, the automated process, alone, may result in consistent results from patient to patient, but results that may lead to a certain amount of mis-sized patient interfaces. The correction factor, which may be empirically extracted from population testing, shifts the results closer to a true measurement helping to reduce or eliminate mis-sizing. This correction factor can be refined or improved in accuracy over time as measurement and sizing data for each patient is communicated from respective computing devices to server210where such data may be further processed to improve the correction factor. The anthropometric correction factor may also vary between the forms of patient interfaces. For instance, the correction factor for a particular patient seeking an FFM may be different from the correction factor when seeking a nasal mask. Such a correction factor may be derived from tracking of mask purchases, such as by monitoring mask returns and determining the size difference between a replacement mask and the returned mask. 8.4.3.3.4 Measure Reference Feature650 In order to apply the facial feature measurements to patient interface sizing, whether corrected or uncorrected by the anthropometric correction factor, the measurements may be scaled from pixel units to other values that accurately reflect the distances between the patient's facial features as presented for image capture. The reference feature may be used to obtain a scaling value or values. Thus, processor310similarly determines the reference feature's dimensions, which can include pixel width and/or pixel height (x and y) measurements (e.g., pixel counts) of the entire reference feature. More detailed measurements of the pixel dimensions of the many squares/dots that comprise a QR code reference feature326, and/or pixel area occupied by the reference feature and its constituent parts may also be determined. Thus, each square or dot of the QR code reference feature326may be measured in pixel units to determine a scaling factor based on the pixel measurement of each dot and then averaged among all the squares or dots that are measured, which can increase accuracy of the scaling factor as compared to a single measurement of the full size of the QR code reference feature326. However, it should be understood that whatever measurements are taken of the reference feature, the measurements may be utilized to scale a pixel measurement of the reference feature to a corresponding known dimension of the reference feature. 8.4.3.3.5 Calculate Scaling Factor660 Once the measurements of the reference feature are taken by processor310, the scaling factor is calculated by processor310as controlled by the application. The pixel measurements of reference feature are related to the known corresponding dimensions of the reference feature, e.g. the reference feature326as displayed by display interface320for image capture, to obtain a conversion or scaling factor. Such a scaling factor may be in the form of length/pixel or area/pixel{circumflex over ( )}2. In other words, the known dimension(s) may be divided by the corresponding pixel measurement(s) (e.g., count(s)). 8.4.3.3.6 Apply Scaling Factor670 Processor310then applies the scaling factor to the facial feature measurements (pixel counts) to convert the measurements from pixel units to other units to reflect distances between the patient's actual facial features suitable for mask sizing. This may typically involve multiplying the scaling factor by the pixel counts of the distance(s) for facial features pertinent for mask sizing. These measurement steps and calculation steps for both the facial features and reference feature are repeated for each captured image until each image in the set has facial feature measurements that are scaled and/or corrected. 8.4.3.3.7 Average Facial Feature Measurements680 The corrected and scaled measurements for the set of images may then optionally be averaged by processor310to obtain final measurements of the patient's facial anatomy. Such measurements may reflect distances between the patient's facial features. 8.4.3.4 Comparison and Output Phase700 In the comparison and output phase700, results from the post-capture image processing phase600may be directly output (displayed) to a person of interest or compared to data record(s) to obtain an automatic recommendation for a patient interface size. 8.4.3.4.1 Display Averaged Results710 Once all of the measurements are determined, the results (e.g., averages) may be displayed by processor310to the user via display interface320. In one embodiment, this may end the automated process. The user/patient can record the measurements for further use by the user. 8.4.3.4.2 Forward Averaged Results720 Alternatively, the final measurements may be forwarded either automatically or at the command of the user to server210from computing device230via communication network220. Server210or individuals on the server-side may conduct further processing and analysis to determine a suitable patient interface and patient interface size. 8.4.3.4.3 Compare Results, Select and Display Recommended Size730&732 In a further embodiment, the final facial feature measurements that reflect the distances between the patient's actual facial features are compared by processor310to patient interface size data such as in a data record. The data record may be part of the application for automatic facial feature measurements and patient interface sizing. This data record can include, for example, a lookup table accessible by processor310, which may include patient interface sizes corresponding to a range of facial feature distances/values. Multiple tables may be included in the data record, many of which may correspond to a particular form of patient interface and/or a particular model of patient interface offered by the manufacturer. Processor310compares the user's measurements to determine an appropriate size or “best fit,” such as by identifying one or more ranges within which the measurements fall and then selecting the interface size, such as from a group of standard sizes (e.g., small, medium, or large, etc.), associated with that identified range(s). Processor310may then recommend the identified patient interface size in the form of a display presented on display interface320. Processor310may even automatically forward the recommendation via email, text message or instant messenger for the user's records. The user may further have the option provided to it via processor310to order a patient interface with the recommended size. The order may be communicated to server210where further steps for order fulfilment may take place. 8.4.4 Alternatives and Additional Application Features The following describes additional and/or alternative features that may be implemented with the above described example methods, systems and devices. The below are not intended to be exhaustive, but are merely examples of the many variations that can be achieved while conforming to the present technology. 8.4.4.1 Alternative Computing Devices In the above examples, the method is at least in part performed by a mobile device as computing device230. However, the facial feature measuring and/or interface sizing can be performed, at least in part, with desktop or laptop232, for example. In such example, the image capture and post-image processing phases500,600would be similar to that described above. However, the method may differ in the pre-capture phase400. In this phase, rather than displaying reference feature326on display interface320and positioning display interface320and user's facial features in front of mirror330so that reference feature326is captured in the image, the reference feature can be printed onto a sheet of paper at a known scale and held by the user. As such, webcam233could display, via processor310, a live action preview of the user and the reference feature on the display interface, which may be a monitor. A targeting box, similar to that described above, would also be displayed, in which case the user may reposition themselves and the reference feature so that the reference feature or user's face is positioned within the targeting box. 8.4.4.2 Alternative Reference Features While example reference feature326displayed by display interface320described above may include a QR code or other processor detectable reference feature, other reference features of known dimensions, either displayed by display interface320or positioned in close proximity to the user, may be utilized. When the reference feature is not a displayed feature captured through a mirror330, the reference feature may be a known physical feature, suggested by the application, and positioned near the user. For example, a sheet of paper, coin, credit card or cardboard cut-out with a QR code superimposed thereon may be used as a reference feature. While such close-positioned reference features could be used in the method implementing a mirror330, such reference features could be particularly useful in a desktop computing device method described directly above. In one example a user may hold up a credit card of known size (standard) such that the processor may detect the card as the reference feature for purposes of determining a scaling factor. In another embodiment, a sheet of paper of known size, such as size A4 paper, can be held in either landscape or portrait orientation. Processor, via sensor233may detect corners and/or aspect ratio of the paper to determine when it is aligned with an alignment box as a precondition to image capture and/or to determine a scaling factor from one or more images including the paper reference feature, which is of known size. A further implementation in which a coin is used as the reference feature is described in more detail below. 8.4.4.2.1 Coin FIG.8contains a flow chart illustrating a method800that may be used in place of the process600to implement the post-capture image processing phase in an implementation in which a coin is used as the reference feature. In such an implementation, there is no need for the pre-capture phase400. The coin1300is placed on the user's forehead1310approximately above the nose, as illustrated inFIG.13A, prior to the image capture phase500described above. Under normal skin conditions the coin will adhere to the user's forehead1310for sufficient time to complete the image capture phase500. The method800is then carried out to implement the post-capture image processing phase, and finally the comparison and output phase700is carried out as described above. The method800starts at step810, which is the first step of a loop over all images captured during the image capture phase. Step810reads the next captured image. Step820detects facial features (eyes and mouth) in the captured image. Step820will be described in more detail below with reference toFIG.9. Step830detects the reference feature (the coin) in the captured image. Step830will be described in more detail below with reference toFIG.10. Step840uses the reference feature to calculate a scaling factor. Step840will be described in more detail below with reference toFIG.11. The next step850makes a measurement of the facial features detected in the captured image at step820. Step850may alternatively be performed before steps830and840. Step850will be described in more detail below with reference toFIG.12. Step860then multiplies the facial feature measurement made at step850by the scaling factor calculated at step840. Step870checks whether the end of the captured image set has been reached. If not (“N”), the method800returns to step810to read the next captured image. Otherwise (“Y”), the final step880averages the scaled facial feature measurements for all captured images to produce a final scaled facial feature measurement ready for the comparison and output phase700described above. FIG.9contains a flow chart illustrating a method900that may be used to implement the facial feature detection step820of the method800according to one implementation. The method900starts at step902, which detects the faces in the image. The faces within the image may be found, for example, using an OpenCV cascade classifier with thresholds on object size. Each pair of eyes and mouth within each detected face is found using corresponding cascade classifiers. This result of step902is a list of rectangles or “boxes” defining the boundary of each detected face within the image. For each detected face, a list of boxes defining the position and extent of the eye(s) and mouth(s) found within the face are returned by step902. Step902also returns, for each detected face, a box for each coin found within the face. These boxes may be used by step830to detect the correct reference feature within the detected face. The following steps905to960are carried out for the largest face box detected at step902. Steps905to960filter the features detected within the face to choose only the “best” matches and remove any duplicates/incorrect matches. Step905checks whether fewer than two eyes or no mouth was found by the face detection step902. If so (“Y”), the method900ends at step960. If not (“N”), step910checks whether exactly two eyes and one mouth were found at step902. If so (“Y”), step915stores the two eye boxes and the mouth box, and the method900then ends at step960. If not (“N”), step920checks whether two eyes were found at step902. If so (“Y”), step925stores the two eye boxes, and the method900proceeds to step940described below. If not (“N”), step930checks whether one mouth was found at step902. If so, step935stores the mouth box, and the method900proceeds to step940. If not (“N”), step940checks whether more than one mouth was found at step902. If so (“Y”), step945stores the widest mouth box of the multiple mouth boxes, and the method900then ends at step960. Otherwise (“N”), step950checks whether no mouth was found at step902. If so (“Y”), step955stores a null mouth box (with corners (0,0) and (0,0)), and the method900then ends at step960. Otherwise (“N”), the method900ends at step960. In other cascade-classifier implementations of step820, other criteria may be used to filter the boxes found within the largest face box at step902to return the most probable eye and mouth boxes. FIG.10contains a flow chart illustrating a method1000that may be used to implement the reference feature detection step830of the method800according to the implementation of the method800in which the method900is used to implement the step820. Steps1010to1090are carried out on the largest face box detected at step902of the method900to identify the “best” detected coin within the face. Step1010checks whether no coin was detected within the face at step902. If so (“Y”), the method1000ends at step1090. Otherwise (“N”), step1020checks whether exactly one coin was detected at step902. If so (“Y”), step1030stores the coin box, and the method1000ends at step1090. Otherwise (“N”), step1040loads a “template image”, i.e. a reference image of the reference feature. Steps1050to1070are then carried out for each of the multiple coins detected in the face at step902. Step1050computes a measure of match between the current coin and the reference image. In one implementation, step1050counts the number of matching points between the current coin and the reference image. Step1060then stores the measure of match found at step1050. Step1070checks whether all the coins have been matched. If not (“N”), the method1000returns to step1050. If so (“Y”), step1080finds the largest measure of match stored at step1060, and stores the box of the coin with the largest match measure. The method1000then ends at step1090. FIG.11contains a flow chart illustrating a method1100that may be used to implement the calculating of a scaling factor step840of the method800according to one implementation. Steps1105to1175are carried out for the “best” coin detected at step830. The first step1105converts the image contained within the coin box to separate hue (H) and saturation (S) channels. Step1110then computes a histogram for each of the H and S channels of the box. Then, step1115finds the peaks of the H and S channel histograms. Steps1120to1150are then carried out for each pair of peaks in the H and S channel histograms. Step1120thresholds the H and S channel images using thresholds equal to the current respective peak locations. Step1130then detects images in the thresholded (binary) H and S images. In one implementation, step1130uses a Canny edge detection filter on the binary images. Step1135then combines the two edge images using a binary “AND” operation, such that the only surviving edge pixels are those that were detected in both H and S binary images. The next step1140fits an ellipse to the combined edge image. Step1140may use any convenient method, e.g. linear regression, to fit an ellipse to the combined edge image. An ellipse is fit to the combined edge image at step1140because a circle rotated three-dimensionally through any angle appears as an ellipse. Step1145calculates the coefficient of determination (written as R2) of the ellipse fitted at step1140. Step1150then removes the ellipse if the coefficient of determination is too low or the number of edge pixels in the combined edge image is too low. After the final pair of H, S histogram peaks has been processed, step1155selects the ellipse with the highest coefficient of determination. Step1160then compares the width (horizontal diameter) and height (vertical diameter) of the selected ellipse. If the width is greater than the height (“Y”), step1165sets the measured diameter of the coin to the width of the ellipse (as a pixel count). Otherwise (“N”), step1170sets the measured diameter of the coin to the height of the ellipse (as a pixel count). Finally, step1175calculates the scaling factor as the true diameter of the coin (a known quantity, e.g. in millimetres) divided by the measured diameter of the coin from step1170or step1165. This calculation is based on the fact that when a circular disc is rotated through any angle its projected outline appears as an ellipse, and the length of the major axis of the ellipse is the diameter of the disc regardless of the amount or direction of rotation. This fact underpins the suitability of circular reference features such as coins for calculating scaling factors for image measurements. FIG.12contains a flow chart illustrating a method1200that may be used to implement the facial feature measurement step850of the method800according to one implementation in which the facial feature measurement is face height. The method1200starts at step1210, which draws an eyeline, i.e. a line between the centers of the two eye boxes selected at step820. The eyeline is illustrated as the line1360inFIG.13B, while the two eye boxes are illustrated as1330and1340. Step1220determines a midpoint of the eyeline. Step1230then draws a midline from the midpoint found at step1220in a direction perpendicularly downwards from the eyeline found at step1210. The midline drawn at step1230is illustrated as1370inFIG.13B. Step1240then measures the face height as the length of the midline to the point where the midline intersects the bottom of the mouth box selected at step820. The face height measured at step1240may differ from the actual face height of the user because of a small rotation of the face around a horizontal axis. The ellipse found at step840can supply a correction for such a small horizontal rotation. The ratio of the true face height (in pixels) to the measured face height from step1240is the same as the ratio of the true height of the coin (in pixels) to the measured height of the ellipse from step1160, if that height is smaller than the measured width (indicating horizontal rotation has taken place). Step1250therefore checks whether the measured height of the ellipse from step1160is less than the measured width, also from step1160. If so (“Y”), the measured face height from step1240may be corrected for horizontal rotation at step1260by multiplying the measured face height by the ratio of the true height of the coin (in pixels) to the measured height of the ellipse from step1160. The true height of the coin in pixels is simply the length of the major axis of the ellipse. An example of an ellipse for a detected coin is illustrated as1320inFIG.13B. In the ellipse1320, the width is less than the height, so there is no need for correction of the measured face height for horizontal rotation. An alternative implementation of the method800makes use of an active shape model (ASM) [1] to detect the facial features at step820. In general, an active shape model uses identified landmarks within a set of training images to develop a deformable model for the relative positions of the landmarks (the shape) and a statistical model of the pixel values provided by the images at those positions. The deformable shape model is defined as: x=x+Pb(Eq. 1) where x is a vector of landmark positions (the shape) as predicted by the model,xis the mean shape, P is a set of eigenvectors also determined from the training set, and b is a vector of weights (the pose) allowing for the shape to be deformed. The statistical model of pixel values is determined by sampling a range of pixels normal to each landmark within each image in the training set. After sampling, a vector of mean pixel values is determined for each landmark as well as the corresponding covariance matrix. The pixel model for each landmark comprises the vector of mean pixel values and the corresponding covariance matrix. The process of searching for landmarks in a captured image using an ASM is iterative. For the first iteration, the mean shapexis used as the shape estimate x and is superimposed on the captured image in an initial location that is presumably not too far from the landmarks in the captured image, e.g. centred within the captured image. A range of pixel values are sampled at each landmark position in the captured image as defined by the current shape estimate x. The new estimated landmark positions are then selected by determining the range of pixels with the smallest Mahalanobis distance (covariance-weighted Euclidean distance) from the mean pixel values in the pixel model. The scale, translation and rotation of the shape estimate x are then updated to best match the new estimated landmark positions. Any residual error that remains is then used to deform the model by updating the current pose estimate b. The shape estimate x is then updated using Eq. 1. These steps are repeated until some high proportion (e.g. at least 90%) of the estimated landmark positions have converged within a small radius (e.g. 2 pixels) of the previous estimated positions; at this point the changes to shape scale, translation, rotation, and pose are presumed minimal. The convergence may be accelerated by repeating the iterative process over a three-level Gaussian pyramid with each level L containing a copy of the captured image decimated by 2L. Changes to landmark positions at coarse levels produce larger relative movements, and once shape convergence occurs, the iterative process moves up a level, producing finer changes in shape and pose.FIG.14illustrates the landmark positions identified by the iterative process in a typical captured image1400. In the implementation of the method800in which the ASM is used to implement step820, the reference feature detection step830may initially use the cascade classifier described above in relation to step902to detect one or more “coin boxes”, and then use the method1000described above to select the “best” detected coin. In the alternative implementation of the method800, the facial feature measurement step850measures the pixel distance between two selected landmarks that are suitable for sizing the mask. In one example illustrated inFIG.14, suitable for sizing a nasal mask (seeFIG.1B), the selected landmarks are the left and right alar crest points1410and1420(seeFIG.3B), yielding a facial feature measurement of nose width. 8.4.4.2.2 Cornea In a further implementation, the reference feature may be a feature of the eye(s) such as the iris or cornea of the user. Iris diameter is remarkably similar across all races, and does not grow after the early teens. The range of corneal diameters (horizontal visible iris diameter) is within 11.0 to 12.5 mm for 95% of adults [2]. The advantage of using the eye feature is that it obviates the need for an extraneous reference feature such as a coin, credit card, QR code etc. to be present in the captured image. In such an implementation, method800may be implemented as follows. The bounding points of one or each cornea may be detected as part of an ASM implementation of the facial feature detection step820, in which the bounding points for each cornea are landmarks in the ASM. A separate reference feature detection step830would therefore not be required. Step840may compute the diameter of one or each cornea as the distance between the bounding points of the or each cornea, and compute the scaling factor as the ratio of the median corneal diameter of 11.75 mm to the measured corneal diameter (in pixels) for one or other eye, or the average of both measured corneal diameters. In a variation of step840, the median corneal diameter is chosen based on knowledge of the user's age, since variation of corneal diameter across people of a given age is less than variation across the general adult population. 8.4.4.3 Assistant Mode A mirror330is described above as being implemented to assist a user in capturing an image. However, the application for measuring and sizing may allow for alternatives. For example, processor310, as controlled by the application, may provide the user with the option to use mirror330or a third party to hold sensor340and aim it directly at the intended mask user. Thus, the intended mask user may have his/her facial features and the reference feature captured by a relative, a friend, or a stationary stand that holds sensor340. As such, the application may include a “partner” or “assistant” mode in which display interface320may present a live camera preview and a targeting box, such as camera live action preview324and targeting box328. The application may then instruct the assistant on how to capture suitable images for mask sizing. For example, in this mode, processor310may optionally operate to allow the assistant to select the front facing camera or rear facing camera, which may be integrated into smartphone234or tablet236. Thus, the assistant may look at display interface320and point the rear facing camera at the patient's facial features and a reference feature that may be held by the patient. “Partner” or “assistant” mode may also provide the user with the option to operate the front facing camera. Optionally, a stand can be used to hold the mobile device, while the user moves with respect to camera340until a reference feature held by the user is properly aligned within a target box displayed on display interface320. 8.4.4.4 Lighting and Light Filters It is also described above that if lighting conditions are unsatisfactory, processor310, as controlled by the application, may notify the user that conditions are unsatisfactory and provide instructions for moving to a location of brighter or dimmer lighting. However, recognizing that satisfying this condition may not always be possible, the application may control the processor310to apply a light filter to the sensor/camera340to allow for operation in a wide array of lighting conditions. If the environment is too bright, a specific filter may be automatically applied so that the user's facial features can be easily detected. Conversely, where lighting conditions are too dark, another filter may be implemented to detect the desired facial features or the computing device's light source to illuminate the patient's facial features. This may be performed during the pre-capture phase400. 8.4.4.5 Alternative Sensors The method described herein is particularly useful for measuring and sizing based on two-dimensional images as cameras for two-dimensional images are ubiquitous. However, the disclosed technology contemplates other types of sensors that may be able to determine scale without the use of a reference feature, such as a laser and detector combination. For example, such a sensor may detect distance to the target, which can be used to calculate a scale. Other sensors may be utilized to obtain three-dimensional renderings. For example, a stereoscopic camera may be used to obtain a three-dimensional image. A similar process to that described above can be performed on the three-dimensional image. In such an embodiment, the reference feature can be a three dimensional object with known x, y, and z dimensions. Further sensors that can be used are a strobing light source and detector combination. Reflected light from the strobing light source can be timed to calculate distance in the processor. 8.4.4.6 Storage Mediums for the Application In the exemplary method detailed above, the application for automatic facial feature measuring and patient interface sizing is downloaded to the computing device's internal memory from a third party server, such as an application-store server. However, in one embodiment, the application may be downloaded to the computing device's internal memory/data storage350via the network from server210or via some other external computer-readable storage medium, such as a flash drive, SD card or optical disc. Alternatively, in another embodiment, the application may be stored in an external computer-readable storage medium and directly linked to processor310. In a further embodiment, the application including its corresponding processor instructions and data, may be stored on a medium external to computing device230, such as server210, and accessed by computing device230via a web browser (e.g., Google Chrome® or Internet Explorer®) and/or web browser extension such as Adobe Flash®. 8.4.4.7 Tracking & Updates The application may include additional functionality such as tracking the user's weight over time and corresponding facial changes as the user's weight fluctuates, which may be integrated into the patient interface recommendation analysis. For example, weight, age and/or height may be a parameter that is considered in the data record for selection of the appropriate mask size. Additionally, the application may record the particular patient interfaces that the user/patient orders and the date that the order occurred so that replacement and/or maintenance reminders can be provided to the user via the application and/or for general health monitoring. In addition, the application can be updated from time to time, which can be provided to users via an application store or server210. These updates can provide users with new reference features and the known dimension information for the reference feature, updated mask sizing tables and new mask type information, and other data processing information, such as updated anthropometric correction factors, which can be can be continuously refined as more and more end users use the application and send their information back through server210. Advantageously, the ability to update the reference feature remotely can enable more accurate measurements to be obtained or improve responsiveness of the application when subsequent reference features are developed. Remote updating may be a seamless background process that requires little or no user interaction, for example, the updating occurring when the application is loaded and an update is available. Remote updating of the application means that the subsequent versions of the application can also take advantage of more powerful, better or additional hardware components that are provided with newer models of computing device230. 8.4.4.8 Other Image Sources In an exemplary method described above, the images are captured by a sensor340such as a camera that is located on the same computing device230as the processor310that carries out the application360for facial feature measuring and patient interface sizing. However, in other implementations, the processor310may receive the images from another source over the network220to which the computing device230is connected. Examples of other sources include an MMS message, email, a web or other image server, e.g. the server210. In still other implementations in which the server210carries out the application360for facial feature measuring and patient interface sizing, the server210may receive the images from another source over the network220to which the server210is connected. 8.5 Other Remarks A portion of the disclosure of this patent document contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in Patent Office patent files or records, but otherwise reserves all copyright rights whatsoever. Unless the context clearly dictates otherwise and where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit, between the upper and lower limit of that range, and any other stated or intervening value in that stated range is encompassed within the technology. The upper and lower limits of these intervening ranges, which may be independently included in the intervening ranges, are also encompassed within the technology, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the technology. Furthermore, where a value or values are stated herein as being implemented as part of the technology, it is understood that such values may be approximated, unless otherwise stated, and such values may be utilized to any suitable significant digit to the extent that a practical technical implementation may permit or require it. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this technology belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present technology, a limited number of the exemplary methods and materials are described herein. When a particular material is identified as being used to construct a component, obvious alternative materials with similar properties may be used as a substitute. Furthermore, unless specified to the contrary, any and all components herein described are understood to be capable of being manufactured and, as such, may be manufactured together or separately. It must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include their plural equivalents, unless the context clearly dictates otherwise. As used herein, the terms “about,” “generally” and “substantially” are intended to mean that deviations from absolute are included within the scope of the term so modified. All publications mentioned herein are incorporated herein by reference in their entirety to disclose and describe the methods and/or materials which are the subject of those publications. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present technology is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates, which may need to be independently confirmed. The terms “comprises” and “comprising” should be interpreted as referring to elements, components, or steps in a non-exclusive manner, indicating that the referenced elements, components, or steps may be present, or utilized, or combined with other elements, components, or steps that are not expressly referenced. The subject headings used in the detailed description are included only for the ease of reference of the reader and should not be used to limit the subject matter found throughout the disclosure or the claims. The subject headings should not be used in construing the scope of the claims or the claim limitations. Although the technology herein has been described with reference to particular examples, it is to be understood that these examples are merely illustrative of the principles and applications of the technology. In some instances, the terminology and symbols may imply specific details that are not required to practice the technology. For example, although the terms “first” and “second” may be used, unless otherwise specified, they are not intended to indicate any order but may be utilised to distinguish between distinct elements. Furthermore, although process steps in the methodologies may be described or illustrated in an order, such an ordering is not required. Those skilled in the art will recognize that such ordering may be modified and/or aspects thereof may be conducted concurrently or even synchronously. It is therefore to be understood that numerous modifications may be made to the illustrative examples and that other arrangements may be devised without departing from the spirit and scope of the technology. 8.6 Reference Label List patient10bed partner20capture40air circuit50humidifier60patient interface100plenum chamber120structure130vent140forehead support150seal-forming structure160connection port170system200server210network220network222wireless network224wireless link226computing device230laptop232webcam233smartphone234tablet236architecture300processor310display interface320display320adetection points321capture display322bounding boxes323live action preview324reference feature326status indicators327targeting box328reference feature image329mirror330user control/input interface331sensor340IMU342memory/data storage350instructions352stored data354application360pre-capture phase400step410step420step430step440step450image capture phase500step510step520post-image processing phase600step610step620step630step640step650step660step670step680output phase700step710step720step730step732method800step810step820step830step840step850step860step870step880method900step902step905step910step915step920step925step930step935step940step945step950step955step960method1000step1010step1020step1030step1040step1050step1060step1070step1080step1090method1100step1105step1110step1115step1120step1130step1135step1140step1145step1150step1155step1160step1165step1170step1175method1200step1210step1220step1230step1240step1250step1260coin1300forehead1310ellipse1320line1360captured image1400right alar crest point1410right alar crest point1420 8.7 Cited References [1] Cootes, T. F., Taylor, C. J., Cooper, D. H., & Graham, J. (1995).Active Shape Models—Their Training and Application. Computer Vision and Image Understanding, 61(1), 38-59.[2] Florian Rufer, MD, Anke Schroder, MD, and Carl Erb, MD.White-to-White Corneal Diameter: Normal Values in Healthy Humans Obtained With the Orbscan II Topography System. Cornea, 24(3), 259-261, April 2005. | 77,360 |
11857727 | DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS As used herein, the singular form of “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise. As used herein, the statement that two or more parts or components are “coupled” shall mean that the parts are joined or operate together either directly or indirectly, i.e., through one or more intermediate parts or components, so long as a link occurs. As used herein, “directly coupled” means that two elements are directly in contact with each other. As used herein, “fixedly coupled” or “fixed” means that two components are coupled so as to move as one while maintaining a constant orientation relative to each other. As used herein, the word “unitary” means a component is created as a single piece or unit. That is, a component that includes pieces that are created separately and then coupled together as a unit is not a “unitary” component or body. As employed herein, the statement that two or more parts or components “engage” one another shall mean that the parts exert a force against one another either directly or through one or more intermediate parts or components. As employed herein, the term “number” shall mean one or an integer greater than one (i.e., a plurality). Directional phrases used herein, such as, for example and without limitation, top, bottom, left, right, upper, lower, front, back, and derivatives thereof, relate to the orientation of the elements shown in the drawings and are not limiting upon the claims unless expressly recited therein. FIG.1is a front perspective view of a patient interface device2according to an exemplary embodiment of the present invention.FIG.9is a side view andFIG.10is a front perspective view showing patient interface device2attached to a patient. Patient interface device2includes a frame member4and a cushion6coupled to frame member4, each of which is described in greater detail herein. FIGS.2,3,4, and5are front, rear, top and side elevational views, respectively, of frame member4of patient interface device2. Frame member4includes a generally annular central member8having first and second main arms10A,10B extending outwardly from opposites sides thereof. Main arm10A includes orifice12A extending therethrough, and main arm10B includes orifice12B extending therethrough. In the exemplary embodiment, orifices12A,12B are positioned at a location on main arms10A,10B adjacent central member8. The purpose of orifices12A,12B is described in detail elsewhere herein. In addition, as seen inFIGS.2and3, central member8defines central orifice14. Frame member4further includes a first branching member16A extending upwardly at an angle from main arm10A and a first branching member16B extending upwardly at an angle from main arm10B. In one particular, non-limiting embodiment, first branching members16A,16B extend upwardly from the respective main arm10A,10B at an angle of about 60 degrees, although other angles are also possible. Furthermore, frame member4also includes a second branching member18A extending downwardly at an angle from main arm10A and a second branching member18B extending downwardly at an angle from main arm10B. In one particular, non-limiting embodiment, second branching members18A,18B extend downwardly from the respective main arm10A,10B at an angle of about 30 degrees], although other angles are also possible. Also in one particular, non-limiting embodiment, main arms10A and10B extend for about 55-60 mm from the center of orifices12A,12B to the inner angles formed between the branching members16A and18A and16B and18B, respectively. Moreover, as seen inFIGS.1-5, the distal end of each of first branching member16A,16B and second branching member18A,18B includes a respective loop member20for receiving a respective strap22of headgear assembly24(FIGS.9and10). In the exemplary embodiment, frame member4is made of a thermoplastic or thermoset material. FIGS.6,7, and8are front perspective, front elevational and rear elevational views, respectively, of cushion6of patient interface device2. In the exemplary embodiment, cushion6is defined from a unitary piece of soft, flexible, cushiony, elastomeric material, such as, without limitation, silicone, an appropriately soft thermoplastic elastomer, a closed cell foam, or any combination of such materials. Cushion6includes a main body portion40having a sealing portion42coupled to a first end thereof. Sealing portion42is structured to form a seal against a face of the patient. In the illustrated embodiment, cushion6is in the form of a nasal mask. However, other types of patient sealing assemblies, such as a nasal/oral mask, nasal cannula, or a nasal cushion, which facilitate the delivery of the flow of breathing gas to the airway of a patient, may be substituted for cushion6while remaining within the scope of the present invention. In addition, main body portion40defines orifice44at the second end thereof opposite the first end. Orifice44is structured to enable cushion6to be fluidly coupled to a fluid connector such as an elbow conduit, which in turn is fluidly coupled a pressure generating device such as a ventilator or a CPAP machine through a gas delivery hose. Cushion6further includes generally cylindrically shaped posts46A and46B extending from first and second sides48A and48B, respectively, of main body40. Each post46A,46B is positioned about midway between the first and send end of cushion6. In addition, each post46A,46B includes inner cylindrical portion50, enlarged portion52, and outer cylindrical portion54. When patient interface device2is assembled, the second end of main body40is inserted through central orifice14defined by central member8. In addition, post46A is inserted through orifice12A and post46B is inserted through orifice12B. More specifically, as seen inFIG.1, in each case, outer cylindrical portion54and enlarged portion52are inserted through the respective orifice12A,12B such that each enlarged portion52rests against the outer surface of main arm10A,10B and prevents outer cylindrical portion54from sliding back through orifice12A,12B. In addition, each inner cylindrical portion50is able to turn within the respective orifice12A,12B. The branching nature of the sides of frame member4, giving it a “T” or “Y” shape, allows for flexing of frame member4in certain directions while at the same time limiting flexing in other directions. In particular, main arms10A,10B are able to flex in the directions shown by the arrows inFIG.4(i.e., parallel to the top and bottom surface of main arms10A,10B), but are not able to freely flex in a direction transverse to the longitudinal axis thereof (i.e., perpendicular to the top and bottom surface of main arms10A,10B). In addition, each of the first branching members16A,16B and second branching member18A,18B are able to flex independently of one another in the directions shown by the arrows inFIG.4(i.e., parallel to the top and bottom surface of the branching members), but are not able to freely flex in a direction transverse to the longitudinal axis thereof (i.e., perpendicular to the top and bottom surface of the branching members). This controlled flexing addresses several issues present in the prior art relating to seal, stability and comfort discussed elsewhere herein, as it passively accommodates for many facial and head geometries to allow for optimal fit and comfort. The branched structure of frame member4also increases the stability of patient interface device2through patient movement and hose torque, which provides an optimal seal for the patient. In addition, the selection of the material for frame member4in conjunction with the geometry of frame member4as described herein allows for flexing to accommodate the vast variation in patient facial structures and head dimensions. In the exemplary embodiment, the material will be soft enough to provide for flexing in the desired directions as described herein, but rigid enough to limit the flexing in non-desired directions as described herein. Also, the geometry will, in the exemplary embodiment, allow for accommodation of not only the temple, cheek and jaw regions, but will also cover varying head sizes and nose locations. The geometry of portions of frame member4may, for example, vary in thickness, existence of ribs or other structures, and/or general dimensioning to accommodate differences in flexing due to the material properties, but will maintain the branching shape described herein. Other alternative methods of controlling the direction of flexing of frame ember4in the various directions can be accomplished with the use of structures such as hinges incorporated therein. The hinge can be accomplished in a number of different ways, such as with mechanical interlocking (removable or permanent) or overmolding with materials such as silicone or other elastomers. Furthermore, the branching nature of the sides of frame member4, giving it the “T” or “Y” shape discussed above, moves the mounting or anchor point (i.e., loops20) for patient interface device2on the head of the patient through headgear assembly24further back along the side of the head. Typical mounting locations of nasal masks have been on one or many of the following: cheeks, forehead, and chin. By moving the mounting point away from the front of the face, it improves the issues with claustrophobia and line of sight infringement. It also limits the pressure and potential discomfort from over-tightening to the less sensitive areas of the face. In addition, the interaction between posts46A,46B and orifices12A,12B provide the connection point for cushion6to frame4. That connection point provides for a passive auto-adjustment mechanism for cushion6, as posts46A and46B, and thus cushion6, are able to rotate relative to frame member4. In the exemplary embodiment, each post46A,46B has enough interference with frame member4to limit excessive rotation but not enough resistance to prevent auto-adjustment. Also in the exemplary embodiment, the cylindrical shape of each post46A,46B, as opposed to an oval or other geometry, allows for an infinite amount of positions instead of discrete positioning. This auto-adjusting feature optimizes the angle of engagement of cushion6to the face of the patient and increases the chance for an optimal seal across many patient faces of differing sizes and shapes. It also decreases the chance of undue pressure along the sealing portion42of cushion6on the face (particularly the upper lip) of the patient. Lastly, this auto-adjusting feature provides the ability of cushion6to adjust during patient movement, thus increasing stability throughout the night. Thus, the combination of the flexing frame member4and the auto-adjusting cushion6allows for placement of frame member4on the face to vary in order to meet the individual patient's needs. This allows an opportunity for the patient to alleviate any possible pressure points and/or optimize seal and stability. In addition, the mounting point of cushion6to frame member4has been moved closer to the patient's face, which increases the stability of patient interface device2by moving the fulcrum closer to the patient's face (moment arm decreases). It also lessens the overall profile of patient interface device2, creating a lower profile that improves overall size and appearance. An alternative exemplary embodiment of the invention is shown inFIGS.11and12, and includes frame assembly60which may be coupled to cushion6as described elsewhere herein or another suitable cushion, such as, without limitation, a known or hereafter developed nasal/oral mask, nasal cushion, pillows style cushion or full face mask. Frame assembly60includes a frame member4as described elsewhere herein having inserts provided therein or attached (e.g., bonded) thereto (i.e., to the exterior surface) in the form of right and left stiffening structures62A and62B. In the exemplary, non-limiting embodiment, frame member4is made of a high durometer silicone, such as, without limitation, 75 Shore A (±5 Shore A) durometer LSR (liquid silicone rubber), overmolded onto right and left stiffening structures62A and62B as shown inFIGS.11and12. Also in the exemplary embodiment, stiffening structures62A and62B are made of a thermoplastic material such as a polycarbonate like HP4, although other materials, such as polypropylene, may also be used. In addition, frame assembly60could have a fabric covering or other surface treatment or texturing for aesthetics, patient comfort, or for the wicking of moisture or patient-caused heat. FIG.13is a side elevational view of left stiffening structure62B. Right stiffening structure62A is identical in structure and symmetrical to left stiffening structure62B. Stiffening structures62A and62B each have a generally double-Y shaped footprint, wherein one of the Y portions faces the patient's ear while the other of the Y portions faces the cushion attached to frame assembly60(which, as discussed elsewhere herein, could be a nasal cushion, a nasal/oral mask, a pillows cushion or a full face cushion). In particular, stiffening structures62A and62B each include main arm64having orifice66, front branches68and70extending at upward and downward angles, respectively, from main arm64, and rear branches72and74extending at upward and downward angles, respectively, from main arm64. In the exemplary embodiment, main body64, front branches68and70, and rear branches72and74each have a thickness of about 0.058 inches and a width of about 0.25 inches. Also in the exemplary embodiment, main arms10A,10B and branching members16A,16B,18A,18B have a thickness of about 0.125 inches and a width of about 0.475 inches. The purpose of stiffening structures62A and62B is to provide vertical support and stabilize cushion6and preserve the patient seal while forces are exerted thereon as a result of patient movement (e.g., hose related forces). The mask-side-Y (front branches68and70) has a generally symmetric shape with respect to line AA shown inFIGS.12and13, while the ear-side-Y (rear branches72and74) is asymmetric with respect to line AA shown inFIGS.12and13. [42] In one particular embodiment, the portion of each stiffening structure62A,62B between each Y has a length (labelled as l1inFIG.12) of 55-60 mm. This size is key in positioning the ear-side-Y such that the headgear connections and force vectors are away from the immediate region of the cushion and yet negotiate around the ear region for the majority of the patient population. The ear-side-Y has an upper member (rear branch72) that has a centerline that positioned at an angle α with respect to the line AA ofFIG.12(the centerline of main arm64). In the illustrated embodiment, a is roughly 60 degrees. The ear-side-lower member (rear branch74) has a centerline that positioned at an angle θ with respect to the line AA ofFIG.12. In the illustrated embodiment, θ is roughly 30 degrees. In addition, in the illustrated embodiment, the upper member of the ear-side-Y (rear branch72) extends along half of associated first branching member16A,16B such that d1=d2as shown inFIG.12. The lower member of the ear-side-Y (rear branch72) extends roughly the length of the associated first branching member18A,18B (up to a point adjacent to where loop member20begins). FIG.14Ais a side elevational view of stiffening structure62B having lines which indicate certain cross-sectional views of stiffening structure62B shown inFIGS.14B-14G. Referring toFIGS.14A-14G, in the exemplary embodiment, the degree of cross-sectional curvature (with reference to the longitudinal axis of main arm64) of the ear-side-Y (i.e., of both rear branch72and rear breach 74) decreases from the first end of the ear-side-Y immediately adjacent to the end of main arm64to the distal end of the ear-side-Y (i.e., the distal end of both rear branch72and rear breach 74). In particular, as shown inFIGS.14B-14G, that decreasing curvature is prescribed by the ear-side-Y having a succession of cross-sectional radii R1through R6that increase from the first end of the ear-side-Y to the distal end of the ear-side-Y (R1<R2<R3<R4<R5<R6). This curvature is designed to match the contours of the human face for the majority of the patient population. In one particular embodiment, R1=116.85 mm, R2=132.59 mm, R3=159.51 mm, R4=223.23 mm, R5=247.66 mm, and R6=421.98 mm. FIG.15Ais a side elevational view of stiffening structure62B having lines which indicate certain cross-sectional views of stiffening structure62B shown inFIGS.15B-15D. Referring toFIGS.15A-15D, in the exemplary embodiment, the degree of cross-sectional curvature (with reference to the longitudinal axis of main arm64) of the mask-side-Y (i.e., of both front branches68and70) increases from the first end of the mask-side-Y immediately adjacent to the end of main arm64to the distal end of the mask-side-Y (i.e., the distal end of both front branch68and front breach 70). In particular, as shown inFIGS.15B-15D, that increasing curvature is prescribed by the mask-side-Y having a succession of cross-sectional radii R7through R9that decrease from the first end of the ear-side-Y to the distal end of the ear-side-Y (R7>R8>R9). In one particular embodiment, R7=32.59 mm, R8=32.31 mm, and R3=30.44 mm. [45]FIG.16Ais a side elevational view of stiffening structure62A, andFIG.16Bis a cross sectional view of stiffening structure62A taken along lines Z-Z ofFIG.16A. As seen inFIG.16B, main arm64has a curvature that is prescribed by radii R10, R11and R12. In one particular embodiment, R10=181.07 mm, R11=1520.95 mm, and R12=121.46 mm. FIG.17is a front perspective view of a patient interface device102according to a further embodiment of the present invention, andFIGS.18and19, are front and side view, respectively, of a frame member104of the patient interface device ofFIG.17. Patient interface device102is generally similar to patient interface device2describe above with some of the differences being discussed in detail below. As in the previous embodiment, a cushion106is attached to a frame assembly160that includes a frame member104such that the cushion is moveable relative to the frame member. Frame member104includes a generally annular central member103having first and second main arms110A and110B. An opening99is defined in central member103. Frame member104includes a first branching member116A extending upwardly at an angle from main arm110A and a first branching member116B extending upwardly at an angle from main arm110B. In one particular, non-limiting embodiment, first branching members116A,116B extend upwardly from the respective main arm110A,110B at an angle of about 63 degrees 3 degrees, although other angles are also possible. Note that branching members116A,116B are more curved or have a more arcuate shape than the branching members of the previous embodiments. This curbed shape is believed to provide a frame that more close conforms to the anatomy of a human head. Furthermore, frame member104also includes a second branching member118A extending downwardly at an angle from main arm110A and a second branching member118B extending downwardly at an angle from main arm110B. In one particular, non-limiting embodiment, second branching members118A,118B extend downwardly from the respective main arm110A,110B at an angle of about 44 degrees±5 degrees, although other angles are also possible. Note that branching members118A,118B are more curved or have a more arcuate shape than the branching members of the previous embodiments. This curbed shape is believed to provide a frame that more close conforms to the anatomy of a human head. The distal end of each of first branching member116A,116B and second branching member118A,118B includes a respective loop member120for receiving a respective strap of headgear assembly24. In this embodiment, the coupling of cushion106to the frame member is accomplished via a coupling assembly107that includes a pair of protrusions109provided on each side of a collar105coupled to cushion106. In the illustrated embodiment, at least a portion of each protrusion109is seated or disposed in a slot or groove108that is provided in frame member104. This arrangement allows cushion106to move relative to frame member104by, for example, pivoting about an axis defined through protrusions109. Such movement allows the cushion to automatically seat itself on the patient when the patient interface device is donned by the user. In the exemplary embodiment, each main arm110A and110B of frame member104is defined by a stiffening member162disposed in a flexible material. In an exemplary embodiment, the stiffening member is defined by a plastic and the flexible material is a compressed foam covered in fabric. Stiffening structures162each include a main arm164, front branches168and170extending at upward and downward angles, respectively, from main arm164, and rear branches172and174extending at upward and downward angles, respectively, from main arm164. In the exemplary embodiment, angle α=63+5 degrees and angle θ=44+5 degrees. Front branches168and170and rear branches172and174are generally longer than in previous embodiments and are also less wide. Although the invention has been described in detail for the purpose of illustration based on what is currently considered to be the most practical and preferred embodiments, it is to be understood that such detail is solely for that purpose and that the invention is not limited to the disclosed embodiments, but, on the contrary, is intended to cover modifications and equivalent arrangements that are within the spirit and scope of the appended claims. For example, it is to be understood that the present invention contemplates that, to the extent possible, one or more features of any embodiment can be combined with one or more features of any other embodiment. | 21,914 |
11857728 | DETAILED DESCRIPTION The information that follows describes embodiments with reference to the accompanying figures, in which certain embodiments of the present invention are shown. The foregoing may, however, be embodied in many different forms and should not be construed as limited to the illustrated embodiments set forth herein. The information that follows details various embodiments of the disclosure. For the avoidance of doubt, it is specifically intended that any particular feature(s) described individually in any one of these paragraphs (or part thereof) may be combined with one or more other features described in one or more of the remaining paragraphs (or part thereof). In other words, it is explicitly intended that the features described below individually in each paragraph (or part thereof) represent aspects of the disclosure that may be taken in isolation and/or combined with other aspects of the disclosure. The skilled person will appreciate that the claimed subject matter extends to such combinations of features and that these have not been recited in detail here in the interest of brevity. As used herein, components of the devices described herein may be referred to as being proximal or distal. Except where explicitly stated to the contrary, use of proximal herein refers to a component or position in the direction of, or relatively closer to, a patient interface or the patient. In contrast, reference to distal components or positions will be understood to relate to a position or component relatively closer to the ventilator. For instance, where a condensation trap is positioned within an expiratory ventilator tubing, the trap may be connected to a proximal segment of ventilator tubing at a proximal end of the trap, and connected to a distal segment of ventilator tubing at a distal end of the trap. In other aspects, the trap may be connected to a proximal segment of ventilator tubing at a proximal end of the trap, and connected to a distal segment of ventilator tubing also at a proximal end of the trap. Embodiments are presented and described below which illustrate this usage. Devices, systems, and methods are disclosed herein that represent improvements regarding issues of rain out during ventilation as discussed above. Generally, condensation traps are described herein for the purpose of collecting condensation within a ventilator tubing, and preventing the condensation from entering an airway of the patient. Condensation traps contemplated herein generally can be applied within a mechanical respiratory ventilator, and ventilator systems are also contemplated herein. In certain aspects, respiratory ventilator systems can comprise a mechanical ventilator, a patient interface, an inspiratory tubing providing air flow from the ventilator to the patient interface, an expiratory tubing providing air flow from the patient interface to the mechanical ventilator, and a condensation trap. In conventional ventilator systems, the position of condensation traps can be limited to positions within the tubing or at the ventilator relatively far away from the patient interface, such that some amount of dead space within the tubing between the trap and the patient remains. Certain aspects disclosed herein can reduce or eliminate the dead space within the ventilator tubing according the placement of the condensation trap. In certain aspects, the condensation trap can be positioned directly adjacent the patient interface, within 3 inches of the patient interface, within 6 inches of the patient interface, within 12 inches of the patient interface, or within 18 inches of the patient interface. In certain aspects, the condensation trap can be connected directly to the patient interface. Additionally, or alternatively, the condensation trap can be positioned above the patient or patient interface without interfering with other equipment and operation of the condensation trap. In certain aspects, the condensation trap can be connected in-line with the tubing at any position described above, such that the trap does not present additional cumbersome equipment adjacent the patient and patient interface. Condensation traps disclosed herein can be connected within an inspiratory tubing line, within an expiratory tubing line, or both. Alternatively, the condensation trap may be formed proximal to a juncture of the inspiratory and expiratory lines, such that each line is serviced by the trap. In such aspects, the condensation trap can be within the patient interface, as a removable and separate piece, or alternatively as an integral molded component of the patient interface. Other arrangements which reduce the dead space where condensation may accumulate without being subject to removal from the tubing are also contemplated herein. In certain aspects, the amount of dead space between the patient interface and the condensation trap can be less than 500 ml, less than 250 ml, less than 100 ml, less than 50 ml, or less than 20 ml. The patient interface is not limited to any particular shape or construction, and generally can be any that provide a junction for inspiratory and expiratory tubing and the patient's airways, such as can allow for ventilation of a patient. In certain aspects, the patient interface can comprise a plastic mask, e.g., a half face mask, full face mask, or complete enclosure. In such aspects, the patient interface can connect directly to a condensation trap described herein at a proximal end of the trap. In certain aspects, the patient interface can comprise an endotracheal tube connector or tracheostomy adapter. Other patient interfaces are contemplated within this disclosure as would be understood by a person of ordinary skill in the art. Further aspects of the ventilator systems disclosed herein can comprise a humidifier positioned at any place in the system. In certain aspects, the air entering the patient via the inspiratory line can be humidified to improve patient comfort. In such aspects, a humidifier can be present within the inspiratory line, or within the ventilator. In certain aspects disclosed herein, an inspiratory humidity of at least 20%, at least 30%, at least 50%, at least 70%, or at least 90% can be maintained without risk of rain out in a dead space within the either the inspiratory or expiratory line. Condensation traps disclosed herein generally can comprise a first connector configured to connect to a proximal segment of ventilator tubing or directly to a patient interface. The trap can further comprise a stem extending distally within the trap. In certain aspects, the stem can extend from the first connector toward a distal end of the trap. The stem can comprise an internal channel to allow passage of humidified air into and through the trap, either from the patient or a humidifier. Thus, in certain aspects, the stem can be a hollow cylindrical component that extends from the first connector at a proximal region into a distal portion of the tubing. Referring toFIG.1, an embodiment of the condensation trap100is shown comprising a first connector110, a reservoir wall120, stem130, and drain140connected to a fluid reservoir formed between the internal surface of the reservoir wall and the external surface of the stem. Also shown are spacing elements132as ridges radially extending from the stem, and substantially along the length of the stem. In certain aspects, these spacing elements can extend to the end of the stem, or beyond the stem, and generally take any form suitable to prevent the distal end of the stem from resting on the interior surface of the ventilator tubing. Spacing elements also can comprise a shape or texture advantageous to the condensation of water, such as would promote condensation of water vapor and direct the condensed water into the fluid reservoir to be drained. Certain aspects can comprise a plurality of spacing elements, and can be in a range from 3 to 12 spacers, from 4 to 8 spacers, or from 4 to 6 spacers. The surface of spacers can be any suitable for the condensation trap, and in certain aspects may be configured to aid condensation. In certain aspects, surface are of the spacers can be augmented by addition of a rough or textured surface to any or all of the spacing elements. In such aspects, the condensation of water vapor may occur preferentially within the ventilator trap, relative to other areas within the tubing. FIG.2provides the embodiment ofFIG.1connected to a proximal segment112at first connector110and a distal tubing segment114at the reservoir wall120. As is shown, the reservoir wall serves as a second connector to ventilator tubing such as allows the condensation trap100to be inserted within the tubing line. Fluid reservoir122is formed by the connection between reservoir wall120and stem130. Drain140is shown as being terminated by closure150and connected to syringe160for removal of fluid within the fluid reservoir. Generally, the volume of the fluid reservoir in condensation traps disclosed herein is not limited to any particular volume, and can be any that allows continuous ventilation. Thus, in certain aspects, the fluid reservoir can have a volume of at least 5 ml, at least 10 ml, at least 20 ml, at least 50 ml, or at least 100 ml. In other aspects, the fluid reservoir can have a volume in a range from about 10 ml to 1 L, from about 50 ml to about 500 ml, or from about 50 ml to about 250 ml. In these aspects, the drain can be accessed by any mechanism or device configured to remove fluid from the fluid reservoir. For instance, closure150can be a needleless valve which opens upon insertion of a Luer connection into the closure. Such closures are described in detail within U.S. Pat. No. 7,713,247. Additional closures allowing straightforward connection between a syringe or other fluid withdrawal device and the fluid within the fluid reservoir are also contemplated within this disclosure. In certain aspects, the reservoir wall can share a dimension with the first connector. For instance, the first connector and reservoir wall can have substantially similar external diameter. Advantageously, the drain configured in this manner can allow the fluid in the fluid reservoir to be removed without interrupting ventilation. Particularly, systems and traps as disclosed above allow for the rain-out condensation to be removed intermittently without disconnecting the condensation trap from the ventilator tubing, without disconnecting the patient from the patient interface, and without interrupting airflow delivered to the patient. Moreover, fluid removal can be achieved without risk of aspirating the condensed fluid into the patient's airways by agitating equipment to disconnect as described. FIG.3shows an alternate configuration of the condensation trap comprising a rigid capsule encompassing the stem. In contrast to the embodiment ofFIGS.1-2, the distal segment of ventilator tubing is not connected to the reservoir wall, but a second ventilator tubing connector provided at the distal portion of the capsule condensation trap. As shown, distal segment114is connected to a capsule170by a second connector172at a position proximal the distal end of stem130. Such aspects have advantages as providing a connection within a ventilator tubing of equal diameter, and also providing a fixed construction surrounding the stem, such as may provide greater assurance that the interior surface of the distal tubing segment114does not contact the exterior surface of stem130during operation. Capsule170is also connected to reservoir wall120at proximal end174of the capsule170to complete the ventilatory circuit. In aspects comprising a capsule, the capsule can be any shape or size suitable for connecting the reservoir wall. In certain aspects, the capsule can be fixed to the reservoir wall, or alternatively, removable from the reservoir wall. In certain aspects, the trap can be entirely monolithic. Thus, the capsule may be formed as a unitary piece with the reservoir wall. In such aspects, the volume of the fluid collection reservoir may be defined by the length of the stem. In certain aspects, the fluid collection reservoir (e.g., sump) may have a drain as depicted by element140inFIGS.1-3. In certain aspects, the drain may be smaller than the inner diameter of the stem. The drain may have a closure, the closure comprising an adapter to allow engagement with a syringe or other suction device for draining off liquid. In certain aspects, the closure may be a Luer adapter. In other aspects, the drain can comprise a valve which permits opening and closing of the valve from negative pressure removal or gravity drainage without disconnecting the ventilatory circuit and therefore maintaining the pressure, volume and flow of gas within the ventilatory circuit without the significant interruption associated with prior art techniques. Systems disclosed herein can comprise a plurality of “respiratory” connectors, including at least one proximal connector and at least one distal connector. In certain aspects, such as shown inFIG.1, the first and second connectors can each be respiratory connectors as defined herein. In other aspects, the reservoir wall also can be a respiratory connector. Respiratory connectors can be any ISO standard respiratory connector. Certain aspects can comprise multiple respirator connectors and multiple respirator connectors of different sizes and the connectors may be monolithic with each other, removable or interchangeable. The stem or central channel may have a distal end that extends distal to the endotracheal tube adapter opening, and may have an inner diameter larger than the inner diameter of a tracheostomy tube or endotracheal tube. The stem and at least one of the respiratory connectors may be in a coaxial relationship. The stem may extend within the ventilator tubing in a coaxial relationship. The invention may than trap fluid on the gravity dependent portions of the tubing from flowing into the stem and into the lungs, by instead collecting around the stem. The fluid could then be drained off the sump without disrupting the ventilation process and avoid the disadvantages of the prior art. The fluid may be drained off the sump by intermittently applying a small amount of negative pressure with a device such as a syringe or intermittent vacuum. The fluid may be removed from sump by intermittently opening a closure and allowing the positive pressure of the system to push the fluid out. In this sense, it will be understood by those of skill in the art that aspects of the present invention can provide a small, portable, inexpensive, mechanical safety device that does not substantially increase dead space and can be positioned above the level of an endotracheal tube or tracheostomy adapter inlet. The invention could provide a simple inexpensive device that could reduce the risks of “backwash” of rainout that may lead to infection, ventilator associated pneumonias, lung damage, patient distress, patient morbidity and patient mortality. Methods of preventing rainout and removing condensation from mechanical ventilation tubing are also disclosed herein. In certain aspects, methods can comprise securing a condensation trap as disclosed herein within an inspiratory or expiratory segment of ventilator tubing in a mechanical ventilator, delivering a gas comprising a water vapor to a subject with the mechanical ventilator, allowing a portion of the water vapor to condense within the inspiratory or expiratory segment of ventilator tubing to form water, collecting the water within the ventilator tubing trap, and draining the water from the ventilator tubing trap. Methods disclosed may comprise these operations conducted in any order appropriate, and generally within the principles applicable to condensation traps and systems discussed above. For example, collecting the water within the trap can comprise collecting at least 5 ml, at least 10 ml, at least 20 ml, at least 50 ml, or at least 100 ml of the fluid within a fluid reservoir, or any other range disclosed herein. Other aspects of the methods will be apparent to those of skill in the art according to details provided in individual aspects below and relevant to the condensation traps and systems described above. The invention is described above with reference to numerous aspects and specific examples. Many variations will suggest themselves to those skilled in the art in light of the above detailed description. All such obvious variations are within the full intended scope of the appended claims. Other aspects of the invention can include, but are not limited to, the following (aspects are described as “comprising” but, alternatively, can “consist essentially of” or “consist of”): Aspect. A ventilator condensation trap comprising:a first connector;a stem extending distally from the first connector;an internal channel extending from the first connector through the stem; anda reservoir wall surrounding at least a portion of the stem to form a fluid collection space between an external surface of the stem and an internal surface of the reservoir wall. Aspect. The condensation trap of the preceding aspect, further comprising a drain is in fluid connection with the fluid collection space. Aspect. The condensation trap of the preceding aspect, wherein the first connector and the second connector are each an ISO 5356-1 compliant respiratory connector. Aspect. The condensation trap of the preceding aspect, further comprising a capsule connected to the second connector, the capsule comprising a capsule connector and a distal segment of ventilator tubing. Aspect. The condensation trap of any one of the preceding aspects, wherein the first, second, and capsule respiratory connectors are each independently any suitable connector disclosed herein, including ISO 5356-1 compliant respiratory connectors. Aspect. The condensation trap of any one of the preceding aspects, wherein the drain comprises a connector that is an ISO complaint 80369-7 connector. Aspect. The condensation trap of any one of the preceding aspects, wherein the drain comprises a connector that is not an ISO complaint 80369-7 connector. Aspect. The condensation trap of any one of the preceding aspects, wherein the first connector is smaller than the second connector. Aspect. The condensation trap of any one of the preceding aspects, wherein the first, second, and capsule connectors each comprise any suitable shape disclosed herein, e.g., cylindrical, conical, non-circular, angled, elongated. Aspect. The condensation trap of any one of the preceding aspects, wherein the first connection is tapered toward the proximal end of the condensation trap, and the second connection is tapered toward the distal end of the condensation trap. Aspect. The condensation trap of any one of the preceding aspects, wherein the first, second, and capsule connectors each independently have any length disclosed herein Aspect. The condensation trap of any one of the preceding aspects, wherein any of the first, second, and capsule connectors are coaxial with each other. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors consist of ISO 5356 compliant respiratory connectors. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors comprise ISO 5356 compliant respiratory connectors for use in neonatal and paediaatric breathing systems. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors consist of ISO 5356 compliant respiratory connectors for use in neonatal and paediaatric breathing systems. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors comprise ISO 5356 compliant respiratory connectors for general use in breathing systems. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors consist of ISO 5356 compliant respiratory connectors for general use in breathing systems. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors comprise ISO 5356 compliant respiratory connectors intended for vaporizers, but not for use in breathing systems. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors consist of ISO 5356 compliant respiratory connectors intended for vaporizers, but not for use in breathing systems. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors comprise ISO 5356 compliant respiratory connectors intended for connection of a breathing system to an anaesthetic gas scavenging system. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors consist of ISO 5356 compliant respiratory connectors intended for connection of a breathing system to an anaesthetic gas scavenging system. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors comprise a combination of ISO 5356 compliant respiratory connectors. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors consist of a combination of ISO 5356 compliant respiratory connectors. Aspect. The condensation trap of any one of the preceding aspects, wherein the stem is any shape disclosed herein, e.g., cylindrical, elongated, etc. Aspect. The condensation trap of any one of the preceding aspects, wherein the stem extends distal to a distal end of the second connector. Aspect. The condensation trap of any one of the preceding aspects, further comprising a spacer extending radially from the stem. Aspect. The condensation trap of any one of the preceding aspects, wherein the spacer comprises a spacing ridge (or a plurality of spacing ridges, e.g., 2, 3, 6, 10, etc.) along its external surface. Aspect. The condensation trap of any one of the preceding aspects, wherein the spacing ridge extends to the distal end of the stem, or within any distance of the distal end of the stem disclosed herein, e.g., ½″, 1″, 2″, etc. Aspect. The condensation trap of any one of the preceding aspects, wherein the spacer extends to the opening of stem. Aspect. The condensation trap of any one of the preceding aspects, wherein the spacer extends beyond the opening of the stem. Aspect. The condensation trap of any one of the preceding aspects, wherein the stem extends beyond the spacer. Aspect. The condensation trap of any one of the preceding aspects, wherein the spacer has a radial width less than one of the connectors. Aspect. The condensation trap of any one of the preceding aspects, wherein the spacer has a radial width less than one of the respiratory connectors. Aspect. The condensation trap of any one of the preceding aspects, wherein the stem extends beyond the respiratory connector on the ventilator end. Aspect. The condensation trap of any one of the preceding aspects, wherein the stem extends within the respiratory connector. Aspect. The condensation trap of any one of the preceding aspects, wherein the stem channel extends between a first and second ISO compliant respiratory connector. Aspect. The condensation trap of any one of the preceding aspects, wherein the spacer is configured to assist positioning of the internal channel of the stem away from an internal wall of a ventilation tube conduit to prevent fluid from entering the internal channel when a portion of the ventilation tube surrounding the stem and the stem are non-parallel. Aspect. The condensation trap of any one of the preceding aspects, wherein the spacing ridge extends proximally within the fluid collection space. Aspect. The condensation trap of any one of the preceding aspects, wherein the spacing ridge comprises a proximal gap adjacent the proximal surface of the fluid collecting space to allow fluid to proceed toward the drain. Aspect. The condensation trap of any one of the preceding aspects, wherein the spacer comprises a circumferential gap adjacent the proximal surface of the fluid collecting space. Aspect. The condensation trap of any one of the preceding aspects, wherein the spacing ridge is arranged in a spiral or longitudinal formation around the stem. Aspect. The condensation trap of any one of the preceding aspects, wherein the devices comprises a surface for increasing condensation such as ridges. Aspect. The condensation trap of any one of the preceding aspects, wherein the spacing ridge comprises any condensing material disclosed herein, e.g., metals. Aspect. The condensation trap of any one of the preceding aspects, wherein the condensing material is different from that of the interior surface of the internal channel and/or the material of the ventilator tubing. Aspect. The condensation trap of any one of the preceding aspects, wherein the fluid collection space has a volume in any range disclosed herein, e.g., from about 1 ml to about 10 ml, greater than 3 ml, greater than 5 ml but less than 10 ml, greater than 5 ml but less than 30 ml, greater than 5 ml but less than 60 ml, so that the fluid can be drained off by a standard plunger syringe. Aspect. The condensation trap of any one of the preceding aspects, wherein the internal channel is cylindrical and has an inner diameter greater than a standard ISO 5356 respiratory connector. Aspect. The condensation trap of any one of the preceding aspects, wherein the internal channel has an inner cross-sectional area larger than that of an endotracheal tube. Aspect. The condensation trap of any one of the preceding aspects, wherein the height of the fluid collection space is greater than that of a typical endotracheal tube adapter. Aspect. The condensation trap of any one of the preceding aspects, wherein the drain comprises any suitable drain connector disclosed herein, e.g., a cap, a syringe membrane, needle membrane, valve, or stopcock valve. Aspect. The condensation trap of any one of the preceding aspects, wherein the drain comprises a Luer adapter. Aspect. The condensation trap of any one of the preceding aspects, wherein the drain comprises a valve positioned adjacent the fluid collection space. Aspect. The condensation trap of any one of the preceding aspects, wherein the stem comprises an outer wall that is spaced from the inner wall of a capsule or ventilation tubing. Aspect. The condensation trap of any one of the preceding aspects wherein the stem comprises an outer wall that is circumferentially spaced from the inner wall of a capsule or ventilation tubing. Aspect. The condensation trap of any one of the preceding aspects, wherein the stem comprises a plurality of spacing ridge with gaps between ridges and the inner wall of a capsule or ventilation tubing. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors comprise ISO 5356 compliant respiratory connectors. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors consist of ISO 5356 compliant respiratory connectors. Aspect. The condensation trap of any one of the preceding aspects, wherein the respiratory connectors do not consist of ISO 5356 compliant respiratory connectors. Aspect. The condensation trap of any one of the preceding aspects, further comprising multiple drains connected with the fluid collection reservoir. Apsect. The condensation trap of any one of the preceding aspects, wherein the drain comprises an ISO complaint 80369-7 connector. Aspect. The condensation trap of any one of the preceding aspects, wherein the drain does not comprise an ISO complaint 80369-7 connector. Aspect. The condensation trap of any one of the preceding aspects, wherein the drain comprises a valve, plug, cap, stopcock, check valve, pierceable membrane, clamp, clamped tubing, a fitting compatible with a luer lock syringe, a fitting compatible with a catheter tip syringe or any combination of these elements. Aspect. A respiratory ventilator comprising the ventilator tubing trap of any of the preceding aspects. Aspect. The respiratory ventilator of the preceding aspect, wherein the ventilator tubing trap is connected to a proximal segment of an expiratory tubing by the first connector and a distal segment of the expiratory tubing by the second connector. Aspect. The respiratory ventilator of any one of the preceding aspects, wherein the ventilator tubing trap is connected to a proximal segment of an expiratory tubing by the first connector and a distal segment of the expiratory tubing by the capsule connector. Aspect. The respiratory ventilator of any one of the previous aspects, further comprising a humidifier. Aspect. A method of removing condensation from mechanical ventilation tubing, the method comprising:securing a condensation trap of any of the preceding aspects within an inspiratory or expiratory segment of ventilator tubing in a mechanical ventilator;delivering a gas comprising a water vapor to a subject with the mechanical ventilator;allowing a portion of the water vapor to condense within the inspiratory or expiratory segment of ventilator tubing to form water;collecting the water within the ventilator tubing trap; anddraining the water from the ventilator tubing trap. Aspect. A method of removing condensation from mechanical ventilation tubing, the method comprising:securing an inline condensation trap of any of the preceding aspects inline within an inspiratory or expiratory segment of ventilator tubing in a mechanical ventilator;delivering a gas comprising a water vapor to a subject with the mechanical ventilator;allowing a portion of the water vapor to condense within the inspiratory or expiratory segment of ventilator tubing to form water;collecting the water within the ventilator tubing trap; anddraining the water from the ventilator tubing trap without interrupting the ventilation process. Aspect. A method of removing condensation from mechanical ventilation tubing, the method comprising:securing a condensation trap of any of the preceding aspects within an inspiratory or expiratory segment of ventilator tubing in a mechanical ventilator;delivering a gas comprising a water vapor to a subject with the mechanical ventilator;allowing a portion of the water vapor to condense within the inspiratory or expiratory segment of ventilator tubing to form water;collecting the water within the ventilator tubing trap; anddraining the water from the ventilator tubing trap without interrupting the ventilation process. Aspect. A method of removing condensation from mechanical ventilation tubing, the method comprising:securing an access port within an inspiratory or expiratory segment of ventilator tubing in a mechanical ventilator;delivering a gas comprising a water vapor to a subject with the mechanical ventilator;allowing a portion of the water vapor to condense within the inspiratory or expiratory segment of ventilator tubing to form water;collecting the water within the ventilator tubing trap; andusing a closed vacuum system to drain the water from the ventilator tubing without disrupting the positive pressure ventilation process. Aspect. The method of the preceding aspect, wherein the condensation trap is secured at a position near the patient, e.g., less than about 3″ or in a range from about 1″ to about 12″. Aspect. The method of any one of the preceding aspects, wherein the condensation trap is secured above the patient. Aspect. The method of any one of the preceding aspects, wherein the condensation trap is positioned above the level of an endotracheal tube adapter or tracheostomy adapter. Aspect. The method of any one of the preceding aspects, wherein the draining step comprises coupling a syringe to a drain, and withdrawing the liquid collected in the trap. Aspect. The method of any one of the preceding aspects, wherein the draining step comprises engaging a valve to maintain the pressure within the ventilation tubing during the draining step. Aspect. The method of any one of the preceding aspects, wherein delivering the humidified gas can be conducted simultaneously with the draining step. Aspect. The method of any one of the preceding aspects, wherein the pressure within the mechanical ventilator settings are maintained within the same range before, during and after draining the fluid. Aspect. The method of any one of the preceding aspects, wherein an alarm notifies a caregiver when there is sufficient buildup of fluid. Aspect. The method of any one of the preceding aspects, wherein fluid is automatically removed from the trap. Aspect. A method of using a condensation sump in line with mechanical ventilation tubing to prevent death. Aspect. The method of any one of the preceding aspects, wherein at least 50% (or at least 80%, or at least 95%, or any other suitable range disclosed herein) of the water condensed in the distal portion of the expiratory tubing segment is collected within the condensation trap. Aspect. The method of any one of the preceding aspects, wherein less than 10% (or less than 5%, or less than 1%, or any other suitable range disclosed herein) of the water condensed in the distal portion of the expiratory tubing segment falls into the lungs. Aspect. The method of any one of the proceeding aspects, wherein rainout within the proximal segment of the expiratory tubing is reduced by at least about 50%, or any other suitable range disclosed herein. Aspect. A condensation drain for a mechanical ventilation inspiratory or expiratory tubing system where the drain comprises, a luer connector, a female luer connector, a male luer connector, a luer lock connector, an occluder, a cap, a valve, membrane, stopper or a pathway that can be opened or pierced without losing pressure in ventilation system. Aspect. A condensation drain for a mechanical ventilation inspiratory or expiratory tubing system where the drain is coaxial with connector, is not coaxial with connector, is perpendicular with respiratory connector, does not extend from stem, does not extend from ET adapter or tracheostomy tube adapter or extends from a wall between ventilator adapter (e.g. for an endotracheal tube or tracheostomy) and ventilator. | 34,437 |
11857729 | DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT A schematic view of a user3areceiving air from a known (prior art) modular assisted breathing unit and humidifier system is shown inFIG.1. Pressurised air is provided from an assisted breathing unit or blower1avia a conduit41to a humidifier chamber2a. Humidified, heated and pressurised gases exit the humidifier chamber2avia a conduit21, and are provided to the patient or user3via a user interface4. The user interface4shown inFIG.1is a nasal mask, covering the nose of the user3. However, it should be noted that in systems of these types, a full face mask, nasal cannula, tracheostomy fitting, or any other suitable user interface could be substituted for the nasal mask shown. A schematic view of the user3receiving air from a known, prior art integrated blower/humidifier unit5is shown inFIG.2. The system operates in the same manner as the modular system shown inFIG.1, except that humidifier chamber2bhas been integrated with the blower unit1bto form the integrated unit5. The integrated blower/humidifier unit6of the present invention can be substituted for the unit5ofFIG.2. The preferred form of the integrated blower/humidifier unit6is shown assembled and ready for use inFIG.3. The unit6has two main parts: An integrated assisted breathing unit7(also known as a blower unit), having an outer shell which forms part of the breathing unit7and also encloses the working parts of the assisted breathing unit—e.g. the fan, internal-ducting and the internal control system; and a humidification unit31(described in detail below). Assisted Breathing Unit The preferred form of assisted breathing unit or integrated unit6will now be described with reference toFIGS.4-17. The integrated unit6consists of two main parts: an assisted breathing or blower unit7and a humidification unit31. The humidification unit31is enclosed within the external casing of the integrated unit6in use, except for the top part. The structure of the humidification unit31is described in greater detail below. The blower unit7has an outer shell which is a generally rectangular block with substantially vertical side and rear walls, and a front face that is angled slightly rearwards. In the preferred embodiment, the walls, base and top surface are all manufactured and connected as far as possible to minimise the occurrence of seams, and any necessary seams are sealed. This outer shell encloses the working parts of the blower unit7, and forms part of the blower unit7. As shown inFIG.4, a control knob8is located on the lower section of the front face of the integrated unit6, with a control display9located directly above the knob8. A patient outlet25is shown passing out of the rear wall of the integrated unit6. In the preferred embodiment, in use the free end of the outlet25faces upwards for ease of connection. However, the preferred form of patient outlet25can be rotated to one side or the other to move or align it in a more convenient position for storage ox for a more convenient use position. The patient outlet25is adapted to allow both pneumatic and electrical connection to one end of a conduit e.g. conduit21—running between the unit6and a patient interface—e.g. interface4. An example of the type of connector that can be used and the type of dual connection that can be made is described in U.S. Pat. No. 6,953,354. It should be noted that for the purposes of reading this specification, the patient interface can be thought of as including both the interface4and the conduit21where it would be appropriate to read it in this manner. InFIG.3, a locking handle22is shown in position on the top surface of the integrated unit6. The locking handle22is a separate item that can be unlocked and removed from the remainder of the integrated unit6. The locking handle22includes a grip30, adapted to act as a handle to allow a user to lift and carry the integrated unit6, and also adapted to enable the handle22to be rotated from a locked position to an unlocked position. The locking handle22can be releasably locked to the remainder of the integrated unit6. The function of the locking handle22will be more fully described below in the ‘humidifier unit’ section. FIG.4shows the integrated unit6with the locking handle22removed and the humidification unit31not shown. That is, just the blower unit7is shown. The top surface of the blower unit7includes a circular humidifier aperture1000, leading to an internal humidifier compartment11. The opening includes a rim24located around the circumference of the opening. In use, a humidifier chamber12is located within the compartment11. The humidifier chamber12will be described in detail below. The humidifier chamber12is in use fully enclosed inside the compartment11, except for the uppermost part. When the chamber12is described as enclosed in the blower unit7, it can be taken to mean fully enclosed except for the uppermost portion, as well as fully enclosed including the uppermost portion. The internal structure of the blower unit7will now be described with reference toFIGS.4,5a, and5b. A heater base23is located at the bottom of the compartment11. The heater base23is mounted to the floor of the compartment11in such a way that it has a small amount of elastic or compression resilience. That is, it can be pushed downwards a short distance within the compartment, but will push back against any downwards force that is applied. In the absence of any downwards force it will return to its initial position. This can be achieved by spring loading the base23, or by any other of the methods that are known in the associated arts. A blower inlet port13and blower outlet port14are located on the wall of the compartment11, towards the top of the compartment11. In the preferred embodiment, these blower ports13,14are aligned so as to mate with humidifier ports15,16located on the humidifier chamber12in use (described in detail below) so as to form a blower-to-humidifier gases route which allows gases to exit the blower7and enter the humidifier chamber12. It should be noted that other forms of blower inlet are possible. For example a conduit running between the blower unit7and e.g. the lid of the humidifier chamber12. As shown inFIGS.7and8, the integrated unit6includes an inlet vent101to draw air in from atmosphere. The integrated unit6also includes a mechanism for providing a pressurised air flow from the inlet vent101to the humidifier chamber. This vent101can be located wherever is convenient on the external surface of the integrated unit6. In the preferred embodiment, as shown inFIG.8, it is located on the rear face of the blower unit7. In the preferred embodiment, air is drawn in through the vent101by a fan unit100which acts as the preferred form of pressured air flow mechanism (described in detail below). The air is inducted or otherwise directed through the casing to the inlet port13. In use, air will exit the main body of the blower unit7via the inlet port13and then enter the humidifier chamber12, where it is humidified and heated, before passing out of the chamber12through the outlet port14, which is directly connected to the patient outlet25. The heated humidified gas is then passed to the user3via e.g. a conduit21. The patient outlet25is adapted to enable pneumatic attachment of the patient conduit21, and in the preferred embodiment, electrical connection at the outlet25is also enabled via an electrical connector19. A combined electrical and pneumatic connection can be useful for example if the conduit21is to be heated. Electrical heating of a conduit such as conduit21can prevent or minimise the occurrence of condensation within the conduit21. It should also be noted that the outlet connection docs not have to be via the housing of the integrated unit6. If required, the connection for the conduit21could be located directly on an outlet from humidifier chamber12. The preferred form and variations can generally be referred to as connection mechanisms. As shown inFIGS.6and7, the inlet port13is offset. That is, the port is positioned facing into or out of the corner of the integrated unit6between the side wall and the front face. In contrast, outlet port14is directly aligned with the rear wall of the integrated unit6. It can also be seen fromFIG.6that the circular compartment11is sized to just fit within the generally square plan view profile of the integrated unit6. Offsetting the inlet port13towards the corner allows a more efficient use of the space within the assisted breathing integrated unit6, and allows the size of the integrated blower/humidifier unit6to be minimised. The locking handle22and the integrated unit6include a locking mechanism for locking the handle22to the integrated unit6. In the preferred embodiment the locking mechanism is as follows: the rim24includes two mating grooves26located just below the rim24, spaced opposite each other on the circumference of the rim24. More than two of the mating grooves26can be used if required. The grooves26correspond to an equal number of mating lugs27on the locking handle22. The mating groove or grooves26have an entry point28on the rim24, with the main part of the groove26located slightly below the rim24. The lugs27are pushed downwards into the entry points28, and the handle is rotated so that the lugs enter the main part of the grooves26to hold the handle22in place. Different locking mechanisms can be used if required. Humidifier Chamber with Lid The humidifier unit31will now be described in more detail with particular reference toFIGS.13a,13b, and17. In the preferred embodiment, the humidifier unit31is comprised of three main parts: humidifier chamber12, lid32and locking handle22(counted as part of the humidifier unit for the purpose of describing the operation of the integrated unit6). The preferred embodiment of the humidifier chamber12is an open-topped container, with a heat conducting base. The chamber12is sized to fit snugly within the compartment11on the integrated unit6. That is, the chamber12is enclosed within the blower unit except for the open top of the chamber12. A fully open topped chamber12is the preferred form. However, an alternative form of the chamber12could have a closed top surface, and would include an opening on the chamber (not necessarily on the top surface), sized appropriately so that a user can easily fill the chamber12. The preferred form of chamber12with an open top, and the alternative form that includes a fill opening on the top are referred to as ‘open top’, or ‘top openings’ within this specification. The open top may also be referred to as a ‘top fill aperture’. It should also be noted that when the humidifier chamber12is referred to as ‘enclosed’, or ‘substantially enclosed’ in relation to the integrated breathing assistance apparatus, this has the meanings defined above. The chamber12is generally circular, but the lower part of the rear (relative to the integrated unit6) is flattened as shown inFIGS.13aand13bto correspond to a ledge33on the lower rear side of the compartment11. This ensures that the chamber12will always be oriented correctly in use. It should be understood that other methods of achieving the same result could also be used. For example, the chamber12and integrated unit6could include complimentary grooves and slots. The chamber12can also include features such as a fill or level line if required. The humidifier inlet port15and a humidifier outlet port16are located in the wall of the humidifier chamber12, towards the top of the chamber wall These are positioned so as to align with the blower inlet and outlet ports13and14when the humidifier chamber12is in position, forming the blower-to-humidifier gases route as described above. It is preferred that the corresponding ports on the blower7and humidifier chamber12are shaped so as to minimise airgaps. A good seal is preferred but not required. In the preferred form, the rim or perimeter of the chamber12includes a chamber seal10, formed from soft silicone or similar. When the chamber12is placed in position in the humidifier compartment11, the chamber seal10is pressed against the wall or walls of the compartment11, and the body of the chamber12and the seal10ensure that the chamber12is scaled, so that air exiting the blower through the port13cannot escape to atmosphere. This helps ensure that a pressurised airstream enters the humidifier chamber12in use. If required, a substantially unbroken ring of sealing material such as soft silicone can be added to the wall of the compartment11at or close to the upper rim of the chamber12, to form a compartment seal (not shown) instead of or as well as the chamber seal10. In alternative embodiments the ports13,14are surrounded by resilient sealing gaskets such as silicone gaskets to assist in forming a seal in use. If preferred, the resilient sealing gaskets around the ports can be used as well as the compartment and/or chamber seals. Air enters the humidifier chamber12through the humidifier inlet port15, and passes along a generally horizontal entry passage34towards the centre of the humidifier chamber12. Passage34is offset towards one of the front corners of the unit to align with the inlet port13as described above. The air exits the entry passage34through a first aperture or opening200in the centre of the humidifier chamber12aligned facing upwards (that is, in the top of the passage). The air is then directed into the main part of the chamber by a baffle35. In cross section, the baffle35is T-shaped, with a vertical central portion to deflect gases entering the chamber12, and a substantially horizontal top ‘umbrella’ portion202, which is circular in plan view, as shown inFIGS.6,13a, and13b. Air is deflected by the baffle35as it exits the passage34, and then enters the main part of the chamber12where it is heated and humidified. The heated and humidified gases then enter an exit passage36on the other side of the baffle35through a second aperture or opening201, with the air passing through the exit passage36to the chamber exit port16and then into the breathing unit outlet port14, and on to the user4as described above. It can be seen that the baffle35prevents air from the inlet passage34from directly entering the exit passage36before it has been heated and humidified. The passage and baffle arrangement also serves the purpose of acting as a splash baffle as well as an air baffle. Water is obstructed from entering the passages34and36if the chamber12is tilted while it contains water. The umbrella portion202of the baffle35acts as a shield for the passages34,36, vertically occluding the apertures200,201, so that when a user is pouring or refilling the chamber12, the user cannot directly pour into either of the apertures200,201. The top surface of the passages34,36also acts as a shield to prevent a user pouring water into the passages34,36. It is preferred that the exit and entry apertures200,201in the passages34,36face upwards, as this helps to prevent water or liquid in the chamber splashing into the passages34,36, or otherwise entering the passages34,36when the chamber12is tilted. The passages,34,36and the baffle35can be generally referred to as the baffle, or the baffle mechanism. In use, the chamber12is positioned (in the correct orientation) within the compartment11. The lid32is then placed on top of the chamber12. The lid32is sized so that it will pass through the top opening of the integrated unit6, with the lower surface of the lid32, close to the edge, sealing onto the upper edge of the chamber12. In the preferred embodiment, the lid32has an. edge perimeter portion that is aligned facing downwards. This has a central recess that is filled with a silicone seal70or similar which is pressed onto the upwards facing edge of the chamber12when the lid32is in position. This arrangement is shown inFIGS.13aand13b. InFIGS.13aand13b, the handle22is also shown vertically above the lid32(separate from the lid32). The lid32is sized to fit into the recess shown in the handle22(if the handle shown inFIGS.13aand13bare pressed vertically downwards onto the lid32). If required, the two contacting portions of the lid32and the chamber12can also be shaped to improve the seal between the two. The central part of the lid32is bulged upwards so that it will stand proud of the baffle35. The lid32is placed in position on the chamber12once the chamber12has been filled. The locking handle22is then positioned above the lid32. As has been described above, lugs27on the circumference of the locking handle22engage with complimentary grooves26on the rim24. In order to engage correctly, it is necessary in the preferred embodiment for the locking handle22to be pressed or pushed downwards, pushing both the lid32and the chamber12downwards onto the heater plate23a. The heater plate23awill give slightly under the downwards pressure, allowing the locking handle22to be rotated so that the lugs27engage with the grooves or slots26. Once the downwards force is removed, the chamber12, lid32, and locking handle22will be pressed upwards by the reaction force from the heater plate23a, with the assembly held in place by the lugs27and slots26. In the preferred embodiment, the slots26are shaped so that the locking handle22cannot be rotated to disengage the lugs27without pressing the locking handle22downwards slightly first. The locking handle22also includes the grip30, which in the preferred embodiment is an arched member passing from one side of the handle22to the other, sized and shaped so that a user can pass at least some of their fingers underneath, so as to manipulate the locking handle22and to carry the integrated unit6if necessary. In the preferred embodiment, the locking handle22and the lid32are separate items, as described. If the handle22is used without the lid32, the chamber will not be sealed, and the heated, humidified air will escape or vent to atmosphere before entering the exit port14. Any air that does enter the port14will be at a lower pressure than required, due to the leaking. To ensure correct operation, the lid must be used to seal the chamber in the preferred embodiment. This ensure that there is less chance of incorrect use of the unit. For example, if a user fills the compartment11directly without using the chamber12, or if a user forgets to place the lid32in position. In the preferred form, the top portion of the lid32fits into a central recess in the handle22, as can best be seen inFIG.6. The lid32and the handle22are sized so that the lid22will snap-fit and be held in place in the handle22to form an integrated lid unit. The lid22can be disengaged from the handle32by pressing on its top surface or similar. However, it is preferred that the snap-fit will keep them engaged in normal usage. £\s the handle recess and the lid22are circular, they can easily rotate relative to one another when engaged. When the handle22is rotated to disengage it from the integrated unit6, it will rotate easily relative to the lid32(which will not rotate easily due to the seal on the perimeter edge). When the handle22has been disengaged from the integrated unit6, it can be lifted away from the integrated unit6to remove both the handle22and the lid32. It should be noted that although a round chamber12, lid32and a locking mechanism (lugs27and slots26) have been described, and locking/unlocking of the lid32is achieved by rotating the separate locking handle22, this is not the only way in which this effect can be achieved. If a different locking mechanism is used in place of the lugs27and grooves26, chambers with different profiles can be used in place of the round chamber12described above. For example, spring loaded clips could be used, with the clips released by a button placed in a convenient location, such as on a handle or on the outer surface of the integrated unit6. A hinged lid could also be used, with a clip and complimentary catch located on the lid and the blower unit, to hold the lid closed in use. Alternatively or as well as, the chamber lid32and the locking handle22could be integrated as a single unit. This single unit could either be separable from the integrated unit6or the humidifier unit31, or an integral part of it, for example a hinged lid similar to that suggested above. The intention of the lid32and handle22in the arrangement described above is that a user can easily remove the lid32in order to access the chamber12for refilling or similar, and that a user can then easily replace the lid32and handle22to hold the lid32and the chamber12in position inside the assisted breathing integrated unit6. It should be noted that as outlined above, use of a round chamber12, with a generally square profile integrated unit6allows an efficient use of space so that the overall size of the integrated unit6can be minimised. This should be considered if using an alternative layout or locking mechanism. Control Knob The preferred form of construction of the control knob assembly including operable control knob8, and attachment to the integrated unit6will now be described with particular reference toFIG.14. The knob8is manipulable by a user to change the settings of the integrated unit. This is achieved by twisting and pushing the knob8to generate control signals. In the preferred embodiment, the integrated unit6includes a removable mounting plate removable faceplate37that removably attaches onto the front face of the integrated unit6—e.g. by friction-fit push clips or similar, sufficient to hold the faceplate37in place in use or during transport, but allowing the faceplate37to be removed e.g. by pressing a knife blade under one side and twisting or similar. The faceplate37includes an aperture that aligns with the control screen9, so that the screen can be viewed through the aperture in use.FIG.14shows a schematic cross-section of the front surface of the integrated unit6, viewed from above. For clarity, the various elements shown inFIG.8are shown not in contact with one another. As shown inFIG.14, the face plate37includes a concave hollow, depression or recess38, into which the knob8locates in use. The depression38is sized and shaped so that the knob8fits snugly. The bottom of the depression38contains a fastening mechanism39. In the preferred embodiment, the fastening mechanism39is formed as an integral part of the plate37. In the preferred embodiment, the fastening mechanism39is a ring or crown of spring fasteners or fastening clips39, with their tips or upper portions60facing or pointing inwards. The fastening clips39are aligned perpendicular to the base of the depression38. The knob8is made up of a central, non-rotating portion or button61and an outer, rotatable portion or boss62that can be rotated either clockwise or anticlockwise by a user. The outer portion62is ring-shaped, with a central aperture. The inner portion61has a T-shape in cross-section, with fasteners63integral with the upright of the T. In use, the fasteners63connect with the sprung fasteners39to hold the inner portion in position. The knob assembly is assembled by placing the outer (rotatable) portion62of the knob8in position in the depression38, and then pushing the inner (non-rotatable) portion61into position. The flat upper part of the inner portion acts as a flange to hold the outer portion62in position. In the preferred embodiment, the outer portion62also has a slight central hollow, with the cross-portion of the T-section of the inner portion62fitting snugly into this hollow so that the inner portion61and the outer portion62together form a flush outer surface. What has been described above is the preferred form of fastening mechanism to hold the knob8in position on the faceplate37. However, any suitable fastening mechanism could be substituted for the one described. The knob8, or more specifically the outer portion62, is fitted with a ring magnet45. The outer portion62generally has the form of a hollow cup, with the open face facing inwards towards the centre of the depression38in use. The ring magnet45is fitted running around the inside of the outer portion, just below the rim. The centre of the ring magnet45is aligned with the axis of rotation of the knob8. As the outer portion62rotates, the ring magnet45also rotates. The front face or wall50of the assisted breathing or integrated unit6is located behind the faceplate37. The front face50includes an aperture43, through which the rearmost part of the depression or recess38passes in use. A connector board44is located just behind, and generally planar with, both the faceplate37and the front face50of the integrated unit6. Magnetic or magnetised sections46are embedded on the inner surface of the connector board44. These are positioned to as to form a generally circular shape, corresponding to the ring magnet45, so that the magnetised sections46align with the ring magnet45. The magnetic fields of the ring magnet45and the magnetised sections46(detector magnetic components, or boss detector magnetic components) interact as the knob is rotated in use. Control circuitry and sensors (not shown) located within the blower unit6are connected to the ring magnet45so that as the boss portion62of the knob8is turned it can detect the fluctuations of the interacting magnetic fields. In the preferred form, the ring magnet45is continuous (that is, a continuous annular component), but divided into a number of discrete magnetic sections (That is, there are no physical gaps between the sections). The number of sections' can be varied depending on the number of positions required. One advantage of using a ring magnet such as ring magnet45is that is has discrete sections. This means that as the boss portion of the knob8is rotated, it will have a number of discrete positions, having preferred ‘rest’ positions as the fields of the magnetised sections46and the fields of the sections of the ring magnet45interact to reach an equilibrium point, an effect known as ‘cogging’. The outer portion62of the knob8will rest at these equilibrium points until acted on by an external force—e.g. a user exerting a rotational force on the rotatable outer portion62of knob8. The knob8will therefore tend to naturally ‘jump’ from one rest position to the next as it is rotated. As the relative positions of the magnets45and46changes, the fluctuations of the relative magnetic fields changes is detected by the sensors, and the results of the fluctuations are passed to the control circuitry300located inside the housing of the respirator7(e.g. located on the circuit board44), which alters the output parameters of the integrated unit6according to pre-programmed responses (e.g. altering the power to the heater base23, fan speed, etc) as required by a user. The preferred form of ring magnet45and magnetised sections46has been described above. It should be noted that the positions of the ring magnet45and magnetised sections46could be reversed. Also, the ring magnet45could be composed of discrete sections, with gaps between them. That is, an annular arrangement of individual magnetic components. Magnetised sections46have been described. These could be actual magnets, or alternatively these could be electromagnetised elements that act both as magnets and sensors to exert a cogging force and provide positioning feedback. In the preferred embodiment, the knob8is also adapted to allow limited movement along its axis of rotation51. That is, it can be pressed inwards to act as a button. This can be achieved in a number of ways. However, in the preferred embodiment, a spring (not shown) is placed inside the circle or crown of the preferred form of fastening mechanism39. When emplaced, this spring is slightly under compression, and pushes outwards against the knob8so that it has a rest position when not depressed and an operative position when depressed. When pressed inwards towards the integrated unit6, the spring is compressed slightly more, and will act to ⋅return the knob8to its initial position once the pressing force is removed. The centre of the knob8also holds a magnet48. A corresponding central magnet49(or button detector magnetic component) is located at the centre of the circle formed by sections46. In a similar fashion to that described above, as the relative positions of the magnets48and49changes, the fluctuations of the relative magnetic fields are detected, and these changes are passed to a control unit which varies the output parameters of the integrated unit6accordingly. For example, using the arrangement described above, the knob8can be rotated clockwise and anticlockwise to scroll between menu options, and then pressed inwards to choose the option to which the user has scrolled. The knob8can also be used as e.g. an on/off switch, either by scrolling to the required on/off menu choice and pressing, or by pressing and holding the knob in for a longer period than would naturally occur if the unit6was accidentally knocked—for example 5 seconds. Alternatively, the controls could be set so that a user is required to pull the knob8slightly out from the unit6to turn it off. What has been described above is an assembly where the medical device (blower unit7) includes a faceplate37which includes a recess, and which fits over the front face50of the blower7. The faceplate is unbroken, in that there are no apertures or gaps through which moisture or dirt can enter the medical device. Also, the components external to the blower7are not moisture or dirt sensitive, so if they get wet or dirty, their operational effectiveness is not adversely affected. It should be noted that what is described above is the preferred embodiment, and the principles of the operation could be applied equally well to a device which does not include a separate faceplate, and which has a single flat face (i.e. no recess), with magnetic elements46,63located behind the face, and the control knob, boss, fastening mechanism, etc located external to the face. It should also be noted that another possible variation of the layout described above could also be used, with the front face50unbroken and including a recess, and the faceplate including an aperture through which the control knob locates into the recess on the faceplate. It should also be noted that the faceplate does not have to present at all, but is present in the preferred forms. Control Menu The preferred form of display shown on the display panel9is shown inFIG.15. In the preferred embodiment, the control menu as displayed on the display9is a single layer menu, in order to keep the operation of the unit6simple. In the preferred embodiment, the display is an LCD display, with a circular ring of options around the outside of the display. As the knob8is rotated, each of the options will light up in turn. When the knob is depressed, that option will be chosen. Once an option is chosen, for example ‘output power’, the level of this parameter can be adjusted by rotating the knob8clockwise and anti-clockwise. A user can then exit this submenu and return to the main menu by, for example, tapping the knob inwards or pulling it outwards. The control circuitry can be programmed as required. Other options can be pre-programmed as required. For example, pushing and holding in the knob8(or pulling it outwards and holding it out) could turn the unit off. It is preferred that the discrete positions (the ‘cogging’ positions) that the knob8reaches as it is rotated correspond to different menu options. Blower Unit The internal structure of the blower unit7will now be described with reference toFIGS.5and7-11. In the preferred embodiment, heater base23is located at the bottom of the compartment11, as described above. It should be noted that the blower unit and humidification chamber could be configured so that the volume of water within the humidifier chamber is heated e.g. through the side walls. That is, contact with a heater element or unit through a heat conducting surface on the side wall of the chamber, rather than on the base of the chamber. This configuration would achieve substantially the same effect. However, heating through the base is preferred for reasons of simplifying the chamber construction and overall operation of the heater/humidifier unit. When ‘heater base’ is referred to in this specification, it should be taken to mean heating through the base of the humidifier chamber, or alternatively the side walls. As described above, the integrated unit6includes an inlet vent101to draw air in from atmosphere. The integrated unit6also includes a mechanism and structure by which a pressurised air flow is provided from the inlet vent101to the humidifier chamber. The vent101can be located wherever is convenient on the external surface of the integrated unit6, but in the preferred embodiment, as shown inFIGS.7and8, it is located on the rear face of the blower unit7, on the right hand side of the rear face (right hand side when looking forwards). In the preferred embodiment, air is drawn in through the vent101by a fan unit100which provides a pressurised gases stream through the blower unit7. The pressurised gases stream is ducted or otherwise directed from the inlet vent101through the casing to the humidifier inlet port13. The air path and the ducting will be described in detail in the Tan Unit and Air Path′ section below. In use, air exits the main body of the blower unit7via the inlet port13and enters the humidifier chamber12, where it is humidified and heated, before passing out of the chamber12through the outlet port14, which is directly connected to the patient outlet25. The heated humidified gas is then passed to the user3via e.g. a conduit21. The patient outlet25is adapted to enable pneumatic attachment of the patient conduit21, and in the preferred embodiment, electrical connection at the outlet25is also enabled via an electrical connector19. As shown inFIGS.4and6, the inlet port13is offset. That is, the port is positioned facing into or out of the corner of the integrated unit6between the side wall and the front face. In contrast, outlet port14is directly aligned with the rear wall of the integrated unit6. It can also be seen that the circular compartment11is sized to just fit within the generally square plan view profile of the integrated unit6. Offsetting the inlet port13towards the corner allows a more efficient use of the space within the assisted breathing integrated unit6, and allows the size of the integrated blower/humidifier unit6to be minimised. Fan Unit The fan unit and ducting of the preferred embodiment will now be described with reference toFIGS.5,7-12and16. The fan unit100is intended to sit in the recess400shown inFIG.5b. Air is drawn into the fan unit100through an inlet vent101. Once inside the housing, the air is then is drawn upwards into the casing of the fan unit100through an aperture110in the centre of the casing of the fan unit100, and is directed outwards through a duct120(shown schematically as hidden detail inFIG.16) to the inlet13. The duct120runs from the recess400up between the side wall and the front wall of the integrated unit6. The air path through the fan unit is shown by arrows130. In the preferred embodiment, fan unit100is electromagnetically powered, with magnetic segments111interacting with electromagnetic coils112, located above the fan unit100, as shown inFIG.7. The fan110is held in place by a bearing unit113that includes a spindle for the fan110. Fan Unit and Air Path The fan unit and ducting of the preferred embodiment will now be described with particular reference toFIGS.8to12. A power supply sub-housing500is located within and integrated with the outer housing or outer shell of the breathing unit7. The power supply sub-housing500is a rectangular cuboid structure at the rear of the blower unit7, integrated as part of the rear wall80of the blower unit7. The cuboid sub-housing500shares one of its two largest faces with the rear wall80of the blower unit7(although it should be noted that the outer dimensions of the sub-housing500are substantially less than the dimensions of the rear wall80). The other large face510is common with the fan recess400, and the humidifier aperture1000. The sub-housing500is generally centrally located on the inner rear wall of the blower unit7. Once the unit is assembled, the sub-housing500is substantially closed off from atmosphere and the rest of the internal volume of the outer shell of the blower unit7, apart from small apertures necessary for external electrical connections or similar (not shown). The power supply component board501is comprised of electrical components connected to a mother board, and slotted into the space within the sub-housing500during assembly. It is not necessary to detail or individually number all of the components used to make up the power supply component board501, as the make-up and variations of the construction of power supply boards is well-known in the art. However, it should be noted that these components generate heat during use, which cannot dissipate or vent to atmosphere due to the power supply being enclosed. This heat therefore builds up, potentially leading to less efficient operation. It is preferred that the sub-housing500is sealed or enclosed in the sub-housing500in this manner in order to protect the components of the power supply component board501, so that dirt, moisture or similar cannot enter the sub-housing500. However, the power supply component board could be merely located within the external casing or shell of the blower unit7. It should be noted that when ‘power supply’ or ‘power supply unit’ are referred to in this specification, this means either the power supply sub-housing500, the power supply component board501, or both together. In order to help reduce the temperature of the sub-housing500and the temperature of the components of the power supply component board501in the sub-housing500, air from atmosphere is drawn into the housing by the fan unit100and then ducted directly over the power supply unit sub-housing500to cool the power supply component board501. It is preferred that the air is ducted over the sub-housing500directly after it enters the outer housing of the integrated unit6, as the air will be at its coolest at this point—direct from the atmosphere. In order to most effectively cool the power supply component board501and the sub-housing500, the air is ducted over the greatest possible surface area of the sub-housing500, while still maintaining the integrity and operation of the integrated unit6, and still maintaining a practical compact and integrated design. Air from atmosphere is drawn in through the air inlet vent101, the side of which is substantially the same height as one of the sidewalls of the sub-housing500. In the preferred embodiment, the inlet101is directly next to the sub-housing500. It should also be noted that in the preferred form, the height of the air inlet101is substantially the same as the dimension of the neighbouring wall502. The air entering the external shell through the inlet101therefore immediately contacts the side wall502of the sub-housing500. This first contact is made across substantially the entire surface area of the wall, as the height dimension of the neighbouring vent101is substantially the same as the height or length of the wall502. This has the advantage that all the air contacting this wall will be at atmospheric temperature as it contacts the wall. The air is then drawn by the fan100upwards and across the top wall503of the sub-housing500, passing across or over the entire outer surface area of the top wall503. The air is then ducted down the other, or inner side wall504of the sub-housing500, passing across the entire outer surface area of wall504. It should be noted that the walls of the sub-housing500are as thin as is practical in order to minimise their insulating effect, and maximise heat transfer between the air flow and the power supply board. The air is then drawn inwards, away from the power supply, along the curved path505, through aperture506into the recess400and then into the fan unit100. Air is drawn into the fan unit100through aperture110, and is then directed outwards through a plenum chamber or duct120inside the blower7to the inlet13(duct120is shown schematically and for the purposes of illustration only as hidden detail inFIG.16. The representation of the duct120as shown inFIG.16does not necessarily match the actual path or size of the duct). The duct120runs from the recess400up between the right side wall (from behind looking forwards) and the front wall of the integrated unit6, up to the blower inlet port13. It can be seen that for an outer casing with a sub-housing500and air path configured in this manner, air passes over the entire surface area of three walls (502,503,504) of the sub-housing500, substantially adding to the cooling of the power supply component board501. This is the most preferred configuration of the cooling path, as manufacture in this configuration allows repeatability and a high number of units within design tolerance, while minimising costs. It has been found that this configuration gives the most efficient use of both space and air cooling, allowing a good degree of cooling, while still ensuring the unit6can be configured compactly to minimise footprint. It should be noted that if the power supply component board501is not enclosed in a sub-housing, the cooling air can be ducted directed over the board and the components thereon. Other configurations are possible. For example, the air could be ducted along a space between the large wall510of the sub-housing500, and the rear wall of the humidifier aperture1000. However, in order to make this configuration work effectively, without the air in this space stagnating, the gap between the fan recess400and the power supply sub-housing500has to be over a certain size, and this can detract from the overall compact nature of the overall structure. Furthermore, it can add to the manufacturing difficulty. It should also be noted that the blower unit could be redesigned to allow the air path to pass over the lower wall of the sub-housing, as well as or instead of, the side and upper walls. As described above, the sub-housing500is located at the rear of the blower unit7. It could of course be located anywhere suitable, such as the sides or base, with the air ducting and inlet configured and located accordingly. The rear is preferred as this configuration allows the other elements of the blower unit to be configured to minimize the overall device ‘footprint’. In the most preferred form, the outer surfaces of the walls502,503and504are ribbed, in order to increase the surface area available for cooling, and to aid in heat dissipation by acting in a similar manner to heat sinks. Also, in the most preferred form, air flows over at least two and preferably three walls of the sub-housing500in order to maximise the cooling. Carry Case As has been noted above, one problem that can occur when a user packs their breathing assistance apparatus in a case for travel is forgetting to empty the humidifier chamber, and the contents may then spill during travel, causing at least inconvenience. It is a long felt want by users of domestic breathing assistance apparatus that this problem is addressed. In the preferred embodiment, a carry case600is used with the integrated unit6described above to help overcome this problem. When a user wishes to pack their breathing assistance device for transport, the carry case600can be used. The carry case600is shown inFIGS.18-20. The carry case600is formed from a rigid plastic in the preferred embodiment. The case600in the preferred form comes in two parts or halves, an upper half604and a lower half605(‘half’ is used in this context as a term of convenience and does not necessarily indicate that the upper and lower halves are required to be exactly or even close to the same size). In the closed position, the carry case600has one generally flat end601, with the opposite end602coming to a rounded point when viewed side on. It is preferred that end602includes a handle609to aid a user in transporting the case600. In the preferred form, the handle609is formed when the case is closed, the upper and lower halves604,605including apertures which align to form one aperture when the case is closed, a user gripping the handle portion thus formed. The parts that form the handle are preferably rounded, and sized to facilitate their acting as a handle. The case600can be stood upright and rested on the flat end, or end base601, in use. Alternatively, the carry case can be rested on the side base603which forms the lower side of the lower half605. It should be noted that ‘upper’ and ‘lower’ are only directional indicators when the. carry case600is resting on the side base603. The two halves are connected by hinges—the upper half604attached to the lower half605so that the case can be opened by e.g. rotating or pivoting the upper half605relative to the stationary lower half605, with the case600resting on side base603, for packing or unpacking. In the fully closed position, the edges of the two come together to enclose a volume of space or an internal volume of the case. The hinges are adapted to allow the two halves a full range of movement—e.g. substantially 180 degrees of rotation relative to one another. This allows the upper half604to be rotated far enough that its outer surface can rest on the same surface as the lower half605, for example a table or similar, and a user can freely access the inside of the case. In the preferred embodiment, the hinges610are located at the flat end601, and form part of the flat base in use. The inside contains packaging or padding606, in the preferred form including a pocket or recess608formed by moulding and shaping the padding606, so that the pocket608conforms generally to the external shape and dimensions of the blower unit7, so that at least the lower portion of the blower unit can be placed in the recess608in the packaging606in an upright position, with the packaging or padding606partially enclosing at least the lower portion of the blower unit7, to hold the blower unit7securely in position during transport. As described above, the preferred form of chamber31is a top fill chamber with a removable lid32. To prevent the user from inadvertently packing their integrated unit6away with chamber31still partially full and containing liquid, the carry case600is adapted in the following manner so that the case600cannot be closed fully if the lid32is still in position on the chamber31. It should be noted that different forms of the carry case could be used to transport other types of systems that provide heated, humidified gases to a user. For example, systems that have push fit chambers filled through their inlets or outlets, rather than through a top fill aperture. When the user needs to transport their integrated blower/humidifier unit, the user packs the integrated unit6in the carry case600by placing the integrated unit6in recess608in the packaging606, the recess608shaped to enclose at least the base of the integrated unit6. It is intended that the case600is as compact as possible. This helps a user to transport their unit as, for example, hand luggage on an aircraft, as it can be fitted in an overhead locker. Therefore, in the preferred form, the humidifier chamber31is located in the same position in which it is used in the blower7, and not in a separate recess: The upper half604of the case600includes at least one protrusion607extending inwards from the inner surface of the upper half604(i.e. downwards towards lower half605). The at least one protrusion607is sized and shaped so that the upper half and lower half604,605cannot be brought fully together (i.e. the case600cannot be closed) when the humidifier chamber lid32is still in position on the chamber31. When the humidifier chamber lid31is removed, the protrusion or protrusions607fit down inside the chamber31. The lid32therefore has to be removed from the chamber31before the carry case600can be shut. It is preferred that the separate handle22can be located onto the blower unit7, with the protrusion or protrusions607extending past the handle22to extend downwards into the chamber31. The carry case600is preferably adapted to include an internal pocket or similar—e.g. in the packaging606—which the user can use to store the lid32for travel. It is preferred that the carry case can also be fitted with a strap or straps, to allow it to be carried in the same manner that a daysac or small knapsack would be carried, or slung over one shoulder and carried by one strap. It should be noted that blower unit7is used as an example for the above described preferred form of carry case. In other, alternative forms, the carry case is adapted to carry respiratory humidification systems of the type where the humidifier chamber and the blower unit rigidly mate. In this alternative form, the padding includes a first pocket and a second pocket. The first pocket is adapted to enclose at least the base of the blower unit, and the second pocket is adapted to at least partly enclose the humidifier chamber. The two pockets are separate, so that the humidifier chamber must be disconnected from the blower before the chamber and the blower can be placed in their respective pockets. That is, the blower and the chamber cannot be mated to be correctly stored in the case in their respective pockets. The inner surface of the upper half includes a protrusion, facing inwards. When the case is closed, the protrusion locates into a space adjacent to the blower pocket, and ensures that the blower cannot be placed into the first pocket with the chamber rigidly mated to the blower, and the lid them closed. The protrusion will interfere with the chamber if a user attempts to close the lid while the chamber is in position on the blower. LIST OF FEATURES 1. Prior art blower2. Prior art chamber3. User/Patient4. User interface5. Prior art integrated blower/humidifier6. Integrated unit of the invention7. Blower of the invention8. Control knob9. Display10. Chamber seal11. Humidifier compartment12. Humidifier chamber13. Blower inlet port14. Blower outlet port15. Humidifier chamber port (inlet)16. Humidifier chamber port (outlet)17.18.19. Electrical connector20.21. Prior art conduit from chamber to patient22. Locking handle23. Heater base24. Rim of humidifier compartment25. Patient outlet (connector)26. Mating locking grooves27. Mating lugs28. Entry point of locking grooves29.30. Grip31. Humidifier unit of the invention32. Humidifier chamber lid33. Ledge34. Entry passage35. Baffle36. Exit Passage37. Front faceplate38. Depression39. Mechanical fastener—clips40.41. Prior art conduit between blower and chamber42.44. Connector Board45. Ring magnet46. Magnetised sections47.48. Magnet49. Magnet50. Front face of (7)51. Axis of rotation52.53.54.56.60. Fastener tips61. Button62. Boss63. Fasteners70. Silicone seal80. Rear wall100. Fan unit101. Air inlet vent102.103.104.105.106.107.108.109.110. Fan entry aperture111. Magnetic segments112. Coils113. Bearing unit120. Duct121. Blower exit130. Air path200. Air entry passage201. Exit aperture202. Umbrella portion300. Control circuitry400. Recess500. Power supply sub-housing501. Power supply board502. Sub housing side wall (outer)50.3. Sub housing top wall504. Sub housing side wall (inner)505. Curved path506. Aperture510. Sub housing range face600. carry case601. carry case flat end602. carry case pointed end604. carry case upper half605. carry case lower half606. carry case packaging607. carry case lid protrusion608. carry case recess609. carry case handle610. carry case hinges1000. Aperture | 51,877 |
11857730 | DETAILED DESCRIPTION Exemplary embodiments of the present disclosure will be described in detail below with reference to the accompanying drawings. It should be understood that the exemplary embodiments described herein are only adopted to illustrate and explain the present disclosure, and are not intended to limit the present disclosure. Electroencephalogram detection is one of methods for detecting function of human nervous system. By placing electrodes on the scalp, detecting a continuous rhythm potential change (that is, a brain electrical signal) in the activity of human brain nerve cells, and transmitting the brain electrical signal to an electroencephalograph for processing, a waveform of the potential change produced by the activity of human brain nerve cells can be recorded to generate an electroencephalogram. The brain electrical signals acquired at different positions of a human head can reflect respective states of human. The brain electrical signal near the forehead of human can reflect a concentration degree and a relaxation degree of the brain, and is generally used for detecting sleep depth of human. An embodiment of the present disclosure provides an eyeshade.FIG.1is a schematic exploded structural diagram of an eyeshade according to an embodiment of the present disclosure, andFIG.2is a schematic structural diagram of a controller according to an embodiment of the present disclosure. As shown inFIGS.1and2, the eyeshade includes an eyeshade main body10, and an electroencephalogram acquisition unit20, a controller30, and a heating unit40(seeFIG.4) which are disposed on the eyeshade main body10. The electroencephalogram acquisition unit20is configured to acquire a brain electrical signal of a wearer. The controller30includes a converter31and is configured to receive the brain electrical signal from the electroencephalogram acquisition unit20, and the converter31is detachably coupled to the electroencephalogram acquisition unit20and is configured to convert the brain electrical signal into a communication signal and transmit the communication signal to outside when the converter31is coupled to the electroencephalogram acquisition unit20. For example, the converter31of the controller30may transmit the communication signal to a server (e.g., a computer, a mainframe computer, or the like) for storage, processing, and/or display, or may transmit the communication signal to a terminal (e.g., a personal digital assistant, a mobile phone, a notebook computer, a personal computers, or the like) for storage, processing and/or display. In some embodiments, the converter31may transmit the communication signal to an upper computer, so that the upper computer may evaluate a degree of relaxation of the brain and/or a degree of stress of the brain of the wearer according to the communication signal. In some embodiments, the controller30receives the brain electrical signal from the electroencephalogram acquisition unit20through the converter31. The upper computer may be a device which receives the communication signal from the converter31in a wired or wireless communication manner and evaluates the degree(s) of relaxation and/or stress of the brain of the wearer according to the communication signal. For example, the upper computer may be a Personal Digital Assistant (PDA), a mobile phone, a laptop computer, a personal computer, a server, and the like. For example, modern scientific researches have shown that frequencies of brain waves includes at least the following four frequency ranges: 1 Hz to 3 Hz (a brain wave having a frequency within this range is referred to as a δ wave), 4 Hz to 7 Hz (a brain wave having a frequency within this range is referred to as a θ wave), 8 Hz to 13 Hz (a brain wave having a frequency within this range is referred to as an α waves), and 14 Hz to 30 Hz (a brain wave having a frequency within this range is referred to as a β wave). In general (e.g., for an 18 year old or older person), the β wave may indicate an extreme fatigue state, a lethargy state, and/or an anesthesia state, the θ wave may indicate a frustrated state and/or a depression state, the α wave may indicate a happy state and/or a meditation state, and the0wave may indicate a mental tension state, an emotional agitation state, and/or a hyperactivity state. Therefore, the processor34of the controller30may extract a frequency of the current brain electrical signal collected by the electroencephalogram acquisition unit20, and then determine a degree of relaxation or tension of the brain of the wearer according to the range to which the frequency belong. It should be understood that the present disclosure is not limited thereto. For example, with the deepening of scientists' understanding of brain waves, the frequencies of the brain waves may be divided into more frequency ranges than those described herein to reflect more mental states and/or physiological states of a person. The heating unit40is configured to heat an eye region of the wearer. For example, the heating unit40may be a heater including a thermistor. In an embodiment of the present disclosure, a side of the eyeshade main body10which is away from (or is distal to) the wearer when the wearer wears the eyeshade is referred to as an outer side of the eyeshade main body10(or may be referred to as a first interface of the eyeshade main body10), and a side of the eyeshade main body10which faces (or is proximal to) the wearer when the wearer wears the eyeshade is referred to as an inner side of the eyeshade main body10(or may be referred to as a second interface of the eyeshade main body10). In an embodiment of the present disclosure, a portion of the electroencephalogram acquisition unit20and the controller30are disposed on the outer side of the eyeshade main body10. In some embodiments, the converter31being detachably coupled to the electroencephalogram acquisition unit20means that the converter31and the electroencephalogram acquisition unit20may be temporarily integrated as a single component, and that the converter31may be separated from the electroencephalogram acquisition unit20. When the converter31and the electroencephalogram acquisition unit20are temporarily formed as a single component, a signal may be transmitted between the converter31and the electroencephalogram acquisition unit20. In some embodiments, as shown inFIG.1, the controller30includes a first coupling structure32which is electrically conductive, the electroencephalogram acquisition unit20includes a second coupling structure21which is electrically conductive, and the electroencephalogram acquisition unit20is detachably coupled to the first coupling structure32of the controller30through the second coupling structure21. When the electroencephalogram acquisition unit20is coupled to the first coupling structure32through the second coupling structure21, the electroencephalogram acquisition unit20is electrically coupled to the converter31, and the brain electrical signal acquired by the electroencephalogram acquisition unit20can be transmitted to the converter31of the controller30. The converter31may include an analog-to-digital conversion circuit311and a wireless transmission circuit312. The analog-to-digital conversion circuit311converts the received brain electrical signal that is an analog signal into a digital brain electrical signal, and the wireless transmission circuit312transmits the digital brain electrical signal to the upper computer. The heating unit40is disposed on the inner side of the eyeshade main body10, and overlaps with the eye region of the wearer when the eyeshade is worn by the wearer. The heating unit40is electrically coupled to the controller30. The analog-to-digital conversion circuit311may be implemented by an analog-to-digital converter (ADC), such as AD997A, AD574A, AD4003, AD4000, and the like. The wireless transmission circuit312may be implemented by a bluetooth module, a Wi-Fi module, a Zigbee module, and the like. For example, the Bluetooth module may be CC2541, CC2640, SKB369, RF-BM-SOA, and the like; the Wi-Fi module may be CC3100 of Ti, MW300 of Marvell, BCM4390 of Broadcom, MT7688 of MTK, and the like; and the Zigbee module may be JN5169 of NXP CC2530 of Ti, and the like. The eyeshade of the embodiment of the present disclosure includes the heating unit40and the electroencephalogram acquisition unit20, and thus the brain electrical signal of the wearer can be acquired while heating the eye region of the wearer. In addition, the electroencephalogram acquisition unit20can be detached from the eyeshade, so that the wearer can detach the electroencephalogram acquisition unit20from the eyeshade when the brain electrical signal is not acquired, and the weight of the eyeshade is reduced. In some embodiments, the first coupling structure32of the controller30includes a data interface including, but not limited to, a type-C interface or a micro-USB interface, and the second coupling structure21of the electroencephalogram acquisition unit20includes a data interface that matches with the data interface of the first coupling structure32. In this case, the electroencephalogram acquisition unit20is detachably coupled to the controller30through the matched data interfaces, and the controller30may receive the brain electrical signal from the second coupling structure21of the electroencephalogram acquisition unit20through the data interface of the first coupling structure32. When the wearer does not use the electroencephalogram acquisition unit20while using the eyeshade to heat the eye region, the electroencephalogram acquisition unit20can be removed to reduce the weight of the eyeshade. In some embodiments, the controller30may communicate wirelessly (for example, via Bluetooth, Wi-Fi, and the like) with the electroencephalogram acquisition unit20. In this case, wireless communication modules that can communicate wirelessly with each other are included in the controller30and the electroencephalogram acquisition unit20, respectively. The controller30may further include a temperature controller33, and the temperature controller33is coupled to the heating unit40and is configured to adjust a heating temperature of the heating unit40. In some embodiments, the controller30may further include a processor34, the processor34is coupled to the temperature controller33and the electroencephalogram acquisition unit20and is configured to generate a control signal according to the brain electrical signal acquired by the electroencephalogram acquisition unit20, and the temperature controller33is configured to adjust the heating temperature of the heating unit40according to the control signal. The temperature controller33and the processor34may be integrated in a single processing device, or may be implemented by different processing devices. The processing device(s) may be, for example, a central processing unit CPU (for example, ARM Cortex-M3), a digital signal processor DSP (for example, CEVA DSP), a micro control unit MCU (for example, STM32, MSP 430), and the like. In some embodiments, a control instruction may be provided to the temperature controller33by the wearer, and the temperature controller33adjusts the heating temperature of the heating unit40according to the control instruction. In some embodiments, the control signal may be generated by the processor34according to the brain electrical signal acquired by the electroencephalogram acquisition unit20, and the temperature controller33adjusts the heating temperature of the heating unit40according to the control signal, so as to achieve automatic adjustment of the temperature. By adjusting the heating temperature of the heating part40, different temperatures can be achieved to heat the eye region of the wearer, and thus the brain electrical signals of the wearer at different heating temperatures can be detected to analyze the brain electrical activities of the wearer at different heating temperatures. In some embodiments, providing the control instruction to the controller30by the wearer may include providing the control instruction through a button or a rotary knob or the like disposed on the controller30, but is not limited thereto. In some embodiments, when the processor34adjusts the heating temperature of the heating unit40according to the brain electrical signal acquired by the electroencephalogram collection portion20, the processor34obtains (for example, calculates or queries according to pre-stored information) a corresponding control signal according to the brain electrical signal acquired by the electroencephalogram collection portion20, and the temperature controller33controls the heating temperature of the heating unit40according to the corresponding control signal, so as to adjust the heating temperature of the heating unit40in real time. In some embodiments, for example, when the wearer is in a relatively nervous state, the brain of the wearer is highly active, and the brain electrical signal varies greatly, the heating temperature of the heating unit40may be increased appropriately to relax the wearer, so that the wearer may enter into a sleep state more quickly. In some embodiments, the heating unit40may have a heating temperature up to about 42° C. to effectively relieve eye fatigue and promote local blood circulation. FIG.3is a schematic diagram of an electroencephalogram acquisition unit according to an embodiment of the present disclosure. As shown inFIG.3, the electroencephalogram acquisition unit20includes a flexible circuit board22and an electrode23disposed on the flexible circuit board22. The controller30is disposed on the outer side of the eyeshade main body10, and the flexible circuit board22is detachably coupled to the controller30through the first coupling structure32and the second coupling structure21. As shown inFIGS.1and3, an opening11is provided in a portion of the eyeshade main body10that overlaps with a forehead of the wearer when the eyeshade is worn by the wearer, and the flexible circuit board22may pass through the opening11, so that the electrode23on the flexible circuit board22is in contact with the forehead of the wearer. In some embodiments, the electrode23includes a plurality of sub-electrodes including differential electrodes231and a reference electrode232. The controller30may include a differential signal receiving port and a reference voltage receiving port. The differential signal receiving port of the controller30is configured to receive a signal acquired by the differential electrodes231, and the reference voltage receiving port of the controller30is configured to receive a signal acquired by the reference electrode232. In some embodiments, two differential electrodes231(which may be electrically coupled to the differential signal receiving port of the controller30) and one reference electrode232(which may be electrically coupled to the reference voltage receiving port of the controller30) are arranged in a direction parallel to a length of the flexible circuit board22. The two differential electrodes231are respectively disposed on both sides of the reference electrode232, and the brain electrical signal is transmitted to a corresponding signal receiving port of the controller30through the electrode23. In some embodiments, an adhesive unit10cis provided on a side of the flexible circuit board22away from (i.e., distal to) the electrodes and/or on both ends of the eyeshade main body10. For example, a portion of the adhesive unit10cis disposed on the outer side of one end of the eyeshade main body10(as shown in the upper right corner ofFIG.4), and the other portion of the adhesive unit10cis disposed on the inner side of the other end of the eyeshade main body10(as shown in the lower left corner ofFIG.4), so that the eyeshade main body10can be fixed to the head of the wearer by the adhesive units10c. In some embodiments, the adhesive unit10cincludes a Velcro. In some embodiments, a fixing member which is electrically conductive is disposed on the outer side of the eyeshade main body10, the controller30is fixed to the eyeshade main body10by the fixing member, and the temperature controller33is electrically coupled to the heating unit40by the fixing member. In some embodiments, the fixing member includes a magnetic clasp. In some embodiments, as shown inFIG.1, the magnetic clasp includes a female clasp12disposed on the eyeshade main body10and a male clasp35disposed on the controller30. The female clasp12is electrically coupled to the heating unit40through a wire inside the eyeshade main body10. In the embodiment shown inFIG.1, each of the number of female clasps12and the number of male clasps35is two (2). In some other embodiments, each of the number of the female clasps12and the number of the male clasps35is four (4), so as to ensure the reliability of connection and make full use of a space on the eyeshade main body10and a space on the controller30. FIG.4is a schematic structural diagram of an eyeshade main body according to an embodiment of the present disclosure. As shown inFIG.4, a light-shielding layer13is disposed on the inner side of the eyeshade main body10, and first recesses14(for example, two first recesses14) are provided in a portion of the light-shielding layer13that overlaps with the eye region of the wearer when the eyeshade is worn by the wearer. In some embodiments, the light-shielding layer13may fit the wearer's face, thereby completely shielding the light. Since the first recesses14are provided in the portion of the light-shielding layers13that overlap with the eye region of the wearer when the eyeshade is worn by the wearer, the light-shielding layer13does not press the wearer's eyeballs. In some embodiments, when a width of the eyeshade main body10(that is, a dimension in the top-to-bottom direction ofFIG.4) is relatively large, a second recess15may be provided in the light-shielding layer13so that the light-shielding layer13fits the wearer's nose when the eyeshade is worn by the wearer to prevent light leakage. In some embodiments, the opening11is located outside an area of the eyeshade main body10that overlaps with the eye region of the wearer when the eyeshade is worn by the wearer to prevent light leakage. In some embodiments, the heating unit40is disposed within the light-shielding layer13. In some embodiments, the heating unit40includes a material of graphene. In some embodiments, as shown inFIG.1, the eyeshade main body10includes a first main body portion10aand two second main body portions10brespectively located on both sides of the first main body portion10a. The opening11, the controller30, the light-shielding layer13, and the heating unit40are disposed on the first main body portion10a. One end of each of the second main body portions10bis coupled to the first main body portion10a, and the other ends of the two second main body portions10bmay be coupled with each other through the adhesive unit1cwhen the eyeshade main body10is wrapped around the head of the wearer (that is, the wearer wears the eyeshade). The first and second main body portions10a,10bmay have relatively large widths so as to disperse pressure from the eyeshade to different locations of the head of the wearer to avoid discomfort of the wearer caused by excessive local pressure. In some embodiments, the controller30further includes a power interface. The power interface is coupled to a power source (for example, a battery or an AC power source) when the eyeshade is worn by the wearer, so as to supply power to the eyeshade. An embodiment of the present disclosure further provides an electroencephalogram detection system including the eyeshade described above and an upper computer, and the upper computer is configured to receive the communication signal transmitted from the converter31and to evaluate the degree(s) of relaxation and/or tension of the brain of the wearer according to the communication signal. The electroencephalogram detection system according to the embodiment of the present disclosure includes the heating unit40and the electroencephalogram acquisition unit20, and thus the eyeshade can acquire the brain electrical signal of the wearer while heating the eye region of the wearer. In some embodiments, the electroencephalogram acquisition unit20is detachable, so that the wearer can detach the electroencephalogram acquisition unit20from the eyeshade when the brain electrical signal is not acquired to reduce the weight of the eyeshade. It will be understood that the above embodiments are merely exemplary embodiments to explain the principle of the present disclosure, and the present disclosure is not limited thereto. It will be apparent to one of ordinary skill in the art that various changes and modifications can be made therein without departing from the spirit and scope of the disclosure, and these changes and modifications are to be considered within the scope of the disclosure. | 21,040 |
11857731 | DESCRIPTION OF EMBODIMENTS The following terms “first” and “second” are merely intended for a purpose of description, and shall not be understood as an indication or implication of relative importance, order, or implicit indication of the number of indicated technical features. Therefore, a feature limited by “first” or “second” may explicitly or implicitly include one or more features. In the description of the embodiment of this application, unless otherwise stated, “multiple” means two or more than two. Terms in various embodiments are first described. Intrinsically photosensitive retinal ganglion cells are main cells on which melatonin synthesis and release depend. Usually, the ipRGC senses an optical signal, and passes the optical signal through the optic nerve to the suprachiasmatic nucleus (SCN) of the hypothalamus and other nervous nuclei. The SCN and the other nervous nuclei regulate a circadian rhythm, including regulating secretion and release of a specific hormone. The specific hormone includes melatonin. Usually, ipRGC sensitive band light is visible light whose wavelength falls within a band range of 380 nm to 550 nm and whose peak value is 480 nm.FIG.1shows a response curve of ipRGC to light in different bands. InFIG.1, the ipRGC is more sensitive to visible light whose wavelength falls within a band range of 380 nm to 550 nm. It may be understood that in the daytime, a percentage of light in the band in light received by an eye is usually relatively high. This may stimulate the ipRGC, so that the SCN decreases a secretion amount of melatonin, to alleviate sleepiness. At night, a percentage of light in the band in light received by the eye is relatively low. This may stimulate the ipRGC, so that the SCN increases the secretion amount of melatonin, to improve sleep quality of a user. Herein, that the wavelength ranges from 380 nm to 550 nm is merely an example. A person skilled in the art may obtain light that is in another band and that is used to regulate a circadian rhythm. This is not limited in this application. In the prior art, a light therapy device is provided to adjust emitted light and provide a sleep assistance function for a user. The light therapy device may provide light with different brightness levels for the user. For example, the light therapy device provides daytime light 1 with a brightness level of 1, and the daytime light 1 may be used to wake up the user in the morning to improve working efficiency. At night, the light therapy device provides nighttime light 2 with a brightness level of 2, and the nighttime light 2 may be used for sleep assistance at night because of low brightness. Further, brightness of the nighttime light 2 may be set to a gradually fading mode, making it easier for the user to sleep. However, in many application scenarios, light required by the user is not necessarily consistent with light provided by the light therapy device. For example, in a time period from 13:00 to 14:00, a body temperature of the user decreases after lunch, and the user is in a fatigue state. In this case, if the light therapy device provides the daytime light 1 for the user, excitability of the brain of the user is improved, which is unfavorable to lunch break of the user. It may be learned that a limited quantity of brightness levels are set for the existing light therapy device, and various types of brightness provided by the light therapy device are relatively fixed. Consequently, light provided by the light therapy device may not meet a real-time requirement of a user, and a method for improving sleep quality is not intelligent enough. In view of this, an embodiment in accordance with the present disclosure provides a light adjustment method. The method may be applied to a system shown inFIG.2. The system includes a terminal20and a server21that can communicate with the terminal. In some embodiments, the system further includes a light source device22. The terminal20may be a mobile phone or a wearable device (such as a wristband, a watch, or a pair of glasses) shown inFIG.2, or may be any terminal with a light detection function, for example, a tablet computer, a notebook computer, an ultra-mobile personal computer (ultra-mobile personal computer, UMPC), or a netbook that is not shown inFIG.2. This is not limited in this embodiment of this application. Referring toFIG.2, the terminal may obtain a second user profile of a user and geographical location information of the user. Herein, the user profile includes but is not limited to a user behavior, a user type, and a user sleep status. In an example of obtaining the sleep status, the wearable device (for example, the wristband inFIG.2) collects sleep data of the user, and feeds back the sleep data to the mobile phone. Alternatively, in a smart household scenario, a smart household object (for example, a smart mattress that is not shown inFIG.2) collects sleep data of the user, to reflect the sleep status of the user. Certainly, the mobile phone or the wristband may alternatively obtain the sleep data of the user from the server21. Then, the terminal determines a light parameter threshold in each sub-period based on the second user profile and the geographical location information of the user. Subsequently, the terminal may detect a light parameter of light received by the user in a current sub-period, and adjust, based on the light parameter in the current sub-period and a light parameter threshold in the sub-period, a light parameter of light emitted by the light source device. The light source device may be disposed inside the terminal, for example, disposed inside the mobile phone. In this case, the mobile phone adjusts the light parameter of the light emitted by the internal light source device (for example, a light source device in a screen of the mobile phone). The light source device may alternatively be disposed independently. For example, the light source device may be a lamp22shown inFIG.2. In this case, after determining that the light parameter in the current sub-period cannot meet a user requirement, the mobile phone may adjust a light parameter of light emitted by the lamp. Certainly, the independent light source device in this embodiment of this application is not limited to a form of a lamp, and may alternatively be another device that includes a light source and that is used for lighting. This is not limited in this embodiment of this application. As shown inFIG.3, a mobile phone30is used as an example to describe this embodiment in detail. It should be understood that the mobile phone30shown in the figure is merely an example of the terminal, and the mobile phone30may include more or fewer components than those shown inFIG.2, may combine two or more components, or may have different component configurations. Referring toFIG.3, the mobile phone30may communicate with electronic devices31and32and a server33other than the mobile phone30. It may be understood that the electronic device31or32may be the light source device shown inFIG.2. The mobile phone30may include a processor301, a memory303, a bus304, a user input module305, a display module306, a light sensing module307, a communications interface308, and other similar and/or suitable components. The bus304may be a circuit that interconnects the foregoing elements and transfers communication (for example, a control message) between the elements. The light sensing module307may detect a light parameter received by the mobile phone, and transfer the detected light parameter to the processor301. The light sensing module307mainly detects the foregoing ipRGC sensitive band light. For detailed description of the ipRGC sensitive band light, refer to the foregoing description. Details are not described herein again. The processor301may receive a command from the foregoing another element (for example, the memory303, the user input module305, the display module306, or the communications interface308) by using the bus304, may interpret the received command, and may perform calculation or data processing based on the interpreted command. For example, the processor301receives light intensity detected by the light sensing module307, calculates, based on the light intensity, an amount of light received by a user in a current sub-period, and then determines whether a light parameter of light emitted by a light source device needs to be adjusted. Herein, the light source device may be an independent device, or may be a light source device disposed inside the mobile phone. In some embodiments, as shown inFIG.3, when the light source device is disposed inside the mobile phone, the mobile phone may further include a light module302. The memory303may store a command or data received from the processor301or another element (for example, the user input module305, the display module306, or the communications interface308), or a command or data generated by the processor301or another element. The user input module305may receive a command or data entered by the user by using an input-output means (for example, a sensor, a keyboard, or a touchscreen), and may transfer the received command or data to the processor301or the memory303by using the bus304. The display module306may display various types of information (for example, multimedia data and text data) received from the foregoing element. For example, the display module306may display a video, an image, or data to the user. The communications interface308may control a short-range communications connection between the mobile phone30and the electronic device31. When the mobile phone30is paired with the electronic device, the communications interface308may stop a scanning operation of waiting for receiving a signal from an adjacent electronic device, or stop a broadcast operation of broadcasting a signal. For example, in response to pairing between the mobile phone30and the electronic device31, the communications interface308stops the scanning operation of waiting for receiving a signal from an adjacent electronic device, or stops the broadcast operation of broadcasting a signal. When the mobile phone30is paired with the electronic device, the communications interface308may control a period of the scanning or broadcast operation. In addition, according to the embodiments disclosed in this application, the mobile phone30may further communicate with another device by using the communications interface308. For example, the mobile phone30may communicate with the another electronic device32and the server33by using the communications interface308. Certainly, when the light source device is an independent device, to adjust the light parameter of the light source device, the mobile phone30may further communicate with a light source device34shown inFIG.3. Specifically, the communications interface308may communicate with the another electronic device32, the server33, the light source device34, or the like directly or by using a network. For example, the communications interface308may perform an operation of connecting the mobile phone30to a network. An embodiment in accordance with the present disclosure provides a light adjustment method. As shown inFIG.4AandFIG.4B, the method includes S401to S408. S401. A terminal determines an awake time period and a sleep time period of a user. In some embodiments, the awake time period and the sleep time period each includes at least one first sub-period and/or second sub-period, the first sub-period is a daytime period, and the second sub-period is a nighttime period. In this embodiment of this application, a day is used as a basic unit, 24 hours in a day are divided into an awake time (awake time, AT) period and a sleep time (sleep time, ST) period, and the awake time period is further divided into at least one daytime (day time, DT) period and/or nighttime (night time, NT) period.FIG.5shows an example division manner. The awake time period includes a daytime period 1 that is from 6:00 to 12:00, a daytime period 2 that is from 14:00 to 19:00, and a nighttime period 1 that is from 19:00 to 24:00. The sleep time period includes a daytime time period 1 that is from 12:00 to 14:00 and a nighttime period 1 that is from 24:00 to 6:00. In some embodiments, to more precisely adjust an amount of light with improved real-time performance, the time period may be further divided by using a finer granularity. For example, as shown inFIG.6, the daytime period 1 included in the awake time period inFIG.5is further divided into a plurality of third sub-periods at a finer granularity. For example, the daytime period 1 included in the awake time period inFIG.5is divided, at an interval of one hour, into six third sub-periods shown inFIG.6. It may be understood that duration of the third sub-periods may be the same or different. This is not limited in this application. In this embodiment, the awake time period and the sleep time period may be determined in the following two manners: Manner 1: The terminal receives time period division data entered by the user, and determines the awake time period and the sleep time period of the user based on the time period division data. As shown inFIG.7(a), the terminal may provide a time period setting function item702in a sleep mode setting interface701. The user may further set the awake time period and the sleep time period by using the time period setting function item702. As shown inFIG.7(b), in a time period setting interface704, there is an awake time period setting item705and a sleep time period setting item706. For example, the user taps the sleep time period setting item706to set a specific time of the sleep time period. For example, after the user taps the sleep time period setting item706, the terminal pops up a sleep time period setting box707shown inFIG.7(b), and the user sets the sleep time period to 24:00 to 6:00 in the sleep time period setting box707. For another example, the user may further set each first sub-period (daytime period) or second sub-period (nighttime period) in the awake time period by using the awake time period setting item705. Specifically, after the user taps the awake time period setting item705, the terminal makes a jump to an awake time period setting interface708shown inFIG.7(c). The awake time period setting interface708includes a (first sub-period) daytime period setting item709and a (second sub-period) nighttime period setting item710. The user may tap the daytime period setting item709to set the at least one daytime period included in the awake time period, and may further tap the nighttime period setting item710to set the at least one nighttime period included in the awake time period. For example, after the user taps the daytime period setting item709, the terminal pops up a daytime period setting box711shown inFIG.7(c), and the user sets the daytime period 1 included in the awake time period to 6:00 to 12:00. Manner 2: The terminal obtains a first user profile of the user, and determines the awake time period and the sleep time period of the user based on the first user profile. The first user profile includes information such as a user behavior and a sleep status. The user behavior is a terminal-related behavior generated when the user uses the terminal. Behavior data is used to reflect the user behavior. The sleep status is used to describe sleep quality of the user, and sleep data is used to reflect the sleep status. The sleep data includes deep sleep duration, a deep sleep percentage (namely, a percentage of duration in which the user is in a deep sleep state in total sleep duration), a sleep score (namely, the sleep quality), and the like. It should be noted that an actual user may be abstracted, based on a use behavior of the user, into a first user profile that includes one or more pieces of information. For example, a user A often watches an animation after 12:00 in the evening by using a mobile phone. In this case, information included in a first user profile obtained through abstraction is {sleep status: late sleep, user behavior: staying up late}. Table 1 shows a user profile of the user A that is in a form of a table. Information 1 (namely, sleep status information) indicates that a sleep status of the user A is late sleep, and information 2 (namely, user behavior information) indicates that a sleep behavior of the user A after 12:00 is staying up late. In addition, the user profile may be stored in a form of a configuration file (profile), a database, or the like. TABLE 1User profile of the user AInformation 1Sleep status: late sleepInformation 2User behavior: staying up late Herein, permission for the terminal to obtain the behavior data and/or the sleep data of the user may be enabled in advance. For example, the user enables the permission for the terminal by using a permission management setting item802in a setting interface801shown inFIG.8(a)andFIG.8(b). For example, the user enables permission to read the sleep data and permission to the read the behavior data. For example, the first user profile includes the behavior data, and the behavior data represents that the user usually uses the terminal from 6:00 to 22:00. If the user has no habit of using the terminal from 22:00 to 6:00, the terminal may determine 6:00 to 22:00 as the awake time period of the user, and determine 22:00 to 6:00 as the sleep time period of the user. For example, the first user profile includes the sleep data. The sleep data of the user may be obtained by using the wearable device (for example, the wristband) shown inFIG.2, or the sleep data of the user may be obtained by using a device such as a smart mattress in a smart household scenario. If the user has a relatively regular sleep cycle, in some embodiments, the terminal determines the time period based on average values of awake times and sleep times. A regular sleep cycle means a relatively fixed daily sleep time, fixed daily sleep duration, and the like. For example, the sleep data represents that the user usually goes to sleep (in other words, falls asleep) at 22:00 and usually wakes up (in other words, awakes) at 6:00. In this case, the terminal determines 22:00 to 6:00 as the sleep time period of the user, and determines 6:00 to 22:00 as the awake time period. If the user has an irregular sleep cycle, in some embodiments, the terminal calculates medians, modes, and the like of awake times and sleep times, to determine the awake time period and the sleep time period. If there is a relatively small amount of sleep data of the user, in some embodiments, an awake time and a sleep time in sleep data of the user in a particular day are randomly selected as a basis for determining the time period, or average values of a plurality of awake times and a plurality of sleep times in a preset quantity of pieces of sleep data are calculated, to determine the awake time period and the sleep time period. In addition, a time period division manner corresponding to relatively good sleep quality may be determined as a current time period division manner. For example, after obtaining the sleep data of the user, the terminal determines that the sleep quality of the user is relatively good in the time period division manner shown inFIG.6. In this case, the terminal uses the time period division manner shown inFIG.6as the current time period division manner. In addition, the terminal may recommend a time period division manner to the user. In a scenario, the terminal obtains the behavior data and the sleep data of the user. If it is determined that a work and rest pattern of the user belongs to a work and rest pattern indicating subhealth, a work and rest policy recommendation box901shown inFIG.9(a)andFIG.9(b)is displayed to prompt the user that the user may tap a work and rest policy item902. After the terminal pops up a work and rest policy menu903, the user may view a specific recommended work and rest policy. S402. The terminal determines a light parameter threshold in each first sub-period and a light parameter threshold in each second sub-period. Alight parameter includes but is not limited to spectral distribution, light intensity, and an amount of light. The light parameter threshold includes a lower light parameter threshold and an upper light parameter threshold. In some embodiments, the terminal determines the light parameter threshold in the following several manners: Manner 1: The terminal calculates the light parameter threshold in each first sub-period and the light parameter threshold in each second sub-period. This manner may include the following several cases: Case 1: The terminal obtains a second user profile of the user, and determines the light parameter threshold in each first sub-period and the light parameter threshold in each second sub-period based on the second user profile. Herein, a meaning of the second user profile is the same as that of the first user profile. A difference between the second user profile and the first user profile lies in that the second user profile and the first user profile include different information. The second user profile includes basic user information, a sleep status, a user behavior, and a user type. The basic information includes a gender, an age, an occupation, and the like of the user. For description of the user behavior and the sleep status, refer to the foregoing description. Details are not described herein again. The user type is used to reflect an individual feature of the user. For example, the second user profile is the sleep status. In this case, the terminal determines the light parameter threshold in each first sub-period and the light parameter threshold in each second sub-period based on sleep data of the user. For description of the sleep data, refer to the foregoing description. Details are not described herein again. For example, when the sleep data represents that the sleep quality of the user is relatively good, to balance a time ratio between work and sleep, a light parameter threshold in the awake time period may be appropriately increased under a condition that the sleep quality is not affected, to suppress melatonin secretion in the awake time period. This further improves working efficiency in the awake time period. For example, the light parameter is the light intensity. In an initial state, the light parameter threshold set by the terminal for the user in the awake time period is first light intensity. Subsequently, if the terminal detects that the sleep quality of the user is relatively good, the terminal may increase the light parameter threshold in the awake time period to second light intensity under a condition that the sleep quality of the user is not affected. In this way, the sleep quality of the user can be ensured and working efficiency of the user can be improved. It should be noted that in this embodiment, secretion of melatonin is related to light at each moment. In addition, in consideration of an accumulative effect of light in a time period, the light parameter that affects the secretion of melatonin may alternatively be an accumulative amount of light (for ease of description, the accumulative amount of light is also referred to as an amount of light in this specification). Herein, the amount of light mainly indicates an amount of a target type of light. The target type of light is light related to regulation of a circadian rhythm. For detailed description, refer to the foregoing description. The amount of light may be calculated based on the light intensity and light duration. For example, if levels of light intensity at all moments in a time period are similar, that is, for any two moments in the time period, light intensity at a first moment is first light intensity, light intensity at a second moment is second light intensity, and a difference between the second light intensity and the first light intensity is less than a threshold, a product of average light intensity in the time period and duration is used as an amount of light in the time period. For another example, if light intensity changes greatly in a time period, the light intensity may be integrated in the time period by using a method such as an integral function, to obtain an amount of light in the time period. In some embodiments, the amount of light is also related to spectral distribution. Usually, a percentage of the target type of light in total light is higher. Therefore, a total amount of light in a time period may be calculated based on the spectral distribution, or a total amount of light in a time period may be calculated based on the spectral distribution, the light density, and the light duration. An example method for calculating a total amount of light may be determined based on an actual application situation. This is not limited in this embodiment of this application. For example, the second user profile is the user behavior. In this case, the terminal obtains behaviors of the user in different daytime or nighttime periods, and determines a light parameter threshold in a current sub-period based on a behavior of the user in the current sub-period. In some embodiments, the user manually enters behaviors of the user in different daytime or nighttime periods. As shown inFIG.7(c), a behavior setting item712of the daytime period 1 is set in the daytime period setting box711. The user may set a behavior in the daytime period 1 by using the behavior setting item712of the daytime period 1. For example, the behavior in the daytime period 1 (6:00 to 12:00) is set to “working” shown inFIG.10. Then, the terminal determines a light parameter threshold in each daytime period and a light parameter threshold in each nighttime period based on the behavior set by the user. In some embodiments, in a working time period, the light parameter threshold may be increased, and in a non-working time period (for example, a leisure time period), the light parameter threshold may be decreased. Alternatively, the terminal collects the behavior data of the user, and determines behaviors of the user in different daytime nighttime periods based on an algorithm. For example, from 20:00 to 21:00, the behavior data represents that the user is playing a game. In this case, the terminal determines that the nighttime period is a leisure time period, and correspondingly sets a light parameter threshold for the leisure time period. For example, the second user profile is the user type. In this case, the terminal determines a type of the terminal user, and sets different light parameter thresholds for different types of users. In some embodiments, the user manually sets the user type. As shown inFIG.7(a), the user sets a specific user type by using a user type setting item703. For example, in a user type setting interface713shown inFIG.7(d), the user may select a user type included in the user type setting interface713, for example, easy to sleep or sleep disorder. Alternatively, the user manually adds the user type. For example, after selecting the easy to sleep type, the user may set an easy to sleep time period in an easy to sleep setting window714popped up on the terminal. Alternatively, the terminal collects the behavior data of the user, and determines the user type based on the behavior data of the user. It may be understood that if the user is easy to sleep in a working time period, the terminal increases a light parameter threshold in the easy to sleep time period, to suppress melatonin secretion in the easy to sleep time period, and improve energy of the user. For a user with a sleep order, the terminal decreases a light parameter threshold of the user in a sleep latency. The sleep latency is a daytime period or a nighttime period that is included in the awake time period and that is before and adjacent to the sleep time period. For example, in the time period division manner shown inFIG.6, in the daytime, the sleep latency is 11:00 to 12:00, and at night, the sleep latency is a preset time period that is before and adjacent to 24:00, for example, may be 23:00 to 24:00. It may be learned that there are different light parameter thresholds for different types of users. The terminal flexibly adjusts a light parameter threshold in each daytime period and a light parameter threshold in each nighttime period based on a user requirement, to help the user improve a circadian rhythm, train a brain of the user, and develop a more appropriate work and rest pattern. It should be understood that the foregoing merely lists several representation forms of the second user profile. In an actual application scenario, the second user profile may alternatively be in another representation form. This is not limited in this embodiment of this application. Case 2: The terminal obtains geographical location information of the user, and determines the light parameter threshold in each first sub-period and the light parameter threshold in each second sub-period based on the geographical location information. The geographical location information includes light intensity, a longitude and a latitude, a season, weather, sunrise and sunset times, and the like at a geographical location. The light intensity is used as an example. When light intensity of natural light at the geographical location is relatively high, to ensure that the terminal is not triggered to adjust, when the user receives relatively strong natural light, a light parameter of light emitted by a light module302, the light parameter threshold in each first sub-period and the light parameter threshold in each second sub-period should be increased. On the contrary, when light intensity of natural light at the geographical location is relatively low, the user receives relatively weak natural light, and correspondingly, the light parameter threshold in each first sub-period and the light parameter threshold in each second sub-period are decreased. The geographical location information may alternatively be implemented in another form. This is not limited in this embodiment of this application. Case 3: The light parameter threshold in each first sub-period and the light parameter threshold in each second sub-period are determined based on combination information of a second user profile and geographical location information of the user. The geographical location information of the user and a user behavior in the second user profile are used as an example. The user settles in Beijing for a long time, and currently the user goes to Qinghai. Natural light intensity in Qinghai is greater than that in Beijing. It may be understood that when sleep quality statuses are similar, the user receives more light in Qinghai. Therefore, when the user is in Qinghai, the light parameter threshold in each first sub-period and the light parameter threshold in each second sub-period may be increased. In a possible implementation, when the user is in Qinghai and a time period is a working time period, a light parameter threshold in the working time period is increased. In this embodiment, priorities of the geographical location and the user behavior may be further set. When the user is in Qinghai and a time period is a rest time period, if the priority of the geographical location is higher than the priority of the user behavior, a light parameter threshold in the rest time period is increased. On the contrary, if the priority of the geographical location is lower than the priority of the user behavior, a light parameter threshold in the rest time period is decreased. Alternatively, weights of the geographical location and the user behavior are set based on a degree to which the sleep quality is affected by the geographical location and the user behavior, and a light parameter threshold in the rest time period is determined based on the weights. Manner 2: The terminal determines a target user, and respectively determines a light parameter threshold of the target user in each nighttime period and a light parameter threshold of the target user in each daytime period as the light parameter threshold in each first sub-period and the light parameter threshold in each second sub-period. A user profile similarity between the target user and the user is greater than a threshold, and the user profile similarity is used to describe a similarity between second user profiles. In some embodiments, example implementation of a manner of calculating the user profile similarity is: obtaining second user profiles of a first user and a second user, quantizing each piece of information included in the profile of the first user, quantizing each piece of information (for example, a sleep status and an occupation) included in the profile of the second user, and calculating a user profile similarity between the first user and the second user based on a quantization result. For example, an information eigenvalue of each piece of information is preset in the terminal. Herein, the information eigenvalue may reflect a sleep score. For example, a sleep moment 24:00 corresponds to an information eigenvalue of 60 (namely, 60 scores). A sleep moment 2:00 is later than the sleep moment 24:00, and an information eigenvalue corresponding to the sleep moment 2:00 may be 50 (namely, 50 scores, indicating that the sleep score is less than a sleep score of a user whose sleep moment is 24:00). Usually, a professional IT programmer sleeps later, and corresponds to an information eigenvalue of 50, and a professional white-collar worker sleeps earlier, and corresponds to an information eigenvalue of 80. A male sleeps later, and this piece of information corresponds to an information eigenvalue of 60, and gender information of a female corresponds to an information eigenvalue of 80. If the second user profile of the first user includes the following information: male, a sleep moment 24:00, and an occupation of an information technology (Information Technology, IT) programmer, and the second user profile of the second user includes the following information: male, a sleep moment 2:00, and an occupation of an IT programmer. With reference to the information eigenvalue of each piece of information, an obtained quantization result of the second user profile of the first user may be as follows: {male: 60; sleep moment 24:00: 60; professional IT programmer: 50}, and an obtained quantization result of the second user profile of the second user may be as follows: {male: 60; sleep moment 2:00: 50; professional IT programmer: 50}. Herein, a weight may be assigned to each piece of information, to obtain a final quantization result. For example, a weight of gender information is 0.1, a weight of sleep time information is 0.6, and a weight of occupational information is 0.3. In this case, a final quantization result of the second user profile of the first user is 60*0.1+60*0.6+50*0.3=57, and a final quantization result of the second user profile of the second user is 60*0.1+50*0.6+50*0.3=51. If the user profile similarity is defined as a difference between quantization values of user profiles, the obtained user profile similarity is 57−51=6. Herein, only an example of a manner of calculating the user profile similarity is provided. Certainly, the user profile similarity may be calculated by using a method such as a Euclidean distance method, a Manhattan distance method, an included angle cosine method, or a Pearson correlation coefficient method. For a process of calculating the user profile similarity by using another method, refer to the prior art. Details are not described in this application. In some embodiments, the terminal obtains sleep data of another user from a server, where the terminal has permission to access the sleep data of the another user, and recommends, to the current user, a light parameter threshold corresponding to the target user with a similar geographical location, a similar second user profile, and relatively good sleep quality. For example, the current user is a male, is 33 years old, is an IT programmer, suffers from a sleep disorder, and lives in Xicheng District, Beijing. If the terminal determines, by accessing the server, that a user 1 has a same gender, age, and occupation as the target user (in other words, a second user profile of the user 1 is similar to that of the current user), and sleep quality of the user 1 is relatively good, the terminal determines the user 1 as the target user, and recommends the light parameter threshold of the target user in each daytime period and the light parameter threshold of the target user in each nighttime period to the current user, to determine the light parameter threshold of the current user in each first sub-period and the light parameter threshold of the current user in each sub-period. Certainly, the target user may alternatively be a user with a relatively high profile similarity to the current user, a similar geographical location, and relatively good sleep quality. This is not limited in this embodiment of this application. In some embodiments, the terminal may use a corresponding light parameter threshold obtained when the sleep quality of the current user is relatively good as a current light parameter threshold. For example, the terminal obtains the sleep data of the user, and determines that the user has best sleep quality on January 20 and that the user has a good health status on a date adjacent to January 20. In this case, the terminal respectively determines a light parameter threshold in each daytime period and a light parameter threshold in each nighttime period on January 20 as the light parameter threshold in each first sub-period and the light parameter threshold in each second sub-period on the current day. According to the method for setting a light parameter threshold in this embodiment of this application, different light parameter thresholds mat be set based on different requirements of the user in different scenarios, and setting of the light parameter threshold is more suitable for an individual feature of the user and is more intelligent. S403. The terminal determines whether the current sub-period is a nighttime period or a sleep time period, and performs S407if the current sub-period is neither a nighttime period nor a sleep time period, or performs S404bif the current sub-period is a nighttime period, or performs S404aif the current sub-period is a sleep latency. In the following embodiment, the light adjustment method in this embodiment described by using an example in which the terminal is a mobile phone. S404a. The terminal adjusts a percentage of a target type of light in light emitted by a light source device to 0. The target type of light is light related to regulation of a circadian rhythm. For example, the target type of light may be the foregoing ipRGC sensitive band light. It may be understood that the ipRGC sensitive band light is closely related to melatonin secretion. If the current sub-period is a sleep latency, a percentage of the ipRGC sensitive band light is adjusted to 0, to reduce stimulation of the ipRGC sensitive band light on an eye of the user. In some embodiments, in the sleep latency, the terminal may pop up a prompt box to prompt the user that “the current time period is a sleep latency (it is late), and please have a rest as soon as possible”. After the user determines to accept the prompt, the terminal adjusts the percentage of the ipRGC sensitive band light to 0. In addition, in the sleep latency, the terminal obtains the behavior data of the user. If the behavior data represents that the user is in a working state in the current sleep latency, the terminal may not adjust a light parameter of light emitted by the light source device. If the behavior data represents that the user is in a leisure state in the current sleep latency, the terminal may decrease the light parameter of the light emitted by the light source device, for example, decrease the percentage of the ipRGC sensitive band light in the light emitted by the light source device. Herein, the light source device may be the light module302inFIG.3. S404b. The terminal determines a total amount of light received in all daytime periods. The time period division manner inFIG.6is used as an example. In this case, the total amount of light in the daytime periods is a total amount of light in a time period from 6:00 to 19:00. S405. The terminal determines whether the amount of light received in the daytime periods exceeds a threshold range of the total amount of light in the daytime periods, and perform S407if the amount of light received in the daytime periods does not exceed the threshold range of the total amount of light in the daytime periods, or performs S406aif the amount of light received in the daytime periods is greater than an upper threshold of the total amount of light in the daytime periods, or performs S406bif the amount of light received in the daytime periods is less than a lower threshold of the total amount of light in the daytime periods, or performs S406cif the amount of light received in the daytime periods is less than or equal to an upper threshold of the total amount of light in the daytime periods, and is greater than or equal to a lower threshold of the total amount of light in the daytime periods. S406a. The terminal adjusts a light parameter of the light source device in each nighttime period to a third light parameter. A third light parameter in a single nighttime period is less than a preset light parameter in the nighttime period. It may be understood that the terminal determines, in a nighttime period that comes first in all nighttime periods (for example, the nighttime period 1 included in the awake time period inFIG.6), the total amount of light received in the daytime periods. When the total amount of light received in the daytime periods is greater than the upper threshold of the total amount of light in the daytime periods, the user receives a relatively large amount of light in the daytime periods, and a little amount of melatonin is secreted. In this case, the user has relatively high working efficiency in the daytime, and the user is relatively tired. To prevent the user from being overly tired, a light parameter threshold in each nighttime period may be decreased, so that the user receives a relatively small amount of light in each nighttime period, to lessen fatigue of the user, and make a preparation for the user to sleep. For example, a preset light parameter 1 is initially set for the nighttime period 1, and a preset light parameter 2 is initially set for the nighttime period 2. When it is detected that the total amount of light received by the user in the daytime periods is greater than the threshold of the total amount of light in the daytime periods, a light parameter in the nighttime period 1 is adjusted from the preset light parameter 1 to a third light parameter 1, and a light parameter in the nighttime period 2 is adjusted from the preset light parameter 2 to a third light parameter 2. The third light parameter 1 is less than the preset light parameter 1, and the third light parameter 2 is less than the preset light parameter 2. The preset parameter 1 may be the same as or different from the preset parameter 2. Similarly, the third light parameter 1 may be the same as or different from the third light parameter 2. In some embodiments, light parameters only in some nighttime sub-periods may be adjusted. For example, the preset light parameter 1 is adjusted to the third light parameter 1, or only the preset light parameter 2 is adjusted to the third light parameter 2. This is not limited in this embodiment of this application. S406b. The terminal adjusts a light parameter of the light source device in each nighttime period to a fourth light parameter. A fourth light parameter in a single nighttime period is greater than a preset light parameter in the single nighttime period. When the total amount of light received in the daytime periods is less than the lower threshold of the total amount of light in the daytime periods, the user receives a relatively small amount of light in the daytime, and a relatively large amount of melatonin is secreted. This may result in lower working efficiency of the user in the daytime. Therefore, it is considered to do part of work at night. In this case, a light parameter threshold in each nighttime period may be increased, so that the user receives a relatively large amount of light in the nighttime period, to improve working energy. It may be understood that when the total amount of light received in the daytime periods is less than the lower threshold of the total amount of light in the daytime periods, the light parameter threshold in each nighttime period may not be adjusted, that is, light with relatively weak light intensity or light in which a percentage of the ipRGC sensitive band light is relatively low in the nighttime period is still maintained, so that the user can quickly sleep. S406c. The terminal maintains a preset light parameter in a nighttime sub-period. If the terminal determines that a total amount of light received in all daytime sub-periods is greater than or equal to a lower threshold of the total amount of light in the daytime sub-periods, and is less than or equal to an upper threshold of the total amount of light in the daytime sub-periods, it indicates that the total amount of light received by the user in the daytime sub-periods meets a user requirement, and the amount of light received by the user does not need to be adjusted by using the light source device. In this case, the terminal maintains the preset light parameter in the nighttime sub-period. S407. The terminal obtains a light parameter in the current sub-period. The light parameter includes but is not limited to light intensity, spectral distribution, and an amount of light. In this embodiment, if the current sub-period is a nighttime period, the terminal may perform the foregoing procedure of adjusting the light parameter threshold in each nighttime period, and determine the light parameter in the current sub-period (nighttime period) after adjusting the light parameter threshold in the nighttime period. If the current sub-period is neither a nighttime period nor a sleep latency, the terminal obtains the light parameter in the current sub-period. In this embodiment of this application, there may be the following two scenarios in which the terminal obtains the light parameter: Scenario 1: When the user holds the mobile phone, light received by the mobile phone may be used as light received by the user. For example, the light parameter is the light intensity and the spectral distribution. In this case, S407may be implemented as follows: A light sensing module307in the terminal may directly detect and obtain light intensity of the light received by the terminal and a percentage of the ipRGC sensitive band light. For example, the light parameter is the amount of light. In this case, S407may be implemented as follows: A light sensing module307in the terminal may directly detect and obtain light intensity of the light received by the terminal and a percentage of the ipRGC sensitive band light, and transfer the obtained light intensity to the processor301shown inFIG.3. The processor301calculates an amount of light in the current sub-period based on the light intensity in the current sub-period. For example, the amount of light is a product of the light intensity and duration of the current sub-period. Herein, it is assumed that the light intensity in the current sub-period is a constant value. In practice, the light intensity may be different at each moment in the current sub-period. In this case, the processor301may calculate the amount of light in the current sub-period based on a specific algorithm. This is not limited in this application. In some embodiments, to more precisely calculate an amount of light received by the user, the terminal may map an amount of light received by the terminal to the amount of light received by the user. In some embodiments, an effective amount of light received by the user when the terminal receives a specific amount of light is determined by using big data analysis or an artificial intelligence algorithm. For specific processing of the big data analysis or the artificial intelligence algorithm, refer to the prior art. Details are not described herein. Scenario 2: When the mobile phone is placed in a bag by the user, a light sensing module307is at a light shielding position, and a light parameter detected by the light sensing module307cannot reflect a light parameter of light received by the user. Alternatively, it is set that a light sensing function of the mobile phone is disabled, and the mobile phone cannot detect a light parameter of received light. In these scenarios, there may be the following two manners of obtaining the light parameter of the light received by the user in the current sub-period: Manner 1: The terminal obtains the light parameter from another terminal. For example, the terminal sends a light parameter obtaining instruction to the another terminal (for example, a wearable device worn by the user), to obtain the light parameter detected by the another terminal. The wearable device is usually worn by the user and is usually not at a light shielding position, and therefore the light parameter detected by the wearable device may be used to reflect the light parameter of the light received by the user. In this way, the mobile phone can still obtain, when the mobile phone is at the light shielding position, the light parameter of the light received by the user. It should be noted that the light parameter of the light received by the terminal changes with an affecting factor. Different light parameters may be obtained in a case of different affecting factors, and similar light parameters are usually obtained in a case of similar affecting factors. The affecting factors include but are not limited to a season, weather, and a geographical location (altitude). For example, in a same region, there are usually different light parameters in spring and summer. For another example, in a same region, in sunny spring days with a temperature of 21° C. and a force 3 wind, daily light parameters from 9:00 a.m. to 12:00 a.m. are usually similar. Based on this, when the mobile phone is in a light shielding scenario, the following manner of obtaining the light parameter of the light received by the user is provided: Manner 2: A light parameter under a condition of a similar affecting factor is used as the light parameter in the current sub-period. Specifically, the mobile phone sends a light parameter under a preset condition to the server based on a preset period. The preset condition includes a weather condition and geographical location information. Herein, the weather condition includes windy, sunny, rainy, snowy, a temperature, air humidity, air quality (including a pollution index), wind force, a wind direction, and the like. Then, the server analyzes and processes the light parameter sent by the mobile phone. Subsequently, when the user does not wear the wearable device or the like and the mobile phone is at the light shielding position, or when the user wears the wearable device and both the wearable device and the mobile phone are at the light shielding position, the mobile phone may obtain, from the server, a light parameter obtained at a current geographical location and in a current weather condition. For example, the preset period is set to an hour, and the mobile phone sends a light parameter in a current one-hour time period to the server every hour. At a start moment of an hour, a light parameter 1 sent by the mobile phone to the server is as follows: {light intensity 1000 lux; weather: sunny; temperature: 18° C.; air humidity: 21%; air quality (including a pollution index): 61, good; wind force: southwest wind; wind direction: force 3 to 4; geographical location: Xicheng District, Beijing}. At a start moment of a next hour, a light parameter 2 sent by the mobile phone to the server is as follows: {light intensity: 500 lux; weather: cloudy; temperature: 17° C.; air humidity: 19%; air quality: 64, good; wind force: southwest wind; wind direction: force 3 to 4; geographical location: Xicheng District, Beijing}. By analogy, the mobile phone or the wearable device sends the light parameter in each daytime period and the light parameter in each nighttime period to the server. Subsequently, when it is inconvenient for the user to collect a current light parameter by using the mobile phone, the wearable device, or the like, the mobile phone or the wearable device obtains a current geographical location of the user and a weather condition, and obtains a light parameter under a similar weather condition and/or a similar geographical location condition from the server. For example, the current geographical location of the user and the weather condition that are obtained by the mobile phone, the wearable device, or the like are as follows: {weather: sunny; temperature: 19° C.; air humidity: 21%; air quality: 61, good; wind force: southwest wind; wind direction: force 3 to 4; geographical location: Xicheng District, Beijing}. The current geographical location of the user and the weather condition are sent to the server. The server queries a stored light parameter, and determines that the geographical location and the weather condition corresponding to the light parameter 1 are most similar to the current geographical location of the user and the weather condition. In this case, the server uses the light parameter 1 as the light parameter in the current sub-period. Certainly, in addition to the foregoing factors such as the season, the weather, and the geographical location that affect the light parameter, there may be another factor that affects the light parameter. This is not limited in this embodiment of this application. S408. The terminal adjusts, based on the light parameter in the current sub-period, a light parameter of light emitted by the light source device in a next sub-period of the current sub-period. In some embodiments, the terminal compares the light parameter in the current sub-period with a light parameter threshold in the current sub-period, to determine how to adjust the light parameter of the light emitted by the light source device. In a first case, if the terminal determines, through comparison, that the light parameter of the light received by the user in the current sub-period is less than a lower light parameter threshold in the current sub-period, it indicates that the user receives a relatively small amount of light in the current sub-period, and a requirement of the user for a large amount of light cannot be met (for example, melatonin secretion cannot be suppressed). In this case, the processor301in the terminal adjusts the light parameter of the light emitted by the light source device in the next sub-period of the current sub-period to a first light parameter. The first light parameter is greater than the light parameter in the current sub-period. In some embodiments, in visible light, the ipRGC sensitive band light is main response light of an ipRGC. Therefore, the processor301increases the percentage of the ipRGC sensitive band light in the total light. Alternatively, the processor301increases overall light intensity. Alternatively, after the percentage of the ipRGC sensitive band light in the total light is adjusted, a color of the total light may change. To prevent the user from perceiving a change of the light, the processor301further adjusts intensity of light other than the ipRGC sensitive band light, that is, adjusts spectral distribution (a percentage of each type of light in a spectrum), so that the color of the total light irradiated into the eye of the user does not change greatly. It should be noted that blue light may damage an eye ground and a retina. Therefore, when adjusting the light module302, the processor301may decrease a percentage of the blue light or shield the blue light. In a second case, if the processor301determines, through comparison, that the light parameter of the light received by the user in the current sub-period is greater than an upper light parameter threshold in the current sub-period, it indicates that there is a relatively large amount of light in the current sub-period, and fatigue is easily caused. In this case, the processor301adjusts the light parameter of the light emitted by the light source device in the next sub-period of the current sub-period to a second light parameter. The second light parameter is less than the light parameter in the current sub-period. In a third case, if the processor301determines, through comparison, that the light parameter in the current sub-period is less than or equal to an upper light parameter threshold in the current sub-period, and is greater than or equal to a lower light parameter threshold in the current sub-period, it indicates that light in the current sub-period meets a user requirement. In this case, the processor301does not instruct to adjust the light module302. In this way, in irradiation of natural light, a melatonin secretion status of the user still meets a rhythm requirement of the user. In comparison with the prior art in which light and an amount of light provided by a light therapy device cannot better meet a user requirement, and cannot more intelligently improve sleep quality of a user, in the light adjustment method provided in this embodiment of this application, the terminal determines the awake time period and the sleep time period of the user; determines the light parameter threshold in each first sub-period and the light parameter threshold in each second sub-period. obtains the light parameter of the light received by the user in the current sub-period; and adjusts the light parameter of the light emitted by the light source device in the next sub-period of the current sub-period based on the light parameter of the light actually received by the user in the current sub-period and the light parameter threshold in the current sub-period. In this way, light received by the user in each sub-period better meets a user requirement, and therefore sleep quality of the user can be more intelligently improved. In this embodiment, the light parameter adjustment procedure may alternatively be performed only in one time period. For example, if the user makes a setting to perform the light adjustment procedure from 9:00 to 11:00, the terminal detects, only in the time period, the light parameter of the light received by the user, and adjusts, based on the light parameter, the light parameter of the light received by the user. In addition, in this embodiment, a terminal that provides a better light parameter adjustment effect may be intelligently selected through interaction between a plurality of terminals, to perform the light parameter adjustment procedure. Specifically, the terminal sends a light adjustment instruction to a target terminal, to instruct the target terminal to perform the light parameter adjustment procedure. For example, for a worker who usually sits in an office and faces a large-screen terminal (for example, a computer), the large-screen terminal may perform the procedure of adjusting the light parameter of the light emitted by the screen. A light parameter adjustment effect is more significant because of a relatively large screen area of the large-screen terminal. In some embodiments, the mobile phone detects whether a face of the user is in front of a screen. If the face of the user is in front of the screen, the mobile phone continues to perform the light parameter adjustment procedure. If the face of the user is not in front of the screen, the mobile phone instructs the large-screen terminal (the face of the user is currently in front of the large-screen terminal) to perform the light parameter adjustment procedure. Certainly, in a scenario in which the mobile phone detects that the face of the user is in front of the screen, to improve a light parameter adjustment effect, the mobile phone may instruct the large-screen terminal to adjust a light parameter related to melatonin secretion for the user. It may be understood that to implement the foregoing functions, the terminal includes a corresponding hardware structure and/or software module for performing each of the functions. With reference to the units and algorithm steps described in the embodiments disclosed in this application, embodiments of this application can be implemented in a form of hardware or hardware and computer software. Whether a function is performed by hardware or hardware driven by computer software depends on particular applications and design constraints of the technical solutions. A person skilled in the art may use different methods to implement the described functions for each particular application, but it should not be considered that the implementation falls beyond the scope of the technical solutions in the embodiments of this application. In the embodiments in accordance with the disclosure, function unit division may be performed on the terminal based on the foregoing method examples. For example, each function unit may be obtained through division based on a corresponding function, or two or more functions may be integrated into one processing unit. The integrated unit may be implemented in a form of hardware, or may be implemented in a form of a software functional unit. It should be noted that, in this embodiment of this application, unit division is exemplary, and is merely a logical function division. In actual implementation, another division manner may be used. FIG.11is a schematic block diagram of a terminal according to an embodiment of this application. The terminal1100may be in a form of software, or may be a chip that can be used for a terminal. The terminal1100includes a processing unit1102and a communications unit1103. For example, the processing unit1102may be configured to support the terminal1100in performing S401and S402inFIG.4AandFIG.4B, and/or another process in the solution described in this specification. The communications unit1103is configured to support the terminal1100in communicating with another network element (for example, the server21inFIG.2or another terminal). In some embodiments, the terminal1100may further include a storage unit1101, configured to store program code and data of the terminal1100. The data may include but is not limited to raw data or intermediate data. The processing unit1102may be a processor or a controller, such as may be a central processing unit (CPU), a general-purpose processor, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field programmable gate array (FPGA), or another programmable logical device, a transistor logical device, a hardware component, or any combination thereof. The processor may implement or execute various example logical blocks, modules, and circuits described with reference to content disclosed in this application. The processor may be a combination of processors implementing a computing function, for example, a combination of one or more microprocessors, or a combination of the DSP and a microprocessor. The communications unit1103may be a transceiver, a transceiver circuit, the communications interface308shown inFIG.3, or the like. The storage unit1101may be the memory303shown inFIG.3. A person of ordinary skill in the art may understand that all or some of the foregoing embodiments may be implemented by using software, hardware, firmware, or any combination thereof. When software is used to implement the embodiments, the embodiments may be implemented completely or partially in a form of a computer program product. The computer program product includes one or more computer instructions. When the computer program instructions are loaded and executed on the computer, the procedure or functions according to the embodiments of this application are all or partially generated. The computer may be a general-purpose computer, a dedicated computer, a computer network, or other programmable apparatuses. The computer instructions may be stored in a computer-readable storage medium or may be transmitted from a computer-readable storage medium to another computer-readable storage medium. For example, the computer instructions may be transmitted from a website, computer, server, or data center to another website, computer, server, or data center in a wired (for example, a coaxial cable, an optical fiber, or a digital subscriber line (DSL)) or wireless (for example, infrared, radio, or microwave) manner. The computer-readable storage medium may be any usable medium accessible by a computer, or a data storage device, such as a server or a data center, integrating one or more usable media. The usable medium may be a magnetic medium (for example, a floppy disk, a hard disk, or a magnetic tape), an optical medium (for example, a digital video disc (Digital Video Disc, DVD)), a semiconductor medium (for example, a solid-state drive (Solid State Disk, SSD)), or the like. In the several embodiments herein it should be understood that the disclosed system, apparatus, and method may be implemented in other manners. For example, the described apparatus embodiment is merely an example. For example, the unit division is merely logical function division and may be other division in actual implementation. For example, a plurality of units or components may be combined or integrated into another system, or some features may be ignored or not performed. In addition, the displayed or discussed mutual couplings or direct couplings or communication connections may be implemented through some interfaces. The indirect couplings or communication connections between the apparatuses or units may be implemented in electronic or other forms. The units described as separate parts may or may not be physically separate, and parts displayed as units may or may not be physical units, may be located in one position, or may be distributed on a plurality of network device (for example, a terminal). Some or all of the units may be selected based on actual requirements to achieve the objectives of the solutions of the embodiments. In addition, functional units in the embodiments of this application may be integrated into one processing unit, or each of the functional units may exist independently, or two or more units are integrated into one unit. The integrated unit may be implemented in a form of hardware, or may be implemented in a form of hardware in addition to a software functional unit. Based on the foregoing descriptions of the implementation manners, a person skilled in the art may clearly understand that this application may be implemented by software in addition to necessary universal hardware or by hardware only. In most circumstances, the former is a preferred implementation manner. Based on such an understanding, the technical solutions of this application essentially or the part contributing to the prior art may be implemented in a form of a software product. The software product is stored in a readable storage medium, such as a floppy disk, a hard disk or an optical disc of a computer, and includes several instructions for instructing a computer device (which may be a personal computer, a server, or a network device) to perform the methods described in the embodiments of this application. The foregoing descriptions are merely specific implementations of this application, but are not intended to limit the protection scope of this application. Any variation or replacement within the technical scope disclosed in this application shall fall within the protection scope of this application. Therefore, the protection scope of this application shall be subject to the protection scope of the claims. | 68,362 |
11857732 | DETAILED DESCRIPTION Embodiments of the invention include methods, systems and luminaires that dynamically generate high efficacy white light that comprises enhanced spectral components that can vary in aspects of spectral and spatial distribution as well as intensity at different times of the day to facilitate circadian regulation or entrainment. Embodiments of the invention include dynamic illumination methods and systems for providing relatively high melanopic flux during the day and relatively low melanopic flux at night. Other embodiments of the invention include lighting systems which provide indirect illumination from the upper portions of the visual field of an observer wherein such illumination is enriched in melanopic light. In some embodiments, the exposure of melanopic light to photoreceptors in the lower hemisphere of the retina may be amplified or attenuated based on time of day in order to facilitate circadian rhythm regulation. Some embodiments include a lighting fixture which provides task lighting and/or indirect illumination from the lower portions of the visual field of an observer that is depleted in melanopic light. Some embodiments include luminaires or lighting fixtures which provide both indirect lighting from the upper portions of visual fields rich in melanopic light and task lighting and indirect lighting from the lower portions of visual fields that are depleted in melanopic light. In some embodiments, a lighting fixture in the form of a table lamp comprises two of more different sources of illumination, differing in their respective output spectrums, and for which the spectral outputs (e.g., amount of melanopic light), the spatial distributions of said illuminations and the relative intensities of the illuminations may be varied. In some embodiments, the spectral, spatial and intensity variations may be coordinated with the local time or user preference to facilitate the coordination of human circadian rhythms or other biological effects. Embodiments of the invention include methods, luminaires and systems for providing biologically relevant light (e.g., melanopic light) from indirect illuminating sources and from sources which direct various spectral types of light in specific spatial directions and illuminate specific areas. When used herein, the term day-time LEDs may be used and is meant to refer to LEDs that produce illumination rich in melanopic light or which have a relatively high melanopic ratio and which generate relatively high equivalent melanopic lux. Similarly, the term night-time LEDs means LEDs that produce illumination that is relatively low or depleted of melanopic light or which have a relatively low melanopic ratio and which generate relatively low equivalent melanopic lux. Embodiments include desk and floor lamps which comprise covers or shades which are edge-lit and comprise different types of LEDs, one set of LEDs producing light which is depleted of melanopic light and another set which produces light rich in melanopic light illuminated. In some embodiments, the biological effective LEDs (those that provide illumination rich in melanopic light) are configured in or in relation to the edge-lit shade such that the illumination provided by those LEDs project upward (i.e., up and outward toward the ceiling and the walls surfaces generally at or above eye level). In some embodiments, the LEDs which are depleted in melanopic light are configured in or in relation to the edge-lit shade such that the illumination from the melanopic-depleted LEDs is projected downward (i.e., toward the floor/desk and outward generally below eye level). In some embodiments, the desk/floor lamp comprises a selective dimmer which allows one or both of the different types of LEDs to be dimmed such that the intensity of the respective illuminations may be adjusted (e.g., the intensity of illumination produced by the daytime and/or nighttime LED may be adjusted). In some embodiments, such dimming may be automatic and may be programmed and/or coordinated with the time of day or user preference. Embodiments also include various configurations of light distribution units for reflecting and/or transmitting and generally directing light spatially. In one embodiment, a desk lamp that comprises a “shade” comprised of light-transmissive guide material is configured such that daytime LEDs illuminate the shade from below, resulting in an edge-lit shade that projects the daytime illumination upwards and outwards, and nighttime LEDs illuminate the shade from above resulting in nighttime illumination projecting downwards and outwards. The daytime light (rich in melanopic light) is projected onto the ceiling and upper portions of surrounding walls or partitions, and is reflected therefrom. This reflected indirect light from above may disproportionately impinge on the lower hemisphere of the retina of a conventionally oriented observer in the lighted space. This type of daytime light spatial distribution may be appropriate for optimal melanopic photoreceptor stimulation because the lower hemisphere of the retina is most sensitive to melanopic light relative to the upper hemisphere. Additionally, illumination from the night time LEDs is projected downward onto the task areas, e.g., a desk. During periods of the day when it would be inappropriate to receive melanopic light (for instance late in the day prior to bedtime), the nighttime LEDs will provide good illumination for task work, but will not be rich in melanopic light and therefore will have no or little impact or disruption the circadian rhythm of the individual(s) exposed to the illumination. Transparent and translucent materials may be used for portions of the light distribution unit (e.g., shade, diffuser, etc.) An example of such material is acrylic. Edge-lit technology is well known and readily available in the lighting industry. Materials for use in embodiments of the invention may be obtained from a number of sources including the firm ACRYLITE. Light guides and other types of edge-lit technologies and materials may be employed in embodiments of the invention. For instance, clear shade acrylic may be used and shaped such that light from one set of LEDs illuminating the acrylic from the bottom edge will be transmitted upwards through the acrylic and outwards from the acrylic to provide the edge-lit effect. Similarly, light from another set of LEDs illuminating the acrylic from the top edge will be transmitted downwards through the acrylic and outwards from the acrylic to provide the edge-lit effect. Holographic diffuser can also be used to provide desired or optimal light distribution. Embodiments of the invention are not limited to any specific material, and a variety of materials and combinations thereof, including transparent, translucent, reflective, opaque, etc., may be used to achieve spectral, spatial, and intensity variations of illuminations are contemplated by embodiments of the invention. In some embodiments, a desk or table lamp may comprise a programmable interface and clock to coordinate the illumination output (spectral, spatial, and/or relative intensity) with the time of day and users schedule, and/or such that the user can input specific idiosyncratic parameters or desires in order to adjust and optimize the illumination of the luminaire, e.g., throughout the day, to match a users schedule, and to facilitate regulation of the individuals circadian rhythm, sleep cycles and period of acute alertness. Examples of such inputs include but are not limited to users desired sleep/wake schedules, desired light color and intensity depending on activity, subjective feelings of sleep quality, desire to shift sleep schedule et cetera. In some embodiments the desk lamp also comprises a sound system capable of producing and projecting music or other sounds such as white or pink noise, bedtime beats, relaxation sounds, etc. In some embodiments, the light from the lamp may be modulated in coordination with the music to produce a show. In some embodiments the sound may be dynamically coordinated with the light to help the individual sleep or wake or concentrate. In some embodiments, the luminaire can dynamically adjust the spectrum (and/or sounds) throughout the day, for instance in the form of a dawn to dusk light show. Additional lighting features according to some embodiments include: a party mode (color, animation, music synchronization etc); jet-lag fighter (e.g., pre-travel shift and post-travel shift); circadian optimizer; calming feature (e.g., beat synch, synch with heart beat or respiration); directional nightlight (e.g., singular facade); Nighttime light sensor (e.g. send text when lamp senses presence of bright or blue light). FIGS.1a-cillustrate embodiments of the invention.FIG.1ashows a desk or table lamp100that comprises a base105, a lamp shade holder110, a light distribution unit in the form of an edge-lit lampshade120(other forms of shades, reflectors, diffusers, etc. may also be used as will be evident to those skilled in the art), daytime LEDs130, nighttime LEDs150, and a control interface165. The daytime LEDs130are attached to the underside or lower portion of the lampshade120or otherwise integrated therein and are oriented such that light emitted from them is generally upward, for example the opaque non-emitting portion of the LED die or package is oriented facing toward the base105. The nighttime LEDs150are attached to the upper side or upper portion of the lampshade120or otherwise integrated therein and are oriented such that light emitted from them is generally downward, for example the opaque non-emitting portion of the LED die or package is facing away the base105. The control interface165may comprise one or more toggle switches for turning the daytime and nighttime LEDs on and off. The control interface165may also comprise a dimming control for adjusting the intensity of the daytime LEDs, the nighttime LEDs or both. An optional clock180is also shown. Desk or table lamp100also includes a power source (not shown). In alternative embodiments, the light distribution unit or lamp shade120is not edge lit and may be designed with various degrees of relative transparency to allow various patterns of illumination (e.g., a uniform cone-like distribution or alternatively a greater degree of the illumination directed in the vertical direction with a less transparent shade). In some embodiments the daytime LEDs provide illumination with a melanopic ratio of greater than 0.8. In other embodiments the melanopic ratio is greater than 1.0. In still other embodiments, the MR is greater than 1.2. In some embodiments the nighttime LEDs provide illumination with a melanopic ratio of less than 0.8. In other embodiments the melanopic ratio is less than 0.6. In still other embodiments, the MR is less than 0.4. The configuration of the daytime LEDs130and Lamp Shade120and the control interface165provide for the projection and control (e.g., dimming) of melanopic rich light illumination upward such that, for example, more melanopic rich light would be more likely to fall on the lower hemisphere of a person's retina who is in proximity to the lamp and surrounding surfaces. The configuration of the nighttime LEDs150and Lamp Shade120and the control interface165provide for the projection and control (e.g., dimming) of light that is depleted in melanopic light downward such that, for example, when an individual is working on a task, e.g., on a desk or table surface, the individuals retina is not exposed to significant amounts of melanopic rich light, light which may not be appropriate at a particular time of day for a particular individual. These configurations allow for an individual to receive the needed melanopic light during the day while being able to avoid melanopic light during periods where it may interfere or disrupt the person's circadian rhythms or sleep patterns. The intensity of the daytime and nighttime LEDs may be varied using the control interface165. FIG.1billustrates another embodiment of the invention. Desk or table lamp100comprises a base105a lamp shade holder110, a light distribution unit in the form a lamp shade120, daytime LEDs130, nighttime LEDs150, and programmable interface (PI)170. The programmable interface170comprises means for both manual and automatic control of the lighting device features including lighting intensity, color and spatial distribution as well as other features described further below. Also shown schematically (although not to scale and not meant to represent the actual illumination pattern but shown for illustrative purposes) are representations of the Upward Projection140of the illumination from the Daytime LEDs130and the Downward Projection160of the illumination from the Nighttime LEDs150. Table lamp100also comprises a sound system (not fully shown integrated in said base) including a woofer or other speaker means175, a clock180, a means for wireless communications (not shown) and may additionally include various optional sensors (not shown) including an ambient light sensor. The programmable user interface170is used for accessing and/or programming these elements. As can be seen from the Figures, the base may be so designed as to optimize acoustics. For instance an offset of the base from the table surface provides a resonant air gap offset185and a cover190may be shaped and configured for sound consolidation and other acoustical performance. In some embodiments the sound system and illumination output may be coordinated to produce a number of desired features as mentioned elsewhere herein. The lighting fixture100comprises a power source not shown. Delivering and regulating electrical power to the components of the desk lamp are well known to those skilled in the art. Examples of power sources are switched mode power supplies and other power supplies that can supply and adjust current and voltage supplied to the LEDs and/or LED light engines, the processing hardware (e.g., circuit board, memory and CPU) and sound system including woofers etc. In some embodiments the power source is wall AC supplied by a conventional pronged plug (not shown). FIG.1cshows a perspective view of a spectrally and spatially tunable lighting device according to some embodiments. According to some embodiments, the lighting fixture100also may also comprise additional activation and/or control interfaces, e.g., manuals switches, dimmers, and means to adjust the orientation of the light distribution unit or shade to spatially direct the light. In some embodiments, the shades transparency may be adjusted (via structural means or electro-optic means) to alter the spatial, spectral and/or intensity distribution of the illumination from the lighting fixture100. The interfaces may be analog, digital or both. In some embodiments, the desk lamp is configured to operate with wireless communications and be capable of receiving programming instructions or actual commands (e.g., on/off, dimming, etc), and transmit data, (e.g., status, user input, etc). The user interface may comprise a digital display for entering inputs. Alternatively a networked interface may allow the user to control and/or program the operation of the desk lamp remotely (e.g., via computer or smart phone). In some embodiments, the desk lamp comprises a programmable microcontroller that allows for fine control over the spectral and spatial illumination output including intensity control. Additional embodiments include programmed light shows throughout the day, coordination with sounds or music from the sound system, and recording and tracking a users habits or preferences and real-time dynamic illumination adjustment capability to facilitate regulation of circadian rhythms, aesthetics and other effects. In some embodiments, the lamp shade is clear or transparent. In some embodiments the portion of the desk lamp interior of the lampshade is empty. FIGS.2a-cillustrate a light distribution device120according to some embodiments of the invention.FIG.2ashows a perspective view andFIGS.2band2cshow top and side views respectively of the light distribution device120. Light distribution device120comprises generally a hollow cylinder that comprises transparent or translucent material. In some embodiments, the material is capable of being edge lit. In these embodiments, daytime LEDS130are affixed to a lower portion of the device120and oriented such that their light emitting surfaces are facing upwards, and the nighttime LEDS150are affixed to an upper portion of the device120and oriented such that their light emitting surfaces are facing downwards. Although the light distribution device is shown as a cylindrical shape with a hollow central structure, embodiments of the invention are not limited to particular shapes, fills, or materials, and many different shapes materials and orientations of light distribution devices120are contemplated by the invention. Additionally, although the daytime LEDs130and nighttime LEDs150are shown as placed around the lower and upper peripheries respectively of the light distribution device120and are generally oriented in a vertical facing direction (i.e., up or down), the invention is not limited to any specific placement of LEDs on the light distribution device120or specific orientations thereof. As will be evident to those skilled in the art, a variety of configurations, placements and orientations of the light distribution device120and the LEDs130and150may be utilized to achieve the desired spectral and spatial illuminations and adjustments thereof, for example, daytime light directed generally upward and/or resulting in indirect illumination from above and nighttime light directed generally downward providing both task lighting and indirect lighting from below. FIGS.3aand3bshow schematically and generally light distribution patterns of a table lamp100on table or platform190comprising both daytime LEDs130and nighttime LEDs150according to some embodiments.FIG.3ashows the light distribution pattern of the lighting fixture100due to the daytime LEDs130when they are powered to illumination. Emitted light210is generally upwardly directed and results in reflected indirect light220that is generally downwardly directed. Daytime LEDs will generate illumination of higher melanopic ratio than nighttime LEDs. FIG.3bshows the light distribution pattern of the lighting fixture100due to the nighttime LEDs150when they are powered to illumination. Emitted light230is generally downwardly directed and results in both task lighting on the table190and reflected indirect light240that is generally upwardly directed. Control interface170provide means to inter alia turn the daytime LEDs130and nighttime LEDs150on or off and adjust their respective intensities. The light distribution patterns shown in the figures are for illustration purposes only and, as will be evident to those skilled in the art, do not represent actual illumination patterns. The patterns shown are meant to illustrate how light from the daytime LEDs130, which is upwardly directed, reflects off of the ceiling and the upper portions of walls resulting in indirect lighting directed downward to an observer in the room, and thereby disproportionately impinges on the lower hemisphere of the observer's retina as compared to upper hemisphere of the retina. Similarly, the illumination from the nighttime LEDs150results in direct task lighting on the desk or table top and otherwise reflects from the floor or lower portions of the walls resulting in indirect light directed generally upward to an observer in the room, and thereby may disproportionately impinge on the upper hemisphere of the observer's retina as compared to lower hemisphere of the retina. In some embodiments, the lighting fixture, e.g., in the form of a table or desk lamp, may be optimized for bedroom or sleep use generally and may include a dynamic light controller that may be programmable and that comprises sensors and/or a receiver for data input and actuators to output sound, illumination or other output signals and/or data. The lighting fixture may include means for wireless communication including WiFi, Bluetooth or other communication protocols. This communication capability allows for a user to access, read and program the lighting device remotely and allows for the lighting device to read or sense ambient data and communication information externally and control local or remote devices. In some embodiments, the lighting device may include any or all of the following: thermometer for measuring ambient temperature, humidity sensor, an ambient light sensor, a bed occupancy sensor, a proximity sensor, geo-location sensor, a speaker for outputting music, speech or other sounds, and a microphone for recording or to receive spoken commands. In some embodiments the proximity and/or bed occupancy sensor may be used to determine which lighting levels to provide via the lighting device to optimize the experience of the user or occupant. In some embodiments, the lighting device comprises a user display that may include inter alia a clock, sensor status, wireless communication status, battery level, etc. The bedroom lighting fixture according to some embodiments has the capability to provide both spectrally tunable light as well as spatially variable light and may be programmed to facilitate both falling asleep and waking up. For example, as an occupant approaches sleep time, light with low melanopic impact may be used instead of light with a higher melanopic effect and may be spatially directed, at for example the floor, to minimize any alerting effect or sub-optimal impact on the occupant's circadian rhythm. Conversely, during a wake up period or when the occupant wishes to remain awake or alert, melanopic light may be generated by the lighting device to suppress or mitigate sleep pressure and/or shift of otherwise effect the circadian rhythm of the occupant. In some embodiments, music or other sounds generated by the lighting device sound system accompanies and is coordinated with the illumination provided thereof to facilitate sleeping or waking. The lighting device may be powered by an AC-DC power supply and may use various voltage and current regulation schemes to optimize efficiency and performance. The lighting device may also include a battery for backup power. While the invention has been described with reference to exemplary embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. It should be understood that the diagrams herein illustrates some of the system components and connections between them and does not reflect specific structural relationships between components, and is not intended to illustrate every element of the overall system, but to provide illustration of the embodiment of the invention to those skilled in the art. Moreover, the illustration of a specific number of elements, such as LED drivers power supplies or LED fixtures is in no way limiting and the inventive concepts shown may be applied to a single LED driver or as many as desired as will be evident to one skilled in the art. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best or only mode contemplated for carrying out this invention, but that the invention will include many variants and embodiments. Also, in the drawings and the description, there have been disclosed exemplary embodiments of the invention and, although specific terms may have been employed, they are unless otherwise stated used in a generic and descriptive sense only and not for purposes of limitation, the scope of the invention therefore not being so limited. Moreover, the use of the terms first, second, etc. do not denote any order or importance, but rather the terms first, second, etc. are used to distinguish one element from another. Furthermore, the use of the terms a, an, etc. do not denote a limitation of quantity, but rather denote the presence of at least one of the referenced item. | 24,465 |
11857733 | DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring now toFIGS.1A-1F, the present invention is advantageously embodied in a smartphone1, such as the iPhone shown therein. The smartphone is particularly advantageous, because the operating system permits an application designer to control the display screen and select a portion or portions thereof to make it flicker at a selected frequency, to adjust its position, its color temperature, its color, its saturation, its contrast, its brightness, the duty cycle of the flickering, and the waveform used to create the flickering. In addition, IOS 12 for the iPhone has the capability to measure the amount of time the user has the display screen on, and to measure the amount of time that a user is viewing a particular app. In addition, there are many apps available for a smartphone that can be used to measure mental acuity and response time. Examples of such apps are Lumosity, Tricky Test, and Peak—Brain Training. As a result, many of the requirements for the apparatus according to the present invention for carrying out the method according to the present invention are available on a smartphone, although the combinations thereof as set forth in the claims are novel. The present invention is also particularly advantageously embodied in a gaming device such as a Nintendo Switch, a Microsoft Xbox or a Sony PlayStation, since users spend a great deal of time exposed to the display screen, the devices provide a record of time played, and the games played on the devices measure reaction time of a user to different visual and audio stimuli. As shown inFIGS.1A-1F, the display screen2has areas3A-3F that flicker at least during the time that the user is exposed to the display screen, e.g., playing a game, watching a video, reading text, etc. The flickering areas are around the edge3A, on the sides3D and3E, on the top and bottom3C and3B or in the corners3F. The flickering areas are preferably positioned so as not to interfere with the operation of any app or video. FIG.2shows an e-reader10, such as an Amazon Kindle, with a display screen11having a text portion13surrounded by a flickering area12. Alternatively, the entire background of the text on the display screen can flicker, all text and other information on the display screen can flicker, or the entire display screen can flicker. FIG.3shows a network using apparatus in accordance with the invention. Tablets20aand20i-20n,such as the Apple iPad and the Samsung Galaxy are wirelessly in communication with server30. The server30keeps track in a database of the display screen exposure time of each user, the results of the responses of the users, and the measurement of the reactions of the users. Alternatively, a device20ican keep a local database record of the display screen exposure time of each user and process the results in software before sending the results to the server. The results of the responses of the users, and the measurement of the reactions of the users on the device itself can be sent to the server. The data in the database with respect to a user or of a plurality of users can be used as feedback to change parameters of the flickering, such as frequency, color temperature, color, saturation, contrast, brightness, position, percentage of display screen, etc. The server30can analyze the data of many users to determine which parameters most affect a particular user and provide feedback accordingly. The feedback can be based upon the gender of the user, the race of the user, the ethnicity of the user, the age of the user, a medical condition of the user, and/or another biological parameter of the user (e.g., natural hair color, eye color, color blindness, epilepsy). FIG.4is a block diagram of the functional elements of a device40in accordance with the invention for a carrying out the method according to the invention. InFIG.4, a main processor41is a microprocessor which interacts with memory42, which is a ROM, RAM or combination of the ROM and RAM, for program instructions. Memory42is also available to store settings for the flicker parameters and to store a database of user records. The processor41also interacts with the display44, the radio45and the front facing camera43. The display of the device includes a display screen and conventional circuitry for driving the display screen. The front facing camera is preferably of the type used for Face ID on an iPhone or Android phone, because it is capable of determining whether or not the user is looking at the display screen. The radio45is preferably a Wi-Fi radio, a Bluetooth radio, and/or a cellular (LTE or 5G) radio or a combination thereof for communicating with server30. The device40also includes a timer48, a flicker control processor46and an effect processor47. These modules can be hardware or software based in processor41and while they are shown as separate elements, they can be embodied in one or more processors and implemented in software. The timer48measures the time that the display screen is on and/or the time the user is exposed to the display screen, for example based upon the front facing camera43or based upon audio prompts or visual prompts to the user on the display screen to see if the user is actually looking at the display screen. The flicker control processor can adjust the parameters of the flickering which can be set by the user, can be based upon feedback from data stored in the memory or it can be based upon feedback from the server30. The effect processor47measures the effect on a user of visual and/or audio prompts. The measuring can be of reaction time, of results on memory tests, of results on mental acuity tests, of speed tests, etc. FIGS.5and6are flowcharts of methods according to the present invention. In the flowchart ofFIG.5, the first step100is to turn on the display screen. The turning on of the display screen leads to the second step110of starting the timer. While it is desirable to time the actual exposure of the user to the flickering, the time that the display screen undergoes controlled flickering is a good approximation. Preferably, a front facing camera can detect that the eyes of the user are on the display screen. Alternatively, visual or audio prompts can require an action by the user to show that the user is paying attention to the display screen. After a predetermined time of exposure to the display screen, in step120an effect on a user is measured. This measurement can take different forms. For example, the effect that is measured is the reaction time of the user to an audio or visual prompt on the display screen. The measurement can be in the form of the results of a memory test displayed on the display screen of the display. Alternatively, a logic test can be displayed on the display screen. Preferably, one of many mental acuity tests that are available as apps for smartphones and other similar devices can be used as a measure. After the effect is measured, in step130feedback can be provided. For example, if the measured effect shows improvement from a previous measurement, the flicker may remain unchanged. If on the other hand there is no improvement, the flicker can be adjusted in step140. Alternatively, the flicker can be adjusted even if there is an improvement, or the flicker may not be adjusted even if no improvement is measured. After there is or is not an adjustment, the timer is started again in step110and the process is repeated as long as the display screen is on. The times and parameters are preferably maintained in storage for review at a later time. The method ofFIG.6starts with turning on the display screen in step200. In this embodiment the device receives feedback from the server30. This feedback can be based upon data received from other users and in particular from users where there was an improvement in the measured effects over time. This feedback can be used to adjust one or more parameters relating to flickering including color temperature, color, frequency, contrast, saturation, brightness, duty cycle, and pulse shape. The feedback can be based upon the gender of the user, the race of the user, the ethnicity of the user, the age of the user, a medical condition of the user, and/or another biological parameter of the user (e.g., natural hair color, eye color, color blindness, epilepsy), where persons having similar characteristics have shown desired changes in measured effects. Upon receiving this feedback, the flicker and/or the predetermined time of exposure can be adjusted in step220. The timer is then started in step230and after the adjusted predetermined time in step240, an effect is measured. Thereafter, the measured effect is reported to the server30in step250. The flicker can then be readjusted in step260and the process can be repeated. The display screen for use with the present invention is preferably an LCD display screen or discrete LED light emitters. Alternatively, the display screen can be an LED or OLED display screen. A user interface on the display screen of the apparatus is preferably an application program interface (API) such as a local API, web API or program API and, alternatively, can be a network interface controller that connects a computer to a computer network or a virtual network interface connecting a computer to a virtual private network. Network shown inFIG.3is preferably a communications network using one or more commercial communications protocols, such as TCP/IP, FTP, UPnP, NFS, or CIFS. The network can be wireless or wired, including a local area network (LAN), a wide-area network (WAN), a virtual private network (VPN), the internet, an intranet, an extranet, a public switched telephone network (PSTN), a cellular network, a satellite communications network, an infrared network, another type of wireless network, and the like, or a combination of the foregoing. An example of the present invention can include a database formed from a variety of data stores and other memory or storage media. These components can reside in one or more of the servers, as discussed above, or may reside in a network of the servers. Alternatively, the database can be stored locally and maintained on the user's smartphone, tablet, computer, or other storage device. In certain embodiments, the information may reside in a storage-area network (SAN). Similarly, files for performing the functions attributed to the computers, servers or other network devices discussed above may be stored locally and/or remotely, as appropriate. Each computing system described above, including the client devices, may incorporate hardware elements that are electrically coupled via data/control/and power buses. For example, one or more processors in such computing systems may be central processing units (CPU) for one or more of the client devices. The client devices may further include at least one user input device (e.g., a mouse, joystick, keyboard, controller, keypad, or touch-sensitive display screen) and at least one output device (e.g., a display, a printer, a speaker, or a device which itself is designed to provide electrical stimulation to the brain, such as transcranial direct-current stimulation devices and transcranial magnetic stimulation devices. Such client devices may also include one or more storage devices, including disk drives, optical storage devices and solid-state storage devices such as a random-access memory (RAM) or a read-only memory (ROM), as well as removable media devices, memory cards, flash cards, storage devices utilizing biological media (e.g., DNA), etc. The computer systems discussed above also can include computer-readable storage media reader, communications devices (e.g., modems, network cards (wireless or wired), or infrared communication devices) and memory, as previously described. The computer-readable storage media reader is connectable or configured to receive, a computer-readable storage medium representing remote, local, fixed and/or removable storage devices as well as storage media for temporarily and/or more permanently containing, storing, transmitting and retrieving computer-readable information. The system and various devices also typically will include a number of software applications, modules, services or other elements stored within at least one working memory device, including an operating system and application programs such as a client application or web browser. It should be appreciated that alternate embodiments may have numerous variations from that described above. For example, customized hardware also might be used, and/or particular elements might be implemented in hardware, in software (including portable software, such as applets), or in both. Further, connection to other computing devices such as network input/output devices may be employed. Storage media and other non-transitory computer readable media for containing code, or portions of code, can include any appropriate media known or used in the art, such as but not limited to volatile and non-volatile, removable and non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules or other data, including RAM, ROM, EEPROM, flash memory or other memory technology, CD-ROM, digital versatile disk (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage, other magnetic storage devices, or any other medium, including biological media such as DNA, which can be used to store the desired information and which can be accessed by a system device. Based upon the disclosure and teachings provided herein, a person of ordinary skill in the art will appreciate other ways and/or methods to implement the various embodiments. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense. It will, however, be evident that various modifications and changes may be made thereunto without departing from the broader spirit and scope of the invention as set forth in the claims. While various embodiments of the present disclosure have been described above, it should be understood that they have been presented by way of example only, and not of limitation. Likewise, the various diagrams may depict an example architectural or other configuration for the disclosure, which is done to aid in understanding the features and functionality that can be included in the disclosure. The disclosure is not restricted to the illustrated example architectures and configurations, but the desired features can be implemented using a variety of alternative architectures and configurations. Indeed, it will be apparent to one of skill in the art how alternative functional, logical, or physical partitioning and configurations can be implemented to implement the desired features of the present disclosure. For example, while a single server and a processor are illustrated, the server functions can be distributed over a number of servers and processors. Additionally, with regard to flow diagrams, operational descriptions, and method claims, the order in which the steps are presented herein shall not mandate that the steps of the various embodiments be implemented in the order presented, unless the context dictates otherwise. Although the disclosure is described above in terms of various example embodiments and implementations, it should be understood that the various features, aspects, and functionality described in one or more of the individual embodiments are not limited in their applicability to the particular embodiment with which they are described, but instead can be applied, alone or in various combinations, to one or more of the other embodiments of the disclosure, whether or not such embodiments are described, and whether or not such features are presented as being a part of a described embodiment. Thus, the breadth and scope of the present disclosure should not be limited by any of the above-described example embodiments, and it will be understood by those skilled in the art that various changes and modifications to the previous descriptions may be made within the scope of the claims. | 16,269 |
11857734 | DESCRIPTION OF EMBODIMENTS Referring now toFIG.1A, an example catheter system14is illustrated, according to some embodiments. In some embodiments, the catheter system14may include a catheter assembly16. In some embodiments, the catheter assembly16may include a catheter adapter18and a catheter20extending distally from the catheter adapter18. In some embodiments, the catheter adapter18may include a side port22in fluid communication with the lumen of the catheter adapter18. In some embodiments, the catheter adapter18may include a proximal end23, a distal end24, and a lumen extending there between. In some embodiments, the catheter20may include a PIVC. In some embodiments, the catheter assembly16may be removably coupled to a needle assembly, which may include a needle hub26and an introducer needle28. In some embodiments, the introducer needle28may include a sharp distal tip30. In some embodiments, a proximal end of the introducer needle28may be secured within the needle hub26. In some embodiments, the introducer needle28may extend through the catheter20when the catheter assembly16is in an insertion position ready for insertion into vasculature of a patient, as illustrated, for example, inFIG.1A. In some embodiments, in response to the introducer needle28being inserted into the vasculature of the patient, flashback of blood may flow through the sharp distal tip30of the introducer needle28and may be visible to a clinician between the introducer needle28and the catheter20and/or at another location within the catheter assembly16. In some embodiments, in response to confirmation via the blood flashback that the catheter20is positioned within vasculature of the patient, the needle assembly may be removed from the catheter assembly16. In some embodiments, when the needle assembly is coupled to the catheter assembly16, as illustrated, for example, inFIG.1A, the introducer needle28of the needle assembly may extend through a septum disposed within the lumen of the catheter adapter18. In some embodiments, the catheter system14may include one or more fluid tubes. In some embodiments, the fluid tubes may include any suitable tube through which fluid may flow to enter the catheter assembly16. In some embodiments, the catheter system14may include a clamp36through which a particular fluid tube may extend. In some embodiments, the fluid tubes may be connected to each other and/or one or more other elements to form a fluid pathway that extends between an IV bag or a fluid delivery device and the catheter assembly16. In some embodiments, the fluid tubes may include an extension tube34, which may be coupled with the catheter assembly16. In further detail, in some embodiments, a distal end of the extension tube34may be integrated with the catheter adapter18, as illustrated, for example, inFIG.1A. For example, the extension tube34may be integrated with the side port22of the catheter adapter18. In some embodiments, the extension tube34may be removably coupled to the catheter adapter18. In some embodiments, the fluid tubes may include another tube, which may be disposed proximal to the extension tube34. For example, the other tube may be coupled to the IV bag or the fluid delivery device. In some embodiments, the other tube may include an IV line that may extend between the IV bag and the extension tube24. In some embodiments, the clamp36may selectively close off the particular fluid tube on which the clamp is disposed to prevent blood or another fluid from flowing through the particular fluid tube. In some embodiments, the clinician may activate the clamp36by removing a battery isolator37or flipping a switch. In some embodiments, an adapter38may be coupled to a proximal end of the extension tube34. In some embodiments, the adapter38may include a Y-adapter or another suitable connector. In some embodiments, a needleless connector40may be coupled to the adapter38. In some embodiments, the adapter38and/or the needleless connector40may be used to connect the catheter20with a medical device for fluid administration or blood withdrawal. The medical device may include a transfusion bag, syringe, or any other suitable medical device. In some embodiments, the catheter system14may include any suitable catheter assembly, and the clamp36may be coupled to any suitable fluid tube. In some embodiments, the extension tube34may extend from the proximal end23of the catheter adapter18. In some embodiments, the catheter assembly16may include a peripheral, central, or midline catheter assembly. In some embodiments, a peripherally inserted central catheter (“PICC”) assembly may include pigtail extension tubes, and a particular clamp36may be coupled to one or more of the pigtail extension tubes. Referring now toFIG.1B, in response to the clamp36being opened, fluid may flow through the fluid tubes, such as, for example, the extension tube34and/or the other fluid tube, and through the catheter assembly16. For example, fluid may be infused into the patient via a medical device coupled to the adapter38or blood may be withdrawn from the patient into a blood collection device coupled to the adapter38. In some embodiments, the clamp36may include a sensor42, which may be configured to detect the clamp36is closed and/or open. In some embodiments, the sensor42may be positioned to detect movement of the clamp36. In some embodiments, the sensor42may include an optical sensor, a magnetic sensor, an electro-mechanical sensor, or another suitable type of sensor. As an example, the optical sensor may include a light barrier, which may be realized by a light emitting diode or a laser diode and a phototransistor. As an example, the magnetic sensor may include a reed relay or Hall sensor. As an example, the electromechanical sensor may include a switch or potentiometer. Referring now toFIG.1C, in response to the clamp36being closed, fluid may be prevented from flowing through the particular fluid tube on which the clamp36is disposed. In some embodiments, the clamp36may include a pinch clamp, which may pinch the particular fluid tube in response to movement of the clamp36to the closed position. In some embodiments, the clamp36may include an arm44, which may include a protrusion that contacts and pinches the particular fluid tube. In some embodiments, the clamp36may include any suitable clamp, and the sensor42may include any suitable sensor. In some embodiments, the sensor42may be disposed at various locations. In some embodiments, the clamp36may provide an alert which may include a sound, a tactile vibration, or a visual cue. In some embodiments, the visual cue may include a change in status of a light.FIGS.1A-1Cillustrate an example light48, according to some embodiments. In some embodiments, the status of the light48may change in response to the clamp36being closed for a predetermined duration of time. For example, the light48may turn on or may change color in response to the clamp36being closed for the predetermined duration of time. As another example, the light48may blink or change a rate of blinking in response to the clamp36being closed for the predetermined duration of time. In some embodiments, the predetermined duration of time may correspond to a time prior to a clinically recommended time to flush the catheter assembly16. In these embodiments, the alert may include a warning, which may indicate to the clinician that a clinically recommended time to flush the catheter assembly16is approaching. In some embodiments, the clinically recommended time to flush the catheter assembly16may be between about 6 hours and about 8 hours from the previous flushing of the catheter assembly16. In some embodiments, the predetermined duration of time may correspond to the clinically recommended time to flush the catheter assembly16. In some embodiments, a first alert may be provided by the clamp36in response to the clinically recommended time to flush the catheter assembly16approaching (such as, for example, in 30 minutes, 10 minutes, or 5 minutes), and a second alert may be provided by the clamp36in response to arrival of the clinically recommended time to flush the catheter assembly16. In some embodiments, the first alert may include a yellow or orange light, and the second alert may include a red light. In some embodiments, the light48may be disposed at various locations on the clamp36, which may be visible to the clinician. In some embodiments, the clamp36may include multiple lights48. In some embodiments, the light48may extend around a curved edge of the clamp36, as illustrated, for example, inFIGS.1A-1C. Referring now toFIG.1D, an example clinician monitoring device46is illustrated, according to some embodiments. Examples of the clinician monitoring device46may include a computing device, a mobile phone, a smartphone, a tablet computer, a laptop computer, a desktop computer, a medical device, or a connected device (e.g., a smartwatch, smart glasses, or any other connected device). In some embodiments, in addition to the clamp36or as an alternative to the clamp36, the clinician monitoring device46may provide the alert. In some embodiments, the clinician monitoring device46may include a display screen50, which may provide the alert. In some embodiments, the alert may include a phrase such as, for example, “Flush Due.” In some embodiments, the alert may include a visual cue on the display screen50, such as a portion51of the display screen50that lights up or changes color. In some embodiments, the portion51of the display screen50may blink or change a rate of blinking to provide the alert. In some embodiments, the clinician monitoring device46may include the light48, as described, for example, with respect toFIG.1C. Referring now toFIG.1E, an example electronic health record52that may be presented on the display screen50of the clinician monitoring device46is illustrated, according to some embodiments. In some embodiments, an indication may be provided on the display screen50in response to opening and/or closing of the clamp36. In some embodiments, the indication may be provided on the display screen50in response to opening the clamp36for a particular predetermined duration of time and/or closing the clamp36for a particular predetermined duration of time. In some embodiments, the indication may include one or more of the following: a time of day 56, a status58, and a duration of time60. In some embodiments, the duration of time60may include a duration of time the clamp36has been closed. In some embodiments, the status58may include “open” and may be adjacent to the time of day 56, indicating to the clinician the time of day at which the clamp36was opened. In some embodiments, the status58may include “closed” and may be adjacent to the time of day 56, indicating to the clinician the time of day at which the clamp36was closed. FIG.2is as block diagram of an example flush management system (FM system)62, arranged in accordance with at least one embodiment described in the present disclosure. In some embodiments, the FM system62may include the clamp63. In some embodiments, the clamp63may include or correspond to the clamp36described with respect toFIG.1. In some embodiments, the clamp63may include a computing system64. In some embodiments, the computing system64may include a processor66, a memory68, a data storage70, and a communication unit72. In some embodiments, the processor66, the memory68, the data storage70, and the communication unit72may be communicatively coupled by a bus74. The bus74may include, but is not limited to, a controller area network (CAN) bus, a memory bus, a storage interface bus, a bus/interface controller, an interface bus, or the like or any combination thereof. In some embodiments, the processor66may include a timer75. In some embodiments, the timer75may be a separate component linked to the processor66. In general, the processor66may include any suitable special-purpose or general-purpose computer, computing entity, or processing device including various computer hardware or software modules and may be configured to execute instructions stored on any applicable computer-readable storage media. For example, the processor66may include a microprocessor, a microcontroller, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a Field-Programmable Gate Array (FPGA), or any other digital or analog circuitry configured to interpret and/or to execute program instructions and/or to process data. Although illustrated as a single processor inFIG.2, the processor66may include any number of processors configured to perform, individually or collectively, any number of operations described in the present disclosure. Additionally, one or more of the processors66may be present on one or more different electronic devices. In some embodiments, the processor66may interpret and/or execute program instructions and/or process data stored in the memory68, the data storage70, or the memory68and the data storage70. In some embodiments, the processor66may fetch program instructions from the data storage70and load the program instructions in the memory68. In some embodiments, after the program instructions are loaded into memory68, the processor66may execute the program instructions. For example, in some embodiments, a flush module76may be included in the data storage70as program instructions. In some embodiments, the flush module76may be configured to manage flushing of the catheter line32and the catheter assembly16. The processor66may fetch the program instructions of the flush module76from the data storage70and may load the program instructions of the flush module76in the memory68. After the program instructions of the flush module76are loaded into the memory68, the processor66may execute the program instructions such that the computing system64may implement the operations associated with the flush module76as directed by the instructions. The memory68and the data storage70may include computer-readable storage media for carrying or having computer-executable instructions or data structures stored thereon. Such computer-readable storage media may include any available media that may be accessed by a general-purpose or special-purpose computer, such as the processor66. By way of example, and not limitation, such computer-readable storage media may include tangible or non-transitory computer-readable storage media including RAM, ROM, EEPROM, CD-ROM or other optical disk storage, magnetic disk storage or other magnetic storage devices, flash memory devices (e.g., solid state memory devices), or any other storage medium which may be used to carry or store desired program code in the form of computer-executable instructions or data structures and which may be accessed by a general-purpose or special-purpose computer. Combinations of the above may also be included within the scope of computer-readable storage media. Computer-executable instructions may include, for example, instructions and data configured to cause the processor66to perform a certain operation or group of operations. In some embodiments, one or more clinician monitoring devices73may be connected to the computing system64via a network78. In these and other embodiments, the network78may include a wired or wireless network, and may have any suitable configuration, such as a star configuration, a token ring configuration, or other configurations. Furthermore, in some embodiments, the network78may include an Ethernet network, a local area network (LAN), a wide area network (WAN) (e.g., the Internet), and/or other interconnected data paths across which multiple devices may communicate. In some embodiments, the network78may include a peer-to-peer network. In some embodiments, the network78may also be coupled to or include portions of a telecommunications network that may enable communication of data in a variety of different communication protocols. In some embodiments, the clinician monitoring devices73may include or correspond to any of the clinician monitoring devices46described with respect toFIG.1. In some embodiments, the network78may include BLUETOOTH® communication networks and/or cellular communications networks for sending and receiving data including via short messaging service (SMS), multimedia messaging service (MMS), hypertext transfer protocol (HTTP), direct data connection, wireless application protocol (WAP), e-mail, etc. The network78may enable communication via a standard-based protocol such as smart energy profile (SEP), Echonet Lite, OpenADR, or another suitable protocol (e.g., wireless fidelity (Wi-Fi), ZigBee, HomePlug Green, etc.). In some embodiments, the communication unit72may be configured to transmit data to and receive data from the clinician monitoring devices73via the network78. In some embodiments, the communication unit72may also be configured to transmit and receive data from a display screen80and/or an electronic health record82. In some embodiments, the display screen80may include or correspond to the display screen50described with respect toFIG.1D or1E. In some embodiments, the electronic health record82may include or correspond to the electronic health record52ofFIG.1E. In some embodiments, the flush module76may be configured to send and receive data via the communication unit72. In some embodiments, the communication unit72may include a port for direct physical connection to the network78and/or another communication channel. For example, the communication unit72may include a universal serial bus (USB) port, a secure digital (SD) port, a category 5 cable (CAT-5) port, or similar port for wired communication with another device. In some embodiments, the communication unit72may include a wireless transceiver for exchanging data with the clinician monitoring device46or other communication channels using one or more wireless communication methods, including IEEE 802.11, IEEE 802.16, BLUETOOTH®, or another suitable wireless communication method. In some embodiments, the communication unit72may include a cellular communications transceiver for sending and receiving data over a cellular communications network including via SMS, MMS, HTTP, direct data connection, WAP, e-mail, or another suitable type of electronic communication. The communication unit72may also provide other conventional connections to the network78for distribution of files or media objects using standard network protocols including transmission control protocol/internet protocol (TCP/IP), HTTP, HTTP secure (HTTPS), and simple mail transfer protocol (SMTP). An example of how the flush module76may manage flushing of a catheter assembly is now provided. In some embodiments, in response to a sensor84detecting the clamp is closed, the flush module76may be configured to start a timer86. In some embodiments, the sensor84may include or correspond to the sensor42described with respect toFIG.1. In some embodiments, in response to the timer86reaching a predetermined duration of time, the flush module76may be configured to generate one or more alerts at the clamp and/or to transmit an alert signal over the network78to the clinician monitoring devices73, which may provide one or more alerts. In some embodiments, the alerts may include any of the alerts described with respect toFIG.1. In some embodiments, the alerts may indicate to the clinician that the clinically recommended time to flush the catheter assembly has arrived or is approaching. In some embodiments, the flush module76may be configured to provide an indication in an electronic health record88of a patient in response to the sensors84detecting the clamp63is closed. In some embodiments, the electronic health record88may be stored and/or displayed on the clinician monitoring devices73. In some embodiments, the electronic health record88may include or correspond to the electronic health record52described with respect toFIG.1. In some embodiments, the indication may include or correspond to the indication54described with respect toFIG.1. In some embodiments, in response to the sensors84detecting the clamp63is open or open for another predetermined duration of time, the flush module76may be configured to stop and/or reset the timer86. In some embodiments, the flush module76may be configured to stop the timer86only after the clamp63has been open for the other predetermined duration of time to prevent opening of the clamp63when adequate flushing could not have occurred. In some embodiments, in response to the sensors84detecting the clamp63is open for the other predetermined duration, the flush module76may be configured to stop the alert at the clamp63or provide a different alert at the clamp63. Additionally or alternatively, in some embodiments, in response to the sensors84detecting the clamp63is open for the other predetermined duration, the flush module76may be configured to transmit another alert signal over the network78to the clinician monitoring devices73to stop the alert or provide a different alert. In some embodiments, the flush module76may be configured to provide another indication in the electronic health record88of the patient in response to the sensors84detecting the clamp63is open for the other predetermined duration of time. In some embodiments, the other indication may include or correspond to the indication54described with respect toFIG.1. In some embodiments, one or more other sensors90may be configured to detect fluid flowing through a fluid tube, such as, for example the extension tube34of the catheter assembly16described with respect toFIG.1or another fluid tube in fluid communication with the catheter assembly16. In some embodiments, the other sensors may include a flow sensor and/or a pressure sensor. Example devices that include flow sensors and/or pressure sensors are described in U.S. Patent Application No. 62/830,707, filed Apr. 8, 2019, entitled “OCCLUSION DETECTION DEVICES, SYSTEMS, AND METHODS,” and U.S. Pat. No. 5,533,412, filed Jun. 7, 1995, entitled “PULSED THERMAL FLOW SENSOR SYSTEM,” which are hereby incorporated by reference in their entirety. In some embodiments, in response to the sensors84detecting the clamp63is open and the other sensors90detecting fluid flowing through the fluid tube, the flush module76may be configured to stop and/or reset the timer86. Although illustrated outside the clamp63inFIG.2, it is understood that the other sensors90may be part of the clamp63. In some embodiments, an external server may include one or more components of the computing system64. In some embodiments, the external server may be connected to the clamp63and/or the clinician monitoring device73via the network78or another network. Modifications, additions, or omissions may be made to the FM system62without departing from the scope of the present disclosure. All examples and conditional language recited herein are intended for pedagogical objects to aid the reader in understanding the invention and the concepts contributed by the inventor to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Although embodiments of the present inventions have been described in detail, it should be understood that the various changes, substitutions, and alterations could be made hereto without departing from the spirit and scope of the invention. | 23,460 |
11857735 | DETAILED DESCRIPTION The present disclosure generally provides additive manufacturing systems and methods for medical devices, such as catheters and leads, that allows for the use of a wider range of filament or pellet materials to create a wide range of resulting catheter or lead characteristics. For example, a wider variety of hardness levels can be achieved compared to existing techniques to produce catheters, catheter components, or implantable devices. Additive manufacturing may also be described as three-dimensional (3D) printing. The additive manufacturing systems of the present disclosure allow feeding soft filaments at high feed forces, which may facilitate a wider range of operating conditions for prototyping or manufacturing. Further, new catheters and implantable devices may be facilitated by the wider range filament materials and operating conditions. Specifically, two or more materials with varying properties may be combined into a new composite with a unique set of properties. The systems and methods described herein allow for 3D printing of medical devices, which may facilitate constructions with unique combinations of properties which may enable new treatments. Unique catheter handling properties may be achieved by combining materials in ways not traditionally combined in catheter manufacturing and may include materials that are new to catheter construction. Further, other catheter properties (e.g., electrical, thermal, fluoro or echo opaque, etc.) may also be achieved by combining materials as described herein. In addition, 3D printing may allow for including other accessories, such as steering capability via pull wires, in a space efficient manner. In some embodiments, the systems and methods described herein may facilitate concurrently depositing multiple and varying stiffness standard geometry 3D printing filament resin at varying blend ratio to produce varying flex modulus and color of deposited material. For example, two durometers of the same polymer may be combined into different types of layering by applying the materials while spinning the medical device. The centrifuge action may cause the medical device to uniformly distribute (e.g., along layers) the two materials (e.g., filament materials or doping agents) in the jacket formed from the system. Further, the rheological properties of the filament materials may also cause a uniform and layered distribution (e.g., due to the rotational motion described herein). In addition to forming varying characteristics from multiple filaments, the process described herein may produce electrode rings and patterns from biocompatible conductive materials that are different than what is currently feasible with traditional methods. Further, the process described herein may be applicable to transferring energy (e.g., similar to a vortex ring gun), electromagnetic applications (e.g., using ferrite beads), marker bands in dimensions and patterns that are different than what is currently feasible with traditional methods, etc. As used herein, the term “or” refers to an inclusive definition, for example, to mean “and/or” unless its context of usage clearly dictates otherwise. The term “and/or” refers to one or all of the listed elements or a combination of at least two of the listed elements. As used herein, the phrases “at least one of” and “one or more of” followed by a list of elements refers to one or more of any of the elements listed or any combination of one or more of the elements listed. As used herein, the terms “coupled” or “connected” refer to at least two elements being attached to each other either directly or indirectly. An indirect coupling may include one or more other elements between the at least two elements being attached. Either term may be modified by “operatively” and “operably,” which may be used interchangeably, to describe that the coupling or connection is configured to allow the components to interact to carry out described or otherwise known functionality. For example, a controller may be operably coupled to a resistive heating element to allow the controller to provide an electrical current to the heating element. As used herein, any term related to position or orientation, such as “proximal,” “distal,” “end,” “outer,” “inner,” and the like, refers to a relative position and does not limit the absolute orientation of an embodiment unless its context of usage clearly dictates otherwise. All scientific and technical terms used herein have meanings commonly used in the art unless otherwise specified. The definitions provided herein are to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure. Reference will now be made to the drawings, which depict one or more aspects described in this disclosure. However, it will be understood that other aspects not depicted in the drawings fall within the scope of this disclosure. Like numbers used in the figures refer to like components, steps, and the like. However, it will be understood that the use of a reference character to refer to an element in a given figure is not intended to limit the element in another figure labeled with the same reference character. In addition, the use of different reference characters to refer to elements in different figures is not intended to indicate that the differently referenced elements cannot be the same or similar. FIG.1shows one example of an additive manufacturing system100according to the present disclosure. The system100may be configured and used to produce a catheter, catheter component, lead, or subassembly. The system100may use or include consumable filament materials or pellet form resins having a wide variety of hardness levels. The system100may be configured to operate a wide variety of process conditions to produce catheters, catheter components, leads, or subassemblies using filaments or pellet form resins of various hardness levels. In general, the system100defines a distal region128, or distal end, and a proximal region130, or proximal end. The system100may include a platform124including a rigid frame to support one or more components of the system. As shown in the illustrated embodiment, the system100may include one or more components, such as a heating cartridge102, a heating element104, a filament handling system106, an optional wire handling system107, a substrate handling system108, a controller110, and a user interface112. The filament handling system106may be operably coupled to the heating cartridge102. The filament handling system106may provide one or more filaments114to the heating cartridge102. The optional wire handling system107may be used to provide one or more wires115to the heating cartridge102. The heating element104may be operably coupled, or thermally coupled, to the heating cartridge102. The heating element104may provide heat to melt filament material in the heating cartridge102from the one or more filaments114provided by the filament handling system106. The optional wires115may not be melted by the heating cartridge102. The substrate handling system108may be operably coupled to the heating cartridge102. The substrate handling system108may provide a substrate116that extends through the heating cartridge. Melted filament material located in the heating cartridge102may be applied to the substrate116. The substrate116or the heating cartridge102may be translated or rotated relative to one another by the substrate handling system108. The substrate handling system108may be used to move the substrate116or the heating cartridge102relative to one another to cover the substrate116with the melted filament material to form a jacket118. The optional wires115may be incorporated into the jacket118(e.g., molded into, bedded within, etc.). The substrate116may also be described as a mandrel or rod. The jacket118may be formed or deposited around the substrate116. In some embodiments, the jacket118may be formed concentrically around the substrate116. In one example, the jacket118is formed concentrically and centered around the substrate116. When the system100is used to make a catheter or catheter component, the jacket118may be described as a catheter jacket. Some or all of the substrate116may be removed or separated from the jacket118and the remaining structure coupled to the jacket may form the catheter or catheter component, such as a sheath. One example of a catheter that may be formed by the system100is shown inFIG.4. The substrate116may be formed of any suitable material capable of allowing melted filament material to be formed thereon. In some embodiments, the substrate116is formed of a material that melts at a higher temperature than any of the filaments114. One example of a material that may be used to form the substrate116includes stainless steel. The controller110may be operably coupled to one or more of the heating elements104, the filament handling system106, the substrate handling system108, and the user interface112. The controller110may activate, or initiate or otherwise “turn on,” the heating element104to provide heat to the heating cartridge102to melt the filament material located therein. Further, the controller110may control or command one or more motors or actuators of various portions of the system100. Furthermore, the controller110may control one or more motors or actuators the filament handling system106to provide one or more filaments114. Further, the controller110may control one or more motors or actuators of the substrate handling system108to move one or both of the heating cartridge102or the substrate116relative to one another. Further still, the controller110may send or receive data to the user interface112, for example, to display information or to receive user commands. Control of the components operably coupled to the controller110may be determined based on user commands received by the user interface112. In some embodiments, the user commands may be provided in the form of a machine-readable code or coding language. Any suitable implementation may be used to provide the substrate handling system108. In some embodiments, the substrate handling system108may include one or more of a head stock120, an optional tail stock122, and one or more motors coupled to or included in the head stock or tail stock. One or both of the head stock120and the tail stock122may be coupled to the platform124. A stock may be defined as a structure that holds or secures the substrate116during formation of the jacket118. The head stock120is defined as the stock closest to the end of the substrate116where formation of the jacket118begins in the formation process. In the illustrated embodiment, the jacket118is shown proximal to the head stock120and distal to the heating cartridge102. When the substrate116is secured by one or both stocks120,122, the substrate is generally positioned to pass through a substrate channel defined by the heating cartridge102. One or both stocks120,122may include a clamp or other securing mechanism to selectively hold the substrate116. Such a clamp may be operably coupled to a substrate motor. In some embodiments, the substrate motor may be used to control opening and closing of the clamp. In some embodiments, the substrate motor may be used to rotate the substrate116in a clockwise or counterclockwise direction about a longitudinal axis126. A translation motor may be operably coupled between a stock120,122and the platform124. In some embodiments, the translation motor may be used to translate the stock120,122in a longitudinal direction along the longitudinal axis126. In some embodiments, the translation motor also may be used to translate the stock120,122in a lateral direction different than the longitudinal axis126. The lateral direction may be oriented substantially orthogonal, or perpendicular, to the longitudinal axis126. In some embodiments, the substrate handling system108may be configured to move the head stock120at least in a longitudinal direction (for example, parallel to the longitudinal axis126) relative to the platform124. The substrate116may be fed through the substrate channel of the heating cartridge102by movement of the head stock120relative to the platform124. A distal portion of the substrate116may be clamped into the head stock120. The head stock120may be positioned close to the heating cartridge102at the beginning of the jacket formation process. The head stock120may move distally away from the heating cartridge102, for example in a direction parallel to the longitudinal axis126. In other words, the head stock120may move toward the distal region128of the system100while pulling the secured substrate116through the heating cartridge102. As the substrate116passes through the heating cartridge102, melted filament material from the filament114may be formed or deposited onto the substrate116to form the jacket118. The heating cartridge102may be stationary relative to the platform124. In some embodiments, the tail stock122may be omitted. In some embodiments, the substrate handling system108may be configured to move the heating cartridge102at least in a longitudinal direction (along the longitudinal axis126) relative to the platform124. The substrate116may be fed through the substrate channel of the heating cartridge102. A distal portion of the substrate116may be clamped into the head stock120. A proximal portion of the substrate116may be clamped into the tail stock122. In one example, the heating cartridge102may be positioned relatively close to the head stock120at the beginning of the jacket formation process. The heating cartridge102may move proximally away from the head stock120. The heating cartridge102may move toward the proximal region130of the system100. As the heating cartridge102passes over the substrate116, melted filament material may be deposited onto the substrate116to form a jacket. The head stock120and the tail stock122may be stationary relative to the platform124. In another example, the heating cartridge102may start near the tail stock122and move toward the distal region128. One or more motors of the substrate handling system108may be used to rotate one or both of the substrate116and the heating cartridge102(e.g., the input die) relative to one another. In some embodiments, only the substrate116may be rotated about the longitudinal axis126. In some embodiments, only a portion of the heating cartridge102(e.g., the input die) may be rotated about the longitudinal axis126. In some embodiments, both the substrate116and the heating cartridge102may be rotated about the longitudinal axis126. The heating cartridge102may be part of a subassembly132. The subassembly132may be coupled to the platform124. In some embodiments, one or more motors of the substrate handling system108may be coupled between subassembly132and the platform124to translate or rotate the subassembly132, including the heating cartridge102, relative to the platform124or the substrate116. In some embodiments, one or more motors of the substrate handling system108may be coupled between a frame of the subassembly132and the heating cartridge102to translate or rotate the heating cartridge relative to the platform124. In some embodiments, the substrate116may be rotated about the longitudinal axis126relative to the heating cartridge102to facilitate forming certain structures of the jacket. In one example, the substrate116may be rotated by one or both of the head stock120and the tail stock122of the substrate handling system108. In another example, the heating cartridge102or subassembly132may be rotated by the substrate handling system108. Rotation of the heating cartridge102(e.g., specifically the input die) relative to the substrate116may assist in maintaining concentricity of the jacket118. In other words, by rotating about the longitudinal axis126while the jacket is formed, the melted filament may form in a more concentric circle and help mitigate eccentricity (e.g., due to the rheological properties of the filament materials) of the filament material. Specifically, the rheological properties of the filament materials may assist in providing a uniform and layered distribution (e.g., due to the rotational motion described herein) Furthermore, the system100may include one or more concentricity guides134. The concentricity guide134may facilitate adjustments to the concentricity of the jacket around the substrate116before or after the substrate passes through the heating cartridge102. The concentricity guide134may be longitudinally spaced from the heating cartridge102. In some embodiments, the spacing may be greater than or equal to 1, 2, 3, 4, or 5 cm. The spacing may be sufficient to allow the jacket118to cool down and no longer be deformable. In some embodiments, one or more concentricity guides134may be positioned distal to the heating cartridge102and to engage the jacket118. In some embodiments, one or more concentricity guides134may be positioned proximal to the heating cartridge102to engage the substrate116. The concentricity guide134may mitigate drooping of the substrate116and may mitigate susceptibility to eccentricity in the alignment of the stock120,122and the heating cartridge102. Any suitable implementation may be used to provide the filament handling system106. One or more filaments114may be loaded into the filament handling system106. For example, filaments114may be provided in the form of wound coils. Filaments114may be fed to the heating cartridge102by the filament handling system106. In some embodiments, the filament handling system106may include one, two, or more pinch rollers to engage the one or more filaments114. In some embodiments, the filament handling system106may include one or more motors. The one or more motors may be coupled to the one or more pinch rollers to control rotation of the pinch rollers. The force exerted by the motors onto the pinch rollers and thus onto the one or more filaments114may be controlled by the controller110. In some embodiments, the filament handling system106may be configured to feed the filaments114including at least a first filament and a second filament. The jacket118may be formed from the material of one or both of the filaments114. The filament handling system106may be capable of selectively feeding the first filament and the second filament. For example, one motor may feed the first filament and another motor may feed the second filament. Each of the motors may be independently controlled by the controller110. Selective, or independent, control of the feeds may allow for the same or different feed forces to be applied to each of the filaments114. The filaments114may be made of any suitable material, such as polyethylene, PEBAX elastomer (commercially available from Arkema S.A. of Colombes, France), nylon 12, polyurethane, polyester, liquid silicone rubber (LSR), or PTFE. The filaments114may have any suitable Shore durometer. In some embodiments, the filaments114may have, or define, a Shore durometer suitable for use in a catheter. In some embodiments, the filaments114have a Shore durometer of at least 25A and up to 90A. In some embodiments, the filaments114have a Shore durometer of at least 25D and up to 80D. In some embodiments, the filament handling system106may provide a soft filament as one of the filaments114. In some embodiments, a soft filament may have a Shore durometer less than or equal to 90A, 80A, 70A, 80D, 72D, 70D, 60D, 50D, 40D, or 35D. In some embodiments, the filament handling system106may provide a hard filament and a soft filament having a Shore durometer less than the soft filament. In some embodiments, the soft filament has a Shore durometer that is 10D, 20D, 30D, 35D, or 40D less than a Shore durometer of the hard filament. The system100may be configured to provide a jacket118between the Shore durometers of a hard filament and a soft filament. In some embodiments, the filament handling system106may provide a hard filament having a Shore durometer equal to 72D and a soft filament having a Shore durometer equal to 35D. The system100may be capable of providing a jacket118having a Shore durometer that is equal to or greater than 35D and less than or equal to 72D. The system100may be configured to provide a jacket118having, or defining, segments with different Shore durometers. In some embodiments, the system100may be capable of providing a jacket118having one or more of a 35D segment, a 40D segment, 55D segment, and a 72D segment. The filaments114may have any suitable width or diameter. In some embodiments, the filaments114have a width or diameter of 1.75 mm. In some embodiments, the filaments114have a width or diameter of less than or equal to 1.75, 1.5, 1.25, 1, 0.75, or 0.5 mm. In some embodiments, the jacket118may include continuous transitions between at least two different Shore durometers, for example, as shown inFIG.4. The controller110may be configured to change a feeding force applied to one or more of the filaments114to change a ratio of material in the jacket over a longitudinal distance. By varying the feeding force, the system100may provide different Shore durometer segments in a jacket118. In one example, sharp transitions between uniform segments may be provided by stopping or slowing longitudinal movement while continuously, or discretely with a large step, changing the feeding force of one filament relative to another filament of the substrate116relative to the heating cartridge102. In another example, gradual transitions between segments may be provided by continuously, or discretely with small steps, changing the feeding force of one filament relative to another filament while longitudinally moving the substrate116relative to the heating cartridge102. By rotating the heating cartridge102(e.g., the input die) relative to the substrate116in a rotational direction, the various materials of the two or more filaments may be more uniformly blended and deliberately layered. As such, materials may be blended and layered more uniformly than what could be accomplished using typical coextrusions. For example, a first filament material may shift to the outer surface of the jacket118and a second filament material may shift inward in the jacket118to form a uniform and deliberate layering that may, e.g., produce reliable properties and characteristics. Further, these processes may provide discrete rings (e.g., tuned pulsing vortex rings) and patterns within the structure of the jacket118(e.g., formed by the mixing of the filament materials). The discrete rings and patterns may, e.g., add hoop strength to the jacket118. The discrete rings may vary in volume and spacing depending on the overall fluid volume. The heating cartridge102(e.g., the input die) and the substrate116may move relative to one another in the rotational direction at a rate of about greater than or equal to 80 RPM and/or less than or equal to 5000 RPM. Specifically, the rate of rotation between the heating cartridge102and the substrate116may be between about greater than or equal to 200 RPM and/or less than or equal to 300 RPM. More specifically, the rate of rotation between the heating cartridge102and the substrate116may be between about greater than or equal to 260 RPM. It is noted that the substrate116moves relative to the heating cartridge102(e.g., the input die) along the longitudinal axis126simultaneously with rotating about the longitudinal axis126. For example, in one or more embodiments, the ratio of movement along the longitudinal direction to movement along the rotational direction may be about 44 revolutions per inch. This combination of axial and rotational movement may result in a specific pitch of the filament materials that form the jacket. Furthermore, the resulting structure of the filament materials may create a distinct internal ring reinforcement structure pattern. Specifically, the structure may be produced via tuned rheological poloidal and toroidal flow pattern within the multiple semi-immiscible fluids of unique durometer. These patterns may be formed at various volume ratios of toroid ring material to encapsulation material. The resulting uniformity of the jacket and properties thereof may be tuned based on the rotational and longitudinal speeds. Further, the optimal speeds (e.g., longitudinal and rotational) may depend on the material properties of the filaments forming the jacket. A uniform transition between two separate filament materials is illustrated inFIGS.5-7. For example, as shown inFIG.5, the catheter may be predominantly formed of a first filament material and, as shown inFIG.6, the catheter may be predominantly formed of a second filament material. By adjusting the feeding force on each of the filaments, the ratio of filament materials may be adjusted.FIG.7illustrates a combination of the first and second filament materials that has be spun to result in a uniform and layered blending or mixture. The pitch of the filament materials (e.g., due to the combination axial and rotational movements) may be shown in the structure (e.g., rings) illustrated inFIG.7. Additionally, the catheter as shown inFIGS.5-7may include discrete rings (e.g., tuned pulsing vortex rings) that are formed from each of the different filament materials due to the rotational force applied to the jacket. In other words, each of the filament materials may form discrete rings that interact and combine at the intersection of the different filament materials (e.g., as shown inFIG.7). Further, the volume and spacing of the discrete rings may be defined by the overall fluid volume used to form the jacket. As noted previously, these discrete rings may add hoop strength to the jacket and provide properties based on the composition of the discrete ring. In one or more embodiments, a particulate material (e.g., a fluoroscopic marking material) may be added to the jacket and may be uniformly dispersed (e.g., throughout, at the outer surface, etc.) due to the rotational force applied to the jacket. Additionally, the two or more filament materials may be layered due to the rotational force applied to the filament materials. For example, the heavier materials may bias towards the exterior surface of the resultant jacket and the lighter materials may bias towards the interior of the resultant jacket. One specific example of blending two filament materials into a medical device may occur as it relates to the bonding of materials of a balloon catheter. If the two filament materials do not bond together well, an adhesive or tie layer may be needed to provide bonding therebetween. By using the rotating processes described herein, the filament materials may uniformly bond. Therefore, the number of material combinations may increase because materials that were previously labeled as not ideally bonding, may result in a uniform blending using the rotational forces of the present processes. In other words, these materials may be optimized in ways that were not previously available. The system100may also be configured to provide a jacket118having varying thicknesses. In some embodiments, the controller110may be configured to vary one or more parameters, for example, at least one of: a longitudinal speed of the substrate116relative to the heating cartridge102, a feeding force applied to one or more filaments114, and an amount of heat provided by the heating element104. Varying one or more of these parameters during formation of the jacket118may be used to change a thickness of the jacket over a longitudinal distance. In some embodiments, the controller110may be configured to vary one or more of these parameters in conjunction with using a particular heating cartridge. The one or more wires115provided by the wire handling system107may be introduced in any suitable manner. In some embodiments, the wires115may be attached to the substrate116and pulled by movement of the substrate. One example of a wire is a pull wire that may be used to steer the catheter produced by the system100. In some embodiments, a particularly shaped heating cartridge may be used to accommodate one or more wires115. Any suitable type of heating element104may be used. In some embodiments, the heating element104may be a resistive-type heating element, which may provide heat in response to an electrical current. Other types of heating elements that may be used for the heating element104include a radio frequency (RF) or ultrasonic-type heating element. The heating element104may be capable of providing heat sufficient to melt the filaments114. In some embodiments, the heating element104may heat the filaments114to greater than or equal to 235, 240, 250, or 260 degrees Celsius. In general, the one or more heating elements104may be used to heat the filaments114to any suitable melting temperature known to one of ordinary skill in the art having the benefit of this disclosure. Any suitable user interface112may be used to communicate with the controller110. Non-limiting examples of user interfaces112include one or more of a stationary or portable computer, a monitor or other display, a touchscreen, a keyboard, a mouse, a tablet, a phone, a knob, a switch, a button, and the like. In some embodiments, the user interface112may allow the user to input direct commands to or to enter code to program operations of the controller110. As used herein, the term “flow rate” refers to a filament feed rate according to any suitable unit of measurement. In some embodiments, material1may be 35D PEBAX and material2may be 72D PEBAX. In general, as the mixture ratio transitions to a softer durometer material, the overall feed rate (F ###) may decrease. Decreasing the feed rate may reduce the tendency for the softer durometer material to jam. Certain techniques described herein may reduce the need to decrease the overall feed rate. The flow rate command (E ###) may directly affect the wall thickness of the printed catheter jacket. FIG.2shows one example of an additive manufacturing apparatus200of the additive manufacturing system100in an end view along the longitudinal axis126, which is illustrated as a circle and cross. More detail of some components of the additive manufacturing system100are shown, such as the heating cartridge102and the filament handling system106. The heating cartridge102may include a heating block202at least partially defining an interior volume204. The interior volume204may be heated by the heating element104. The heating element104may be thermally coupled to the heating block202to melt filament material in the interior volume204. In general, the system100may be configured to melt any portion of the filaments114in the interior volume204. The heating element104may be disposed in an exposed or exterior volume502defined in the heating block202. The heating element104may be positioned proximate to or adjacent to the interior volume204. In some embodiments, one, two, three, or more heating elements104may be thermally coupled to the heating block202. The heating block202may allow the substrate116, which may be an elongate substrate or member, to pass through the heating block. The substrate116may be able to extend, or pass, through the interior volume204. The substrate channel206defined by the heating cartridge102may extend through the interior volume204. The substrate channel206may extend in a same or similar direction as the substrate116. The substrate channel206may extend along the longitudinal axis126. A width or diameter of the interior volume204is larger than a width or diameter of the substrate116. The width or diameter of the interior volume204or the substrate116is defined in a lateral direction, which may be orthogonal to the longitudinal axis126. In one example, the lateral direction may be defined along a lateral axis210. In some embodiments, the clearance between the substrate116and interior volume204is relatively small to facilitate changes in composition of filament material used to form the jacket118(FIG.1) around the substrate116. The portion of the interior volume204around the substrate116may receive a flow of melted filament material from the filaments114. When more than one filament material is provided to the interior volume204, the filament materials may flow and blend, or mix, around the substrate116. In the illustrated embodiment, the filaments114includes a first filament212and a second filament214. The first filament212may be provided into the interior volume204through a first filament port216at least partially defined by the heating block202. The second filament214may be provided into the interior volume204through a second filament port218at least partially defined by the heating block202. Each filament port216,218may be at least partially defined by the heating block202. Each filament port216,218may be in fluid communication with the interior volume204. The filaments114may be delivered to the interior volume204in the same or different manners. In the illustrated embodiment, the first filament212is delivered to the interior volume204in a different manner than the second filament214. The filament handling system106may include a first handling subassembly220. The first handling subassembly220may deliver the first filament212to the interior volume204. The first handling subassembly220may include one or more pinch rollers222. Each of the one or more pinch rollers222may be operably coupled to a motor. Any suitable number of pinch rollers222may be used. As illustrated, the first handling subassembly220may include two sets of pinch rollers222. Pinch rollers222may be used to apply a motive force to the first filament212to move the first filament, for example, toward the interior volume204. The heating cartridge102may include a first guide sheath224. The first guide sheath224may extend between the filament handling system106and the interior volume204. The first guide sheath224may be coupled to the heating block202. The first guide sheath224may extend into the first filament port216from an exterior of the heating block202. The first guide sheath224may define a lumen in fluid communication with the interior volume204. An inner width or diameter of the lumen may be defined to be greater than a width or diameter of the first filament212. The first filament212may extend through the first guide sheath224from the pinch rollers222of the first handling subassembly220to the first filament port216and extend distally past the first guide sheath224into the interior volume204. As used herein with respect to the filaments114, the term “distal” refers to a direction closer to the interior volume204and the term “proximal” refers to a direction closer to the filament handling system106. In some embodiments, a proximal end of the first guide sheath224may terminate proximate to one of the pinch rollers222. A distal end of the first guide sheath224may terminate at a shoulder226defined by the first filament port216. A distal portion or distal end of the first guide sheath224may be positioned proximate to or adjacent to the interior volume204. The inner width or diameter of the lumen of the first guide sheath224may be defined to be substantially the same or equal to an inner width or diameter of the first filament port216, such as a smallest inner width or diameter of the first filament port. In other words, an inner surface of the first guide sheath224may be flush with an inner surface of the first filament port216. In some embodiments, the heating cartridge102may include a support element228. The support element228may be coupled to the first guide sheath224. The first guide sheath224may extend through a lumen defined by the support element228. The support element228may be proximate to the heating block202. In the illustrated embodiment, the support element228is coupled to the heating block202. The support element228may include a coupling protrusion configured to be mechanically coupled to a coupling receptacle230defined by the first filament port216. In some embodiments, the coupling receptacle230may define threads and the coupling protrusion of the support element228may define complementary threads. The coupling receptacle230may terminate at the shoulder226of the first filament port216. The coupling protrusion of the support element228may be designed to terminate at the shoulder226. In some embodiments, a distal end of the support element228and the distal end of the first guide sheath224may engage the shoulder226. In other embodiments, the distal end of the support element228may engage the shoulder226and the distal end of the first guide sheath224may engage a second shoulder (not shown) defined by the first filament port216distal to the shoulder226. When the first filament port216defines one shoulder, the first filament port216may define at least two different inner widths or diameters. The larger inner width or diameter may be sized to thread the support element228and the smaller inner width or diameter may be sized to match the inner width or diameter of the first guide sheath224. When the second filament port218defines two shoulders, the first filament port216may define at least three different inner widths or diameters. The largest inner width or diameter may be sized to thread the support element228. The intermediate inner width or diameter may be sized to receive a distal portion of the first guide sheath224. The smallest inner width or diameter may be sized to match the inner width or diameter of the first guide sheath224. The filament handling system106may include a second handling subassembly232. The second handling subassembly232may deliver the second filament214to the interior volume204. The second handling subassembly232may include one or more pinch rollers222. Each of the one or more pinch rollers222may be operably coupled to a motor. Any suitable number of pinch rollers222may be used. As illustrated, the second handling subassembly232may include one set of pinch rollers222. Pinch rollers222may be used to apply a motive force to the second filament214. The heating cartridge102may include one or more of a second guide sheath234, a heat sink236, and a heat break238. The second guide sheath234may extend at least between the second handling subassembly232and the heat sink236. The second guide sheath234may be coupled to the heat sink. The second guide sheath234may be coupled to the second handling subassembly232. The heat sink236may be coupled to the heat break238. The heat break238may be coupled to the heat block202. The heat break238may extend into the second filament port218from an exterior of the heating block202. The second guide sheath234may define a lumen in fluid communication with the interior volume204. The second filament214may extend through the second guide sheath234from the second handling subassembly232to the heat sink236, through the heat sink236, through the heat break, and through the second filament port218. In some embodiments, the second guide sheath234may extend to the pinch rollers22in the second handling subassembly232. In some embodiments, the second guide sheath234may extend at least partially into the heat sink236. The heat break238may be proximate to the heating block202. The heat break238may be positioned between the heat sink236and the heating block202. The heat break238may include a coupling protrusion configured to mechanically couple to a coupling receptacle240defined by the second filament port218. In some embodiments, the coupling receptacle240may define threads and the coupling protrusion of the heat break238may define complementary threads. The second filament port218may include one or more shoulders such as those described with respect to the first filament port216, except that the second filament port218may not be configured to receive the second guide sheath234. The inner width or diameter of the support element228may be larger than the inner width or diameter of the heat break238, for example, to accommodate the outer width or diameter of the first guide sheath224. In other embodiments, the second filament port218may be configured to receive the second guide sheath234in a similar manner to the first filament port216receiving the first guide sheath224. Any suitable material may be used to make the guide sheaths224,234. In some embodiments, one or both guide sheaths224,234may include a synthetic fluoropolymer. One or both guide sheaths224,234may include polytetrafluoroethylene (PTFE). Another suitable material may include an ultra-high molecular weight polyethylene (UHMWPE). Any suitable material may be used to make the support element228. In some embodiments, the support element228may be a thermal insulator. The support element228may include a thermoplastic. The support element228may be made of a polyamide-imide, such as a TORLON polyamide-imide (commercially available from McMaster-Carr Supply Co. of Elmhurst, Illinois). Other suitable materials may include liquid-crystal polymer, polyaryletherketone (PAEK), polyphenylene sulfide, and polysulfone. The support element228may provide mechanical support to the first guide sheath224. The support element228may include a substantially rigid material. In some embodiments, the support element228include a material having a higher durometer than material used to make the first guide sheath224. Any suitable material may be used to make the heat sink236. The heat sink236may include a high thermal conductivity material. In some embodiments, the heat sink236includes aluminum. Any suitable material may be used to make the heat break238. The heat break238may include a low thermal conductivity material. In some embodiments, the heat break238includes titanium. The heat break238may include a necked portion to reduce the amount of material between a proximal portion and a distal portion of the heat break. The necked portion may facilitate a reduced thermal conductivity between the proximal portion and the distal portion of the heat break238. In general, use of the apparatus200may facilitate using softer filaments at high feed forces and pressures, which tend to compress the soft filament and may result in jamming. Using higher feed forces and pressures may allow for a greater range of process conditions and may provide a consistent jacket around the substrate. In particular, use of the first guide sheath224extending at least partially into the first filament port216may facilitate the use of softer filament and greater “push-ability.” Additionally, or alternatively, the use of the support element228may also facilitate the use of softer filament and greater “push-ability.” FIG.3shows a partial cross-sectional side view of one example of the heating cartridge102. The heating cartridge102or the heating block202may extend from a proximal side410to a distal side412. In some embodiments, the heating cartridge102may include one or more of the heating block202, an inlet die402coupled to the proximal side410of the heating block, an outlet die404coupled to the distal side412of the heating block, a proximal retaining plate406to facilitate retaining the inlet die adjacent to the heating block, and a distal retaining plate408to facilitate retaining the outlet die adjacent to the heating block. The inlet die402and the outlet die404may be retained in any suitable manner. In the illustrated embodiment, the outlet die404may be retained by a distal shoulder of the distal retaining plate408. In some embodiments, the inlet die402may be retained by the proximal retaining plate406between a distal shoulder of the proximal retaining plate406and a fastener500, such as a nut with a lumen extending through, which may be threaded to the retaining plate to engage a proximal surface of the inlet die. The retaining plates406,408may be fastened to the heating block202in any suitable manner. The inlet die402may at least partially define a substrate inlet port414. The outlet die404may at least partially define a substrate outlet port416. The inlet die402may at least partially define the interior volume204. The outlet die404may at least partially define the interior volume204. In some embodiments, an exterior surface of the inlet die402, an interior surface of the outlet die404, and an interior surface of the heating block202may cooperatively define the interior volume204. The substrate channel206may be described as extending from the proximal side410to the distal side412of the heating cartridge102, or vice versa. The substrate channel206may extend through the interior volume204. As shown, the substrate channel206may extend through one or more of the proximal retaining plate406, the inlet die402, the heating block202, the outlet die404, and the distal retaining plate408. FIG.4shows one example of a catheter600that may be manufactured using the system100before the substrate116is removed. The substrate116may include a lubricious coating on its exterior surface to facilitate removal. The lubricious coating may extend around the circumference of the substrate116. One example of a lubricious coating is a PTFE coating. The substrate116may be covered with a liner602, such as a PTFE layer. The liner602may be placed over the lubricious coating. The liner602may extend around the circumference of the substrate116. The liner602may be covered with a braid604, such as a stainless-steel braid layer. The braid604may be placed over the liner602. The braid604may extend around the circumference of the liner602. The braid604may be porous. The jacket118may be applied to the braid604. When the jacket118is formed, the liner602may adhere to the jacket118through pores in the braid604. In the illustrated embodiments, the catheter600includes a first segment606, a second segment608, and a third segment610. Each segment606,608,610may have different durometers. In some embodiments, the first segment606may have a high durometer, the third segment610may have a low durometer, and the second segment608may have a continuously varying durometer in a longitudinal direction between the durometers of the first and third segments. For example, the first segment606may have a Shore durometer equal to 72D, the third segment610may have a Shore durometer equal to 35D, and the second segment608may have a Shore durometer that gradually changes from 72D to 35D over its length. FIG.8shows one example of a method800of using the system100(FIG.1) for additive manufacturing. The method800may be used to manufacture an implantable medical catheter. The method800may include feeding the substrate802, for example, through a substrate channel in a heating cartridge. The substrate channel may be in fluid communication with an interior cavity of the heating cartridge. The method800may include feeding a first filament804through a filament port of the heating cartridge into the interior cavity and feeding a second filament806through another filament port into the interior cavity. The method800may include melting one or more of the filaments808, for example, in the interior cavity. Any portion of the filaments contained in the interior cavity may be melted. For example, melting the first and second filaments in the interior cavity. The method800may include moving the heating cartridge relative to the substrate810, for example, in a longitudinal direction to form a catheter jacket comprising material from at least the first and second filaments. Further, the method800may include moving the heating cartridge (e.g., the input die) relative to the substrate812in a rotational direction about the longitudinal axis such that the first and second filaments create discrete rings when forming the catheter jacket. In some embodiments, the method800may also include adjusting a ratio of the first filament relative to the second filament over a longitudinal distance to change the Shore durometer of the catheter jacket over the longitudinal distance. In one or more embodiments, the change in ratio of material in the jacket over the longitudinal distance may be continuous. In one or more embodiments, moving the heating cartridge relative to the substrate in a rotational direction may include moving at a rate of about greater than or equal to 200 RPM and/or less than or equal to 300 RPM. Specifically, the rotational rate may be about 260 RPM, while the axial or linear rate may be about 2 inches per minute. In one or more embodiments, moving the heating cartridge relative to the substrate may include moving at a rotational direction to longitudinal direction ratio of about greater than or equal to 25 revolutions per inch, greater than or equal to 35 revolutions per inch, greater than or equal to 44 revolutions per inch, etc. and/or less than or equal to 150 revolutions per inch, less than or equal to 100 revolutions per inch, less than or equal to 50 revolutions per inch, etc. Specifically, the rotational direction to longitudinal direction ratio may be about 44 revolutions per inch (e.g., 44 discrete material rings per inch). It is noted that, in addition to the rotational to linear ratio, the rheological properties may also be affected by pressure, material viscosities, the geometry encapsulating the flow, etc. In one or more embodiments, the method may also include adding particulate to the catheter jacket prior to moving the heating cartridge relative to the substrate. Illustrative Embodiments While the present disclosure is not so limited, an appreciation of various aspects of the disclosure will be gained through a discussion of the specific examples and illustrative embodiments provided below. Various modifications of the examples and illustrative embodiments, as well as additional embodiments of the disclosure, will become apparent herein.A1. An additive manufacturing system comprising:a heating cartridge extending from a proximal side to a distal side and comprising a substrate inlet port at the proximal side and a substrate outlet port at the distal side, the heating cartridge defining an interior volume and a substrate channel extending through the interior volume from the proximal side to the distal side, wherein the heating cartridge defines a first filament port in fluid communication with the interior volume to receive the first filament and a second filament port in fluid communication with the interior volume to receive the second filament;a heating element thermally coupled to the heating cartridge to heat the interior volume;a filament handling system comprising one or more motors to feed at least a first filament through the first filament port and a second filament through the second filament port into the interior volume;a substrate handling system comprising:a head stock comprising a distal clamp to secure a distal portion of an elongate substrate, wherein the substrate is positioned to pass through the substrate channel along a longitudinal direction when secured by the head stock; andone or more motors to translate or rotate one or both of the substrate when secured by the headstock and the heating cartridge relative to one another; anda controller operably coupled to the heating element, one or more motors of the filament handling system, and one or more motors of the substrate handling system, the controller configured to:control the one or more motors of the filament handling system to selectively control the feeding of the first filament and the second filament into the interior volume;activate the heating element to melt any portion of the first filament or the second filament in the interior volume; andcontrol one or more motors of the substrate handling system to move one or both of the substrate and the heating cartridge relative to one another in a longitudinal direction to form an elongate catheter jacket around the substrate, wherein the catheter jacket comprises material from at least the first filament and the second filament; andcontrol one or more motors of the substrate handling system to move one or both of the substrate and the heating cartridge relative to one another in a rotational direction about the longitudinal axis such that the first and second filaments create discrete rings.A2. The system according to embodiment A1, wherein the substrate and the heating cartridge move relative to one another in the rotational direction at a rate of about 260 RPM.A3. The system according any preceding A embodiment, wherein the substrate and the heating cartridge move relative to one another in the longitudinal direction and the rotational direction at a ratio of about 44 revolutions per inch.A4. The system according any preceding A embodiment, wherein the elongate catheter jacket comprises particulate proximate an outer surface of the catheter jacket.A5. The system according to any preceding A embodiment, wherein the first filament has a Shore durometer less than or equal to 90A, 80A, 70A, 80D, 72D, 70D, 60D, 50D, 40D, or 35D.A6. The system according to any preceding A embodiment, wherein the first filament has a Shore durometer 10D, 20D, 30D, 35D, or 40D less than a Shore durometer of the second filament.A7. The system according to any preceding A embodiment, wherein the heating cartridge comprises an inlet die, a heating block, and an outlet die, wherein heating block defines the first filament port and the second filament port.A8. The system according to any preceding A embodiment, wherein the controller is configured to change a feeding force applied to at least one of the first filament and the second filament to change a ratio of material in the catheter jacket over a longitudinal distance.A9. The system according to embodiment A8, wherein the change in ratio of material in the catheter jacket over the longitudinal distance is continuous.A10. The system according to any preceding A embodiment, further comprising the substrate, wherein the substrate comprises a lubricious coating, a liner, and a braid, and the catheter jacket is formed around the braid.B1. A method for additive manufacturing of an implantable medical device, the method comprising:feeding a substrate through a substrate channel in a heating cartridge along a longitudinal axis, the substrate channel in fluid communication with an interior cavity of the heating cartridge;feeding a first filament through a filament port into the interior cavity;feeding a second filament through another filament port into the interior cavity;melting the first and second filaments in the interior cavity;moving the heating cartridge relative to the substrate at least in a longitudinal direction to form a catheter jacket comprising material from at least the first and second filaments; andmoving the heating cartridge relative to the substrate in a rotational direction about the longitudinal axis such that the first and second filaments create discrete rings in forming the catheter jacket.B2. The method according to embodiment B1, further comprising adjusting a ratio of the first filament relative to the second filament over a longitudinal distance to change the Shore durometer of the catheter jacket over the longitudinal distance.B3. The method according to embodiment B2, wherein the change in ratio of material in the catheter jacket over the longitudinal distance is continuous.B4. The method according to any preceding B embodiment, wherein moving the heating cartridge relative to the substrate in a rotational direction comprises moving at a rate of 260 RPMB5. The method according to any preceding B embodiment, wherein moving the heating cartridge relative to the substrate comprises moving at a rotational direction to longitudinal direction ratio of about 44 revolutions per inch.B6. The method according to any preceding B embodiment, wherein the first filament has a Shore durometer less than or equal to 90A, 80A, 70A, 80D, 72D, 70D, 60D, 50D, 40D, or 35D.B7. The method according to any preceding B embodiment, wherein the first filament has a Shore durometer 10D, 20D, 30D, 35D, or 40D less than a Shore durometer of the second filament.B8. The method according to any preceding B embodiment, further comprising adding particulate to the catheter jacket prior to moving the heating cartridge relative to the substrate in the rotational direction. Thus, various embodiments described herein are disclosed. It should be understood that various aspects disclosed herein may be combined in different combinations than the combinations specifically presented in the description and accompanying drawings. It should also be understood that, depending on the example, certain acts or events of any of the processes or methods described herein may be performed in a different sequence, may be added, merged, or left out altogether (e.g., all described acts or events may not be necessary to carry out the techniques). In addition, while certain aspects of this disclosure are described as being performed by a single module or unit for purposes of clarity, it should be understood that the techniques of this disclosure may be performed by a combination of units or modules associated with, for example, a medical device. In one or more examples, the described techniques may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions may be stored as one or more instructions or code on a computer-readable medium and executed by a hardware-based processing unit. Computer-readable media may include non-transitory computer-readable media, which corresponds to a tangible medium such as data storage media (e.g., RAM, ROM, EEPROM, flash memory, or any other medium that can be used to store desired program code in the form of instructions or data structures and that can be accessed by a computer). Instructions may be executed by one or more processors, such as one or more digital signal processors (DSPs), general purpose microprocessors, application specific integrated circuits (ASICs), field programmable logic arrays (FPGAs), or other equivalent integrated or discrete logic circuitry. Accordingly, the term “processor” as used herein may refer to any of the foregoing structure or any other physical structure suitable for implementation of the described techniques. Also, the techniques could be fully implemented in one or more circuits or logic elements. All references and publications cited herein are expressly incorporated herein by reference in their entirety for all purposes, except to the extent any aspect directly contradicts this disclosure. Unless otherwise indicated, all numbers expressing feature sizes, amounts, and physical properties used in the specification and claims may be understood as being modified either by the term “exactly” or “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the foregoing specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by those skilled in the art utilizing the teachings disclosed herein or, for example, within typical ranges of experimental error. As used herein, the term “configured to” may be used interchangeably with the terms “adapted to” or “structured to” unless the content of this disclosure clearly dictates otherwise. The singular forms “a,” “an,” and “the” encompass embodiments having plural referents unless its context clearly dictates otherwise. As used herein, “have,” “having,” “include,” “including,” “comprise,” “comprising” or the like are used in their open-ended sense, and generally mean “including, but not limited to.” It will be understood that “consisting essentially of,” “consisting of,” and the like are subsumed in “comprising,” and the like. Reference to “one embodiment,” “an embodiment,” “certain embodiments,” or “some embodiments,” etc., means that a particular feature, configuration, composition, or characteristic described in connection with the embodiment is included in at least one embodiment of the disclosure. Thus, the appearances of such phrases in various places throughout are not necessarily referring to the same embodiment of the disclosure. Furthermore, the particular features, configurations, compositions, or characteristics may be combined in any suitable manner in one or more embodiments. The words “preferred” and “preferably” refer to embodiments of the disclosure that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful and is not intended to exclude other embodiments from the scope of the disclosure. | 60,894 |
11857736 | DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Reference will now be made in greater detail to preferred embodiments of the invention, examples of which is illustrated in the accompanying drawings. Wherever possible, the same reference numerals will be used throughout the drawings and the description to refer to the same or like parts. FIG.1A,FIG.1B, andFIG.1Cillustrates one embodiment of adapter10coupled to distal end213of medical device200. An example of a suitable medical device200is a catheter. Medical device200can be referred to as a parent. Adapter10includes distal portion20and proximal portion30. Proximal portion30is predominately or entirely inside lumen211of target medical device200. Distal portion20of adapter10is predominately outside of target medical device200. Adapter10is co-axial with medical device200as shown by longitudinal axis11. Proximal portion30of adapter10includes coil12. Preferably coil12can be made of nitinol. Coil12can be comprised of wire with a cross-sectional size wound to form a general coil shape. Coil12interfaces with lumen211of medical device200in a manner that secures adapter10to medical device200. Adapter10can be secured to medical device200by an interference fit of coil12with lumen211. Surface220of coil12can directly engage surface212of lumen211. Coil12can have an austenitic finish temperature (Af) less than body temperature, such as an average of 37° C. of normal body temperature, and greater than a temperature typically expected in an operating room or catheter lab, for example about 25 degrees to about 30 degrees C. Coil12can be twisted and or elongated to reduce a size or diameter of coil12such that coil12has a smaller size or diameter than a size or diameter of lumen211to facilitate positioning adapter10inside medical device200. As adapter10warms to body temperature during use in-vivo, coil12can expand to provide additional securement to medical device200. Alternatively, coil12can be designed to be physically restrained or constrained to have a size or diameter smaller than internal lumen211of medical device200in an operating room environment and coil12can expand to interface with the internal lumen211of the target catheter or device200when the physical restraint is removed, once the adapter10is seated within medical device200. Coil12is shown with a constant round cross-section, alternatively the coil12can have a rectangular cross-section of a flat wire coil design. A flat wire design provides the benefit of a lower profile coil12but still provides sufficient securement through an interference fit with lumen211. The cross-section can be variable along the length of coil12. A variable cross-section coil12design provides the advantage of biased securement towards either one of the ends of adapter10. Coil12can have variable flexibility and bending about longitudinal axis11. In one embodiment, coil12provides additional reinforcement of medical device200to improve the kink resistance. Adapter10includes tube16, coupled to distal portion20of adapter10and is co-axial with coil12. Tube16is an elongated element. Tube16has funnel portion13located at proximal end30of adapter10. Funnel portion13can facilitate tracking of a guide wire from a proximal end (not shown) of medical device200to distal portion20of adapter10. Tube16preferably is a polymer tube and can include braiding or other reinforcement. Coil12includes proximal end15that is coupled, bonded or otherwise attached near proximal end19of tube16. Proximal end15of coil12can be retained to a size smaller than a size of lumen211to facilitate loading of adapter10into medical device200in use. Distal end14of coil12can be retained to a size smaller than a size of lumen211. For example, proximal end15or distal end14can be heat shaped or formed to a smaller size than the size of lumen211. Distal end14provides a location on coil12that can be grabbed or held in order to twist and or elongate coil12to make it smaller in size to facilitate positioning the adapter10inside medical device200. Distal portion20of adapter10is preferably made from a thermoplastic elastomer. Example thermoplastic elastomers or soft polymers include but are not limited to, polyether urethane and polyether block amide, such as for example ˜40 D PEBAX manufactured by Arkema. In this embodiment, distal portion20is designed to modify medical device200that has a single guidewire access to have a two guidewire access. Distal portion20includes first lumen21for a first guidewire and second lumen22. Second lumen22connects to lumen211of medical device200by way of tube16of adapter10. This allows the user extra flexibility, for example to exchange guidewires, or to administer contrast or medications through the target catheter or device lumen211. The path of a first guidewire is illustrated by first lumen centerline23and the path of a second guidewire is illustrated by the second lumen centerline24. Accordingly, the path of lumen centerline23is outside of device200. Distal portion20includes reduced size portion17at proximal end26of distal portion20which is designed through choice of materials, for example thermoplastic elastomers or soft polymers, and of a geometry to interface with lumen211of medical device200. A slight interference fit between reduced size portion17and lumen211provides a stable structure during introduction of the coupled adapter10and medical device200into a body cavity or vessel. Adapter10can include a tapered distal end27of distal portion20which facilitates tracking the medical device200with attached adapter10inside a body lumen. FIG.2illustrates adapter10in a configuration where coil12has been reduced to a smaller size by elongating coil12.FIG.3illustrates adapter10in a configuration where the coil12has been reduced to a smaller size by rotating or twisting coil12. An alternate embodiment of adapter10is where a combination of coil12twisting and elongating reduces the size of coil10such that it can fit within medical device200. Distance Ds2between distal end14of coil12and proximal end26of distal portion20inFIG.2andFIG.3is smaller than distance Ds1between distal end14of coil12and proximal end26of distal portion20as illustrated inFIG.1C. In an alternate embodiment of adapter10, if the user twists and or elongates coil12such that distal end14of coil12is within a predetermined distance of proximal end26of distal portion20, then the user would know adapter10is safe to insert into medical device200. For example, tube16can be marked to indicate the appropriate location of distal end14of coil12. FIG.4illustrates an alternate embodiment of the present invention shown as adapter40. Adapter40has distal portion41and proximal portion42similar to distal portion20and proximal portion30of adapter10as shown inFIGS.1A,1B and1C. Adapter40includes tube16with funnel portion13located at proximal portion42of adapter40. Tube16is coupled to distal portion41. Coil12is also coupled to distal portion41and interfaces with lumen211of medical device200in a manner that secures adapter40to medical device200. Securement can be achieved in a similar manner as previously described for adapter10. FIG.5illustrates an alternate embodiment of the present invention shown as adapter50. Adapter50has distal portion51and proximal portion52similar to distal portion20and proximal portion30of adapter10as shown inFIGS.1A,1B and1C. Adapter50is similar to adapter40, except portion53of coil12that interfaces with lumen211has a larger pitch than that of adapter40. For example, the pitch can be in the range of about 2 to about 10 times the size of the coil-sectional size of the wire of coil12. Adapter50also includes proximal end25of coil12which is similar to distal end14of adapter10in both use and form, except coil12is elongated and or twisted toward the proximal portion52of adapter50to make the size of coil12smaller to facilitate insertion of adapter50into medical device200. FIG.6illustrates an alternate embodiment of the present invention shown as adapter60. Adapter60has distal portion61and proximal portion62similar to distal portion20and proximal portion30of adapter10as shown inFIGS.1A,1B and1C, as well as other similar features. Proximal portion62includes coil12which has a reduced sized portion18such that it grips tube16. Coil12can be heat shaped or formed with a portion that interfaces with lumen211of medical device200. Reduced sized portion18has an inside diameter dia1smaller than outside diameter dia2of tube16to contact and grip tube16during use. Reduced diameter portion18of coil12can be bonded, glued, or heat reflowed to tube16, for example, to further couple coil12to proximal portion62. FIG.7illustrates an adapter70in a configuration where coil12has been reduced to a smaller size by elongating and or twisting coil12, similarly illustrated inFIG.2andFIG.3. Adapter70has distal portion71and proximal portion72similar to distal portion20and proximal portion30of adapter10as shown inFIGS.1A,1B and1C. Distal portion71includes single lumen tip73, co-axial with longitudinal axis11. Single lumen tip73has been reinforced with reinforcement section74. For example, reinforcement section74can be a coil or braid. Reinforcement section74includes proximal coil portion75which extends past the proximal end of single lumen tip73. Proximal coil portion75provides a slight interference fit with lumen211and a stable interface during initial insertion of adapter70into medical device200by the user. Reinforcement section74reinforces distal portion71and can facilitate tracking medical device200through a tight lesion. FIG.8A,FIG.8B,FIG.8C,FIG.8D,FIG.8E, andFIG.8Fillustrate an alternate embodiment of the present invention shown as adapter100. Adapter100has distal portion170and proximal portion110. Proximal portion110includes coil130. Coil130is wound from wire136and has multiple diameters along its length. In one embodiment, wire136is flat with a rectangular or square cross-section. For example, coil130can have a wound length A131at a diameter øA137at proximal end of coil130. The wound pitch of wire136along wound length A131is variable, not constant, and changes from a pitch that is approximately twice the width162of flat wire136at proximal end of the wound length A131, to a pitch that is approximately equal to a width of flat wire136, such that wire136is close wrapped at distal end of wound length A131. A variable pitched wound length has advantages in that the farther spaced pitched coil can be more flexible, and the close wrapped coil can be stiffer and stronger in torsion or bending. A variable pitched wound length also has advantages in that the farther spaced pitched coil can also provide a better bonding geometry such that a bonding agent or adhesive can flow between wraps of coil130. As wire136is wound distally to form coil130, the diameter of the coil130transitions from a size øA137to a larger size a138over length transition132. Wire136is wound over length B133at a size a138. The wound pitch of wire136along wound length B133is variable, not constant, and changes from a pitch that is approximately equal to width162of wire136, such that wire136is close wrapped, to a significantly wider pitch that is approximately more than 5 times the close wrapped pitch. A dramatic or rapid change in pitch from close wrapped to more than 5 times width162of flat wire136is advantageous because it creates a wedge when coil130is constrained within internal lumen211of medical device200during use and can improve the interference fit and retention properties of adapter100within medical device200. Typically, øA137would be dimensionally smaller than lumen211of the target medical device200and a øB138would be dimensionally larger than lumen211of the medical device200. As wire136is wound distally to form coil130the diameter of coil130transitions from a size a øB to a smaller size øD139over length transition134. The wound pitch of wire136along wound length transition134is approximately uniform. In an alternate embodiment, the wound pitch of wire136along wound length transition134is variable. Wire136is wound distally from length transition134to continue to form coil130at a size øD139over a wound length D135. Typically, øD139would be dimensionally smaller than lumen211of medical device200. A portion of wound length D135of coil130at a size øD139is within cavities178and177of distal portion170of adapter100. Cavity177is sized to interface with a distal end of medical device200and cavity178is sized to accommodate the coil130at a size øD139. Cavity178is sized to allow wound length D135of coil130to move freely within cavity178when there is not an external mechanism gripping, pinching or clamping proximal end of distal portion170in the area of cavity178. When there is an external mechanism gripping, pinching or clamping the proximal end of distal portion170in the area of cavity178, cavity178is sized to prevent a portion of coil130in wound length D135from rotating or moving, holding coil130, which has been previously rotated/twisted to a smaller size state to facilitate insertion of proximal portion110of adapter100into medical device200. Coil130can be made from Nitinol and have an austentic finish temperature (Af) approximately equal to or less than an ambient temperature of the operating room or catheter lab environment so coil130will expand when released from a smaller size state after insertion into medical device200. Alternatively, coil130can be made from Nitinol and have an austenitic finish temperature (Af) less than body temperature but greater than the temperature typically expected in an operating room or catheter lab, for example about 25 C-30 C, except in zone T161where coil130has been selectively heat treated to have an austentic finish temperature (Af) approximately equal to or less than an ambient temperature operating room or catheter lab environment, for example less than about ˜18 C, to enable zone T161of Nitinol coil130to expand when released from a smaller size state after insertion into medical device200in the catheter lab environment. Coil130having multi-zone or variable thermal properties has advantages in that it can be easier to insert adaptor100into medical device200with some of coil130having a higher Af temperature. The selectively heat treated portion of coil130in zone T161is biased to engage internal lumen211of medical device200more than the rest of coil130to facilitate creating the wedge, as described above, after coil130is released from a smaller size state and constrained within internal lumen211of medical device200. As adapter100warms to body temperature during use in-vivo the zone T is161of coil130provides additional securement and structure to adapter100. Zone T161as shown includes portion of length A131, transition132and portion of length B133. Alternatively, zone T161can include just a portion of transition132and a portion of length B133or other combinations. Coil130is coupled to, bonded to or otherwise attached to central tube182of central lumen183of adapter100at part or all of the wound length A131at øA137. Proximal end120of proximal portion110of adapter100includes inner element122and outer element121. Inner element122and outer element121can form a funnel shape. Outer element121can be radiopaque or partially radiopaque to provide a landmark for proximal end120of adapter100when used in-vivo. The funnel shape of proximal end120of the adapter100can facilitate the back loading of a guidewire through the medical device200and adapter100during use. Proximal end120of adapter100is coupled, bonded or otherwise attached to the central tube182. In one embodiment, central tube182can be unitary with inner element122. Central tube182connects proximal end of coil130, in the area of Length A131and proximal end120to distal portion170. Distal portion170of adapter100has an outer body179that is typically cylindrical or a revolved shape. Alternatively, outer body can have a non-revolved profile in portions or entirely. Outer body179can be made from a polymer. Outer body can be reinforced with metal, polymer or ceramic fibers, wire, laser cut hypotube and the like. Outer body179can be a laminated structure which can include multiple tube elements or materials. Outer body179can have a stepped tapered shape with first outside diameter185and second outside diameter184connected by tapered portions. Distal portion170has first exit lumen186of central lumen183and second exit lumen187of central lumen183at opposite each other in outer body179. First exit lumen186is angled at angle A1toward proximal portion110of adapter100from the central axis of central lumen183. An angle in a direction of angle A1can be advantageous when a guidewire is tracked through central lumen183starting at distal tip181of distal portion170, exiting through first exit lumen186. Second exit lumen187is angled at angle A2toward distal end of adapter100from the central axis of central lumen183. An angle in a direction of angle A2can be advantageous when a guidewire is tracked through central lumen183at proximal end120of proximal portion110, exiting through second exit lumen187. Central tube182terminates proximal to distal tip181such that a portion of central lumen183is formed only by outer body179. Alternatively, central tube182could extend to distal tip181or terminate at a more proximal location within outer body179. Central tube182can form central lumen183for a majority of the length of distal portion170to add strength and rigidity if required, for example if central tube182was a braided or wire reinforced structure. In one embodiment, coil130has been rotated or twisted about the longitudinal axis of coil130and central tube182, while central tube182and a portion of wound length A131at øA137attached to central tube182are held fixed to decrease its size, specifically in transition132, length B133, and transition134. After coil130has been rotated or twisted to decrease the size of transition132, length B133, and transition134, a portion of distal end198of coil130, length D135, which is already at a small diameter, can be held and fixed relative to distal portion170and coupled central tube182such that the coil130will remain at a reduced diameter. When a portion of distal end198of coil130, length D135that was held is released, coil130will expand back from the small size state to its unconstrained size state and this expansion will tend to happen starting at unattached distal end197, length D135as coil130starts to expand/unwind from the distal end and progressively expands/unwinds moving proximal. In one embodiment, as coil130progressively expands/unwinds from distal end197to proximal end of coil130, distal elements of coil130do not substantially inhibit the expansion and engagement of the portion transition132and Length B133to internal lumen211of medical device200, to facilitate creating the wedge. FIG.9A,FIG.9B,FIG.9C,FIG.9D,FIG.9E,FIG.9GandFIG.9Hillustrate an alternate embodiment of the present invention shown as adapter101. Adapter101is similar to Adapter100and has distal portion171and proximal portion111. Proximal portion111includes coil140which is similar to coil130. Coil140is wound from wire136and has multiple diameters along the length of coil140. Coil140as shown has a wound length A141at a diameter øA137at proximal end157of coil140. The wound pitch of wire136along wound length A141is variable, not constant, and changes from a pitch that is approximately twice the width162of flat wire136at the proximal end of the wound length A141, to a pitch that is approximately equal to the width162of wire136, such that wire136is close wrapped at the distal end of wound length A141. A variable pitched wound length has advantages that the farther spaced pitched coil can be more flexible, and the close wrapped coil can be stiffer and stronger in torsion or bending. A variable pitched wound length can have advantages in that the farther spaced pitched coil can also provide an improved bonding geometry such that a bonding agent or adhesive could flow between wraps of coil140. As wire136is wound distally to form coil140, the diameter of the coil140transitions from a size øA137to a larger size a138over length transition160. Wire136is wound over a length B133at a size a138. The wound pitch of wire136along wound length B133is variable, not constant, and changes from a pitch that is approximately equal to width162of wire136, such that wire136is close wrapped, to a significantly wider pitch that is approximately more than 5 times width162of the flat wire136. A dramatic or rapid change in pitch from close wrapped to more than 5 times the width162of wire136as shown is advantageous because it creates a wedge when coil140is constrained within internal lumen211of medical device200during use and can improve the interference fit and retention properties of adapter101within the catheter or device200. Typically, øA137would be dimensionally smaller than lumen211of medical device200and a138would be dimensionally larger than lumen211of the medical device200. As wire136is wound distally to form coil140the diameter of coil140transitions from size øB138to a smaller size øC144over length transition142, the wound pitch of wire136along wound length transition142is substantially uniform. Alternatively, wound pitch of wire136along wound length transition142is variable. Wire136is wound distally from length transition142to continue to form coil140at a size øC144over wound length C143. øC144can be dimensionally similar to or slightly smaller than lumen211of medical device200so that as coil140was unconstrained from a small size state in use to secure adapter101to internal lumen211, wound length C143of coil140at size øC144would be less likely to inhibit wound length B133of coil140at size øB138from engaging and securing coil140to internal lumen211of medical device200. As wire136is wound distally to form coil140the diameter of coil140transitions from size øC144to a smaller size øD139over length transition146, the wound pitch of wire136along wound length transition146is substantially uniform. Alternatively, wound pitch of wire136along wound length transition146is variable. Wire136is wound distally from length transition146to continue to form coil140at a size øD139over wound length D145. Typically, øD139would be dimensionally smaller than lumen211of medical device200. A portion of the wound length D145of coil140at a size øD139is within cavities178and177at proximal end199of distal portion171of adapter101. Cavity177is sized to interface with distal end (not shown) of medical device200and cavity178is sized to accommodate coil140at a size øD139. Cavity178is sized to allow wound length D145of coil140to move freely within cavity178when there is not an external mechanism gripping, pinching or clamping proximal end199of distal portion171in the area of cavity178. When there is an external mechanism gripping, pinching or clamping proximal end199of distal portion170in the area of cavity178, cavity178sized to prevent a portion of coil140in wound length D145from rotating or moving, holding coil140, which has been previously rotated/twisted to a smaller size state to facilitate insertion of proximal portion111of adapter101into medical device200. Coil140is coupled to, bonded to or otherwise attached to second tube element190forming a portion of second lumen191of adapter101at or along part or all of the wound length141at øA137. It may be advantageous for wound length141to be attached to second tube element190predominately close to transition160such that an uncoupled portion of wound length141could extend proximally to add more structure and support to adapter101and medical device200. Proximal end120of adapter101is attached to second tube element190in a similar manner as proximal end120of adapter100is attached to central tube182. Distal portion171of adapter101has outer body179that is typically cylindrical or a revolved shape. Alternatively, distal portion171of adapter101has outer body179that has a non-revolved profile in portions or throughout, similar to outer body179of adapter100shown inFIG.8A. Second tube element190is attached or coupled to outer body179, thereby connecting proximal end of coil140in the area of Length A141and proximal end120to distal portion171. Distal portion171has first tube element188which forms a portion of first lumen189. As shown, first tube element188terminates proximal to distal tip181such that a portion of first lumen189is formed only by the outer body179. First tube element188could extend to distal tip181or terminate at a more proximal location within outer body179. Second lumen191and first lumen189exit outer body179in a manner similar to second exit lumen187and first exit lumen186. Second tube element190and first tube element188are shown extending to edge230of outer body179of distal portion171. Alternatively, second tube element190and first tube element188can terminate before edge230and such that a portion of second lumen191and first lumen189can be formed by outer body179of distal portion171. FIG.10A,FIG.10B,FIG.10C,FIG.10D,FIG.10E,FIG.10FandFIG.10Gillustrate an alternate embodiment of the present invention, adapter102. Adapter102is similar to adapter100and has distal portion172and proximal portion112. Proximal portion112includes coil130located closer to distal portion172and coil147located closer to proximal end123. Coil130is a left handed helix and coil147is a right handed helix. Coil130has been described as part of adapter100. Coil147is similar to coil130. Coil147is wound from wire153and has multiple diameters along the length of the coil147. Wire153can be a flat wire. Coil147as shown has a wound length E148at a diameter (ø) øE151at the proximal end of coil147. As wire153is wound distally to form coil147the diameter of coil147transitions from a size øE151to a larger size øF152over a length transition149. Wire153is wound over a length F150at a size øF152. The wound pitch of153along wound length F150is variable, not constant, and changes from a pitch that is approximately equal to the width of wire153, such that wire153is close wrapped, to a significantly wider pitch that is approximately more than 5 times the width of wire153. A dramatic or rapid change in pitch from close wrapped to more than 5 times the width of wire153is advantageous because it creates a wedge when coil147is constrained within internal lumen211of medical device200during use and can improve the interference fit and retention properties of adapter102within medical device200. Typically, øE151would be dimensionally smaller than lumen211of medical device200and the øF152would be dimensionally larger than lumen211of medical device200. Adapter102includes coaxial tube elements, central tube192and reinforcing tube member194. Central tube192forms a portion of central lumen193of adapter102. Proximal end123of adapter102is attached or coupled to the central tube192. Proximal end123is comprised of funnel element124. Central tube192and funnel element124can be unitary such that funnel element124is a flared end of central tube192. Funnel element124is advantageous in that it can facilitate back loading a guide wire through the medical device200and adapter102. Central tube192and reinforcing tube member194are both attached, bonded or coupled to distal portion172of adapter102. As shown, reinforcing tube member194terminates proximally to central tube192which terminates proximal to distal end181of proximal portion172of adapter102. An alternate embodiment or configuration can have reinforcing tube member194attached to distal portion172and central tube192attached to reinforcing tube member194to form adapter102. This embodiment has advantages if reinforcing tube member194were to terminate closer to distal tip181to include features to optimize the tip performance, for example as a crossing support device, while central tube192predominately provides a more optimized central lumen193for a guide wire as an example. In this embodiment, reinforcing tube member194and central tube192can terminate approximately together or central tube192can be more proximal than reinforcing tube member194. Coil147is attached, bonded or otherwise coupled to the reinforcing tube member194at all or a portion of length E148. This could be accomplished using an adhesive to attach a portion of length E148to reinforcing tube member194. In a similar manner as previously described, a portion or all of the length A131of coil130is bonded or attached to reinforcing tube member194. The inside diameter of coil130at a size of øD139is typically larger than the outside diameter of second tube element190or central tube182or reinforcing tube member194. FIG.11A,FIG.11B,FIG.11C, andFIG.11D, illustrate adapter102while coil130has been rotated or twisted in a manner that wraps or winds it down to a smaller diameter a155. Coil130has been rotated or twisted such that transition132, wound length B133and transition134have been made to be held in a state at a smaller diameter a155over a combined wound length of transitions132and length B154. Diameter øB155is approximately equal to or smaller than internal lumen211of medical device200to facilitate inserting adapter102. Temporary constraining element195is positioned around this portion of coil130to secure coil130at smaller diameter øB155. Temporary constraining element195is advantageous to allow coil130to be held in smaller diameter a155without the need to hold or restrain from moving length D135section of coil130. Length D135is not attached or coupled to reinforcing tube member194. FIG.11A,FIG.11B,FIG.11C, andFIG.11Dshow clamping element196pinching or holding a portion of Length D135from rotating such that temporary constraining element195can be removed and coil130would still be held in a state that includes smaller diameter a155. It may be advantageous to include a temporary constraining element195such that only temporary constraining element195holds coil130in a state at a smaller diameter a155in an adapter packaging suitable for terminal sterilization and or shipping, transportation and inventory at the customer site, which would minimize the amount of time the load at the attached portion of coil130in Length A131would need to be reacted. When the adapter is ready to be used in an operating room or catheter lab, clamping element196can be applied and temporary constraining element195can be removed to allow insertion into medical device200. FIG.12A,FIG.12B,FIG.12C, andFIG.12D, illustrate adapter102after it has been initially inserted into medical device200while coil130has been rotated or wound down to a smaller diameter øB155and held in that position by clamping element196. Coil147is shown after it has been inserted in internal lumen211of medical device200. As coil147is inserted the portion of length F150and transition149as shown inFIG.11A,FIG.11B,FIG.11C, andFIG.11Dconforms to the size of inner lumen211of medical device200and becomes a smaller diameter ø″159by elongating and or rotating. Similarly to as described previously, a dramatic or rapid increase in pitch from close wrapped to more than 5 times the close wrap pitch, which is approximately the width of wire153, as shown, is advantageous because it creates a wedge with an angle A127, equal to or greater than approximately 15 degrees, when coil147is constrained within internal lumen211of medical device200during use, and can improve the interference fit and retention properties of adapter100within medical device200. In the embodiment of adapter102, coil147is the leading coil inserted into internal lumen211of medical device200. As coil147is inserted into internal lumen211, the wraps of wire153that are at a size approximately equal to internal lumen211, located within transition149and length F150, engage surface212of internal lumen211and reduce in size by elongating and rotating (predominately elongating) such that the transition and length F158is longer than the combination of transition149and length F150, and the entire coil147can be inserted into medical device200. This mode of action is different than that of coil130. As shown inFIG.13A,FIG.13B,FIG.13C, andFIG.13D, after adapter102is inserted into target device or catheter200and clamping element196is removed, coil130will rotate and expand to the size of internal lumen211to engage surface212of internal lumen211over a combined wound length of length B156, which includes portions of transition132, length B133, and transition134. Coil130is designed such that, upon expansion to conform to internal lumen211as described, within coil130geometry there is a dramatic or rapid increase in pitch from close wrapped to more than 5 times the close wrap pitch, which is approximately the width of wire136, and which creates a wedge with an angle B163equal to or greater than approximately 15 degrees. An advantage to the mode of action of coil130versus the mode of action of coil147is that by predominantly rotating coil130to conform to the internal lumen211instead of predominately elongating coil147to conform to the internal lumen211, coil130will be less likely to have axial re-coil when allowed to expand, and the force to insert adapter is removed. Coil147can be pulled into the lumen211of medical device200as adapter102is inserted into medical device200via the bonded connection in Length A131to reinforcing tube member194. After adapter102has been inserted into medical device200, coil147will tend to axially re-coil toward distal end of adapter102, whereas coil130rotates into position without an external pulling force. Including both modes of action in one adapter is advantageous because it provides redundancy in case one mode is less effective than the other in retaining adapter102in medical device200. Additionally, coil130and coil147are wound in opposite directions such that if adapter102is placed under an external torsional load, adapter102optimally reacts in either direction of an external torsional load. FIG.14A,FIG.14B, andFIG.14Cillustrate adapter103after it has been inserted into medical device200, and coil130has been deployed to engage internal lumen211securing adapter103. Adapter103includes distal portion173and proximal portion113very similar to the previously described proximal portion110and proximal portion111. Distal portion173of adapter103has outer body179that is typically cylindrical or a revolved shape. Alternatively, distal portion173of adapter103can have a non-revolved profile in portions or throughout. Outer body179has a stepped tapered shape with first outside profile185, second outside profile184and third outside profile180connected by tapered portions. Distal portion173has first tube element188which forms a portion of first lumen189. First tube element188terminates proximal to distal tip181such that a portion of first lumen189is formed only by outer body179. First tube element188could extend to distal tip181or terminate at a more proximal location within outer body179. Second tube element190, which forms a portion of second lumen191, connects coil element130of proximal portion113to distal portion173. Second lumen191and first lumen189exit outer body179in a manner similar to second exit lumen187and first exit lumen186. Second tube element190and first tube element188are shown partially extending to edge230of outer body179of distal portion173where a portion of second tube element190and first tube element188terminate before230edge of outer body179, such that a portion of second lumen191and first lumen189are formed by outer body179of distal portion173. Third outside profile180of outer body179includes first cavity166and second cavity169, as shown in longitudinal cross section and transverse cross section Z-Z. First cavity166and second cavity169are shown as open cavities. Alternatively, first cavity166and second cavity169can be a closed cavity, such as a circle shaped cavity. First cavity166and second cavity169are shown to be 180 degrees opposite each other. Alternatively, first cavity166and second cavity169can have alternative orientations. FIG.15A,FIG.15B, andFIG.15Cillustrate adapter103, as shown inFIG.14A,FIG.14B, andFIG.14Cwith the addition of first wire167and second wire168. Preferably, first wire167originates with a first end outside the patient (not shown) and extends distally along the outside of medical device200, then through first cavity166and first lumen189, exiting distal end181of distal portion173and extends to second end231of first wire167. Preferably, second wire168originates with a first end outside the patient (not shown) and extends distally through proximal end (not shown) of medical device200and continues inside lumen211of medical device200, through second lumen191then wrapping to extend back proximally through second cavity169extending proximally along the outside of medical device200, and extends to second end (not shown) of second wire168. Second end (not shown) of second wire168can terminate outside the patient body. Adapter103can be advantageous when medical device200is a percutaneous transluminal angioplasty balloon, for example. First wire167can act a guide wire to track medical device200which is a percutaneous transluminal angioplasty balloon to the site of an arterial lesion or blockage as well as provide a mechanism to induce a stress concentration into the wall of the artery and lesion, preferentially dissecting or disrupting the lesion to improve dilation performance of the balloon at the target lesion. Second end of second wire168can extend proximally past the balloon in medical device200such that second wire168also provides a mechanism to induce a stress concentration similar to first wire167. Second wire168can have curve164. For example, second wire168can be manufactured from Nitinol and be heat treated to set a shape with curve164. Alternately, second wire168can be designed to be readily shaped to curve164. For example, second wire168can be manufactured from Nitinol and be heat treated to have an Af temperature such that second wire168is easily bent to curve164and stays in that shape during use, for example at an Af temperature above body temperature (37 C). Second wire168can be positioned into adapter103and medical device200of a balloon prior to introduction of adapter103and medical device200into the patient. After the ballooning procedure is completed, second wire168can be withdrawn from proximal end (not shown) of medical device200. Alternatively, second wire168is tracked through medical device200and positioned in-vivo. FIG.16A,FIG.16B, andFIG.16C, illustrate adapter104which is similar to adapter103. Adapter104includes distal portion174which includes third outside profile126of outer body179. Second wire125includes first end232which is coupled or attached to outer body179at top or edge233of third outside profile126. Second wire125extends proximally from outer body179and distal portion174along the outside of medical device200and extends to second end (not shown) of second wire125. Second end (not shown) of second wire125can terminate within the artery or body vessel in a loop or fold to minimize any chance of incidental vessel trauma, or extend all the way proximally exiting the patient. As shown in transverse cross section view Z-Z of third outside profile126, there is no cavity in third outside portion126for first wire167. First wire167alternatively extends distally alongside third outside profile126. The size of first outside profile185, second outside profile184, and third outside portion126generally increase in size from first outside profile185to third outside profile126. However, third outside profile126has a reduced size portion165which is approximately equal in size to second outside profile184. This can be advantageous in that there would be room for second wire125to fold back and extend distally as medical device200and adapter104is withdrawn from the artery and patient. FIG.17A,FIG.17B, andFIG.17Cillustrate adapter105which is similar to adapter101. Adapter105includes distal portion175. Distal portion175has outer body179that is typically made from a soft polymer or elastomeric polymer. Distal portion175incorporates first tube element188that forms a portion of first lumen189in outer body179. First lumen189exits outer body179distally at distal tip181. First lumen189is formed partially by first tube element188and outer body179. First lumen189exits outer body179proximally at exit253which is proximal to distal exit254of second lumen191from outer body179. Second lumen191is formed partially by second tube element190and outer body179. As shown in section Y-Y, second lumen191transitions from a closed section as it exits outer body179. Tube element188and tube element190are side by side and overlap for length251within outer body179. First lumens189and second lumen191overlap for length255. An alternate embodiment of distal portion175includes first lumen189formed entirely by outer body179without tube element188. Distal portion179also includes a hole or passage252into cavity178close to distal end234of cavity178. Hole252can be beneficial to facilitate flushing air out of cavity178prior to use. Hole252can also provide an additional conduit to deliver fluids or contrast through lumen211of medical device200. FIG.18A,FIG.18B,FIG.18C,FIG.18D,FIG.18E, andFIG.18Fillustrate alternate embodiments of coil257of proximal portion113of an adapter105of the present invention. Coil257has a variable diameter and pitch. Similar to the other coil embodiments, coil257has a proximal diameter (ø) øE151and a larger diameter (ø) øF152at distal end270of coil257. Coil257transitions in diameter from øE151to øF152. Coil257is bonded or otherwise attached to central tube263that forms a portion of a central lumen271similar to central tube182over a length G258. The unbonded distal portion, Length H1272, of coil257includes a portion at a diameter øE151, a portion at diameter øF152and a portion where the diameter transitions between those two diameters. The unbonded distal portion, Length H1272, of coil257is shown with a variable pitch that are not close wrapped, but could include close wrapped pitch. A close wrapped pitch in the unbonded distal portion272at the smaller diameter and in the transition to the larger diameter can be advantageous as there can be less axial movement of central tube263under an axial load after the adapter105is attached to a target medical device200.FIG.18Billustrates coil257of proximal portion113of an adapter105after adapter105has been inserted and seated into medical device200with lumen211as previously described. As coil257is inserted, the unbonded distal portion elongates to a length H2259, such that a portion of coil257forms an angle A127as previously described. Proximal portion113also includes proximal end120and is comprised of inner element122that forms a funnel and outer element256. Outer element256is similar to outer element121and could be radiopaque or partially radiopaque to provide a landmark for the proximal end of the adapter in-vivo, but is shorter and doesn't fully cover inner element122, and is longitudinally shorter in length than inner element122. FIG.18Cshows an embodiment of proximal portion113and coil257such that after inserting and seating into a target device200as described and the central tube263is placed under an axial load F261, the unbonded distal portion, Length H3260, of coil257becomes shorter than the length H2259prior to the axial load F261. Additionally, a portion of the unbonded coil wraps that formed unbonded distal portion length H2compress together axially under the axial load F261and touch each other, effectively completing the wedge formed by angle A127, as illustrated in the enlarged detail viewFIG.18E. FIG.18Dshows yet another embodiment of the proximal portion113and coil257such that after inserting and seating into medical device200as described and the central tube263is placed under an axial load F261, the unbonded distal portion, Length H4262, of coil257becomes shorter than the length H2259prior to the axial load F261. Additionally, a portion of the unbonded coil wraps that formed unbonded distal portion length H2259compress together axially under the axial load F261and touch each other as well as nest inside or invaginate, effectively completing the wedge formed by angle A127, as illustrated in the enlarged detail viewFIG.18F. Nested coil wraps as illustrated inFIG.18DandFIG.18Fmay be advantageous as it may increase the securement of the adapter. It could be envisioned that multiple coils similar to coil257could be bonded to a central tube263in series to create proximal portion113. Proximal portion113of this design can increase the robustness of the securement of the adapter to medical device200. A multiple coil configuration of this nature can include both left and right hand coils as previously described to minimize a bias or potential securement issue when central tube263is place under a torsional load. FIG.19illustrates an embodiment of proximal portion114of an adapter that includes a coil264similar to coil257. Coil264includes all the elements of coil257plus a section of unbonded length J265that transitions from a larger diameter øF152to a smaller diameter that is preferentially smaller than the diameter of the inner lumen211of medical device200, similar to a diameter øE151. A coil design of this nature can be advantageous as it allows proximal portion114to be removed from medical device200. Proximal portion114can be removed by a user gripping a coil wrap in length J265and pulling distally elongating and or rotating coil264, releasing the wedge securement at the inside diameter of lumen211of target device200. For example, if a proximal portion114were coupled to a distal portion similar to102to form an adapter, and a portion of length J265of coil264extended into cavity178after proximal portion114were inserted and seated into medical device200, similar to length D135as shown inFIG.13D, effectively extending out the distal end213of medical device200, the user could cut distal portion102at a point along cavity178, effectively separating distal portion102from proximal portion114such that the user can grip and pull distally a coil wrap in length J265, removing proximal portion114from medical device200. It is understood that a length of wire153or an extension of wire153extending out of medical device200is gripped to remove proximal portion114. FIG.20AandFIG.20Bshow proximal portion115with coil266that is similar to coil130. Coil266includes a transition267that varies in diameter and pitch. Coil266also includes a length K268at a diameter øB138that is predominately a wider spaced pitch and a variable pitch transition to a diameter øD139. A design similar to this may have an advantage in securement when inserted into medical device200as described for coil130. It is understood that coils constructed similar to coil130and coil266can alternatively be inserted into medical device200, similarly to coil257, and still provide securement after insertion. FIG.21AandFIG.21Billustrate an alternate embodiment of a distal portion176of adapter106. Adapter106includes distal portion176. Adapter106has been inserted into medical device200. Distal portion176includes first lumen273, outer body179, and second tube element190forming a portion of second lumen191of adapter106. First lumen273exits outer body179proximally at exit253which is proximal to distal exit254of second lumen191from outer body179. Outer body179includes taper portion274to proximally interface and engage with surface212of distal inner lumen211of medical device200. Taper portion274interfaces and engages with medical device200and can reduce the overall size or profile of adapter106. Distal portion176includes reinforcing coil275which spans transition portion276between medical device200and distal portion176. Reinforcing coil275can reduce the chance of the medical device200or adapter106kinking at or near transition276. Reinforcing coil275is smaller in size or diameter than inner lumen211and is partially attached to outer body179and distal portion176. Distal portion176also includes distal tip181. When attached to a medical device200, the first lumen273can be used as a guide for a first guidewire, while the second lumen191can be used to introduce a second guidewire or other accessory into the patient. For example, an accessory with drill bit like features or characteristics that could be used to penetrate the cap of a completely occluded lesion may be advantageous. FIG.22A,FIG.22B,FIG.22C, andFIG.23illustrate adapter107. Adapter107includes distal portion277, which is similar to distal portion176as shown inFIG.21A, but includes an embedded or incorporated camera module280in outer body179and a proximal portion117. Outer body179is typically made from a polymer or elastomeric polymer. Outer body179includes a portion with a diameter a286that is less than the diameter of inner lumen211such that a portion of the outer body179can fit within inner lumen211. Adapter107includes central tube281that forms central lumen282, similar to tube190and lumen191shown inFIG.21A. Central tube281connects distal portion277and proximal portion117of adapter107. Proximal portion117is similar to the previously described proximal portions and includes a coil283, similar to coil257previously described with reference toFIG.8A. Central tube281includes one or more conductors284embedded in wall285of central tube281, for illustration purposes a portion of central tube281is shown with the conductors exposed. For example, conductors284could be embedded in Polyimide or Polyimide and PEBAX to form central tube281. Conductors284can also run longitudinal along the X axis of central tube281instead of spiraling as shown. In one embodiment six (6) conductors are shown embedded in wall285of central tube281and spiral around the x axis of central tube281connecting camera module280to connector289near proximal end287of central tube281. It will be appreciated that the numbers of conductors can include those required to supply power to camera module280and send signals from camera module280and could be more or less than six. As illustrated inFIG.23, proximal end287of central tube281and adapter107extend out proximal end292of target medical device200. It is common for a proximal end of a medical device to terminate with a luer fitting. As shown, connector289has six (6) pads293that individually connect to six (6) conductors284that spiral along central tube281. Connector289can be designed such that a cable (not shown) with the appropriate mating connectors can couple camera module280to an appropriate viewing device or device that can interpret the electrical signals and interface with camera module280. The diameter øC290of connector289must be smaller than the lumen of the target medical device200. Also shown is proximal end291of adapter107. Proximal end291is designed to potentially interface with a syringe for flushing of liquids through the central lumen282and allow access of guidewires or other devices and equipment through the central lumen282as shown inFIGS.22A and22B. Camera module280incorporates elements that allow visualization both distally through distal viewing port279and in the proximal direction through proximal viewing port278. In a similar manner as the described with regard to camera module280and adapter107, electrically activated element294could be embedded, incorporated or attached to distal portion277of adapter107. Electrically activated elements can be, for example, sensors or transducers. Connector289and conductors284electrically connect distal portion277of adapter107to the outside of the patient, proximal to the medical device, or parent200. For example, electrically activated element294can be one or more electrically activated elements including a sensor or transducer. For example, electrically activated element294can be an IntraVascular UltraSound (IVUS) sensor/transducer, Optical Coherence Tomography (OCT) sensor/transducer, pressure transducer, flow transducer, or other imaging or sensor technology could be attached and electrically coupled to a suitable interface device as described. FIGS.24,25A,25B,25C, and25Dillustrate adapter108. Adapter108includes distal portion310and proximal portion118. Adapter108includes central tube315that is co-axial with inside tube322where inside tube322forms central lumen326as shown inFIG.25B, similar to tube190and lumen191as shown inFIG.21A. Referring toFIG.24, central tube315connects distal portion310and proximal portion118of adapter108. Proximal portion118is similar to the previously described proximal portions and includes coil313, similar to coils previously described, bonded, coupled or otherwise attached to central tube315. Distal portion310of adapter108includes balloon assembly311. Balloon assembly311includes balloon312coupled to central tube315and inside tube322through polymer body316at proximal end320of balloon312and polymer tip330at distal end181of adapter108. Polymer body316extends proximally from balloon312and includes channel317that runs longitudinally along the length of polymer body316. Polymer body316, balloon312, and central tube315are coupled, bonded or otherwise attached together to create sealed balloon assembly311at proximal end320. Distal end339of balloon312is similarly coupled, bonded or otherwise attached to inside tube322through distal tip330. In this embodiment, central tube315terminates proximally to inside tube322, and end337of central tube315can be plugged by seal element329. Seal element329being bonded, coupled or attached to outside surface of inside tube322. Seal element329could also be unitary with proximal end338of polymer body316, for plugging end337of central tube315. In an alternate embodiment, central tube315can extend to distal end of balloon312such that distal tip330also plugs and seals end337of central tube315. In this alternate embodiment, polymer body could extend distally and be unitary or joined with distal tip330. Space327between outside surface351of inside tube322and inside surface352of central tube315is a conduit to pressurize balloon312. Space327can form a lumen. Space327runs between balloon312and connector assembly314. Water, saline or other fluid/gas can be injected into space327at connector assembly314to pressurize balloon312through opening328in central tube315and polymer body316. In an alternate embodiment, polymer body316is optional or terminates proximal to opening328in central tube315which allows the pressurizing media into balloon312. Connector assembly314near proximal end of the adapter108is comprised of outer member323with a distal end325and a proximal end324. Inside tube322runs coaxial to outer member323and along the entire length of outer member323. Distal end325and proximal end324seal the ends of outer member323. Inside tube322is shown terminating distal to the proximal edge344of proximal end324. Alternately, inside tube322can extend to or beyond proximal edge344of proximal end324. Space327to inject the pressurizing media into balloon312connects to space345between outside surface of inside tube322and inside surface of outer member323. Opening318in outer member323allows the pressurizing media to be injected into space345, which is connected to space327, which is in turn connected to inside of balloon312, allowing balloon312to be inflated. Space345can be a lumen. In one embodiment, outer member323of connector assembly is metallic, such as stainless steel, where distal end325and proximal end324are polymers. Alternatively, outer member323and ends324and325could be of unitary construction, for example made of a polymer such as PEEK. The cross-sectional view illustrates central axis347of adapter108. FIG.26illustrates adapter108after adapter108has been attached to target medical device200that has central lumen211. For the purposes of illustration,FIG.26illustrates adapter108attached to balloon catheter201of medical device200. Balloon catheter201is comprised of balloon214, tubular member218that makes up the bulk length of balloon catheter201, and fitting assembly215. Fitting assembly215includes port216that connects to central lumen211in tubular member218, and port217that connects an inflation lumen (not shown) in tubular member218to balloon214. Fitting assembly215can be composed of a plastic or polymer with ports217and216terminated with a luer fitting for connection to a syringe or inflation device.FIG.26shows adapter108attached to balloon catheter201such that there is gap321between distal end319of balloon catheter201and proximal end320of balloon312. In this illustration, polymer body316with channel317extends from balloon312into distal end319of central lumen211of balloon catheter201, spanning the gap321. Channel317is connected to central lumen211, which is connected to port216. Adapter108extends all the way through balloon catheter201such that opening318of connector assembly314is beyond proximal end219of balloon catheter port216. FIGS.27,28A and28Billustrate adapter108attached to balloon catheter201as shown inFIG.26, along with fitting340coupled to port216and fitting331coupled to connector assembly314. Fitting340includes port341to couple to port216of fitting assembly215(Y-fitting) of balloon catheter201. In one embodiment, port341can be a male luer fitting that is compatible with female luer fitting216. Fitting340also includes sealing mechanisms343at proximal end342of fitting340. Sealing mechanism343can be a Tuohy borst valve or hemostasis valve, O-ring, or other seal. Fitting340also includes a side port such that fluids can be introduced to the space (lumen)346between the outside surface of central tube315and lumen211. Fitting340can be available valve assemblies, such as a standard Hemostasis valve with locking seal described in U.S. Pat. No. 5,591,137. Fitting331includes side port333with distal sealing mechanism336and proximal sealing mechanism335on either side of side port333. Sealing mechanisms335and336seal on outer member323, effectively isolating opening318. Once opening318is isolated, side port333can be used to pressurize the balloon312via opening318, space345, space327and opening328. Sealing mechanisms335and336can be O-rings, hemostasis valves, Tuohy borst valves or other seals. Fitting331also includes end port332that connects to lumen326of inside tube322. As shown, fitting331is an assembly of two (2) seals, end port332, side port333, and end cap334to hold seal336in place. Fitting331in one embodiment can be manufactured from three (3) molded plastic components bonded, coupled or joined together holding sealing mechanism336and335in place. Adapter108effectively partitions lumen211of medical device200, shown as balloon catheter201into three lumens,346,326, and327. Sealing mechanism343of fitting340is shown sealing around central tube315. Alternatively, sealing mechanism343can seal around outer member323of connector assembly314. FIGS.29A,29B,29C,29D,29E and29Fillustrate an adapter360prior to being attached to balloon catheter201.FIG.29Aillustrates adapter360which includes a plurality of slender elements364that extend proximally from the outer body363of the distal portion361past the proximal end120of proximal portion362of adapter360. Slender elements364obscure some of the elements of adapter360. Accordingly, for clarity,FIG.29Bshows a view wherein the slender elements364are omitted, and illustrates the obscured elements not shown or visible inFIG.29A.FIG.29Bshows the proximal portion362which includes a right handed coil370, similar to coil257previously described with reference toFIG.18A, and a left handed coil371also similar to coil257previously described with reference toFIG.18A. Coils370and371are bonded or attached to central tube365. Adapter360includes central tube365that forms central lumen366, similar to tube190and lumen191shown inFIG.21A. Outer body363is typically made from a polymer or elastomeric polymer, but may be manufactured from metallic elements or include metallic elements, such as a stainless steel braid, nitinol coil or similar material. Outer body363includes a portion372with a diameter that is less than the diameter of inner lumen211of medical device201such that a portion of the outer body179can fit within inner lumen211. Proximal portion362also includes a proximal end120. Distal portion361also includes a distal tip181. Slender elements364may be fibers or wires manufactured from metals such as stainless steel or Nitinol, or manufactured from a polymer such as PEEK or PVDF or other suitable material. Slender elements364may be a single constituent or a composite structure. As non-limiting examples, the slender elements364may include features or characteristics that improve scoring of the target artery or lesion, may include texture or features such as a reservoir for delivering a therapeutic agent, or may include receptors for gathering tissue, cells or other molecules for diagnostic purposes. FIGS.29D,29E and29Fillustrate the cross section of adapter360to better illustrate the slender elements364and the central tube365, with coil370omitted for clarity. The cross section views show an example of thirty (30) individual slender elements364attached to outer body363and that traverse past the proximal portion362of adapter360. Slender elements364are shown in a circular pattern368and unconnected to each other except at the outer body363of the distal portion361and in the spiral bond portion369. In the spiral bond portion369, the side by side slender elements364may be welded, fused, bonded, glued or attached in a spiral configuration as shown, or other suitable organized configuration. As shown in cross section X-X ofFIG.29E, at any given cross section in the spiral bond portion369, three (3) of the side by side slender elements364are bonded together by a bonding element367. Bonding element367can be a composed of a different material than the slender element364or the same material as the slender element364as in a welded or fused junction or joint. The spiral bond portion369is shown progressing twice around and with a constant pitch. The spiral bond portion369could include a plurality of turns and a variable or constant pitch. Adapter360could also include a plurality of spiral bond portions369. The cross section of the slender elements364are shown circular but could also be other shapes, for example a triangular shape may be advantageous when scoring a lesion or artery. Additionally, the slender elements364may form a circular pattern368as shown or a non-circular pattern, and any number of slender elements364may be bonded together to form a suitably stable arrangement facilitating the joining of the adapter360with a balloon catheter201, as illustrated inFIGS.30A,30B and30Cfor example. FIGS.30A,30B and30Cillustrate adapter360attached to balloon catheter201. As shown inFIG.30A, the balloon214is not inflated, which would be the case while medical device200and adapter360would be tracked to and from the inflation site by the user. The parent module or medical device module, such as the balloon catheter201, is a physically separate module from the adapter360, and only the adapter360is physically integrated with slender elements364through attachment to outer body363of adapter360as described previously. When the parent module is attached to the adapter360of an adapter module, at least a portion of the parent module will reside inside and underneath a circumference defined by the slender elements364, and such that slender elements364are presented on the outside of the assembled parent and adapter360module. In an example where the parent module or medical device module is a balloon catheter201, once connected to adapter360, the balloon214is placed underneath or inside a circumference defined by the slender elements364, and while an inner lumen211of balloon214will be coupled to adapter360such as via coils370,371or other mechanisms as described previously, the balloon's outer surface will not be physically joined or otherwise directly integrated with the slender elements364, though the elements may or may not be in physical contact or communication with the outer surface when the balloon214is in a deflated state. This enables, as shown inFIGS.30B and30C, the slender elements364to flexibly and freely separate and space apart from each other equidistantly around the outer surface of balloon214when it is inflated, through the action of the outer surface of balloon214radially pushing against the slender elements364equally in all directions. In another example, depending on the number and positioning of the slender elements364, one or more of the slender elements364may flexibly but unevenly distribute around the outer surface of balloon214when it is inflated. Either configuration may have utility depending on the type of tissue scoring or cutting desired. FIGS.31A,31B,31C,31D, and31Eillustrate an adapter380prior to being attached to balloon catheter201. Adapter380is similar to adapter360which includes distal portion381, similar to distal portion361, and proximal portion362(obscured/not shown) which is the same proximal portion of adapter360. As shown inFIGS.31A and31B, adapter380includes a plurality of slender elements382that extend proximally from the outer body363of the distal portion381past the proximal end120of proximal portion362of adapter380. Slender elements382obscure some of the elements of adapter380, and in this example comprise a rectangular cross-sectional geometry as opposed to the circular geometry of slender elements364. For example, this rectangular cross-sectional geometry may further facilitate the cutting or scoring of target tissue. It may be appreciated that other cross-sectional geometries, including triangular, etc. are possible. As shown in the orthographic views ofFIGS.31A,31B and31Cand cross sections V-V and W-W ofFIGS.31D and31E, slender elements382are attached to each other by a plurality of bonding elements367. As shown inFIGS.31D and31E, the slender elements382are attached to each other by bonding elements367in a bond pattern384around the adapter380. As shown inFIGS.31A,31B, and31C, a bond pattern384of bonding elements367connecting or attaching slender elements382around the adapter380occurs at different points along the length of the adapter380. As shown, the bond pattern384alternates along the length of the adapter380which encourages the slender elements382to remain approximately evenly disposed around the balloon as the balloon is inflated, i.e. not gathered on one side of the balloon, similar to as shown inFIG.30C. As shown inFIGS.31A and31B, the slender elements382extend proximally from the outer body363in lengths that create a gradual reduction in the number of slender elements382extending proximally. Two pairs of orthogonal slender elements382extend completely proximal, such that they would extend out of the patient body. As shown, a slender element382extension stops at a bonding element367. This eliminates free proximal edges of the slender elements382, which could inhibit withdrawing the target medical device catheter201and attached adapter380from the patient body. In the illustrative embodiment ofFIGS.31A,31B,31C,31D, and31E, there are shown an example of sixteen (16) slender elements382disposed around the central tube365of the adapter380. As shown inFIG.31E, every other slender element382is attached to a neighboring slender element382by a bonding element367, for a total of eight (8) bond joints for a full complement of slender elements to create a bond pattern384. The longitudinally adjacent bond pattern384of bonding elements367, or bond joints, have an alternating pattern of side by side slender element382connections or bonds via bonding element367around the adapter380. In the longitudinal position along the adapter as depicted inFIG.31D, Section V-V, there is shown an example of eight (8) slender elements382attached in pairs by four (4) bonding elements367. However, any suitable number of bonds is envisioned to optimize the functionality of adapter380with a balloon catheter201such that slender elements382are sufficiently stable and organized during use. In alternate embodiments, the slender elements360,382could be replaced by a mesh structure or weave/braid of fibers. The described slender element360,382bonding element367configuration could include varied bond patterns384organized along the length of the adapter380. It is to be understood that the above-described embodiments are illustrative of only a few of the many possible specific embodiments, which can represent applications of the principles of the invention. Numerous and varied other arrangements can be readily devised in accordance with these principles by those skilled in the art without departing from the spirit and scope of the invention. For example, the nitinol coil structure could be replaced by a braided wire structure as it could readily change size by elongating to facilitate insertion into medical device200. A braided wire structure can be manufactured from nitinol and have similar thermal-mechanical properties as the nitinol coil or can be made from a more traditional alloy, such as stainless steel and be designed to collapse to a smaller diameter as it is inserted or prior to insertion into medical device200. A braid structure could be designed to have a similar wedge geometry when inserted into the lumen of a target catheter. Further, instead of the user reducing the size of the nitinol coil or similar, the adapter can be manufactured and delivered to the customer pre-constrained in that shape and ready to be inserted into the target catheter or device. This would remove some of the burden from the user and possibly make it easier to use. The coil could also be a more traditional alloy without shape memory or superelastic thermal-mechanical properties such as stainless steel. The coil could be manufactured from a polymer such as PEEK or polyimide. The coil itself could be coated with a polymer. Additionally, for configurations where the nitinol coil is coupled to the distal portion of adapter, the tube could be optional. Although the distal portion of the adapter described herein is generally shown to be a similar size as the target catheter or device, this is not required, but may be desired. Similarly, the distal portion of the adapter can be smaller than the inner lumen of the target medical device or parent and be inserted completely within the parent device, not extending distally from the target medical device or parent at all. If a second lumen or central lumen is not required, the elongated element that the proximal portion of coil structure is attached to could be solid as in a wire or mandrel instead of a tube. The tube, wire or mandrel could extend proximally all the way out the proximal end of the target catheter or device. Further, the outer body of the distal portion could have multiple and varied profiles. Lumens exiting outer body of the distal portion could be at varied angles instead of 180 degrees opposite each other, including on the same side of the outer body of the distal portion. | 71,225 |
11857737 | DETAILED DESCRIPTION OF THE INVENTION The foregoing and other features and advantages of the invention will become more apparent from the following detailed description of exemplary embodiments, read in conjunction with the accompanying drawings. The detailed description and drawings are merely illustrative of the invention rather than limiting, the scope of the invention being defined by the appended claims and equivalents thereof. Certain terminology is used in the following description for convenience only and is not limiting. Unless specifically set forth herein, the terms “a”, “an” and “the” are not limited to one element but instead should be read as meaning “at least one”. The words “right”, “left”, “lower” and “upper” designate directions in the drawings to which reference is made. The words “inwardly” or “distally” and “outwardly” or “proximally” refer to directions toward and away from, respectively, the patient's body, or the geometric center of the preferred occlusion balloon catheter and related parts thereof. The words, “anterior”, “posterior”, “superior,” “inferior”, “lateral” and related words and/or phrases designate preferred positions, directions and/or orientations in the human body to which reference is made and are not meant to be limiting. The terminology includes the above-listed words, derivatives thereof and words of similar import. It should also be understood that the terms “about,” “approximately,” “generally,” “substantially” and like terms, used herein when referring to a dimension or characteristic of a component of the invention, indicate that the described dimension/characteristic is not a strict boundary or parameter and does not exclude minor variations therefrom that are functionally the same or similar, as would be understood by one having ordinary skill in the art. At a minimum, such references that include a numerical parameter would include variations that, using mathematical and industrial principles accepted in the art (e.g., rounding, measurement or other systematic errors, manufacturing tolerances, etc.), would not vary the least significant digit. While the invention has been described in connection with various embodiments, it will be understood that the invention is capable of further modifications. This application is intended to cover any variations, uses or adaptations of the invention following, in general, the principles of the invention, and including such departures from the present disclosure as, within the known and customary practice within the art to which the invention pertains. Certain terminology is used in the following description for convenience only and is not limiting. The words “lower,” “bottom,” “upper” and “top” designate directions in the drawings to which reference is made. The words “inwardly,” “outwardly,” “upwardly” and “downwardly” refer to directions toward and away from, respectively, the geometric center of the vascular occlusion catheter system, and designated parts thereof, in accordance with the present disclosure. Unless specifically set forth herein, the terms “a,” “an” and “the” are not limited to one element, but instead should be read as meaning “at least one.” The terminology includes the words noted above, derivatives thereof and words of similar import. It should also be understood that the terms “about,” “approximately,” “generally,” “substantially” and like terms, used herein when referring to a dimension or characteristic of a component of the invention, indicate that the described dimension/characteristic is not a strict boundary or parameter and does not exclude minor variations therefrom that are functionally similar. At a minimum, such references that include a numerical parameter would include variations that, using mathematical and industrial principles accepted in the art (e.g., rounding, measurement or other systematic errors, manufacturing tolerances, etc.), would not vary the least significant digit. Vascular Occlusion Systems Furthermore, while the invention is described as a balloon catheter occlusion system, it will be understood that the described variants of the preferred balloon catheter system may be used clinically for a variety of different therapeutic or diagnostic indications involving vascular interventions, including, for example and without limitation, arterial occlusion, angioplasty, stent delivery, atherectomy, drug delivery, imaging or the like. In accordance with an exemplary and preferred embodiment, the preferred balloon catheter system is well suited for use as an arterial occlusion balloon catheter, and in particular an aortic occlusion balloon catheter. Applications making advantageous use of embodiments of the invention may use any suitable access site for vascular intervention. For example, applications of the catheter system may involve access at the femoral artery, the brachial artery, the subclavian artery, or any other blood vessel suitable for use as an access site for catheterization, including venous vessels. Moreover, it will be understood that while a balloon is referred to herein as an example of occlusion member, other types of occlusion members are contemplated as being expressly within the scope of the present invention. In addition to balloons, the occlusion members may include stents, coils, grafts, sheaths, cages, plugs, supported or unsupported membranes, or the like. The occlusion member, including the occlusion balloons, may be fabricated of biocompatible polymer or biocompatible metal, or combinations thereof, and may be woven or non-woven in structure. Biocompatible metals include, but are not limited to, stainless steel, titanium, nitinol, cobalt, vanadium, aluminum, nickel, tantalum, zirconium, chromium, silver, gold, silicon, magnesium, niobium, scandium, platinum, cobalt, palladium, manganese, molybdenum and alloys thereof, such as cobalt-chromium-molybdenum or zirconium-titanium-tantalum alloys. The metals and/or the polymers may be elastic, shape memory or superelastic. More recent advanced materials may also be used, including carbon fibers, carbon nanotubes or carbon composites, such as carbon/polyetheretherketone (PEEK). In the present application, when the term “balloon” is used it is intended to mean a fluid Tillable member capable of expanding from a first smaller diameter to a second larger diameter under the influence of fluid introduced into the balloon. Unless otherwise stated, a balloon is not limited in size, shape, geometry, material or construction. When used in this application, the term “occlusion member” is intended to be inclusive of balloons and other structures, including stents, coils, grafts, sheaths, cages, plugs or supported or unsupported membranes. In one aspect of the invention, a pressure relief apparatus for a balloon catheter is provided. The balloon catheter includes a shaft having a balloon attached to the distal end of the shaft, an inflation/deflation lumen for inflating and deflating the balloon and a pressure relief port. The pressure relief port may alternatively be formed through the wall of the inflation/deflation lumen, through the wall of the proximal hub, or may be part of the fluid pathway that couples to the proximal hub. A pressure relief member is secured either across or within the pressure relief port to form a fluid tight seal. The fluid tight seal is configured to open or fail (e.g. open, burst, rupture, tear or leak) at a predetermined pressure to release pressure from the inflation/deflation lumen through the pressure relief port. The predetermined pressure may be less than or equal to the rated burst pressure of the balloon. In one variation, the pressure relief port comprises a first outwardly opening passage and a second passage in fluid communication with the first passage. The second passage extends inwardly from the first passage and opens into the inflation/deflation lumen. In this variation, the cross-sectional area of the first passage may be larger than the cross-sectional area of the second passage. In one embodiment, a wall extends radially between an inside end of the first passage of the pressure relief port and an outside end of the second passage of the pressure relief port. The pressure relief member may be disposed adjacent the wall and across the outside end of the second passage of the pressure relief port to block the pressure relief port and form a fluid tight seal. The pressure relief member may be a plastic film, a thin metallic film, a pop-off valve or other similar biased valve. The bias of the pressure relief member is less than or equal to a predetermined pressure known to protect the device from overpressure and burst and to protect the patent from injury. In another aspect, a pressure relief apparatus for a balloon catheter having a balloon with a rated burst pressure includes a proximal hub adapted for connection to a proximal end portion of a balloon catheter shaft wherein a pressure relief port is formed in the proximal hub. In one embodiment, the proximal hub may comprise a plastic body that defines an inflation/deflation lumen and a may or may not include guide wire lumen or a working lumen. The proximal hub may be formed from a substantially rigid material and includes a wall defining the inflation/deflation lumen for directing a fluid into and from an inflation/deflation lumen of the catheter shaft. In this alternative embodiment, the proximal hub includes a pressure relief port formed through the wall of the hub and a pressure relief member disposed across or in the pressure relief port, forming a fluid tight seal across the pressure relief port. The pressure relief member is configured to open or fail, (e.g. open, rupture, tear, burst or leak), at a predetermined pressure to release pressure from the inflation/deflation lumen through the pressure relief port. In the case of an occlusion balloon, it is preferable that the balloon be of a compliant or partially compliant balloon material and typically formed relatively distensible plastic or polymer material. The balloons may also be constructed of substantially compliant or partially compliant polymeric, biocompatible materials, such as PBAX or other related polymers. The balloon may alternatively be constructed of a non-compliant material, which will typically expand less than about ten percent (10%), and more typically less than about five percent (5%), when pressurized from their rated operating pressure to the balloon's rated burst pressure. Where an occlusion balloon is the occlusion member, the proximal and distal ends of the balloon may be attached to the catheter shaft using techniques known in the art, for example, with an adhesive such as a medical grade epoxy adhesive or may be reflowed to become an integral part of the catheter shaft wall. In the following description, when reference is made to the terms “proximal” or “proximally” it is intended to mean a portion or component of the preferred vascular occlusion catheter system that is oriented away from the body into which the system is or is intended to be placed. Conversely, when reference is made to the terms “distal” or “distally” it is intended to mean a portion or component of the preferred balloon catheter system that is oriented toward the body into which the system is or is intended to be placed. Thus, for example, the guiding atraumatic tip described hereinafter is located at a distal end of the balloon catheter system, while the proximal hub is located at a proximal end of the balloon catheter system. As shown in the accompanying figures, the vascular occlusion catheter system100generally includes a catheter assembly having a first catheter member130having a first lumen230, a second catheter member110having a second lumen210, a third catheter member120having a third lumen220, an occlusion member140, a proximal hub190and a guiding atraumatic tip150. The first lumen230of the first catheter member130extends longitudinally through the first catheter member and is coupled at its proximal end to the proximal hub190and at its distal end to a proximal section of the third catheter member120and in communication with the third lumen220of the third catheter member. The second lumen210of the second catheter member110also extends longitudinally through the second catheter member110, and terminates in a first port160distal to a proximal end of and within a space142at least partially bounded by the occlusion member140, best seen inFIGS.9and9A. Where the occlusion member140is a balloon, the second lumen210is in communication with the space142bounded by the balloon140and conveys inflation fluid to and from the balloon140from a source external to the balloon catheter system100. The third catheter member120is coupled at a proximal end thereof to a distal end of the first catheter member130such that the third lumen220of the third catheter member120is in communication with the first lumen230of the first catheter member130. As best seen inFIG.1, the second catheter member110and the third catheter member120are positioned in longitudinal co-axial spaced apart relationship from one and other along a longitudinal axis131of the first catheter member130thereby defining an intermediate region115of the first catheter member130within the space142that is not covered by either the second catheter member110or the third catheter member120. When a balloon is the occlusion member140, balloon140is attached, at its proximal end144to a distal end of the second catheter member110and at its distal end146to a proximal end of the third catheter member120. Referring toFIGS.2-5, a proximal radio opaque marker158may be affixed to the first catheter member130at or near the first port160, which is near the attachment position of the inflatable balloon at the proximal end144of the balloon140. A distal radio opaque marker159may be affixed to the first catheter member130near the attachment position on the distal end146of the balloon140. The proximal and distal radio opaque markers158,159may be implemented as bands made of a radio opaque material. In one example, the radio opaque material is a metal that is radio opaque such as stainless steel, or an alloy, such as a platinum iridium alloy. In another example, the proximal and distal radio opaque markers158,159may be sections of the catheters that have been impregnated with radio opaque material such as for example stainless steel or a suitable alloy. In another example, the proximal and distal radio opaque markers158,159may be implemented as bands or sections of plastic or a polymer such as PEBAX that has been mixed with barium sulfate. The implementation of the proximal and distal radio opaque markers158,159on the catheter system would aid in visualization of the balloon position within the vasculature using fluoroscopy or x-ray. When a balloon is used as the occlusion member140, in operation, balloon140is inflated by introducing an inflation fluid, such as saline, from an external source, such as a syringe, coupled to the proximal hub190, into and through the second lumen210, out of the first port160and into the space142within the balloon140. As is known in the art, the inflation fluid is introduced until the balloon140is inflated to a desired diameter or a desired fluid pressure of the inflation fluid is achieved, or both. Deflation of the balloon140is simply the reverse process of withdrawing the inflation fluid from the space142of the inflation balloon140. In its deflated or collapsed state, the inflation balloon140will be positioned either within or adjacent to the intermediate region115of the first catheter member130, thereby providing a lower profile to the entire balloon catheter system100. When a fluid is used as the pressure source to activate the occlusion member, such as to fill an occlusion balloon, that fluid may be a liquid, including water, saline, contrast medium or any combination thereof, or may be a gas, including carbon dioxide, helium, air or oxygen. Catheter balloons may be inflated with gas, rather than liquid, because the balloon can be inflated and deflated more quickly than a comparable volume of saline or other liquid inflation media. Although air is relatively easy to load into an inflation device, air is not an ideal inflation medium, because air does not rapidly dissolve in blood. In the event that the balloon bursts or leaks, bubbles could be formed in the arterial blood, impeding blood flow. In addition, as nitrogen is a chief component of air, nitrogen has thrombogenic properties that may present clinical risks in the event the balloon bursts. Accordingly, it is desirable to use a gas other than air and to prevent air contamination of the gas used. A preferable gas used for balloon inflation is either carbon dioxide or helium. As will be described in more detail hereinafter, with exemplary reference toFIGS.19-22, the present invention also includes alternative embodiments of occlusion control systems that regulate the position of the occlusion member140and the apposition of the occlusion member140against a vascular wall surface. It is understood that when the occlusion member140is at least partially in non-apposition with the vascular wall surface, that fluid flow or perfusion pas the occlusion member may or will occur. This fluid flow or perfusion may be of circulatory blood, or may be of fluids introduced through the preferred vascular occlusion catheter system, or through another fluid introduction system, such as a catheter. The third catheter member120is depicted more particularly inFIGS.4-5. The third catheter member120is coupled at its proximal end concentrically about a distal end of the first catheter member130. A plurality of side ports170pass through a side wall of the third catheter member120and provides fluid communication between the third lumen220and external environments proximate the external surface of the third catheter member130, such as the inside of the patient's major vessel when inserted into the patient. The distal end of the first catheter member130is preferably positioned within the third lumen220and does not occlude the plurality of side ports170, but terminates proximal to the plurality of side ports170such that fluid may be freely communicated between the first lumen230, the third lumen220and the plurality of side ports170to either introduce fluid or withdraw fluid through the plurality of side ports170. The plurality of side ports170may also be utilized for power injection of a contrast medium into the major vessel of the patient distally relative to the occlusion member140, as will be described in further detail herein. It will also be understood by those skilled in the art that maintaining fluid communication between the first lumen230, the second lumen220and the plurality of side ports170also permits introduction of tethered sensors, such as flow sensing wires, pressure sensing wires, ischemia sensors or the like to the distal end of the balloon catheter system100. Finally, a guiding atraumatic tip150is coupled to a distal end section of the third catheter member120. The guiding atraumatic tip150may be made of an elastic, shape memory and/or superelastic material, such as a metal or polymer. A reinforcing member152(depicted in phantom) may optionally be included either within the guiding atraumatic tip150or wound about an external surface of the guiding atraumatic tip150to offer additional reinforcement to the tip150. A proximal end of the guiding atraumatic tip150is coupled to a distal end of the third lumen220of the third catheter member120and a distal end of the guiding atraumatic tip150projects distally from the third catheter member120and preferably has a generally circular profile when viewed from the side in a relaxed configuration. The atraumatic tip150preferably curves proximally from the longitudinal axis131upwardly and then back toward the central longitudinal axis131of the balloon catheter system100, but leaves an unconnected end161of the distal end of the guiding atraumatic tip150as it returns to a position proximate the longitudinal axis131. The atraumatic tip150is designed and configured to permit the tip150to assume a linear or delivery configuration co-axial with the central longitudinal axis131of the balloon catheter system100for delivery and introduction into the patient's vessel through a catheter. Once the atraumatic tip150is introduced into the vessel and emerges from the introduction catheter, the atraumatic tip150preferably returns to the relaxed configuration to inhibit introduction of the catheter system100into smaller vessels as it moves into the patient. In the first embodiment of the preferred balloon catheter system100illustrated inFIGS.1-8, the balloon catheter system100, when the inflatable balloon140is in an uninflated condition, is of sufficiently small cross-segmental dimension to pass through a 6 to 8 French (2-2.67 mm)-percutaneous sheath, such as, for example 7 French (2.33 mm). Thus, the balloon catheter system100has a greatest outer diameter, when the inflatable balloon140is uninflated, of less than 2-2.67 mm. It will be understood by those skilled in the art that the balloon catheter system100is not limited to a dimension sufficient to pass through a 2-2.67 mm (6 to 8 French) percutaneous sheath, but that such lower profile or smaller is generally considered desirable to enable passage of a balloon catheter system100through tortuous vasculature and to a desired position within the body for purposes of arterial occlusion. The balloon catheter system100is, therefore, not intended to be limited to this dimensional size, but may be made of smaller or larger dimension as desired or needed. In one embodiment of the invention, the first catheter member130is formed of stainless steel metal and is radio opaque, in accordance with another embodiment of the invention, it is constructed of nitinol and in accordance with still another embodiment of the invention it is formed of biocompatible polymers. The first catheter member130lends columnar strength to the balloon catheter system100and provides a functional backbone for carrying the second catheter member110, the third catheter member120and the inflatable balloon. The outer diameter of the first catheter member130is smaller than the inner diameter of the second lumen210of the second catheter member110, thereby forming an annular space212between the outer surface of the first catheter member130and the inner surface of the second catheter member110, as best shown inFIG.7. In one embodiment of the invention, the distal end of the second catheter member110may have a tapering or narrowing diameter of the outside surface and/or the second lumen210diameter. Preferably, there is a minimal amount of narrowing on the second catheter member110and the proximal lumen210to allow the annular space212to remain sufficiently large down the length of the second catheter member110to permit adequate flow of the inflation fluid through the annular space212. Turning now toFIGS.4-5, the distal portion of the balloon catheter system100is illustrated. The first lumen230of the first catheter member130may be used as a pressure monitoring line, such as by using a fluid column therein to sense pressures through the plurality of side ports170. The first lumen230may alternatively be used to introduce or withdraw fluids, such as drugs, contrast media or blood through the plurality of side ports170. Referring toFIG.5, the outer surface of the first catheter member130is coupled to at least a portion of the inner surface of the distal lumen220, such that there is no annular space between the outer surface of the first catheter member130and the inner surface of the second lumen220. In one embodiment, the portion of the inner surface of the distal lumen220may be the length of the second lumen220. Referring now toFIG.4, the third catheter member120or the proximal shaft of the atraumatic tip150may include a plurality of segments of distally decreasing durometer polymer to provide a step-down transition to the guiding atraumatic tip150. The number of step down durometer segments may be between one (1) and six (6) and may step down in decreasing fashion by regular or irregular increments, such, for example 75D, 63D, 55D, 40D, etc. Alternatively, the third catheter member120may be made of a single durometer polymer, but having distally tapering wall thicknesses to impart a flexibility gradient to the third catheter member120. The plurality of segments of decreasing durometer plastic may be abutted and be bonded together or may be manufactured from a single extrusion including decreasing durometer hardness. Referring now toFIG.5, the guiding atraumatic tip150is shown in its unstrained and undeformed state as it would assume when in the body. The guiding atraumatic tip150is used to minimize trauma to or perforation of the vasculature as the balloon catheter system100is advanced through the patient's tortuous anatomy, and to prevent departure from an intended vessel path, such as diversion into an undesired branch vessel. The size, shape and material of the distal section of the tip150are such that it will not pass into collateral vessels during delivery. The guiding atraumatic tip150has a constrained state when passing through an introducer sheath in which the distal section of the tip150is substantially linear and co-axial with the longitudinal axis131of the balloon catheter system100, and a relaxed state, as depicted, which is assumed upon exiting the introducer sheath and entering a blood vessel. In one embodiment, the guiding atraumatic tip150may be formed of an elastomeric, shape memory or superelastic material, including metals and polymer. In another embodiment, the guiding atraumatic tip150may have a reinforcing elastic, shape memory or superelastic core152which aids in transition between the unstressed state and the stressed state of the guiding atraumatic tip150. In accordance with an exemplary embodiment of the tip150, the outer diameter of the guiding atraumatic tip150(in the relaxed state) may be between 1-7 mm, preferably between 2-6 mm and most preferably between 4-6 mm. Turning now toFIG.6, the proximal portion of the balloon catheter system100is illustrated. The second catheter member110is coupled to the proximal hub190and the distal end of the first catheter member130may be operably coupled to the proximal hub190at a proximal bonding site using an adhesive180to bond an inner wall surface of the proximal hub190to an outer wall surface of the first catheter member130. As illustrated, the proximal hub190has two fluid pathways192and194. A first fluid pathway192communicates with the first lumen230of the first catheter member and a second fluid pathway194communicates with the second lumen210of the second catheter member120. It will be understood that the proximal hub190may be configured to have more than two fluid pathways, with each fluid pathway communicating with a different lumen in the balloon catheter system100. The first fluid pathway192of the proximal hub190may be connected to an external pressure sensor, which would transduce pressure from a fluid column within the first lumen230and through the plurality of side port170(FIG.5). Referring toFIGS.1-5, in the first preferred embodiment, the balloon catheter system or occlusion catheter system100also includes the plurality of side ports170positioned between the occlusion member140and the atraumatic tip150in the third catheter member120, the proximal shaft of the atraumatic tip150and/or the first catheter member130. The plurality of side ports170preferably facilitates power injection of a contrast medium into the patient's major vessel distally relative to the occlusion member140during use. Such power injection may be utilized for procedures such as angiography or arteriography. In the first preferred embodiment, the plurality of side ports170include a first side port170a, a second side port170b, a third side port170c, a fourth side port170d, a fifth side port170eand a sixth side port170f. The plurality of side ports170is not limited to including six (6) side ports170a,170b,170c,170d,170e,170fand the occlusion catheter system100may include more or less side ports170a,170b,170c,170d,170e,170fand the plurality of side ports170may be sized and configured in nearly any manner desired by the designer and/or medical technician for pressure sensing, power injection or other related procedures utilizing the plurality of side ports170. Turning now toFIGS.9and9A-9D, an alternative or second preferred embodiment of the balloon catheter system300is illustrated. The balloon catheter system300includes generally a catheter assembly including a first catheter member310having at least two lumens210,330passing longitudinally through the first catheter member310, a second catheter member320having a single lumen230passing longitudinally through the second catheter member320and an inflatable balloon140. The first catheter member310is coupled at its proximal end to a proximal hub190(not shown) and at a distal end thereof to a proximal end of the inflatable balloon140. The second catheter member320is coupled at its distal end to a proximal end of the first catheter member310such that one of the first lumen210or the second lumen330is in fluid flow communication with the second catheter member320. The other of the first lumen210or the second lumen230terminates at the distal end of the first catheter member310. For purposes of illustration only and for clarity in the following description, it will be assumed that second lumen330terminates at the distal end of the first catheter member310and has a distal port opening160, it will also be assumed that the first lumen210is in fluid flow communication with the second catheter member320. As with the first embodiment of the balloon catheter system100described above, the second embodiment of the balloon catheter system300, when the inflation balloon140is in an uninflated condition, is of a sufficiently small cross-sectional diameter to pass through a 6-8 French (2-2.67 mm)-percutaneous sheath, such as, for example, 7 French (2.33 mm). Thus, the balloon catheter system300has a greatest outer diameter, when the inflatable balloon140is uninflated, that is less than 2-2.67 mm. It will be understood by those skilled in the art that the balloon catheter system100is not limited to a dimension sufficient to pass through a 2-2.67 mm (6 to 8 French) percutaneous sheath, but that such lower profile or smaller is generally considered desirable to enable passage of a balloon catheter system300through tortuous vasculature and to a desired position within the body for purposes of arterial occlusion. The balloon catheter system300is, therefore, not intended to be limited to this dimensional size, but may be made of smaller or larger dimension as desired or needed. Referring now toFIG.9A, the first catheter member310includes first lumen330and a second lumen210. The second catheter member320includes a first lumen220. The first catheter member310terminates at its distal end within the space defined under the balloon140, where it is both coupled to the second catheter member320and terminates with an open port160in fluid communication with lumen330, permitting fluid to be delivered to and from the balloon140for inflation and/or deflation. In accordance with an alternative embodiment, the distal end of the first catheter member310may, optionally, be tapered, such as by narrowing the wall thickness of the catheter member310or by crimping the first catheter member310to a smaller diameter, thereby compressing and reducing the open area of the first lumen330and the second lumen210. If the first catheter member310is crimped to a tapered diameter, it is preferable that the extent of the crimping does not compress the open area of the first lumen330and the second lumen210in a manner that significantly reduces fluid flow there through of fluid flow pressures therein, particularly with the second lumen330when it is used for the inflation fluid for the inflation balloon140. The third catheter member130is positioned within one of the first lumen210or the second lumen330of the first catheter member310. As depicted in the figures, this arrangement is illustrated with the third catheter member130being positioned within the first lumen210of the first catheter member310and also within the first lumen220of the second catheter member320. The outer diameter of the third catheter member130is less than the inner diameter of the first lumen210of the first catheter member310as well as smaller than the inner diameter of the first lumen210of the second catheter member320, such that an annular space212is formed therebetween as depicted inFIG.9C. In the more distal region of the first catheter member310, within the region of the distal taper discussed above, the annular space212is compressed and either closes or is substantially closed to fluid flow, thereby effectively sealing the distal end of the first lumen210near the transition to the proximal attachment point of the inflatable balloon140, as depicted inFIG.9A. The third catheter member130passes longitudinally into the first lumen230of the second catheter member320and has a first lumen230passing longitudinally through the third catheter member130. As with the first catheter member130of the first alternative embodiment described above, the first lumen230of the third catheter member130permits monitoring of conditions within the body, such as arterial pressure monitoring by hydrostatic pressure within a fluid column within the first lumen230, or allows for the introduction of tethered sensors, such as flow sensing wires, pressure sensing wires or the like to the distal end of the balloon catheter system300. First lumen230may also be used to deliver drugs, contrast media, or permit the introduction or withdrawal of fluids to and from the body. As with the alternative embodiment discussed above with reference toFIGS.1-8, the embodiment depicted inFIGS.9-9Dmay, optionally, include the second catheter member320being constructed of plural segments having distally increasing flexibility, such as by making the segments of distally decreasing durometer polymer or fashioning the second catheter member320to have a distally tapering wall thickness. The second catheter member320may be formed of discrete segments abutted and coupled together to form an elongated second catheter member320with either distally decreasing durometer or distally tapering wall thicknesses. Alternatively, the second catheter member320may be made by extrusion or molding polymers of distally decreasing durometer or distally tapering wall thicknesses. As with the alternative embodiment of the balloon catheter system100, the second catheter member320includes an open port170that is in fluid flow communication with the first lumen230of the third catheter member. Similarly, as with the balloon catheter system100, the balloon catheter system300of the second preferred embodiment includes a guiding atraumatic tip (not shown inFIGS.9-9D) as described above with reference to guiding atraumatic tip150of the first preferred embodiment, which is coupled to a distal end of the second catheter member320. With reference toFIGS.10and11, there is depicted an alternative embodiment of the guiding atraumatic tip450. It will be understood that guiding atraumatic tip450may be employed with any of the foregoing embodiments of the preferred balloon catheter system100or of the second preferred balloon catheter system300. The guiding atraumatic tip450is comprised generally of a polymeric cylindrical or tubular member452that has a distal section454that has been formed into a generally flattened cylinder having two generally planar opposing surfaces455,457and two generally curved opposing surfaces458,459. The two generally planar opposing surfaces455,457include an inner planar surface455and an outer planar surface457. The distal section454has a distally extending section453that projects distally and a curved section456continuous with the distally extending section that curves away from the central longitudinal axis131of the balloon catheter system100,300then proximally toward the occlusion balloon140and subtends a generally circular arc toward the central longitudinal axis131of the balloon catheter system100,300. The angle of the curve may be between about one hundred eighty degrees (180°) and three hundred fifty-five degrees (355°), more preferably between about two hundred seventy degrees (270°) and three hundred fifty degrees (350°) and even more preferably between about three hundred degrees (300°) and three hundred fifty degrees (350°) such that a gap is provided between the terminal end of the generally cylindrical flattened distal section454and the more proximal surface of the distal section454. It will also be understood that the distally extending section453and curved section456may be formed as a generally in-plane circular shape or may be formed as an out-of-plane generally helical shape, where a terminal end of the curved section456is laterally displaced from the central longitudinal axis131of the balloon catheter system100or balloon catheter system300. In this manner, the generally flattened distal section454is characterized by a generally circular profile. The atraumatic tip550preferably operates in a manner similar to the guiding atraumatic tips150,350of the previously described preferred embodiments, but is made of a polymer material without the need for a reinforcing member152, as described above. In the preferred embodiment, a tip thickness Ttis defined between the inner planar surface455and the outer planar surface457and tip width Wtis defined between the opposing curved lateral surfaces458,459. The tip width Wtis preferably greater than the tip thickness Ttsuch that the atraumatic tip450is readily flexible about a central tip axis450a. The atraumatic tip450is preferably flexible about the central tip axis450afrom the substantially circular profile in the relaxed configuration to the introduction configuration, wherein the atraumatic tip450is relatively straight or positioned on the longitudinal central axis431. In the preferred embodiment, the tip thickness Ttis less than the tip width Wt. The relatively smaller tip thickness Ttin comparison to the tip width Wtfacilitates the flexing of the atraumatic tip450from the relaxed configuration with the substantially circular profile to the introduction configuration, wherein the atraumatic tip450is substantially straight and is positioned on the longitudinal central axis431and renders bending of the atraumatic tip450laterally more difficult. A tapered transition section451may, optionally, be provided between the polymeric cylindrical or tubular member452and the generally flattened cylindrical distal section454. Guiding atraumatic tip450may be integral with the third catheter member120of balloon catheter system100or the second catheter member320of balloon catheter system300. Alternatively, guiding atraumatic tip450may be fabricated as a discrete member and joined to the third catheter member120of balloon catheter system100or the second catheter member320of balloon catheter system300. The guiding atraumatic tip450, which may be made of polyether block amide (PBAX, Arkema, Paris France) having a durometer of forty (40D), or a similar polymer, such as polyurethane or polyethylene, that is compatible with the catheter shaft and balloon to make bonding easier and more secure. As discussed above, the guiding atraumatic tip450may be either cylindrical or tubular, or have a solid cylindrical section and a tubular section. The curve of the guiding atraumatic tip450may be made by any of a wide number of processes, including, for example, injection molding, round extrusion, flattening and post-processing into the curved distal section456, a flat extrusion bonded to a round extrusion, or an extrusion that is pressed into a hot die having a shape of the desired curved distal section450. The atraumatic tip450may include a radio opaque tip marker460. The radio opaque tip marker460may be implemented as a band surrounding the tip450or as a two-dimensional planar material on one or both of the planar opposing surfaces455. Alternatively, the radio opaque tip marker460may be located at the most distal point of the atraumatic tip450indicated at460′ inFIG.11. The band or the planar material may be composed of any suitable radio opaque material, such as for example, stainless steel or a suitable alloy such as platinum iridium. In another example embodiment, the tip450may be made of a plastic or polymer, such as for example, PEBAX that is impregnated with a radio opaque material. In another example embodiment, the plastic or polymer composition forming the tip450may be mixed with a radio opaque compound such as for example barium sulfate sufficient to permit visualization of the tip450using x-ray or fluoroscopy. In an alternative embodiment described herein with reference toFIGS.12-18, a balloon catheter system500generally includes a catheter assembly having a stiffener member530, which is preferably comprised of a solid wire, an inflation catheter member510having an inflation lumen610, a distal catheter member520, an inflatable balloon540, a proximal hub590and a guiding atraumatic tip550. The stiffener member530is secured to the proximal hub590and extends longitudinally through the inflation catheter member510along the longitudinal axis531of the stiffener member530, which substantially comprises the longitudinal axis531of the catheter system500. The stiffener member530includes a proximal end530b, a distal end530cand defines the longitudinal axis531. The stiffener member530is coupled at the proximal end530bto the proximal hub590and at the distal end530cto a proximal section of the distal catheter member520. The proximal hub590includes an inflation connection port590awith an inflation fluid pathway594therein. The inflation lumen610of the inflation catheter member510is in fluid communication with the inflation fluid pathway594and extends longitudinally through the inflation catheter member510. The inflation lumen610preferably terminates at a first port560distal to a proximal balloon end544of and within a space542defined by the inflatable balloon540, such that the inflation lumen610is in fluid flow communication with the space542within the inflatable balloon540to convey an inflation fluid to and from the inflatable balloon540from a source external the balloon catheter system500that is preferably connected to the inflation connection port590a. The distal catheter member520is coupled at a proximal end thereof to a distal end of the stiffener member530. The inflation catheter member510and the distal catheter member520are positioned in longitudinal co-axial spaced apart relationship from one and other along a longitudinal axis531of the stiffener member530, thereby defining an intermediate region530aof the stiffener member530within the space542within the inflatable balloon540that is not covered by either the inflation catheter member510or the distal catheter member520. In this preferred embodiment of the balloon catheter system500, when the occlusion balloon540is in an uninflated condition, the catheter system500is of sufficiently small cross-segmental dimension to pass through a five to six (5-6) French (1.67-2 mm) percutaneous sheath, such as, for example six (6) French (2 mm) introduction sheath. Thus, the balloon catheter system500has a greatest outer diameter, when the occlusion balloon540is uninflated, of less than 1.67-2 mm. The balloon catheter system500of the preferred embodiment ofFIGS.12-18preferably has a smaller greatest outer diameter when the occlusion balloon540is uninflated than the above-described preferred catheter system100because of the solid stiffener member530, which replaces the first catheter130with the first lumen230therein. It will be understood by those skilled in the art that the balloon catheter system500is not limited to a dimension sufficient to pass through a five to six (5-6) French percutaneous sheath, but that such lower profile or smaller maximum diameter when the occlusion balloon540is uninflated is generally considered desirable to enable passage of a balloon catheter system500through tortuous vasculature and to a desired position within the body for purposes of arterial occlusion. In addition, the reduced maximum diameter limits the size of the percutaneous introduction puncture in the patient's skin and may limit the clinical requirements for the medical professionals performing the procedure. The balloon catheter system500is, therefore, not intended to be limited to this dimensional size, but may be made of smaller or larger dimension as desired or needed. In general, the alternative embodiment described herein with reference toFIGS.12-18includes the stiffener member530, preferably the solid wire, instead of a tube with a lumen. The solid stiffener member530may be implemented as a solid flexible wire made of any suitable material that may be formed into a wire-like component. Examples of materials that may be used include polymeric materials, biocompatible metals, nitinol and stainless steel. The stiffener member530of this preferred embodiment may be constructed of a solid nitinol hypotube. The nitinol hypotube stiffener member530provides flexibility and sufficient stiffness along the longitudinal axis531and is generally a small diameter tube or wire. The stiffener member530implementation without a lumen removes the fluid communication with a third lumen. The stiffener member530does, however, allow for the implementation of a catheter system having a lower profile than the first embodiment of the catheter system100. In the alternative embodiment ofFIGS.12-18, the catheter system500preferably includes a pressure sensor533mounted distally of the occlusion balloon540or on a surface of the occlusion balloon540proximate its distal balloon end546. The pressure sensor533preferably communicates with a processor501that may be wired to the pressure sensor533or may receive pressure readings from the pressure sensor533through wireless communication techniques. In the preferred embodiment, the pressure sensor533is wired to and in communication with the processor501by an electrical wire533athat carries pressure signals from the pressure sensor533to the processor501. The electrical wire533aof the preferred embodiment extends at least partially through the inflation lumen610and is in electrical contact with the pressure sensor533and the processor501. The preferred pressure sensor533is mounted to an external surface of the distal catheter member520to sample and detect pressures at the distal side of the inflatable balloon540. For example, the pressure sensor533may sample pressure near the distal balloon end546of the inflatable balloon540during use and transmit the pressure readings to the processor501for review by an operator, medical technician or physician. The pressure sensor533may also be utilized to provide pressure measurements at predetermined intervals to the processor501. The processor501may adjust the inflation of the occlusion balloon540to permit limited flow through the vessel to the distal balloon end546of the occlusion balloon540. The processor501may be controlled to maintain a range of pressures at the distal balloon end546or a minimum pressure based on inflation and deflation of the occlusion balloon540. Referring toFIGS.12-18, the inflatable balloon540is attached at its proximal balloon end544to a distal end of the inflation catheter member510and at its distal balloon end546to a proximal end of the distal catheter member520. In operation, the inflatable balloon540is inflated by introducing an inflation fluid, such as saline, from an external source, such as a syringe, coupled to the proximal hub590, into and through the inflation lumen610, out of the first port560and into the space542within the inflatable balloon540. Inflation and deflation of the inflatable balloon540inFIGS.1-8is performed as described above with reference toFIGS.1-8. Referring toFIGS.15and16, the distal catheter member520is fixedly coupled at its proximal end concentrically about a distal end of the stiffener member or solid wire530. In the preferred example shown inFIG.16, the distal catheter member520has a lumen620extending longitudinally through the distal catheter member520and coupled concentrically about a proximal end of the atraumatic tip550. The distal catheter member520is not limited to including the lumen620and may be configured as substantially solid between its proximal and distal end or integrally formed with or fixed to the atraumatic tip550. The guiding atraumatic tip550may be constructed of an elastic, shape memory and/or superelastic material, such as a metal or polymer. A reinforcing member552(depicted in phantom) may optionally be included either within the guiding atraumatic tip550or wound about an external surface of the guiding atraumatic tip550to offer additional reinforcement to the tip550. The guiding atraumatic tip550projects distally from the distal catheter member520and preferably has a generally flattened configuration, curving proximally and then toward the central longitudinal axis531of the balloon catheter system500, but leaving a unconnected end561at the distal end of the guiding atraumatic tip550. The atraumatic tip550is preferably designed and configured such that the atraumatic tip550is able to unfold from a relaxed configuration (FIG.16) and assume a linear configuration co-axial with the central longitudinal axis531of the balloon catheter system500for delivery. During introduction, the atraumatic tip550is preferably straightened along the longitudinal axis531in an introduction configuration such that the atraumatic tip may be positioned within a catheter for introduction and returns to the substantially circular-shape in the relaxed configuration when the atraumatic tip550emerges from the catheter in the patient's vessel. Specifically, the atraumatic tip550preferably has sufficient flexibility such that the substantially circular curve of the atraumatic tip550, in the relaxed configuration, may be straightened coaxially with the longitudinal axis531for introduction of the catheter system500into the patient's vessel through an introduction catheter. The atraumatic tip550of the preferred embodiment has a smaller thickness between the inner and outer planar surfaces555,557than the lateral outer opposing surfaces558,559of the atraumatic tip550. This flattened shape of the atraumatic tip550facilitates the folding or flexing of the atraumatic tip along the longitudinal axis531. The shape and configuration of the preferred atraumatic tip550preferably limits bending and folding of the atraumatic tip550laterally relative to the longitudinal axis531. In addition, the relatively flattened atraumatic tip550provides manufacturing advantages when the atraumatic tip is constructed of a polymeric material compared to the substantially cylindrical atraumatic tip150shown in the first preferred embodiment. In the preferred embodiment, the lateral outer surfaces558,559are substantially arcuate, but are not so limited and may be relatively planar or otherwise configured. In the preferred embodiment, a tip thickness Ttis defined between the inner planar surface555and the outer planar surface557and tip width Wtis defined between the opposing curved lateral surfaces558,559. The tip width Wtis preferably greater than the tip thickness Ttsuch that the atraumatic tip550is readily flexible about a central tip axis550a. The atraumatic tip550is preferably flexible about the central tip axis550afrom the substantially circular profile in the relaxed configuration to the introduction configuration, wherein the atraumatic tip550is relatively straight or positioned on the longitudinal central axis531. In the preferred embodiment, the tip thickness Ttis less than the tip width Wt. The relatively smaller tip thickness Ttin comparison to the tip width Wtfacilitates the flexing of the atraumatic tip550from the relaxed configuration with the substantially circular profile to the introduction configuration, wherein the atraumatic tip550is substantially straight and is positioned on the longitudinal central axis431and renders bending of the atraumatic tip550laterally more difficult. The atraumatic tip550of the alternative preferred embodiment of the catheter system500is preferably configured and functions similar to the above-described atraumatic tip450of the preferred embodiment ofFIGS.10and11. The atraumatic tip550is preferably formed into the generally flattened frusta-cylinder having the two generally planar opposing inner and outer surfaces555,557and two generally curved opposing lateral surfaces558,559. The atraumatic tip550has a distally extending section553that projects distally and a curved section556continuous with the distally extending section553that curves away from the central longitudinal axis531of the balloon catheter system500then proximally toward the occlusion balloon540and subtends a generally circular arc toward the central longitudinal axis531of the balloon catheter system500. In the relaxed configuration, the atraumatic tip550preferably has a substantially circular profile when viewed from the side, but is not so limited and may have nearly any sized and shaped profile that limits introduction of the atraumatic tip550into an alternative or smaller vessel path than desired by the physician or medical professional. The angle of the curvature may be between about one hundred eighty degrees (180°) and three hundred fifty-five degrees (355°), more preferably between about two hundred seventy degrees (270°) and three hundred fifty degrees (350°) and even more preferably between about three hundred degrees (300°) and three hundred fifty degrees (350°) such that a gap561ais provided between the unconnected end561of the generally cylindrical flattened distal section554and the more proximal surface of the distal section554. The generally flattened section554provides manufacturing and functional advantage when compared to a cylindrical atraumatic tip, such as the atraumatic tip150described inFIGS.4and5. The flattened atraumatic tip550of this alternative preferred embodiment permits flexibility of the atraumatic tip550about a plane or axis extending substantially laterally through the atraumatic tip550, generally perpendicular to the longitudinal axis531to accommodate straightening of the atraumatic tip550coaxially with the longitudinal axis531for introduction. In addition, the greater lateral thickness of the atraumatic tip550laterally relative to the longitudinal axis531provides stiffness to the atraumatic tip550such that the tip550is more difficult to bend or flex out of its preferred shape laterally relative to the longitudinal axis531during placement of the balloon540and movement of the catheter system550through the major vessels of the patient. A tapered transition section551is preferably provided between a substantially cylindrical portion of the distal catheter member520and the generally flattened distal section554. The preferred guiding atraumatic tip550is integral with the distal catheter member520of balloon catheter system500. Alternatively, the guiding atraumatic tip550may be fabricated as a discrete member and joined to the distal catheter member520of balloon catheter system500. The guiding atraumatic tip550is preferably constructed of a polyether block amide (PBAX, Arkema, Paris France) having a durometer of forty (40D), or a similar polymer, such as polyurethane or polyethylene, that is compatible with the distal catheter member520and the balloon540to make bonding easier and more secure. As discussed above, the guiding atraumatic tip550may be generally flattened, cylindrical or tubular, or have a solid cylindrical section and a tubular section. The curve of the guiding atraumatic tip550may be made by any of a wide number of processes, including, for example, injection molding, round extrusion, flattening and post-processing into the curved distal section556, a flat extrusion bonded to a round extrusion, or an extrusion that is pressed into a hot die having a shape of the desired curved distal section550. The atraumatic tip550may include a radio opaque tip marker560aat the unconnected end561. The radio opaque tip marker560amay be implemented as a band surrounding the tip or unconnected end561or as a two-dimensional planar material on one or both of the planar opposing surfaces555,557. The radio opaque marker560amay be constructed of any suitable radio opaque material, such as for example, stainless steel or a suitable alloy such as platinum iridium. In another example embodiment, the tip550may be constructed of a plastic or polymer, such as for example, PEBAX that is impregnated with a radio opaque material to define the radio opaque tip marker560a. In another example embodiment, the plastic or polymer composition forming the atraumatic tip550may be mixed with a radio opaque compound such as for example barium sulfate sufficient to permit visualization of the tip550using x-ray or fluoroscopy to define the radio opaque tip marker560a. As noted above in the description of the first preferred embodiment of the balloon catheter system100illustrated inFIGS.1-8, the balloon catheter system100, when the inflatable balloon140is in an uninflated condition, is of sufficiently small cross-segmental dimension to pass through a 6 to 8 French (2-2.67 mm) percutaneous sheath, such as, for example, 7 French (2.33 mm). Thus, the balloon catheter system100has a greatest outer diameter, when the inflatable balloon140is uninflated, of less than 2-2.67 mm. It will be understood by those skilled in the art that example implementations of the alternative embodiment of the balloon catheter system500described herein with reference toFIGS.12-18may have an even smaller cross-sectional dimension due to the use of the stiffener member or solid wire530instead of a catheter with a lumen. The diameter of the stiffener member530is smaller than the inner diameter of the inflation lumen610of the inflation catheter member510, thereby forming an annular space612between the outer surface of the solid stiffener member530and the inner surface of the inflation catheter member510. The dimensions of the inner diameter of the inflation lumen610and the diameter of the stiffener member530may be specified in example implementations to provide optimal inflation fluid flow as well as a reduced profile that may further ease deployment. Turning now toFIGS.14-16, the distal portion of the balloon catheter system500is illustrated. As shown inFIG.16, the outer surface of the stiffener member530is coupled to at least a portion of the inner surface of the second lumen620, such that there is no annular space between the outer surface of the stiffener member530and the inner surface of the second lumen620. Referring now toFIG.15, the distal catheter member520may include a plurality of segments of distally decreasing durometer polymer to provide a step-down transition to the guiding atraumatic tip150. The number of step down durometer segments may be between one (1) and six (6) and may step down in decreasing fashion by regular or irregular increments, such, for example 75D, 63D, 55D, 40D, etc. Alternatively, the distal catheter member520may be made of a single durometer polymer, but having distally tapering wall thicknesses to impart a flexibility gradient to the third catheter member520. The plurality of segments of decreasing durometer plastic may be abutted and be bonded together or may be manufactured from a single extrusion including decreasing durometer hardness. In an alternative embodiment, the stiffener member530may extend completely into the space shown for the second lumen620such that the distal catheter member520completely covers the distal end of the stiffener member530. The atraumatic tip550may by formed as an extension of the second catheter body520. Turning now toFIG.17, the proximal portion of the balloon catheter system500is illustrated. The inflation catheter member510is coupled to the proximal hub590and the proximal end of the stiffener member or solid wire530is fixedly coupled to the proximal hub590at a proximal bonding site, preferably using an adhesive580, to bond an inner wall surface of the proximal hub590to an outer wall surface of the solid stiffener member530. The amount of adhesive580used is preferably sufficient to fixedly couple the solid stiffener member530to the proximal hub590. As shown inFIG.17, the adhesive580may fill the entire portion592of the proximal hub590that holds the stiffener member530. The proximal end of the stiffener member530is not limited to being adhesively bonded to the proximal hub590and may be otherwise fastened, secured or fixed to the proximal hub590, as long as the stiffener member530is substantially secured to the proximal hub590such that the stiffener member530provides stiffness for the balloon catheter system500, the stiffener member530is substantially secured relative to the inflation catheter member510and the occlusion balloon540, the assembly is able to withstand the normal operating conditions of the catheter system500and securement results in a structure able to perform the preferred functions of the catheter system500, as is described herein. Since the solid stiffener member530has no lumen, no fluid pathway is needed in the portion592that holds the stiffener member530and the stiffener member530can have a relatively small diameter, thereby reducing the overall diameter of the catheter system500. As illustrated, the proximal hub590has an inflation fluid pathway594. The inflation fluid pathway594communicates with the inflation lumen610of the inflation catheter member520. In this alternative preferred embodiment, the inflation lumen610is defined between the outer surface of the stiffener member530and an inner surface of the inflation catheter member510. It will be understood that the proximal hub590may be configured to have more than the inflation fluid pathway594, with each fluid pathway communicating with a different one of any additional lumens in the balloon catheter system500. It will be understood that when reference is made to coupling two or more component sections, members or pieces of the balloon catheter system, that conventional catheter material bonding modalities are intended to be encompassed and employed. For example, a wide variety of biocompatible adhesives useful in catheter manufacture are known, similarly, thermobonding techniques used in catheter manufacture are also known. Thus, for example, where it is described that the guiding atraumatic tip is coupled to the third catheter member or to the distal catheter member, it is contemplated that such coupling may be made using thermobonding, biocompatible adhesives or other methods of fixedly bonding two components in medical devices. It will also be understood by those skilled in the art that it is well known to manufacture catheters of a variety of medical grade, biocompatible polymers, such as, for example and without limitation, silicone, nylon, polyurethane, PETE, latex, thermoplastic elastomers, polyether block amides (PBAX, Arkema, Paris, France). Alternatively, it is known to manufacture catheters of metals, such as nitinol or stainless steel. Similarly, it is known to manufacture catheters of metal-reinforced polymer, such as, for example and without limitation, stainless steel braiding over polyurethane, stainless steel helical windings over silicone or nitinol reinforced polymer. Thus, any or all of the first catheter member, the second catheter member, the inflation catheter member, the distal catheter member, or the third catheter member in any of the foregoing embodiments may be fabricated of biocompatible polymers, biocompatible metals or metal-reinforced polymers, as is known in the art. It will also be understood by those skilled in the art that while the implementation of radio opaque markers are described in the context of embodiments described with reference toFIGS.1-8, it may be desirable to include radio opaque marker bands positioned at the proximal and distal ends of the balloon in implementations of embodiments described above with reference toFIGS.9-11, and embodiments described above with reference toFIGS.12-18. It is also desirable to include length markers on the outer catheter shaft to indicate to the physician the insertion depth of the balloon catheter system100, the balloon catheter system300, or the balloon catheter system500. The length markers may be printed or laser etched onto the outside of the catheter shaft. In each of the foregoing described embodiments of the vascular occlusion systems depicted inFIGS.1-18, the catheter may also include sensors, transmitters, receivers, interrogators or other means for measuring physical and/or physiological parameters distal and/or proximal one or more of the expandable occlusion members, including, for example blood pressure sensors, heart rate sensors, flow sensors, chemical sensors, temperature sensors, oxygenation sensors, biological sensors, imaging sensors or the like. The preferred catheters, sheaths, guide wires, balloons or other occlusion members, or other components that are introduced into the vasculature may be coated with a variety of coatings, including without limitation, antibacterial, antimicrobial, lubricants, anticoagulant and/or antifouling coatings. Thus, any or all components of any of the preferred systems described herein may further include one or more biocompatible coatings. Occlusion Control System Control over the apposition of the occlusion member against the vessel walls is preferably accomplished by controlling the inflation of the preferred balloons, selection of the size of the occlusion member, placement of the occlusion member or other methods and techniques that provide control to users of the preferred systems. Aortic occlusion may result in arterial hypertension upstream of an occlusion site as pressure builds against the occlusion member. If the arterial pressure reaches a deleterious hypertensive state, vascular rupture, stroke or other undesirable events may occur that could potentially injure the patient. Conversely, after the vascular occlusion is complete and blood flow is restored, there is a potential for concomitant drop in arterial blood pressure potentially leading to a hypotensive event that could result in a dangerously low blood pressure and, in extreme cases, cardiac arrest. The preferred control systems are not limited to their utility with the preferred vascular occlusion catheter systems100,300,500of the present invention, but may be used virtually with any type of vascular occlusion system. Thus, inFIG.19, there is shown a generic type of vascular occlusion system700, while inFIGS.20-22, the vascular occlusion catheter system is generically shown schematically and is designated by box710, to denote a non-specific vascular occlusion catheter system, including, for all ofFIGS.19-22, without limitation, the first, second and third preferred vascular occlusion catheter systems100,300,500described above. Other vascular occlusion catheter systems that rely upon a pressure being applied to an occlusion member to urge the occlusion member into apposition with a vascular wall, thereby at least partially occluding the blood vessel are expressly included within the scope of occlusion control system of the present invention, such as the additional occlusion/perfusion systems described herein. In each of the preferred embodiments of the occlusion control systems, the pressure sources are denominated schematically by a generic box or oval to denote that a wide variety of pressure sources are intended to be included within the preferred embodiments of the invention. The pressure source may be a syringe or syringe-like inflation device, an endoflator device, a pump or other similar means of applying a pressure to the occlusion member in the vascular occlusion catheter710. As noted above, when a fluid is used as the pressure medium to activate the occlusion member, such as to fill an occlusion balloon, that fluid may be a liquid, including water, saline, contrast medium or any combination thereof, or may be a gas, including carbon dioxide, helium, air or oxygen. The fluid source may, in the instance of a liquid, be a liquid reservoir, a pre-measured volume of liquid in a vessel that is removably engageable with the pressure source or other similar container for holding and dispensing liquid from the fluid source to the pressure source. In the instance of a gas, the fluid source may be a gas reservoir or a pre-measured volume of pressurized gas in a canister that is removably engagement with the pressure source to deliver the pre-measured volume of gas to the pressure source. A canister with a pre-measured gas volume at a known pressure is also contemplated, for example, a carbon dioxide cartridges that are commercially available in a wide variety of mass of pressurized gas, including without limitation eight, twelve, sixteen, twenty-five or thirty-three grams (8 g, 12 g, 16 g, 25 g, 33 g). Converting mass to volume of a gas at standard temperature and pressure (STP) typically entails resolving the gas constant equation, as follows: V=nRT/P wherein V is volume, n is mass, R is the molar volume of the gas, T is temperature (Kelvin) and P is pressure (atm). The volume of gas needed to inflate a specific occlusion member to a given inflation volume and inflation pressure may be calculated utilizing this preferred formula. Referring toFIG.19, a first embodiment of the occlusion control system700includes a vascular occlusion catheter711has a proximal hub790that includes at least one pressure line port794. The pressure line port794communicates with a pressure conduit or lumen712in the vascular occlusion catheter711. The pressure conduit712may be a lumen within the vascular occlusion catheter711or may be a tubular conduit placed within a lumen in the vascular occlusion catheter711. A pressure accumulator or reservoir730communicates with the pressure line port794via pressure line732that is, in turn, coupled to a connecting conduit720associated with pressure line port794. An actuator744, such as a fluid pump, is coupled to the pressure accumulator730and to a fluid source (“FS”)742. The actuator744is also operably coupled to a controller or central processing unit (“CPU”)750. The controller750operates as a computer control and may have an interface, not shown, that permits programming of computer control software that monitors and controls activation of the actuator744to regulate pressure in the occlusion member740and to collect data from sensors associated with the occlusion control system700. In accordance the preferred embodiment of occlusion control system700, the occlusion member740has a first pressure Pmax, which is below the failure pressure of the occlusion member740. The pressure accumulator730is preferably pressurized, such as with a fluid, to an accumulator pressure Pa, where the accumulator pressure Pa<Pmax, and where the accumulator pressure Pa is less than a predetermined maximum safe blood pressure Pbp within the vascular system being occluded, such that Pa<Pbp<Pmax. When the occlusion member740is in apposition with the vascular wall and the vessel is substantially occluded, the pressure exerted at the occlusion member740may be considered the apposition pressure Papp, wherein the apposition pressure Papp is substantially equal to the pressure in the accumulator730or the accumulator pressure Pa. In this preferred embodiment, when during occlusion the blood pressure Pbp against the occlusion member740exceeds the apposition pressure Papp, the accumulator pressure Pa in the accumulator730and in the occlusion member740is exceeded and the occlusion member740may yield to the blood pressure Pbp and release apposition against the vascular wall surface and allow fluid flow past the occlusion site. Since the apposition pressure Papp within the occlusion member740and the accumulator pressure Pa within the accumulator730is preferably a closed system, the pressure in the accumulator730, such as the accumulator pressure Pa, will rise and when blood pressure reduces to be less than the accumulator pressure Pa in the accumulator730and the apposition pressure Papp within the occlusion member740, the occlusion member740will preferably reestablish occlusion. This effect of automatically adjusting apposition pressure Papp in response to an elevation in blood pressure Pbp, causing a release of apposition against the vascular wall and, therefore, releasing the occlusion and permitting fluid flow past the occlusion site, in turn lowers the blood pressure head against the occlusion member740. When the blood pressure Pbp upstream of the occlusion member740has downwardly adjusted to below the accumulator pressure Pa and the apposition pressure Papp, the occlusion member740, under the influence of the elevated pressure in the accumulator740, reestablishes apposition and, therefore, occlusion is reestablished. This cycle may be likened to “burping” as a pressure release. One further aspect of the occlusion control system700illustrated inFIG.19, is that the preferred computer controller750preferably monitors the accumulator pressure Pa, the blood pressure Pbp and the apposition pressure Papp and, when required, either automatically or after providing audible or visual notification to a medical practitioner and input from the medical practitioner, actuates the actuator744to draw fluid from fluid source742and communicates the drawn fluid to the occlusion member740to increase the apposition pressure Papp. Conversely, where apposition pressure Papp is determined by the computer controller750or by the medical practitioner to be too high, the actuator744may be controlled to withdraw fluid from the occlusion member740, lowering apposition pressure Papp and moving fluid from the occlusion member740to the fluid source742. The occlusion control system700is preferably a bidirectional system capable of increasing the occlusion pressure or apposition pressure Papp or decreasing the occlusion pressure or apposition pressure Papp under either manual control or under control of the computer processor750. Moreover, the preferred occlusion control system700is operable to automatically release the apposition when the blood pressure Pbp impinging on the occlusion member740is above a pre-determined level (typically that regarded as safe for the patient). Accordingly, the occlusion control system700preferably includes a pressure sensor that is able to sense blood pressure on the proximal or distal side of the balloon740to measure the blood pressure Pbp impinging on the occlusion member740and to adjust inflation pressure or apposition pressure Papp of the occlusion member740to at least partially control the blood pressure Pbp in the vessel. An alternative or second preferred embodiment of occlusion control system751is depicted inFIG.20. In alternative or second preferred embodiment of the occlusion control system751, the occlusion catheter710is under control of a pressure source (“I”)752, which in the case of a fluid is coupled to a fluid source (“FS”)751. Similar to the first preferred occlusion control system700, the pressure source752may be under manual control, under automatic control of a computer processor753, or under manual control interfacing with the computer processor753. A pressure conduit754preferably bifurcates into a free line756and a regulated line758. A check valve760is preferably positioned in-line in the regulated line758. An actuable valve762is preferably interposed in both the free line756and the regulated line758, and is operable to select the free line756, the regulated line758or both the free line756and the regulated line758. A fluid conduit766leads from the actuable valve762to the occlusion catheter710. A pressure sensor764may be interposed within fluid conduit766to monitor pressure during operation of the second preferred occlusion control system751and may alternatively be positioned in the occlusion control system751to detect pressure at various locations relative to the system751, such as within an occlusion balloon or at proximal and/or distal ends of the occlusion balloon. The pressure sensor764may be a pressure gauge, electronic pressure sensor or pressure sensor that provides visual signal to the medical practitioner directly or may feed a pressure signal to the computer processor753that controls the occlusion control system751, in turn, upon the pressure signal and/or displays pressure data to the medical practitioner. Referring toFIG.21, there is shown yet another alternative or third preferred embodiment of an occlusion control system800. Unlike the occlusion control system751of the second preferred embodiment, the preferred occlusion control system800preferably has a single pressure conduit communicating between the occlusion catheter710, which is utilized herein as a generic occlusion catheter710, and a pressure source (“I”)752, which, in the case of a fluid, is coupled to a fluid source (“FS”)801. Similar to the occlusion control system700of the first preferred embodiment, the pressure source (“I”)802of the third preferred embodiment may be under manual control, under automatic control of a computer processor803, or under manual control interfacing with the computer processor (“CPU”)803. A pressure conduit804preferably provides fluid communication between the pressure source802and the occlusion catheter710. A check valve806is preferably in-line with the pressure conduit804. The check valve806may be any type of manual or automatically actuatable valves that operate both to prevent back-flow of an inflation fluid and as a pressure relief if there is an overpressure in the occlusion catheter710. A fluid conduit866leads from the check valve806to the occlusion catheter710. A pressure sensor808may be interposed within the fluid conduit804,866to monitor pressure during operation of the occlusion control system800. The pressure sensor808may be a pressure gauge that provides visual signal to the medical practitioner directly or may output a pressure signal to computer control803that controls the occlusion control system800, in turn, upon the pressure signal and/or displays pressure data to the medical practitioner. An additional feature of the occlusion control system800may be the addition of a timer810. The timer810is preferably incorporated into the computer processor803or may be positioned in-line with the fluid conduit804,866. The timer810preferably communicates a time signal to the check valve806, to the computer control803and/or to the pressure source802, as indicated by dashed lines inFIG.21. The time signal may be a regular, consistent signal representative of the timer status, or may be a single time elapse signal that activates the check valve806, the pressure source802and/or the CPU803to withdraw pressure communicated to the occlusion catheter710. Similarly, the timer810may issue a series of time signals according to a pre-programmed routine stored in the CPU803or in the timer810itself, to control cycling of the pressure source802and/or opening and closing cycles of the check valve806. In a fourth preferred embodiment of the occlusion control system820, the pressure source802is again in communication with the occlusion catheter710via a pressure conduit826. An actuable valve828is preferably in-line in the pressure conduit826and operates under the influence of a controller822. The controller822is preferably operably coupled, such as by electrical, mechanical or electromechanical coupling, to both the actuable valve828and to the pressure source802. The controller822may also communicate with a computer control or CPU803. In this preferred embodiment, the actuable valve828is operable under the control of the controller822to open or close to allow pressure from the pressure source802to be applied to the occlusion catheter710or to withdraw pressure from the occlusion catheter710, depending upon the pressure state at the occlusion member740of the preferred occlusion catheter710. Again, similar to the above-described embodiments the pressure source802is operable to increase pressure or decrease pressure applied to the occlusion catheter710, such as by drawing fluid from fluid source801and supplying the fluid to the occlusion catheter710to inflate the occlusion balloon740. In the reverse, the pressure source802is operable to decrease pressure by drawing fluid from the occlusion balloon740, thereby deflating the occlusion balloon740, releasing apposition and occlusion at the vascular wall and permitting perfusion past the occlusion member740when the occlusion member740is positioned in the vessel. Pressure sensors764,808may be positioned external the occlusion catheter710, as shown in the second and third preferred embodiments ofFIGS.20and21, or may be incorporated in the occlusion catheter710itself and be positioned distal the occlusion member740with either an electrical connection at the proximal hub790, may be wireless or may be comprised of pressure sensors positioned both distal and proximate relative to the occlusion member740and external relative to the occlusion catheter710to sense pressure both distal relative to the occlusion member740, proximal the occlusion member740, within the occlusion member740and within the pressure line804,866,826,766proximal the occlusion member740. In each of the foregoing described preferred embodiments of the occlusion control systems700,751,800,820depicted and described with reference toFIGS.19-22, the systems may also include sensors, transmitters, receivers, interrogators or other means for measuring physical and/or physiological parameters distal and/or proximal one or more of the expandable occlusion members, including, for example blood pressure sensors, heart rate sensors, flow sensors, chemical sensors, temperature sensors, oxygenation sensors, ischemia sensors, biological sensors, imaging sensors or the like. Occlusion/Perfusion Systems The preferred occlusion control systems700,751,800,820described above function to control the apposition of the occlusion member140,540,740against the vascular wall of the patient's vessel by regulating the pressure applied to the occlusion member140,540,740. These preferred systems700,751,800,820regulate and mitigate both hypertension and hypotension, by controlling the relative degree of occlusion and perfusion, such as during and after a vascular repair procedure. The occlusion catheter system100,300,500,700, itself, can also be configured to regulate the degree of occlusion and perfusion. Referring toFIGS.23-34, there are provided alternative preferred occlusion balloon geometries that at least partially occlude the vascular lumen of the patient's vessel, thereby permitting at least a partial perfusion flow of blood past the occlusion site, if desired by the physician or medical technician performing a procedure with the preferred systems. A first preferred embodiment of the occlusion/perfusion balloon system1200is depicted inFIGS.23-28A, a second preferred embodiment of the occlusion/perfusion balloon1220is depicted inFIGS.29A and29B, a third preferred embodiment of the occlusion/perfusion balloon1230is depicted inFIGS.30A and30B, a fourth and fifth preferred embodiment of the occlusion/perfusion balloon system1240is depicted inFIGS.31-31B, a sixth preferred embodiment of an occlusion/perfusion balloon system1260is depicted inFIGS.32and32A, a seventh preferred embodiment of the occlusion/perfusion balloon system1270is depicted inFIG.33, an eighth preferred embodiment of the occlusion/perfusion balloon system1280is depicted inFIG.34, a ninth preferred embodiment of the occlusion/perfusion balloon system2000is depicted inFIGS.35A and35Band a tenth preferred embodiment of the occlusion/perfusion balloon system2100is depicted inFIG.35D. Referring toFIGS.23-28A, a balloon1201of the occlusion/perfusion balloon system1200of the first preferred embodiment is fabricated of a substantially compliant biocompatible material, which may be a polymer, metal or composite material. The balloon1201of the occlusion/perfusion balloon system1200may alternatively be constructed of a substantially compliant material such that the balloon has a substantially defined shape in a fully inflated configuration that facilitates at least partial flow of fluid through channels1206a. The term “substantially non-compliant” is intended to mean a compliance range of about zero to fifteen percent (0-15%) of its expanded diameter when inflated to its rated pressure. The balloon1201of the occlusion/perfusion balloon1200is preferably constructed of polymeric balloon materials, including, but not limited to, polyethylene terephthalate (“PET”), nylon, polyethylene, polyether block amides, such as PEBAX, polyurethane and polyvinyl chloride. Highly compliant polymer materials may be made substantially non-compliant by incorporation of composite materials, such as carbon fibers or other substantially non-elastic materials, into or on the polymer material of the preferred balloon1201. Similarly, a compliant balloon material may be constrained by a substantially non-compliant material, including polymer, metal or composite. While the first preferred balloon1201is depicted in the accompanying figures in an elliptical-shape, it may have a different geometric shape than elliptical, including, without limitation, spherical, elliptical, conical, square, rectangular, dog-boned, tapered, stepped, or combinations thereof, such as, for example, conical/square or conical/spherical. The first preferred occlusion/perfusion balloon system1200has a plurality of radially projecting members1204on the balloon1201when the occlusion/perfusion balloon system1200is in a partially-inflated to nearly fully-inflated configuration. The projecting members1204preferably project outwardly relative to a central longitudinal axis1200aof the balloon1201. Landing areas1206and channels1206aare preferably defined between adjacent pairs of the projecting members1204when the balloon1201is partially-inflated to nearly fully-inflated. The balloon1201has a proximal end1208and a distal end1212that engage with and are joined to a proximal catheter member1200band a distal catheter member1200c. The proximal catheter member1200bincludes an inflation lumen1210therein that facilitates inflation of the balloon. The balloon1201may be utilized with any of the preferred occlusion catheter systems100,300,500,700,800,1300,1350described herein by mounting the proximal and distal ends1208,1212to the associated catheters. The first preferred balloon1201defines an open envelope within the balloon1201, which receives an inflation fluid or gas to expand the balloon1201from a collapsed configuration (not shown), wherein the balloon1201is folded to have substantially the same diameter as the proximal and/or distal catheters1200b,1200cfor introduction into a patient's vessel, to its fully expanded state or inflated configuration (FIGS.28and28A). In the inflated configuration, the projecting members1204and landing areas1206are nearly, visually imperceptible from each other, as the balloon1201has a substantially smooth, continuous outer surface shape in the inflated configuration. In contrast, in partially inflated configurations (FIGS.23-27), the projecting members1204and the landing areas1206or channels1206aare visually identifiable with the projecting members1204typically positioned further from the central longitudinal axis1200athan the associated landing areas1206, with the channels1206adefined in the spaces between the projecting members1204. In this first preferred embodiment of the occlusion/perfusion balloon system1200, the channels1206aof the balloon1201permit flow of fluid and blood past the balloon1201, substantially parallel or along the longitudinal axis1200awhen the system1200is inserted into a patient's vessel. The balloon1201of the first preferred occlusion/perfusion system1200may take on numerous shapes, each with channels1206adepending on the level of inflation. For example, in a minimal inflation configuration (FIGS.23-25), the balloon1201has relatively deep and large channels1206ato accommodate relatively significant blood and fluid flow, in a low inflation configuration (FIG.26), the balloon1201has comparatively smaller channels1206a, in a medium inflation configuration (FIG.27), the balloon1201has again comparatively smaller channels1206aand, in a full inflation configuration (FIG.28), the balloon1201does not include perceptible channels, such that the vessel may be completely occluded when the balloon1201is inflated to the fully inflated configuration. The plurality of radially projecting members1204and landing areas1206preferably extend along or substantially parallel to the central longitudinal axis1200aof the balloon1201. The radially projecting members1204may be oriented substantially parallel to the longitudinal axis1200aof the balloon1201or may extend at an angle relative to the longitudinal axis1200aof the balloon system1201. For example, the projecting members1204may spiral in a curved manner along an outside surface1200dof the balloon1201, such that the channels1206aextend in a substantially spiral or arcuate orientation relative to the longitudinal axis1200a. The angular orientation of the projecting members1204and landing areas1206are preferably sufficient to channel blood or fluid flow along the length of the balloon1201within the vessel and to generally not impede flow or contribute substantially to highly disrupted blood flow that may result in thrombose. A preferred angular offset of the projecting members1204and landing areas1206may be between zero and forty-five degrees (0-45°) relative to the longitudinal axis1200athe balloon1201. The radially projecting members1204may have either a generally linearly extending orientation, as is shown in the first preferred embodiment, a curvilinear orientation or nearly any other orientation that permits formation of the landing areas1206between the projecting members1206such that blood and fluid may flow through the landing areas1206when the balloon1201is inserted in the vessel and is at least partially inflated. In the first preferred embodiment, the occlusion/perfusion balloon system1200includes four (4) regularly arrayed radially projecting members1204on or incorporated into the balloon1201. The balloon1201is not limited to including four (4) regularly arrayed radially projecting members1204and associated landing areas1206and the number of radially projecting members1204may be any number greater than two (2) that permit blood and fluid to flow through the landing areas1206when the balloon1201is in one of its partially inflated configuration. In the first preferred embodiment, there is sufficient surface area on the radially projecting members1204to seat in apposition with a vascular wall surface of the patient's vessel and that there is sufficient surface area in the landing areas1206to channel fluid or blood flow along a length of the balloon1201when the balloon1201is in one of its partially inflated configurations, such as the partially inflated configurations ofFIGS.23-27. In the first preferred embodiment of the occlusion/perfusion balloon system1200, each of the plurality of radially projecting members1204has a generally circular or arcuate transverse profile, as depicted inFIG.27, on an upper aspect1205thereof, and a stem portion1207that extends from the landing area1206. The stem portion1207connects with the upper aspect1205of each radially projecting member1204such that the stem portions1207have a smaller stem width than an upper aspect width (SeeFIG.24). In the first preferred embodiment, the projecting members1204each have an apex1218that is preferably located intermediate a length of each radially projecting member1204or centrally between the proximal end1208and distal end1212of the preferred balloon1201. The projecting members1204of the first preferred embodiment also preferably include a proximal, generally flattened or planar area1214and a distal, generally flattened or planar area1216on an outermost surface of each radially projecting member1204relative to the central longitudinal axis1200a. The proximal and distal generally flattened or planar areas1214,1216preferably extend proximally and distally, respectively, from the apexes1218. As will be seen from the series ofFIGS.23-28, representing a sequence of the balloon1201of the first preferred occlusion/perfusion balloon system1200with increasing degrees of inflation, the apex1218forms the outermost equatorial circumference at the longitudinal midpoint of the balloon1201along the longitudinal axis1200a. The proximal and distal generally flattened or planar areas1214,1216facilitate diametric expansion and transition to the preferred fully elliptical-like shape of the fully expanded balloon1201in its full inflation configuration (SeeFIG.28). The first preferred embodiment of the occlusion/perfusion balloon system1200may be constructed by forming the balloon1201of two or more materials having differing hardness or moduli of elasticity. In the first preferred embodiment, as depicted inFIG.28A, the balloon1201may be formed such that the plurality of projecting members1204are made of a higher durometer material, while the landing areas1206are made of a relatively lower durometer material. These materials may be co-extruded or molded to define the preferred balloon1201. In addition, the occlusion/perfusion balloon1201may be alternatively designed and configured with different materials that are able to take on the general size and shape of the occlusion/perfusion balloon1201, particularly the minimal inflation, low inflation, medium inflation and full inflation configurations and related inflation configurations between these configurations shown in the drawings, and withstand the normal operating conditions of the occlusion/perfusion balloon1201. The size, shape and configuration of the plurality of projecting members1204of the first preferred balloon1201is but one exemplary embodiment and may take on other various sizes, shapes and configurations. As described above, the plurality of projecting members1204are preferably an integral part of the balloon1201itself, and form the wall surfaces of the balloon1201. Alternatively, the projecting members1204may be elongate filaments, tubes, cylinders or other members that are either joined to or integrally formed with an outer wall surface of the occlusion/perfusion balloon1201. For example, the projecting members1204may be constructed of a high durometer polytetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP), polyether block amide (PBAX) or other similar biocompatible material, formed in solid or tubular members having a circular, elliptical, quadrilateral, polygonal or other suitable transverse cross-sectional shape. These alternative projecting members1204may also be separately connected to the balloon1201and separately inflatable and deflatable to control the inflation configuration of the occlusion/perfusion balloon1201. The preferred projecting members1204may be configured in nearly any shape, size and configuration such that the occlusion/perfusion balloon1201is able to selectively permit flow of fluid and blood past the projecting members1204, at least in certain inflation configurations, along the longitudinal axis1200a. In addition, the occlusion/perfusion balloon1201may be configured such that the channels1206are comprised of flow channels or holes (not shown) that are surrounded by the material of the occlusion/perfusion balloon1201to permit flow of blood and fluid through or around the occlusion/perfusion balloon1201generally parallel or along the longitudinal axis1200a. Referring toFIGS.29A and29B, an occlusion balloon system1220in accordance with a second preferred embodiment includes a balloon1222with a plurality of projecting members1224projecting from an outer wall surface1223of the balloon1222. The balloon1222is connected to a proximal catheter member1220band a distal catheter member1220c, which may be incorporated into any of the preferred occlusion catheter systems100,300,500,700,1700,1800, described herein. The proximal catheter member1220bincludes an inflation lumen therein that facilitates inflation of the balloon1222. The projecting members1224preferably extend substantially radially away from the outer surface1223of the balloon1222and extend along the outer surface1223substantially longitudinally relative to the longitudinal axis1220a. The preferred projecting members1224preferably extend along an entire length of a substantially tubular section1223aof the balloon1222, which tapers to the proximal and distal catheters1220b,1220cin a substantially funnel-shape at its ends. The outer surface1223of the balloon1222preferably has a constant diameter in the tubular section1223a. The projecting members1224are not limited to extending substantially longitudinally along the entire length of the tubular section1223aand the tubular section1223ais not limited to having a substantially constant diameter and the balloon1222may be otherwise designed and configured such that the balloon1222is able to partially and fully occlude a vessel and withstand the normal operating conditions of the preferred occlusion balloon system1220. The projecting members1224preferably define channels1224abetween the projecting members1224or adjacent the projecting members1224that permit flow of blood and fluid substantially parallel to the longitudinal axis1220awhen the occlusion balloon system1220is positioned within a vessel. The balloon of the system1220may be inflated to various levels to enhance or reduce the channels1224a, depending on the preferred procedure, preferences of the medical technician or conditions encountered or detected within the vessel. Referring toFIGS.30A and30B, an occlusion/perfusion balloon system1230in accordance with a third preferred embodiment includes a balloon1232and a plurality of vanes1234that project from an outer wall surface1233of the balloon1232. In this third preferred embodiment of the occlusion/perfusion balloon system1230, the vanes1234are preferably resilient in nature and are capable of deforming or folding over against an outer wall surface1233of the balloon1232, as depicted by phantom lines1238(FIG.30B), when the balloon1232is in apposition against a vascular wall surface and occluding the vessel or partially occluding the vessel. The vanes1234of the third preferred embodiment also preferably extend substantially radially away from the outer surface1233and extend along the outer surface1233substantially longitudinally relative to the longitudinal axis1230a. The vanes1234preferably extend along an entire length of a substantially tubular section1233a, which tapers to the proximal and distal catheters1230b,1230c. The proximal catheter1230bincludes an inflation lumen therein that facilitates inflation and deflation of the balloon1232. The outer surface1233preferably has a constant diameter in the tubular section1233a. The vanes1234preferably extend to tips1234athat are spaced at a greater distance from the outer surface1233when compared to the similar projecting members1224of the second preferred embodiment. The outer surface1233of the balloon1232preferably has a constant diameter in the tubular section1233a. The projecting members1234are not limited to extending substantially longitudinally along the entire length of the tubular section1233aand the tubular section1233ais not limited to having a substantially constant diameter and the balloon1232may be otherwise designed and configured such that the balloon1232is able to partially and fully occlude a vessel and withstand the normal operating conditions of the preferred occlusion balloon system1220. In this third preferred embodiment of the system1230, the vanes1234preferably define channels1234btherebetween and with the walls of the vessel that permit flow of blood and fluid through the vessel along or substantially parallel to the longitudinal axis1230a. The channels1234bmay be manipulated or controlled by the user or designer by the inflation of the balloon1232, the stiffness of the vanes1234, the height of the vanes1234, the separation of the vanes1234and related other factors that may increase or decrease the size of the channels1234bthat facilitate flow of fluid through the vessel when the balloon1232is inflated. Referring toFIGS.31-31B, fourth and fifth preferred embodiments of the occlusion/perfusion system1240includes a compliant occlusion balloon1242and at least one restraining filament1250connected to proximal and distal catheters1240b,1240cwith the restraining filament1250positioned on an outside of an outer surface1243of the balloon1242. The proximal catheter1240bincludes an inflation lumen therein that carries fluid or gas to and from the balloon1242to facilitate inflation and deflation of the balloon1242, respectively. The restraining filament1250deforms at least one section of the occlusion balloon1242radially inward toward a longitudinal axis1240aof the balloon1242and away from the vascular wall or allows an adjacent portion of the balloon1242to extend further away from the longitudinal axis1240athan the portion proximate the filament1240. The inclusion of the restraining filament1250preferably creates a reverse curvature in the balloon1242and permits fluid to flow past the balloon1242, substantially parallel to the longitudinal axis1240awhen the balloon1242is positioned within the vessel. When a desired time elapses, a desired arterial blood pressure is achieved, or when other indicators suggest, the tension on the restraining filament1250may be released, the reverse curvature will expand and the balloon1242and the balloon1242will return to its occlusion position in apposition with the vessel wall. In the occlusion/perfusion system1240of the fourth preferred embodiment, the catheters1240b,1240cpreferably accommodate the at least one restraining filament1250within the catheter1240b,1240c, such that the filament1250exits the catheter1240b,1240cproximate the balloon1242, overlay the balloon1250along a portion of the length of the balloon1250and is configured to provide tension against the outer surface1243of the balloon1250to define channels or flow paths along the balloon1250, preferably substantially parallel to or along the direction of the longitudinal axis1240a. In order to accommodate this arrangement, the catheter1240b,1240cof the fourth preferred embodiment is provided with a distal port1246passing through the outer wall of the distal catheter1240cand a proximal port1248also passing through the outer wall of the proximal catheter1240b. The restraining filament1250is preferably lead from the proximal end of the proximal catheter1240b, where it is accessible to the medical practitioner for tensioning, is passed through a lumen in the proximal catheter1240b(not shown), exits the proximal port1248, passes over the balloon1242and adjacent the outer surface1243of the balloon1242, and anchor or is attached at the distal port1246to the distal catheter1240c. In this manner, tensioning the at least one filament1250at the proximal end of the proximal catheter1240bpreferably causes the filament1250to tension against the balloon1242or block expansion of the balloon1242proximate the filament1250. When the balloon1242is inflated, the portions of the balloon1242spaced from the filament1250expand away from the longitudinal axis1240a, while the portions of the balloon1242adjacent and beneath the filament1250are blocked from expansion by the filament1250. Accordingly, the outer surface1243of the balloon1242forms or defines channels1254extending substantially parallel to the longitudinal axis1240aor along the length of the filament1250between the expanded portions of the balloon1242between the filament1250that permit fluid flow in the channels1254created between the vessel wall1252(shown in phantom inFIG.31A) and the reverse curve of the outer surface1243of the balloon1242. Referring specifically toFIG.31B, the fifth preferred occlusion/perfusion balloon system1240entails running the at least one restraining filament1250within the interior space or within the material defined by the balloon1242and joining the at least one filament1250to the inner wall surface of the balloon1242. This joining between the at least one restraining filament1250and the inner wall surface of the balloon1242may be accomplished by adhesives, thermobonding or reflowing. Alternatively, one or more lumens may be co-extruded with the inner wall surface of the balloon1242or tubular members joined to the inner wall surface of the balloon1242, and the at least restraining filament1250run within this at least one lumen or tubular member and anchored therein. The balloon1242may alternatively be formed from different materials, with the filament1250being constructed of a stiffer material than the remainder of the balloon1242, such that the portion of the balloon1242with the filament1240therein does not expand at the same rate or to the same extent as the remainder of the balloon1242. In this fifth preferred embodiment, occlusion/perfusion balloon system1240does not necessarily include the proximal port1248and the distal port1246, as the filament1250may be positioned within the catheters1240b,1240cor within a lumen of the catheters1240b,1240c. The filament1250would, therefore, typically not be exposed to the blood vessel or blood flow in such a configuration, as the filament1250would be encased within the balloon1242and the catheters1240b,1240c, where the filament1250would not typically be exposed to fluid and blood flow during use. Referring toFIGS.32and32A, a sixth preferred embodiment of an occlusion/perfusion balloon system1260includes a plurality of balloons1264carried commonly on a catheter1262. The plurality of balloons1264may be incorporated with any of the preferred occlusion catheter systems100,300,500,700,1700,1800, described herein. The plurality of balloons1264are preferably independently expandable though inflation lumens or an inflation lumen1265in the catheter1262. The inflation lumen1265preferably communicates independently with each one of the plurality of balloons1264. The catheter1262preferably includes a seal member1266movably mounted therein and a plurality of openings1268that pass through the outer wall of catheter1262and communicate with the fluid flow lumen1265. The seal member1266is reciprocally movable within the fluid lumen1265and selectively occludes or opens one or more of the plurality of openings1268in the outer wall of the catheter1262, thereby permitting fluid flow through the fluid flow lumen1265and independently or concurrently into each of the plurality of balloons1264. In this manner, the volume and rate of fluid flow into the plurality of occluding balloons1264may be adjusted by the relative position of the seal member1266within the fluid flow lumen1265. Referring toFIGS.33and34, a seventh preferred embodiment of an occlusion/perfusion balloon system1270preferably does not rely upon an occlusion balloon or upon a fluid pressure to activate an occlusion balloon. Rather, in this seventh preferred embodiment, the occlusion member consists of a supporting cage structure1272formed of a plurality of structural members, which may be longitudinally oriented struts1276that taper distally, connect to a distal catheter member1274and taper proximally where the struts1276connect to a proximal catheter member1275. An occluding membrane1278is preferably coupled to the supporting cage structure and may consist of a partial covering on the supporting cage structure1272or may be comprised of a full covering (on the supporting cage structure1272, as illustrated inFIG.34with reference to occlusion/perfusion system1280of the eighth preferred embodiment. The struts of the supporting cage structure1272are preferably, fixedly coupled at their distal ends to the distal catheter member1274and at their proximal end are preferably, fixedly coupled to the proximal catheter sleeve member1275. The proximal catheter sleeve member1275is reciprocally movable relative to the distal catheter1274. The relative movement of the proximal catheter sleeve member1275relative to the distal catheter1274preferably causes deformation of the supporting cage structure1272and allows the cage structure1272to diametrically expand or diametrically contract under the influence of such relative movement. Such diametric expansion preferably brings the supporting cage structure1272and the occluding membrane1278into an occlusive position within the lumen of a blood vessel, while diametric contraction preferably reduces the diametric profile of the supporting cage structure1272and the occluding membrane1278, thereby allowing for fluid and blood flow past the occlusion site or past the cage structure1272. The supporting cage structure1272of the seventh and eighth preferred embodiments, like a balloon, may assume a wide variety of geometries, including, without limitation, spherical, elliptical, conical, square, rectangular, dog boned, tapered, stepped, or combinations thereof, such as, for example, conical/square or conical/spherical. The supporting cage structure1272and its struts1276may be made of any suitable biocompatible material, including polymers, metals and/or composites or combinations thereof. The biocompatible material may be an elastic, superelastic, shape memory material and is preferably able to take on the general size and shape of the cage structure1272, perform the functions of the preferred cage structure1272and withstand the normal operating conditions of the cage structure1272. The occluding membrane1278preferably covers at least a portion of the supporting cage structure1272in order to at least partially occlude the blood vessel into which the occlusion/perfusion systems1270,1280are placed. The occluding membrane1278may cover a proximal portion of the supporting cage1272, a distal portion of the supporting cage1272, the entire cage1272, such as is shown in the eighth preferred embodiment (FIG.34), or it may cover only portions of the cage1272to permit partial or partially occluded flow through the vessel. The supporting cage1272may facilitate pre-conditioning systems that infuse fluid into the vessel to pre-emptively and prophylactically mitigate possible ischemia during occlusion. The catheters1272,1275,1284,1285may include infusion holes1284atherein that facilitate infusion of fluid into the vessel and the infusion holes1284may extend along all or a portion of the longitudinal length of the catheters1272,1275,1284,1285. Furthermore, the occluding membrane1278may have an opening1279in a proximal end to allow fluid flow therethrough to facilitate partial occlusion and perfusion. The occluding membrane1278is preferably constructed of a woven or non-woven biocompatible material, such as polymers, metals, composites and combinations thereof, and may be elastic, superelastic or shape memory. The occluding membrane1278may cover the outer surface of the supporting cage1272, the inner surface of the supporting cage1272, or both. The occluding membrane1278may be joined to the supporting cage1278by sutures, biocompatible adhesive, by reflow, by thermal welding, or by joining to another layer of occluding membrane1278on the opposing surface of the supporting cage1272such that the struts of the supporting cage1278are at least partially encapsulated by the occluding membrane1278. Methods and materials for joining the occluding membrane1278to supporting cage1272may include adhesive bonding, fastening, clamping, co-molding and other related engagement techniques. Referring toFIGS.35A-35C, in a ninth preferred embodiment, an occlusion balloon system2000includes a balloon or inflatable occlusion member2001with a plurality of projecting members2002projecting from an outer wall surface2003of the balloon2001. The balloon2001is connected to a proximal catheter member2004and a distal catheter member2005, which may be incorporated into any of the preferred occlusion catheter systems100,300,500,700,1700,1800, described herein. The proximal catheter member2004includes an inflation lumen therein that facilitates inflation of the balloon2001. The projecting members2002preferably extend substantially radially away from a central longitudinal axis2006of the balloon2001and extend along the outer surface2003substantially laterally or circumferentially around the longitudinal axis2006. The preferred projecting members2002preferably extend around an entire circumference of the balloon2001, but are not so limited and may extend partially around the outer surface2003, may extend at angles relative to the longitudinal axis2006, may be comprised of various pockets on the surface2003or may be otherwise configured to create spacing between a vessel2008and the outer surface2003, at least when the balloon2001is partially inflated. The balloon2001of the ninth preferred embodiment includes four projecting members2002longitudinally spaced along the length of the balloon2001. The end projecting members2002taper in an arcuate shape to connections with the proximal and distal catheters2004,2005. The outer surface2003of the balloon1222preferably has a constant diameter at the peaks of the projecting members2002, but is not so limited and may have tapered or variable spacing relative to the longitudinal axis2006. Lateral channels2007are preferably defined between the projecting members2002when the balloon2001is at least partially inflated and are comprised of circumferentially extending voids wherein the vessel2008is out of contact with the outer surface2003in the channels2007. In contrast, when the balloon2001is fully inflated or is in an inflated configuration, the balloon2001expands such that the outer surface2003is substantially consistent and channels2007are not formed. In this fully inflated configuration or at least close to the fully inflated configuration, the outer surface2003is in direct contact with the vessel2008and fluid and blood flow are substantially occluded in the vessel2008. The projecting members2001defined in at least the partially inflated configuration are not limited to extending substantially laterally or circumferentially around the longitudinal axis2006and the projecting members2002are not limited to having a substantially constant diameter. The balloon2001may be otherwise designed and configured such that the balloon2001is able to partially and fully occlude the vessel2008and withstand the normal operating conditions of the preferred occlusion balloon system2000. The projecting members2002in the partially inflated configuration of the balloon2001preferably permit at least partial flow of blood and fluid substantially parallel to the longitudinal axis2006when the occlusion balloon system2000is positioned within the vessel2008. The balloon2001of the system2000may be inflated to various levels to enhance or reduce the channels2007and the position of the projecting members2002relative to the inner wall of the vessel2008, depending on the preferred procedure, preferences of the medical technician or conditions encountered or detected within the vessel. Generally, as the pressure is increased within the balloon2001, the projecting members2002come into closer positioning relative to the inner surface of the vessel2008and, therefore, limit flow of fluid and blood through the vessel2008. Referring toFIG.35D, in a tenth preferred embodiment, an occlusion/perfusion balloon system2100includes a balloon or inflatable occlusion member2101with a spiral-shape projecting from a longitudinal axis2106of the tenth preferred occlusion/perfusion balloon system2100. The inflatable occlusion/perfusion balloon2101includes channels2107defined between projecting portions2102of the spiral-shaped balloon2010that permit flow of blood past the balloon2101when inserted into the vessel and at least partially inflated. Similar to the ninth preferred occlusion balloon system2000, the tenth preferred occlusion/perfusion balloon system2100may be fully inflated within the vessel and substantially or completely occlude the vessel. The tenth preferred occlusion/perfusion system2100also includes a proximal catheter2104and a distal catheter2105connected to proximal and distal balloon ends of the balloon2101, which may be incorporated into any of the preferred occlusion catheter systems and other preferred systems having inflatable balloons or occlusion members described herein. In each of the foregoing described embodiments of the occlusion/perfusion balloon systems depicted and described with reference toFIGS.23-35C, the systems may also include sensors, transmitters, receivers, interrogators or other means for measuring physical and/or physiological parameters distal and/or proximal one or more of the expandable occlusion members, including, for example blood pressure sensors, heart rate sensors, flow sensors, chemical sensors, temperature sensors, oxygenation sensors, ischemia sensors, biological sensors, imaging sensors or the like. Data collection of the readings from the sensors may be utilized with a controller or processor to control inflation of the balloons or occlusion members of the preferred systems to facilitate partial flow of fluid and blood through the vessel2008when desired or to fully occlude the vessel2008, as desired by the medical technician. Pre-Conditioning Systems Referring toFIGS.36-37C, pharmacologically active agents, such as pressors, anticoagulants, anti-inflammatory agents, anti-hypertensive agents, anti-hypotensive agents, anti-arrhythmic agents, or any other indicated agent may be delivered using a fourth preferred embodiment of and occlusion catheter system1300or a pre-conditioning system1300. Larger volume infusions are also deliverable using the pre-conditioning system or the fourth preferred embodiment of the occlusion catheter system1300, including blood, blood products, extracorporeal membrane oxygenation adjuncts, hypothermia adjuncts, saline, contrast or other therapeutic or diagnostic agents. A four preferred occlusion catheter system or pre-conditioning system1300generally comprises a balloon catheter that has a plurality of proximal side ports1308positioned proximal an occlusion member or balloon1304and a plurality of distal side ports1310positioned distally relative to the occlusion member or balloon1304. The plurality of proximal side ports1308and the plurality of distal ports1310are operable independently of each other to deliver fluids from the forth preferred occlusion catheter system1300to the blood vessel into which the forth preferred system130is introduced. The pre-conditioning system1300, synonymously termed “infusion system,” includes a second catheter member1302that is connected to a proximal hub1301attached to a proximal end of the second catheter member1302. The occlusion member1304is coupled toward a distal end of the second catheter member1302. The occlusion member1304, while depicted inFIG.43as a balloon, may be any type of member capable of vascular occlusion, such as those other embodiments of occlusion members disclosed herein or as are known in the art. The second catheter member1302has a second lumen1303passing along a substantial longitudinal length of the second catheter member1302. The second catheter member1302also has at least one, but preferably the plurality of proximal side ports1308passing through an outer wall of the second catheter member1302. The plurality of proximal side ports1308is preferably in fluid flow communication with the second lumen1303. The plurality proximal side ports1308may be in a regular or irregular pattern and may be positioned about the circumference of the second catheter member1302or may have only a single orientation relative to the central longitudinal axis1331of the infusion catheter system1300. A third catheter member1320of the fourth preferred occlusion catheter system1300extends distally relative to the occlusion member1304and terminates in an atraumatic tip1306or forms a proximal shaft or portion of the atraumatic tip1306. The third catheter member1320has a third lumen1322passing along a substantial longitudinal length of the third catheter member1302, preferably along and coaxially with the longitudinal axis1331near the distal end of the infusion catheter system1300. The atraumatic tip1306is described above in greater detail with reference to the embodiments of the occlusion catheter100,300,500, and serves to guide the catheter system1300as it traverses the vasculature and prevents the fourth preferred catheter system1300from tracking into collateral vessels, while preferably eliminating the need for a guide wire for placement of the occlusion catheter system1300. The occlusion catheter system1300may also incorporate the atraumatic tip450,550of the second the third preferred embodiments of the occlusion catheter system300,500, as is described herein. At least one of and preferably all of the plurality of distal side ports1310pass through the outer wall of the third catheter member1320and communicate with the third lumen1322to communicate fluid distally relative to the occlusion member1304. The plurality of distal side ports1310may be in a regular or irregular pattern and may be positioned about the circumference of the third catheter member1320or may have only a single orientation relative to the central longitudinal axis1331of the infusion catheter system1300. In the fourth preferred embodiment of occlusion catheter system1300where the occlusion member1304is a balloon, three lumens are preferred to service inflation of the occlusion member1304and fluid delivery to or sample collection from both of the plurality of proximal side ports1308and the plurality of distal side ports1308. At least one hypotube or second catheter member1312is disposed within the second lumen1303. Where the second catheter member or hypotube1312is employed, the second catheter member1312preferably has at least a first hypotube lumen1314and a second hypotube lumen1316, with the first hypotube lumen1314configured to communicate an inflation fluid to the occlusion balloon1304and the second hypotube lumen1316configured to communicate fluid to the third catheter member1320and the plurality of distal side ports1310through the third lumen1322, such that the third lumen1322is in fluid communication with the second hypotube lumen1316. The second lumen1303, between the second catheter member1312and the first catheter member1302, preferably communicates fluid from the proximal hub1301to the plurality of proximal side ports1308. The at least one hypotube or second catheter member1312is preferably constructed of a material having different material properties than the first catheter member1302or the third catheter member1320, such that the first lumen1312increases the column strength, pushability and pullability of the occlusion/infusion catheter system1300within the vasculature. In accordance with the fourth preferred embodiment of the occlusion catheter system1300, the second catheter member1312is constructed of a relatively strong metal, preferably stainless steel or nitinol. The second catheter member1312may alternatively be constructed of a polymer, preferably a polymer having a higher hardness than that of either the first catheter member1302or the third catheter member1320, but is not so limited. The first catheter member1302, second catheter member1312and third catheter member1320may also be combined in construction and configuration to have a transitioning stiffness, to include a separate stiffening member, such as a nitinol wire or braided shaft, to have sufficient pushability to have the appropriate amount of column strength. Referring toFIGS.37-37C, a fifth preferred embodiment of the occlusion/infusion system1350is generally similar to the infusion system or occlusion catheter system1300of the fourth preferred embodiment. The occlusion/infusion system or occlusion catheter system1350of the fifth preferred embodiment employs a first hypotube1362and a second hypotube1364within a second lumen1353of a second catheter member1352. The second hypotube1364extends from the proximal end of the second catheter member1352and terminates in communication with the occlusion balloon1354. Inflation fluid is communicated through a second hypotube lumen1365of the second hypotube1364, through an inflation port1357in the second catheter member1352that is positioned within a space1355defined within the balloon1354and fills the space1355to inflate the balloon1354. A seal1349is positioned within the second catheter member1352distal to the inflation port1357to seal the second lumen1353distally of the seal1349and permit the inflation fluid to flow through the inflation port1357and into the balloon1354, but not distally of a distal end of the balloon1354in the second lumen1353. The first hypotube1362extends within the second lumen1353of the second catheter member1352, extends beyond the seal1349and terminates within the third lumen1368in the distal portion of the second catheter member1352or a proximal portion of the atraumatic tip (not shown) to communicate with a plurality of distal side ports1360. In this manner, fluid introduced into the first hypotube1362is communicated through the first hypotube lumen1363to the plurality of distal side ports1360for release through the plurality of distal side ports1360distal to the occlusion balloon1354. It will be appreciated, therefore, that fluids may be infused through either the plurality of proximal side ports1358or the plurality of distal side ports1360, independently, or through both, concurrently. The same or different infusion fluids may be infused through the plurality of proximal side ports1358and the plurality of distal side ports1360, as well. The size, shape and position of the plurality of proximal side ports1358and that of the plurality of distal side ports1360may be configured to be the same or different and may be configured depending upon the type of fluid being infused. Furthermore, the plurality of proximal side ports1358, the plurality of distal side ports1360, the first hypotube1362and the second hypotube1364may be constructed of materials and tolerances suitable for powered injection at higher pressures and flow rates. Alternatively, an adjunctive or secondary infusion catheter, such as those that are known in the art, that comprises a low-profile catheter shaft, a fluid connector at a proximal end of the catheter shaft and a plurality of fluid openings at a distal end of the catheter shaft, may be engaged to pass within the second lumen1353, down the length of the second catheter member1352and out of a port distal to the occlusion member1354. In this manner, the fourth and fifth preferred occlusion catheter systems1300,1350may or may not have the plurality of proximal and distal side ports1308,1310,1358,1360, but may simply employ a secondary infusion catheter that is inserted into the second lumen1303,1353of the second catheter member1302,1352, or, where the preferred occlusion catheter systems1300,1350include the plurality of proximal and distal side ports1308,1310,1358,1360, the secondary infusion catheter may be inserted into a lumen, for instance the second hypotube lumen1316, such that it will be able to extend a substantial longitudinal length of second catheter member1302,1352and deliver fluid through the plurality of distal side ports1310,1360. Finally, it will be understood by those in the art, that the terminus of the third lumens1322,1368may be configured to laterally guide a guiding tip of a guide wire or catheter out of either the plurality of distal side ports1310,1360or out of a dedicated skive (not shown) formed in the distal wall surface of third catheter member1320,1370. An alternative configuration of the fourth and fifth preferred occlusion catheter systems1300,1350may employ a secondary or adjunctive infusion catheter that is utilized for the primary occlusion, then as infusion is required, to endoluminally delivery the secondary infusion catheter laterally to the already placed occlusion catheter, diametrically collapse the occlusion member to permit luminal space for the infusion catheter to pass the occlusion member, then reestablish occlusion when the infusion catheter is positioned distal to the occlusion member, thereby forming occlusion around the infusion catheter. In each of the foregoing described embodiments of the pre-conditioning systems or the fourth and fifth preferred embodiments of the occlusion catheter systems1300,1350depicted and described with reference toFIGS.35-36C, the systems1300,1350may also include sensors, transmitters, receivers, interrogators or other means for measuring physical and/or physiological parameters distal and/or proximal one or more of the expandable occlusion members1304,1354, including, for example blood pressure sensors, heart rate sensors, flow sensors, chemical sensors, temperature sensors, oxygenation sensors, ischemia sensors, biological sensors, imaging sensors or the like. Hemorrhage Exclusion and Flow Restoration Systems The foregoing described embodiments of the vascular occlusion catheter system operate by creating a luminal obstruction to blood flow to the hemorrhage site to at least partially stem the outflow of blood and permit vascular repair of the hemorrhage site while preserving blood flow to the patient's brain and other vital organs. Alternative embodiments of the present invention operate to create an obstruction and occlude the hemorrhage site within the vascular wall. Moreover, rather than create luminal obstruction to blood flow, typically superior to the hemorrhage site, these alternative embodiments, restore patency of the blood vessel at the hemorrhage site and permit blood flow past the hemorrhage site while obstructing and occluding the trauma or injury to the vessel wall itself. FIG.38illustrates a first preferred embodiment a hemorrhage exclusion system1400in accordance with the present invention. The preferred hemorrhage exclusion system1400is conceptually similar to occlusion/perfusion system1270depicted inFIG.33. In the first preferred hemorrhage exclusion system1400, an elongate support structure1412is formed of a plurality of structural support members, and is connected to a longitudinally extending catheter or catheter sleeve1406. The structural support members, which may be longitudinally oriented struts, form a distal cage section1408and a proximal cage section1402. The distal cage section1408is preferably, immovably coupled to a distal end of the catheter1406and, when an atraumatic guiding tip1404is provided, proximal to the atraumatic guiding tip1404. The proximal cage section1410is coupled to the catheter sleeve member1406. An intermediate cage section1416extends between the proximal cage section1410and the distal cage section1408. The hemorrhage exclusion system1400also includes an elongate support structure in the intermediate cage section1416that is preferably comprised of a continuation of the structural support members of the proximal and distal cage sections1410,1408with a large open volume within the support structure. The open volume between the structural support members of the proximal cage section1410and distal cage section1408facilitates blood flow longitudinally through the elongate support structure along the outside of the catheter sleeve1406. The elongate support structure—may be constructed of any appropriate biocompatible material, including polymers, metals, composite materials or combinations thereof, as discussed above with reference to the occlusion members. An exclusion member1414is carried on the intermediate cage section1416by the structural support members. The exclusion member1414extends along at least a substantial extent of the intermediate cage section1416. The exclusion member1414may be fabricated of any appropriate woven or non-woven biocompatible material, including polymers, metals, composite materials or combinations thereof, as discussed above in reference to the occlusion members. The exclusion member1414may be plastically deformable, elastically deformable, or have shape memory or superelastic properties. The exclusion member1414is preferably, generally tubular and may be porous, non-porous or bio-absorbable. The exclusion member1414may be coupled to either the outer or inner surface of the elongate support structure1412, or both. Coupling between the exclusion member1414may be in accordance with any methods and materials for joining biomaterials to support structures, including, without limitation, sutures, biocompatible adhesive, by reflow, by thermal welding, or by joining to another layer of exclusion member1414on the opposing surface of the support structure1412such that the struts of the support structure1412are at least partially encapsulated by the joined layers of the exclusion member1414. The catheter sleeve or catheter1406is preferably comprised of proximal and distal sections that are movably coupled to each other such that relative movement of the proximal and distal catheter sleeve members1406translates to diametric expansion or contraction of the elongate support structure1412and the exclusion member1414. The proximal and distal portions of the catheter sleeve member1406are preferably comprised of a tubular structure with a lumen through which an opposing catheter passes. The catheter sleeve1406is not so limited and may be constructed of nearly any assembly or construction that permits collapse and expansion of the elongate support structure1412, wherein the elongate support structure1412has a similar diameter to the catheter sleeve1406in the collapsed configuration and has an expanded (FIG.38) diameter that allows blood flow through the intermediate cage section1416in the expanded configuration. The elongate support structure1412, may assume a wide variety of geometries, provided that the exclusion member1414supported on the elongate support structure defines a fluid flow pathway to restore patency to the vessel and allow blood to flow past the hemorrhage site. In use, the hemorrhage exclusion system1400is advanced to a hemorrhage site. Contrast may be injected through the catheter1406and out of a port1403near the distal end of the catheter1406to image the hemorrhage, determine its position in the vessel wall and preferably estimate its relative size. The exclusion member1414is preferably positioned in such a manner as to span the hemorrhage site and extend both proximal and distal relative to the hemorrhage site. The support structure1412and the exclusion member1414are diametrically expanded into apposition with the vascular luminal wall surface, by relative movement of the proximal and distal portions of the catheter sleeve1406. The exclusion member1414preferably blocks flow of blood out of the hemorrhage site and allows blood to continue to flow through the vessel and, preferably, preventing flow of blood out of the hemorrhage. Further imaging using injected contrast may be employed to verify successful positioning of the exclusion member1414and coverage of the hemorrhage site to stem the outflow of blood from the vessel trauma or injury. Alternatively or additionally blood pressure and/or blood flow data may be obtained by pressure and/or flow sensors operably associated with the hemorrhage exclusion system1400, to also verify successful placement of the exclusion member1414and restoration of vascular patency and blood flow through the lumen of the exclusion member1414, through the elongate support structure1412and through the vessel. The exclusion member1414is preferably maintained in place blocking the hemorrhage site at least until the medical practitioner is able to develop a plan to repair the hemorrhage. An alternative preferred embodiment of the occlusion catheter system, which is similar to the foregoing hemorrhage exclusion system1400of the first preferred embodiment, involves eliminating the central catheter sleeve member1406and affixing the proximal cage section1402to a more proximal section of the catheter1406. A constraining sheath (not shown) is then placed over the catheter1406, the elongate structural support1412and the exclusion member1414, constraining the structural support1412and exclusion member1414in a reduced diametric state until the constraining sheath is withdrawn. This configuration is particularly well suited where the elongate structural support1412is made of an elastic, shape memory or super elastic material. This alternate preferred embodiment is conceptually similar to the manner in which self-expanding or shape memory stents are endovascularly delivered and placed. Referring toFIGS.39-39B, another or second preferred embodiment of the occlusion catheter system or hemorrhage exclusion system1450does not employ an elongate support structure1414, as is utilized in the first preferred embodiment of the hemorrhage exclusion system1400. The second preferred system1450includes a catheter1452having a relatively larger diametric profile which carries within a lumen in the catheter1452a furled or rolled sheet of an exclusion material1456. An elongate spindle member1453carrying a rolled sheet of exclusion material1456is preferably positioned within a lumen of the catheter1452. The catheter1452has an elongated slot1455passing through a wall surface of the catheter1452. The exclusion material1456preferably has a leading edge that projects out of an elongate slot1455and, when the elongate spindle member1453is rotationally moved within the lumen of catheter1452, the exclusion material1456unfurls or unrolls out of the elongated slot1455. As the exclusion material1456fully unrolls from within the catheter lumen, the exclusion material1456preferably forms a diametrically enlarged generally tubular structure with at least one region of overlap of the exclusion material1456, such that a first winding of the exclusion material1456forms an outer layer1459of the tubular structure and a second winding of the exclusion material1456forms an inner layer of the tubular structure. The tubular structure so formed defines a central lumen1460that allow blood flow through the tubular structure while the exclusion member1456is deployed in its diametrically expanded state. In use, the hemorrhage exclusion system1450of the second preferred embodiment is endoluminally delivered to a hemorrhage site. Similar to the hemorrhage exclusion system1400of the first preferred embodiment, the hemorrhage site may be imaged by contrast injection to position the exclusion system1450relative to the hemorrhage site. Once properly positioned, the elongate spindle1453is rotatably actuated to unfurl or unroll the exclusion member1456through the elongate slot1455until it assumes its enlarged tubular shape and defines the blood flow central lumen1460and is preferably in apposition with the vascular wall surface and excludes or bypasses the hemorrhage site. Exclusion or bypass of the hemorrhage may be verified by contrast imaging or by blood pressure and/or blood flow data obtained from the patient or from blood pressure and/or blood flow sensors operably associated with, preferably attached to the exclusion system1450. In each of the foregoing preferred embodiments of the hemorrhage exclusion systems1400,1450depicted and described with reference toFIGS.38-39B, the systems1400,1450may also include sensors, transmitters, receivers, interrogators or other means for measuring physical and/or physiological parameters distal and/or proximal one or more of the expandable occlusion members, including, for example blood pressure sensors, heart rate sensors, flow sensors, chemical sensors, temperature sensors, oxygenation sensors, ischemia sensors, biological sensors, imaging sensors or the like. The sensors may communicate with a controller, which may control various aspects of the operation of the systems140,1450, such as unfurling the exclusion member1456or collapsing the exclusion member1456. Inflation Control Systems Referring toFIG.40, a first preferred of an inflation control system1500may be utilized with any of the preferred occlusion catheter systems and other preferred systems having inflatable balloons or occlusion members described herein. In the first preferred embodiment, the inflation control system1500is preferably connected in-line between an inflation device (i.e. pressure source) and the balloon catheter, such as the first preferred occlusion catheter system100. The inflation control system1500preferably helps to prevent the user from overinflating the balloon, such as the occlusion member140and damaging the blood vessel into which the occlusion member or balloon140is inserted. The inflation control system1500preferably includes a pressure source1502, such as a syringe, which may be manually actuated or may be coupled to any of a large number of known automated injectors or pressure systems. The pressure source1502has a fluid source contained within the syringe, and is coupled to a bifurcated pressure conduit1506, that in turn communicates with a free line and a regulated line. A one-way check valve1508is interposed in the regulated line to prevent both backpressure and backflow to the syringe1502. A selectable flow valve1504is interposed in the free line and communicates with the regulated line. The selectable flow valve1504is operable to select the free line, the regulated line or both the free line and the regulated line. A fluid conduit leads from the selectable flow valve1504to a pressure sensor1510. A coupling1512, preferably a luer lock fitting, is provided to couple the occlusion catheter (not shown) to the pressure sensor1510. While an analog pressure gauge is shown inFIG.55, the analog pressure gauge is not limiting and a wide variety of analog or digital pressure sensors1510are capable of being used to provide the medical practitioner with information concerning the pressure in the inflation control system1500. In use, the inflation control system1500allows the practitioner to apply fluid pressure to the occlusion catheter, e.g., by advancing the syringe plunger, to inflate the occlusion balloon, while simultaneously preventing both backpressure and backflow. When the selector valve1504is positioned to open the regulated line and close the free line, fluid is free to flow through the check valve1506to the occlusion catheter and ultimately to the balloon. Pausing during inflation will not result in deflation of the balloon because when force is no longer applied to the syringe plunger, the fluid no longer advances through the check valve1508and the backpressure from the elastic balloon causes the fluid to try to exit the balloon/catheter, thereby causing the check valve1508to close. The pressure sensor1510preferably senses the applied pressure at the pressure source1502, but not necessarily at the occlusion balloon. Namely, because of the length of the occlusion catheter and the high resistance of the fluid passing through the narrow annular space of the catheter shaft, the pressure at the pressure gauge1510may be higher than the actual pressure in the balloon, but allowances and compensation may be calculated to predict or measure the pressure within the balloon with the gauge1510. A dwell time typically exists between the time pressure is applied at the pressure source1502and when the pressure equilibrates at the occlusion balloon, but the pressure in the system between the check valve1508and the balloon quickly equalizes and the pressure sensor1510accurately reads the true pressure in the balloon. Excluding backpressure and backflow via the check valve1508creates a closed system in which the pressure can be allowed to equilibrate, as represented by a constant pressure readout on the pressure sensor1510, which will then represent the pressure at the occlusion balloon. Additional fluid pressure may then be applied at the pressure source1502. As should be understood, the pressure sensor1510may have a “target occlusion pressure” identified thereon (i.e. such as a blue zone of the gauge1510) that the practitioner knows to keep inflating until the needle comes a rest in the blue zone. This would indicate occlusion but not over inflation. Therefore, since this system is based on pressure and not volume, it is not necessary to know the vessel diameter before inflating the balloon. Rather, the practitioner need only fill the balloon until the needle of the pressure gauge1510comes to a rest in the “blue zone”. Pressure may be withdrawn from the occlusion balloon by means of the selector flow valve1504being switched to open the free line, by-passing the check valve1508, and releasing pressure back to the pressure source1502from the occlusion balloon. The syringe plunger is preferably retracted and the fluid is drained from the balloon back into the syringe1502. Referring toFIG.41, a preferred second embodiment of an inflation control system1550is useful in the preferred inflation method of the present invention. A conventional balloon inflation device1562is illustrated inFIG.41(such as a QL Inflation Device, Atrion Medical, Arab, Alabama). The inflation device1562has a fluid chamber and a plunger1564. The plunger1564is preferably threaded to allow for rotation of the plunger1564relative to the fluid chamber and controlled depression of the plunger1564within the fluid chamber. A fluid conduit1563communicates with an outlet1561in the inflation device1562to communicate the inflation fluid to the occlusion catheter (not shown), such as the occlusion catheter system100of the first preferred embodiment or any of the other preferred occlusion systems described herein, that is coupled to the inflation device1550via a coupling1561. A pressure sensor1560is preferably provided in the outlet line of the inflation device1550. A lock1566is preferably provided that engages the threaded plunger1564during pressurization and disengages from the threaded plunger1564during depressurization. The lock1566acts, essentially, to isolate the pressure within the occlusion balloon, catheter and fluid conduit1563and resists transmitting backpressure or fluid backflow to the plunger1564. Essentially, the lock1566functions in a manner similar to the check valve1508in the preceding first preferred embodiment of the inflation control system1500. The method of inflating the occlusion balloon (not shown) using the inflation device1562entails the practitioner filling the fluid chamber with an inflation fluid by withdrawing the plunger1564to fill the fluid conduit1563and the fluid chamber. Expelling any air present in the fluid chamber and fluid conduit and connecting the inflation device1550to the occlusion catheter (not shown). To inflate the occlusion balloon, the plunger1564is actuated either by linear force or by rotating the plunger1564to engage the threads for a controlled pressurization. The lock1566should be engaged with the plunger1564to resist backpressure as the balloon occlusion member inflates. The pressure sensor1560will sense the applied pressure at the inflation device1550, but not necessarily at the occlusion balloon. Because of the length of the occlusion catheter, a dwell time exists between the time pressure is applied at the inflation device1550and when the pressure equilibrates at the occlusion balloon. By excluding backpressure and backflow, the lock1566serves to creates a closed system in which the pressure can be allowed to equilibrate, as represented by a constant pressure readout on the pressure sensor1560. When the pressure indicated on the pressure sensor1560is stable, this will then represent the pressure at the occlusion balloon. Additional fluid pressure may then be applied or pressure may be withdrawn from the occlusion balloon by either reversing the rotation of the plunger, essentially unthreading the plunger1564, and depressurizing the balloon, or by means of releasing the lock1566and withdrawing the plunger1564. The second preferred inflation device1550is not limited to the specific arrangement described and shown herein and further mechanisms may be employed to prevent the user/practitioner from overinflating the balloon and damaging the blood vessel or the balloon. For example, as shown inFIG.41A, any of the preferred vascular occlusion catheter systems, such as the first, second or third preferred occlusion catheter systems100,300,500, may include a spring biased valve1501positioned within the catheter, proximal the atraumatic guiding tip150,450,550, including a plunger1501asealingly engaging the catheter lumen and occluding a port1503located distally therefrom. The spring1501bbiases the piston1501ainto the position occluding the port1503and may define a spring constant configured to be overcome by a counteracting force corresponding to a pressure equal to or less than the cracking pressure of the vessel. Therefore, prior to overinflating the balloon and damaging the vessel, the pressure within the catheter overcomes the spring1501bbias and pushes the plunger1501adistally to expose the port1503and permit pressure release therethrough. The spring1501bwill push the plunger1501aback into the position occluding port1503once sufficient pressure is released. Infection/Contamination Control System Rapid endovascular occlusion or exclusion of a traumatic hemorrhagic injury while on the battlefield or on the street involves not only a non-sterile environment, but an environment that is may be highly contaminated and prone to a wide variety of sources of bacterial or viral infections. It is desirable to design, construct and deploy a device that facilitates vascular access and endovascular delivery of a vascular occlusion catheter while minimizing infections resulting from contamination when used in austere environments, i.e., on the battlefield or on the street, rather than in a hospital or other sterile or controlled environment. Referring toFIGS.42A and42B, a first preferred infection control catheter sleeve system1600provides a substantially sterile field for the occlusion catheter1602and the occlusion balloon1608during access and endovascular delivery and through the vascular occlusion procedure. The occlusion catheter preferably includes an inflation catheter1602apositioned proximate the balloon1608and a distal catheter member1602bpositioned distally relative to the balloon1608. The inflation catheter member1602apreferably has an inflation lumen similar to the inflation lumens described herein with respect to the preferred occlusion catheter members that has a port opening into an inner area of the occlusion balloon1608to permit inflation and deflation of the occlusion balloon1608. The catheter sleeve system1600generally comprises a sleeve1610that is preferably comprised of an elongate tubular structure fabricated of a highly resilient material capable of being sterilized. The catheter sleeve1610is preferably a thin walled, elastic in inelastic polymer material that is capable of being longitudinally collapsed in an accordion-like fashion to ease insertion of the catheter1602into the sterile lumen of the elongate tubular structure1610and thereafter elongated in an accordion-like fashion as needed to cover substantially the entire shaft of the catheter1602in a covered configuration. The catheter sleeve1610preferably has hub members1604,1606at respective proximal sleeve and distal sleeve ends1610a,1610bof the catheter sleeve tubular structure1610that permit the catheter1602to extend into and through the catheter sleeve1600while generally maintaining hemostasis and a sterile field within the catheter sleeve1600. The preferred system1600includes proximal and distal hub members1604,1606that may be constructed and configured as any type of hemostatic valve that permits the catheter1602to pass through the valve, such as, for example, without limitation, a Tuohy Borst valve. The distal hub member1606may also include surfaces, such as flanges, wings, or other projections from the distal hub member1606that facilitate close approximation with the patient's skin and application of a shield dressing or other adhesive dressing to retain the distal hub member1606, catheter sleeve1600and catheter1602positioned on the patient after the occlusion catheter has been delivered. In use, as the distal tip of the catheter1602is inserted into an introducer sheath or the patient's body with the atraumatic tip1605substantially straightened along the longitudinal axis1601and the distal hub member1606of the catheter sleeve1600preferably remains mated to the introducer sheath during insertion of the catheter1602. The preferred thin polymer of the catheter sleeve1610collapses in an accordion-like manner as the catheter1602is advanced into the body. Therefore, if something non-sterile comes into contact with the outside of the catheter sleeve1610, it generally does not contaminate the catheter shaft1602that is inserted into the body. In addition, as the catheter1602is withdrawn from the patient, the sleeve1610is able to expand from its working configuration to the covered configuration such that materials, such as blood, from the vessel of the patient is substantially maintained within the sleeve1610or is swiped from the catheter1602by the distal hub1606. Guide Wire Compatibility As indicated above, the vascular occlusion catheter systems, such as, for example, without limitation, the first, second and third preferred vascular occlusion catheter systems or occlusion catheter systems100,300,500, are preferably capable of use without the need for a guide wire1700. Guide wires1700are typically designed to navigate vessels to reach a desired vessel segment. Once the guide wire1700arrives at the destination in the vessel, the guide wire1700acts as a guide that facilitates delivery of the catheter system to the destination vessel segment. The atraumatic tip described above in detail with reference to the preferred embodiments of the occlusion catheter system100,300,500, serves to guide the catheter as it traverses the vasculature and typically prevents the catheter from tracking into collateral vessels, while preferably eliminating the need for a guide wire for catheter placement. Practitioners, may desire for the preferred vascular occlusion catheter systems described herein to include guide wire capability for familiarity purposes. Accordingly, as shown inFIGS.43and43A, an eighth preferred vascular occlusion catheter system1701is provided with guide wire capability, while not requiring the guide wire1700for use. In this preferred embodiment, the spiral or substantially circular shape of the atraumatic tip1706, which is preferably configured in the same manner as the atraumatic tips450,550of the second and third preferred embodiments, is positioned proximate an exit port1702of the catheter system1701. The atraumatic tip1706may alternatively be removed and replaced with a distal end defining a substantially straight, compliant end and having the exit port1702. The exit port1702is in communication with a guide lumen1703defined in a tip shaft1705of the atraumatic tip1706. The guide lumen1703is preferably positioned coaxially or substantially parallel and proximate a longitudinal axis1707of the catheter system1701. The catheter system1701preferably includes multiple lumens therein for inflation of an occlusion balloon1708and sliding receipt of the guide wire1700. In the preferred embodiment, the guide wire1700may be comprised of an eighteen thousandths of an inch (0.018″) to an approximately twenty-five thousandths of an inch (0.025″) or thirty-five thousandths (0.035″) diameter guide wire1700. The guide lumen1703and other lumens in the catheter system1701are designed and configured to accept sliding acceptance of the guide wire1700. The guide wire1700may be slidably inserted and extend through the catheter system1701, preferably coaxially or proximate and substantially parallel to the longitudinal axis1707, and extend out of the distal end of the system1701through the exit port1702. Accordingly, after the guide wire1700is inserted into a patient's body, the catheter system1701is capable of advancing over the guide wire1700to reach the desired vascular destination and the guide wire1700may subsequently be removed from the patient while retaining the system1701, particularly the occlusion balloon1708therein. The preferred catheter system1701includes a proximal hub (not show) that is the same or similar to the proximal hub of the herein described preferred embodiments. The proximal hub is connected to an inflation catheter member1709that is positioned at a proximal end of the occlusion member or occlusion balloon1708. The inflation catheter member1709has an inflation lumen1709atherein that opens into an internal space of the occlusion balloon1708at a first port1709b. The inflation lumen1790aand inflation catheter member1709are preferably position on or along the longitudinal axis1707. The occlusion balloon1708preferably has a proximal end1708aand a distal end1708b, wherein the proximal end is connected to the inflation catheter member1709. A distal catheter member1705, which may be comprised of the tip shaft1705or may be a separate catheter member is positioned substantially on the longitudinal axis1707and is connected to the distal end1708bof the balloon1708. The atraumatic tip1706is connected to or formed integrally with the distal catheter member or tip shaft1705. The guide lumen1703is formed within the distal catheter member or tip shaft1705for slidable receipt of the guide wire1700, preferably substantially along the longitudinal axis1707. In the preferred embodiment, the catheter system1701may maintain the generally spiral or substantially circular shaped atraumatic tip1706during insertion and the guide wire1700exits the catheter system1701through the exit port1702below the atraumatic tip1706such that the guide wire1700may be initially inserted into the patient and the system1701is guided into position along the guide wire1700. The lumens of the preferred system1701, including the guide lumen1703are in communication with the exit port1702and are appropriately dimensioned to accommodate the desired diameter guide wire1700. In the preferred embodiment, the exit port1702is positioned on a lower side of the atraumatic tip1706, opposite the circular profile, such that the circular profile is preferably oriented in its relaxed configuration after insertion into the patient's vessel and during the guiding movement into the appropriate location for the procedure in the vessel. The catheter system1701of the eighth preferred embodiment may also be configured such that the exit port1702is located on an opposite side of the atraumatic tip1706in the tip shaft1705. Referring toFIGS.43B and43C, the alternative eighth preferred embodiment of the catheter system1701′ has similar features when compared to the preferred catheter system1701and like reference numerals are utilized to identify and describe like features with a prime symbol (′) utilized to distinguish the eighth preferred embodiment from the alternative preferred embodiment. In the alternative preferred embodiment, the exit port1702′ is positioned proximate an inner tip surface1709′ of the atraumatic tip1706′ such that the guide wire1700would extend out of the alternative preferred system1701′ into the inner surface1709′ of the atraumatic tip1706′. The guide wire1700is preferably sufficiently flexible to deflect out of the way of the atraumatic tip1706′ as it extends out of the exit port1702′ to guide the catheter system1701′ to the appropriate location in the vessel and position the occlusion member (not shown) in the appropriate zone, such as zone I, II or II, as is described above in the Summary of the Invention section. The alternative eighth preferred embodiment otherwise operates substantially the same as the eighth preferred embodiment of the system1701with the guide wire1700. Power Injection Capability Injecting contrast media into a patient's vasculature enables increased visualization using fluoroscopy. Contrast delivery is most effective and efficient using a medical device called a “power injector” that can be programmed to deliver specific amounts of contrast agent at specific flow rates. Referring toFIG.44, in a ninth preferred embodiment, an occlusion catheter system1800includes multiple or a plurality of side ports1809to distribute contrast medium in the vasculature rapidly and evenly, preferably distally relative to an occlusion member1808. At least one side port1809(multiple side ports in the illustrated embodiment) is in fluid communication with a lumen, e.g., the first, second and/or third lumen as described above with respect to the preferred catheter systems100,300,500,1300,1350, accessible from the proximal hub (not shown), such as, for example, without limitation, the proximal hubs190,590,790. Accordingly, contrast medium pumped into the catheter1800from the proximal hub is dispensed from the plurality of side ports1809and into the surrounding vasculature. The catheter1800is preferably configured in a similar manner to the occlusion catheter system100with the first catheter member130having the first lumen230, the second catheter member110having the second lumen210and the atraumatic tip150with a proximal portion comprised of the third catheter member120with the third lumen220. The multiple side ports1809are preferably formed in the proximal portion of the atraumatic tip150, the third catheter member120or the first catheter member130and may also be formed in each of these components of the catheter1800. The plurality of side ports1809are in fluid communication with the first lumen230through the first catheter member130, which is preferably in fluid communication with a power injection mechanism (not shown) through the first fluid pathway192in the proximal hub190. The space within the occlusion member1808is preferably in fluid communication with an injection mechanism, such as the inflation control system1500through the second fluid pathway194and the second lumen210, which introduces pressurized fluid or gas into the occlusion member1808through the distal port opening160. In the illustrated embodiment, the side ports1809are located distally from the occlusion member1808. The side ports1809, however, may be located proximally and/or distally of the occlusion member1808and the number of side ports1809may be determined according to the desired dispensing rate. The plurality of side ports1809may also be located in a single plane or in a circumferential manner around the catheter shaft. The plurality of side ports1809may also be utilized to withdraw fluids from the patient's vasculature, such as, for example, for blood sampling. The lumen in fluid communication with the side ports1809may be a hypotube constructed of a metal (e.g., nitinol), a polymer, a reinforced polymer (e.g., braided), or a composite material in order to withstand power injection pressures. The catheter hub, extension lines, and connectors are also constructed of the appropriate polymer/composite material in order to withstand power injection pressures. For example, extension lines may be braid reinforced or otherwise reinforced to withstand the power injection pressures. The catheter1800is, therefore, capable of being used safely with a power injector for contrast injections. The catheter1800may also be used for visualization of hemorrhage using fluoroscopy by injecting visualization agent into the patient and visualizing flow and, particularly hemorrhage. Infusion Catheter Referring toFIG.45, an infusion catheter or occlusion catheter system1900in accordance with a tenth preferred embodiment (not including an occlusion member) can be utilized to infuse and withdraw fluids from a patient's vascular system. Similarly to the occlusion catheter100,300,500, the infusion catheter1900includes a distal, curled/spiral, polymeric atraumatic tip1906to assist the catheter1900to track up a blood vessel and remain in the central lumen of the vasculature. The catheter shaft1910is configured to have an appropriate stiffness to be pushable without kinking, while also being sufficiently flexible to not damage blood vessels. The catheter shaft1910may be constructed of a polymeric material, a metallic material, or a combination of plastic, metal, and composite materials (e.g., fiberglass, carbon fiber, nylon, etc.) to achieve the appropriate stiffness. The catheter shaft1910may be approximately five French (5 Fr) or five and twenty-four hundredths millimeters (5.24 mm), but may alternatively be constructed in other sizes as necessary. Similarly, the diameter of the generally circular profile of the atraumatic tip1906(discussed below) may also be sized appropriately according to the destination vessel size. The atraumatic tip1906is preferably designed and configured similar to the atraumatic tips450,550of the second and third preferred embodiments of the occlusion catheter system300,500, as is described above. Similarly to the occlusion catheter systems100,300,500of the first, second and third preferred embodiments, the infusion catheter1900of the tenth preferred embodiments is intended to be used without a guide wire for rapid insertion. The combination of the atraumatic tip1906and catheter shaft1910substantially negates the need for a separate guide wire, as is typically utilized in procedures introducing catheters, stents, screws or other devices into the patient. The infusion catheter1900preferably has a single lumen1912connected to a hub (not shown), e.g., with a standard luer lock fitting (not shown) at the proximal end of the occlusion catheter system1900. The occlusion catheter system1900may alternatively be connected with a hub via any of numerous different connectors/fittings, that are currently known or that later become known. The catheter shaft1910of the tenth preferred embodiment includes a plurality of side ports1909(a plurality of ports1909in the illustrated embodiment) proximal relative to the atraumatic tip1906. The plurality of side ports1909is in fluid communication with the lumen1912. A fluid may be injected at the catheter hub and exit into the vasculature at the plurality of side ports1909. The plurality of side ports1909preferably assist in distributing the fluid evenly to prevent the fluid stream from causing damage to the blood vessel. The plurality of side ports1909maybe be positioned in a single plane or spiral around the catheter shaft1910or may otherwise be arranged and configured to facilitate injection in a manner desired by the medical professional or designer. As explained above, the catheter shaft1910is preferably constructed of a material capable of withstanding the pressures and flow rates of power injection for contrast visualization. The catheter shaft1910could be braided or non-braided. The catheter1900may also be used for blood pressure monitoring via an external pressure sensor or to withdraw fluids (i.e. blood sampling, blood filtration/oxygenation (extracorporeal membrane oxygenation (“ECMO”), etc.). The infusion catheter1900may be used in combination with an occlusion catheter system, but is not so limited. For example, an occlusion catheter system could be placed in the right femoral artery and advanced to the aorta and the occlusion member inflated to occlude the vessel. The infusion catheter1900could be inserted via the left femoral artery and used to infuse fluids (i.e. blood products, hyperoxygenated perfusate, crystalloids, etc.). The infusion catheter1900could also be used with a power/hand injector to inject radiopaque contrast (CO2, Isovue, etc.) to visualize the hemorrhage. The infusion catheter1900may be packaged with a pre-installed “peel-away sheath” that is used to straighten the atraumatic tip1906for insertion into the valve of the introducer sheath or directly into the blood vessel. The peel-away sheath is advanced distally to capture and straighten the atraumatic tip1906and then can be retracted proximally toward the catheter hub and peeled off the catheter shaft1910if necessary. Decision Support Systems Intelligent systems are becoming widely accepted and are finding their way into acceptance in medical diagnostics and in the performance and predictive analysis of medical device clinical trials. Articles and presentations have been given related to this subject matter. An approach based on Bayesian statistics is an approach for learning from evidence as it accumulates. In clinical trials, traditional statistical methods may use information from previous studies only at the design stage. Then, at the data analysis stage, the information from these studies is considered as a complement to, but not part of, the formal analysis. In contrast, the Bayesian approach uses Bayes' Theorem to formally combine prior information with current information on a quantity of interest. The Bayesian idea is to consider the prior information and the trial results as part of a continual data stream, in which inferences are being updated each time new data become available. The Bayes theorem may be used to calculate the probability of coronary artery disease based upon clinical data and non-invasive test results. Pre-test probabilities of disease are assigned based on clinical data and the equation is used to calculate post-test probabilities after multiple sequential tests. When good prior information on clinical use of a device exists, the Bayesian approach enables this information to be incorporated into the statistical analysis of a given decisional matrix. Good prior information is often available for medical devices because of their mechanism of action and evolutionary development. The mechanism of action of medical devices is typically physical. As a result, device effects are typically local, not systemic. Local effects can sometimes be predictable from prior information on the previous generations of a device when modifications to the device are minor. Good prior information can also be available from studies of the device overseas. Bayesian methods are usually less controversial when the prior information is based on empirical evidence such as data from clinical trials. Bayesian methods can, however, be controversial when the prior information is based mainly on personal opinion. Bayesian analyses are often computationally intense. Recent breakthroughs in computational algorithms and computing speed have, however, made it possible to carry out calculations for very complex and realistic Bayesian models. These advances have resulted in an increase in the popularity of Bayesian methods. A basic computational tool is a method called Markov Chain Monte Carlo (“MCMC”) sampling, which is a method for simulating from the distributions of random quantities. As the Bayesian predictive modeling scheme has become well known, it is useful in conjunction with the various control systems of the present invention, as described above, as predictive analysis profiling during a vascular occlusion procedure. In connection with the present invention, the various preferred embodiments of the occlusion catheter systems and related components and devices described herein, and the occlusion or the occlusion/perfusion control over the vascular occlusion devices, is well suited to oversight and control using intelligent systems, such as those in which Bayesian probability analysis is applied. In each of the above-described embodiments, including without limitation, the vascular occlusion devices, the occlusion catheter systems, the control systems for controlling apposition of the occlusion member against the vessel wall or for excluding the hemorrhage site, the pre-conditioning systems or the occlusion/perfusion systems, both physical and/or physiological data is either acquired or is capable of being acquired. Acquisition of real-time physical and/or physiological data during an occlusion procedure or during a vascular repair involving a vascular occlusion includes, without limitation, blood pressure, heart rate, flow, chemistry, temperature, oxygenation, imaging or the like. In combination with prior data obtained from clinical practice guides, standard of care protocols, process flowcharts, and other data acquired during prior procedures, intelligent predictive analysis may be applied in software or firmware resident at the computer controllers, e.g., controllers750,753,803, to either automatically control the preferred systems described herein or to output intelligently processed information to the medical practitioner to aid in decision making during the occlusion procedure. It will be appreciated by those skilled in the art that changes could be made to the embodiments described above without departing from the broad inventive concept thereof. For example, nearly any of the individual components of the various embodiments may be incorporated with other preferred embodiments without departing from the spirit and scope of the preferred inventions. The plurality of proximal and distal side ports may be incorporated in nearly any of the preferred occlusion catheter systems, the atraumatic tips may be mixed and matched with the various embodiments of the occlusion catheter systems, nearly any of the preferred occlusion members, such as the first preferred occlusion balloon system1200with the projecting members1204may be incorporated with any of the preferred occlusion catheter systems and other similar arrangement of the disclosed features of the preferred systems may be employed without departing from the spirit and scope of the disclosed preferred inventions. It is understood, therefore, that the invention is not limited to the particular embodiments disclosed, but it is intended to cover modifications within the spirit and scope of the present invention, as defined by the appended claims. | 175,139 |
11857738 | DETAILED DESCRIPTION As used herein, the terms “about” or “approximately” for any numerical values or ranges indicate a suitable dimensional tolerance that allows the part or collection of components to function for its intended purpose as described herein. More specifically, “about” or “approximately” may refer to the range of values ±10% of the recited value, e.g. “about 90%” may refer to the range of values from 81% to 99%. As used herein, a “subject” or “patient”, including a blood vessel from a subject or a patient, may refer to any applicable human patient as well as any mammal, veterinarian animal, livestock animal or pet type animal, etc. As an example, the animal may be a laboratory animal specifically selected to have certain characteristics similar to a human (e.g., rat, dog, pig, rabbit, monkey, or the like). As used herein, “operator” may include a doctor, surgeon, or any other individual or instrumentation associated with the medical procedure used with the device(s) of this disclosure. In addition, the terms “patient,” “host,” “user,” and “subject” refer to any human or animal subject and are not intended to limit the systems or methods to human use, although use of the subject disclosure in a human patient represents a preferred embodiment. As used herein, the term “computing system” is intended to include stand-alone machines or devices and/or a combination of machines, components, modules, systems, servers, processors, memory, detectors, user interfaces, computing device interfaces, network interfaces, hardware elements, software elements, firmware elements, and other computer-related units. By way of example, but not limitation, a computing system can include one or more of a general-purpose computer, a special-purpose computer, a processor, a portable electronic device, a portable electronic medical instrument, a stationary or semi-stationary electronic medical instrument, or other electronic data processing apparatus. As used herein, the terms “component,” “module,” “system,” “server,” “processor,” “memory,” and the like are intended to include one or more computer-related units, such as but not limited to hardware, firmware, a combination of hardware and software, software, or software in execution. For example, a component may be, but is not limited to being, a process running on a processor, an object, an executable, a thread of execution, a program, and/or a computer. By way of illustration, both an application running on a computing device and the computing device can be a component. One or more components can reside within a process and/or thread of execution and a component may be localized on one computer and/or distributed between two or more computers. In addition, these components can execute from various computer readable media having various data structures stored thereon. The components may communicate by way of local and/or remote processes such as in accordance with a signal having one or more data packets, such as data from one component interacting with another component in a local system, distributed system, and/or across a network such as the Internet with other systems by way of the signal. Computer readable medium can be non-transitory. Non-transitory computer-readable media include, but are not limited to, random access memory (RAM), read-only memory (ROM), electronically erasable programmable ROM (EEPROM), flash memory or other memory technology, compact disc ROM (CD-ROM), digital versatile disks (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other tangible, physical medium which can be used to store computer readable instructions and/or data. As used herein, the term “trace” includes a conductive path in an electrical circuit such as a path integral to a printed circuit, an individual wire, a conductor within a ribbon cable, or other such structure as appreciated and understood by a person of ordinary skill in the art according to the teachings of the present disclosure. As used herein, the terms “tubular” and “tube” are not limited to a structure that is a right cylinder or strictly circumferential in cross-section or of a uniform cross-section throughout its length. For example, the tubular structure or system is generally illustrated as a substantially right cylindrical structure. However, the tubular system may have a tapered outer surface, a curved outer surface, and/or a partially flat outer surface without departing from the scope of the present disclosure. Turning now toFIG.1, it illustrates a stabilized coronary sinus catheter system that includes a coronary sinus catheter100configured to enter the coronary sinus20of a heart10(seeFIGS.5and6). During an electrophysiological (EP) cardiac procedure, the coronary sinus (CS) catheter100may be inserted into the heart10, to provide a reference for the procedure. The CS catheter100has a proximal section102, a medial section104and a distal section106. A handle300can be disposed proximal of the proximal section102to allow the use to control the movement and deployment of the features of the CS catheter100. The medial section104can be distal of the proximal section102and have a medial stiffness. The proximal section102can have a proximal stiffness and the distal tip202can have a flexibility greater than the proximal stiffness, the medial stiffness, and a stiffness of the shape memory portion200. While stiffness is a general term, there are many ways to form the catheter sections102,104,106with different stiffness or conversely, flexibility. Each section can be formed from one or more polymers and or materials having different hardness or durometer. Additionally, braids or other stiffeners can be used inside, around the outside or molded directly into the catheter sections102,104,106. Alternately or additionally, strain relief features (such as physical scoring) can be added to increase flexibility. FIGS.2A and2Billustrate the features of the distal section106. The distal section106can have electrodes or sensors208along its surface. The signals acquired by the sensors208are used as references for other signals acquired in the procedure, such as for EP mapping of heart10. In order to act as a good reference, the CS catheter100should not move within its retaining chamber (the CS20), or any movement must be allowed for. To that end, the distal section106also includes a memory shape portion200and a distal tip202, distal of the memory shape portion200.FIGS.2A and2Billustrate the memory shape portion200in a deployed configuration. Here, the memory shape portion200forms a predetermined shape approximately conforming to the shape of the coronary sinus20. Shapes can include a helix or basket. When the memory shape portion200takes the deployed shape (and in this example, a helical shape), the electrodes208are pushed into contact with the CS20wall. The pressure of the memory shape portion200into the wall locks the catheter100in position. The distal tip202can also include a single axis location sensor224to help guide it into the CS20before the sensors208are deployed. To facilitate the locking aspect, the memory shape portion200has a proximal end206and a distal section axis204running from the proximal end206to the distal tip202. In the example illustrated inFIGS.2A,2B and3, the predetermined shape of the shape memory portion200has some exemplary measurements when in a tapered helical shape. A proximal section bending radius210can measure between approximately 8.5 mm and approximately 9.5 mm and a distal section bending radius212can be between approximately 7.0 mm and approximately 8.0 mm. A proximal section helix angle214can be between approximately 110° to approximately 120°. A distal section helix angle216can be between approximately 150° to approximately 160°. The shape memory portion can have a length218, when deployed between approximately 42.5 mm to approximately 44.5 mm. A major diameter220of a first helix coil can be approximately 14.0 mm to approximately 16.0 mm, and a taper angle222between approximately 3.5° and approximately 5.5°. FIG.4illustrates an example of a cross-section of the catheter100. In this example, there can be a guide wire lumen108that allows the catheter100to ride over a guide wire40to guide the catheter100from the insertion point (typically a groin puncture) to the heart10. Once near or in the CS20, the guide wire40can be removed to allow for the further functionality of the handle300, which is described in more detail below. A sensor wire lumen110can contain a sensor wire50(seeFIG.14) connecting the sensors208back to a system to read the data from the sensors and display it for the user. In one example, there can be at least forty (40) sensors208deployed along the distal section106. The sensor wire50can also transmit signals from the single axis location sensor224. The movement of the catheter100is tracked with at least the single axis location sensor224to allow for proper placement in the CS20. Once the catheter100is properly placed and the shape memory portion200is deployed, the catheter100is tracked and the CS chamber is fully demonstrated in a mapping system for a user. Tracking of the catheter100can use any known tracking technology such as CARTO®. In the example of the shape memory portion200illustrated inFIGS.5and6, its helical structure also serves as anchoring mechanism that locks the catheter100in place in the CS20. This also places the sensors208in continuous contact in the CS20chamber walls to provide a stable reading free from the artifacts like heart beat and respiration. These are improvements over prior art CS catheters. Electrocardiogram (ECG) artifacts are generated from the inter-motion between the electrodes and the CS wall during the heart retraction and movements related to the respiratory related motion. As the shape memory portion200anchors the catheter100, the distal tip202following medial section104is used as strain relief. Being radially soft, the retraction of the guide-wire can leave this section handing in the right atria with minimal applied force on the shape memory portion200. As the proximal section102can be firmer, pushing it somewhat forward after the guide-wire is fully retracted, builds in a section of strain relief. This prevents motion of the heart due to respiration and heartbeat from applying forces in the shape memory portion200. This can further prevent risk of movement of the shape memory portion200in the CS20. With the catheter100firmly stable in the CS20, any motion of the catheter100is monitored and used to alert the mapping system and user. Having many sensors208(with an example of 2-3 mm spacing) surrounding the CS20chamber, allows selection of the sensors208that have atria activity or ventricle activity to permit selective detection of atria or ventricle activity. Moreover, in the case of left and right atria disassociation, each atria activity can be tracked independently. The sensors208can be oriented to be sensitive both along and transverse to the distal section axis204, providing an accurate view of activity in any direction. This can be achieved by taking a wide bipolar signal for subtracting not just the nearest neighbor electrode. Having a full view of the CS20provides better tracing of the activation morphology, which represents both the FAR field (activity further from the CS20) and the near field (activity related to ECG originated near the CS20). This capability provides a more robust tracking tool allowing detection of similar ECG activities and support stitching different positions of a mapping catheter (as is used by CARTO® during LAT mapping). Some of the tachycardia involves activation in the CS20. Mapping the CS20is challenging with current tools as the activity may be on the side proximal to the heat wall or opposite. With the shape memory portion200in a helical shape, a full activation map in the CS is possible. Other elements of the catheter100are the lead wire lumen112and the shape memory lumen114. The shape memory lumen114contains a shape memory alloy116(seeFIG.14). The shape memory alloy116can be made from a material capable of recovering its shape automatically once released from a highly strained delivery configuration. A superelastic shape memory material such as Nitinol or an alloy with similar properties is particularly suitable. These materials have sufficient elastic strain capacity such that the elastic limit would not be exceeded when the shape memory portion200is constrained in a delivery configuration. This elastic strain capacity allows the shape memory portion200to self-expand when deployed. The shape memory lumen114can run the length of the catheter100, or in one example is only the length of the shape memory portion200or distal section106. The catheter100can also include a pull wire lumen118containing a pull wire120. The pull wire120can be used to deflect the distal tip202. The pull wire120can be anchored at its proximal end to the handle (described in more detail below). The pull wire120can be made of any suitable metal, such as stainless steel or Nitinol, and is preferably coated with Teflon7 or any other coating that imparts lubricity to the pull wire120. FIGS.7A-13illustrate different examples of the handle300. The handle300can include a body301, a distal tip deflection actuator302, a memory shape portion deployment actuator304, and a center axis306. The handle300is designed for ease of use.FIG.7Aillustrates the handle controls302,304in a neutral position and delivery configuration. In the neutral position the distal tip202can be approximately in line with the center axis306. In the neutral position the distal tip deflection actuator302is at a first position. The first position is the most proximal position of the distal tip deflection actuator302.FIG.7Aalso illustrates the delivery configuration where the memory shape portion200and the distal tip202are approximately in line with a center axis306. Here, the memory shape portion deployment actuator304can be at its most distal position. The distal tip deflection actuator302is at the first position and the memory shape portion deployment actuator304is at its first location. The neutral position and delivery configuration allow the catheter100to ride over the guidewire40to deliver the distal section106into the CS20. FIG.7Billustrates the handle300and catheter100in a deflected position. Here, the guidewire40has been removed, either completely or into the medial section104and the distal tip202is deflecting out of alignment with the center axis306. The deflection can be caused by the distal tip deflection actuator302being moved to a second position, more distal than the first.FIGS.8,9A,9B, and13illustrate the deflection mechanism. The pull wire120has a first end anchored in the distal tip202and a second end attached to a fixed point303(a tension screw as illustrated) in the body301. The distal tip deflection actuator302can be attached to the pull wire120such that any movement along the center axis306displaces the pull wire120. Extending the distal tip deflection actuator302can cause the distal tip302to deflect over a deflection angle between approximately 0° and approximately 180°. Deflecting the distal tip202allows the distal section106to be directed to the proper position within the CS20and the distal tip202in to the inferior vena cava (FIG.6). FIGS.9A and9Billustrate the locked and unlocked position of a deflection actuator lock310. In this example, a simple twist can lock and unlock the ability to deflect the distal tip202. Thus, the deflection actuator lock310has an unlocked position permitting the distal tip deflection actuator302to move between the first position (most proximal) and the second position (most distal). Also, the locked position prevents the distal tip deflection actuator310from moving between the first position and the second position. Additionally, a handle deflection brake308is apparent on the handle300to have stops at different deflection angles so the user can look at the handle300and determine how much the distal tip202is deflected. The distal tip202can be deflected when the shape memory portion200is undeployed and/or in the delivery configuration. FIGS.7C and10-13illustrate the deployed configuration of the shape memory portion200. The shape memory alloy116, as noted above, can be disposed at least along the shape memory portion200and comprising one end fixed in the body301. The shape memory alloy116has been preset to an expanded shape that is configured to anchor the distal section106of the coronary sinus catheter100in the coronary sinus20. As illustrated, that preset shape is a helix offset from the center axis306, but any shape can be considered that is atraumatic and can fit to the walls of the CS20. To facilitate the delivery and deployed configurations, a cover tube312can be disposed over the shape memory portion200or even a portion of the shape memory alloy116. In one example, the cover tube312can have a memory shape portion deployment end314fixed to the memory shape portion deployment actuator304. In the delivery configuration, the cover tube312constrains the shape memory portion200/shape memory alloy116and in the deployed configuration the shape memory portion200/shape memory alloy116is unconstrained by the cover tube312. FIGS.10and11illustrate the memory shape portion deployment actuator304at the most distal position (its first location) that maintains the cover tube312over the shape memory portion200/shape memory alloy116which prevents the shape memory alloy116from returning to its predetermined shape. Moving the memory shape portion deployment actuator304to a proximal position (its second location) withdraws the cover tube312away from the shape memory portion200/shape memory alloy116allowing the shape memory alloy116to return to the predetermined shape. This position is illustrated inFIGS.12and13. Said differently for one example, the cover tube312overlays almost the entire catheter100from the handle300to just before the distal tip202. The cover tube312can be flexible, made from Nitinol, stainless steel, or semi-stiff polymer, the tube can also be laser cut to allow for additional flexibility. The cover tube312needs to be stiff enough to constrain the shape memory portion200/shape memory alloy116from returning to its preformed shape, but flexible enough to allow the catheter100to traverse the vascular to be deployed in the CS20. The shape memory alloy116is fixed at one end inside the body301and the cover tube312is deployed over it. The cover tube312can be over the outside of the entire catheter100or coaxial inside the shape memory lumen114. The cover tube312is shorter in length than the shape memory alloy116to the point that when the memory shape portion deployment actuator304is distal at the first location, the cover tube312covers and constrains the shape memory portion200. Once the cover tube312is pulled back by the memory shape portion deployment actuator304being moved to the second location, the difference in length causes the shape memory alloy116to now be unconstrained and able to return to its preset shape. Additionally, either during or after the procedure, the memory shape portion deployment actuator304can be moved distal (i.e. back to the first location) to reconstrain the shape memory alloy116, bringing the catheter100back to its delivery configuration to then remove it from the vascular. The shape memory alloy116can also be reconstrained if the shape memory portion200needs to be repositioned during the procedure for any reason. FIGS.15and16illustrate other examples of coronary sinus catheters.FIG.15illustrates an example where the pull wire120can be used to both deflect the distal tip202and then pulled with additional force to deform the shape memory portion200into its deployed configuration. In this example, the shape memory alloy116can be preset to be straight and the tension pulls the alloy “out of shape” into, for example, a helical shape. In the illustrated example the pull wire120in within the pull wire lumen118only until the medial section104. The pull wire120is then outside a lumen until the distal tip202. This allows the distal section106to deform under tension. FIGS.16A and16Billustrate yet another stabilized coronary sinus catheter400having a main sensor probe402. The main sensor probe402can act similar to the distal tip202above having at least single axis location sensor424to guide the catheter400and include a plurality of main sensors406disposed along a length of the main sensor probe402. However, instead of the shape memory portion200, this example has a plurality of secondary sensor probes404. The plurality of secondary sensor probes404have a second length shorter than the first length and at least one secondary sensor406disposed at a distal position/tip. The second (shorter) length can be a plurality of different sub lengths and one or more of the secondary sensor probes404can have a different sub length. A sheath catheter450can have a lumen configured to allow the main sensor probe402and the plurality of secondary sensor probes404to pass therethrough. During delivery, a sheathed position can have the plurality of secondary sensor probes404enclosed in the lumen and at least a portion of the main sensor probe402outside the lumen. This allows a compact delivery profile to move the catheter400through the vascular to the CS20. Once in the CS20, the catheter400can be unsheathed, and the unsheathed position can have both the main sensor probe402and the plurality of secondary sensor probes404outside the lumen. Further, the plurality of secondary sensor probes404can angle α away from the main sensor probe402and apply a lateral force against the coronary sinus20. This lateral force acts as an anchoring force to stabilize the catheter400in the CS20, for all the reasons noted above. Descried differently, the catheter400can have a midline axis408and the main sensor probe402is disposed approximately along the midline axis408. Then, the plurality of secondary sensor probes404can be approximately parallel to the midline axis408in the sheathed position and form the angle α away from the midline axis in the unsheathed position. Specifically, the secondary sensor probe angle α is formed between at least one of the secondary sensor probes404and the midline axis408. The secondary sensor probe angle α can be between approximately 0° and approximately 90° and more particularly between approximately 0° and approximately 10°. The secondary sensor probes404can angle away from the midline axis408because they have shape memory alloy or some other form of bias to move them away. The bias can also be formed from thin shaped spring steel or other metals. FIG.17illustrates a method of using a coronary sinus catheter (i.e.100,400) to map electrical activity of the heart10. The coronary sinus catheter100,400can include a distal section106with a memory shape portion200, and a distal tip202, distal of the memory shape portion200. Also included is a handle300, disposed proximal of the proximal section102of the catheter with a body301, a distal tip deflection actuator302, a memory shape portion deployment actuator304, a cover tube312disposed over a portion of the memory shape portion200, and a center axis306. Examples of the steps can include delivering the coronary sinus catheter to the coronary sinus in a delivery configuration so that a distal section of the coronary sinus catheter is approximately in line with a center axis (1700). The distal tip402can be deflected out of alignment with the center axis306to steer the coronary sinus catheter100by actuating the distal tip deflection actuator302(1702). The memory shape portion200of the distal section106can be deployed in the coronary sinus20(1704). Deploying the memory shape portion200can have the additional steps of withdrawing the cover tube from the memory shape portion (1706) and returning the memory shape portion to a preformed shape (1708). Additionally, the method can include applying a lateral force against the coronary sinus20with the deployed memory shape portion200(1710). Certain aspects of the general disclosure can include two configurations, one straight, and another with a helical shape. The helical shape is created with a pre-formed wire of shape memory alloy (nitinol). The configurations are toggled by extending/retracting a tube internal to the catheter shaft. There is a deflectable tip for steerability. Multiple sensors allow visualization in a mapping system. A locking ring is disposed on the plunger/distal tip deflection actuator to prevent unwanted deflection while extending/retracting the tube. A multiple lumen plastic extrusion can be used to keep components separated e.g., electrical wires, nitinol and tube. The electrodes over helical length to allow for multi-circumferential cardiac information. As to the attachment points within the handle, the puller wire can be anchored distally at distal area of deflectable tip and proximally to a shaft in the proximal area of the handle body. The proximal anchor point of the pull wire allows for adjustment of tension in the wire during assembly. The nitinol wire with a pre-formed helix shape can be anchored distally to the catheter tip, distal of the helix shape. The nitinol wire can be further anchored proximally at the proximal end of the plunger part. This allows the entire length of nitinol wire to move together with the shaft during tip deflection. The tube's distal end floats free in the catheter lumen and is anchored to a stud located in the handle. The nitinol and tube also have an exemplary behavior where the nitinol wire acts as a guide and bearing surface for the tube which passes over it. The tube has two sections, a distal section is more flexible to facilitate motion over the helical shape, and through the anatomy. The proximal section is stiffer to allow higher force transmission. To reduce friction during tube extension/retraction, a lubricant is used on the interfaces of nitinol wire and tube. The lubricant can also be used between the tube and catheter lumen. The tube assembly can have protrusions with smooth contours (“beads”) around the outer circumference, spaced along the distal length, including at the distal tip, to reduce friction during tube extension/retraction. The plunger and handle have clearance for the tube anchoring stud to allow for movement of the tube relative to these components. Examples regarding the tip deflection which include that the handle has a stroke limiting feature that allows adjustment of allowable pull wire deflection during assembly. Wire coils can be used in the shaft section immediately proximal and distal of the helical area, but not in the helical area, to add stiffness to the catheter which improves tip deflection. However, the distal deflectable tip is soft yet allows for deflection. Other features of a stabilized coronary sinus catheter with distal strain relief have a proximal section including a proximal stiffness, a medial section, distal of the proximal section, including a medial stiffness, and a distal section, distal of the medial section. The distal section can include a memory shape portion, a distal tip, distal of the memory shape portion, a shape memory lumen disposed along the shape memory portion, and a shape memory alloy, disposed in the shape memory lumen. There can be a delivery configuration including the memory shape portion and the distal tip approximately in line with a center axis and a deployed configuration including the memory shape portion forming a shape approximately conforming to the shape of the coronary sinus. The distal tip can include a flexibility greater than the proximal stiffness, the medial stiffness, and a stiffness of the shape memory alloy. The stabilized coronary sinus catheter can have the distal tip configured to hang in the right atria when in the deployed configuration. The shape of the shape memory portion can have an approximately helix shape and configured to apply a lateral force to the coronary sinus. Also, the helix can be formed along a distal section axis offset from the center axis. A plurality of sensors can be disposed along the distal section and a sensor wire lumen, including a sensor cable disposed therein, can connect the plurality of sensors. A guidewire lumen can be further disposed from the proximal section to the distal section so that the delivery configuration further has the distal section conforming to a shape of a guidewire disposed in the guidewire lumen. Then the deployed configuration occurs when the guidewire is partially removed from the guidewire lumen. A pull wire lumen can additionally be disposed from the proximal section to the distal tip and a pull wire disposed in the pull wire lumen. A neutral position can include the distal tip approximately in line with the center axis and a deflected position displacing the pull wire with the distal tip moving out of alignment with the center axis. Another stabilized coronary sinus catheter system can have the coronary sinus catheter with a proximal section, a distal section (including a memory shape portion, and a distal tip, distal of the memory shape portion), a shape memory lumen disposed along the shape memory portion, and a shape memory alloy disposed in the shape memory lumen. The handle can be disposed proximal of the proximal section and include a distal tip deflection actuator, a memory shape portion deployment actuator; and a center axis. A neutral position can include the distal tip approximately in line with the center axis and the distal tip deflection actuator at a first position and the deflected position including the distal tip moving out of alignment with the center axis and the distal tip deflection actuator at a second position. Next a delivery configuration can include the memory shape portion and the distal tip approximately in line with a center axis and the memory shape portion deployment actuator at a third position, and a deployed configuration including the memory shape portion forming a shape approximately conforming to the shape of the coronary sinus and the memory shape portion deployment actuator at a fourth position. The pull wire lumen can be disposed from the proximal section to the distal tip with a pull wire disposed in the pull wire lumen. The distal tip deflection actuator can be attached to the pull wire, and the second position displaces the pull wire. The guidewire lumen is disposed from the proximal section to the distal section. A medial section, distal of the proximal section, can include a medial stiffness, the proximal section comprises a proximal stiffness, and the distal tip include a flexibility greater than the proximal stiffness, the medial stiffness, and a stiffness of the shape memory alloy. A plurality of sensors can be disposed along the distal section, and a sensor wire lumen has a sensor cable disposed therein connecting the plurality of sensors. A method of using a coronary sinus catheter to map electrical activity of a heart, includes the steps of delivering the coronary sinus catheter to the coronary sinus in a delivery configuration so that a distal section of the coronary sinus catheter is approximately in line with a center axis. Deploying a memory shape portion of the distal section of the coronary sinus catheter in the coronary sinus and dangling a distal tip of the distal section in the right atria when the memory shape portion is deployed. The method further includes applying a lateral force against the coronary sinus when the memory shape portion is deployed. A further stabilized coronary sinus catheter includes a main sensor probe including a plurality of main sensors disposed along a first length of the main sensor probe and a plurality of secondary sensor probes. The secondary sensor probes each including a second length shorter than the first length, and a secondary sensor disposed on the distal position. A sheath catheter can have a lumen configured to allow the main sensor probe and the plurality of secondary sensor probes to pass therethrough. A sheathed position can have the plurality of secondary sensor probes enclosed in the lumen and at least a portion of the main sensor probe is outside the lumen. The unsheathed position includes both the main sensor probe and the plurality of secondary sensor probes are outside the lumen, and the plurality of secondary sensor probes angled away from the main sensor probe and applying a lateral force against the coronary sinus. The stabilized coronary sinus catheter second length has a plurality of sub lengths, and a portion of the plurality of secondary sensor probes each have a different sub length. A midline axis is included, and the main sensor probe is disposed approximately along the midline axis. Also, the plurality of secondary sensor probes are approximately parallel to the midline axis in the sheathed position and form an angle away from the midline axis in the unsheathed position. A secondary sensor probe angle can be formed between a secondary sensor probe and the midline axis. Here, the secondary sensor probe angle can be between approximately 0° and approximately 90°. More specifically, the secondary sensor probe angle can be between approximately 0° and approximately 10°. The descriptions contained herein are examples of embodiments of the disclosure and are not intended in any way to limit the scope of the disclosure. As described herein, the disclosure contemplates many variations and modifications of ablation tools and diagnostic tools, including alternative numbers of electrodes, alternative combinations of electrodes, combinations of components illustrated in separate figures, alternative materials, alternative component geometries, and alternative component placement. Modifications and variations apparent to those having ordinary skill in the art according to the teachings of this disclosure are intended to be within the scope of the claims which follow. | 34,246 |
11857739 | DETAILED DESCRIPTION OF THE BEST MODE OF THE INVENTION FIG.1shows the distal end10of a catheter12for dialysis. An outlet14is provided at the distal end10, by means of which the extracted blood can be fed to a dialyzer. An inlet16is also provided, by means of which purified blood can be supplied to the patient. A tube section18is provided on the outlet14and on the inlet16, the two tube sections18opening into a coupling part20. In the coupling part20, the lumens of the two tube sections18are coupled into a two-lumen tube section22. On the single-lumen tube sections18, clamping means25are additionally arranged with which the tube sections18can be closed. When using the catheter12, the proximal end (not shown in the Figures) is inserted into a blood vessel, in particular into the right auricle. Especially in long-term application, the catheter12remains in or on the patient for several weeks or months. In order to securely fix the catheter12to the patient, the catheter12provides two fixing means26and28, which are shown as an individual part inFIGS.2and3. The insertion and placement of the catheter12is executed without the two fixing means26and28. After the catheter12has reached its final position, the fixing means26,28can be clipped onto the respective tube section18,22of the catheter12. The fixing means26then surrounds the two single-lumen tube sections18. The fixing means28surrounds the double-lumen tube section22. As is clear fromFIGS.2and3, the fixing means26and28each have a receiving part30and an opening part32, wherein the opening part32can be moved from an opening position, which is shown inFIGS.2a,2cand3a,3c, to a closing position, which is shown inFIG.2b,2dandFIG.3b,3d. The opening part32is arranged on the receiving part30by means of a film hinge34. The fixing means26,28are preferably made of plastic and are formed in one piece. The receiving parts30each have a latching section36which, in the closing position, interacts with a counter-latching section38provided on the opening part32. In the closing position, the latching section36, or the teeth thereof, is in the counter-latching section38, or between the teeth thereof. As is clear fromFIG.2, a total of three eyelets40,42and44are formed on the receiving part30. The two eyelets40and42are arranged parallel to one another and have a common longitudinal axis46. On the underside, the receiving part30has a flat support section48which extends into the underside of the eyelets40,42and44. The support section48is used for contact with the patient. As is also clear fromFIG.2, an eyelet50is likewise provided on the opening part32and, in the closing position, as is clear fromFIGS.2band2d, comes to rest between the two eyelets40,42adjacent to the receiving part. Consequently, in the closing position, the eyelet50of the opening part32is between the two eyelets42,40adjacent to the receiving part. The receiving part30and the opening part32have a circular inner contour52, which corresponds to the outer contour of the tube section22, but has a somewhat smaller diameter, such that the tube section22is arranged in the closing position under slight prestress in the fixing means and is secured in the axial direction. The fixing means28is sewn onto the patient by means of suitable threads onto the patient. A thread is passed through the eyelets42,50and40and is attached to the patient. Another thread is passed through the eyelet44and is also sewn to the patient. In the long-term application of the catheter12, the fixing means28, which is close to the point at which the catheter12is inserted into the patient, can be removed after 4-6 weeks for hygienic reasons. The fixing means26shown inFIG.3essentially corresponds to the fixing means28. Each component is provided with corresponding reference numerals. In contrast to the fixing means28, the fixing means26receives the two tube sections18extending parallel to one another. For this reason, the inner contour54of the fixing means26is designed to be complementary to the outer contour of the tube sections18. In contrast to the fixing means28, the fixing means26can also be opened when it is sewn on the patient. Both fixing means26and28have the advantage that they can only be placed onto the respective tube sections18,22after the catheter12has been inserted and placed in the patient. | 4,345 |
11857740 | DETAILED DESCRIPTION Examples of the present disclosure relate to medical device introducer sheaths for introduction of an elongate body of the medical device into a seal, valve, scope, or port of an insertion device. The introducer sheath may be used to assist in delivery of the elongate body into any appropriate insertion device. Reference will now be made in detail to examples of the present disclosure described above and illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts. The terms “proximal” and “distal” are used herein to refer to the relative positions of the components of an exemplary medical device or insertion device. When used herein, “proximal” refers to a position relatively closer to an operator using the medical device or insertion device or closer to the exterior of the body or patient. In contrast, “distal” refers to a position relatively further away from the operator using the medical device or insertion device, or closer to the interior of the body or patient. FIG.1illustrates a system100including an insertion device102, a medical device10, and an introducer sheath20. The insertion device102may be a ureteroscope (e.g., LithoVue™ Single-Use Digital Flexible Ureteroscope by Boston Scientific Corp.), an endoscope, a hysteroscope, a bronchoscope, a cystoscope, or any other similar device. The insertion device102may include a handle108, a delivery sheath110, and an actuator112on the handle for steering a distal end106of the delivery sheath110. A port104, which could be a T-connector as shown, may internally connect one or more lumens extending through the delivery sheath110to one or more distal openings in distal end106such that various medical devices may be inserted through the delivery sheath110of the insertion device102. Port104of the insertion device102may include a removable valve30(shown detached inFIGS.1and2and attached to insertion device102inFIG.6). Valve30may form a seal by itself or in combination with an element passing through the valve by the valve's seal returning to its normally closed state (e.g., a Urolock™ Adaptor by Boston Scientific Corp.) or by the compression of a grommet by a user's hand (e.g., a Touhy Borst valve). The insertion device102may include an integral camera at distal end106that is connected to processing software and a display via a communication and power conduit114. Medical device10will be described as a retrieval basket device; however, it is understood that medical device10may be any type of medical device used in conjunction with insertion device102to deliver medical therapy to a target site inside a patient. For example, the medical device may alternatively be a laser fiber, an irrigation and/or aspiration tube, a snare, forceps, and/or a needle. As shown inFIGS.1and2, the medical device10may include a handle12and an elongate body14. Handle12may include an actuator32for controlling the opening (FIG.1) and closing (FIG.2) of a retrieval basket16of medical device10. Elongate body14may have a length of between 70 cm and 220 cm and may extend from the handle12to a distal end36of the medical device10. Elongate body14may include a shaft34connecting the handle12to retrieval basket16. Elongate body14may also include a sheath38connected to actuator32to sheath and unsheath retrieval basket16corresponding to the open and closed basket configurations shown inFIGS.1and2, respectively. As shown inFIGS.1-3, introducer sheath20may be positioned about elongate body14and include a proximal end21and a distal end23, and may include a lumen extending from the proximal end21to the distal end23. The lumen may extend to a proximal end face of the proximal end. In particular, introducer sheath20may include a first opening26in the distal end23. A tab22may be formed distal to the first opening26and extend distal to the lumen. Tab22may be a flattened integral portion of introducer sheath20, a curved portion, or may take any shape that allows a user to hold or pinch the distal end23of the introducer sheath20extending from the first opening26. Tab22may also be formed of a separate member from a body of the introducer sheath. A second opening28may also be included in the proximal end21of introducer sheath20. Introducer sheath20may include a frangible portion24along the length of the introducer sheath20, extending between the distal end23and the proximal end face of the proximal end21. Frangible portion24may be formed by cutting a slit along the length of the introducer sheath20. Frangible portion24may also be formed by a perforation or reduced thickness portion of the introducer sheath20, or by a longitudinally extending gap or discontinuity in the introducer sheath20. Frangible portion24may be formed from the first opening26at the distal end23to the proximal end face of proximal end21, and frangible portion24may run in a straight line from the first opening26at the distal end23to the proximal end face of proximal end21. Frangible portion24may be the same length as the introducer sheath20, or a shorter length. Frangible portion24may be located circumferentially opposite tab22and aligned with a longitudinal axis of second opening28so that the frangible portion24ends at a distal end of second opening28and starts again at a proximal end of second opening28. It is understood, however, that frangible portion24may be located at any circumferential position along introducer sheath20. Introducer sheath20may be circular (FIG.3), hexagonal, oval, or any cross-sectional shape. Moreover, introducer sheath20may have a C-shaped cross-section such that the introducer sheath20may be snapped or wrapped around the elongate body14. In such a C-shaped configuration, frangible portion24is formed by the gap of the C-shape. Introducer sheath20may be formed by a tubular extrusion. Introducer sheath20may also be formed by sizing a tubular extrusion to the outer diameter of elongate body14. Frangible portion24may then be formed in the introducer sheath20. For example, frangible portion24may be formed by cutting a slit with a scalpel inserted into the outer diameter of introducer sheath20. The introducer sheath20may be dragged against the scalpel lengthwise to form frangible portion24. Alternatively, frangible portion24may be formed by cutting a slit in introducer sheath20while introducer sheath20is being formed or extruded. Moreover, frangible portion24may be formed as the gap in a C-shaped tubular extrusion forming introducer sheath20. Such a C-shaped introducer sheath20may be reheated to form a circular cross-sectional shape, where the edges of the C-shaped configuration overlap. A C-shaped introducer sheath may also be formed by heating a flat strip of material through a smaller die to create a C-shaped configuration or a circular cross-sectional shape, where the edges of the C-shaped configuration overlap. Introducer sheath20may be formed of elastomeric. Introducer sheath20may also be formed of silicone, thermoplastic elastomer, ethylene-propylene, fluorocarbon, or other similar materials. The introducer sheath20may be matched to a specific elongate body14of a specific medical device10such that the introducer sheath's inner diameter and length correspond to the specific elongate body14and specific medical device10. In another example, the introducer sheath20may have an inner diameter slightly smaller than the outer diameter of the elongate body14of the medical device10such that, when coupled, the introducer sheath20snugly encircles the elongate body14. In a further example, the introducer sheath20may have an inner diameter equal to or slightly larger than the outer diameter of the elongate body14of the medical device10such that, when coupled, the introducer sheath20is free to slide along the elongate body14when the introducer sheath20and the elongate body14are in a straight condition, but are friction coupled when either the introducer sheath20or elongate body14, or both elements, are curved, bent, or otherwise not straight. The introducer sheath20and elongate body14may form alternative or additional frictional engagements, couplings, or associations. For example, as shown inFIGS.1and2, valve30may be removed from port104and positioned about and coupled to the proximal end21of the introducer sheath20. Valve30may provide enough compression force on introducer sheath20to couple introducer sheath20with elongate body14. For example, valve30may be positioned about the second opening28and compress this more flexible portion of introducer sheath20to frictionally couple the introducer sheath20and the elongated device14. Next,FIGS.4-6illustrate the rapid introduction of the medical device10into insertion device102through the use of introducer sheath20. As shown inFIG.4, the distal end36of the elongate body14, which extends distally beyond the introducer sheath20, is introduced into the insertion device102via a port104. The tab22of introducer sheath20may be angled away from the port104such that the tab22can be held by a user. As shown inFIG.5, the tab22can be pulled away from and deflected by port104to separate the introducer sheath20from the elongate body14about the frangible portion24. Due to the coupling between the introducer sheath20and the elongate body14, as the user pulls the tab22toward a distal end of handle108to further separate the introducer sheath20from the elongate body14, the elongate body14is moved distally therewith and thus is rapidly introduced into the insertion device102. Continued pulling of the tab22distally causes introducer sheath20to separate from the elongate body14until the valve30reaches port104of the insertion device102. Further distal pulling on the tab22fully separates the introducer sheath20from both the elongate body14and valve30, resulting in the valve30being located adjacent port104of the insertion device102(FIG.6). Lastly, the valve30may be threaded, capped, or otherwise attached to the port104to complete the introduction of the elongate body14into the insertion device102. It should be noted that the relationship of the length of the elongate body14and introducer sheath20determines the position of the distal end36of the elongate body14, and thus the retrieval basket16, relative to the distal end106of the insertion device102after completing the introduction via introducer sheath20. Different types of scopes vary in working length from approximately 70 cm to approximately 220 cm. In some examples, the introducer sheath20has a length such that, when the proximal end21of introducer sheath20is located adjacent port104, the distal end36of the elongate body14and the retrieval basket16are positioned flush with the distal end106, just proximal to the distal end106, or just distal to the distal end106(FIG.6). For example, introducer sheath20may have a length between 70 cm and 80 cm when used in conjunction with a 75 cm scope. As noted above, the introducer sheath20may range in length depending on the type of medical device10, elongate body14, retrieval basket16, insertion device102, medical procedure, and other factors. Another aspect of the present disclosure is described with reference toFIGS.7and8. In this example, an introducer sheath70is used to protect fragile or sensitive components in the elongate body14and the retrieval basket16as they move in a direction D to pass through a normally closed seal or valve40attached to port104of the insertion device102(FIG.8). Here, the normally closed seal or valve40may be part of a valve system that includes valve30, as previously discussed with respect toFIGS.1-6. Normally closed seal or valve40may be used in conjunction with valve30to form an adjustable seal. FIG.7illustrates the introducer sheath70with tapered tip75at the distal end73and a first opening76at the proximal end71. Although tapered tip75is narrower than the remaining portion of introducer sheath70, tapered tip75is open such that elongate body14may pass fully through and out of either end of introducer sheath70. A frangible portion74runs the length of the introducer sheath70from the tapered tip75to the first opening76, and a tab72extends from the first opening76on the proximal end of the introducer sheath70and circumferentially opposite to the frangible portion74. This introducer sheath70may range in length between approximately 1 cm and approximately 10 cm depending on the type of medical device10, elongate body14, retrieval basket16, insertion device102, medical procedure, and other factors. Moreover, the inner diameter of the introducer sheath70may be slightly larger than the outer diameter of the elongate body14so that the elongate body14may slide axially through the introducer sheath70and the introducer sheath70may slide axially over the elongate body14, as shown inFIG.8. To insert the fragile or sensitive components of the elongate body14, including the retrieval basket16through the normally closed seal or valve40, the introducer sheath70surrounds the elongate body14, including the distal end36which is not shown inFIG.8as it is surrounded by the introducer sheath70. The tapered tip75, which includes an axial opening large enough for elongate body14to pass through, is inserted into the normally closed seal or valve40to prop open the valve. The elongate body14may then axially slide in the distal direction through the inner diameter of the introducer sheath70and through the tapered tip75in direction D, such that distal end36of elongate body14may emerge and slide distal to the tapered tip75and be selectively positioned distal to the normally closed seal or valve40. After the distal end36of elongate body14has been positioned past the normally closed seal or valve40, the tapered tip75of the introducer sheath70may be retracted proximally to close the normally closed seal or valve40around the elongate body14. The user may elect to leave the introducer sheath70on the elongate body14proximal to the normally closed seal or valve40, allowing the user to prop open the normally closed seal or valve40again with tapered tip75to adjust the position of the normally closed seal or valve40relative to elongate body14. The user may also elect to remove the introducer sheath70by pulling the tab72in a direction E away from the elongate body14, such that the frangible portion74splits and separates the introducer sheath70from the elongate body14. Removing the introducer sheath70from the elongate body14may allow for a longer working length of the elongate body14and avoid interference or obstruction from the introducer sheath70during manipulation of the elongate body14during the medical procedure. Valve30may also then be threaded, capped, or otherwise attached to normally closed seal or valve40. Alternatively, the tapered tip75may be inserted into the normally closed seal or valve40, and the distal end36of elongate body14together with the surrounding introducer sheath70may pass in direction D through the normally closed seal or valve40, allowing for the introducer sheath70to shield the fragile or sensitive components in the elongate body14. Once the distal end36of elongate body14has been positioned distally to the normally closed seal or valve40, the introducer sheath70and the tapered tip75may be retracted proximally such that the elongate body14emerges from the opening in tapered tip75and such that normally closed seal or valve40closes around the elongate body14. The user may elect to leave the introducer sheath70on the elongate body14proximal to the normally closed seal or valve40, allowing the user to prop open the normally closed seal or valve40again with tapered tip75and introducer sheath70to adjust the position of the normally closed seal or valve40relative to elongate body14. The user may also elect to remove the introducer sheath70by pulling the tab72in a direction E away from the elongate body14, such that the frangible portion74splits and separates the introducer sheath70from the elongate body14, which may allow for a longer working length of the elongate body14and avoid interference or obstruction from the introducer sheath70during manipulation of the elongate body14during the medical procedure. Valve30may also then be threaded, capped, or otherwise attached to normally closed seal or valve40. In this example where introducer sheath70passes through normally closed seal or valve40together with elongate body14, introducer sheath70may be longer than the 1 cm to 10 cm length previously discussed with respect to this aspect of the disclosure. Another aspect of the present disclosure is described with reference toFIGS.9and10. In this example, an introducer sheath90is used to protect fragile or sensitive components in the elongate body14and the retrieval basket16as they move in a direction F and pass through a normally closed seal or valve50that is not coupled to an insertion device. Using introducer sheath90allows normally closed seal or valve50, which is manufactured separately from medical device10, to be selectively positioned along elongate body14of medical device10more quickly while protecting the fragile or sensitive components. Moreover, as a result, insertion of elongate body14into a port104of an insertion device102similar to that inFIG.1or any scope or medical device channel is made easier because positioning the normally closed seal or valve50proximally along elongate body14reduces resistance and thus provides for a better insertion. Here,FIG.9illustrates the introducer sheath90with a tapered tip95at a distal end93. Although tapered tip95is narrower than the remaining portion of introducer sheath90, tapered tip95is open such that distal end36of elongate body14may pass fully through and out of either end of introducer sheath90. Again, this introducer sheath90may range in length between approximately 1 cm and approximately 10 cm depending on the type of medical device10, elongate body14, retrieval basket16, medical procedure, and other factors. In this example, the inner diameter of the introducer sheath90may be slightly larger than the outer diameter of the elongate body14so that the elongate body14may slide axially through the introducer sheath90and the introducer sheath90may slide axially over the elongate body14, as shown inFIGS.9and10. To insert the fragile or sensitive components of the elongate body14through the normally closed seal or valve50in direction F, the introducer sheath90surrounds the elongate body14, including the distal end36which is not shown inFIG.9as it is surrounded by the introducer sheath90. The tapered tip95is inserted into the normally closed seal or valve50to prop open the valve. The elongate body14of the medical device10may then follow through the normally closed seal or valve50by sliding axially through the inner diameter of the introducer sheath90in the distal direction. After the distal end36of the elongate body14has been selectively positioned past the normally closed seal or valve50, the tapered tip95of the introducer sheath90may be retracted proximally to close the normally closed seal or valve50around the elongate body14, allowing the user to prop open the normally closed seal or valve50again with tapered tip95to adjust the position of the normally closed seal or valve50relative to elongate body14. Alternatively, once the tapered tip95has been inserted to prop open the normally closed seal or valve50, both the introducer sheath90and the elongate body14may be inserted in direction F through the normally closed seal or valve50with the introducer sheath90protecting the fragile or sensitive components of the elongate body14and the retrieval basket16. After the distal end36of the elongate body14has been selectively positioned past the normally closed seal or valve50, that is, when the normally closed seal or valve50is selectively positioned along the elongate body14, the user may retract the introducer sheath90and its tapered tip95to close the normally closed seal or valve50and may elect to leave the introducer sheath on the elongate body14on the proximal side of the normally closed seal or valve50, allowing the user to prop open the normally closed seal or valve50again with tapered tip95and introducer sheath90to adjust the position of the normally closed seal or valve50relative to elongate body14. The user may also elect to remove the introducer sheath90after the distal end36of the elongate body14has been selectively positioned past the normally closed seal or valve50by pulling the introducer sheath90distally fully past the normally closed seal or valve50in direction F such that the normally closed seal or valve50closes around the elongate body14. Then, the user may continue to slide the introducer sheath90in direction F off the distal end36of the elongate body14, removing the introducer sheath90. As a result, the normally closed seal or valve50may be positioned more quickly on the elongate body14at the desired position, as shown inFIG.10, and the introducer sheath90will not interfere or obstruct the manipulation of the elongate body14during the medical procedure. Moreover, insertion of elongate body14into a port104of an insertion device102similar to that inFIG.1or any scope or medical device channel is made easier because positioning the normally closed seal or valve50proximally along elongate body14reduces resistance and thus provides for a better insertion. Normally closed seal or valve50could then be threaded, capped, or otherwise attached to the port104of the insertion device102. In this example where introducer sheath90passes through normally closed seal or valve50together with elongate body14, introducer sheath90may be longer than the 1 cm to 10 cm length previously discussed with respect to this aspect of the disclosure. While principles of the present disclosure are described herein with reference to illustrative examples for particular applications, it should be understood that the disclosure is not limited thereto. Those having ordinary skill in the art and access to the teachings provided herein will recognize additional modifications, applications, embodiments, and substitution of equivalents all fall within the scope of the features described herein. Accordingly, the claimed features are not to be considered as limited by the foregoing description. | 22,379 |
11857741 | DETAILED DESCRIPTION Numerous details are set forth to provide an understanding of the examples described herein. The examples may be practiced without these details. The description is not to be considered as limited to the scope of the examples described herein. Endovascular repair of aortic aneurysms are particularly challenging for certain patient anatomies. Considerations include, but are not limited, the direction of a blood vessel, the relative orientation of a blood vessel, as well as the direction of blood flow can all influence the technical difficulty of placing an endograft or a bridging stent in the blood vessel. For example, advancing a covered balloon expandable stent through a downgoing branch in a branched endograft and into an upgoing blood vessel (typically an upgoing renal artery) can be difficult, if not impossible. Additional challenges are also present if the endograft is not appropriately aligned. The endograft can be misaligned if all branches or fenestrations cannot be lined up with target blood vessels, due to variations in patient anatomy. Human error plays a factor, due to limitations in fluoroscopic and angiographic guidance techniques. Blood vessel tortuosity and delivery device torqueing can also lead to misalignment. Furthermore, positioning an endograft often faces technical challenges such as wire wrapping, wire trapping on hooks, blood vessel resistance, or failure to remove the delivery catheter. The looped wires, systems, and methods described herein are intended to reduce the execution time of endograft procedures, as well as to provide an alternative or secondary procedure for stenting if standard endovascular procedures fail to deploy a stent at the target location of a blood vessel. In current procedures, if stenting with existing endograft designs cannot be performed due to difficult anatomy or variations in anatomy, patients then require a highly invasive open surgery for aneurysm repair. Proper placement of the endograft is crucial since improper placement may result in, for example, partial or complete blockage of the endograft fenestrations or branches that can lead to tissue infarction. Endoleaks, which are leaks into the aneurysm sac after endovascular repair, are another concern that can lead to rupture. In some embodiments, the looped wire and methods disclosed herein reduces the execution time of endovascular aneurysm repair procedures and allows for greater ease of use of current endograft systems. The looped wire is used as a pre-cannulation wire and/or for facilitating the placement of endovascular wires through fenestrations or branches prior to deployment of the endograft into the aneurysm. In an embodiment, the looped wire also acts as a guide wire for positioning a stent in a target location. These pre-cannulation wires facilitate endovascular repair of aneurysms, such as but not limited to, iliac artery aneurysms (requiring internal iliac preservation), thoracoabdominal aneurysms, and ascending or aortic arch aneurysms. One advantage of using the looped wire and methods as disclosed herein as a pre-cannulation wire for endovascular aneurysm repair is that the risk of wire wrapping is reduced or eliminated. One system of covered stents is described in US Patent Application Publication No. 2017/0340461, the contents of which are incorporated herein by reference in its entirety. This system uses a guiding mate mounted onto the distal end portion of a delivery catheter. The guiding mate is used to thread a guiding element and thereby guiding the delivery catheter towards a distal end of the guiding element. However, such a system requires multiple tools (a catheter with a guiding mate and wire) and the endograft needs to be modified to include a guiding element that allows stenting of target vessels. The looped wires, systems, and methods described herein require minimal tools, namely the looped wire itself, and the endograft does not need to be modified to utilize the looped wire for stenting. Accordingly, the looped wires described herein can be used with commercially available endografts. Since a single tool, the looped wire, is used to accomplish multiple different actions during aneurysm repair, the overall procedure is made much simpler, which in turn reduces the time required for the procedure. In other embodiments, the looped wire disclosed herein is used as a snare to lasso a thread, a suture, or an endovascular wire for threading the thread, suture, or endovascular wire through a cavity or lumen of a structure. In yet other embodiments, the looped wire disclosed herein is used as a probe for introducing a medical device or tool into a lumen of a bodily structure, such as but not limited to, blood vessels, lymph vessels, the gastrointestinal tract, or the genitourinary tract. As used herein, an “access hole”, “entry point” or “access sites or point” all refer to a puncture location allowing for access into a vessel or tract, such as a blood vessel. An access site is where an endovascular wire or endograft in introduced into the blood vessel. Examples include, but are not limited to, open surgical exposure options and percutaneous options, percutaneous femoral access, percutaneous arm access (brachial artery or axillary artery), or percutaneous carotid artery access. Typically an introducer sheath is partially passed into the blood vessel through the puncture location, to allow for subsequent introduction of other devices (such as catheters, endovascular wires, and stents). As used herein, “to advance” or “advancing” refers to passing or moving an object forward into or through a lumen (such as a blood vessel) or a tubular structure (such as a catheter). The term also refers to passing or moving a tubular structure (such as a catheter or stent) over, for example, a wire, such that the wire slides through the tubular structure acting as a track to guide the tubular structure to a target location. As used herein, a “vessel” or a “tract” refers to a tubular structure in a body. Examples include, but are not limited to, blood vessels, lymph vessels, gastrointestinal tracts, genitourinary tracts, or respiratory tracts. References to vessels include references to tracts. Examples of blood vessels include, but are not limited to, arteries, aorta, or veins. References to “artery” should not be interpreted at limiting the application of the subject matter disclosed herein. Accordingly, references to “artery” should be interpreted to include references to any blood or fluid vessel in the body, for example, arteries, veins, or lymph vessels. As used herein, the term “branch blood vessel” refers to a blood vessel that arises from a blood vessels splitting into a plurality of smaller blood vessels (such as the common iliac arteries), or a blood vessel that extends off from a main blood vessel (such as the renal arteries extending from the abdominal aorta). As used herein, the term “target location” refers to any location within a vessel or tract for treatment or diagnosis. For example, a target location or vessel includes location for deployment of a stent. As used herein, “anterior” refers to the front, while “posterior” refers to the back. These terms are anatomical terms of location used to describe the relative position of one structure to another in a patient. For example, the heart is posterior to the sternum because it lies behind it, and the sternum is anterior to the heart because it lies in front of it. As used herein, “superior” refers to higher, while “inferior” means lower. These terms are anatomical terms of location used to describe the relative position of one structure to another in a patient, relative to a vertical axis. For example, the head is superior to the neck, while the liver is inferior to the lungs. As used herein, “medial” refers to towards the midline, while “lateral” means away from the midline. These terms are anatomical terms of location used to describe the relative position of a structure in a patient with reference to a midline. For example, the eye is lateral to the nose, while the nose is medial to the ears. As used herein, references to “proximal” and “distal” are relative to a user of a device. For example, a distal end of a device refers to an end that is further away from the user than a proximal end. The distal end may also be referred as a “leading” end which is inserted or advanced first into or through a vessel, while the proximal end may also be referred to as the “lagging” end following the leading end as the device is advanced through a vessel. In the context of anatomical terms of location, “proximal” and “distal” are used in structures that are considered to have a beginning and an end (such as the upper limb, lower limb and blood vessels). They describe the position of a structure with reference to its origin, where “proximal” means closer to its origin and “distal” means further away from the origin. For example, the wrist joint is distal to the elbow joint. As used herein, a “sheath” or “introduction sheath” refers to a blunt cannula adapted for insertion into a cavity or vessel, and is used to introduce a catheter or other devices to perform endoluminal procedures. Sizes of a sheath are identified using the French scale. Appropriate sheaths and methods of using such sheaths are known and available to a skilled person. Example catheters include, but are not limited to, angiocatheters, urological catheters, gastrointestinal catheters, neurovascular catheters, or ophthalmic catheters. These catheters are made of, for example and not limited to, silicone, nylon, polyurethane, polyethylene terephthalate (PET), latex, and thermoplastic elastomers. Example angiocatheters are 3Fr, 4Fr, 5Fr, 6Fr, 7Fr, 8Fr, 9Fr, 10Fr, 11Fr, or 12Fr, preferably 3Fr to 6Fr catheters are used. Example angiocatheters also include, but are not limited to, KMP™, SOS™, RIM™, Pigtail™, and Shepherd's hook catheters. Endovascular wires are thin and flexible medical grade wires typically used as a guide for placement or positioning of a larger medical device, such as a catheter or a sent, in a patient. Standard endovascular wires come in two basic configurations: solid steel or nitinol core wires and solid core wire wrapped in a smaller wire coil or braid. Coiled or braided wires offer a large amount of flexibility, pushability and kink resistance. As used herein, the term “pushability” is defined as the ability to transmit force from the proximal end of a wire or catheter to the distal end. As used herein, the term “kink resistance” refers to a property of a wire or catheter that tends to avoid forming into tight curl, twist, or bend. One example endovascular wire is a wire from Boston Scientific™ which uses a nitinol tube with micro-cut slots instead of braided wire to improve torque control. Nitinol wire, used by itself or braided with stainless steel, helps increase flexibility and allows the wire to spring back into shape after navigating a tortuous vessel segment. The Cook Medical™ amplatzer wire or lunderquist wire is another example of an endovascular wire. Some endovascular wires are coated with a polymer, such as silicone or polytetrafluoroethylene (PTFE), to increase lubricity. Hydrophilic coatings reduce friction during positioning and for easier movement in tortuous vessels. Wire diameters are measured in thousandths of an inch, usually between 0.014 and 0.038 inches. Lengths are measured in centimeters, ranging from 80 to 450 cm. As used herein, the term “threading” refers to passing a thread, a suture, an endovascular, or similar thread-like material, through an opening. As used herein, “pre-cannulate” or “pre-cannulation” refers to threading a wire or a number of wires through the fenestrations or branches, or other openings, of an undeployed endograft during the manufacturing process of an endograft or after the manufacturing process just prior to insertion of the endograft into a patient through pre-cannulation tubes such as in the Gore TAMBE™ device. Typically pre-cannulated wires are used in a through-and-through access technique but are not limited to this. As used herein, a “stent” or a “stent graft” is a tubular support structure inserted into the lumen of an anatomic vessel or duct to keep the passageway open, and the term “stenting” refers to placement of a stent. One example of a stent is an aortic stent graft or an “endograft” typically used in EVAR procedures. An endograft is a fabric covered metallic stent intended for insertion and deployment at an aortic aneurysm. Example endografts include, but are not limited to, the Gore Medical™ (Flagstaff, Arizona, USA) Thoracoabdominal Branch Endoprosthesis (TAMBE™ device), iliac branch graft devices such as the Gore Iliac Branch Endoprosthesis™ or the Cook Zenith™ Iliac branch graft, or aortic arch aneurysm branch devices. Examples of current endovascular aneurysm repair procedures using some of these endografts is disclosed in https://www.goremedical.com/video/brightcove/excluder-iliac-branch-endoprosthesis-animation-video and https://www.cookmedical.eu/products/e2f94fbc-c83e-459e-9caf-aee8bd245cb7/ the disclosures of which is incorporated herein by reference in its entirety. Some endografts have one or more holes or “fenestrations” on the graft body to maintain the patency of branch blood vessels extending from the stented blood vessel. For example, an endograft may be attached to the abdominal aorta with one fenestration positioned over the opening to each of the renal arteries, thereby allowing blood flow to the kidneys. Some endografts have one or more “branches”, that extend from a “main body stent”, or a main portion, of the endograft. The branches are intended to be portals for other stents to be deployed from the main body stent into each branch blood vessel. Some endografts have both fenestrations and branches. As used herein, a “bridging stent” refers to a stent that is used for stenting a branch blood vessel and for connecting to a fenestrated or branched endograft. A bridging stent is deployed separately from the endograft, with at least one end in fluid communication with the main body stent of the endograft so as to allow for blood flow to the branch blood vessel. In some cases, a bridging stent is introduced through a different access point and blood vessel than the one use to advance the endograft. One example of a typical bridging stent is a covered balloon-expandable of self-expanding stent. As used herein, the term to “deploy” or “deployment” of a stent refers to releasing a stent from its cover or by other mechanisms so as to allow the stent to expand and stent a vessel. Typically, deployment of a stent is irreversible. Looped Wire Embodiments In some embodiments, the looped wire described herein is intended for facilitating the placement of an endograft into a blood vessel. The blood vessel can be an artery, such as the aorta. In an embodiment, the looped wire facilitates placement of an endograft into the aortic arch or the abdominal aorta. The looped wire comprises a flexible guidewire having a leading end and a lagging end and one or more loops distributed along the length of the guidewire. The lengths of the guidewire are not limited by the embodiments described herein, but may come in various lengths depending on the application. For example, in some embodiments, the guidewire is 200 cm, 250 cm, 300 cm, 350 cm, or 400 cm long. In one embodiment, the guidewire is 300 cm long. The guidewire is flexible and kink resistant, and requires minimal pushability for advancing itself through a blood vessel. In one embodiment, the guidewire is a nitinol guidewire The guidewire has a diameter of about 0.014 inches, 0.018 inches, 0.025 inches, or 0.035 inches In a preferred embodiment, the guidewire has a diameter of about 0.018 inch. In one embodiment, the guidewire is an endovascular wire. In another embodiment, the guidewire is a hybrid wire made of part endovascular wire and part suture material, which is used in circumstances where greater flexibility is desired. For example, a hybrid guidewire or a guidewire made of a suture material is more advantageous when advancing catheters over the guidewire at sharper or more acute angles that what standard wires allow. Optionally, the guidewire is hollow. The looped wire disclosed herein is intended for threading a thin strand of material through the one or more loops, and for sliding the one or more loops and in turn the looped wire along the length of the strand of material. For example, the strand of material is an endovascular wire, a suture, a thread, or any thread-like material. Each of the one or more loops has an inner diameter that is greater than the thickness of, for example, an endovascular wire, so that the endovascular wire can be threaded through the one or more loops. The diameter of each of the one or more loops also needs to be small enough such that the looped wire maintains a low overall profile. However, the diameter is also large enough such that a catheter or sheath can push the one or more loops along the length of the endovascular wire, while advancing the catheter or sheath over the endovascular wire. Therefore, in preferred embodiments, the one or more loops have an inner diameter that is about 0.002 to 0.003 inches larger than the diameter of the endovascular wire. In a preferred embodiment, the one or more loops have an inner diameter of about 0.038 inches for threading a 0.035 inch endovascular wire through the one or more loops. In another preferred embodiment, the one or more loops have an inner diameter of about 0.040 inches for threading a 0.038 inch endovascular wire through the one or more loops. The specific sizes and dimensions of the loops are not limited by the embodiments described herein, but may be sized and shaped based on the particular endovascular wires and catheters used in the endovascular aneurysm repair procedures. In some embodiments, the looped wire has a plurality of loops. In one embodiment, the looped wire has a first loop located proximate to the leading end of the guidewire, and preferably at the leading end of the guidewire. In another embodiment, the looped wire has a second loop located proximate to the lagging end of the guidewire, preferably at the lagging end of the guidewire. Turning toFIG.1A, an embodiment of a looped wire10is shown, having a circular first loop20at the leading end14of a nitinol guidewire12and a circular second loop25at the lagging end16of the guidewire12. The loops20and25are generally circular or elliptical, but can also be of any shape that allows for sliding along the length of an endovascular wire. The loops have an inner diameter (di) of 0.038 inches for threading through a 0.035 inch endovascular wire (seeFIG.1C). The loop can be made of the same material as the guidewire, for example nitinol, or a different material than the guidewire. In some embodiments, the one or more loops are flexible ellipses that are compressible into a compressed state for inserting the looped wire through a catheter. As shown inFIGS.1B and1C, the first loop is compressible from a non-compressed state22having a sufficient inner diameter for threading an endovascular wire or suture through and for sliding along the length of the endovascular wire or suture, to a compressed state21having sufficiently small outer diameter (do) for inserting the looped wire through a catheter. In one embodiment, the one or more loops have an outer diameter of less than 0.035 inches, less than 0.030 inches, or less than 0.025 inches for insertion through a 0.035 inch catheter. Various other outer diameters are possible in the compressed state, as long as the outer diameters of the one or more loops in the compressed state are less than the diameter of the catheter lumen. Optionally, the one or more loops are open loops, each having a fastening means for opening and closing the loops. For example, the open loops are pliable and can be bent into a closed loop, or the open loops comprise hooks on the open end of the loops for hooking the loops closed. The open loops can also be opened and closed by other mean known to a person skilled in the art. Optionally, the one or more loops are detachable from the guidewire where, for example, the one or more loops are attached to the guidewire by complementary screw and thread mechanism. Other designs for the detachable attachment of the one or more loops to the guidewire is known to a person skilled in the art. In some embodiments, the first and/or second loops20,25are formed by bending the leading and/or lagging ends14,16back on itself and attaching the ends to the guidewire23to form a ring or a noose. A coil around the wire, such as a platinum coil, can be used to keep the loop in the closed position. Alternatively, the first and/or second loops20,25are manufactured separately from the guidewire12and affixed onto the guidewire. Optionally, the one or more loops can be attached to the guidewire at an angle to facilitate sliding of the one or more loops along the length of, for example, an endovascular wire. In one embodiment of the looped wire10, the leading end14of guidewire12comprises a floppy tip. The floppy tip extends about 10 cm, 15 cm, 20 cm, 25 cm, or 30 cm from the leading end14of the guidewire12. Preferably, the floppy tip extends about 20 cm from the leading end14of the guidewire12. The floppy tip is intended to assist in navigating the looped wire through various vessel anatomies, and has greater flexibility than the rest of the guidewire. In some embodiments, the tip is made floppy by heating up an end portion of the nitinol guidewire to soften the guidewire. Alternatively, in other embodiments, an end potion (for example, 20 cm from the leading or lagging end) of the guidewire is ground down so that it is tapered over the length of this end portion. The thinned end portion of the guidewire is more floppy than the rest of the guidewire, thereby creating a floppy tip. One of the advantage of having a floppy tips is that a stiffer guidewire can be used for support and guiding a stent to a target location, while the flexibility of the floppy tip allows atraumatic advancement or introduction of the looped wire through a blood vessel. Either the leading or lagging end of the looped wire, can be made floppy. The lagging end is preferably made floppy, for example, when the looped wire is used as a snare during an endovascular procedure, so that the looped wire can bend on itself and fit through a sheath. In one embodiment of the looped wire, used for pre-cannulation, the guidewire is a PTFE coated nitinol wire having 0.018 inches in diameter and measuring 300 cm. One or both of the leading and lagging ends of the guidewire are tapered down to 0.005 inches in diameter to form a floppy tip, and the one or both ends are further looped on itself to form a loop. The loop is held in place with a platinum coil. Optionally or in addition, the distal 40 cm of the leading end is heated to soften the wire. Endograft Systems with Looped Wires The looped wires described herein are intended for use together with endografts for endovascular aneurysm repair. In an embodiment, one or more looped wires are threaded through the fenestrations or branches of an endograft before or after deployment of the endograft. This configuration is particularly useful for thoracoabdominal branch devices. The Gore TAMBE™ (Thoracoabdominal Branch Endoprosthesis) is one example system that benefits from pre-cannulating with the looped wire as described herein. Turning toFIG.2, a pre-cannulated endograft system100is shown comprising a deployed branched endograft102or a branched aneurysm stent graft that is pre-cannulated with a looped wire110. The system100also includes a deployment catheter140for deploying the endograft102, and a sheath150for placement at an access point in the blood vessel for subsequent introduction of other devices. The looped wire110has a first loop120at the leading end114of the wire, and the first loop120is threaded and anchored onto a primary endovascular wire130. The primary endovascular wire is used for advancing the endograft to a target location. One of the branches104ais pre-cannulated with the looped wire110. The looped wire extends from where it is anchored to the primary endovascular wire130, through the main body stent of the branched endograft102, and out through branch104a. The other branches104b,104c, and104dcan similarly be pre-cannulated with separate looped wires (not shown). The looped wire110has a second loop125at the lagging end of the wire116. This second loop125can be used to facilitate bridging stent placement as described in Example 3. Similar configuration or arrangement is used for fenestrated endografts. In some embodiments, the looped wire210can be threaded through the main body stent203of a branched endograft202, and out through a branch204to facilitate, for example, an arm approach to place bridging stents (seeFIG.3A). A first loop220at the leading end214of the looped wire210is anchored to the primary endovascular wire230. This configuration is compatible with the current Gore TAMBE™ device. An alternate embodiment is shown inFIG.3B, where the looped wire310is threaded from the outside of a branched endograft302, through a branch304and into the main body stent303to facilitate, for example, a femoral approach for placing the bridging stent. A first loop320at the leading end314of the looped wire310is anchored to the primary endovascular wire330. Preferably, the first loop220or230are threaded onto the primary endovascular wire230or330ahead of the endograft202or203. Similar configurations or arrangements are used for fenestrated endografts. One pre-cannulated fenestrated endograft system is described in Joseph, G. et al. “Externalized Guidewires to Facilitate Fenestrated Endograft Deployment in the Aortic Arch”, J Endovasc Ther. 2016 February; 23(1): 160-171, the disclosure of which is incorporated herein by reference in its entirety. This endograft system uses externalized guidewires to facilitate aortic arch endovascular repair. However, the endovascular repair techniques of Joseph et al. does not reduce or eliminate wire wrapping. If more than one fenestration is pre-cannulated using their technique then wire-wrapping and entanglement would become a major issue. The looped wires, systems, and methods described herein are intended for reducing or eliminating wire-wrapping, and at the same time accommodate pre-cannulation of multiple branches or fenestrations. By providing an endograft having fenestrations and/or branches pre-cannulated with multiple looped wires, this enables the treatment of more complicated aneurysms and overall makes the procedures simpler with reduced time and less complications for patients. Where the endograft is pre-cannulated with multiple looped wires each having a first loop at the leading end, the first loops are threaded onto the primary endovascular wire based on the order of use. For example, the most distally anchored first loop is the first one to be used or removed from the endovascular wire. This process is repeated for as many branches or fenestrations as needed. This process can be performed prior to the stent graft or endograft being sheathed or constrained for delivery, or after deployment. Once all of the first loops of the looped wires have been positioned as described above, the stent graft or endograft is advanced over the primary endovascular wire. As the stent graft or endograft is advanced forward, the tapered tip of the graft pushes the freely moving first loops up the primary endovascular wire, sliding the looped wires distally forward. One advantage of pre-cannulating an endograft with one or more looped wires is that these looped wires allow the endograft to rotate or twist as much as needed for adjustment and positioning of the endograft and for aligning the fenestrations or branches with the branch blood vessels without wire-wrapping or entanglement of wires. The looped wires are also anchored to the primary endovascular wire, and therefore do not inadvertently fall out of the fenestrations or branches. Furthermore, the pre-cannulation configuration described above allows the endograft to maintain an extremely low profile when advanced through blood vessels. Maintaining a low-profile is extremely important given that many currently used endografts have large profiles. In an embodiment, an endograft is provided in a delivery system by first pre-cannulating the endograft with one or more looped wires as described herein and then compressing or sheathing the endograft. By providing the endograft delivery system with the endograft pre-cannulated, the one or more looped wires are already in position for use when the endograft is deployed in an aneurysm. Such an endograft delivery system is beneficial since it reduces endovascular aneurysm repair procedure time, improves accuracy and efficiency of aligning fenestrations and branches with branch blood vessels, as well as prevents wire tangling. The delivery system comprises the endograft, a primary endovascular wire extending through a main body stent of the endograft, and one or more looped wires each anchored to the primary endovascular wire by a first loop at the leading end of the looped wire and in sliding engagement with the primary endovascular wire. The endograft has one or more fenestrations and/or branches, and the one or more looped wires extend through the main body stent of the endograft and out through the one or more fenestrations and/or branches. In some embodiments, only some of the fenestrations and/or branches are pre-cannulated with looped wires. In other embodiments, all the fenestrations and/or branches are pre-cannulated with looped wires. In a preferred embodiment, each fenestrations and/or branches are pre-cannulated with one looped wire per fenestration and/or branch. In an alternative embodiment, each fenestration and/or branched is pre-cannulated with one or more looped wires. In some embodiments, each or at least one of these looped wires further comprises a second loop at the lagging end of the looped wire. EXAMPLES Example 1 Pre-Cannulation with Looped Wires A through-and-though primary endovascular wire430was separately placed from femoral access point455band sheath450b, and out through the upper extremity access point455aand sheath450ain a “body-floss” configuration (seeFIG.4A). The primary endovascular wire430passes through a segment of the aorta470, and through an aneurysm in the aorta490. An endograft may also be separately deployed using this primary endovascular wire430(not shown). A first looped wire410awas threaded onto this primary wire430extending out of the upper extremity access point455a, by threading a first loop420aof the first looped wire410aonto the primary wire (seeFIG.4B). The first looped wire410awas inserted through the upper extremity access point455aand advanced out of the body through the femoral access point455bby sliding the first looped wire410aalong the primary wire430(seeFIG.4C). The looped wire410ais unthreaded from the primary wire430by sliding the first loop420aoff the primary wire from its free end extending out of the femoral access point455b(seeFIG.4D). At this point, a catheter and/or an endovascular wire can then be placed or passed over the first looped wire410afrom its lagging end416a, and inserted into the aorta from the upper extremity access point455awire to facilitate antegrade placement of a stent, such as a bridging stent, if an endograft was previously deployed using the primary wire. For example, a catheter was passed over the first looped wire410afrom the upper extremity access point455auntil a target location (such as a fenestration or a branch of an endograft) was reached. The first looped wire410awas then removed from the catheter. A secondary endovascular wire was then inserted through the catheter from its free end at the upper extremity access point455a, and the catheter was withdrawn out of the body from the upper extremity access point455aleaving behind the secondary endovascular wire with its distal end positioned at the target location. A stent was advanced over the catheter or the secondary endovascular wire until the target location was reached and then deployed to stent the target location. Alternatively, a long catheter was placed over the first looped wire410afrom its leading end414a, and inserted into the aorta from the femoral access point455band out through the upper extremity access point455a. The first looped wire410awas removed out of the body and replaced with a secondary endovascular wire by inserting the secondary endovascular wire through the long catheter to facilitate stent placement, such as a bridging stent in a similar manner described above. The process was repeated for however many branches or fenestrations require bridging stents are stented. In another example pre-cannulation procedure, after the looped wire410awas unthreaded from the primary wire430, four other looped wires410b,410c,410d, and410ewere threaded onto the primary wire430extending out of the femoral access point455b, by threading the respective first loops420b,420c,420d, and420e(seeFIG.4E). In some cases, these four looped wires410b,410c,410d, and410eare those used to pre-cannulate an endograft as illustrated in for example inFIG.2, where the lagging ends of these four looped wires are threaded through fenestrations or branches of the endograft. To advance the four looped wires420b,420c,420d, and420e(and in some cases also the endograft pre-cannulated by these four looped wires) into the aorta through the femoral access point455b, the first looped wire410awas threaded back onto the primary endovascular wire430behind the first loops420b,420c,420d, and420e. The first looped wire410awas then pulled from its lagging end416aextending out of the upper extremity access point455a, thereby pulling the four looped wires410b,410c,410d, and410ealong the primary endovascular wire430. Example 2 Contralateral Gate Cannulation of a Bifurcated Endograft A looped wire510was used to thread a secondary wire532through the contralateral limb504of a bifurcated EVAR endograft502. As shown inFIG.5A, the endograft502has a reverse curve catheter540extending through the main body stent503and into the contralateral limb504. The free end of the catheter540terminates in the contralateral limb504. The endograft502was placed into position by advancing the endograft over a primary endovascular wire530. A suture560was threaded through a first loop520on the leading end514of the looped wire510(seeFIG.5B). This looped wire510was inserted through the catheter into the main body stent503and around into the contralateral limb504, such that the leading end514and the first loop520extended out of the free end of the catheter540(seeFIG.5C). The suture was then locked into place using a hemostat545, such that the first loop520remained in a fixed position relative to the free end of the catheter540. The looped wire510was further inserted through the catheter to so that a length of the looped wire510extends out of the free end of the catheter540to form a large loop or a snare518(seeFIG.5D). A secondary endovascular wire532, inserted from a separate access point, was captured by the snare518(seeFIG.5E). The looped wire510was then pulled from its lagging end516tightening the snare, until a segment of the secondary endovascular wire532was pulled into the contralateral limb504adjacent the free end of the catheter540(seeFIG.5F). A second catheter542was advanced over the secondary endovascular wire532, until the distal end of the second catheter542was positioned in the contralateral limb504(seeFIG.5G). At this point, the secondary endovascular wire532was pulled from the proximal end of the second catheter542, until the free end of the secondary endovascular wire532extended into the contralateral limb504(seeFIG.5H). With the secondary endovascular wire532in the configuration as illustrated inFIG.5H, a bridging stent can now be advanced over the secondary wire and a bridging stent can be placed in the iliac artery extending into the contralateral limb504. Similar procedures can also be used for other applications where the looped wire is used as a snare. One variation of the above procedure uses a looped wire810with a plurality of loops, as shown inFIG.8. A single suture860was threaded through the plurality of loops820aand820b, such that when this looped wire was inserted through a catheter840and out of the free end of the catheter, each segment818aand818bof the guidewire between each adjacent loops formed a snare. This allows more snares to be deployed at the same time, thereby increasing the chances of snaring a wire. Example 3 Looped Wire with Two Loops for Bridging Stent Placement In this example, a looped wire610has a first loop620at its leading end614and a second loop625at its lagging end616. This example procedure was used for treating patients with thoracoabdominal aneurysms with a branched endograft602pre-cannulated with the looped wire610, which extends through a branch604of the endograft602. A primary endovascular wire630was passed from a femoral access point to an upper extremity access point in a “body floss” configuration as described in Example 1 (seeFIG.4Afor this configuration). The branched endograft602with looped wire610was advanced over this primary endovascular wire630and deployed (seeFIG.6A). The leading end614of looped wire610was pushed out of the upper extremity access sheath from the femoral artery access sheath (as described above in Example 1). A secondary endovascular wire632was advanced from the femoral access point and directed to a target vessel in a retrograde fashion. In some cases, the secondary endovascular wire632was advanced from the femoral access point, through a target vessel, and out through a third access point. The second loop625of the looped wire610was threaded onto the secondary endovascular wire632extending out of the femoral access point. The looped wire610was then pulled from the upper extremity access point to advance the lagging end616of the looped wire610into the femoral access point, the second loop625sliding along the length of the secondary endovascular wire632(seeFIG.6B). In some cases, a catheter640was advanced over the secondary endovascular wire632from the femoral access point, to push the second loop625along the length of the secondary endovascular wire632to a target location in the target vessel (seeFIG.6C). Alternatively, a low profile sheath can be used instead of catheter640. Since the second loop625is anchored or threaded to the secondary endovascular wire632, the position of the second loop625is dictated by the secondary endovascular wire632. Furthermore, by having the looped wire610anchored to the secondary endovascular wire632by the second loop625, this prevents the looped wire610from slipping off when a stiff device (such as an expandable balloon or a self-expanding covered bridging stents and sheaths) are advanced over the looped wire610from its leading end614and into the target vessel. As shown inFIG.6D, a bridging stent605was advanced from the upper extremity access point over the looped wire610, through branch604of the endograft602, and to the target vessel. The bridging stent605was then deployed, with one end of the bridging stent605attached to the branch604of the endograft602. One the bridging stent605was deployed, the secondary endovascular wire632was pulled out of the target vessel releasing the second loop625. This releases the looped wire610, which can then be removed from the upper extremity access point. This process was repeated for the other target vessels as required. This procedure allows for efficient stenting of challenging blood vessels to be stented during endovascular aneurysm repairs Example 4 Aortic Arch Endograft Turning toFIG.7A, an aortic arch endograft702with two branches was pre-cannulated with three looped wires710a,710b, and710c, and the respective first loops720a,720b, and720cwere anchored on the primary endovascular wire730ahead of the endograft. A carotid-subclavian bypass with embolization of the proximal left subclavian is shown, allowing the need for only two vessel revascularization in this example. One of the looped wires710akeeps the other two710band710cfrom slipping off the primary endovascular wire730when manipulation is occurring. This pre-cannulated endograft was advanced retrograde up to the aortic arch770from a first access point, aligned with a branch blood vessel775(seeFIG.7B), and deployed. A long sheath750was advanced over looped wire710cfrom the first access point (seeFIG.7C), with the lagging end716cof looped wire710cextending out of the proximal end of the sheath750outside the body (not shown). This lagging end716cof looped wire710cwas turned around and advanced back into the sheath750towards the deployed aortic arch endograft, and the lagging end716cwas positioned near the opening to the branch blood vessel775(seeFIG.7D). A loop was formed in the sheath. The other looped wire710a, or the distal-most looped wire, was held taunt so that the looped wire does not slip off the primary endovascular wire730, during this step. At this point, a snare780was introduced from a second access point downstream of the branch blood vessel775to snare the lagging end716cof looped wire710c, pulling the lagging end716cout of the branch blood vessel out through the second access point (seeFIG.7E). The entire length of the looped wire716cwas pulled out from the second access point, such that it now extends from its anchor point on the primary endovascular wire730, through a branch in the aortic arch endograft702, through the branch blood vessel775, and out the second access point (seeFIG.7F). The above steps are repeated for the other looped wires through other branch vessels. In this final configuration, a bridging stent was then introduced, for example, from the second access point to stent the branch blood vessel to the aortic arch endograft702. When all the stenting was completed, the primary endovascular wire730is pulled out, releasing all the looped wires710a,710b, and710c. In this example, looped wire710aanchors looped wires710band710c, while they are being manipulated. In other examples, the anchoring looped wire is optional. In this example, looped wire710aalso enables pulling of the front end (nose cone) of the endograft to facilitate placement in the aortic arch, which is often angulated. Although the embodiments have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein. Moreover, the scope of the present application is not intended to be limited to the particular embodiments or examples described in the specification. As can be understood, the examples described above and illustrated are intended to be exemplary only. Moreover, the various features of the embodiments that have been described may be combined in various ways to produce numerous additional embodiments. It should also be understood that Figures are not presented to scale, and are instead shown as schematic illustrations. | 43,479 |
11857742 | DESCRIPTION OF REFERENCE NUMBERS 1) tip head;2) balloon protective sheath;3) balloon;4) inner tube;5) imaging mark;6) outer tube;7) hypotube;8) heat shrink tube;9) hub;10) rapid exchange port;11) dimension marking;12) transition member;13) push member. DETAILED DESCRIPTION OF EMBODIMENTS Next, a detailed reference will be made to embodiments of the present application, examples of which are shown in the accompanying drawings and described below. Although this application will be described in combination with exemplary embodiments, it should be understood that this description is not intended to limit this application to those exemplary embodiments. On the contrary, the present application is intended to cover not only these exemplary embodiments, but also various alternations, modifications, equivalents and other embodiments that may be included in the spirit and scope of the present application as defined by the appended claims. Hereinafter, various exemplary embodiments of the invention will be described more specifically with reference to the accompanying drawings. First, in order to describe the embodiments of the invention more clearly, “proximal end” and “distal end” are defined according to common terms in the field of interventional medicine. When a physician carries out normal operations with a hand-held tool or device in the face of a patient, and the tool or device is located between the physician and the patient, the end close to the physician is called the “proximal end”, while the end away from the physician (the end close to the patient) is called the “distal end”. The above definitions of “proximal end” and “distal end” are only for the convenience of describing embodiments of the invention, and do not limit structures of the invention. Alternatively, the “proximal end” may also be referred to as the first end, while the “distal end” may be referred to as the second end accordingly. According to an exemplary embodiment of the present application, a balloon catheter of a rapid exchange type is provided, which includes a hub9and a balloon catheter body, wherein the balloon catheter body is composed of a push member, a transition member, a balloon loading member, a balloon3, a imaging mark5and a tip head1. The distal end of the hub9is connected with the proximal end of the push member, the proximal end of the transition member extends from the distal end of the push member, and the distal end of the transition member is nested inside the proximal end of the outer tube6of the balloon loading member. The balloon loading member is capable of loading the balloon3. Specifically, the proximal end of the balloon3is nested and fixed outside the distal end of the outer tube6. The inner tube4is nested in the inner side of the outer tube6from the rapid exchange port10to form a coaxial structure, and the inner tube4extends so that its distal end exceeds the distal end of the outer tube6. The distal end of the balloon3is provided with a tip head1. The distal end of the inner tube4, the distal end of the balloon3and the proximal end of the tip head1are fixed so that the distal end of the balloon3is located between the distal end of the inner tube4and the proximal end of the tip head1. For example, laser welding, hot-air fusion welding, physical bonding, etc. are the fixing ways among various parts, preferably laser welding. The imaging mark5is arranged on the inner tube4of the balloon loading member. Various components of the balloon catheter body are connected and fixed by laser welding, heat sealing and other processes. In one embodiment, the hub9and the balloon catheter body are fixed and strengthened by a heat shrink tube8. Further, the balloon catheter body is coated with a coating that increases lubrication and reduces vascular damage, such as a super lubricated hydrophilic coating. The coating materials include: one or more of PTFE, PU, polyvinyl pyrrolidone (PVP), polyvinyl pyrrolidone containing coupling iodine, polyvinyl alcohol (PVA), polyethylene oxide (PEO) or polyethylene glycol (PEG). The wall of the balloon3of the exemplary embodiment of the present application is thinner and softer than that of the prior art by adopting specific materials, structures and processes (such as electric heating forming process, etc.). For example, the balloon3is made of a softer material selected from block polyether amide elastomer, nylon, polyurethane, polyester, polyacylamide compound, etc. The single wall thickness of the balloon3is about 10-15 microns, such as 10 microns, 11 microns, 12 microns, 13 microns, 14 microns and 15 microns. In contrast, the wall thickness of the balloon of the prior art is 20-25 microns. For the balloon of the same specification, the balloon3of the exemplary embodiment of the present application deflects to about 45 degrees in the upright state, which is much larger than that of the balloon of the prior art. Owe to the thinner and softer wall, the nominal dilation pressure (NP) of the balloon of the application can be set as 3-4 atm, such as 3 atm, 3.2 atm, 3.4 atm, 3.6 atm, 3.8 atm, 4 atm, preferably 3 atm. In contrast, the nominal dilation pressure of the balloon of the prior art is set as 6-8 atm. For the balloon catheter of the same specification, the balloon size achieved by dilating the present balloon catheter under 3 atm is the same as or similar to that achieved by dilating the balloon catheter of the prior art to 6-8 atm. In order to ensure the safety performance during the use of the balloon catheter, the rated burst pressure (RBP) of the balloon catheter is relatively high, which is set as 10-12 atm, such as 10 atm, 10.5 atm, 11 atm, 11.5 atm, 12 atm, preferably 12 atm. In order to achieve relatively small nominal pressure and the rated burst pressure sufficient for safe space, special process should be adopted to form the balloon. First of all, it is necessary to select an appropriate initial tube, which requires the outer diameter of the tube to be 0.5 mm-1.4 mm, the wall thickness to be 0.20 mm-0.60 mm, and the concentricity to be 80%-100%. A suitable balloon molding mold is selected, such as a mold made from beryllium copper alloy, copper, PEEK and other materials. Through several steps, such as two steps, after heating the tube and reaching the glass transition temperature, the tube is inflated and stretched to shape in the mold. It needs to be stretched many times (for example, 2-4 times) to form different parts, and finally cooled and shaped. In the process of balloon molding, the tube has a stretching rate of 150%-400%, and an inflation ratio of 2.5-4.0. Products having different specifications have their own unique molding parameters, which are a combination of factors such as temperature of 80-150° C., pressure of 10-40 bar, stretching distance of 10-25 mm, setting time of 10-25 s, stretching force of 20-60 N in a period of time. The following is a table summarizing the parameters of the balloon realized by several embodiments of the combination of different factors according to the process of the application obtained from experiments, as well as comparison with the balloon of the prior art. TABLE 1Initial tubeMolding parametersBalloon parametersOuterWallTemper-Temper-Stretch-Stretch-Walldiam-thick-Concen-ature inature inStretch-Infla-Infla-ingSettingingthick-eternesstricitystep 1step 2ingtion 1tion 2distancetimeforcenessNPRBPNo.(mm)(mm)(%)(° C.)(° C.)times(bar)(bar)(mm)(s)(N)(μm)(atm)(atm)10.500.2010095125310351410201031220.780.3310095130310302015401131230.850.3710085135210321515401131240.910.4010090140210301512401341250.910.4010090135310301210401231260.910.4010085140410321020401231271.050.409595135310321812401231281.150.448095140310401625401241291.400.60100801503104025126015312Refer-0.790.28100/852/26/201020612ence With high flexibility and low nominal pressure of the balloon3, the balloon should be inflated slowly compared with the balloon in the prior art. After the balloon3is folded, its folded wing is in a spiral shape to reduce its outer diameter. The balloon3is formed by folding with two folded wings, three folded wings or five folded wings. The folding structure cooperates with the thin and soft wall of the balloon, so that the balloon3of the application has a suitable crossing profile, i.e., a suitable passing outer diameter, and good refolding, and can be inflated several times. Compared with the balloon of the prior art, the balloon3of the exemplary embodiments of the present application has a smaller crossing profile, which ranges from 0.66 mm to 0.90 mm, such as 0.66 mm, 0.72 mm, 0.78 mm, 0.84 mm and 0.90 mm. The balloon3also has certain shape memory. The balloon loading member is composed of an outer tube6and an inner tube4. The outer tube6and the inner tube4can be a single layer or a multi-layer structure, so as to realize the function of transporting balloon and work stably under a certain pressure. The materials of the outer tube6and the inner tube4are block polyether amide elastomer, nylon, polyurethane or high-density polyethylene and other polymer materials or composite tubes. The hardness of the outer tube6and the inner tube4can be kept unchanged or orderly varied from the proximal end to the distal end. The outer diameter of the outer tube6is 0.80 mm-1.00 mm, for example, 0.80 mm, 0.90 mm, 1.00 mm, preferably 0.90 mm. The inner diameter of the outer tube6is 0.60-0.90 mm, for example, 0.60 mm, 0.70 mm, 0.80 mm, 0.90 mm, preferably 0.70 mm. The length of the outer tube6is 360 mm-480 mm, for example 360 mm, 400 mm, 440 mm, 480 mm, preferably 450 mm. The outer diameter of the inner tube4is 0.55 mm-0.65 mm, for example, 0.55 mm, 0.60 mm, 0.65 mm, preferably 0.57 mm. The inner diameter of the inner tube4is 0.40 mm-0.45 mm, for example, 0.40 mm, 0.45 mm, 0.50 mm, preferably 0.42 mm. The length of the inner tube4is 280 mm-380 mm, for example, 280 mm, 315 mm, 380 mm, preferably 300 mm. The inner tube4is provided with a imaging mark5. The material of the imaging mark5is gold, platinum, platinum iridium alloy, tungsten rhenium alloy, etc. Compared with the balloon catheter of the prior art, the structural design and assembly of the application are improved and optimized. The length of the coaxial structure of the hose section from the tip head1to the rapid exchange port10is lengthened, and the outer diameter, length dimension and gradual changing structure of the transition member are designed to transfer the operation of the end of the hub9to the tip head1to the most extent, without losing the overall flexibility. The assembling and combination of various connecting parts are more optimized to achieve smooth transition and smoother force transmission. Thus, the balloon catheter of the present application can smoothly reach the lesion in the tortuous and narrow intracranial vessels. In order to improve the intravascular transporting performance of the product to a greater extent, the length of the coaxial structure of the hose section of the balloon catheter is lengthened to 300-400 mm, such as 300 mm, 320 mm, 340 mm, 360 mm, 380 mm, 400 mm, preferably 310 mm. The length of the distal hose section of the balloon of the prior art is 200-250 mm. The effective length of the present application is about 50-100 mm longer than that of the prior art, so that the overall effective length reaches 1450-1650 mm, preferably 1550 mm. The transition member includes, but is not limited to, one structure or combination of structures of a spring, a hypo tube having screw structure and a core wire having variable diameter structure. The spring or screw can be of variable pitch structure. According to an exemplary embodiment shown inFIG.2, the transition member is a spiral cut structure made of metal. In other words, the main body of the transition member is in tubular shape, and the tube is cut along the spiral line. Preferably, the pitch of the spiral line gradually decreases from the end connected with the push member to the end of the balloon3. At one end of the balloon3, the end of the transition member forms a shovel like structure having gradually changing size. Compared with the balloon catheter of a coaxial structure, the balloon catheter having a rapid exchange structure is more convenient and efficient to use, but the conductivity of force decreases with respect to the coaxial structure because of dispersion of the rapid exchange port10. However, properly increasing the length of the coaxial structure segment is beneficial for the balloon and the whole hose section to deliver and reach lesion in the blood vessel. The combination of the relatively long hose section of the balloon and the spiral metal reinforcing section of the application can greatly improve the transporting performance of the whole product in the intracranial vessels. In vitro laboratory data, it show that the thrust and withdrawal force required for the delivery of the balloon catheter in simulated blood vessels are 30%-40% less than that of the balloon of the prior art, which can achieve or even be superior to the transporting performance of the coaxial balloon catheter. The push member is composed of tubes such as a metal-based hypo tube7and a braided tube with a cavity structure, which is characterized in that the length range of the tube is 800 mm-1400 mm, the preferred range is 1150 mm-1250 mm, such as 1150 mm, 1200 mm, 1250 mm. The tube can be of the same diameter or variable diameter structure, which only needs to ensure having appropriate support strength, good pushing performance and the fluid in the cavity flowing smoothly under a certain pressure, with an outer diameter of 0.40 mm-0.70 mm, and a thickness of 0.05 mm-0.15 mm. Preferably, the outer wall of the tube of the push member has a dimension marking11. The balloon catheter according to the application can maintain the overall mechanical balance, so that the force can be accurately transmitted from the hub9to the working end of the balloon, so that it has good pushing performance and can be smoothly transmitted to the intracranial vascular site. At the same time, it has excellent flexibility and trafficability, so that the balloon catheter can easily reach the brain through a tortuous vascular pathway to carry out treatment. The design of nominal dilation pressure and rated burst pressure is based on the characteristics of intracranial vessels. As there is no muscle tissue support protection outside the intracranial vessels, the vessels are tortuous and soft, easy to be damaged, so it is not suitable for over dilation and long-term stent implantation. Therefore, the interventional treatment of intracranial vessels is more conservative than that of coronary intervention treatment to ensure the safety of patients during operation. The higher the pressure, the greater the damage to blood vessels, and many of the vascular intimal damage cannot be evaluated by imaging. On the other hand, the intracranial vessels are not like the vessels of coronary artery which will be stressed correspondingly due to the beating of the heart, the intracranial lesion vessels will not be easily retracted after being dilated. Simple balloon dilation does not need much pressure, just right. To achieve the purpose of dilating vascular lesions under low pressure will greatly reduce the pulling and damage to blood vessels, and provide more security and safety for patients and doctors. The thinner and softer wall of the balloon used in this application allows to set less dilation pressure, which means that the balloon can contact with the wall of blood vessels under a lower pressure and give a proper radial action intensity, which can realize moderate dilation of the lesion blood vessel, and reduce or even eliminate the damage to the blood vessels to a greater extent. The higher rated burst pressure can ensure that the balloon will not burst in the process of continuous pressure rise, so as to avoid unnecessary damage to the blood vessels. Similarly, to the characteristics of tortuosity and softness of the intracranial vessels, the balloon catheter suitable for this application should have high trafficability and transportability. The balloon used for the balloon catheter of the present application has a folding structure, and wall of the balloon is thin and soft, and is further coated with a coating for lubrication, providing better trafficability. In addition, the balloon hose section used in the balloon catheter of the present application is relatively long, which is combined with the spiral metal reinforcing section to provide better transportability. In the simulated use test in vitro, the transportability. performance of the catheter in this application is 30%-40% higher than that of the ordinary intracranial balloon catheter. In conclusion, the application further reduces damage to blood vessels. In the interventional treatment using the balloon catheter of the present application, the lesion position in the blood vessel is first determined by angiography, then the catheter sheath is fed into the blood vessel from the femoral artery or brachial artery, the guide wire is penetrated into the catheter sheath and passed through the lesion, the balloon catheter is introduced into the blood vessel, and the balloon catheter is pushed along the guide wire to the lesion site, and the hub is connected with an inflation device, the balloon cavity is filled with an appropriate volume of contrast medium, the balloon dilates to open the blocked lesions, the balloon catheter is deflated, the balloon changes from a filled state to a negative pressure state, and then the balloon catheter is withdrawn from the body. The foregoing description of the specific exemplary embodiment of the present application is for the purpose of explanation and description. The above description is not intended to be exhaustive, or that the application is strictly limited to the specific form disclosed. Obviously, many changes and modifications may be made according to the above teachings. The purpose of selecting and describing exemplary embodiments is to explain the specific principles and practical applications of the present application, so that other technicians in the art can realize and utilize various exemplary embodiments of the present application and various selections and modifications. The scope of this application is intended to be limited by the appended claims and their equivalents. | 18,514 |
11857743 | DETAILED DESCRIPTION To provide an overall understanding of the devices and methods described herein, certain illustrative embodiments will be described. Although the embodiments and features described herein are specifically described for use in connection with internal balloon sheaths for use in intravascular procedures involving catheter based ventricular assist devices, it will be understood that all the components and other features outlined below may be combined with one another in any suitable manner and may be adapted and applied to other types of procedures requiring an internal balloon sheath. The devices and methods described herein relate to an internal balloon sheath that comprises a tubular sheath body and an inflatable balloon. The tubular sheath body comprises a longitudinal axis, an open proximal end, an open distal end, an outer surface and an inner surface, the inner surface defining a lumen between the proximal and distal ends for passage of a catheter device. The inflatable balloon is disposed within the lumen and is configured to occupy a longitudinal space in the lumen between the inner surface of the sheath body and the catheter device when the catheter device is disposed within the sheath and the balloon is inflated, and fluidically seal the lumen. Such a sheath prevents ingress of fluid after the balloon has been inflated thereby preventing the stagnation of blood and clotting within the lumen of the sheath when the sheath is positioned within the vasculature of the patient. As the lumen within the sheath is sealed from the arteriotomy of the sheath, there is no need for the provision of a flow of irrigation fluid through the lumen of the sheath, thereby simplifying the sheath delivery system. Further, the inflated balloon forms an interference fit between the external surface of the catheter device and the inner surface of the sheath, thereby fixing or locking the position of the catheter device during use. This does away with any bulky and cumbersome fixation techniques that would be otherwise attached to the surface of the patient's skin. Additionally, as the inflatable balloon takes up any space between the catheter body and the sheath, the internal balloon sheath can be used with any size of catheter as the balloon appropriately occupies any difference in dimension within the sheath. In some embodiments the internal balloon may be attached to at least a portion of the inner surface of the sheath body. Here the internal balloon may be attached to the inner surface of the distal end of the sheath body. Alternatively, the internal balloon may span the entire length of the sheath body and be attached to a plurality of attachment points on the inner surface of the sheath body. In certain embodiments, the balloon may be an inline radially symmetric balloon which is coaxially arranged with the sheath body such that the catheter device traverses through the balloon. In other embodiments, the balloon may be an asymmetric balloon. When inflated, the balloon forms an interference fit with the sheath and the catheter body in which the balloon grips onto the catheter thereby locking it in position. In other embodiments the internal balloon may be attached to a balloon sleeve external to the sheath body. The sleeve may be arranged to have a tight fit over the catheter of the medical device while being slideable thereon. The sleeve may be configured such that it can be slid about the catheter and positioned within the lumen of the sheath. The balloon may be attached to the external surface of the distal end of the sleeve. Alternatively, the balloon may span the entire length of the sleeve and be attached to a plurality of attachment points on the external surface of the sleeve. In certain embodiments, the balloon may be an inline radially symmetric balloon which is coaxially arranged with the sleeve such that the catheter device traverses through the sleeve. In other embodiments, the balloon may be an asymmetric balloon. When inflated, the balloon forms an interference fit with the sheath and the catheter body in which the balloon grips onto the catheter thereby locking it in position. In other embodiments, the balloon sleeve is positioned parallel to the catheter of the medical device, thereby not requiring the medical device to be threaded through the balloon sleeve. FIG.1shows a conventional sheath delivery system100for positioning a catheter device140in a blood vessel of a patient. Depicted inFIG.1is a sheath120after it has been inserted through the skin110and into the arteriotomy112of the patient. The sheath120is positioned in the vessel, such as a femoral artery114, through which blood flows116. The sheath120facilitates the insertion of a catheter device140into the artery114. The catheter device140may comprise a ventricular assist device such as a percutaneous pump. An example of such a percutaneous pump is the Impella 2.5™ pump system from Abiomed, Inc. of Danvers, Massachusetts. Such pumps generally comprise a catheter body with a pump head at a distal end of the catheter body (not shown) and a handle at a proximal end of the catheter body (not shown). In most situations the pump head would have a larger diameter than the diameter of the catheter body. It will be understood that while a percutaneous heart pump is described herein, any other percutaneous or intravascular medical device can be used in conjunction with the present disclosure. The proximal end of sheath HO120may be coupled to a hub130. In order to facilitate traversal of the catheter device through the sheath100, the inner diameter dshiof the sheath120is configured to be equal to or larger than an outer diameter dcathoof the largest portion of the catheter device, i.e. dshi≥dcatho. In the case of the Impella 2.5™ pump system as exemplified in the foregoing, the largest portion of the device is the pump head. After the pump head passes through the sheath body120, a space128exists between the inner surface126of the sheath120and the outer surface of the catheter device140, as depicted inFIG.2. This space128exists due to the difference in the inner diameter of the sheath dshiand the outer diameter of the catheter body dcatho, as shown inFIG.2. Such a space facilitates blood ingress within the sheath120while the sheath body is still in the arteriotomy of the patient. As the space may not have flowing fluids within it, stagnation of blood is likely to occur which results in the formation of clots118,119in the space128of the sheath body120, as illustrated inFIG.3. Such clot formation complicates intravascular medical procedures as they may be accidentally dislodged from the sheath and freely move with the blood in the vessel (e.g., as illustrated by clot117inFIG.3), embolizing downstream (such as, for example, into distal limb, up to right heart and lungs, etc.). Additionally, in some instances clot formation can increase likelihood of blocking the blood flow through the vessel. Further, once a clot begins to form it can continue to increase in size and block the lumen of the vessel. In some cases, to minimize clot formation, the sheath delivery system is provided with a flow of irrigation fluid that is fed into the lumen of the sheath120. This flow may be provided to the lumen continuously or at a predetermined frequency, which complicates the sheath delivery system as an additional control and monitoring mechanism for such irrigation needs to be employed. Further, when the catheter device140is deployed the proximal end of the device may be attached to the hub130by tape or sutures. Such fixation may not ensure that the portion of the device within the patient's arteriotomy will not move. Additionally, such external fixation may be bulky and cumbersome, and may come loose as the patient moves. FIG.4shows an expanded view of an internal balloon sheath400according to an embodiment of the present disclosure. The sheath400is suitable for insertion into the arteriotomy of a patient, such as the femoral artery. The sheath400comprises a sheath body402having an inner surface404and extending along a longitudinal axis406. The sheath body402comprises a lumen408of diameter d that extends along the longitudinal axis406. In certain embodiments, the sheath body402may be tubular with a circular cross section, however the sheath body402may be of any shape and configuration. The sheath body402has an internal diameter of dshiand is suitable for introducing an intravascular medical device420into a vessel of the patient. As previously mentioned, the medical device420may be a catheter based device such as a percutaneous pump. An example of such a percutaneous pump is the Impella 2.5™ pump system from Abiomed, Inc. of Danvers, Massachusetts Such pumps generally comprise a catheter body422with a pump head424at a distal end of the catheter body. In most situations the pump head424has a larger diameter dcathothan the diameter of the catheter body dcatho. It will be understood that while a percutaneous heart pump is described herein, any other percutaneous or intravascular medical device can be used in conjunction with the present disclosure. Once the sheath400is in the correct position in the vessel, the medical device420is deployed from the distal end403of the sheath body402. In order for the medical device420to emerge from the sheath400, the internal diameter of the sheath body402is configured to be at least equal to the diameter of the pump head424, i.e. dshi≥dcatho. However this means that once the medical device420is deployed into the vessel, the difference between the internal diameter dshiof the sheath body402and the external diameter of the catheter body dcatholeads to a space developing that may result in the formation of clots, as described in the foregoing. According to an embodiment of the present disclosure, an inflatable balloon410is positioned in the lumen408of the sheath body402. In some embodiments, the balloon410may be positioned at the distal end403of the sheath body402. In the embodiments the balloon410may be positioned elsewhere along the sheath body402. In further embodiments, the balloon410may extend along the entire length of the sheath body402. The balloon410is configured such that it is able to assume two states and transition therebetween: a first state in which it is deflated, and a second state in which it is inflated. In the first state the balloon410does not come into contact with the catheter body422of the medical device420, while in the second state the balloon410contacts the catheter body422of the medical device420. In order to transition from the first state, in which the balloon410is deflated, to the second state, in which the balloon410is inflated, a fluid is supplied to the balloon410. In some embodiments, the fluid may be air, saline or water, for example, however any biocompatible fluid may be used to inflate the balloon410. Such fluid may be supplied to the balloon via a fluid lumen which will be described in detail in the following sections. When the balloon410is inflated, it reduces the diameter of the lumen408such that the opening in the sheath body402is less than the diameter of the catheter body422of the medical device420, i.e. in the second state d<dcatho. As the balloon is inflated (with saline or air) it fills the void/space between the catheter body422and inner surface404of the sheath thereby preventing blood ingress, stagnation, and clotting. It should be noted that during use, after the catheter device is positioned in the arteriotomy of the patient, the lumen408of the sheath400may be first flushed with an irrigation fluid prior to inflation of the balloon410. This removes any blood ingress that may have accumulated while the sheath400or the catheter device was being positioned. In the second state the inflated balloon410comes into contact with the catheter body422of the medical device420and exerts a compressive force on the medical device420. Additionally, in the second state, frictional forces between the balloon410and the catheter body422along the length of the catheter-balloon interface assist in the fixation of the position of the catheter body422relative to the sheath400. In some embodiments (when the balloon410is not attached to the sheath400, as will be described below), frictional forces between the balloon410and the inner surface404of the sheath body402along the balloon-sheath interface also assist in fixating the location of the catheter body422relative to the sheath400. WhileFIG.4shows an axially symmetric balloon410, it will be appreciated that the balloon410can be of any shape or configuration. For example, the balloon410may be axially symmetric (as depicted inFIG.4) in which it has a circular ring shape aligned about the longitudinal axis406of the sheath400. In such a configuration, when the balloon410is inflated, it exerts a radial compressive force on the catheter body422from all directions about the longitudinal axis406, thereby effectively gripping the catheter body422and locking it in position. In other embodiments, the balloon410may be asymmetric about the longitudinal axis406of the sheath400. For example, the balloon410may be positioned on one side of the longitudinal axis406of the sheath400. In such configurations, when the balloon410is inflated and assumes the second state, it exerts a compressive force on the catheter body422from one general direction. When that happens, the compressive force from the balloon410effectively pins the catheter body422against the inner surface404of the sheath body402and locks its position. It will be understood that when the balloon410is in the second state, the balloon410prevents any axial or radial translation of the medical device420, thereby locking it in a fixed position. FIG.5Aillustrates an exemplary internal balloon sheath500according to an embodiment of the present disclosure. It will be understood that the internal balloon sheath500has similar features to sheath400ofFIG.4as described in the foregoing. Sheath500has a lumen for the passage of an intravascular medical device, the catheter end505of which is shown inFIG.5A. Sheath500comprises a sheath body510having a distal end512and a proximal end514. Sheath500also comprises an inflatable balloon515positioned within the lumen of the sheath500and located at the distal end512of the sheath body510. InFIG.5A, the inflatable balloon515has a fixed length and does not span the entire length of the sheath body510. In some embodiments, the balloon515may be positioned at other locations along the sheath body510. Further, in certain embodiments of the present disclosure, balloon515may be attached to the inner walls of the sheath body510, as will be described in the following sections. Alternatively, the balloon515may be positioned within the sheath500by the insertion of a balloon sleeve into the lumen of the sheath body510, as will be described in the following sections. FIG.5Billustrates another exemplary internal balloon sheath550according to an embodiment of the present disclosure. It will be understood that the internal balloon sheath550has similar features to sheath500ofFIG.5Aas described in the foregoing. Sheath550has a lumen for the passage of an intravascular medical device, the catheter end555of which is shown inFIG.5B. As with sheath500, sheath550comprises a sheath body560having a distal end562and a proximal end564. However, inFIG.5B, sheath550comprises an inflatable balloon565positioned within the lumen of the sheath500, that spans the entire length of the sheath body560. In certain embodiments of the present disclosure, balloon565may be attached to the inner walls of the sheath body560, as will be described in the following sections. Alternatively, the balloon565may be positioned within the sheath550by the insertion of a balloon sleeve into the lumen of the sheath body560, as will be described in the following sections. According to some embodiments of the present disclosure, the balloons510,560inFIGS.5A and5Bmay be axially symmetric. In other embodiments, the balloons510,560may be asymmetric about the longitudinal axis of the sheath body. As shown inFIG.5A, the proximal end514of the sheath body510may be coupled to a hub520. Hub520serves as a handle which the physician can grip while positioning the sheath500into the vasculature of the patient. The hub may also have features to facilitate fixation of the hub to the skin of the patient once the sheath500has been positioned in the vasculature of the patient. Such fixation may be via sutures or tape. Additionally, the hub520may have at least one sideport525,530. Each sideport may be connected to a flexible tube526,531as shown inFIG.5A, and, optionally, a two-way or three-way stopcock. Each sideport may be in fluid communication with the lumen of the sheath body510. In some embodiments, the sideport may be in fluid communication with additional lumens in the sheath body510, such as, for example, and inflation lumen as will be described in the following sections. In the embodiment ofFIG.5A, sideport525is in fluid communication with the lumen of the sheath body510, while sideport530is in fluid communication with the inflatable balloon515. Sideport520may connected to tube526such that irrigation fluid can be used to flush the lumen of the sheath body510prior to inflation of the balloon515. Flushing the lumen prior to inflation of the balloon515removes any stagnation of blood which may have collected during insertion of the sheath into the arteriotomy of the patient. Sideport530may connected to tube531such that inflation fluid can be used to inflate the balloon515(described below). In some embodiments, sideport530may be in fluid communication with the balloon515via a fluid lumen formed in the sheath body510, or via internal tubing that connects the source of inflation fluid to the balloon515. It should be noted that in the case ofFIG.5Bin which the balloon565spans the length of the sheath body560, there is no need for an inflation lumen within the walls of the sheath body as the proximal end of the balloon565may be in direct fluid communication with the inflation port on the hub. Once in sheath500and hub520are in position, the physician may attach a saline syringe and/or pull vacuum to the sideport(s)525,530to deliver fluid through the sideport up the shaft of the sheath (in the wall of the sheath body, for example, as will be described in the following sections) and into the inside of the balloon. Once the balloon515is inflated the physician could shut off the stopcock on the sideport to lock the volume in place. Returning to the embodiment inFIG.4, the balloon410may be attached to the inner surface404of the sheath body402and inflated and deflated therefrom. Such attachment is implemented via a heat or solvent bond. This bond is critical to ensure the balloon410does not rupture, during inflation, for example. In certain embodiments, the inner surface404of the sheath body402may be pretreated with plasma activation or coronary treatment to improve the likelihood of bonding the balloon410to the sheath body402. In some embodiments, the balloon410may be located at a specific position on the sheath body402. In such embodiments, the point of attachment of the balloon410may be local to the position of the balloon in the sheath400. For example, for balloons410that are positioned at the distal end403of the sheath body402, the point of attachment of the balloon410to the inner surface404of the sheath body402is at the locale of the distal end403of the sheath body402. In other embodiments, the balloon410may extend along the length of the sheath body402. In such configurations, the balloon410may be attached to the inner surface404of the sheath body402, along the entire length of balloon410. In other configurations, the balloon410may only be attached to the inner surface404of the sheath body402at certain points, such as, for example, the proximal and/or distal ends of the sheath body402. In other embodiments, the balloon410may not be attached to the inner surface404of the sheath body402. Instead, the balloon410may be positioned in the lumen408of the sheath body402using a balloon sleeve, which will be described in the following sections. As mentioned in the foregoing, and with respect to the embodiment depicted inFIG.4, when in the first state, the balloon410is not inflated with fluid and does not come into contact with the catheter body422. According to an embodiment of the present disclosure, the balloon410may be configured to be compliant whereby the balloon410sits flush and tight against a surface within the sheath400when in the first state. In some embodiments, this surface may be the inner wall404of the sheath body402. In other embodiments, the surface on which the compliant balloon is attached may be an additional balloon sleeve (as will be detailed in the following sections). The compliant balloon410does not have excess balloon material when deflated and therefore allows for the unimpeded insertion and removal of medical devices420within the lumen408of the sheath body402. Such compliant balloons may be easier to fabricate and process as there is no excess balloon material to manage during bonding of the balloon410to the inner surface404of the sheath body402. When the compliant balloon410is inflated, the balloon material is elastically deformed by pressure from the inflating fluid (which, in turn, may be delivered to the balloon410via a syringe, for example) causing it to seal against the catheter body422, thereby closing off the lumen to entrants from the arteriotomy (such as, for example, blood and clots). In other embodiments, the balloon410may be configured to be non-compliant where the balloon is attached to a surface within the sheath400when in the first state. In some embodiments, this surface may be the inner wall404of the sheath body402. In other embodiments, the surface on which the compliant balloon is attached may be an additional balloon sleeve (as will be detailed in the following sections). The non-compliant balloon410material sits within the lumen408of the sheath400when deflated (shown inFIGS.6-8, and as described in the following sections). Non-compliant balloons may be used so that a fixed volume of fluid will always yield appropriate and predictable inflation characteristics. In some embodiments, a fixed volume syringe containing the inflation fluid may be provided with the sheath400to ensure the correct fluid volume of fluid is provided to the balloon410each time the balloon410is inflated. In certain embodiments, a syringe (and, optionally, a fixed volume syringe) may be provided with any of the internal balloon sheaths described in this disclosure, in a sheath kit. With all the internal balloon sheaths of the present disclosure, it will be understood that the lumen of the internal balloon sheath is flushed with irrigation fluid to remove any blood ingress that may have occurred while positioning the sheath in the arteriotomy of the patient. After flushing the lumen, the balloon is inflated. Once the balloon is inflated, the lumen within the sheath body is sealed from the arteriotomy of the patient. It will be understood throughout this disclosure that ‘seal’ is to be taken to mean substantially sealing of a lumen so as to eliminate fluid flow of any amount that would enable formation of clots. Thus, unlike conventional introducer sheaths, the present disclosure does away with the need for a constant flow of irrigation fluid to flush the sheath lumen during treatment. Further, as the balloon expands so as to seal the lumen via an interference fit with the catheter of the medical device, the sheath can be used with any diameter catheter, so long as the internal diameter of the sheath body is larger than the external diameter of the most distal end of the catheter device. FIG.6illustrates an axial cross section of a distal section of an internal balloon sheath600according to an embodiment of the present disclosure. As in the embodiments described in the foregoing, sheath600comprises a sheath body610having an inner surface615which defines a lumen620for the passage of an intravascular medical device having a catheter body630. An inflatable balloon640is positioned at the distal end612of the sheath body610. The balloon640may be compliant or non-compliant, and may be axially symmetric about the longitudinal axis605of the sheath body610, or asymmetric, the configurations of which have been described in the foregoing. In some embodiments, in order to inflate distally positioned balloons, such as balloon640, sheath600may also be provided with an inflation lumen650within the walls of the sheath body610. Such an inflation lumen650may extend from the distal end612of the sheath body610along the length of the sheath600to the proximal end (not shown). The proximal end of the sheath600may be coupled to a hub (similar to that shown inFIGS.5A and5B). The inflation lumen650is in fluid communication with the interior of the balloon640via an opening655(or radial lumen655) formed in the wall of the sheath body610, at the interface between the balloon640and the inner surface615of the sheath body610. In some embodiments, balloon640may be attached to the inner surface615of the sheath body610via a heat or solvent bond, as also described in the foregoing. These bonds are critical to ensure that the balloon640does not rupture. In certain embodiments, the sheath body610may comprise a plurality of lumens similar to lumen650for other purposes, such as, for example, localized irrigation and flushing, or for the passage of a guidewire. FIG.7shows a cross section700of sheath600taken about the line X-X′ inFIG.6, showing the inflation lumen650formed in the wall of the sheath body610. InFIG.7the balloon640is shown as a non-compliant axially symmetric balloon whereby the balloon material resides in the lumen620of the sheath body610when in the deflated state. However, as mentioned in the foregoing, any type of balloon (compliant, non-compliant, axially symmetric, asymmetric) may be used in conjunction with the embodiments of the present disclosure. Inflation fluid is provided to the inflation lumen650at the hub from a syringe, for example, which then forces the fluid652into the inflation lumen650, through the opening655and into the balloon640to inflate it. According to embodiments of the present disclosure, inflation fluids may comprise any biocompatible fluid such as, but not limited to, air, water and saline, for example. As mentioned in the foregoing, when the balloon640is inflated, it reduces the diameter of the lumen620such that the opening in the sheath body610is less than the diameter of the catheter body630of the medical device. As the balloon is inflated it fills the space between the catheter body630and inner surface615of the sheath600thereby preventing blood ingress, stagnation, and clotting. Once fully inflated, the balloon640comes into contact with the catheter body630of the medical device and exerts a compressive force on the catheter body630. Frictional forces between the balloon640and the catheter body630along the length of the catheter-balloon interface may also assist in the fixation of the position of the catheter body630relative to the sheath600. In some embodiments (when the balloon is not attached to the inner surface of the sheath, as will be described below, for example), frictional forces between the balloon640and the inner surface615of the sheath body610along the balloon-sheath interface also assist in fixating the location of the catheter body630relative to the sheath600. FIG.8illustrates an axial cross section of a section of an internal balloon sheath800according to an embodiment of the present disclosure. Sheath800comprises similar features to sheath600inFIG.6, however the balloon820in sheath800is positioned along the sheath body810and not at the distal end as inFIG.6. InFIG.8the balloon820is shown as non-compliant (and in the deflated state), however it will be understood that the balloon820may be configured in any manner as described in the foregoing. Balloon820is attached to the inner surface815of the sheath body810with a heat or solvent bond at locations distal and proximal to the opening835. As described in relation to sheath600, opening835fluidically connects the inflation lumen830to the balloon820for the inflation thereof. These bonds are critical to ensure the balloon does not rupture. It will be understood that the configuration depicted in the cross-section ofFIG.8may vary depending at least on (i) where the balloon820is located along the length of the sheath body810, (ii) how the ends of the balloon820are affixed to the inner walls of the sheath body810, and (iii) the location of the opening835relative to the length of the balloon820. In certain embodiments in which the balloon spans the entire length of the sheath body, the balloon may be inflated directly from the hub without the need for an inflation lumen in the sheath body. In some embodiments, the inflation lumens as described in with respect toFIGS.6-8may be formed in the sheath body by using a mandrel during lamination and reflow of the sheath body. The mandrel does not melt into the layers comprising the sheath body610, and so can be extracted after reflow thereby leaving the inflation lumen for the passage of inflation fluid to the balloon. The opening that fluidically connects the inflation lumen to the balloon may be formed using a similar process whereby a radially oriented mandrel is positioned in the sheath body before reflow, and subsequently removed. Alternatively, the opening can be punched out of the sheath body after the inflation lumen is formed. Notwithstanding, it will be appreciated that the formation of the inflation lumen and opening may involve complex processing due to the dimensions and tolerances involved. FIGS.9A-9Billustrate an exemplary internal balloon sheath900according to an embodiment of the present disclosure. Internal balloon sheath900comprises a balloon sleeve910and an access sheath920, the balloon sleeve910comprising an in-line sleeve that is insertable into the lumen of the access sheath920. Internal balloon sheath900is configured for the passage of a catheter based medical device930therethrough. The balloon sleeve910comprises a sleeve body912with a lumen911running therethrough. The distal end of the balloon sleeve910may comprise an inflatable balloon915. Balloon915may be attached to the external surface of the distal end of the balloon sleeve910using any the attachment means as described in the foregoing. Any type of balloon (compliant, non-compliant, axially symmetric, asymmetric, as described in the foregoing) may be used in conjunction with the embodiments of the present disclosure. The proximal end of the balloon sleeve910may comprise a valve913that seals the lumen911of the balloon sleeve910against the ingress of external fluids. In some embodiments the valve913may comprise a haemostatic valve, for example. The proximal end of the balloon sleeve910may also comprise a side port914that is in fluid communication with the lumen911and/or the balloon915. In certain embodiments, the side port914may be in fluid communication with the balloon915via an inflation lumen formed in the sleeve body912, such as inflation lumen650shown inFIG.6. Side port914is similar to side ports525,530as discussed in the foregoing with respect toFIG.5A. In some embodiments, a plurality of side ports may be present on the balloon sleeve910. Additionally, in certain embodiments, the proximal end of the side port914may be coupled to a connector916to prevent the backflow of fluid, such as, for example, a Tuohy-Borst adaptor. In some embodiments, the balloon sleeve910may be axially aligned with the catheter930of the medical device such that the sleeve910is in-line with the catheter930. In this configuration, the balloon sleeve910is co-axially arranged around the catheter930of the medical device, as depicted inFIG.9A. The balloon sleeve910may be tightly fit around the catheter930, while allowing the sleeve910to be moved or translated along the catheter930into the access sheath920. In certain embodiments, the catheter930of the medical device may be pre-threaded through the lumen911of the balloon sleeve prior to use. In some embodiments, the catheter of the medical device may be manufactured with the balloon sleeve910coaxially arranged around the catheter930. The access sheath920is similar to the sheaths that have been described in the foregoing in relation toFIGS.4-8. Access sheath920comprises a sheath body922having a proximal end924, a distal end926and a lumen928running between the proximal and distal ends. The proximal end924may be coupled to a hub940. Hub940is similar to hub520depicted inFIG.5A, and may have at least one side port942positioned thereon. The side port942may be in fluid communication with the lumen928of the access sheath920for irrigation and flushing, for example. As previously described, the distal end of intravascular medical devices usually has the largest diameter compared to the catheter body. The sheath body922is configured such that the diameter of the lumen928is large enough to allow the distal end of the medical device to pass through the lumen928. Additionally, the lumen928may be configured such that it allows the balloon sleeve910to pass therethrough, i.e. the lumen928has a diameter that is larger than the external diameter of the balloon sleeve910. In certain embodiments of the present disclosure, the diameter of the lumen928is such that a space950develops between the external surface of the balloon sleeve body912and the internal surface of the sheath body922when the balloon sleeve910is inserted into the lumen928of the access sheath920. This space is similar to that as described in the foregoing in relation toFIG.4. In some embodiments, the axial length of the balloon sleeve910may be larger than the axial length of the access sleeve920. This ensures that at least a portion of the proximal end of the balloon sleeve910sticks out of the hub940of the access sheath920when the balloon sleeve910is inserted into the access sheath920. This allows for the proximal end of the balloon sleeve910(and the side ports attached thereto) to be easily accessed, for inflation of the balloon915, or example. FIG.9Bshows the cross section of the internal balloon sheath900once the balloon sleeve910is moved along the catheter930of the medical device and into the lumen928of the access sheath920. The balloon sleeve910would be positioned within the access sheath920after the lumen928is flushed with an irrigation fluid (e.g. saline or water) via side port942. InFIG.9B, the balloon915is shown as being in the inflated state. The balloon915may be inflated with an inflation fluid provided via side port942. While not shown inFIG.9A, this may be via an inflation lumen formed within the balloon sleeve body912. As mentioned in the foregoing, when the balloon915is inflated, the balloon material may be elastically deformed by the pressure from the inflating fluid (which, in turn, may be delivered to the balloon915via a syringe, for example) causing it to seal against the catheter body930, thereby closing off the lumen to entrants from the arteriotomy (such as, for example, blood and clots). When the balloon915is inflated, it exerts a radially expansive force on the inner surface of the access sheath body922from all directions, thereby effectively fixing the position of the balloon sleeve910relative to the access sheath920. In some embodiments, the access sheath920may be made of a material that deforms under the influence of such compressive forces, as will be described in relation toFIG.13in the following section. Additionally, when the balloon915is inflated, it also exerts a radially compressive force on the catheter body930from all directions about the catheter, thereby effectively gripping the catheter body930and locking it in position. FIG.10Ashows a cross section1000of the in-line internal balloon sheath900taken about the line Y-Y′ inFIG.9Bbefore balloon915is inflated.FIG.10Ashows the balloon sleeve910coaxially arranged around the catheter body930of the medical device. As mentioned, the balloon sleeve910is tightly fit around the catheter body930while being slidable on the catheter body930. The balloon sleeve910is inserted into the lumen928of the access sheath920. As previously described, in some embodiments, the balloon sleeve910may comprise an inflation lumen that fluidically connects an inflation port914on the proximal end of the balloon sleeve910to the balloon915for inflation of the balloon.FIG.10Ashows the space950between the external surface of the balloon sleeve body912and the internal surface of the sheath body922when the balloon sleeve910is inserted into the lumen928of the access sheath920. While the balloon915is illustrated as being coaxially arranged with the balloon sleeve910, any orientation of the balloon915with respect to the balloon sleeve body912may be used. For example, the balloon915may be positioned on at least one portion of the external surface of the balloon sleeve body912. FIG.10Bshows a cross section1050of the in-line internal balloon sheath900taken about the line Y-Y′ inFIG.9Bafter balloon915is inflated. When the balloon915is inflated, the balloon material may elastically deform by the pressure from the inflating fluid (which, in turn, may be delivered to the balloon915via a syringe, for example) causing it to seal against the inner surface of the access sheath920. As can be seen, the balloon915occupies the space950upon inflation, thereby preventing fluid ingress (such as, for example, blood and clots) into the lumen928of the access sheath920. It will be understood throughout this disclosure that ‘seal’ is to be taken to mean substantially sealing of a lumen so as to eliminate fluid flow of any amount that would enable formation of clots. When the balloon915is inflated, it exerts a radially expansive force on the inner surface of the access sheath body922from all directions, thereby effectively fixing the position of the balloon sleeve910relative to the access sheath920. In some embodiments, the access sheath920may be made of a material that deforms under the influence of such compressive forces, as will be described in relation toFIG.13in the following section. Additionally, when the balloon915is inflated, it also exerts a radially compressive force on the catheter body930from all directions about the catheter, thereby effectively gripping the catheter body930and locking it in position. FIGS.11A-11Billustrate an exemplary internal balloon sheath1100according to an embodiment of the present disclosure. Internal balloon sheath1100comprises a balloon sleeve1110and an access sheath1120. Unlike the balloon sleeve910inFIGS.9A-9B, the balloon sleeve1110shown inFIGS.11A-11Bis not positioned in-line with the catheter of a medical device. Balloon sleeve1110comprises a sleeve body1112having a balloon1115located at the distal end1113thereof. In some embodiments, the balloon1115may be located at any point along the sleeve body1112. The sleeve body1112may have a central lumen that is fluidically connected to the balloon1115for inflation. The balloon1115may be oriented in any manner with respect to the balloon sleeve body1112may be used. For example, the balloon1115may be symmetrically arranged about the sleeve body1112, or the balloon1115may be asymmetrically arranged about the sleeve body1112. Further, balloon1115may be attached to the external surface of the distal end1113of the sleeve body1112using any of the attachment means as described in the foregoing. Any type of balloon (compliant, non-compliant, axially symmetric, asymmetric, as described in the foregoing) may be used in conjunction with the embodiments of the present disclosure. The proximal end of the balloon sleeve1110may be coupled to a sleeve hub1116, which, in turn, may be provided with at least one side port1117. The side port1117may be in fluid communication with the central lumen in the sleeve body1112and/or the balloon1115. As described in the foregoing, the side port may be used as an inflation port to inflate the balloon1115with an inflation fluid after the sheath1100is positioned in the arteriotomy of the patient. Hub1116may also be provided with a connector port1118for the coupling of an additional adaptor to prevent the backflow of fluid, such as, for example a Tuohy-Borst adaptor. Access sheath1120is similar to access sheath920inFIG.9Aas described in the foregoing. Access sheath1120comprises a sheath body1122having a proximal end1124, a distal end1126and a lumen1128running between the proximal and distal ends. The proximal end1124may be coupled to a hub1140. Hub1140is similar to hub520depicted inFIG.5A, and may have at least one side port1142positioned thereon. The side port1142may be in fluid communication with the lumen1128of the access sheath1120for irrigation and flushing the lumen1128, for example. The sheath body1122is configured such that the diameter of the lumen1128is large enough to allow the distal end of the medical device to pass through. Additionally, the lumen1128is configured such that it allows both the balloon sleeve1110and the catheter body1130of the medical device to pass therethrough, i.e. the lumen1128has a diameter that is larger than the combined external diameters of both the sleeve body1112and the catheter body1130. In certain embodiments of the present disclosure, the diameter of the lumen1128is such that a space1150develops between the external surface of the balloon sleeve body1112, the external surface of the catheter body1130, and the internal surface of the sheath body1122when the catheter1130of the medical device and the balloon sleeve1110are both inserted into the lumen1128of the access sheath1120(seeFIG.12A, described below). This space is similar to that as described in the foregoing in relation toFIG.4. In some embodiments, the axial length of the balloon sleeve1110may be larger than the axial length of the access sleeve1120. This ensures that at least a portion of the proximal end of the balloon sleeve1110sticks out of the hub1140of the access sheath1120when the balloon sleeve1110is inserted into the access sheath1120, as shown inFIG.11B. This allows for the proximal end of the balloon sleeve1110(and the side ports attached thereto) to be easily accessed, for inflation of the balloon1115, or example. FIG.12Ashows a cross section1200of the internal balloon sheath1100taken about the line Z-Z′ inFIG.11Bbefore balloon1115is inflated. The balloon sleeve1110is inserted into the lumen1128of the access sheath1120, and comprises a sleeve body1112having an inflation lumen formed therethrough, the lumen being in fluid communication with the balloon1115. In some embodiments, the balloon sleeve body1112may comprise an inflation lumen that fluidically connects the inflation port1117on the proximal end of the balloon sleeve1112to the balloon1115for inflation of the balloon.FIG.12Ashows the space1150between the internal surface of the sheath body1122, the external surface of the catheter body1130and the external surface of the balloon sleeve1110, after the medical device and the balloon sleeve1110have been inserted into the lumen1128of the access sheath1120. While the balloon1115is illustrated as being concentrically arranged around the balloon sleeve body1112, any orientation of the balloon1115with respect to the balloon sleeve body1112may be used. For example, the balloon1115may be positioned on at least one portion of the external surface of the balloon sleeve body1112. FIG.12Bshows a cross section1250of the internal balloon sheath1100taken about the line Z-Z′ inFIG.11Aafter balloon1115is inflated. When the balloon1115is inflated, the balloon material may elastically deform by the pressure from the inflating fluid (which, in turn, may be delivered to the balloon1115via a syringe, for example) causing it to seal against the catheter body1130. As can be seen, the balloon1115occupies the space1150upon inflation, thereby preventing fluid ingress (such as, for example, blood and clots) into the lumen1128of the access sheath1120. It will be understood throughout this disclosure that ‘seal’ is to be taken to mean substantially sealing of a lumen so as to eliminate fluid flow of any amount that would enable formation of clots. When the balloon1115is inflated, it exerts a radially expansive force on the inner surface of the access sheath body1122from all directions, thereby effectively fixing the position of the balloon sleeve1110relative to the access sheath1120. Additionally, when the balloon1115is inflated, it exerts a radially compressive force on the catheter body1130so as to pin the catheter body1130of the medical device against the inner surface of the access sheath1120, thereby effectively gripping the catheter body1130and locking it in position. In some embodiments, the access sheath1120may be made of a material that deforms under the influence of such expansive forces, as will be described in relation toFIG.13in the following section. FIG.13illustrates an exemplary internal balloon sheath1300according to an embodiment of the present disclosure. Internal balloon sheath1300comprises an inflatable balloon sleeve1310and an access sheath1320. Balloon sleeve1310may be similar to balloon sleeves910,1110as described in the foregoing with respect toFIGS.9-12. Sleeve1310comprises a sleeve body1311having a proximal end1312and a distal end1313. An inflatable balloon1315may be attached to the distal end1313of the outer surface of the sleeve body1311. The proximal end1312may be coupled to a hub1316, which, in turn, may be provided with an inflation port1314. Inflation port1314is configured to be in fluid communication with the balloon1315such that inflation fluid input at the inflation port1314inflates the balloon1315. In some embodiments, the inflation port1314may be fluidically connected to the balloon1315via an inflation lumen formed in the walls of the sleeve body1311. The balloon1315may be oriented in any manner with respect to the balloon sleeve body1311. For example, the balloon1315may be symmetrically arranged about the sleeve body1311, or the balloon1315may be asymmetrically arranged about the sleeve body1311. Further, balloon1315may be attached to the external surface of the distal end1313of the balloon sleeve1310using any of the attachment means as described in the foregoing. Any type of balloon (compliant, non-compliant, axially symmetric, asymmetric, as described in the foregoing) may be used in conjunction with the embodiments of the present disclosure. As with the balloon sleeve1310, access sheath1320may be similar to access sheaths920,1120as described in the foregoing with respect toFIGS.9-12. Access sheath1320comprises a sheath body1321having a proximal end1322, a distal end1323and a lumen1324running between the proximal and distal ends. The proximal end1322may be coupled to a hub1325. Hub1325may have at least one side port (not shown) positioned thereon which may be in fluid communication with the lumen1324of the access sheath1320for irrigation and flushing the lumen, for example. The sheath body1321is dimensioned such that the diameter of the lumen1324is large enough to allow a distal end of the medical device to pass through. Additionally, the lumen1324is configured such that it allows the balloon sleeve1310to pass through. In certain embodiments of the present disclosure, the diameter of the lumen1324is such that a space develops between the external surface of the balloon sleeve body1311and the internal surface of the sheath body1321when the balloon sleeve body1311(positioned in-line with the catheter1330of the medical device) is inserted into the lumen1324of the access sheath1320. WhileFIG.13depicts the balloon sleeve1310to be in-line with the catheter1330of the medical device (such as inFIGS.8-9), the balloon sleeve1310may, alternatively, be adjacent the catheter1330of the medical device (such as inFIGS.10-11). As described in the foregoing embodiments, when the balloon1315is inflated with fluid, the balloon occupies the aforementioned space between the external surface of the balloon sleeve body1311and the internal surface of the sheath body1321, thereby sealing the lumen1324from ingress of blood from the arteriotomy of the patient. In the embodiment depicted inFIG.13, the sheath body1321is capable of elastic deformation such that when the balloon1315expands in size, the expansive force from the inflating balloon1315also causes the sheath body1321adjacent the balloon to deform. This causes bulging in the access sheath1320which prevents axial movement of the internal balloon sheath1300after insertion into the patient. Thus, in addition to sutures or tape that fixes the location of the hub1325to the skin1305of the patient, the bulge in the access sheath1320when the balloon1315is inflated locks the position of the sheath1300thereby further securing the sheath1300to the patient. In all the embodiments described in the foregoing, the sheath may comprise a rigid material. The rigid material may be a polyethylene (PE) or polyurethane (PU) material. In certain embodiments, the rigid material may have an elastic modulus of about 40 ksi (285 MPa). Ksi is a unit of pressure, representing thousands of pounds per square inch. In some embodiments the rigid material contains a radiopaque filler such as bismuth oxychloride or barium sulfate in concentrations of 5% to 40% by weight. In some embodiments, the rigid material may be any one of a polyether block amide (such as PEBAX or PebaSlix®), a polyethylene material, a polytetrafluoroethylene (PTFE) material, a high-density polyethylene (HDPE) material, a medium-density polyethylene (MDPE) material, a low-density polyethylene (LDPE) material, polyether ether ketone (PEEK), a polyether block amide (such as PEBAX) and nylon. In certain implementations, the rigid material is a crack-resistant material. In some embodiments, the rigid material may also be a material with a low coefficient of friction. Additionally, in all the embodiments described in the foregoing, the hub may also comprise any one of the above rigid materials. Generally the strength of the sheath is dependent on the modulus of the rigid material as well as the thickness of the sheath wall. For rigid materials having a lower elastic modulus, the resulting sheath will require a wall of greater thickness. Conversely, rigid materials having a higher modulus allows for a sheath having a lower wall thickness. In all the embodiments described in the foregoing, the sheath body may comprise a coaxially layered structure as described in U.S. Provisional Patent Application No. 62/777,598, the contents of which are hereby incorporated by reference in entirety. Each layer of the structure may comprise a different polymer. The layering of the polymers improves the strength of the sheath while maintaining flexibility, which is ideal for application to intravascular applications as detailed in the present disclosure. The polymers may comprise any one of PEBAX® 7233SA, PEBAX® 7033SA, PEBAX® 6333SA, PEBAX® 5533SA, PEBAX® 3533SA, and PEBAX® 2533SA. In other embodiments, the sheath may comprise various sections that are sequentially arranged, each section comprising a different polymer. Such an arrangement provides for a varying mechanical strength along the length of the sheath body. The polymers may comprise any of the aforementioned rigid materials. In certain embodiments, the sheath body may be reinforced with braids or coils to improve mechanical strength, these structures being constructed from wires made from any one of the aforementioned rigid materials. In some embodiments, the structure of the sheath body may be strengthened by laser cutting the tubular sheath body with features that enhance its strength. Further, in all the embodiments described in the foregoing, the balloon may comprise a flexible material. The flexible material may comprise a polyethylene or polyurethane material with an elastic modulus of about 40 ksi. In some embodiments the material may be any one of urethane, polyurethane, polyethylene, polypropylene, polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyethylene, cross-linked polyethylene, a polyether block amide (PEBA), and nylon. In some embodiments, the balloon sleeve may also comprise a flexible material as defined in the foregoing. Additionally, in all the embodiments described in the foregoing, the hub may comprise a rigid material. The rigid material may be a polyethylene or polyurethane material with an elastic modulus of about 40 ksi. In some implementations, the rigid material is any one of a high-density polyethylene (HDPE) material, a medium-density polyethylene (MDPE) material, a low-density polyethylene (LDPE) material, polyether ether ketone (PEEK), and a polyether block amide (such as PEBAX). In certain implementations, the rigid material is a crack-resistant material. In some implementations, the rigid material may also be a material with a low coefficient of friction. In all the embodiments described in the foregoing, a coating may be applied to the balloon so as to reduce the friction during passage of interventional devices through the internal balloon sheath. In certain embodiments, the coating may be hydrophilic or hydrophobic. In some embodiments, the thickness of this coating may be varied to achieve desired inflation characteristics of the balloon. Additionally, in all the embodiments described in the foregoing, the inner surface of the sheath may be pretreated to improve the likelihood of bonding with the balloon. Such pretreatment may include, but is not limited to, plasma activation or coronary treatment. Alternatively, or in addition to the aforementioned coatings, a coating may be applied to the catheter based medical device itself prior to insertion into the internal balloon sheath. Additionally, in all the embodiments described in the foregoing, the sheath body may additionally comprise a distal tip made up of a softer material than that used for the sheath body, i.e. the distal tip may comprise a material that has a lower elastic modulus than that of the material used for the sheath body. In some embodiments, the distal tip may be beveled to aid with insertion of the sheath into the arteriotomy of the patient. Such distal tips can seal down on catheters of smaller diameters. By sealing on the catheter, blood is prevented from entering the sheath body and clot. In certain embodiments the distal tip may contain a radiopaque filler such as bismuth oxychloride or barium sulfate in concentrations of 5% to 40% by weight. FIG.14illustrates an exemplary method1400of fabricating an internal balloon sheath, such as any of the balloon sheaths as described in the foregoing description, according to an embodiment of the present disclosure. The method1400begins at step1410in which a sheath body is made available for fabrication. The sheath body may be provided by extrusion of lamination. As described in the foregoing, the sheath body having a longitudinal axis and comprising an open proximal end, an open distal end, an outer surface and an inner surface, the inner surface defining a lumen between the proximal and distal ends. In some embodiments, the method may include the fabrication of a tubular sheath. In certain embodiments, the method may comprise the fabrication of a sheath with a diameter that is larger than the external diameter of a distal end of catheter based intravascular medical device, such as, for example, a heart pump, so as to allow the passage of the medical through the lumen of the sheath body. In certain embodiments, the method may include the fabrication of a sheath body that may comprise a coaxially laminated layered structure. Further, in some embodiments, the sheath body may comprise structural reinforcements such as a coil or braid. Such layered and/or reinforced body structures enable the sheath to withstand larger pushing forces, such as those experienced during the positioning of the internal balloon sheath in the arteriotomy of the patient. In some embodiments, the structure of the sheath body may be strengthened by laser cutting the tubular sheath body with features that enhance its strength. In certain embodiments, the inner surface of the sheath body may be pretreated (via plasma activation or coronary treatment, for example) to improve the likelihood of bonding with a balloon. The method then continues to step1420, in which an inflatable balloon is provided within the sheath body. In some embodiments, the balloon is provided by extrusion or blow molding. In certain embodiments, the method comprises attaching the balloon to the inner wall of the sheath body where the balloon is contained within the inner diameter of the sheath body. In some embodiments, the method further comprises attachment of the balloon to a balloon sleeve which is insertable into the lumen of the sheath body. In some embodiments, the method comprises the attachment of a balloon that extends along the entire length of the sheath body. In other embodiments, the method comprises attachment of a balloon that only extends along a portion of the length of the sheath body. In some embodiments, the method comprises the attachment of the balloon at only a portion of the inner surface of the sheath body, such as, for example, the distal end of the sheath body. In other embodiments, the method comprises attachment of the balloon to the inner surface of the sheath body (or the outer surface of the balloon sleeve) along the entire length of the balloon. Further, in some embodiments, the method comprises attachment of the balloon along the entire circumference of the sheath body (or the balloon sleeve). In other embodiments, the method comprises attachment of the balloon along at least a portion of the circumference of the sheath body (or the balloon sleeve). Additionally, in some embodiments, the method comprises the attachment of a balloon that is in-line with (i.e. radially symmetrical about) the catheter body of a medical device traversing through the lumen of the sheath. In other embodiments, the method comprises the attachment of a balloon that is radially asymmetrical about the catheter body of a medical device traversing through the lumen of the sheath. FIG.15illustrates an exemplary method1500of using an internal balloon sheath, such as any of the balloon sheaths as described in the foregoing description, according to an embodiment of the present disclosure. The method1500begins at step1510in which an internal balloon sheath is positioned into the arteriotomy of the patient. As previously mentioned, any of the sheaths described in the foregoing may have a tip formed on a patient proximate end of the sheath body. Such a tip may be beveled to aid with insertion into the patient. In some embodiments, the sheath body may have a laminated structure that is able to withstand large pushing forces, such as those used to insert the sheath into the patient, without kinking, bending or buckling. In certain embodiments, a dilator may be inserted into the lumen of the sheath before insertion into the patient. The dilator assists with positioning the sheath in regions of the patient's body which are difficult to penetrate with the sheath alone. Once inserted, the dilator is removed from the lumen of the sheath. In step1520, the catheter based medical device is inserted into the lumen of the sheath. The medical device is advanced into the lumen of the sheath body until it emerges from the distal tip of the sheath and is positioned in the arteriotomy of the patient. In some embodiments, the physician may manipulate the position of the medical device by holding onto a hub affixed to the proximal end of the catheter body of the medical device. Once in position, the catheter hub may be coupled to the hub of the sheath located on the exterior surface of the patient. In some embodiments, the sheath may comprise an internal balloon attached to the internal surface of the sheath body, as described in the foregoing. In other embodiments, the balloon may be located on an additional balloon sleeve that is slidably arranged along the catheter body of the medical device. Once the sheath is in position and the medial device is inserted into the arteriotomy of the patient, the balloon sleeve may be slid into position, along the catheter body. The balloon sleeve is positioned between the internal surface of the sheath body and the external surface of the catheter body. The various configurations and attachments of the internal balloon to the sheath and/or the balloon sleeve that have been described in the foregoing description, while omitted here for brevity, are applicable to the method1500. As described in the foregoing, a space may exist between the inner surface of the sheath body and the external surface of the catheter body. In order to prevent stagnation and clotting during positioning of the medical device, the once the medical device is positioned in the arteriotomy of the patient, the method may optionally comprise the flushing of the lumen of the sheath body (and hence the space) with an irrigation fluid, such as, for example, saline or water. Such irrigation fluid may be provided to the lumen via an irrigation side port fluidically connected to the lumen, as described in the foregoing. In step1530, a balloon is inflated within the lumen of the sheath with an inflation fluid, thereby fluidically sealing the lumen, and the space between the inner surface of the sheath body and the external surface of the catheter body. It will be understood throughout this disclosure that ‘seal’ is to be taken to mean substantially sealing of a lumen so as to eliminate fluid flow of any amount that would enable formation of clots. Inflation fluids may include saline, air or water, for example. Such inflation fluid may be provided to the balloon via an inflation side port fluidically connected to the balloon, as described in the foregoing. In some embodiments an inflation lumen may be provided within the sheath body to deliver the inflation fluid to the balloon. Once the balloon is inflated, the balloon forms an interference fit with the inner surface of the sheath body and the external surface of the catheter body, thereby also preventing any axial movement of the catheter body. As such the balloon effectively locks the medical device in place after the balloon is inflated. In certain embodiments, inflation of the balloon also causes the elastic deformation of the sheath body, whereby the sheath body adjacent the inflated balloon expands into a bulge within the arteriotomy o the patient. Such a bulge will further fix the position of the internal balloon sheath within the vasculature of the patient while the medical device is in use, thereby securing it. If desired, the different steps discussed herein may be performed in a different order and/or concurrently with each other. Furthermore, if desired, one or more of the above described steps may be optional or may be combined. The foregoing is merely illustrative of the principles of the disclosure, and the devices and methods can be practiced by other than the described implementations, which are presented for purposes of illustration and not of limitation. It is to be understood that the devices and methods disclosed herein, while shown for use in manufacture of an internal balloon sheath, may be applied to other systems in which sealable sheaths of a single diameter for insertion into the vasculature of the patient are required during intravascular procedures. Variations and modifications will occur to those of skill in the art after reviewing this disclosure. The disclosed features may be implemented, in any combination and subcombination (including multiple dependent combinations and subcombinations), with one or more other features described herein. The various features described or illustrated above, including any components thereof, may be combined or integrated in other systems. Moreover, certain features may be omitted or not implemented. Examples of changes, substitutions, and alterations are ascertainable by one skilled in the art and could be made without departing from the scope of the information disclosed herein. All references cited herein are incorporated by reference in their entirety and made part of this application. ILLUSTRATIVE EMBODIMENTS A1. A sheath for delivery of a catheter device through an arteriotomy of a patient, the sheath comprising:a tubular sheath body having a longitudinal axis, an open proximal end, an open distal end, an outer surface and an inner surface, the inner surface defining a lumen between the proximal and distal ends for passage of a catheter device; andan inflatable balloon disposed within the lumen and configured to:occupy a longitudinal space in the lumen between the inner surface of the sheath body and the catheter device when the catheter device is disposed within the sheath and the balloon is inflated, and fluidically seal the lumen.A2. The sheath according to A1, wherein the balloon forms an interference fit between the catheter device and the inner surface of the sheath body when inflated.A3. The sheath according to any of A1-A2, wherein the balloon is positioned at least at the distal end of the sheath body.A4. The sheath according to any of A1-A3, wherein the balloon is positioned along the entire length of the sheath body.A5. The sheath according to any of A1-A4, wherein the balloon is attached to the inner surface of the sheath body.A6. The sheath according to A5, wherein the balloon is attached at least at the distal end of the inner surface of the sheath body.A7. The sheath according to A4, wherein the balloon is attached along the entire length of the inner surface of the sheath body.A8. The sheath according to any of A5-A7, wherein the balloon is attached along at least a portion of the circumference of the sheath body.A9. The sheath according to any of A5-A8, wherein the balloon is attached along at least any of the following portions of the sheath body: about 25%, about 50%, about 75%, about 100% of the inner circumference of the sheath body.A10. The sheath according to any of A5-A9, wherein the inner surface of the sheath body is pretreated to improve attachment of the balloon to the inner surface of the sheath body.A11. The sheath according to any of A5-A10, wherein the balloon is attached to the inner surface of the sheath body via heat or solvent bond.A12. The sheath according to A10, wherein the inner surface of the sheath body is pretreated via any one of: plasma activation and coronary treatment.A13. The sheath according to any of A11-A12, wherein the balloon is inflated via an inflation opening located on the inner surface of the distal end of the sheath body.A14. The sheath according to A13, wherein the sheath body comprises an inflation lumen that extends from the proximal end of the sheath body to the inflation opening.A15. The sheath according to A14, wherein the inflation lumen is in fluid communication with the inflation opening.A16. The sheath according to any of A14-A22, wherein the inflation lumen extends along the length of the sheath body linearly or curvilinearly.A17. The sheath according to any A1-A4, further comprising:a balloon sleeve on which the inflatable balloon is attached, the sleeve aligned in-line with the catheter device and configured to traverse the lumen of the sheath body.A18. The sheath according to A17, wherein the proximal end of the balloon sleeve comprises a hemostasis valve that seals with the catheter device.A19. The sheath according to any of A17-A18, wherein the balloon sleeve comprises an inflation lumen in fluid communication with the balloon for inflation.A20. The sheath according to A19, wherein the proximal end of the balloon sleeve comprises an inflation port in fluid communication with the inflation lumen for inflation.A21. The sheath according to any A1-A16, wherein the proximal end of the sheath body is coupled to an inflation port that is in fluid communication with the balloon for inflation.A22. The sheath according to any of A19-A21, wherein the inflation lumen is in communication with a fixed volume syringe for inflation of the balloon at the proximal end of the sheath body.A23. The sheath according to any of A21-A22, wherein the balloon is inflated via the inflation port with any one of: water, saline and air.A24. The sheath according to any of A1-A23, wherein the balloon is positioned in-line with the catheter device.A25. The sheath according to any of A1-A24, wherein the balloon is radially symmetric with respect to the longitudinal axis of the sheath body.A26. The sheath according to any of A1-A25, wherein the balloon is ring-shaped through which the catheter device traverses.A27. The sheath according to any of A1-A26, wherein the balloon applies a radial force on the catheter device when inflated, thereby locking the catheter device in position.A28. The sheath according to any of A1-A18, wherein the balloon is asymmetric with respect to the longitudinal axis of the sheath body.A29. The sheath according to A28, wherein the balloon exerts a force on the catheter device so as to push the catheter device towards a portion of the inner surface of the sheath body when inflated, thereby locking the catheter device in position.A30. The sheath according to any of A1-A29, wherein the sheath body comprises a lamination of a plurality of polymer layers arranged coaxially with each other about the longitudinal axis.A31. The sheath according to any of A1-A29, wherein the sheath body comprises a combination of a plurality of tubular polymer layer portions arranged sequentially from the proximal to the distal end of the sheath body.A32. The sheath according to any of A30-A31, wherein each polymer layer comprises a different polymer material type.A33. The sheath according to A32, wherein the polymer material type comprises any one of: PEBAX® 7233SA, PEBAX® 7033SA, PEBAX® 6333SA, PEBAX® 5533SA, PEBAX® 3533SA, and PEBAX® 2533SA.A34. The sheath according to any of A1-A33, wherein the sheath body comprises reinforced structures to prevent kinking.A35. The sheath according A34, wherein the reinforced structures comprise any one of: braids, coils and laser cut features.A36. The sheath according to any of A1-A35, wherein the balloon is fabricated from any one of: urethane, polyurethane, polyethylene, polypropylene, polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyethylene, cross-linked polyethylene, a polyether block amide (PEBA), and nylon.A37. The sheath according to any of A1-A36, wherein the sheath body is fabricated from any one of: a polyether block amide (such as PEBAX® or PebaSlix®), a polyethylene material, a polytetrafluoroethylene (PTFE) material, a high-density polyethylene (HDPE) material, a medium-density polyethylene (MDPE) material, and a low-density polyethylene (LDPE) material.A38. The sheath according to any of A1-A37, wherein the distal end of the sheath body is fabricated from a softer elastic material than that used for the rest of the sheath body.A39. The sheath according to A38, wherein the distal end of the sheath body comprises a smaller diameter so as to seal onto the catheter device.A40. The sheath according to any of A17-A19, wherein the balloon sleeve is fabricated from any one of: urethane, polyurethane, polyethylene, polypropylene, polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyethylene, cross-linked polyethylene, a polyether block amide (PEBA), and nylon.A41. The sheath according to any of A1-A40, wherein the balloon is compliant and held flush against the inner surface of the sheath body when deflated.A42. The sheath according to A1, wherein the balloon is non-compliant and not held flush against the inner surface of the sheath body when deflated.A43. The sheath according to any of A1-A42, wherein the balloon is coated with a hydrophilic coating.A44. The sheath according to any of A1-A42, wherein the balloon is coated with a hydrophobic coating.A45. The sheath according to any of A1-A44, wherein the coating is of a thickness that ensures appropriate balloon inflation characteristics.A46. The sheath according to any of A1-A45, wherein the sheath body deforms when the balloon is inflated, thereby fixing the position of the sheath in the arteriotomy of the patient.A47. The sheath according to any of A1-A46, wherein the proximal end of the sheath is coupled to a hub for manipulating the sheath as it is positioned within the arteriotomy of the patient.A48. The sheath according to any of A14-A16 and A19-A22, wherein the hub comprises an inflation sideport that is in fluid communication with the fluid lumen, thereby enabling the attachment of a source of balloon inflation fluid.A49. The sheath according to any of A47-A48, wherein the hub comprises an irrigation port that is in fluid communication with the space between the catheter device and the inner surface of the sheath body, thereby enabling the space to be flushed with fluid prior to inflation of the balloon.A50. A sheath kit for delivery of a catheter device to an arteriotomy of a patient, the sheath kit comprising:a sheath according to any of A1-A49; anda fixed volume syringe filled with fluid and coupled to the sheath for inflating the balloon with the fluid.B1. A method of fabricating a sheath with an internal balloon, the method comprising the steps of:providing a tubular sheath body, the sheath body having a longitudinal axis, an open proximal end, an open distal end, an outer surface and an inner surface, the inner surface defining a lumen between the proximal and distal ends for passage of a catheter device; andproviding an inflatable balloon positioned in the lumen, the balloon configured to occupy a space in the lumen between the inner surface of the sheath body and the catheter device when the balloon is inflated thereby sealing the space from the arteriotomy.B2. The method of B1, further comprising:attaching the inflatable balloon to at least a portion of the inner surface of the sheath body.B3. The method of any of B1-B2, further comprising the step of:pretreating the inner surface of the sheath body to improve adhesion between the balloon and the inner surface of the sheath body.B4. The method of B3, wherein the pretreatment comprises any one of: plasma activation and coronary treatment.B5. The method of B1, further comprising:providing a balloon sleeve for insertion into the lumen of the sheath body, the sleeve aligned in-line with the catheter device; andattaching the inflatable balloon to at least a portion of the sleeve.B6. The method of any of B2-B5, wherein attachment of the balloon is carried out via heat or solvent bond.B7. The method of any of B1-B6, further comprising the step of:coating the surface of the balloon with either a hydrophilic coating or a hydrophobic coating.B8. The method of B7, further comprising:coating the surface of the balloon up to a predetermined coating thickness to achieve particular inflation characteristics of the balloon.B9. The method of any of B1-B8, further comprising the step of:coupling a proximal end of the sheath body to a hub.C1. A method of fabricating a sheath with an internal balloon according to any of A1-A49.D1. A method of using a sheath with an internal balloon for treating a patient with a catheter device, the method comprising the steps of:positioning a sheath according to any one of A1-A49 in an arteriotomy of the patient;inserting the catheter device into the lumen to position a distal end of the catheter device in the arteriotomy of the patient;flushing the space with an irrigation fluid; andinflating the balloon with an inflation fluid so as to seal the space from the arteriotomy.D2. A method of using a sheath according to D1, further comprising the step of:inserting a balloon sleeve on which the inflatable balloon is attached into the lumen, the sleeve aligned in-line with the catheter device.E1. A method of inserting a catheter based device through an arteriotomy of a patient, the method comprising the steps of:inserting a sheath having a lumen running therethrough into the arteriotomy of the patient;inserting the catheter based device into the lumen; andinflating a balloon within the lumen between the sheath and the catheter based device so as to fluidically seal the lumen.E2. The method of E1, further comprising flushing the lumen prior to inflating the balloon.E3. The method of any of E1-E2, wherein inserting the sheath comprises inserting a dilator into the lumen of the sheath for positioning the sheath into the arteriotomy of the patient.E4. The method of any of E1-E3, wherein the balloon is attached to the sheath.E5. The method of any of E1-E3, further comprising inserting a balloon sleeve, onto which the balloon is attached, into the lumen of the sheath between the sheath and the catheter based device, before inflating the balloon.E6. The method of E5, wherein the balloon sleeve is tightly coaxially arranged around the catheter based device. | 77,516 |
11857744 | DETAILED DESCRIPTION The present disclosure concerns embodiments of multi-lumen cannulae that comprise multiple lumens capable of facilitating a variety of different procedures that may be performed during a heart valve operation and/or other medical procedure. The disclosed multi-lumen cannulae can be used to conduct fluid into or out of vessels during minimally invasive surgery or open heart surgeries. Because the multi-lumen cannulae disclosed herein can comprise multiple lumens within a single cannula body, additional separate cannulae may not be necessary. The disclosed multi-lumen cannulae can therefore provide more efficient means for providing alternative blood flow routes during surgery as multiple different cannulae may not need to be introduced and/or removed from the patient, which can reduce physical stress to the patient and can increase the speed of application of the cannulae. The disclosed multi-lumen cannulae can also be used to control and/or localize cardioplegia solution delivery to particular sections of the heart, such as the right atrium, thereby preventing mixing in undesired regions of the patients' circulatory system. For example, in some embodiments, blood from the inferior vena cava (referred to herein as “IVC”) and the superior vena cava (referred to herein as “SVC”) can be isolated from the cardioplegia solution as it is delivered to the patient's heart. The disclosed multi-lumen cannulae also can be kink-resistant, and may not require braided tubing or structure-reinforcing materials for operation. The examples provided below describe various features of the disclosed multi-lumen cannulae as well as configurations of various portions of the cannulae that can facilitate their use in medical procedures, such as heart valve repairs (e.g., tricuspid valve procedures, mitral valve repairs, or aortic valve repairs), coronary artery bypass grafts, or extracorporeal membrane oxygenation (ECMO) (e.g., veno-arterial ECMO or veno-venous ECMO). Embodiments of the cannulae can be used for blood drainage, blood delivery, and/or cardioplegia solution delivery during certain procedures. These particular applications are intended to be exemplary; the cannulae can also be used to facilitate other types of heart procedures, non-heart related procedures, and/or patient support. FIG.1shows a multi-lumen cannula embodiment100, particularly a distal end portion102of the multi-lumen cannula, which comprises elongated body or shaft having a distal region104, an intermediate region106, and a proximal region108. The distal end portion102of the multi-lumen cannula100is understood herein to be the end of the multi-lumen cannula inserted into the patient during a procedure. In some embodiments, the distal end portion can be inserted into a patient's vena cava. In some embodiments, the distal end portion can be positioned within a patient's vena cava so that the distal region of the distal end portion is positioned within the IVC and the proximal region of the distal end portion is positioned with the SVC, such as when the multi-lumen cannula is introduced into the patient through the patient's internal jugular vein. In other embodiments, the distal end portion can be positioned within a patient's vena cava so that the distal region of the distal end portion is positioned within the SVC and the proximal region of the distal end portion is positioned within the IVC, such as when the multi-lumen cannula is introduced into the patient through the patient's femoral vein. Blood can be conducted from a patient's vein to an external reservoir through the multi-lumen cannula. The blood can be conducted using passive or active conduction. Passive conduction is understood herein to mean conducting blood through at least one lumen of a multi-lumen cannula without applying an external vacuum to facilitate flow. Active conduction is understood herein to mean conducting blood through at least one lumen of a multi-lumen cannula by applying an external vacuum. As shown inFIG.1, the distal region104of the distal end portion102can comprise a tapered tip110that tapers to form distal end112, which can comprise one or more distal openings (not illustrated) that can be coupled to a central lumen144, which is illustrated inFIG.2. Any number of distal openings suitable for facilitating fluid flow from the patient's vasculature into the central lumen144can be included in the distal end112, and the distal openings can have any shape and configuration. The distal region104can also comprise at least one distal fluid port114(which can also be referred to as a side port) (FIG.1), which can be fluidly coupled to the central lumen144(FIG.2), one or more sidewall lumens152(as illustrated inFIG.2), or both the central lumen and the one or more sidewall lumens. Any number of distal fluid ports114can be included within the distal region104to conduct blood from the patient. For example,FIG.1illustrates a cannula embodiment wherein one or more distal fluid ports114, such as the two distal fluid ports shown in solid lines inFIG.1, can oppose one or more different distal fluid ports114, such as the two distal fluid ports shown in dashed lines inFIG.1. Including multiple distal fluid ports oriented around the perimeter of the distal region104can facilitate fluid conduction through the multi-lumen cannula. For example, the inclusion of a plurality of distal fluid ports114around the distal region104increases the surface area through which fluid can enter the cannula100. The distal fluid ports114can be formed by punching and/or drilling holes in the exterior perimeter of the distal region104through to the central lumen144(FIG.2) of the multi-lumen cannula, through to one or more sidewall lumens (e.g.,152), and/or through to one or more sidewall lumens and further from the sidewall lumens through to the central lumen. In some embodiments, the distal region104can comprise a single lumen tube. In such embodiments, the distal fluid ports114can be fluidly coupled with a single central lumen, which is the only lumen in the distal region. Thus the distal fluid ports114can be located at any position around the single lumen tube. As illustrated inFIG.1, the proximal region108of the distal end portion102can also comprise a plurality of fluid ports, such as proximal fluid side ports115. Similar to the distal fluid ports114, proximal fluid side ports115can be fluidly coupled to the central lumen144(FIG.2), one or more sidewall lumens, or combinations thereof. The sidewall lumens to which the proximal fluid ports may be coupled may be the same as or different from the sidewall lumens to which the distal fluid ports are coupled. In some embodiments, the one or more sidewall lumens to which the proximal fluid ports and/or the distal fluid ports are fluidly coupled can be the conduction sidewall lumens152illustrated inFIG.2. The proximal fluid ports115can be made using the same technique described for the distal fluid ports. The number and arrangement of proximal fluid ports can be the same as or different from the number of distal fluid ports. In embodiments where the proximal fluid ports115are coupled to the sidewall lumen152, the ports115can be arranged in an axially aligned pattern (as shown inFIG.1) that overlies the lumen152. The distal fluid ports114, proximal fluid ports115, or combinations thereof can be configured to access blood flowing within the patient's SVC and/or IVC and conduct the blood to an external reservoir. The distal fluid ports114and proximal fluid ports115can be configured to have any shape and any arrangement within the distal end portion102that is suitable for conducting blood from a biological lumen to a central lumen and/or one or more sidewall lumens. In some embodiments, the size, shape, and arrangement of the distal fluid ports and the proximal fluid ports can be selected to provide (or improve) a maximum flow requirement for a particular procedure. Multi-lumen cannulae embodiments disclosed herein also can comprise one or more intermediate fluid ports positioned within an intermediate region of the distal end portion of the cannula. Such intermediate fluid ports can be used for a variety of purposes. In some embodiments, the intermediate fluid ports can be used to deliver a cardioplegia solution to a patient during an operation. The intermediate fluid ports also can be utilized to conduct fluids other than a cardioplegia solution (such as oxygenated blood, deoxygenated blood, etc.) to and from the patient. An exemplary embodiment of a multi-lumen cannula comprising intermediate fluid ports is illustrated inFIG.1. The distal end portion102of multi-lumen cannula100can comprise intermediate fluid side ports124positioned in the intermediate region106that can facilitate flow into, or out of, one or more sidewall lumens located in the sidewall of the multi-lumen cannula. In the particular embodiment illustrated inFIG.1, a plurality of intermediate fluid ports124are arranged in two rows on one side of the intermediate region. Such an arrangement can be used to facilitate increased fluid flow to or from a particular target location of the patient, such as the patient's right atrium. As with the distal and proximal fluid ports114,115, any size, shape, number, and/or arrangement of the intermediate fluid ports124can be included. The size, shape, number, and/or arrangement of the intermediate fluid ports can be selected independent of the size, shape, number, and/or arrangement of the distal and/or proximal fluid ports. One or more of the intermediate fluid ports124can be independently fluidly coupled to one of the two conduction sidewall lumens150illustrated inFIG.2, and the remaining intermediate fluid ports124can be independently fluidly coupled to the other conduction sidewall lumen150. The multi-lumen cannulae embodiments disclosed herein can also comprise one or more balloons capable of being inflated and deflated. In some embodiments, the balloons can be inflated to facilitate a particular medical procedure. For example, the balloons can be inflated to isolate the right atrium of the heart from the IVC and the SVC. As illustrated inFIG.1, balloons116and118can be positioned on the exterior surface of multi-lumen cannula100within the distal end portion102of the multi-lumen cannula. Balloon116can be positioned between the distal region104and intermediate region106, and balloon118can be positioned between the intermediate region and the proximal region108. FIG.1further illustrates balloon ports120and122, which can be positioned underneath balloons116and118, respectively. The balloon ports120and122can pass through the exterior perimeter of the multi-lumen cannula100to at least one sidewall lumen that runs parallel to the central lumen144(FIG.2), such as balloon sidewall lumen148(FIG.2). Balloon ports120and122can be used to conduct an inflation fluid (e.g., air, a saline solution, or other liquid) to and from balloons116and118to inflate and deflate the balloons during a procedure.FIG.7illustrates an embodiment of a multi-lumen cannula700comprising two inflated balloons702and704. In some embodiments, a single sidewall lumen148can be included to conduct an inflation fluid to and from both balloon ports120and122. Balloons116and118can therefore be inflated and deflated at substantially the same time by conducting the inflation fluid through the single balloon sidewall lumen148to both balloon ports120and122. In other embodiments, each balloon can be coupled to an independent lumen such that each balloon can be inflated or deflated at different times. FIG.2is a cross-sectional view of the multi-lumen cannula100taken proximal to the proximal fluid ports115.FIG.2illustrates a circumferential arrangement of the plurality of sidewall lumens (e.g., conduction sidewall lumens150and152and balloon sidewall lumen148) with respect to the central lumen144. Referring toFIG.2, the multi-lumen cannula100comprises an outer perimeter142and an inner perimeter146surrounding the central lumen144. The outer perimeter142and an inner perimeter146define a sidewall154of the cannula100therebetween with the lumens148,150,152being formed in the sidewall154. Another embodiment of the disclosed multi-lumen cannulae is illustrated inFIGS.3-5. As illustrated inFIG.3, a distal end portion302of multi-lumen cannula300comprises a distal region304, an intermediate region306, and a proximal region308. The distal region304can comprise a plurality of distal fluid ports310, and the proximal region308of the distal end portion can comprise a plurality of proximal fluid ports311. The proximal fluid ports311can be fluidly coupled to a common central lumen332, as shown inFIG.5. Similarly, the distal fluid ports310can also be fluidly coupled to the central lumen332. FIG.4is a cross-section taken at a point proximal to the proximal region308. As illustrated inFIG.4, a plurality of different sidewall lumens322,324, and326can be circumferentially positioned within sidewall328between the outer perimeter330and inner perimeter334. The sidewall lumens322,324, and326can run parallel to a central lumen332. FIG.5is another cross-sectional view of the multi-lumen cannula300taken within the proximal region308of the distal end portion302.FIG.5illustrates how proximal fluid ports311are fluidly coupled to central lumen332. The proximal fluid ports311, as illustrated inFIG.5, do not pass through sidewall lumens322,324, or326, thereby segregating flow through the proximal fluid ports to the central lumen332from flow through sidewall lumens322,324, and326. The proximal fluid ports311can be arranged as illustrated inFIG.5so that each proximal fluid port is positioned between sidewall lumens322,324, and326. As sidewall lumens322,324, and326can terminate prior to entering the distal region304, the distal fluid ports310can be arranged in any orientation independent of proximal fluid ports311. In some embodiments, however, the distal fluid ports can be arranged the same as the proximal fluid ports. As illustrated inFIG.3, intermediate portion306comprises a plurality of intermediate fluid ports320. The intermediate fluid ports320are fluidly coupled to sidewall lumen326and thus may be placed along one side of the intermediate region306adjacent to the sidewall lumen326. The intermediate fluid ports320are aligned in one row on one side of the multi-lumen cannula in this particular embodiment; however, this illustration is exemplary and in other embodiments, the intermediate fluid ports320can be differently arranged. As discussed above, including the intermediate ports306on one side of the multi-lumen cannula can facilitate procedures wherein the right atrium of the patient is to be isolated from blood flowing through a patient's vena cava. The intermediate fluid ports306can be positioned to face the entrance to the right atrium and facilitate fluid delivery specifically to the right atrium. Multi-lumen cannula300, as illustrated inFIG.3, can further comprise two balloons312and314connected to the exterior of the distal end portion302. Balloon312covers balloon port316and balloon314covers balloon port318. Each balloon port316and318can be independently fluidly coupled to a different sidewall lumen. For example, balloon port316can be fluidly coupled to sidewall lumen322, which is illustrated inFIGS.4and5, and balloon port318can be fluidly coupled to sidewall lumen324, which is also illustrated inFIGS.4and5. Using this configuration, each balloon312and314can be connected to a separate sidewall lumen thereby permitting selective inflation and/or deflation of the balloons. In some embodiments, the balloons can be inflated (and ultimately deflated) sequentially to ensure that the balloon positioned within the IVC is positioned in a suitable location before the balloon positioned within the SVC is inflated. For example, the balloon that is to be positioned within the IVC can be positioned so that it blocks the right atrium from blood flowing from the IVC to the right atrium. In some embodiments, the balloon is positioned within the IVC so that the outer periphery of the balloon sits approximately 4 cm from the inferior end of the right atrium to avoid covering the patient's hepatic veins and thereby prevent disrupted blood flow to the hepatic system. Alternatively, the SVC balloon can be inflated before the IVC balloon. In other procedures, the balloons316,318can be inflated (and ultimately deflated) simultaneously, or substantially simultaneously. Simultaneous inflation can be accomplished by administering an inflation fluid into the two independent sidewall lumens322,330at the same time, such as from a common source. FIG.6is a cross-sectional view of another exemplary multi-lumen cannula600. Cannula600comprises a plurality of sidewall lumens arranged circumferentially around a central lumen610. The plurality of sidewall lumens can comprise, for example, two independent sidewall lumens602coupled to intermediate ports located in an intermediate region between two balloons, two independent sidewall lumens604and606independently coupled to the two balloons, and four sidewall lumens608coupled to distal fluid ports, proximal fluid ports, or any combination thereof. The sidewall lumens can be positioned substantially equidistant from one another, or they can be positioned with an uneven spacing. Any suitable arrangement can be chosen. Additionally, each sidewall lumen can vary in size with respect to the other sidewall lumens, and any number of sidewall lumens can be included. The cannula can also comprise a proximal end portion connected to, or continuing from the distal end portion. The proximal end portion of the multi-lumen cannula can comprise a handle portion suitable for manipulating/controlling flow through the multi-lumen cannula. In some embodiments, the handle can be used to deliver a fluid to the patient. For example, the cardioplegia solution and/or the inflation fluid discussed above can be delivered to the different intermediate fluid ports and/or balloon ports disclosed herein via the corresponding conduction sidewall lumens and/or balloon sidewall lumens that extend from the proximal end portion of the elongated body to the distal end portion of the elongated body. In some embodiments, the handle can be used to facilitate oxygenated blood flow into the cannula from an external heart/lung machine or other source during ECMO. Exemplary embodiments of a handle that can be included with a multi-lumen cannula are illustrated inFIGS.8and9. As illustrated inFIG.8, the handle128can be positioned at the proximal end portion126of multi-lumen cannula100and can comprise two external delivery ports130and132that extend outward from handle128. These external delivery ports130and132can be connected to one or more delivery devices (not illustrated), such as a delivery device or fluid source that provides a cardioplegia solution, an inflation fluid, and/or blood to the patient using multi-lumen cannula100. The two external delivery ports130and132can be arranged in any suitable configuration. Additionally, any number of external delivery ports130and/or132can be attached to the handle. One or more adaptor ridges134and tapered tip136can be included in the proximal region138of the proximal end portion126, as illustrated inFIG.8. Tapered tip136and adaptor ridges134can facilitate connection to a vacuum device, which can actively conduct fluid from the cannula through one or more openings located in proximal end140. In some embodiments, the proximal region138of the proximal end portion126can comprise a single lumen tube. Another embodiment of a multi-lumen cannula comprising a handle is illustrated inFIG.9. Cannula900comprises a handle902including three delivery ports904,906, and908, and a proximal region910. The sidewall lumens of the multi-lumen cannula can terminate at different axial locations along the cannula, independently of the central lumen. For example, a sidewall lumen that is fluidly coupled to an intermediate fluid port within an intermediate region of the distal end portion can terminate within the intermediate region so that it does not extend into a distal region. In some embodiments, the distal region of the distal end portion can comprise a single lumen tube. Sidewall lumens fluidly coupled to balloon ports also can also be configured to terminate prior to the distal region of the distal end portion of the cannula. Thus, the number of lumens can decrease moving axially toward the distal end of the cannula. The multi-lumen cannulae disclosed herein can comprise a variety of suitable materials, including polymers (e.g., polyurethane, nylon, polytetrafluoroethylene, polyvinylchloride, and the like), metals (e.g., stainless steel or Ninitol), alloys, composites, or combinations thereof. In certain embodiments, the cannula can be extruded or wire wound. Extruded embodiments can be sufficiently strong such that exterior support (such as a metal coil) around the cannula may not be necessary. In some embodiments, however, the cannula can be reinforced with a material that promotes crush resistance, such as a coil or sheath. The diameter of the elongated body of a multi-lumen cannula can vary thereby affording different cannula embodiments that can be used in differently sized patients and in different biological lumens present in a patient's vasculature, such as the vena cava (including the SVC and the IVC), the internal jugular vein, the femoral vein, and the like. For example, the elongated body of a multi-lumen cannula can have an outer diameter of about 0.2 inches to about 0.4 inches, with some embodiments having an outer diameter of about 0.27 inches to about 0.33 inches. The diameter of the cannula can be larger in the regions of the elongated body that include a handle or a balloon. As the multi-lumen cannulae disclosed herein can be introduced into the patient through the femoral vein or the internal jugular vein or other vessels, the length of a particular cannula can be selected to accommodate the particular biological lumen into which it is to be placed. In some embodiments, the elongated body can have a length of about 55 cm to about 65 cm from the distal tip to the end of the proximal region of the distal end portion. Such embodiments can be used for a femoral approach. In other embodiments, the elongated body can have a length of about 20 cm to about 45 cm from the distal tip to the end of the proximal region of the distal end portion. Such embodiments can be used for an internal jugular approach. Each of the distal region and the proximal region of the distal end portion of the elongated body can have a length ranging from about 3 cm to about 20 cm. Referring toFIG.10as an example, the distal region can have a length1000ranging from about 3 cm to about 20 cm as measured from the distal end of the cannula to the distal end of the balloon positioned closest to the distal end of the cannula. The proximal region can have a length1002ranging from about 3 cm to about 20 cm as measured from the proximal end of a proximal fluid port that is positioned closest to the proximal end of the cannula to the proximal end of the balloon positioned closest to the proximal end of the cannula. In embodiments wherein a femoral approach is used, the distal region of the distal end portion of the elongated body can have a length1000ranging from about 3 cm to about 7 cm and the proximal region of the distal end portion can have a length1002ranging from about 5 cm to about 20 cm. When a multi-lumen cannula is inserted through an internal jugular vein of the patient, the distal region of the distal end portion can have a length1000of about 5 cm to about 20 cm, and the proximal region of the distal end portion can have a length1002of about 3 cm to about 10 cm. The balloons used with the disclosed multi-lumen cannulae can be made of any suitable material, such as, but not limited to, latex, silicone, polyethylene, polyurethane, or combinations thereof. The outer surface of the balloons can be textured or smooth. The balloons can be bonded to the exterior surface of the cannulae using a suitable adhesive typically used in the art. The balloons can be separated by a distance1004of about 5 cm to about 15 cm, as measured from the proximal end of the balloon positioned closest to the distal end to the distal end of the balloon positioned closest to the proximal end. In some embodiments, the distance1004is about 14 cm. The balloons can have a length1006of up to about 2 cm, with some embodiments comprising balloons having a length1006of about 1 cm. Sidewall lumens can be formed within a multi-lumen cannula by using a suitable extrusion method, for example. In particular disclosed embodiments, the cross-sectional area of the sidewall lumens can be maximized to facilitate actively conducting blood and/or a fluid to and from the patient. The cross-sectional area of the sidewall lumens also can be configured to minimize the amount of cannula material present within the body of the multi-lumen cannula so as to maximize the area of each sidewall lumen and/or the central lumen. Additionally, the distance or area between the sidewall lumens and the outer perimeter of the cannula and/or the outer perimeter of the central lumen can be minimized to facilitate use. In some embodiments, a suitable distance or area between the sidewall lumens and the outer perimeter of the cannula and/or the outer perimeter of the central lumen is maintained to prevent, or substantially prevent kinking of the cannula. In different embodiments, any suitable spacing/positioning can be used. The sidewall lumens also may have any shape and/or size suitable for performing a desired function, such as cardioplegia delivery, active or passive conduction, inflation and/or deflation. In some embodiments, the sidewall lumens can be oval-shaped and have a major diameter1100, as illustrated inFIG.11, of about 0.02 inches to about 0.04 inches, with some embodiments having a major diameter1100of about 0.028 inches. In other embodiments, the sidewall lumens can be crescent shaped having a width1200, as illustrated inFIG.12, ranging from about 0.01 inches to about 0.020 inches, such as about 0.015 inches. The sidewall lumens can be positioned to be about 0.01 inches from the outer perimeter of the cannula body and about 0.01 inches from the outer perimeter of the central lumen. The central lumen can have a diameter of about 0.15 inches to about 0.3 inches. In exemplary embodiments, the diameter of the central lumen can be about 0.2 inches to about 0.24 inches. The disclosed multi-lumen cannulae can be used in various different procedures. In some implementations, all or some of the lumens and ports can be used for common blood drainage from the vena cava and right atrium without inflating the balloons to isolate the right atrium.FIG.13illustrates one such example. In such implementations, lumens of the cannula (such as the central lumen and one or more sidewall lumens) can be used to drain blood from all ports to a common external reservoir. As illustrated inFIG.13, the multi-lumen cannula1300is positioned within a patient's vena cava and blood flowing from the SVC (represented by arrows1302and1304) flows into a central lumen through distal end1306and also through distal fluid ports1308in the distal region1310. Blood drained from the right atrium1312flows into the cannula through intermediate ports1314in intermediate region1316, such as into one or more of the sidewall lumens. Blood flowing from the IVC1318can flow into the cannula through proximal fluid ports1320of proximal region1322, such as into the central lumen or into one or more of the sidewall lumens. In the embodiment illustrated inFIG.13, balloons1324and1326are left deflated such that the right atrium is not isolated from the SVC and IVC. Thus, all of the ports and lumens are used for the same purpose to drain blood from the vena cave and right atrium region. This implementation of the multi-lumen cannula can be useful during aortic valve repair, mitral valve repair, or other cardiac procedures that do not require incision into the right portion of the heart. Another exemplary implementation of the multi-lumen cannula1300is illustrated inFIG.14. In this embodiment, balloons1324and1326are inflated to isolate the right atrium from the SVC and the IVC, and the blood drained from the right atrium can be isolated from the blood drained from the SVC and the IVC. For example, blood drained from the SVC (represented by arrows1302and1304) and blood drained from the IVC (represented by arrows1318) can be conducted from the patient through a central lumen to a first location, while blood flowing from the patient's right atrium (represented by arrows1312) can be conducted through one or more sidewall lumens to a second location to segregate the blood. In other implementations, the disclosed multi-lumen cannulae can be used for cardioplegia delivery during a heart procedure. In such implementations, the two balloons are inflated to isolate the right atrium from the SVC and the IVC. The central lumen and/or one or more of the sidewall lumens is used to drain blood from the SVC and the IVC, such as to an external cardiotomy reservoir for recirculation, while intermediate fluid ports of the cannula are fluidly coupled to one or more sidewall lumens and selectively drain blood from the right atrium to an external cell saver for hemoconcentration. This selective drainage can occur when a cardioplegia solution is being delivered to allow the cardioplegia solution to be selectively removed from circulation. This use of the intermediate ports and sidewall lumens can reduce the need for hemoconcentration at a later stage in the operation thereby reducing any negative impacts on the patient's blood chemistry. Single- or multiple-dose cardioplegia can be delivered with the disclosed multi-lumen cannulae. The disclosed multi-lumen cannulae also can be used during a procedure that requires incision into the right portion of the heart, such as the right atrium (e.g., tricuspid valve repair). In such embodiments, the multi-lumen cannulae can be manipulated to facilitate the procedure by stopping flow through the sidewall lumens in communication with the ports in the intermediate region between the two balloons such that no fluid is conducted into or out of the right atrium. Blood can then be drained from the SVC and the IVC through the central lumen and/or sidewall lumens without effecting the right atrium. The surgeon may then optionally snare around the right atrium prior to performing the desired right-heart procedure.FIG.15illustrates an exemplary implementation of the multi-lumen cannula1300for blood drainage during a right-heart surgical procedure, such as a tricuspid valve repair. Balloons1324and1326are inflated to isolate the patient's right atrium from the SVC and the IVC. Blood flowing from the SVC (represented by arrows1302) is conducted through a central lumen through distal end1306and distal fluid ports1308located in distal region1310. Blood flowing from the IVC (represented by arrows1318) is conducted from the patient through proximal fluid ports1320located in proximal region1322into the central lumen and/or one or more sidewall lumens. In other implementations, the disclosed multi-lumen cannulae can be used in an ECMO procedure, such as veno-arterial ECMO. In some implementations, the central lumen and optionally one or more of the sidewall lumens can be used to facilitate blood drainage from the SVC and the IVC, while one or more of the sidewall lumens are used to re-infuse oxygenated blood into the right atrium from an external source, such as a heart/lung machine. The re-infused blood can be introduced into the right atrium through intermediate ports positioned between the two balloons of the cannula. In such embodiments, the balloons need not be inflated; however, the balloons of the multi-lumen cannulae can be inflated to avoid mixing oxygenated and deoxygenated blood, thereby improving the oxygen saturation of blood being delivered to the right atrium.FIG.16illustrates an exemplary implementation use multi-lumen cannula1300to drain deoxygenated blood from the SVC and the IVC while re-infusing oxygenated blood into the right atrium. Blood flowing from the patient's SVC (represented by arrows1302and1304) is conducted through distal end1306and through distal fluid ports1308of distal region1310. Blood flowing from the IVC (represented by arrows1318) is conducted into the cannula through proximal fluid ports1320. Balloons1324and1326are inflated inFIG.16to isolate the right atrium. Intermediate fluid ports1314in the intermediate region1316are fluidly coupled to one or more sidewall lumens and selectively deliver oxygenated blood into the right atrium. For purposes of this description, certain aspects, advantages, and novel features of the embodiments of this disclosure are described herein. The disclosed methods, apparatuses, and systems should not be construed as limiting in any way. Instead, the present disclosure is directed toward all novel and nonobvious features and aspects of the various disclosed embodiments, alone and in various combinations and sub-combinations with one another. The methods, apparatuses, and systems are not limited to any specific aspect or feature or combination thereof, nor do the disclosed embodiments require that any one or more specific advantages be present or problems be solved. Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed. Although the operations of some of the disclosed methods are described in a particular, sequential order for convenient presentation, it should be understood that this manner of description encompasses rearrangement, unless a particular ordering is required by specific language. For example, operations described sequentially may in some cases be rearranged or performed concurrently. Moreover, for the sake of simplicity, the attached figures may not show the various ways in which the disclosed methods can be used in conjunction with other methods. As used herein, the terms “a”, “an”, and “at least one” encompass one or more of the specified element. That is, if two of a particular element are present, one of these elements is also present and thus “an” element is present. The terms “a plurality of” and “plural” mean two or more of the specified element. As used herein, the term “and/or” used between the last two of a list of elements means any one or more of the listed elements. For example, the phrase “A, B, and/or C” means “A”, “B,”, “C”, “A and B”, “A and C”, “B and C”, or “A, B, and C.” As used herein, the term “coupled” generally means physically, chemically, electrically, magnetically, or otherwise coupled or linked and does not exclude the presence of intermediate elements between the coupled items absent specific contrary language. In view of the many possible embodiments to which the principles of the disclosed technology may be applied, it should be recognized that the illustrated embodiments are only preferred examples of the disclosed technology and should not be taken as limiting the scope of the technology. Rather, the scope of the disclosed technology is at least as broad as the following claims. We therefore claim all that comes within the scope of these claims. | 36,434 |
11857745 | DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention comprises the provision and use of a novel implantable one-way valve, and a novel method for treating a patient using the novel implantable one-way valve, so as to provide a direct connection between the abdominal cavity and the venous system of the patient. The present invention also comprises the provision and use of a novel implantable one-way valve, and a novel method for treating a patient using the novel implantable one-way valve, so as to provide a direct connection between a first body cavity (e.g., the pleural cavity) and a second body cavity (e.g., the abdominal cavity). And the present invention further comprises the provision and use of a novel implantable one-way valve, and a novel method for treating a patient using the novel implantable one-way valve, so as to provide a direct connection between a first body cavity (e.g., the pleural cavity) and the venous system of the patient. For purposes of the present disclosure, the terms “proximal” and “distal” are used in the context of the fluid flow through the anatomy, i.e., the “proximal” direction is the direction towards the abdominal cavity (or first body cavity) containing the ascetic fluid (or other body fluid) and the “distal” direction is the direction towards the interior of the blood vessel (or second body cavity) which is to receive the ascetic fluid (or other body fluid). Thus, for purposes of the present disclosure, the “proximal” end of the novel implantable one-way valve (see below) refers to the end of the novel implantable one-way valve directed toward the abdominal cavity (or first body cavity) containing the ascetic fluid (or other body fluid) and the “distal” end of the novel implantable one-way valve (see below) refers to the end of the novel implantable one-way valve directed toward the blood vessel (or second body cavity) which is to receive the ascetic fluid (or other body fluid). Novel One-Way Valve In one preferred form of the invention, and looking now atFIGS.5-8, there is shown a novel implantable one-way valve25. One-way valve25generally comprises a body30, a valve element35, a proximal connection element40and a distal connection element45. More particularly, valve body30generally comprises a tube50having a proximal end55, a distal end60, and a lumen65extending therebetween. Lumen65comprises an inlet70disposed at proximal end55of tube50and an outlet75disposed at distal end60of tube50. In a preferred form of the present invention, tube50(and hence, lumen65) comprises a generally circular cross-section and is radially compressible in order to aid in implantation of one-way valve25into a blood vessel, as will hereinafter be discussed in further detail. It should be appreciated that in a preferred form of the invention, the length of tube50can be selected such that the length of tube50is at least equal to the thickness of the wall of the blood vessel into which one-way valve25is to be implanted, plus the thickness of interstitial tissue (disposed between the wall of the blood vessel and the peritoneal layer) which tube50will need to extend through in order to reach the wall of the blood vessel, plus the thickness of the peritoneal layer which tube50will need to extend through. Furthermore, if desired, the diameter of tube50can be selected such that tube50will comprise a diameter smaller than the diameter of the blood vessel into which one-way valve25is to be implanted. Valve element35is disposed within lumen65of tube50, intermediate proximal end55of tube50and distal end60of tube50. In one preferred form of the invention, valve element35comprises a one-way, slit-type valve such that fluid may enter into inlet70, pass through the proximal portion of lumen65, pass through valve element35, pass through the distal portion of lumen65and exit out of outlet75, but which does not allow fluid to flow in the opposite direction (i.e., from the blood vessel, through valve element35and into the abdominal cavity). As a result, when one-way valve25is implanted into a blood vessel (e.g., a vein) in the region of the abdominal cavity such that inlet70is open to ascetic fluid within the abdominal cavity and outlet75is open to the interior of the blood vessel, ascetic fluid can flow from the abdominal cavity, through one-way valve25and into the vein, but fluid cannot flow in the opposite direction. It should be appreciated that valve element35is preferably configured such that valve element35is “closed” (i.e., does not permit fluid to flow) until the pressure differential between (i) the pressure of the fluid entering inlet70, and (ii) the pressure of the fluid entering outlet75, rises above a pre-determined threshold. By way of example but not limitation, valve element35may be configured to “open” (i.e., allow fluid to flow from inlet70, through valve element35and out of outlet75) when the pressure differential on the two sides of the valve element is less than 10 mmHg and, more preferably, when the pressure differential is between 2 mmHg and 5 mmHg. Proximal connection element40is preferably mounted to proximal end55of tube50of valve body30, and distal connection element45is preferably mounted to distal end60of tube50of valve body30. Proximal connection element40and distal connection element45are preferably spaced apart from one another such that when one-way valve25is deployed at an internal site (e.g., across the wall of a blood vessel such as a vein, plus any interstitial tissue, plus the peritoneal layer), the blood vessel wall (plus interstitial tissue, plus the peritoneal layer) is captured between proximal connection element40and distal connection element45, whereby to anchor one-way valve25in place within the wall of the blood vessel. To this end, the distance between proximal connection element40and distal connection element45is preferably equal to the thickness of the vessel wall to be spanned by one-way valve25, plus any intervening tissue through which the deployed one-way valve25will pass (e.g., interstitial tissue, peritoneal layer, etc.). Proximal connection element40preferably comprises a plurality of legs80extending radially outward from tube50and terminating in a plurality of distally-directed contact surfaces85. Legs80are preferably spring-biased such that they can be radially constrained when one-way valve25is being delivered to an internal anatomical site (e.g., via a delivery sheath), and thereafter spring outward (e.g., when the delivery sheath is removed) such that legs80and/or distally-directed contact surfaces85engage the wall of the blood vessel (or the intervening tissue), whereby to anchor proximal connection element40(and hence, one-way valve25) in position, as will hereinafter be discussed in further detail. Distal connection element45preferably comprises a plurality of legs90extending radially outward from tube50and terminating in a plurality of proximally-directed contact surfaces95. Legs90are preferably spring-biased such that they can be radially constrained when one-way valve25is being delivered to an internal anatomical site (e.g., via a delivery sheath), and thereafter spring outward (e.g., when the delivery sheath is removed) such that legs90and/or proximally-directed contact surfaces95engage the wall of the blood vessel (or the intervening tissue), whereby to anchor distal connection element45(and hence, one-way valve25) in position, as will hereinafter be discussed in further detail. In one preferred form of the invention, the distal end of one-way valve25(i.e., the portions of the one-way valve which extend into the interior of the blood vessel) are formed so as to be as smooth as possible so as to minimize thrombus formation. Although one-way valve25is depicted inFIGS.5-8as having two connection elements (i.e., a proximal connection element40and a distal connection element45), it should be appreciated that, if desired, one-way valve25may comprise only a single connection element. By way of example but not limitation, distal connection element45may be omitted. In this form of the invention, proximal connection element40is configured to anchor one-way valve25in the blood vessel (e.g., proximal connection element40might comprise a sewing ring for suturing proximal connection element40to the wall of the blood vessel or the intervening tissue). This may be advantageous in some applications, inasmuch as distal connection element45would otherwise be disposed within the interior of a blood vessel, and the omission of distal connection element45(i.e., legs95of distal connection element45), which is typically disposed within the interior of the blood vessel, can minimize the incidence of thrombosis at the site of implantation. Exemplary Use of One-Way Valve25 In use, and looking now atFIG.9, one-way valve25is preferably implanted into the peritoneum/interstitium (sometimes hereinafter referred to as the “peritoneal layer” and the “interstitial tissue” or “interstitial layer”, respectively) and the wall of a blood vessel100(e.g., the vena cava, the vena iliaca, etc.) such that inlet70of one-way valve25is in fluid communication with the abdominal cavity105(e.g., such that inlet70is in fluid communication with the ascetic fluid), and outlet75is in fluid communication with the interior of blood vessel100. Proximal connection element40contacts the outer wall of blood vessel100(or contacts the intervening tissue, e.g., the peritoneal layer and/or interstitial tissue), and distal connection element45contacts the inner wall of blood vessel100, thereby anchoring one-way valve25within the wall of blood vessel100such that one-way valve25spans the blood vessel wall (and any intervening tissue) and provides a one-way fluid pathway from abdominal cavity105, through tube50(and through valve element35) into the interior of blood vessel100. As a result, fluid is able to flow from abdominal cavity105, into inlet70of one-way valve25, through valve element35and out of outlet75of one-way valve25, into the interior of blood vessel100. As will hereinafter be discussed in further detail, a delivery system may be provided for implanting the one-way valve into the wall of the blood vessel. As will also hereinafter be discussed in further detail, one-way valve25may be implanted using an “abdominal approach” in which the one-way valve is advanced from the abdominal cavity, through the wall of the blood vessel, and into the lumen of the blood vessel. Alternatively, one-way valve25may be implanted using an “endoluminal approach” in which the one-way valve is advanced from the lumen of the blood vessel, through the wall of the blood vessel, and into the abdominal cavity. Delivery System for Delivering and Deploying One-Way Valve25 As discussed above, one-way valve25is configured to be implanted into the side wall of a blood vessel (e.g., a vein) at an internal anatomical site in order to facilitate treatment of ascites. To this end, it is desirable to provide a novel delivery system for delivering one-way valve25to an internal anatomical site, and for deploying one-way valve25into the side wall of the blood vessel. Looking next atFIG.10, there is shown a novel delivery system110. Delivery system110generally comprises a puncture device115, a guidewire120, a deployment catheter125and a delivery sheath130. Also shown inFIG.10is one-way valve25loaded on guidewire120and disposed within deployment catheter125. More particularly, puncture device115preferably comprises an elongated shaft having a sharp distal end which may be used to penetrate through tissue (e.g., through the peritoneal layer, through interstitial tissue, through the wall of a blood vessel, etc.). Guidewire120comprises a flexible guidewire of the sort well known in the art which may be used to guide one-way valve25to an internal site, as will hereinafter be discussed in further detail. Deployment catheter125generally comprises a tube having an open distal end, an open proximal end, and a lumen extending therebetween. The lumen of deployment catheter125is sized so as to hold one-way valve25in a radially-contracted condition, e.g., with legs80of proximal connection element40and legs90of distal connection element45being held parallel to valve body30, whereby to provide a reduced profile for delivery of one-way valve25to an internal anatomical site, as will hereinafter be discussed in further detail. Delivery sheath130generally comprises a tube having an open distal end, an open proximal end, and a lumen extending therebetween. Delivery sheath130is sized so as to fit over deployment catheter125, whereby to protect deployment catheter125and one-way valve25during delivery to an internal anatomical site, as will hereinafter be discussed in further detail. Method of Implanting and Deploying One-Way Valve25 As discussed above, one-way valve25is intended to be deployed in the side wall of a blood vessel proximate to the abdominal cavity such that fluid can flow from the abdominal cavity, through one-way valve25, and into the interior of the blood vessel. One-way valve25may be deployed at an internal anatomical site using various methods (e.g., open surgery, percutaneous deployment, endoluminal deployment, etc.) or combinations thereof. By way of example but not limitation, and looking now atFIGS.11-13, one-way valve25may be implanted using an “abdominal approach” in which the one-way valve is advanced from the abdominal cavity, through the wall of the blood vessel, and into the lumen of the blood vessel. By way of example but not limitation, in order to prepare the internal site for implantation of one-way valve25, the surgeon first extracts the ascetic fluid from the abdominal cavity (e.g., using a syringe, a collection bag, suction, etc.). The abdominal cavity is then rinsed (e.g., with saline) and drained (e.g., using a syringe, collection bag, suction, etc.). If desired, one or more access ports (e.g., access cannulas) may be inserted into the patient's abdomen (i.e., through the skin) in order to provide the surgeon with access to the abdominal cavity and to visualize/access the blood vessel into which one-way valve25is to be implanted. By way of example but not limitation, the surgeon may use the access ports to insert optical devices, instruments, etc. into the abdominal cavity in order to help the surgeon locate the blood vessel (e.g., the inferior vena cava, the common iliac veins, etc.) into which one-way valve25is to be implanted. Puncture device115of delivery system110may be advanced from the abdominal cavity (e.g., through delivery sheath130) so that it passes through the side wall of the blood vessel so as to form a hole in the side wall of the blood vessel, and then deployment catheter125(passing through delivery sheath130) may be used to bring one-way valve25(with its proximal connection element40and its distal connection element45in their radially contracted conditions) through the hole formed in the side wall of the blood vessel. Then deployment catheter125is removed so that proximal connection element40and distal connection element45assume their radially expanded conditions, whereby to secure one-way valve25in the side wall of the blood vessel. Delivery sheath130may then be removed. At the conclusion of the procedure, one-way valve25is securely anchored within the side wall of the blood vessel (e.g., the inferior vena cava), held in position by proximal connection element40and distal connection element45. Inlet70of tube50of one-way valve25is fluidically connected to the abdominal cavity and outlet75of tube50of one-way valve25is fluidically connected to the blood vessel (e.g., the interior of the inferior vena cava). As a result, fluid (e.g., fluid resulting from ascites) is able to flow from the abdominal cavity, into inlet70of tube50, along lumen65of tube50, through valve element35and out outlet75of tube50into the interior of the blood vessel (e.g., the interior of the inferior vena cava), but fluid is unable to flow in the opposite direction. Thus, fluid can exit the abdominal cavity and enter the blood vessel without the need for a long catheter or the need for external access to the abdominal cavity. Alternatively, and looking now atFIGS.14and15, one-way valve25may be implanted using an “endoluminal approach”. In a preferred form of the present invention, one-way valve25is implanted using an endovascular approach in which the one-way valve is advanced from the lumen of the blood vessel, through the wall of the blood vessel, and into the abdominal cavity. By way of example but not limitation, in order to prepare the internal site for implantation of one-way valve25, the surgeon first extracts the ascetic fluid from the abdominal cavity (e.g., using a syringe, a collection bag, suction, etc.). If desired, fluid may also be drained from the abdominal cavity using novel delivery system110(e.g., by draining the abdominal cavity using deployment catheter125and/or delivery sheath130). The abdominal cavity is then rinsed (e.g., with saline) and drained (e.g., using a syringe, collection bag, suction, etc.). If desired, one or more access ports (e.g., access cannulas) may be inserted into the patient's abdomen (i.e., through the skin) in order to provide the surgeon with access to the abdominal cavity and to visualize/access the blood vessel into which one-way valve25is to be implanted, however, it should be appreciated that such access ports in the patient's abdomen are generally unnecessary when using an endovascular approach to implant one-way valve25. By way of example but not limitation, the surgeon may use the access ports to insert optical devices, instruments, etc. into the abdominal cavity in order to help the surgeon locate the blood vessel (e.g., the inferior vena cava, the common iliac veins, etc.) into which one-way valve25is to be implanted. After the surgeon has located a suitable blood vessel for implantation and identified a suitable implantation site (i.e., a suitable blood vessel for receiving one-way valve25proximate to the abdominal cavity), puncture device115is used to puncture the skin of the patient so as to access the interior of a blood vessel. In a preferred form of the invention, access to the vasculature is made by puncturing the jugular vein (FIG.15A) using a puncture device115and then the one-way valve is advanced to the selected internal site endoluminally. Alternatively, access to the vasculature may be achieved by puncturing the subclavian vein (also known as the vena subclavia) and then one-way valve is advanced to the internal site endoluminally. In still another form of the invention, access to the vasculature is made via the vena femoralis (FIG.15B) at a location remote from the patient's abdomen (e.g., the thigh, groin, etc.) in order to allow endoluminal advancement of one-way valve25to the selected internal anatomical site. Guidewire120is then inserted into the blood vessel (e.g., the jugular vein) and advanced through the puncture site endoluminally until the guidewire is disposed at the internal anatomical site (e.g., the desired location within the inferior vena cava). Delivery sheath130is then advanced to the internal anatomical site by passing delivery sheath130over guidewire120. Puncture device115is then advanced to the internal anatomical site and used to puncture the side wall of the blood vessel (e.g., the distal inferior vena cava, distal to the inflow of the renal veins so as to avoid damaging the duodenum) at the internal anatomical site where one-way valve25is to be implanted, and to puncture any intervening tissue, whereby to create a path between the interior of the blood vessel and the abdominal cavity. Deployment catheter125, carrying one-way valve25within the lumen of deployment catheter125, is then advanced to the internal anatomical site through the lumen of delivery sheath130, and deployment catheter125is advanced through the puncture site in the side wall of the blood vessel (e.g., the inferior vena cava) and into the abdominal cavity. It should be appreciated that at this time, one-way valve25is disposed just inside the distal end of deployment catheter125(or, alternatively, one-way valve25may be advanced to a position just inside the distal end of deployment catheter125). When one-way valve25is disposed in the desired position, the surgeon deploys one-way valve either by (i) pushing one-way valve25such that proximal connection element40is advanced out of the lumen of deployment catheter125, or (ii) by withdrawing deployment catheter125such that proximal connection element40is freed from the lumen of deployment catheter125, or (iii) by a combination of the foregoing techniques. As the radially-constricted legs80of proximal connection element40are released from deployment catheter125, legs80expand radially outward, with distally-directed contact surfaces85contacting the outer wall of the blood vessel (or the interstitial tissue covering the outer wall of the blood vessel). Next, deployment catheter125is withdrawn further until distal connection element45, which is disposed within the interior of the blood vessel (e.g., the interior of the inferior vena cava), is uncovered. As the radially-constricted legs90of distal connection element45are released from deployment catheter125, legs90expand radially outward into their radially-expanded configuration, with proximally-directed contact surfaces95contacting the inner wall of the blood vessel. At this point, one-way valve25is locked in position within the side wall of the blood vessel. Finally, deployment catheter125is withdrawn so as to remove the deployment catheter from the patient's body, and then guidewire120and delivery sheath130are also withdrawn from the patient's body. At the conclusion of the procedure, one-way valve25is securely anchored within the side wall of the blood vessel (e.g., the inferior vena cava), held in position by proximal connection element40and distal connection element45. Inlet70of tube50of one-way valve25is fluidically connected to the abdominal cavity and outlet75of tube50of one-way valve25is fluidically connected to the blood vessel (e.g., the interior of the inferior vena cava). As a result, fluid (e.g., fluid resulting from ascites) is able to flow from the abdominal cavity, into inlet70of tube50, along lumen65of tube50, through valve element35and out outlet75of tube50into the interior of the blood vessel (e.g., the interior of the inferior vena cava), but fluid is unable to flow in the opposite direction. Thus, fluid can exit the abdominal cavity and enter the blood vessel without the need for a long catheter or the need for external access to the abdominal cavity. Alternative One-Way Valve Looking now atFIGS.16-19, there is shown another one-way valve25A formed in accordance with the present invention. One-way valve25A is substantially identical to the one-way valve25discussed above, however, proximal connection element40and distal connection element45are replaced by proximal connection element40A and distal connection element45A, respectively. More particularly, one-way valve25A generally comprises a body30A, a valve element35A, a proximal connection element40A and a distal connection element45A. Body30A generally comprises a tube50A having a proximal end55A, a distal end60A, and a lumen65A extending therebetween. Lumen65A comprises an inlet70A disposed at proximal end55A of tube50A and an outlet75A disposed at distal end60A of tube50A. In one form of the present invention, tube50A (and hence, lumen65A) comprises a generally circular cross-section and is radially compressible in order to aid in implantation of one-way valve25A into a blood vessel, as will hereinafter be discussed in further detail. It should be appreciated that in a preferred form of the invention, the length of tube50A can be selected such that the length of tube50A is at least equal to the thickness of the wall of the blood vessel into which one-way valve25A is to be implanted, plus the thickness of interstitial tissue which tube50A will need to extend through in order to reach the wall of the blood vessel, plus the thickness of the peritoneal layer which tube50A will need to extend through. Furthermore, if desired, the diameter of tube50A can be selected such that tube50A will comprise a diameter smaller than the diameter of the blood vessel into which one-way valve25A is to be implanted. Valve element35A is disposed within lumen65A of tube50A, intermediate proximal end55A and distal end60A of tube50A. In one form of the invention, valve element35A comprises a one-way slit-type valve which allows fluid to enter into inlet70A, pass through the proximal portion of lumen65A, pass through valve element35A, pass through the distal portion of lumen65A and exit lumen65A out of outlet75A, but which does not allow fluid to flow in the opposite direction (i.e., from the blood vessel, through valve element35A and into the abdominal cavity). As a result, when one-way valve25A is implanted into a blood vessel (e.g., a vein) in the region of the abdominal cavity such that inlet70A is open to fluid within the abdominal cavity and outlet75A is open to the interior of a blood vessel, fluid can flow from the abdominal cavity, through one-way valve25A and into the blood vessel, but fluid cannot flow in the opposite direction. It should be appreciated that valve element35A is preferably configured such that valve element35A is “closed” (i.e., does not permit fluid to flow) until the pressure differential between (i) the pressure of the fluid entering inlet70A, and (ii) the pressure of the fluid entering outlet75A, rises above a pre-determined threshold. By way of example but not limitation, valve element35A may be configured to “open” (i.e., allow fluid to flow from inlet70A, through valve element35A and out of outlet75A) when the pressure differential on the two sides of the valve element is less than 10 mmHg and, more preferably, when the pressure differential is between 2 mmHg and 5 mmHg. Proximal connection element40A is preferably mounted to proximal end55A of tube50A of valve body30A, and distal connection element45A is preferably mounted to distal end60A of tube50A of valve body30A. Proximal connection element40A and distal connection element45A are preferably spaced apart from one another such that when one-way valve25A is deployed at an internal site (e.g., across the wall of a blood vessel such as a vein), the blood vessel wall is captured between proximal connection element40A and distal connection element45A, whereby to anchor one-way valve25A in place within the wall of the blood vessel. To this end, the distance between proximal connection element40A and distal connection element45A is preferably equal to the thickness of the vessel wall to be spanned by one-way valve25A plus any intervening tissue through which the deployed one-way valve25A will pass (e.g., interstitial tissue, peritoneal layer, etc.). Proximal connection element40A is similar to the aforementioned proximal connection element40, however, proximal connection element40A comprises a radially expandable mesh basket155, rather than a plurality of legs80, for engaging the outer wall of the blood vessel. More particularly, basket155of proximal connection element40A is preferably spring-biased such that basket155will automatically deploy radially outward when proximal connection element40A is unconstrained (i.e., released from deployment catheter125in the manner discussed above). Distal connection element45A is similar to the aforementioned distal connection element45, however, distal connection element45A comprises a radially expandable mesh basket160, rather than a plurality of legs80, for engaging the inner wall of the blood vessel. More particularly, basket160of distal connection element45A is preferably spring-biased such that basket160will automatically deploy radially outward when distal connection element45A is unconstrained (i.e., released from deployment catheter125in the manner discussed above). Although one-way valve25A is depicted inFIGS.16-19as having two connection elements (i.e., a proximal connection element40A and a distal connection element45A), it should be appreciated that, if desired, one-way valve25A may comprise only a single connection element. By way of example but not limitation, distal connection element45A may be omitted. In this form of the invention, proximal connection element40A is configured to anchor one-way valve25A in the blood vessel (e.g., proximal connection element40A might comprise a sewing ring for suturing proximal connection element40A to the wall of the blood vessel or the intervening tissue). This may be advantageous in some applications, inasmuch as distal connection element45A would otherwise be disposed within the interior of a blood vessel, and the omission of distal connection element45A (i.e., radially expandable mesh basket160of distal connection element45A), which is typically disposed within the interior of the blood vessel, can minimize the incidence of thrombosis at the site of implantation. Alternative Valve Elements In the foregoing descriptions, valve elements35/35A are shown and described as slit-type valves which automatically open in order to allow fluid flow in a single, pre-determined direction (i.e., from the abdominal cavity, through valve element35/35A and out to the interior of the blood vessel) when the pressure differential across the valve element exceeds a pre-determined threshold. However, it should be appreciated that valve elements35/35A may be provided in various other configurations if desired. By way of example but not limitation, and looking now atFIG.20, there is shown a valve element35B which comprises a flexible flap165which pivots away from a stop170when the pressure differential across the valve exceeds a predetermined threshold, whereby to allow fluid flow, but which seats against stop170when the pressure differential across the valve falls below a predetermined threshold. In this way, valve element35B provides one-way flow through lumen65of one-way valve25. By way of further example but not limitation, and looking now atFIG.21, there is shown a valve element35C which comprises a spring-biased plunger175which is configured to move longitudinally away from a stop180when the pressure differential across the valve exceeds a predetermined threshold, whereby to allow fluid flow, but which seats against stop180when the pressure differential across the valve falls below a predetermined threshold. In this way, valve element35C provides one-way flow through lumen65of one-way valve25. By way of further example but not limitation, and looking now atFIG.22, there is shown a valve element35D which comprises a ball185which is configured to move longitudinally within a cage190, so that ball185can move away from a stop195when the pressure differential across the valve exceeds a predetermined threshold, whereby to allow fluid flow, but which seats against stop195when the pressure differential across the valve falls below a predetermined threshold. In this way, valve element35D provides one-way flow through lumen65of one-way valve25. By way of further example but not limitation, and looking now atFIG.23, there is shown a valve element35E which comprises a disc200which is configured to move longitudinally within a chamber205, so that disc200can move away from a stop210when the pressure differential across the valve exceeds a predetermined threshold, whereby to allow fluid flow, but which seats against stop210when the pressure differential across the valve falls below a predetermined threshold. In this way, valve element35E provides one-way flow through lumen65of one-way valve25. By way of further example but not limitation, and looking now atFIG.24, there is shown a valve element35F which comprises a wheel215which is configured to rotate in one direction within a chamber220when the pressure differential across the valve exceeds a predetermined threshold, whereby to allow fluid flow through lumen65of one-way valve25, but which is prevented from rotating in the opposite direction within the chamber by a stop225when the pressure differential across the valve falls below a predetermined threshold, whereby to prevent fluid flow through lumen65of one-way valve25. In this way, valve element35F provides one-way flow through lumen65of one-way valve25. It will be appreciated by those skilled in the art that still other configurations are possible for valve element35. Alternative Connection Elements In the foregoing description, one-way valve25is described as being having a body50which extends through the wall of a blood vessel, and having a proximal connection element40contacting the outside surface of the blood vessel, and a distal connection element45contacting the inside surface of the blood vessel, and with connection elements40,45being spaced apart from one another such that when one-way valve25is deployed across the wall of a blood vessel, the blood vessel wall is captured between proximal connection element40and distal connection element45, whereby to anchor one-way valve25in place. And in the foregoing description, proximal connection element40was described as comprising a plurality of legs80terminating in a plurality of distally-directed contact surfaces85, and distal connection element45was described as comprising a plurality of legs90terminating in a plurality of proximally-directed contact surfaces95. However, it should be appreciated that it is possible to anchor one-way valve25in place across the wall of a blood vessel using various other configurations of connection elements. By way of example but not limitation, and looking now atFIG.25, in another form of the invention, there is shown a one-way valve25B having a body30B, wherein body30B is in the form of an expandable stent50B, and having a valve element35disposed within body30B. In this form of the invention, stent50B is capable of expanding laterally, such that one end of stent50B forms proximal connection element40B and the other end of stent50B forms distal connection element45B, with proximal connection element40B contacting the outside surface of the blood vessel and distal connection element45B contacting the inside surface of the blood vessel, whereby to anchor one-way valve25B in place. Expandable stent50B is preferably a covered stent. By way of further example but not limitation, and looking now atFIG.26, in another form of the invention, there is shown a one-way valve25C having a body30C, wherein body30C is in the form of a shaft50C, and having a valve element35disposed within shaft50C. In this form of the invention, one end of shaft50C comprises barbs230so as to form proximal connection element40C and the other end of shaft50C comprises a flange235so as to form distal connection element45C, with proximal connection element40C engaging the wall of the blood vessel and distal connection element45C contacting the inside surface of the blood vessel, whereby to anchor one-way valve25C in place. It will be appreciated by those skilled in the art that still other configurations are possible for connection elements40,45. Alternative One-Way Valve Looking now atFIG.27, there is shown another one-way valve300formed in accordance with the present invention. One-way valve300is generally similar to the one-way valves25,25A discussed above, however, the valve element is disposed on the distal end of the one-way valve so that the valve element extends into the blood vessel, as will hereinafter be discussed in further detail. More particularly, one-way valve300generally comprises a body305, a valve element310, a proximal connection element315and a distal connection element320. Body305generally comprises a tube325having a proximal end330, a distal end335, and a lumen340extending therebetween. Lumen340comprises an inlet345disposed at proximal end330of tube325and an outlet350disposed at distal end335of tube325. In one form of the present invention, tube325(and hence, lumen340) comprises a generally circular cross-section and is radially-compressible in order to aid in implantation of one-way valve300into a blood vessel, as will hereinafter be discussed in further detail. It should be appreciated that in a preferred form of the invention, the length of tube325can be selected such that the length of tube325is at least equal to the thickness of the wall of the blood vessel into which one-way valve300is to be implanted, plus the thickness of interstitial tissue which tube325will need to extend through. Furthermore, if desired, the diameter of tube325can be selected such that tube325will comprise a diameter smaller than the diameter of the blood vessel into which one-way valve300is to be implanted. Valve element310preferably comprises a flexible length of tubing355having a proximal end360, a distal end365and a passageway370extending therebetween. Proximal end360of tubing355comprises a valve element inlet362in fluid communication with passageway370. Tubing355is mounted to outlet350of lumen340such that valve element inlet362(and hence, passageway370) is fluidically connected to lumen340. Distal end365of tubing355comprises a valve element outlet367in fluid communication with passageway370. Passageway370of tubing355is preferably configured such that valve element outlet367of passageway370is closed (i.e., tubing355is flattened) when valve element310is in its resting state such that fluid cannot enter into, or exit out of, valve element outlet367, i.e., such that valve element310is “closed”. When the pressure differential between (i) the pressure of the fluid entering valve element inlet362(which is equal to the fluid pressure entering inlet345of lumen340), and (ii) the pressure of fluid entering valve element outlet367of valve element310rises above a pre-determined threshold, valve element outlet367“opens”, whereby to permit fluid to flow from inlet345, through lumen340, through outlet350, through passageway370of tubing355(i.e., through valve element310) and out of valve element outlet367such that the fluid exits out of one-way valve300and into the interior of the blood vessel. By way of example but not limitation, valve element310may be configured to “open” (i.e., allow fluid to flow from inlet345, though lumen340, through passageway370and out valve element outlet367of passageway370) when the pressure differential on the two sides of the valve element is less than 10 mmHg and, more preferably, when the pressure differential is between 2 mmHg and 5 mmHg. It should be appreciated that in this form of the invention, valve element310generally comprises a one-way slit-type valve which allows fluid to enter inlet345, pass through lumen340, pass through outlet350and into passageway370of tubing355and pass out through valve element outlet367, but which does not allow fluid to flow in the opposite direction (i.e., from the blood vessel, through valve element310and into the abdominal cavity). As a result, when one-way valve300is implanted into a blood vessel (e.g., a vein) in the region of the abdominal cavity such that inlet345is open to fluid within the abdominal cavity and valve element outlet367of valve element310is open to the interior of a blood vessel, fluid can flow from the abdominal cavity, through one-way valve300and into the blood vessel, but fluid cannot flow in the opposite direction. In a preferred form of the present invention, tubing355of valve element310is curved so as to be disposed generally transverse to the longitudinal axis of lumen340of body305when one-way valve300is implanted into the side wall of a blood vessel, and so as to extend along a distance of the blood vessel into which one-way valve300is implanted. If desired, tubing355of valve element310may comprise a smooth outer surface (e.g., Teflon) in order to minimize thrombus formation. It should also be appreciated that, if desired, an additional valve element (e.g., valve element35,35A etc.) may be disposed within lumen340of body305of one-way valve300in addition to (or in lieu of) valve element310. Alternatively, a valve element (e.g., valve element35,35A, etc.) may be disposed within passageway370of tubing355. Proximal connection element315is preferably mounted to proximal end330of tube325of valve body305, and distal connection element320is preferably mounted to distal end335of tube325of valve body305. Proximal connection element315and distal connection element320are preferably spaced apart from one another such that when one-way valve300is deployed at an internal site (e.g., across the wall of a blood vessel such as a vein), the blood vessel wall is captured between proximal connection element315and distal connection element320, whereby to anchor one-way valve300in place within the wall of the blood vessel. To this end, the distance between proximal connection element315and distal connection element320is preferably equal to the thickness of the vessel wall to be spanned by one-way valve300plus any intervening tissue through which the deployed one-way valve300will pass (e.g., interstitial tissue, peritoneal layer, etc.). Proximal connection element315preferably comprises a plurality of legs375extending radially outward from tube325and terminating in a plurality of distally-directed contact surfaces380. Legs375are preferably spring-biased such that they can be radially constrained when one-way valve300is being delivered to an internal anatomical site (e.g., via a delivery sheath), and thereafter spring outward (e.g., when the deliver sheath is removed) such that legs375and/or distally-directed contact surfaces380engage the wall of the blood vessel (or the intervening tissue), whereby to anchor proximal connection element315(and hence, one-way valve300) in position, as will hereinafter be discussed in further detail. In a preferred embodiment of the present invention, one-way valve300comprises four legs375, however, it should be appreciated that one-way valve300may comprise a greater number of legs375(or a lesser number of legs375) without departing from the scope of the present invention. Distal connection element320preferably comprises a plurality of legs385extending radially outward from tube325and terminating in a plurality of proximally-directed contact surfaces390. Legs385are preferably spring-biased such that they can be radially constrained when one-way valve300is being delivered to an internal anatomical site (e.g., via a delivery sheath), and thereafter spring outward (e.g., when the delivery sheath is removed) such that legs385and/or proximally-directed contact surfaces390engage the wall of the blood vessel (or the intervening tissue), whereby to anchor distal connection element320(and hence, one-way valve300) in position, as will hereinafter be discussed in further detail. In a preferred form of the present invention, one-way valve300comprises four legs385, however, it should be appreciated that one-way valve300may comprise a greater number of legs385(or a lesser number of legs385) without departing from the scope of the present invention. In one preferred form of the invention, the distal end of one-way valve300(i.e., the portions of the one-way valve which extend into the interior of the blood vessel) are formed so as to be as smooth as possible so as to minimize thrombus formation. Although one-way valve300is depicted inFIGS.27and28as having two connection elements (i.e., a proximal connection element315and a distal connection element320), it should be appreciated that, if desired, one-way valve300may comprise only a single connection element. By way of example but not limitation distal connection element320may be omitted. In this form of the invention, proximal connection element315is configured to anchor one-way valve300in the blood vessel (e.g., proximal connection element315might comprise a sewing ring for suturing proximal connection element315to the wall of the blood vessel or the intervening tissue). This may be advantageous in some applications, inasmuch as distal connection element320would otherwise be disposed within the interior of a blood vessel, and the omission of distal connection element320(i.e., legs385of distal connection element320), which is typically disposed within the interior of the blood vessel, can minimize the incidence of thrombosis at the site of implantation. Exemplary Use of One-Way Valve300 In use, and looking now atFIG.28, one-way valve300is preferably implanted into the peritoneum/interstitium and the wall of a blood vessel100(e.g., the vena cava, the vena iliaca, etc.) such that inlet345of one-way valve300is in fluid communication with the abdominal cavity105(e.g., such that inlet345is in fluid communication with the ascetic fluid), and valve element outlet367of valve element310is in fluid communication with the interior of blood vessel100. Proximal connection element315contacts the outer wall of blood vessel100(or contacts the intervening tissue, e.g., the peritoneal layer and/or interstitial tissue), and distal connection element320contacts the inner wall of blood vessel100such that one-way valve300spans the blood vessel wall (and any intervening tissue) and provides a one-way fluid pathway from abdominal cavity105, through tube325, through valve element310into the interior of blood vessel100. As a result, fluid is able to flow from abdominal cavity105, into inlet345of one-way valve25, through valve element310and out valve element outlet367of tubing355of valve element310, into the interior of blood vessel100. A delivery system (e.g., the aforementioned delivery system110or another novel delivery system, as will hereinafter be discussed) may be provided for implanting one-way valve300into the wall of a blood vessel. Although an “endoluminal approach” (e.g., an endovascular approach) is preferably used to implant one-way valve300into the side wall of a blood vessel, if desired, an “abdominal approach” may be used. Alternative Delivery System As discussed above, one-way valve300(or one-way valve25,25A, etc.) is configure to be implanted into the side wall of a blood vessel (e.g., a vein) at an internal anatomical site in order to facilitate treatment of ascites. To this end, it is possible to use the novel delivery system110discussed above in order to deliver one-way valve300to the internal anatomical site and to deploy the one-way valve into the side wall of the blood vessel. However, in one preferred form of the present invention, it is desirable to provide additional control over implanting and deploying one-way valve300by utilizing an alternative form of delivery system. To that end, and looking now atFIGS.29-36, there is shown an alternative novel delivery system400formed in accordance with the present invention. Delivery System400generally comprises a puncture device (e.g., the aforementioned puncture device115), a guidewire410, a dilator415, a deployment catheter420and a delivery tool425. More particularly, the puncture device (not shown inFIGS.29-36) preferably comprises an elongated shaft having a sharp distal end which may be used to penetrate through tissue (e.g., through the peritoneal layer, through interstitial tissue, through the wall of a blood vessel, etc.). If desired, the puncture device (e.g., puncture device115) may be omitted, and a guidewire410may be used to penetrate tissue. Guidewire410comprises a flexible guidewire of the sort well known in the art which may be used to guide the one-way to an internal site, as will hereinafter be discussed in further detail. If desired, guidewire410may comprise a pre-curved tip (FIG.32) to facilitate addressing the side wall of a blood vessel where one-way valve300is to be implanted. Dilator415comprises an elongated tube430having a tapered distal end435. In a preferred form of the present invention, tapered distal end435comprises an opening for receiving guidewire410so that dilator415may be passed over guidewire410and advanced to an internal anatomical site, as will hereinafter be discussed in further detail. Deployment catheter420generally comprises a tube440having an open distal end445, an open proximal end450, and a lumen455extending therebetween (FIG.33). Lumen455of tube440is sized so as to hold the one-way valve in a radially-contracted condition, e.g., with the legs of the proximal connection element and the legs of the distal connection element being held parallel to the body of the one-way valve, whereby to provide a reduced profile for delivery of the one-way valve to an internal anatomical site, as will hereinafter be discussed in further detail. In one preferred form of the present invention, deployment catheter420also comprises a spring460disposed in the distal portion of lumen455which biases a push rod465(which is slidably disposed within lumen455) proximally, whereby to prevent premature deployment of the one-way valve out of distal end445of deployment catheter420, as will hereinafter be discussed in further detail. Delivery tool425comprises a handle470and a steerable access sheath475extending distally from handle470. Steerable access sheath475comprises a flexible distal end480and a proximal end485mounted to handle470with a lumen490extending therebetween. A passageway495(FIG.30) is aligned with lumen490and extends through handle470, opening on the proximal end of handle470. Passageway495(and lumen490) are sized to receive deployment catheter420, as will hereinafter be discussed in further detail. In a preferred form of the present invention, flexible distal end480of steerable access sheath475can be selectively articulated using handle470by various means, which will be apparent to those skilled in the art in view of the present disclosure. Method of Implanting and Deploying a One-Way Valve Using Delivery System400 As discussed above, a one-way valve (e.g., one-way valve25,25A,300, etc.) is intended to be deployed in the side wall of a blood vessel proximate to the abdominal cavity such that fluid can flow from the abdominal cavity, through the one-way valve, and into the interior of the blood vessel. The one-way valve may be deployed at an internal anatomical site using various methods (e.g., open surgery, percutaneous deployment, endoluminal deployment, etc.) or combinations thereof. For clarity of illustration, implantation of one-way valve300using novel delivery system400will be discussed hereinbelow in the context of an endovascular approach. By way of example but not limitation, in order to prepare the internal site for implantation of one-way valve300, the surgeon first extracts the ascetic fluid from the abdominal cavity (e.g., using a syringe, a collection bag, suction, etc.). If desired, the ascetic fluid may also be drained from the abdominal cavity using an endovascular drain of the sort well known in the art, or by draining the ascetic fluid endovascularly via delivery system400. The abdominal cavity is then preferably rinsed (e.g., with saline) and drained again. After the surgeon has located a suitable blood vessel for implantation and identified a suitable implantation site (i.e., a suitable blood vessel for receiving one-way valve300proximate to the abdominal cavity), the puncture device (e.g., puncture device115) is used to puncture the skin of the patient so as to access the interior of a blood vessel. In a preferred form of the invention, access to the vasculature is made by puncturing the jugular vein (FIG.15A) using puncture device115and then the one-way valve is advanced to the selected internal site endoluminally. Alternatively, access to the vasculature may be achieved by puncturing the subclavian vein (also known as the vena subclavia) and then the one-way valve is advanced to the internal site endoluminally. In still another form of the invention, access to the vasculature is made via the vena femoralis (FIG.15B) at a location remote from the patient's abdomen (e.g., the thigh, groin, etc.) in order to allow endovascular advancement of one-way valve300to the selected internal anatomical site. Steerable access sheath475is then advanced into the blood vessel (e.g., the jugular vein) and advanced endovascularly until flexible distal end480of steerable access sheath475is proximate to the implantation site. The surgeon then selectively articulates flexible distal end480of steerable access sheath475(e.g., via handle470) until flexible distal end480of steerable access sheath475appropriately addresses the side wall of the blood vessel for facilitating implantation of one-way valve300. Guidewire410is then inserted into passageway495of handle470and through flexible access sheath475and advanced endovascularly until the guidewire is disposed at the internal anatomical site (e.g., the desired location within the inferior vena cava). SeeFIG.37. It should be appreciated that, if desired, guidewire410may be advanced to the internal anatomical site first, and flexible access sheath475can be advanced over the guidewire. Dilator415is then passed over guidewire410and advanced to the internal anatomical site (FIG.37). Tapered distal end435of dilator415is then passed through the side wall of the blood vessel (and through interstitial tissue, the peritoneal layer, etc.) in order to form an enlarged passageway sized to received one-way valve300(FIG.38). Deployment catheter420, carrying one-way valve300within lumen455of the deployment catheter, is then advanced to the internal anatomical site by passing deployment catheter420over guidewire410and over dilator415. After distal end445of deployment catheter420is passed through the side wall of the blood vessel, through the interstitial tissue and through the peritoneal layer, such that distal end445is disposed within the abdominal cavity (FIG.38), dilator415and guidewire410are removed (i.e., withdrawn proximally) leaving deployment catheter420in place within the anatomy (FIG.39). It should be appreciated that at this time, one-way valve300is disposed just inside the distal end of deployment catheter420(or, alternatively, one-way valve300may be advanced to a position just inside the distal end of deployment catheter420). When one-way valve300is disposed in the desired position, the surgeon deploys one-way valve300by moving pushrod465distally against the power of spring460such that pushrod465engages one-way valve300and ejects the proximal end of one-way valve300out of deployment catheter420, such that legs375expand radially outward, with distally-directed contact surfaces380contacting the outer wall of the blood vessel (or the interstitial tissue covering the outer wall of the blood vessel). Next, deployment catheter420is withdrawn further until distal connection element320, which is disposed within the interior of the blood vessel (e.g., the interior of the inferior vena cava), is uncovered. As this occurs, radially-constricted legs385expand radially outward into their radially-expanded configuration, with proximally-directed contact surfaces390contacting the inner wall of the blood vessel. If necessary, steerable access sheath475can also be retracted slightly in order to provide room for radial expansion of legs385. At this point, one-way valve300is locked in position within the side wall of the blood vessel. SeeFIGS.40and41. Finally, deployment catheter420is withdrawn so as to remove the deployment catheter from the patient's body and steerable access sheath475is also withdrawn, leaving one-way valve300implanted within the side wall of the blood vessel. At the conclusion of the procedure, one-way valve300is securely anchored within the side wall of the blood vessel (e.g., the inferior vena cava), held in position by proximal connection element315and distal connection element320. Inlet345of tube325of one-way valve300is fluidically connected to the abdominal cavity and valve element outlet367of tubing355of valve element310of one-way valve300is fluidically connected to the blood vessel (e.g., the interior of the inferior vena cava). As a result, fluid (e.g., fluid resulting from ascites) is able to flow from the abdominal cavity, into inlet345of tube325, along lumen340of tube325, through tubing355of valve element310and out valve element outlet367of tubing355into the interior of the blood vessel (e.g., the interior of the inferior vena cava), but fluid is unable to flow in the opposite direction. Thus, fluid can exit the abdominal cavity and enter the blood vessel without the need for a long catheter or the need for external access to the abdominal cavity. Novel Valve for Draining Body Fluid from a Body Cavity, and in Particular for Draining Fluid from the Pleural Cavity In addition to the foregoing, it should also be appreciated that any of the one-way valves discussed above (e.g., one-way valve25, one-way valve25A, etc.) and/or any of the delivery systems discussed above (e.g., delivery system110) may also be used to drain fluid from a first body cavity into a second body cavity, and/or to drain fluid from a body cavity into the venous system of the patient. By way of example but not limitation, one such instance where it may be desirable to drain fluid from a first body cavity into a second body cavity is where there is fluid build-up in the pleural cavity (i.e., the space between the visceral pleural layer and the parietal plural layer) such as can occur in association with conditions such as cancer, heart disease, etc. Such fluid-build up in the pleural cavity is commonly referred to as pleural effusion. In accordance with the present invention, pleural effusion may be treated by implanting a novel one-way valve in the body such that the proximal end of the one-way valve is in fluid communication with the fluid inside the pleural cavity and the distal end of the one-way valve is in fluid communication with the abdominal cavity. To this end, and looking now atFIGS.43-45, there is shown a novel one-way valve500formed in accordance with the present invention which is sized and configured for implantation into a patient's body so as to facilitate draining of a first body cavity (e.g., the pleural body cavity) to a second body cavity (e.g., the abdominal cavity), and/or to facilitate draining of a first body cavity (e.g., the pleural cavity) to the venous system of the patient (e.g., the vena cava). One-way valve500preferably comprises a proximal end505, a distal end510and a body515extending therebetween. If desired, body515of one-way valve500may be structured and/or textured so as to facilitate implantation of one-way valve500into the body of a patient. By way of example but not limitation, body515may comprise a “stent structure” (FIG.43) for promoting ingrowth of adjoining tissue and/or for anchoring body515in the tissue of the patient. Body515comprises a tube520having an inlet525disposed at proximal end505of one-way valve and an outlet530disposed at distal end510of one-way valve500, with a lumen535extending therebetween. In one preferred form of the invention, tube520comprises expanded polytetrafluoroethylene (ePTFE). The length of body515of one-way valve500can be selected such that the length of tube520of one-way valve500is at least equal to the thickness of the tissue (e.g., the diaphragm) into which one-way valve500is to be implanted, plus the thickness of tissue which tube520will need to extend through in order to reach the pleural cavity (e.g., the parietal pleura, etc.). A valve element540(FIG.45) is preferably disposed in lumen535of tube520intermediate inlet525and outlet530, with valve element540being configured to permit one-way flow of fluid through lumen535from inlet525to outlet530, but to prevent fluid from flowing in the opposite direction (i.e., from outlet530to inlet525). In one preferred form of the invention, valve element540comprises a one-way, slit-type valve such that fluid may enter into inlet525, pass through the proximal portion of lumen535, pass through valve element540, pass through the distal portion of lumen535and exit out of outlet530, but which does not allow fluid to flow in the opposite direction (i.e., from the abdominal cavity, through valve element540and into the pleural cavity). As a result, when one-way valve500is implanted into the body of a patient such that inlet525is open to fluid disposed in a first body cavity (e.g., the pleural cavity) and outlet530is open to the interior of a second body cavity (e.g., the abdominal cavity), fluid can flow from the first body cavity (e.g., the pleural cavity), through one-way valve500and into the second body cavity (e.g., the abdominal cavity), but fluid cannot flow in the opposite direction. It should be appreciated that valve element540is preferably configured such that valve element540is “closed” (i.e., does not permit fluid to flow) until the pressure differential between (i) the pressure of the fluid entering inlet525, and (ii) the pressure of the fluid entering outlet530, rises above a pre-determined threshold. By way of example but not limitation, valve element540may be configured to “open” (i.e., allow fluid to flow from inlet525, through valve element540and out of outlet530) when the pressure differential on the two sides of the valve element is less than 10 mmHg and, more preferably, when the pressure differential is between 2 mmHg and 5 mmHg. Alternatively and/or additionally, if desired, outlet530of tube520may comprise valve element540. By way of example but not limitation, distal end530of tube520may be flattened, e.g., in the manner of a “duckbill valve” so as to form valve element540, whereby to permit fluid to flow from inlet525through lumen535, through valve element540(i.e., the flattened proximal portion of tube520), and out outlet530while preventing fluid from flowing in the opposite direction (i.e., from outlet530through lumen535and out inlet525). Novel Method for Draining Body Fluid from a First Body Cavity to a Second Body Cavity, and in Particular for Draining Fluid from the Pleural Cavity to the Abdominal Cavity If desired, a one-way valve may be implanted into the body such that the one end of the one-way valve is in fluid connection with a first body cavity, and the other end of the one-way valve is in fluid communication with a second body cavity. For purposes of illustration, the present invention will now be discussed in the context of a one-way valve implanted between the pleural cavity and the abdominal cavity, however, it should be appreciated that a one-way valve may be implanted so as to span (and be in fluid connection with) substantially any two body cavities without departing from the scope of the present invention. As will also hereinafter be discussed in further detail, one-way valve500may be implanted using an “abdominal approach” in which the one-way valve is advanced from the abdominal cavity, through the diaphragm, and into the pleural cavity. Alternatively, one-way valve500may be implanted using an “thoracic approach” in which the one-way valve is advanced from the pleural cavity, through the diaphragm, and into the abdominal cavity. Looking now atFIGS.46-48, in one preferred form of the invention, novel one-way valve500may be implanted into the body such that inlet525of tube520located at proximal end505of one-way valve500is disposed in, and fluidically connected to, a pleural cavity545and such that outlet530of tube520located at distal end510of one-way valve500is disposed in, and fluidically connected to, the abdominal cavity550, such that body515of one-way valve500passes through the intervening tissue (i.e., the diaphragm, the parietal pleura, etc.) disposed between pleural cavity545and abdominal cavity550. More particularly, and still looking atFIGS.46-48, in one preferred form of the invention, one-way valve500is implanted endoscopically (e.g., laparoscopically or thorascoscopically) by accessing the abdominal cavity (e.g., via a surgical access cannula), locating an appropriate position on the diaphragm for implantation of one-way valve500(e.g., taking into consideration any diseased tissue proximate to the diaphragm, connective tissue, muscular tissue, etc.) and then puncturing (e.g., with a needle, puncturing device, etc.) diaphragm555and the parietal pleura560(and any intervening tissue) so as to form an “access tunnel” through the tissue disposed between abdominal cavity550and pleural cavity545. If desired, a guidewire (not shown) may be inserted into the “access tunnel” so as to guide insertion of one-way valve500into the “access tunnel.” Alternatively and/or additionally, a delivery system (e.g., the aforementioned delivery system110) may be used to deliver one-way valve500to the surgical site in the manner discussed above. After the “access tunnel” has been formed, proximal end505of one-way valve500is advanced into “access tunnel” (e.g., over a guidewire, if used), through the diaphragm555, through the parietal pleura560and into the pleural cavity545such that inlet525of tube520of one-way valve500is fluidically connected to the pleural cavity, and such that outlet530of tube520of one-way valve500is disposed in, and fluidically connected to, abdominal cavity550. Body515preferably engages diaphragm555and/or any intervening tissue that body515of one-way valve500passes through. Once one-way valve500is implanted such that it fluidically connects pleural cavity545with abdominal cavity550, fluid disposed in pleural cavity545is able to flow enter one-way valve500via inlet525of tube520, flow through lumen535of tube520, pass through one-way valve540, and exit out of outlet530of tube520into abdominal cavity550. If desired, a camera (e.g., a surgical camera inserted via an access portal into the abdominal cavity) may be used by the surgeon in order to ensure correct device placement and/or to inspect for blood dryness, etc. After the device is implanted in the desired position (and confirmed by the surgeon), the delivery device (if used), guidewire, camera(s), surgical access cannula(s), etc. are removed from the surgical site and any access portals are closed and dressed. As a result, fluid can now be continuously drained from pleural cavity545to abdominal cavity550, where the fluid may be reabsorbed by the body (or drained from the abdominal cavity via another method), whereby to treat pleural effusion. It should be appreciated that one-way valve500may be implanted into the diaphragm so as to fluidically connect pleural cavity545to abdominal cavity550at substantially any location where the surrounding anatomy permits implantation. By way of example but not limitation, one-way valve500may be implanted into the medial, paraaortal portion of the diaphragm (i.e., near where the central tendon is located) as shown inFIG.46. By way of further example but not limitation, one-way valve500may be implanted into the left portion of the diaphragm as shown inFIG.47. By way of further example but not limitation, one-way valve500may be implanted into the central area of the left portion of the diaphragm as shown inFIG.48. By way of still further example but not limitation, one-way valve500may be implanted into the costal muscle fibers of the diaphragm (i.e., the outer portion of the diaphragm). It should also be appreciated that, if desired, multiple one-way valves500may be implanted into the diaphragm so as to fluidically connect pleural cavity545to abdominal cavity550. Although implantation of one-way valve500has been discussed above in the in the context of a laparoscopic approach (i.e., implanting one-way valve500into the diaphragm using an endoscopic, abdominal-to-pleural cavity implantation approach), if desired, one-way valve500may be instead implanted thoracosopically (i.e., one-way valve500may be implanted by accessing the thoracic cavity/pleural cavity first, and then inserting the distal end through the intervening tissue and the diaphragm so that the distal end of one-way valve500is disposed in the abdominal cavity). Novel Method for Draining Body Fluid from a Body Cavity to a Blood Vessel, and in Particular for Draining Fluid from the Pleural Cavity to a Veneous Blood Vessel If desired, a one-way valve may be implanted into the body such that the one-way valve is in fluid connection with a first body cavity and with a blood vessel (e.g., the vena subclavia, the vena cava, etc.). For purposes of illustration, the present invention will now be discussed in the context of a one-way valve implanted between the pleural cavity and the vena cava so as to fluidically connect the pleural cavity and the vena cava, however, it should be appreciated that a one-way valve may be implanted so as to fluidically connect substantially any body cavity and substantially any blood vessel without departing from the scope of the present invention. Looking now atFIG.49, in one preferred form of the invention, novel one-way valve500is implanted into the body such that inlet525of tube520located at proximal end505of one-way valve500is disposed in, and fluidically connected to, a pleural cavity545such that outlet530of tube520located at the distal end510of one-way valve500is disposed in, and fluidically connected to, the interior of a venous blood vessel (e.g., the vena cava)565such that one-way valve500passes through the intervening disposed between the pleural cavity545and venous blood vessel565, whereby to fluidically connect pleural cavity545to venous blood vessel565. More particularly, and still looking atFIG.49, in one preferred form of the invention, one-way valve500is implanted using an endovascular approach. After the surgeon has located a suitable blood vessel for implantation and identified a suitable implantation site (i.e., a suitable blood vessel for receiving one-way valve500proximate to the pleural cavity), a puncture device (e.g., the aforementioned puncture device115) is used to puncture the skin of the patient so as to access the interior of the blood vessel. In a preferred form of the invention, access to the vasculature is made by puncturing the jugular vein using a puncture device and then the one-way valve is advanced to the selected internal site endoluminally. Alternatively, access to the vasculature may be achieved by puncturing the subclavian vein (also known as the vena subclavia) and then one-way valve is advanced to the internal site endoluminally. In still another form of the invention, access to the vasculature is made via the vena femoralis at a location remote from the patient's chest (e.g., the thigh, groin, etc.) in order to allow endoluminal advancement of one-way valve500to the selected internal anatomical site. When one-way valve500(and/or the appropriate delivery system) is disposed at the desired location along venous blood vessel565(e.g., in the vena cava proximate to the pleural cavity), an “access tunnel” is formed in the side wall of the vasculature so as to pass through the intervening tissue and into pleural cavity545. The proximal end505of one-way valve500is then advanced through the “access tunnel” and into pleural cavity545such that inlet525of tube520disposed at proximal end505of body515of one-way valve500) is fluidically connected to pleural cavity545, and such that outlet530of tube520(disposed at distal end510of body515of one-way valve500) is fluidically connected to the interior of venous blood vessel565. If desired, a guidewire (not shown) may be inserted into the “access tunnel” so as to guide insertion of one-way valve500into the “access tunnel”. Alternatively and/or additionally, if desired, a delivery system (e.g., the aforementioned delivery system110) is to be used to deliver the one-way valve to the surgical site. Body515preferably engages the side wall of the vasculature and/or the intervening tissue into which one-way valve500is implanted. After one-way valve500is implanted such that it fluidically connects pleural cavity545with the interior of venous blood vessel565, fluid disposed in pleural cavity545is able to enter one-way valve500via inlet525of tube520, flow through lumen535of tube520, pass through one-way valve540, and exit out of outlet530of tube520into venous blood vessel565. If desired, an endoluminal ultrasound device (e.g., an ultrasound device inserted endoluminally and advanced to the surgical site) may be used by the surgeon in order to ensure correct device placement and/or to inspect for blood dryness, etc. After the device is implanted in the desired position (and confirmed by the surgeon), the delivery device (if used), guidewire, ultrasound device, surgical access portal(s), etc. are removed from the surgical site and any access portals are closed and dressed. As a result, fluid can now be continuously drained from pleural cavity545to venous blood vessel565, where the fluid is reabsorbed by the body, whereby to treat pleural effusion. It should be appreciated that multiple one-way valves500may be implanted into the side wall of venous blood vessel565so as to fluidically connect pleural cavity545to the interior of venous blood vessel565as discussed above. Alternatively and/or additionally, multiple one-way valves500may be implanted into the side wall of multiple venous blood vessels so as to fluidically connect pleural cavity545to the interior of venous blood vessels as discussed above. Although implantation of one-way valve500has been discussed above in the in the context of a endoluminal approach (i.e., implanting one-way valve500into the side wall of a venous blood vessel using an endoluminal, venous blood vessel-to-pleural cavity implantation approach), if desired, one-way valve500may be instead implanted thoracosopically (i.e., one-way valve500may be implanted by accessing the thoracic cavity/pleural cavity first, and inserting the distal end of one-way valve500through the intervening tissue and the side wall of veneous blood vessel565so that the distal end of one-way valve500is disposed in the interior of the venous blood vessel). Modifications of the Preferred Embodiments It should be understood that many additional changes in the details, materials, steps and arrangements of parts, which have been herein described and illustrated in order to explain the nature of the present invention, may be made by those skilled in the art while still remaining within the principles and scope of the invention. | 74,571 |
11857746 | DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT Referring toFIGS.1to10and14, the apparatus (1) for cleansing wounds comprisesa conformable wound dressing (2), havinga backing layer (3) which is capable of forming a relatively fluid-tight seal or closure over a wound and bears an adhesive film, to attach it to the skin sufficiently to hold the wound dressing (2) in place;a cleansing means (4) for selectively removing materials that are deleterious to wound healing from wound exudate, which means is under the backing layer (3) and sits in the underlying wound in use; anda moving device (7) for moving fluid through the cleansing means. Optional means for bleeding or supplying fluid to the cleansing means (4) or to exudate under the backing layer, e.g. a regulator, such as a valve are omitted in most of the Figures. InFIG.1, a reversing system is shown (wound exudate passes through the cleansing means at least once in opposing directions). The microbe-impermeable film backing layer (3) bears a centrally attached proximally projecting recessed boss (11). A porous film (12) and a permeable membrane (13) mounted in the recess (14) of the boss (11) define a cleansing chamber (15), which contains a solid particulate (not shown) for sequestering deleterious materials from, but initially separated from the wound exudate. These integers form the cleansing means (4). An annular chamber (16) about the boss (11) is defined by a fluid-impermeable film (17) that extends between and is attached to the boss (11) and the underside of the backing layer (3). it is filled with a flexibly resilient foam (18) An inlet and outlet pipe (19) passes centrally through the boss (11) and communicates between the interior of the boss (11) and a syringe barrel (20), which is part of a syringe moving device (7). In use, movement of the syringe plunger (22) sucks and forces wound exudate to and fro through the cleansing means (4). The apparatus (1) inFIG.2may be operated as a circulating system or as both a circulating system and as a reversing system. It is similar in construction toFIG.1, but differs mainly in that an inlet pipe return loop (19) passes in a bend through the boss (11) and communicates between the interior of the chamber (16) and the syringe barrel (20) via a non-return valve (21), the resistance of which to flow is low relative to the resistance of the cleansing means (4). Means for bleeding fluid from the chamber (16), such as a valve, is omitted fromFIG.2. In use, the plunger (22) of the syringe moving device (7) is withdrawn to suck wound exudate into the cleansing means (4), which sequesters deleterious materials from the wound exudate. The plunger (22) of the syringe moving device (7) is then returned to force cleansed wound exudate through the valve (21) into the annular chamber (16), and thence through the porous film (17) back into the wound. A proportion of cleansed wound exudate is also pushed back through the cleansing means (4) at each return stroke of the syringe plunger. The proportion will depend largely on the position of the return loop (19) on the syringe barrel. The amount pumped to the annular chamber (16) will decrease the further from the proximal end of the syringe the return loop links to the syringe barrel, as the plunger cuts off the return loop (19) in the later part of the return stroke. Depending largely on the type of cleansing means that is employed in this embodiment of the apparatus of the present invention, the resistance of the valve (21) relative to the resistance of the cleansing means (4) may also affect the proportion through the chamber (16) and through the porous film (17), Excess pressure in the chamber (16), e.g. from wound exudate from a wound in a highly exuding state, may be relieved by a bleed valve, if fitted. The apparatus (1) inFIG.3differs mainly from that inFIG.2in the position of the porous film (12) in the flow path. The mode of use is the same: movement of the syringe plunger (22) sucks and, forces wound exudate to and from through the cleansing means (4). The apparatus (1) inFIGS.4A and4Bdiffers from that inFIG.2in the moving device (7). This is a press-button pump in place of a syringe. The pump (7) is mounted on the distal face of the backing layer (3). It comprises a resiliently compressible intake chamber (26), connected by an outlet pipe (19) to the cleansing means (4) and by a transfer tube (27) via a low resistance first non-return valve (31) to a resiliently compressible output chamber (36), connected via an inlet pipe (20) and a low resistance second non-return valve (32) to the interior of the chamber (16). In use, the intake chamber (26) is manually compressed and released, its return to its original configuration causing wound exudate to be drawn through the cleansing means (4). The output chamber (36) is then manually compressed and released, its return to its original configuration causing cleansed wound exudate to be drawn through the first non-return valve (31) from the intake chamber (26). The intake chamber (26) is then manually compressed again and released, its compression causing cleansed wound exudate to be pumped into the output chamber (36) through the first non-return valve (31) from the intake chamber (26), and its return to its original configuration causing wound exudate to be drawn through the cleansing means (4). The output chamber (36) is then manually compressed again and released, its compression causing cleansed wound exudate to be pumped into the chamber (16) through the second non-return valve (32) from the output chamber (36), and its return to its original configuration causing cleansed wound exudate to be drawn through the intake chamber (26). The cycle is repeated as long as desired, and from the second cycle onwards, when the output chamber (36) is manually compressed, it causes cleansed wound exudate to be forced through the annular chamber (16), and thence through the porous film (17) back into the wound. Referring toFIGS.5to7and10, the apparatus (1) in each comprises a cleansing means (4), which comprises a chamber (5), here a conformable hollow bag, defined by the backing layer (3) and a polymer film (6) that is permeable and permanently attached to the proximal face of the backing layer (3). It sits under the domed backing layer (3) in the underlying wound in use, and contains a cleansing fluid absorbed in a resiliently flexible foam (41). FIGS.5to7and10show different methods of moving wound exudate in and out of the cleansing means (4). InFIG.5, an electromechanical oscillator or piezoelectric transducer (43) is mounted centrally in contact with the backing layer (3) on a rigid frame (44) mounted at the periphery of the backing layer (3), and is connected electrically to an appropriate alternating electrical power source (45) (shown schematically). The chamber (5) is provided with a bleed valve (8). If exudate build up under the backing layer (3) becomes excessive during use, the bleed valve (8) may be opened and excess fluid vented off, and any excess pressure relieved. InFIG.6, the foam (41) has a resiliently flexible, balloon core (47), which is inflatable and deflatable with a fluid, such as a gas, e.g. air or nitrogen, or a liquid, such as water or saline, to apply varying pressure to the chamber (5) via an inlet and outlet pipe (48) mounted at the periphery of the backing layer (3). The pipe (48) is connected to a suitable moving device (58) (not shown) for moving the inflating fluid in and out of the core (47) and thus to move wound exudate in and out of the cleansing means (4). Such a device is suitably one that is capable of optionally pulsed, reversible fluid movement. It may in particular be a small peristaltic pump or diaphragm pump, e.g. preferably a battery-driven miniature portable diaphragm or peristaltic pump, e.g. mounted centrally on the backing layer (3) above the chamber (5) and is releasably attached to the backing layer (3). FIG.7shows a variant of the apparatus (1) ofFIG.6. The resiliently flexible, balloon core (47) under the backing layer (3) is replaced by a resiliently flexible, balloon chamber (49), defined by the backing layer (3) and a rigid polymer dome (50) that is impermeable and permanently attached to the distal face of the backing layer (3). The balloon chamber (49), defined by the backing layer (3) and the rigid polymer dome (50) is also inflatable and deflatable with a fluid, such as a gas, e.g. air or nitrogen, or a liquid, such as water or saline, to apply varying pressure to the chamber (5) via an inlet and outlet pipe (51) mounted at the periphery of the backing dome (50). A suitable moving device (58) (not shown) is used for moving the inflating fluid in and out of the balloon chamber (49) and thus to move wound exudate in and out of the cleansing means (4), as noted in respect ofFIG.6, and may be mounted on the dome (50) rather than the backing layer (3). InFIG.10, an electromagnetic solenoid core (53) within an electrical coil (54) is mounted centrally in contact with the backing layer (3) on a rigid flange (55). The electrical coil (54) is connected electrically to an appropriate alternating electrical power source (60) (shown schematically). The chamber (5) is provided at its base with an attached disc (56) of a ferromagnetic material sheathed from the wound exudate and cleansing fluid. As the direction of current flow alternates, the solenoid core follows, and so compresses and releases the chamber (5), and hence causes wound exudate to be forced to and, fro through the cleansing means (4). FIGS.8and9show a variant of the apparatus (1) ofFIGS.1and4A and4B. The moving device (7) in both cases that respectively replaces the syringe and the press-button pump is a small peristaltic pump or diaphragm pump. It is preferably a battery-driven miniature portable diaphragm or peristaltic pump, e.g. mounted centrally on the backing layer (3) above the chamber (5) and is releasably attached to the backing layer (3). FIG.11shows apparatus with a single-phase means for wound exudate cleansing in which the wound exudate passes through the cleansing means one or more times in only one direction. It is similar in structure to the apparatus shown inFIGS.5to7and10. The apparatus (1) comprises a cleansing means (4), which comprises a chamber (5), here a conformable hollow bag, defined by the backing layer (3) and a polymer film (6) that is permeable and permanently attached to the proximal face of the backing layer (3). It contains a cleansing fluid absorbed in a resiliently flexible foam (41). The resiliently flexible foam (41) is contained in a permeable membrane (43) and contains a material for sequestering deleterious materials from the wound exudate. These integers form the cleansing means (4). An outlet pipe (69) passes centrally through the backing layer (3) and communicates between the interior of the chamber (5) and a pump, e.g. preferably a battery-driven miniature portable diaphragm or peristaltic pump, e.g. mounted centrally on the backing layer (3) above the chamber (5) and releasably attached to the backing layer (3). An inlet pipe (20) passes peripherally through the backing layer (3) and communicates between the wound space and the pump. In use, wound exudate is moved by the pump (7) through the cleansing means (4), and the foam (41) sequesters deleterious materials from the wound exudate. FIGS.12Aand B shows apparatus with a two-phase means for wound exudate cleansing in which the cleansing phase moves. FIG.12Ashows apparatus in which the only the cleansing phase moves. FIG.12Bshows apparatus in which the cleansing phase and the wound exudate phase move. In both Figures, the apparatus (1) comprises a cleansing means (4), which comprises a chamber (5), here in the form of tubules in an array under the backing layer (3) between a first boss (71) and a second boss (72) both mounted in the backing layer (3). The tubules are made from a polymer membrane that is selectively permeable to deleterious materials in the wound exudate, and contain a dialysate fluid. An inlet pipe (20) passes from the first boss (71) and communicates between the interior of the chamber (5) and a pump (7), e.g. preferably a battery-driven miniature portable diaphragm or peristaltic pump, e.g. mounted centrally on the backing layer (3) above the chamber (5) and releasably attached to the backing layer (3). An outlet pipe (21) passes from the second, boss (72) and communicates between the interior of the chamber (5) and the pump (7). In use, dialysate fluid is moved by the pump (7) through the cleansing means (4), and it removes deleterious materials from the wound exudate. InFIG.12B, a third boss (78) with a wound exudate outlet passing centrally through it and a fourth boss (79) with a wound exudate inlet passing centrally through it are both mounted peripherally and mutually diametrically opposed in the backing layer (3). A wound exudate outlet tube (80) is connected to the third boss (78) and communicates between the interior of the wound and the inlet of a second pump (82) (not shown), e.g. preferably a battery-driven miniature portable diaphragm or peristaltic pump, mounted centrally on the backing layer (3). A wound exudate inlet tube (81) is connected to the fourth boss (79) and communicates between the interior of the wound and the outlet of the second pump. In use, not only is dialysate fluid moved by the first pump (7) through the cleansing means (4), where it removes deleterious materials from the wound exudate, but the wound exudate phase is moved under the backing layer (3) through the wound space by the second pump in a counter-current direction to enhance the removal from the wound exudate. FIG.13shows apparatus with a two-phase means for wound exudate cleansing in which the cleansing phase moves. The apparatus (1) comprises a cleansing means (4), which comprises a chamber (5), here in the form of bag under the backing layer (3) and under a foam filler (81). This bag is made from a polymer membrane and contains a dialysate fluid, which contains a material as a solute or disperse phase species that is for sequestering or degrading deleterious materials from the wound exudate. The membrane is chosen to be selectively permeable to allow, perfusion of deleterious material species targeted for sequestration or destruction from the wound exudate into the dialysate, but not to allow any significant amounts of antagonist in the dialysate fluid phase to diffuse freely out of the dialysate into the wound fluid. An outlet pipe (89) passes through the backing layer (3) and communicates between the interior of the chamber (5) and a pump, e.g. preferably a battery-driven miniature portable diaphragm or peristaltic pump, e.g. mounted centrally on the backing layer (3) above the chamber (5) and releasably attached to the backing layer (3). An inlet pipe (90) passes peripherally through the backing layer (3) and communicates between the chamber (5) and the pump. In use, dialysate is moved by the pump (7) through the cleansing means (4). Deleterious material species targeted for sequestration or destruction from the wound exudate into the dialysate, where the antagonist in the dialysate fluid phase removes deleterious materials from the wound exudate, without diffusing out into the exudate. InFIG.14, a reversing system is shown (wound exudate passes through the cleansing means at least once in opposing directions) that is similar in structure to the apparatus shown inFIGS.1and3. The microbe-impermeable polyurethane film backing layer (3), formed by solution casting or extrusion, bears a centrally attached proximally projecting boss (11) with a luer for connection to a mating end of a fluid supply and offtake tube (19), which communicates between the interior of the boss (11) and a syringe barrel (20), which is part of a syringe moving device (7). A lower porous film (12) and an intermediate porous membrane (13), both made of permeable polyurethane membrane with small apertures or pores, define a cleansing chamber (15), which contains a solid particulate (not shown). This is for sequestering deleterious materials from, but initially separated from, the wound exudate. These integers, with a coextensive impermeable upper sheet (24) with an upper aperture adapted to register with the conduit in the boss (11), form an upper chamber (25), and all together form the cleansing means (4). This is mounted on the lower face of the boss (11) with the upper aperture in register with the conduit in the boss (11). In use, movement of the syringe plunger (22) sucks and forces wound exudate to and fro through the cleansing means (4). The apparatus (1) inFIG.15is a circulating system (wound exudate passes through the cleansing means one or more times in only one direction). It is a variant of the apparatus (1) ofFIGS.8and9. The microbe-impermeable polyurethane film backing layer (3), formed by solution casting, bears a centrally mounted proximally projecting boss (11) with a uniform cylindrical-bore conduit through it and a luer for connection to a mating end of a fluid supply tube (20), which communicates between the interior of the boss (11) and the outlet of moving device (7). The moving device (7) is a battery-driven miniature portable diaphragm or peristaltic pump, mounted centrally on the backing layer (3) and is releasably attached to the backing layer (3). A second proximally projecting boss (82) with a luer for connection to a mating end of a fluid offtake tube (83) is mounted peripherally on the backing layer (3). The fluid offtake tube (83) communicates between the wound space and the inlet of the pump (7). A lower porous film (12) and an intermediate porous membrane (13), both made of permeable polyurethane membrane with small apertures or pores, define a cleansing chamber (15), which contains a solid particulate (not shown) for sequestering deleterious materials from, but initially separated from, the wound exudate. These integers, with a coextensive impermeable upper sheet (24) with an upper aperture adapted to register with the conduit in the boss (11), form an upper chamber (25), and all together form the cleansing means (4). This is mounted on the lower face of the boss (11) with the upper aperture in register with the conduit in the boss (11). In use, wound exudate is moved by the pump (7) through the cleansing means (4), and the particulate (not shown) sequesters deleterious materials from the wound exudate The use of the apparatus of the present invention will now be described by way of example only in the following Examples: Example 1 Cleansing Fe(II) from Aqueous Solution with the Apparatus of FIG.1: Single-Phase Hand-Syringe Pumped Dressing Containing Solid Sequestrant (Cadexomer-desferrioxamine) A hand-syringe pumped dressing as shown inFIG.14was made up. The cleansing chamber (15) contains a solid particulate (not shown) desferrioxamine supported on Cadexomer (50 mg) to sequester and remove deleterious Fe(II) ions from surrogate exudate. The porous film (12) and a permeable membrane (13), both made of Porvair permeable membrane, are chosen to allow perfusion and flow under syringe pumping through the cleanser but to contain the solid reagent. In triplicate, the dressing as shown inFIG.1was applied to a 9.60 ml capacity circular wound cavity (cast in Perspex) containing an aqueous solution of ferrous chloride tetrahydrate (Aldrich) (9.60 ml, 200 μmolar). The solution was repeatedly completely withdrawn and completely reinjected using the device syringe. At each withdrawal, a 100 microlitre aliquot of solution was assayed using a ferrozine assay as follows: each 100 ul aliquot was added immediately to a 1.5 ml capacity, 1 cm path-length UV cuvette containing 1 ml Ferrozine stock solution (73.93 mg Ferrozine was made up to 250 ml in distilled water (600 uM)). Absorbance (562 nm) readings were taken after at least 5 min. incubation. The absorbance was measured using UNICAM UV4-100 UV-Vis spectrophotometer V3.32 (serial no. 022405). Six passes were made in total, at four minute intervals. The same method was repeated in the absence of flow (i.e. without syringe pumping through the cleanser) and sampled at equivalent time points. Results and Conclusions The resulting iron concentration profiles were averaged and the standard deviations were determined. The Fe(II) concentration is effectively depleted to background level in 3 full cycles (12 minutes). In the control, insignificant concentration change has occurred in the same time period. The dressing as shown inFIG.1effectively sequesters Fe(II) from aqueous solution such as water, saline or wound exudate. Example 2 Neutralising the pH of an Acidic Solution with the Apparatus of FIG.15: Single-Phase Recirculatirg Pumped Dressings: Containing Solid Acid Scavenuer, ScavengePore® Phenethyl Morpholine A recirculating pumped dressing as shown inFIG.15was made up. The cleansing chamber (15) contains a solid particulate (not shown) of ScavengePore® phenethyl morpholine (Aldrich) (50 mg), which is a low-swelling macroporous highly crosslinked polystyrene/divinylbenzene ion-exchanger resin matrix, with 200-400 micron particle size, to scavenge and remove protons, which are acidic species which adversely affect the pH in the wound exudate, from surrogate exudate. The porous film (12) and a permeable membrane (13), both made of Porvair permeable membrane, are chosen to allow perfusion and flow under pumping through the cleanser but to contain the ion-exchange reagent. In triplicate, 4.80 ml DMEM was In triplicate, Device 2 was applied to a 9.60 ml capacity circular wound cavity (cast in Perspex) containing Dulbecco's Modified Eagles Medium (DMEM) (Sigma) (4.80 ml, pH adjusted to pH 6.6 using hydrochloric acid (0.975 N in water, 75 μl). The remaining cavity volume was filled with glass beads. The solution was circulated through the cavity at a flow rate of 2.35 ml min-1. 100 μl samples were taken at 5 min. time points up to 40 min, and pH was recorded using a flat-bed pH meter. The same method was repeated in the absence of flow (i.e. no pump circulation of the solution) and sampled at equivalent time points. Results and Conclusions The resulting pH profiles were averaged and standard deviations determined. The pH was effectively adjusted to pH 7.4 in 40 min. In the control, a slower change in pH was observed in the same time period to pH 7. Example 3 Cleansing Elastase from Aqueous Solution by Diffusion Across a Dialysis Membrane with the Apparatus of FIG.12: Two-Phase Recirculating Pumped Dressing Containing No Reagent A recirculating pumped dressing as shown inFIGS.12Aand B was made up. The cleansing chamber (5) is in the form of tubules made from a polymer membrane that is selectively permeable to a deleterious materials in wound exudate (elastase). These in an array under the backing layer (3) within the wound space between a first boss (71) and a second boss (72) both mounted in the backing layer (3). The tubules contain a dialysate fluid and are in a circuit with a pump (7). In triplicate, the dressing as shown inFIGS.12Aand B was applied to a 9.60 ml capacity circular wound cavity (cast in Perspex) containing elastase solution (porcine pancreatic elastase, Sigma) (4.80 ml, 0.5 mgml-1 in TRIS buffer, pH 8.2, 0.2 M). The remaining cavity volume was filled with glass beads. The inlet and outlet ports were connected to the circulating pump. The dialysate system was prefilled with TRIS (pH 8.0, 0.2 M). This was circulated through the dressing at a flow rate of 2.35 ml min-1. 10 μl samples of the circulating solution were taken at 5 min. time points up to 45 min, and the activity was recorded using a standard N-succinyl-(ala)3-p-nitroanilide colorimetric assay. The same method was repeated in the absence of flow (i.e. no pump circulation of the solution) and sampled at equivalent time points. Results and Conclusions The activity of the samples was determined from their absorbances at 405 nm using a UV/Vis spectrometer. Results were averaged and standard deviations determined. Effective transfer of elastase across the dialysis membrane is seen in 45 min. In the control, no effective transfer was observed in the same time period. Example 4 Cleansing Fe(II) from Aqueous Solution with the Apparatus of FIG.13: Two-phase Recirculating Pumped Dressing Containing Liquid Phase Sequestrant (starch-Desferrioxamine (DFO) Conjugate) An analogue of the apparatus (1) inFIG.13was made up, i.e. with a circulating system (wound exudate passes through the cleansing means one or more times in only one direction) with a two-phase means for wound exudate cleansing in which the cleansing phase moves. The apparatus (1) comprises a cleansing means (4), which comprises a chamber (5) which is made from a polymer membrane and contains a dialysate fluid, which contains a material as a solute or disperse phase species that is for sequestering or degrading deleterious materials from the wound exudate. The membrane is chosen to be selectively permeable to allow perfusion of deleterious material species targeted for sequestration or destruction from the wound exudate into the dialysate, but not to allow any significant amounts of antagonist in the dialysate fluid phase to diffuse freely out of the dialysate into the wound fluid. The analogue is a circuit containing a 0.5-1.0 ml capacity Slide-A-Lyzer dialysis unit, with an upper chamber and a lower chamber in which wound exudate and cleansing fluid, respectively are separated from each other by a polymer membrane chosen to have the properties noted above (MWCO 10000). The lower chamber, through which cleansing fluid passes, has diagonally opposed inlet and outlet ports, which are opened with needles, connected to a circuit of 5 ml capacity containing a dialysate reservoir and a battery-driven miniature portable diaphragm or peristaltic pump. The circuit contains an aqueous high molecular weight starch—DFO conjugate (5 ml, 4 mg/ml). An aliquot of ferrous chloride tetrahydrate (Aldrich) solution (0.5 ml 3 mM) was placed in the upper cavity of the slide and dialysed with 3.6 ml/min. flow in the circuit and (as a control) in the absence of flow in the circuit. 10 microlitre aliquots were removed for 30 minutes at 5 minutes intervals (including t=0). The 10 microlitre aliquot of solution was assayed using the ferrozine iron(II) determination assay as described in Example 1 above. These experiments were performed in triplicate. Results and Conclusions The resulting iron concentration profiles were averaged and standard deviations determined. The Fe(II) concentration was effectively depleted to approximately 50% of the initial level in 30 minutes. Without circuit flow, Fe(II) concentration was depleted to approximately 75% of the starting value in the same time period. The apparatus effectively sequesters Fe(II) from aqueous solution. | 27,117 |
11857747 | DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT While this invention is susceptible of embodiments in many different forms, there are shown in the drawings and will herein be described in detail preferred embodiments of the invention with the understanding that the present disclosure is to be considered as an exemplification of the principles of the invention and is not intended to limit the broad aspect of the invention to the embodiments illustrated. The present invention discloses a dispenser actuator assembly that can be used in conjunction with a dispenser to activate the dispenser and dispense flowable material from the dispenser. The dispenser actuator assembly may also be referred to as an ampoule actuator assembly or a dispenser holder or ampoule holder. The dispenser can take various forms and in one particular application, the dispenser may take the form of a glass ampoule assembly. The dispenser in the form of the glass ampoule assembly will be described followed by describing the dispenser actuator assembly including the connection of the components and actuating the dispenser. FIGS.1-4disclose a dispenser used in accordance with an exemplary embodiment of the invention and generally designated with the reference numeral10. The dispenser10generally includes a first container12, a second container14, or outer container14, and an applicator assembly16. A cover member18or cap member18may optionally be utilized as explained in greater detail below. In this configuration, the dispenser10may also be referred to as a glass ampoule assembly10. The glass ampoule assembly10generally has an elongated longitudinal axis. It is understood that the dispenser10or glass ampoule assembly10may take different forms as well such as other devices having rupturable containers. FIGS.1-4further the first container12. The first container12is generally structured to contain the flowable material M to be dispensed from the dispenser10. The flowable material M is typically a liquid in an exemplary embodiment. It is understood, however, that flowable materials in other forms could be used such as gels or powders etc. The first container12defines a chamber20therein that contains the flowable material M. The first container12has a first end22that is closed and also has a second end24that is closed as well as an intermediate section26therebetween. The intermediate section26of the first container12is generally cylindrical in shape and has a generally circular cross-section. The first end22is generally dome-shaped and the second end24is generally dome-shaped. Other configurations are also possible. As further shown inFIGS.1-4, a first interface area28is defined at or proximate the juncture between the first dome-shaped end22and an end of the intermediate section26. Similarly, a second interface area30is defined at or proximate the juncture between the second dome-shaped end24and the other end of the intermediate section26. Thus, the first interface area28is at the location of the first container12that transitions from an end of the intermediate section26to the dome shape of the first end22. Similarly, the second interface area30is at the location of the first container12that transitions from an end of the intermediate section26to the dome shape of the second end24. The first container12may be dimensioned to have a diameter and length to define the first chamber20in a size to contain a desired amount of the flowable material M. The first container12is designed to be fracturable, frangible, rupturable or crushable as described in greater detail below. In an exemplary embodiment, the first container12is made from a rigid frangible or crushable material such as glass. The first container12may be a traditional glass ampoule. Glass ampoules are known in the art and provide a hermetically-sealed chamber for containing the flowable material M. In one exemplary embodiment, a single glass ampoule12is used. It is understood that the dispenser10could be configured to use multiple glass ampoules12as described in greater detail below. FIGS.1-4further show the second container14, or outer container14, which can be in the form of an applicator body. The second container14has an open first end36and a closed second end38, and an outer wall40therebetween. The outer wall40of the second container14defines a second chamber42. The second chamber42is cooperatively dimensioned and configured to receive at least a portion of the first container12, and typically the entire first container12is received in the second container14. Thus, in an exemplary embodiment, the second container14is generally cylindrical and receives the first container12in a generally snug-fit configuration. The second container14is made from a flexible resilient material such as plastic in an exemplary embodiment. The second container14may be transparent or translucent plastic wherein the flowable material M in the first container12can be visible through the second container14and also through the first container12. The second container14may also be made from opaque material when the flowable material M or other contents are light sensitive. FIGS.1-4also show the applicator16or applicator assembly16. The applicator assembly16assists in dispensing the flowable material M from the dispenser10to a receiving surface. Any applicator assembly16that performs this function can be used in the dispenser10. Thus, the applicator assembly16can take various forms including a swab assembly, a dropper assembly, a roller ball or a brush assembly. The applicator assembly16can further be a sponge, foam applicator, fabric, gauze, pen-type applicator or flocked tip. The swab applicator may also take various forms such as being made from absorbent, porous material, and that relies on a wicking action to dispense the flowable material M. It is also understood that the applicator assembly16may have a filter member44operably associated therewith. The filter member44is structured to allow passage of the flowable material M through the filter member44while preventing passage of glass shards from the fractionated glass ampoule12. The filter member44may be positioned between the first end22of the first container12and the applicator assembly16. Further, the filter member44may be positioned between the glass ampoule12and a tip of the applicator assembly16. In the exemplary embodiment of the applicator assembly16ofFIGS.1-4, the applicator assembly16has a hub46or base member46having a first end48and a second end50. It is understood that the base member46has an internal conduit that is in fluid communication with the second container14for the flowable material M to pass through the conduit and onto a receiving surface. The first end48is dimensioned to fit into the open first end of the second container36. The second end has a post52that receives a tip54. The tip54can be made from the various materials as described above wherein the flowable material M can be dispensed from the tip54and onto a receiving surface. In one exemplary embodiment, the tip54could be a flocked tip for enhanced dispensing of the flowable material M. In another exemplary embodiment, the applicator assembly16could be in the form of a swab assembly. The swab assembly can be made from material that promotes dispensing of the flowable material M through the swab assembly and onto a receiving surface. The applicator assembly16can also include other types of tips capable of applying flowable material onto a receiving surface. In another exemplary embodiment, the applicator assembly16can be in the form of a dropper assembly. The applicator assembly16has a base having a protrusion extending therefrom at one end. The base has a dropper tip member extending from an opposite end. The applicator assembly16has a central conduit extending therethrough from a distal end of the protrusion to a distal end of the dropper tip member. The protrusion has a generally annular configuration and is dimensioned to be received by the open first end36of the second container14. In an exemplary embodiment, the protrusion and the open first end36of the second container14are cooperatively dimensioned wherein the protrusion is received in the open first end36in an interference fit. As further described below, the applicator assembly16is configured to receive the flowable material M from the fractionated or crushed first container12and to dispense the flowable material M onto a receiving surface. To fabricate the dispenser10, the first chamber20of the first container12is filled with a desired flowable material M. The open end of the first container12through which the flowable material passed to fill the first container12is sealed as is known in glass ampoule technology. A sealed glass ampoule12having the flowable material M therein is thereby provided. The filled first container12is then inserted through the open first end36and into the second chamber42of the second container14. Preferably, the first container12is positioned in its entirety within the second chamber42of the second container14. The filter member44, if utilized, is inserted into the open first end36of the second container14and adjacent the first end of the first container12. Once the first container12is positioned in the second container14as well as the filter member44, the applicator assembly16is connected to the second container14. Thus, the filter member44is positioned between the glass ampoule12and the applicator assembly16. As can be appreciated fromFIGS.1-4, the first end48of the applicator assembly16is inserted into the open first end36of the second container14. This connection may be in an interference fit, snap-fit or connected with adhesives as well. The tip54is secured to the post52. The cover member18is designed to initially cover the applicator assembly16prior to activating the dispenser10. The cover member18is dimensioned to fit snugly over the applicator assembly16, cover the tip54and extend over a portion of the dispenser10. A distal end of the cover member18is a closed end. When preparing to activate the dispenser10, the cover member18is removed from the dispenser10. With the present invention as described in further detail below, the cover member18is not used during activation of the dispenser10. It is also understood that the dispenser10can incorporate an identifying label. It is understood that the dispenser10utilizes the cover member18in a single-use type container as described above and shown inFIGS.1-4. The dispenser10may also eliminate the cover member18and be packaged in other outer packaging such as blister packaging. FIGS.5-8disclose another exemplary embodiment of a glass ampoule assembly. The assembly has generally similar structures as the glass ampoule assembly10ofFIGS.1-4and like structures will be designated with identical reference numerals. As shown inFIGS.5-8, the glass ampoule assembly10generally includes a first container12, a second container14, or outer container14, and an applicator assembly16. The elements are structured and connected as with the glass ampoule assembly ofFIGS.1-4. An alternative form of the cap member18is utilized in the embodiment ofFIGS.5-8. If desired, the dispenser10may also utilize the cover member18in the form of a cardboard sleeve, as is known the art. The cover member is designed to initially cover the applicator assembly16prior to activating the dispenser10. The cover member18is dimensioned to fit snugly over the applicator assembly16and extend over a portion of the dispenser10. One end of the cover member18may be closed although it is understood that both ends of the cover member18could be open ends. When preparing to activate the dispenser10, the cover member18is removed from the dispenser10. In certain prior art applications, an end of the dispenser10opposite of the applicator assembly16is inserted into the cover member18. With the present invention as described in further detail below, the cover member18is not used during activation of the dispenser10. As discussed, the cover member18is a cardboard or paper-based material in an exemplary embodiment. It is also understood that the dispenser10can incorporate an identifying label. As shown inFIGS.9-18, the present invention utilizes a dispenser actuator assembly generally designated with the reference numeral100. The dispenser actuator assembly100may also be referred to as an ampoule actuator assembly100or dispenser/ampoule holder100. As explained in greater detail below, the dispenser actuator assembly100cooperates with the dispenser10to actuate the dispenser10. The structure of the dispenser actuator assembly100will first be described followed by a description of the cooperation and operation of the dispenser actuator assembly100with the dispenser10. As further shown inFIGS.9-18, the dispenser actuator assembly100generally includes a base member102and an actuator assembly104. The actuator assembly104is operably connected to the base member102as further described below. FIGS.9-16show the base member102of the dispenser actuator assembly100. The base member102is generally a rounded member that fits around at least a portion of the glass ampoule assembly10. The base member102is further an annular member that in one exemplary embodiment is dimensioned to fit over the dispenser or glass ampoule assembly10as described in greater detail below. The base member102generally includes an annular ring member106and a connector member108. The annular ring member106is a full ring member in an exemplary embodiment that defines an opening110therethrough to receive the dispenser as explained in greater detail below. Thus, in an exemplary embodiment, the annular ring member106is dimensioned to fit circumjacently around the glass ampoule assembly and, in particular, the second container14. It is understood that in other exemplary embodiments, the ring member106may not be a full ring member and have an interruption, slot or break in the member. The annular ring member106has an inner surface112that defines the opening110. The inner surface112has a plurality of ribs114extending radially inwardly into the opening110. In an exemplary embodiment, the ribs114extend axially or longitudinally along the inner surface112of the annular ring member106. Furthermore, four ribs114are utilized and are spaced circumferentially on the inner surface112at 12 o'clock, 3 o'clock, 6 o'clock and 9 o'clock positions. It is further understood that a single rib114could be employed or other numbers of ribs114, and further at other annular locations. The ribs114could also take the form of ribs extending circumferentially along the inner surface112of the annular ring member106. The ribs114assist in providing an interference fit with the second container14of the glass ampoule assembly10when the base member102is mounted on the second container14. The annular ring member106further has a flange116extending circumferentially around the ring member106at a proximate end of the ring member106. The flange116assists in adding rigidity and strength to the proximal end of the base member102. The added rigidity and strength provided by the flange116also helps when ejector pins push the base member102off of the mold member during the injection molding process. FIGS.9-16further show the connector member108of the base member102. The connector member108generally connects to the actuator assembly104. The connector member108extends from a proximate end of the annular ring member106towards the actuator assembly104. The connector member108has a first slot118or upper slot118defined therein as well as a second slot120or lower slot120defined therein. As a result, the connector member108has a first segment122and a second segment124defined between the first slot118and the second slot120. The first segment122is positioned generally opposite to the second segment124. The first slot118and the second slot120extend partially circumferentially having respective ends that confront in spaced relation to define the first segment122and the second segment124. The first slot118and the second slot120are generally opposite to one another. As explained in greater detail below, the slots118,120assist in the flexing of the actuator assembly104, or pivoting movement of the actuator assembly104. The first segment122has a first end connected to the base member102and a second end connected to the actuator assembly104, or a flex plate of the actuator assembly to be described. The second segment124has a first end connected to the base member102and a second end connected to the actuator assembly104, or a flex plate of the actuator assembly to be described. The second segment124has a second raised tab126positioned on a central portion of the first segment122and that extends from the flange116towards the actuator assembly104(or to a flex plate as described in greater detail below). Similarly, the second segment124has a second raised tab128positioned on a central portion of the second segment122and that extends from the flange116to the actuator assembly104. The raised tabs126,128assist in providing rigidity for an enhanced connection between the base member102and the actuator assembly104. The rigidity provided by the raised tabs126,128further help when ejector pins engage the base member102proximate the raised tabs126,128to smoothly remove the assembly100from a mold member after formation in an injection molding process. As shown inFIGS.9-16, the base member102is formed as a full annular ring member in one exemplary embodiment. The base member102is designed to receive or hold the dispenser10or glass ampoule assembly10, and it is understood that the base member102may not have a full ring-shaped configuration. For example, the base member102can have certain segments eliminated and not utilized while still having a configuration to receive or hold the glass ampoule assembly10. The base member102could have a slot formed therein to define separate segments that may be resiliently flexible. The base member102further defines the annular ring member106that defines the opening110for the glass ampoule assembly10. The inner surface112of the base member102is tapered such that the entry of the base member is slightly larger at one end. In a particular exemplary embodiment, the base member102tapers to a larger dimension towards the actuator assembly104. This provides for easier insertion of the glass ampoule assembly at that end. In one exemplary embodiment, there is a 2-degree taper of the inner surface112. In other exemplary embodiments, the taper could be 1-3 degrees. It is further understood that the taper can be in an opposite direction as well. The outer container14of the glass ampoule assembly10may have a rounded end that also assists insertion/mounting between the dispenser actuator assembly100and the glass ampoule assembly10. FIGS.9-16further show the actuator assembly104of the dispenser actuator assembly100. In one exemplary embodiment, the actuator assembly104generally includes a first actuator arm132aand a second actuator arm132b. As explained in greater detail below, the first actuator arm132aand the second actuator arm132bare connected to the base member102via the connector member108and, in particular, the first segment122and the second segment124of the connector member108. It is understood that the first actuator arm132aand the second actuator arm132bare similar in structure and positioned generally symmetrically as described in greater detail below. The first actuator arm132aand the second actuator arm132bextend from the base102(or flex plate to be described) in generally opposed relation. It is also understood that description regarding the first actuator arm132awill generally apply to the second actuator arm132b. The structures of the first actuator arm132aare referenced with an “a” designation while the structures of the second actuator arm132bare referenced with a “b” designation. FIGS.9-16further show the first actuator arm132a. The first actuator arm132ahas a proximal end134a, a distal end136aand an intermediate segment138a. The proximal end134ais angled to be generally parallel to the flange116. The proximal end134ais connected to the first segment122of the connector member108and the second segment124of the connector member108. As shown further inFIGS.9and10, the intermediate segment138adefines a floor segment140aand an outer peripheral flange142a. The floor segment140ais recessed with respect to the outer peripheral flange142a. The intermediate segment138ahas a plurality of apertures144aextending into the first actuator arm132aproximate the proximal end134a. In an exemplary embodiment, the apertures144ado not extend entirely through the arm132a. The apertures144aassist in removing certain material in the formation of the assembly100to avoid having large block of material associated with the assembly100which is generally undesirable in an injection molding process used to form the assembly100. The apertures144afurther define additional walls to add further rigidity and strength to the assembly100. The floor segment140afurther has a finger pad146ain the form of a plurality of raised ridges148a. The recessed features of the floor and ridges with respect the flange provide for a tactile feel for the user for more proper finger/digit placement, as well as helping to maintain engagement of the fingers/digits with the actuator arms132a,132b. It is understood that the structures of the first actuator arm132aapply to the second actuator arm132bwith the “b” designations. As shown inFIGS.9-22, the first actuator arm132afurther has a depending protrusion150apositioned on an underside of the first actuator arm132a. The depending protrusion150ahas a first segment152aand a second segment154a. The first segment152adefines a platform156aproximate to the proximal end of the first actuator arm132a. The second segment154aextends from the first segment152aat an interface edge158a. The interface edge158amay be considered as defining a lined projection to be described in greater detail below. The lined projection is useful in providing a concentrated force against the glass ampoule assembly10as described in greater detail below. The second segment154ahas a plurality of channels160adefined therein wherein the second segment154adefines a plurality of spaced walls162a. In an exemplary embodiment, the second segment154ahas a pair of channels160athat define three spaced walls162a. The walls162aadd stiffness to the actuator arm132a. The second segment154and the walls162aare dimensioned such that they follow the extension of the first actuator arm132a. The second segment154ainclines upward towards the distal end136aof the arm132a, thus the second segment154adefines an inclined surface. As explained in greater detail below, this configuration allows the second segment154to be generally parallel to a longitudinal axis of the glass ampoule assembly10when a user manipulates material from the assembly10by further squeezing the actuator arm132a. With the walls162adepending from an underside surface of the floor segment140aof the actuator arm132a, the actuator arm132ais designed similar to an I-beam wherein the structure provides strength, rigidity and stiffness to the actuator arm132a. The walls162depend from an underside surface of the actuator arm132a. The top of the actuator arm132aremote from the proximal end remains a solid structure without openings to provide tactile feel while the spaced walls162aprovide strength etc. to the actuator arm132a. As shown inFIG.15, a boss164ais defined at a distal end of the second segment154aof the depending protrusion152a. In an exemplary embodiment, a boss164ais defined at the distal end of each spaced wall162a. The boss164ais configured to be engaged by ejector pins in ejecting the molded part from a mold during an injection molding process used to form the dispenser actuator assembly100as described in greater detail below. As further shown inFIGS.15and16, an indentation166a, or indentation slot166ais defined in the actuator arms132aadjacent the bosses164a. The indentation166ais generally defined between an underside surface of the actuator arm132aand the boss164a. As described in greater detail below, during the injection molding process used to form the assembly100, fingers defined in the mold part extend into the mold cavity to define the indentations166a. The fingers will maintain the actuator arms132a,132bagainst an internal mold part until ejector pins can engage the bosses164a. This minimizes the chance for the actuator arms132a,132bto prematurely come off of the internal mold piece which could affect later operation of the assembly. The shape of the second segment154aallows the second segment154ato manipulate the glass ampoule assembly10to provide an enhanced pumping action to expel more fully the flowable material M from the glass ampoule assembly. As discussed, the above description of the structure of the first actuator arm132ais applicable for the structure of the second actuator arm132band having “b” designations. The dispenser actuator assembly100is used with a dispenser10such as the glass ampoule assembly10to crush the glass ampoule assembly10and dispense flowable material from the glass ampoule assembly10. As can be appreciated fromFIG.8, the glass ampoule assembly10is prepared such as by removing a cardboard sleeve if the sleeve is being used or removing the glass ampoule assembly10from any blister packaging. Alternatively, the glass ampoule assembly10may use the cover member18which is removed in preparation for dispensing flowable material from the glass ampoule assembly10. As can be appreciated fromFIGS.29-34, the glass ampoule assembly10is inserted into the base member102. The opening110defined by the base member102receives the glass ampoule assembly10wherein the base member102slides onto the second container14. Thus, the actuator assembly100is slidably movable along the second container14. In one exemplary embodiment, the base member102slides onto the second container14in a frictional interference fit. The ribs114assist in engaging the outer surface of the outer container14of the glass ampoule assembly10to achieve a snug interference fit. In one exemplary embodiment, the glass ampoule assembly10is inserted into a distal end of the base member102opposite the flange116. Even if the taper is such that the distal end of the base member102is more narrow, the outer container14of the glass ampoule assembly10has a rounded edge that assists in smooth insertion/mounting. It is also understood that the dispenser actuator assembly10could also be slid over the glass ampoule assembly10at the proximal end of the base member102. Regardless of the insertion, the actuator arms132a,132bextend away from the applicator16of the ampoule assembly10. As further shown inFIGS.29-30, when the dispenser actuator assembly100is properly located on the glass ampoule assembly, the first depending protrusion150aand the second depending protrusion150bare positioned proximate the first interface area28of the glass ampoule12. In particular, the interface edge158aof the first depending protrusion150aand the interface edge158bof the second depending protrusion150bare positioned at the first interface area of the first container12of the glass ampoule assembly10. In addition, the first actuator arm132aand the second actuator arm132bextend towards the closed end38of the second container14of the glass ampoule assembly10. It is understood that the one of the dispenser actuator assembly100and the glass ampoule assembly10could have a locating structure thereon to properly position the dispenser actuator assembly100on the glass ampoule assembly10so that the actuator arms132a,132bare properly positioned to crush the glass ampoule12. The location structure can also take the form of a cooperative structure on one of or both of the dispenser actuator assembly100and the glass ampoule assembly10. For example, the second container14of the glass ampoule assembly10could have an annular, radially-inwardly formed indentation that the base member102is received therein to automatically locate the dispenser actuator assembly100on the proper location on the glass ampoule assembly10. Similarly, an outwardly extending protrusion could be located on the second container wherein the base member102slides over the protrusion until the actuator assembly100fits adjacent the protrusion to be properly located. Multiple protrusions could also be used such as outwardly extending spaced protrusions wherein the actuator assembly100fits within spaced protrusions to be properly located. FIGS.29and30show the dispenser actuator assembly100positioned on and operably connected to the glass ampoule assembly10. The glass ampoule assembly10is now ready to be actuated. The first container12, or glass ampoule12, is in a position to be crushed wherein the flowable material M can be dispensed from the assembly10. As further shown inFIG.29, the first depending protrusion150aof the first actuator arm132aand the second depending protrusion150bof the second actuator arm132bare spaced from the second container14and positioned over and proximate the first interface area28. Thus, a gap or space is initially maintained between the protrusions130a,130band the second container14. In such position as shown inFIG.29, the actuator arms132a,132bare in a first position, or first neutral position NP. As can be further appreciated fromFIGS.29-30, a user holds the dispenser actuator assembly100wherein a forefinger wraps around an underside of the base member102and engages the second actuator arm132b. A thumb of the user engages the first actuator arm132a. In particular, a user's forefinger and thumb engage the respective finger pads146a,146bof the first actuator arm132aand the second actuator arm132b. The user squeezes the actuator assembly100thereby applying a compressive force F (FIG.30) to the first actuator arm132aand the second actuator arm132b. Thus, the actuator arms132a,132bare pivotable about the base102from the first neutral position to a second position or an actuating position AP. In response to this compressive force, the depending protrusion150aof the first actuator arm132ais deflected towards and engages the second container14and the depending protrusion150bof the second actuator arm132bis deflected towards and engages the second container14. As the user continues to depress the first actuator arm132aand the second actuator arm132b, the depending protrusion150aof the first actuator arm132adeflects the second container14wherein the second container14engages the glass ampoule12at proximate a top or upper portion of the first interface area28, and the depending protrusion150bof the second actuator arm132bdeflects the second container14wherein the second container14engages the glass ampoule12at proximate a bottom or lower portion of the first interface area28(e.g. opposite ends of the first interface area28), wherein the glass ampoule12is crushed at the first interface area28. In particular, it is understood that the first interface area28is engaged by the protrusion interface edge158a,158b(ridge) of the protrusions150a,150bof the actuator arms132a,132b. The protrusion interface edges158a,158bassist in concentrating the force F onto the outer container14and glass ampoule12. It is further understood that the first slot118or upper slot118and the second slot120or lower slot120assist on providing sufficient flexibility for the actuator arms132a,132b. As the slots118,120separate the actuator arms132a,132bfrom the base member102, the actuator arms132a,132bcan pivot independently from the base member102. This allows the base member102to continue to provide support for holding the glass ampoule assembly10independently of the pivoting of the actuator arms132a,132b. It is further understood that the actuator arms132a,132bthemselves do not generally bend or flex as the arms132a,132bare more rigid, but the arms132a,132bflex or pivot. Upon crushing or rupture, the flowable material M passes from the glass ampoule12and into the applicator16. Because force F is applied to the glass ampoule12at the first interface area28, the domed portion of the glass ampoule12breaks into multiple pieces allowing enhanced flow of the flowable material M out of the glass ampoule12and into the second container14and to the applicator assembly16. It has been determined by the inventors that if the glass ampoule12is crushed at the interface area28, the domed-section will break into multiple pieces rather than remaining intact while breaking away from the intermediate section of the glass ampoule12. The flowable material M passes from the second container14and into the applicator assembly16.FIGS.31and32disclose partial views of the actuation of the glass ampoule assembly10wherein the depending protrusions150a,150bof the first and second actuator arms132a,132bengage the second container14of the glass ampoule assembly10. As further can be appreciated fromFIGS.30and33, the user can continue to squeeze the actuator assembly100wherein the user engages the first actuator arm132aand the second actuator arm132bthereby continuing to apply the compressive force F wherein the depending protrusions150a,150bare further deflected towards and engage the second container14. As the user continues to depress first and second actuator arms132a,132b, the respective second segments154a,154bof the protrusions150a,150bdeflect the second container14wherein the second container14engages the glass ampoule12further along the glass ampoule12. In this configuration such as shown inFIG.33, the respective segments154a,154bare generally positioned parallel to one another. In certain embodiments, the glass ampoule12may be sized such that the respective second segments154a,154bcan be positioned at proximate the second interface area30wherein the glass ampoule12further ruptures. Upon this additional rupture, the flowable material M more easily passes from the glass ampoule12and into the second container14and into the applicator16. Because force F is applied to the glass ampoule12at the second interface area30, the domed portion of the glass ampoule12breaks into multiple pieces allowing enhanced flow of the flowable material M out of the glass ampoule12and into the second container14and to the applicator assembly16. It is further understood that the user can use the actuator arms132a,132band second segments154a,154bto further deflect and manipulate the second container14and force the flowable material M through the applicator assembly16and, therefore, to enhance dispensing of the flowable material M from the glass ampoule assembly10. It is understood that the applicator assembly16assists in minimizing the chance of glass shards from the ruptured glass ampoule12from passing out of the glass ampoule assembly10. In addition, the outer wall of the second container14prevents glass shards from cutting fingers of the user thereby protecting the user's fingers from injury by the fractionated glass shards of the glass ampoule12that remain in the second container14. Because a user engages the actuator assembly100to crush the glass ampoule assembly10rather than engaging the glass ampoule assembly10directly, the chance of cutting a user's fingers/thumb from glass shards is further minimized. It is understood that additional structures could be incorporated into the glass ampoule assembly10such as filter assemblies44to minimize the chance of glass shards from passing through the applicator assembly. As shown inFIG.34, the flowable material M can be dispensed from the glass ampoule assembly10and onto a receiving surface. The receiving surface S can vary depending the particular type of flowable material M being dispensed. In one exemplary embodiment, the flowable material M may be a medicine that is dispensed onto a skin surface S of a patient. As further appreciated from the figures, the user dispenses the flowable material M from the glass ampoule assembly10with the aid of the dispenser actuator assembly10. Once the flowable material M is emptied from the glass ampoule assembly10, the dispenser actuator assembly100can be removed from the glass ampoule assembly10. In this fashion, the dispenser actuator assembly10can be reused with multiple dispenser assemblies10or glass ampoule assemblies10. In this configuration, the dispenser actuator assembly100can be formed from a more robust and higher-cost material. In other configurations, the material used to form the dispenser actuator assembly100could be a lower cost material that is designed as a one-time use wherein the dispenser actuator assembly100is disposable. In such case, the location structured used to position the dispenser actuator assembly100on the glass ampoule assembly10could be structured to permanently attach the dispenser actuator assembly100to the glass ampoule assembly10. Once the flowable material M is fully dispensed from the glass ampoule assembly, the attached structures can be simply discarded together. It is understood that the dispenser actuator assembly100can be formed in an injection molding process to form a unitary one-piece member. A wide variety of materials can be used to form the dispenser actuator assembly100wherein the actuator arms132a,132bare resiliently pivotable to actuate the glass ampoule assembly and then be reused on additional glass ampoule assemblies. As discussed, it is understood that in an exemplary embodiment, the actuator arms132a,132bare generally rigid and do not bend or flex themselves, but rather pivot about the connector members or in relation to the base member102. Similarly, the depending protrusions150a,150bare rigid and do flex themselves. In an exemplary embodiment, the dispenser actuator assembly is made from one of the polyolefin family of resins. As discussed herein, the dispenser actuator assembly100has been described herein as having a base member102and an actuator assembly104having a first actuator arm132aand a second actuator arm132b. A connector member108has been described that connects the base member102and the actuator assembly104. It is understood that the actuator arms132a,132bpivot towards one another, and pivot with respect to the base member102and connector member108. It is understood that the assembly100could also be considered that the first actuator arm132aand the second actuator arm132bare connected by a central hub member180or flex plate180, or torsion plate180. In particular, a proximal end134aof the first actuator arm132ais connected to a top portion or first end of the flex plate180, and a proximal end134bof the second actuator arm132bis connected to a bottom portion or second end of the flex plate180. The first end of the flex plate180is generally opposite to the second end of the flex plate180. In one exemplary embodiment, the flex plate180is then considered to be part of the actuator assembly104. The flex plate180is generally connected between the actuator arms132a,132band, as discussed, the first end, or upper end of the flex plate180is connected to the proximal end134aof the first actuator arm132a, and an opposite second end, or lower end of the flex plate180is connected to the proximal end134bof the second actuator arm132b. In this configuration, the base member102is still operably connected to the actuator assembly104by the connector member108. The flex plate180serves as a transition structure from the base member102to the actuator arms132a,132b. FIG.18shows the flex plate180in greater detail. The flex plate180has a central portion182and a first side rail184and a second side rail186, generally opposite the first side rail184. The central portion182of the flex plate180has an opening188therethrough. The flex plate opening188is generally aligned with the opening110of the base member102as further described below. The flex plate opening188may be slightly larger than the opening110of the base member102or the same size. Thus, the flex plate opening has a diameter larger than a diameter of the opening of the base member102. The central portion182further has a first flexion segment190or upper flexion section190, and a second flexion segment192or lower flexion segment192as further described below. An upper portion of the first flexion segment190is adjacent the proximal end134aof the first actuator arm132aat a first connection line194, generally at the first end of the flex plate180. A bottom portion of the second flexion segment192is adjacent the proximal end134bof the second actuator arm132bat a second connection line196, generally at the second end of the flex plate180. As further shown inFIG.18, the central portion182of the flex plate180, including the first flexion segment190and the second flexion segment192, have a lesser thickness than the thickness of the first side rail184and the second side rail186. As further shown inFIGS.29and33, it is understood that the first flexion segment190is positioned generally between a midpoint of the vertical length of the flex plate180and the location where the first actuator arm132ais connected to the flex plate180. Similarly, the second flexion segment192is positioned generally between a midpoint of the vertical length of the flex plate180and the location where the second actuator arm132bis connected to the flex plate180. The flex plate180generally flexes or bends at positions between where the connector member108connects to the flex plate (the first segment122and the second segment124) and where the actuator arms132a,132bconnect to the flex plate180. As discussed, the first slot118is defined between the first end of the flex plate180and the base102. The second slot120is defined between the second end of the flex plate180and the base102. As can be further appreciated fromFIG.18, the flex plate180is connected to the first actuator arm132aand the second actuator arm132b. In this exemplary embodiment of the invention, the flex plate180and the first actuator arm132aand the second actuator arm132bdefine the actuator assembly104. The upper portion of the first flexion segment190and upper portions of the first and second side rails184,186are connected to the proximal end134aof the first actuator arm132aat the first connection line194. Similarly, the lower portion of the second flexion segment192and lower portions of the first and second side rails184,186are connected to the proximal end134bof the second actuator arm132b. As further shown inFIG.18, the first segment122of the connector member108is connected to the central portion of the flex plate180and also to the base102. Thus, the first segment122has a first end connected to the base102and a second end connected to the flex plate180. The first raised tab126is connected to the first side rail184and also connected to the flange116of the base102. The second segment124of the connector member108is connected to the central portion of the flex plate180and also to the base102. Thus, the second segment124has a first end connected to the base102and a second end connected to the flex plate180. The second raised tab128is connected to the second side rail186and also to the flange116of the base102. With these connections, the flex plate opening188is generally aligned with the opening110of the base member102. Accordingly, the connector member108operably connects the base member102to the actuator assembly104. As discussed, the segments122,124of the connector member108are connected to the flex plate180. It is further understood that the flex plate180could have location structures thereon to properly position the dispenser actuator assembly100on the glass ampoule assembly10. It can further be appreciated fromFIGS.18and31, for example, that the flex plate180is dimensioned to extend beyond the outer periphery of the base member102. As previously discussed and as shown inFIGS.17and29, the dispenser actuator assembly100is mounted on the glass ampoule assembly10and in a position wherein the protrusions150,152can crush the glass ampoule12. This configuration may be considered the first position or neutral position. In this configuration, the flex plate180is unflexed and is generally in a planar configuration such as shown inFIGS.17and29. Similar to the description above, a user engages the first actuator arm132aand the second actuator arm132band applies a force F wherein the arms132a,132bare forced towards one another. Thus, the arms132a,132bmove from the first neutral position to an actuating position AP. The flex plate180flexes generally at the first flexion segment190and the second flexion segment192. This flexion of the flex plate180is shown inFIGS.30-33. The first flexion segment190and the second flexion segment192provides for flexion over a greater radius, which lessens the stress on the assembly100. If the actuator arms132a,132bpivoted specifically at, for example, the first connection line194and the second connection line196, stresses are more locally focused at a smaller area, which is undesirable as it can promote plastic deformation of the material. The first flexion segment190and the second flexion segment192provide elastic deformation of the flex plate180, which allows the flex plate180to return to its first or neutral position NP. Thus, the flex plate180is resiliently deflectable.FIG.31shows the flexion of the first flexion segment190and the second flexion segment192represented by the angular configuration “A” and which further provides for the majority of the flexing of the flex plate180. Additional arrows A inFIG.31further show the flexion of the flex plate180. It is understood that the actuator arms132a,132bare generally more rigid and do not pivot around the first connection line194and the second connection line196. The flexion is concentrated at the flex plate180as shown. As further shown inFIG.33, a user can continue to press the actuator arms132a,132bto manipulate flowable material from the glass ampoule assembly100wherein the second segments154a,154bof the actuator arms132a,132bare configured to be generally parallel to one another to further deform the outer container14of the glass ampoule assembly10. Furthermore, the walls162a,162bengage the outer container14and further manipulate the glass ampoule12wherein the walls162a,162bare generally parallel to the longitudinal axis of the glass ampoule assembly100. It is further understood that the dispenser actuator assembly10can be slid along the outer container14to reposition the assembly10and further manipulate the outer container14with the second segments154a,154bto expel flowable material M from the assembly10. The base member102utilizing the slots118,120or the flex plate180and slots118,120provides structural and functional advantageous features. As discussed, the actuator arms132a,132bdo not pivot or flex towards one another at a specific point or location. The flex plate180flexes as shown inFIGS.30-33and such flexing occurs over a greater distance, e.g., a more substantial distance associated with the flex plate180. In particular, much of the bending or flexing occurs at the first flexion segment190and the second flexion segment192. This distributes stresses associated with the flexing over a greater distance on the flex plate180as opposed to a flexing configuration at a point such as a living hinge. With flexing and distributed stresses over a greater distance, any breaking point is minimized wherein the material of the assembly100is not pushed past its elastic limits. This allows the actuator arms132a,132bto return to the first or neutral position NP wherein the assembly100can be used with further glass ampoule assemblies10. If the flexing structure was a living hinge structure, force would be focused at a more localized point, which would promote a failure or breaking of the actuator arm132a,132bfrom the base member102. This configuration further provides for substantially rigid actuator arms132a,132bthat have little flexing from the arms132a,132bthemselves. While the material of the actuator arms132a,132bprovide for minimal flexing, the flex plate180flexes to allow the substantially rigid actuator arms132a,132bto pivot or move towards one another, which allows for the depending protrusions150a,150bto provide a more direct, localized force to the glass ampoule assembly10. This configuration also provides for flexing/movement of the actuator arms132a,132bindependently of the support of the outer container14by the base member102. The base member102supports the outer container14of the glass ampoule assembly10as the outer container14is inserted through the base member102. With the slots118,120and the flex plate180, the actuator arms132a,132bpivot via the flexing of the flex plate180, which is independent of the support the base member102provides to the outer container14. In other designs where wings or arms project directly from or an integral connection to a base, the base member can distort or deform in response to the movement of the arms132a,132b. As a result, the support for the ampoule assembly10can be lessened, altered or otherwise adversely affected. With the present design, the support of the glass ampoule assembly10by the base member102is isolated from the actuator arms132a,132band not affected by the movement of the actuator arms132a,132b. Finally, the structural features of the flex plate180and actuator arms132a,132bminimize unwanted lateral movement of the actuator arms132a,132b. The actuator arms132a,132bare connected laterally across the entire lateral dimension of the flex plate180, e.g., the first and second connection lines194,196, which connection generally resists lateral movement of the actuator arms132a,132b. Minimizing any lateral movement of the actuator arms132a,132bis desirable as it can affect the proper crush of the glass ampoule12as the protrusion150a,150bmay slip to the side of the glass ampoule12preventing crushing. As shown inFIG.13, the base member12supports the glass ampoule assembly10across a lateral distance “a” that may generally correspond to a diameter of the glass ampoule assembly10, e.g. a diameter dimension. The actuator arms132a,132bare connected along connection lines194,196across a lateral dimension “b” that is greater than the diameter dimension “a.” Thus, the lateral dimension of the flex plate180extends beyond the diameter of the glass ampoule assembly10. With a greater dimension “b”, the actuator arms132a,132bmove towards the glass ampoule assembly in a generally perpendicular or normal direction to the elongated longitudinal axis L (FIG.33) of the glass ampoule assembly10. These structural and functional features of the dispenser actuator assembly100provide benefits over prior assemblies. As discussed, in an exemplary embodiment, the dispenser actuator assembly100is formed as a single unit in an injection molding process.FIGS.19-28Bdisclose multiple mold members used to injection mold the dispenser actuator assembly100.FIGS.19-23disclose a core mold member200used in making the dispenser actuator assembly100.FIGS.24-25show an upper mold member202and a lower mold member204. The core mold member200, the upper mold member202and the lower mold member204are positioned in adjacent spaced relation to cooperate to define and form a mold cavity206(FIG.24A) to receive the injected molded material. It is understood that additional mold members can be used as well as other structures and mechanisms such as gates known in the art of injection molding. FIGS.19-22show the core mold member200. The core mold member200has a central post208extending from a main body210having inclined surfaces212each having slotted indentations214. The central post208helps form the base member102and the slotted indentations186help form portions of the actuator assembly104. The central post208has channels209therein corresponding to the longitudinal ribs114on the base102. It is understood that the central post208may be designed to be screwed into the main body210or otherwise removably attached to the main body210. In such design, the central post208can comprise multiple types of central posts208each having channels209of different depths. In such case, the longitudinal ribs114can be made of varying sizes to accommodate differently-sized glass ampoule assemblies10. The main body210has certain openings or conduits through the body210used to assist in ejecting the form part at the end of the injection molding process. As shown inFIG.23, the main body210has pair of finger projections216a,216bthat extend toward the central post208. FIGS.24-25further show the upper mold member202and the lower mold member204. The mold members202,204are positioned adjacent and in spaced relation to the core mold member200to define the mold cavity206. It is understood that the mold members200-204cooperate to correspond to surfaces of the dispenser actuator assembly100. For example, the core mold member200and portions of the upper mold member202and the lower mold member204cooperate to define the first and second actuator arms132a,132b. The finger projections216a,216bon the core mold member200extend into the mold cavity206. As discussed, the mold members200,202,204cooperate with a gate that receives a source of injection molded material and delivers the material into the mold cavity206.FIG.24Bschematically shows molded material MM in the process of being injected into the mold cavity206. It is understood that the molded material MM is injected into the entire mold cavity206to form the dispenser actuator assembly100. It is understood that the molded material MM cools and hardens in the mold cavity206wherein the dispenser actuator assembly100is formed. Once formed and properly cooled, the dispenser actuator assembly100can be removed from the mold. It is understood that the dispenser actuator assembly100is formed in the mold cavity including the first actuator arm132aand the second actuator arm132b. As shown inFIG.25, the upper mold member202and the lower mold member204are spaced away from the core mold member200. It is desirable for the actuator arms132a,132bto maintain contact with the core mold member200until the assembly100can be ejected from the core mold member200. With such movement of the mold members202,204, the actuator arms could “stick” to the mold members202,204where the actuator arms132a,132bwill pivot upwards following movement of the mold members202,204. This premature flexing of the actuator arms132a,132bwill have a detrimental effect on operation of the actuator arms in actuating a dispenser10.FIGS.26-27Bshow the dispenser actuator assembly100still on the core mold member200after removal of the upper mold member202and the lower mold member204(The mold members202,204are not shown for clarity.). As previously discussed, the finger projections216a,216bextend into the mold cavity206. The finger projections216a,216bare positioned above the bosses164a,164band, therefore, keep the actuator arms against the core mold member200. The finger projections216a,216bare positioned between the bosses164a,164band the underside surface of the actuator arms132a,132b. As can be appreciated fromFIGS.28A and28B, ejector pins are inserted through passageways in the core mold member200to engage the bosses164a,164band eject the assembly100from the core mold member200. As shown inFIG.28B, the finger projections216a,216bare removed from the respective indentations166a,166bof the assembly100. Once removed, it is understood that the indentation slots166a,166bare revealed. The dispenser actuator assembly100is then properly formed and ready for further processing and use. It is understood that additional features can be incorporated into the molding process. The gates for injecting molded material MM into the mold cavity206can be varied to achieve desired characteristics in the assembly. In a further exemplary embodiment, a multi-shot molding process could be utilized. For example, a two-shot molding process could be utilized wherein the flex plate structure is molded from a more flexible material while other structures of the assembly100such as the base member102and the actuator assembly104are formed from a more rigid material. The dispenser actuator assembly100can be formed in the injection molding process from a variety of different injected molded materials. Selection of the material will depend on the desired operational characteristics of the assembly100such as the amount of rupturing force to be generated. The assembly100could be formed from polyolefin family of resins. The material could be polyethylene or polypropylene and a combination thereof. The material could also be nylon. Because of the structural features described above, it is possible to use more rigid/brittle materials as well as materials having a higher flexural modulus. The material could also be amorphous polymers including acrylic, acrylonitrile butadiene styrene, or polycarbonate. The material for the assembly100could further be a polyvinylidene fluoride (PVDF) material. With the broader selection of materials possible, the assembly100can also be used in a broader range of applications requiring rupturing of different types of containers. The dispenser actuator assembly100could also be made of materials for specialty application such as materials that are capable of being autoclavable. It is understood that the dispenser actuator assembly100can have certain modified structures to enhance the operability of the assembly100. FIGS.35-36disclose another alternative embodiment of the dispenser actuator assembly100according to an exemplary embodiment of the invention. The structure of the dispenser actuator assembly100ofFIGS.35-36is similar to the structure of the dispenser actuator assembly100ofFIGS.9-19. The description ofFIGS.9-19is applicable to the dispenser actuator assembly100ofFIGS.35-36regarding structure and operation. Certain differences are discussed herein. In this embodiment, the apertures144extend completely through the actuator arms132a,132b. Thus, the apertures144extend through the first segments152a,152bof the protrusions150a,150b. In addition, the ridges148a,148bof the finger pads146a,146bhave different segments. For example, one segment of the ridges148a,148bon the intermediate segment138a,138bof the actuator arms132a,132bare generally transverse to other ridges148a,148bon the actuator arms132a,132b. In addition, the depending protrusions150a,150balso have a different configuration. The second segment154a,154bof the protrusion150tapers towards a minimal dimension generally at an intermediate portion on an underside of the actuator arm132a,132b. An additional boss164(FIG.36) is also included at an intermediate portion of the second segment152a,152bof the depending protrusion150a,150b. The description ofFIGS.9-19is applicable to the dispenser actuator assembly100ofFIGS.35-36regarding structure and operation. FIGS.37-38disclose another alternative embodiment of the dispenser actuator assembly100according to an exemplary embodiment of the invention. The structure of the dispenser actuator assembly100ofFIGS.37-38is similar to the structure of the dispenser actuator assembly100ofFIGS.9-19. Similar to the embodiment ofFIGS.35-36, the apertures144extend completely through the actuator arms132a,132b. The depending protrusions150a,150bare rigid and have a similar configuration to the previous embodiments and also have a thinner dimension at the second segments154a,154b. The description ofFIGS.9-19is applicable to the dispenser actuator assembly100ofFIGS.37-38regarding structure and operation. FIGS.39-40show a plurality of dispenser actuator assemblies100. It is shown that the length of the first and second actuator arms132a,132bcan vary such as for adjusting the moment arms and desired forces required to deflect the arms132a,132b. Also, the actuator arms132a,132bcould have a change in angle formed at an intermediate portion of the arms132a,132b. It is understood that such angle could vary as desired. Other structures of the dispenser actuator assembly100inFIGS.39-40are similar to the dispenser actuator assembly100ofFIGS.9-19. The description ofFIGS.9-19is applicable to the dispenser actuator assembly100ofFIGS.39-40regarding structure and operation. Prior to the invention, a user typically must squeeze, via finger pressure, the outer container14of the glass ampoule assembly10to crush the glass ampoule12. The squeezing thumb/fingers provides a force to deform the outer container14and crush the glass ampoule12. The required finger pressure could be considered significant for certain users having limited strength in their respective digits. The dispenser actuator assembly100provides mechanical advantage from the actuator arms132a,132bwherein the required finger pressure can be reduced.FIG.41shows graphically, the reduction in finger pressure required to crush the glass ampoule. The upper line represents the finger pressure required to crush the glass ampoule assembly10when a user directly squeezes, via finger pressure, the outer container14of the glass ampoule assembly10. The required pressure is typically approximately 15-20 psi. The lower line represents the finger pressure required to crush the glass ampoule assembly10when the dispenser actuator assembly100is used. As can be seen, the finger pressure required is typically less than 5 psi and could be approximately 3-4 psi. A significant reduction in required psi is achieved with the dispenser actuator assembly100. A lower, more constant and predictable breakage force is also achieved. It is understood that the dispenser actuator assembly100could include alternative features to provide further reduction is required psi as desired. It is understood that the angle that the actuator arms132a,132bextend from the base member102or flex plate180can vary and set at a greater angle that would allow more force to be generated. This can lead to a more difficult grip for certain users and, therefore, a sufficient angle is determined to provide the necessary rupturing force with an ergonomically-friendly grip of a user. It is understood that the dispenser actuator assembly100and the glass ampoule assembly10may be distributed or sold as a kit, e.g., together as a single unit package.FIG.42shows a representative package assembly220, which may be a blister package220. The blister package220containing the dispenser10and actuator assembly100may be referred to as a dispenser and actuator assembly package assembly. The dispenser actuator assembly100is mounted on the glass ampoule assembly10generally proximate a central intermediate segment of the outer container14of the glass ampoule assembly10to form a tandem unit. The package assembly200is provided having a bottom member222or blister layer222. The blister layer222has a blister recess224dimensioned to receive the tandem unit. The recess224has a first recess section226and a second recess section228. The first recess section226has a greater longitudinal dimension than a lateral dimension to receive and accommodate the glass ampoule assembly10. The second recess section228is generally rectangular and intersects the first recess section226at generally a central portion of the first recess section226. The second recess section228defines an outer wall229. The second recess section228is generally dimensioned to receive the dispenser actuator assembly100mounted on the glass ampoule assembly10. When the tandem unit is placed in the recess224, package spaces PS are defined between the actuator arms132a,132band the glass ampoule assembly10. The bottom member222can be formed from materials that resist inadvertent forces being placed onto the actuator arms of the dispenser actuator assembly inside the package. The blister layer222can be made from a variety of different materials. In one exemplary embodiment, the blister layer222is made of a thermoplastic material, such as polyvinyl chloride or polyolefin. Still other materials are possible and the blister layer222can also be laminated with other layers such as a tear resistant layer. As discussed, the package assembly220may be considered a blister package wherein a cover member230or film member230is adhered over the blister layer222to seal the tandem unit in the package assembly200until ready to be used. The cover member230can also be made from a variety of materials including a paper material, a thermoplastic film layer or a foil layer or still other materials. The foil member could be an aluminum foil. The cover member230could also be formed from a laminate material of a paper and a metal foil layer. The foil layer could also be coated with a film of a thermoplastic material such as polyethylene, polystyrene or the like. The cover member230is secured to the blister layer222by sealing through the application of heat and pressure. Other sealing techniques between the cover member230and the blister layer222can also be utilized. In one exemplary embodiment, the cover member230is releasably secured or releasably sealed to the blister layer222. The cover member230may define a pull tab for a user to pull the cover member230from the blister layer222. In other exemplary embodiments, the cover member230can be punctured or torn to gain access to the dispenser and actuator assembly tandem unit. The tandem unit in the package assembly220can then be further packaged, boxed, shipped or otherwise transported in preparation for use. FIGS.43A-Cshow additional features associated with the package assembly220.FIG.43Ashows the package assembly220containing the tandem unit of the dispenser actuator assembly100mounted on the glass ampoule assembly10. The tandem unit is positioned in the blister recess224. As further shown inFIG.43A, wedge members232, or first and second blocking members232, can be utilized between the glass ampoule assembly10and the actuator arms132a,132bof the dispenser actuator assembly100. The blocking member232, or wedge member232, generally has a right-triangle-type shape having an angled surface234and a primary linear surface236, as well as a secondary linear surface238. A right angle is defined between the linear surfaces236,238. In this exemplary embodiment, two wedge members232are utilized, e.g. a first blocking member232and a second blocking member232. As further shown inFIG.43A, a first blocking member232is positioned in the package space PS or recess space PS in the second recess section228generally between the first actuator arm132aand the second container14of the glass ampoule assembly10. In particular, the first angled surface234of the first blocking member232is positioned in confronting relation to the second segment154aof the depending protrusion150a. The second segment154aof the first depending protrusion150defines an inclined surface as shown inFIG.43A. In an exemplary embodiment, the respective surfaces of the angled surface234of the blocking member232and depending protrusion150engage one another. It is understood that a small gap could be present if desired. The primary linear surface236engages the outer surface of the second container14of the glass ampoule assembly10, e.g. the straight cylindrical surface of the second container14. The secondary linear surface238engages a rear wall portion of the second recess section228. Thus, the first blocking member232is confined or wedged between the first actuator arm132aand the second container14of the glass ampoule assembly10. Similarly, a second blocking member232is positioned in the package space PS or recess space PS in the second recess section228generally between the second actuator arm132band the second container14of the glass ampoule assembly10(e.g., generally opposed to the first blocking member232). In particular, the second angled surface234of the second blocking member232is positioned in confronting relation to the second segment154bof the depending protrusion150b, that defines a second inclined surface of the second actuator arm132b. In an exemplary embodiment, the respective surfaces of the second angled surface234and depending protrusion150engage one another. It is understood that a small gap could be present if desired. The primary linear surface236of the second blocking member232engages the outer surface of the second container14of the glass ampoule assembly10, e.g. the straight cylindrical surface of the second container14. The secondary linear surface238engages a rear wall portion of the second recess section228. Thus, the second wedge member232is confined or wedged between the second actuator arm132band the second container14of the glass ampoule assembly10. As further shown inFIG.43A, the respective distal ends136a,136bof the first and second actuator arms132a,132bconfront and engage outer walls229of the second recess section228of the blister recess224. As can be appreciated fromFIG.43A, in this configuration, the first blocking member232and the second blocking member232prevent movement of the actuator arms132a,132btowards one another to prevent premature crushing of the glass ampoule12of the glass ampoule assembly10. Even if a small gap is provided between the actuator arms132a,132band the angled surfaces234of the blocking members, the gap is controlled such that the actuator arms132a,132bcannot move enough to crush the glass ampoule12. Thus, in this configuration, the package assembly220can be further packaged, shipped and transported wherein any jostling of the package will not allow for inadvertent or premature actuation of the glass ampoule assembly10. FIG.43Bshows an alternative embodiment of the package assembly220. In this embodiment, the first blocking member232and the second blocking member232are integrally formed in the blister layer222of the package assembly220. In an exemplary embodiment, the blocking members232can be pressed to be integrally formed such as in the shape of the blocking member232shown inFIG.43A. Other processes can be used to form the integral blocking members232such as blow molding or the like. Thus, the integral blocking member232formed in the blister layer222can have the angled surface234, primary linear surface236and the second linear surface238. The integral blocking members232are positioned between the actuator arms132a,132band the glass ampoule assembly10as described above. As can be appreciated fromFIG.43B, in this configuration, the blocking members232prevent movement of the actuator arms132a,132btowards one another to prevent premature crushing of the glass ampoule12of the glass ampoule assembly10. Thus, in this configuration, the package assembly220can be further packaged, shipped and transported wherein any jostling of the package will not allow for inadvertent or premature actuator of the glass ampoule assembly10. It is appreciated that the integral blocking members232inFIG.43Bwould look the same as inFIG.43A. FIG.43Cshows a further alternative embodiment of the package assembly200. The blister layer222further has integral blocking members232formed therein. In this configuration, the blocking members232are generally round or circular members, e.g. having a circular cross-section. Similar to the other embodiments, the blocking members232are formed and dimensioned to be positioned between the actuator arms132a,132band the second container14of the glass ampoule assembly10. As can be appreciated fromFIG.43C, in this configuration, the blocking members232prevent movement of the actuator arms132a,132btowards one another to prevent premature crushing of the glass ampoule12of the glass ampoule assembly10. Thus, in this configuration, the package assembly220can be further packaged, shipped and transported wherein any jostling of the package will not allow for inadvertent or premature actuator of the glass ampoule assembly10. The kit described above may include the dispenser10, the dispenser actuator assembly100and the package assembly220including any desired blocking members232. It is understood that the kit could include different combinations of such elements or additional elements. For example, the kit could contain multiple applicator assemblies16to be used for dispensing flowable materials in different applications. The applicator assembly16may also be provided having different tips54for different applications. As discussed above, the dispenser actuator assembly100can be utilized to actuate a glass ampoule assembly such as shown inFIGS.1-4. The dispenser actuator assembly100can also be used with other types of glass ampoule assemblies such as the assembly10shown inFIGS.5-8.FIGS.44-45show the dispenser actuator assembly100mounted on the glass ampoule assembly ofFIGS.5-8, and in the first neutral position NP. It is understood that the cardboard sleeve18is not utilized in this connection where the cardboard sleeve18has been previously removed. The glass ampoule assembly10is actuated similar as described above and shown inFIG.45. A user engages the first actuator arm132aand the second actuator arm132band applies a force F wherein the arms132a,132bmove towards one another from the neutral position NP to the actuating position AP and wherein the second container14is deformed and the glass ampoule12is crushed. Flowable material M is then dispensed from the glass ampoule assembly10as described above. As described above, the dispenser actuator assembly100can be used with a dispenser10such as a glass ampoule assembly10. It is understood that the dispenser actuator assembly100can also be used with other types of dispensers10that utilize a rupturable feature in order to dispense flowable materials M from the dispenser10.FIG.46-48show another dispenser10in the form of a plastic ampoule assembly60. The plastic ampoule assembly has an outer wall62and a fracturable membrane64defining a chamber66for containing a flowable material M. The membrane64has a weld seam68formed during an injection molding process wherein a first segment of injected molding material abuts a second segment of injected molding material to form the weld seam68such as disclosed in U.S. Pat. No. 6,641,319, which patent is expressly incorporated herein. The membrane64having the weld seam68could also be formed in a conical shape such as disclosed in U.S. Pat. No. 10,392,163, which patent is expressly incorporated herein. It is understood that the plastic ampoule60can also utilized an applicator16for dispensing the flowable material M.FIG.47discloses the dispenser actuator assembly100mounted on the plastic ampoule assembly60. The dispenser actuator assembly100and actuator arms132a,132bare in the first neutral position NP. It is understood the mounting is such that the interface areas158a,158bare positioned proximate the fracturable membrane64. Similar to the operation described above, after the dispenser actuator assembly100is mounted on the plastic ampoule60, a user applies a compressive force F to the actuator arms132a,132bwherein the protrusions150a,150bat the interface areas158a,158bengage and deflect the outer wall62of the plastic ampoule60thereby applying the force proximate the membrane64wherein the weld seam68is fractured. Thus, the actuator arms132a,132bmove the from the neutral position NP to the actuating position AP. Upon fracturing of the weld seam68, the flowable material M can pass through the membrane64and into the applicator16to be dispensed from the plastic ampoule60. It is understood that the protrusions150a,150bare positioned proximate the membrane64to apply the force F to the membrane64to fracture the weld seam68. FIGS.49-52disclose use of the dispenser actuator assembly100in use with another alternative embodiment of a glass ampoule assembly10. The structure of the glass ampoule assembly10is generally similar in structure to the glass ampoule assembly100ofFIGS.1-4. The glass ampoule assembly10inFIGS.49-52utilizes multiple glass ampoules12in a tandem unit for a two-part flowable material configuration. Thus, the second container14contains a rear glass ampoule12and a front glass ampoule12. The rear glass ampoule12contains a first flowable material M1. The front glass ampoule12contains a second flowable material M2.FIG.49shows the dispenser actuator assembly100mounted on the glass ampoule assembly10wherein the interface areas158a,158bof the protrusions150a,150bare positioned proximate a first interface28of the rear glass ampoule12. This represents the neutral position NP.FIG.50shows a user applying a force F to the actuator arms132a,132bto move from the neutral position NP to the actuating position AP to crush the rear glass ampoule12. After crushing the rear glass ampoule12, the user can slide the dispenser actuator assembly100along the second container14of the glass ampoule assembly10wherein the interface areas158a,158bare positioned proximate the first interface area28of the front glass ampoule12. This configuration is shown inFIG.51.FIG.52shows the user applying a force F to the actuator arms132a,132bfrom a second neutral position NP to a second actuating position AP to crush the front glass ampoule12. After crushing the rear glass ampoule12and the front glass ampoule12, the respective flowable materials M1,M2of the ampoules12can mix together to form a mixture MX. The user may shake the glass ampoule assembly10to assist in the mixing to form the mixture MX. The user can dispense the mixture MX from the applicator16of the glass ampoule assembly10onto a receiving surface as described above. The dispenser actuator assembly100provides several benefits. The actuator assembly provides mechanical advantage for a user to crush, rupture or fracture the dispenser. The actuator arms can vary in length and resiliency to provide a desired mechanical force in rupturing the dispenser. Because the dispenser actuator assembly allows for a user to apply an increased force than from finger pressure alone, the assembly can be used to rupture more robustly designed dispensers. Such dispensers may be designed to crush under an increased force to minimize the chances of inadvertent rupture. In addition, the dispenser actuator assembly is designed to crush the glass ampoule at the optimal location at the interface area proximate the domed-portion of the glass ampoule to enhance the rupturing of the glass ampoule. Furthermore, as the user engages the actuator arms of the assembly rather than directly engaging the outer container of the dispenser, the chances that glass shards from the crushed glass ampoule can injure the fingers or hand of the user is minimized. The dispenser actuator assembly can also be adjustably mounted along a length of the glass ampoule assembly. For example, the dispenser actuator assembly can be slid along a length of the outer container of the glass ampoule assembly to a desired location. This helps in further manipulating flowable material from the glass ampoule assembly. In addition, the dispenser actuator assembly100can be removable attached to the dispenser. Once the dispenser is crushed and the flowable material is dispensed from the dispenser, the dispenser actuator assembly can be removed from the dispenser and used to crush multiple other dispensers. It is understood as well that the dispenser actuator assembly100could be manufactured as a single-use assembly that is discarded. It is further understood that the assembly100can be positionally adjusted on the glass ampoule assembly10to manipulate flowable material as desired or break the glass ampoule at a particular location. It is further understood that the flex plate structure provides several benefits as discussed above including flexing across a greater distance on the plate as well as providing for movement of the actuator arms independently of the support of the glass ampoule assembly by the base member. It is understood that any reference to an element using designations such as “first” or “second” or the like does not limit the quantity or order of those elements, unless such limitation is explicitly stated. These designations are used to distinguish between elements or other references to an element. Accordingly, a reference to a first element or a second element does not mean that only two elements may be employed or that the first element must precede the second element in some manner. In addition, a set of elements may comprise one or more elements. In addition, references to “top” or “bottom” or “front” or “rear” are used to reference relative positions of elements and should be construed as a limiting positional requirement. It is further understood that the present description includes several different embodiments with different features depending on the embodiment being described. It is understood that the various features or structures can be combined among the various embodiments in further exemplary embodiments of the invention. The dispenser10is permitted to be used in a wide variety of uses and applications, and contain and dispense a large variety of fluids and other flowable substances. The following is a non-exhaustive discussion regarding the many possible uses for the dispenser of the present invention, and in particular, the types of materials that are capable of being contained in the dispensers and dispensed therefrom. It is understood that related uses to those described below are also possible with the dispenser. It is also understood that the following discussion of potential uses is applicable to any of the dispenser embodiments disclosed and discussed herein. The dispenser used with the dispenser actuator assembly of the present invention is designed to primarily contain and dispense flowable materials that are fluids. Other flowable materials can also be dispensed. For example, the flowable material could be a liquid, powder, gel or other type of flowable substance or flowable material. Also, in other embodiments such as dispensers containing multiple chambers for different flowable materials, the flowable materials M1, M2could both be fluids. In another embodiment, the first flowable material M1could be a liquid, and the second flowable material M2could be a powder to be mixed with the fluid. Other combinations depending on the use are also permissible. This permits the dispenser10to be used in a wide variety of uses and applications, and contain and dispense a large variety of fluids and other flowable substances. The following is a non-exhaustive discussion regarding the many possible uses for the dispenser of the present invention, and in particular, the types of materials that are capable of being contained in the dispensers and dispensed therefrom. It is understood that related uses to those described below are also possible with the dispenser. It is also understood that the following discussion of potential uses is applicable to any of the dispenser embodiments disclosed and discussed herein. In one example, the dispenser of the present invention can be used in medical applications. In one particular exemplary embodiment, the dispenser may contain a surgical antiseptic such as for cleaning and preparing a body area for incision, and sometimes referred to as a surgical prep solution. One type of antiseptic may be chlorohexidine gluconate (CHG). This CHG-based antiseptic could also be combined with a medical sealant such as cyano-acrylic wherein the dispenser is used to contain and dispense cyano-acrylic chlorohexidine gluconate (CACHG). Other types of medical sealants could also be used. Other types of antiseptics could be iodine-based such as iodophoric skin tinctures, which are commercially available. Other antiseptics and antimicrobial agents could also include other iodine-based complexes, alcohol-based complexes or peroxides. Additional additives may also be used with the antiseptic such as colorants. A single chamber dispenser may be used in such an application, but a multi-chamber dispenser such as disclosed herein may also be used. In another example, the dispenser of the present invention can be used in adhesive-type applications. The dispenser can dispense a flowable material or mixture that is an adhesive, epoxy, or sealant, such as an epoxy adhesive, craft glue, non-medical super glue and medical super glue. The dispenser could also be used with shoe glue, ceramic epoxy and formica repair glue. The dispenser could further be used for a variety of other adhesive dispensing applications, mastic-related resins or the like. In another example, the dispenser of the present invention can be used in automotive applications. The dispenser can dispense a flowable material or mixture that is an automotive product, such as a rear view mirror repair kit, a vinyl repair kit, auto paints, an auto paint touch up kit, a window replacement kit, a scent or air freshener, a windshield wiper blade cleaner, a lock de-icer, a lock lubricant, a liquid car wax, a rubbing compound, a paint scratch remover, a glass/mirror scratch remover, oils, radiator stop-leak, a penetrating oil, or a tire repair patch adhesive. Other automotive applications could include acetone-based products such as windshield primer. Additional automotive applications could be for general auto/motorcycle or bicycle repair kits including chain oils. In another example, the dispenser of the present invention can be used in chemistry-related applications. The dispenser can dispense a flowable material or mixture that is a chemistry material such as a laboratory chemical, a buffer solution, a rehydration solution of bacteria, a biological stain, or a rooting hormone. The dispenser may also be used as a chemical tester. In one such application, the dispenser can be used for testing drinks for various “date rape” drugs. Other types of chemical testers are also possible. The dispenser could be used to contain various types of chemicals including solvents. In a particular application, the additional material formulations used to form the dispenser allow the dispenser to store and dispense methyl ethyl ketone. In another example, the dispenser of the present invention can be used to dispense a flowable material or mixture is a cosmetic and beauty supply/toiletry product. For example, the dispenser can be used for a nail polish, lip gloss, body cream, body gel, body paints, hand sanitizer, nail polish remover, liquid soaps, skin moisturizers, skin peels, tooth whiteners, hotel samples, mineral oils, toothpastes, mouthwash or sunscreens. The flowable material could also be a fragrance such as women's perfume or men's cologne. The flowable material could also be tattoo inks. The flowable material could be used for solutions for treating and/or removing tattoo ink. The cosmetic applications could also include hair care type applications. In another particular example, the dispenser of the present invention can be used in a hair dye kit. Certain hair dye kits come in multiple components that are separately stored wherein the dispenser embodiment disclosed herein having a dividing wall that cooperates to define separate chambers can be utilized. Thus, the dispenser of the present invention can be used in a two-part hair care product such as a hair dye kit. A first flowable substance of the hair dye kit can be carried in the first chamber, and a second flowable substance of the hair dye kit can be carried in the second chamber. The membrane is ruptured wherein the two flowable substances can be mixed together to form a mixture or solution. The mixture or solution can then be dispensed from the dispenser onto the hair of a user. The dispenser can also dispense a flowable material or mixture in other hair care products, such as hair bleaches, hair streaking agent, hair highlighter, shampoos, other hair colorants, conditioners, hair gels, mousse, hair removers, or eyebrow dye. In another example, the dispenser of the present invention can be used in crafting applications or stationary products. The dispenser can also dispense a large variety of stationery or craft products, such as magic markers, glitter gels, glitter markers, glitter glues, gel markers, craft clues, fabric dyes, fabric paints, permanent markers, dry erase markers, dry eraser cleaner, glue sticks, rubber cement, typographic correction fluids, ink dispensers and refills, paint pens, counterfeit bill detection pen, envelope squeeze moisturizers, adhesive label removers, highlighters, and ink jet printer refills. In another example, the dispenser of the present invention can also dispense a flowable material or mixture that is an electronics-related product. For example, the electronics product could be a cleaning compound, a telephone receiver sanitizer, cell phone cleaner or protectants, a keyboard cleaner, a cassette recorder cleaner, audio/video disc cleaner, a mouse cleaner, or a liquid electrical tape. In another example, the dispenser of the present invention can dispense a flowable material or mixture in food product applications. For example, the food product may be food additives, food colorings, coffee flavorings, cooling oils, spices, flavor extracts, food additives, drink additives, confections, cake gel, pastry gel, frostings, sprinkles, breath drops, condiments, sauces, liquors, alcohol mixes, energy drinks, or herbal teas and drinks. In another example, the dispenser of the present invention can be used in home repair product and home improvement applications. The dispenser can also dispense a flowable material that is a home repair product, such as a caulking compounds or materials, a scratch touch up kit, a stain remover, a furniture repair product, a wood glue, a patch lock, screw anchor, wood tone putty or porcelain touch-up. The dispenser could also dispense a plumbing flux applicator, rust remover and tree wound treatment. In certain home repair or home improvement applications, the dispenser can be used in paint applications. The dispenser can dispense a variety of paint products such as general paints including interior/exterior paints, novelty paints, paint additives, wood stain samples, varnishes, stains, lacquers, caulk, paint mask fluid or paint remover. In another example, the dispenser of the present invention can be used in household related products. For example, the dispenser could be used for cleaning agents, pest control products, a fish tank sealant or a fish tank treatment, a leak sealant, a nut/bolt locker, screw tightener/gap filler, a super glue remover or goo-b-gone. The dispenser could also be used for a colorant dispenser, or disinfectants, a plant food, fertilizers, bug repellants or a cat litter deodorant. The dispenser could also dispense toilet dyes and treatments, eyeglass cleaners, shoe polishes, clothing stain removers, carpet cleaners and spot removers, multi-purpose oils, and ultrasonic cleaner concentrate. The household product could include a variety of pet-related products including but not limited to an animal medicine dispenser, pet medications, animal measured food dispenser, pet shampoos or odor eliminator liquids. A large variety of pest control products can be dispensed by the dispenser, including insect attractants, pesticides, pet insect repellants, pest sterilizers, insect repellants, lady bug attractant and fly trap attractant. The household product could also include various types of polishes, reagents, indicators and other products. In another example, the dispenser of the present invention can be used in lubricant applications. The dispenser can dispense a large variety of lubricants including industrial lubricants, oils, greases, graphite lubricants or a dielectric grease. The dispenser of the present invention can also be used in other medical applications including medical related products, medicinal products and medicaments. Additional medical related product applications can include skin adhesive kits to be used in place of traditional stitching products. As discussed, the dispenser could also be used with topical antiseptics, antimicrobials and surgical scrub products. In addition, the dispenser10can dispense a large variety of medicinal products, such as blister medicines, cold sore treatments, insect sting and bite relief products, skin cleaning compounds, skin sealing solutions, skin rash lotions, nasal sanitizers, nasal medications, tissue markers, topical antimicrobials, topical demulcent, treatments for acne such as acne medications, umbilical area antiseptics, cough medicines, waterless hand sanitizers, toothache remedies, cold medicines, sublingual dosages or wart treatments. For example, the dispenser could contain a medicinal product containing hydrogen-peroxide used for dermatological conditions such as warts, seborrheic keratosis or similar skin conditions. The dispenser could also be used to dispense compositions for treating various other skin conditions. The dispenser could also be used in conjunction with a medical device product. Other medical related applications could include various types of dental related products including different types of compounds and treatments applied to a patients' teeth. The dispenser could also be used in veterinary related products. In another example, the dispenser of the present invention can be used in novelty products. For example, the dispenser can contain materials in a glow-stick device. In such instance, the dispenser is a container that may contain multiple components separately stored until activation to create a glowing state in response to mixture of the components. Furthermore, the dispenser can dispense a flowable material or mixture that is a chemiluminescent light, a Christmas tree scent, a glitter gel, and a face paint. Other types of novelty paints could also be used with the dispenser. In another example, the dispenser of the present invention can be used in sports products. The dispenser can dispense a variety of sports products including sports eye black, football hand glue, and baseball glove conditioner and pine tar. The dispenser can also dispense wildlife lures. The dispenser can be used in various camping related applications including portable lighting fuels for camp lights or other devices and tent repair kits. The dispenser can also be used in bingo or other game markers. In another example, the dispenser of the present invention can be used in test kit applications. The dispenser can dispense a flowable material or mixture that is a test kit, such as a lead test kit, a drug kit, a radon test kit, a narcotic test kit, a swimming pool test kit (e.g., chlorine, pH, alkalinity etc.), a home water quality tester, a soil test kit, a gas leak detection fluid, a pregnancy tester, or a respirator test kit. The dispenser can also dispense a flowable material or mixture that as part of a medical device test kit, such as a culture media, a drug monitoring system, a microbiological reagent, aStreptococcustest kit, or a residual disinfectant tester. The dispenser may also be used in diagnostic testing kits, explosive testing kits or other test kits. The dispenser can be used in breathalyzer tests, culture media samples and drug test kits. In another example, the dispenser of the present invention can be used in personal care products or wellness-related products. The dispenser can also dispense a flowable material or mixture that is a personal care product, such as shaving cream or gel, aftershave lotion, skin conditioner, skin cream, skin moisturizer, petroleum jelly, insect repellant, personal lubricant, ear drops, eye drops, nose drops, corn medications, nail fungal medication, aging liquids, acne cream, contact lens cleaner, denture repair kit, finger nail repair kit, liquid soaps, sun screen, lip balm, tanning cream, self-tanning solutions, eye wash solution finger nail repair kits. The dispenser can also be used with aroma therapy products and homeopathic preparations. The dispenser can also dispense various vitamins, minerals, supplements and pet vitamins. The dispenser can also dispense a flowable material or mixture in a variety of other miscellaneous applications. Such miscellaneous applications may include, but not be limited to use in connection with a suction device for culture sampling, taking various liquid samples or taking various swabbing samples. The dispenser could also be used for float and sinker devices, dye markers, microbiological reagents, and also for manufacturing parts assembly liquids and irrigation solutions. The dispenser may also be used as a chalk dispenser such as in construction applications. Thus, the dispenser can be used in many different applications including mechanical, chemical, electrical or biomedical uses. The dispenser can dispense any variety of flowable materials including liquids and powders, and further including a liquid and a powder, two or more powders, or two or more liquids. The dispenser may be used as part of 2-part system (mix before use) including a liquid with a powder, a liquid with a liquid, a powder with a powder, or sealed inside another tube or product container or partially sealed, connected or attached to another container. The dispenser may also be used as part of a plunger dispensing system. While the invention has been described in its preferred embodiments, it is to be understood that the words which have been used are words of description rather than limitation and that changes may be made within the purview of the appended claims without departing from the true scope and spirit of the invention in its broader aspects. | 97,701 |
11857748 | DETAILED DESCRIPTION An exemplary composition delivery device10for enhanced delivery of a composition to a body region of a patient utilizing radiofrequency energy is illustrated inFIGS.1and5. Although radiofrequency energy is described, other energy modalities, such as ultrasound or laser energy by way of example, may be utilized. The composition delivery device10includes a first longitudinal member12including electrodes14(1) and14(2), a radiofrequency energy source16, and a composition delivery element18, although the composition delivery device10could include other types and/or numbers of elements, components, and/or devices in other configurations, such as additional electrodes and/or longitudinal members. This exemplary technology provides a number of advantages including providing more efficient and effective composition delivery to a region within the body of a patient. Referring more specifically toFIG.1, the composition delivery device10includes a first longitudinal member12that is configured to be advanced into the body of a patient and located near a body region of the patient. The body region may be various regions in the body, including organs, body lumens or cavities, such as various ducts or vessels, blood vessels, grafts, glands. In one example, the body region may be an area in the body including an occlusion or a tumor that requires treatment. In this example, the first longitudinal member12includes a lumen19extending between a proximal end20and a distal end22of the first longitudinal member12, although the longitudinal member12may include additional lumens. The lumen19is configured to receive additional longitudinal members therein, such as guidewires, catheters, microcatheters, or probes, by way of example only. In this example, the longitudinal member12has electrodes14(1) and14(2) located thereon to provide a bipolar arrangement of the electrodes14(1) and14(2), although the electrodes14(1) and14(2) may be located on other elements in other configurations to provide a bipolar arrangement. In another example, as shown inFIG.2, the composition delivery device10further includes a second longitudinal member13that is configured to be inserted into the lumen19of the first longitudinal member12to be delivered proximate to the body region of the patient. In this example, the second longitudinal member13is a guidewire or a catheter with the electrodes14(1) and14(2) located thereon to provide the bipolar arrangement. In yet another example, as shown inFIG.3, the composition delivery device10further includes a third longitudinal member23that is configured to be inserted into the lumen19of the first longitudinal member. The third longitudinal member23may be a guidewire or a catheter, by way of example only. The second longitudinal member13and the third longitudinal member23, which are independent, non-overlapping guidewires or catheters, may be delivered to the body region in the same direction or in opposition directions as described below. In a further example, one of the electrodes14(1) or14(2) is located on a patch that may be placed on the patient's skin proximate the body region of the patient to be treated. The patch is placed in close proximity to the body region to allow for the bipolar arrangement between the electrodes14(1) and14(2). Referring now toFIG.4, in one example the lumen19of the first longitudinal member12includes multiple lumen sections to deliver the second longitudinal member13and the third longitudinal member23separately to the body region. In yet another example, the second longitudinal member13may be configured to receive the third longitudinal member23such that the third longitudinal member23is located within the second longitudinal member13. Referring again toFIG.3, in this example the electrodes14(1) and14(2) are located on the second longitudinal member13and the third longitudinal member23, respectively, in order to provide the bipolar arrangement. In one example, the electrodes14(1) and14(2) may be balloon markers, although other types of electrodes may be utilized. Referring toFIG.5, the electrodes14(1) and14(2) are coupled to the radiofrequency energy source16via wires17(1) and17(2). The wires17(1) and17(2) are wrapped in a helical configuration about the first longitudinal member12. The wires17(1) and17(2) deliver radiofrequency energy from the radiofrequency energy source16to provide radiofrequency energy to the body region, although other energy sources configured to supply other energy modalities may be employed. Referring now toFIG.6, the electrodes14(1) and14(2) are insulated, such as with a dielectric barrier, such that the two electrodes14(1) and14(2) are capable of generating an electric field in the body region. Further, the insulation is selected to allow the electrodes14(1) and14(2) to be capable of withstanding the generation of a plasma discharge around the electrodes14(1) and14(2). The electrodes14(1) and14(2) may further have a dielectric barrier located at an exposed portion of the electrodes14(1) and14(2) to further aid in withstanding plasma generation. Referring again more specifically toFIGS.1and5, the radiofrequency energy source16provides a source of radiofrequency energy that is delivered to the body region through electrodes14(1) and14(2), although other energy modalities may be employed. In one example, the radiofrequency energy source16provides modulated pulses of radiofrequency energy to the electrodes14(1) and14(2). In one example, the radiofrequency energy source16is configured to provide modulated pulses having a pulse width between about 0.05 to about 500 microseconds, although modulated pulses having a pulse width of less than 0.05 microseconds or between 500 microseconds and 1 second may be employed. The radiofrequency energy source16may further be configured to provide the modulated pulses in packets. Each packet of modulated pulses may have between 2 and 10 pulses, by way of example only. In another example, the modulated pulses are grouped into bursts having a burst width between 100 ms to 1 s and an interval between each burst between 1 ms to 100 ms, by way of example only. The radiofrequency energy source16provides radiofrequency energy at a voltage between 400V to 4000V, although voltages less than 400V may be utilized in some examples. The radiofrequency energy source16is capable of providing radiofrequency energy at a level that produces a delivery condition in the body region that enhances delivery of the composition, such as cavitation, microjets, shockwaves, electrical stimulation, or a chemical reaction. In one example, the radiofrequency energy source16provides energy to generate shockwaves having an instantaneous magnitude between 0.1 MPa to 20 MPa. In another example, the radiofrequency energy source16provides energy to generate one or more regions of cavitation bubbles in the body region having a diameter between 1 μm and 10 mm. The cavitation bubbles may be formed from the composition delivered to the body region using the composition delivery device10. Referring again toFIGS.1and5more specifically, the composition delivery device10further includes the composition delivery element18located at the distal end22of the first longitudinal member12. The composition delivery element18includes a composition layer24of the composition to be delivered to the body region located on a surface25of the composition delivery element18. The composition layer24is coated on and/or imbedded within the surface25of the composition delivery element18. Methods of applying the composition layer24can include spraying, dip coating, vapor deposition, plasma deposition, using a chemical bond, or using an electrical bond, by way of example only. In another example the composition, rather than being placed on the outside of the composition delivery element, is injected inside the composition delivery element18. The composition delivery element18includes pores50that allow the composition to escape through the pores50and be delivered into the body region, such as an occlusion or vessel wall as shown inFIG.10. This delivery of the composition is enhanced by activation of radiofrequency energy as described further below. In another example the composition is located on the composition delivery element as a charged compound. The radiofrequency energy is then delivered with a similar charge so the composition is repelled from the composition delivery element18and into the tissue. Additionally or alternatively, an electrically neutral therapeutic agent may be modified by adding a charged moiety such that the modified therapeutic agent comprising the charged moiety may be more susceptible to the influence of the energy field. Additionally, the therapeutic agent may be submerged or dissolved in a conductive fluid, whereby the conductive fluid path under the influence of the energy field as described above serves as a vehicle to facilitate the delivery of the therapeutic agent to the treatment region. By way of example, drugs to treat anemia may be used. The composition is a therapeutic agent or a pharmaceutical compound. Non-limiting examples of the compositions that may be utilized with the composition delivery device include a thrombolytic agent, a fibrinolytic enzyme, a thrombin inhibitor, an antiplatelet agent, an anticoagulant, an anti-restenotic agent, or an anti-cancer agent, although other therapeutic agents or pharmaceutical compounds may be delivered using the composition delivery device10. The composition can be a drug, gas, or liquid which can have an effect on the targeted body region. As an example, the composition could be Paclitaxel or a drug taken from the limus family of drugs and used to be delivered to the vessel body of an occlusion to reduce the likelihood of such vessel from reoccluding or restenosing. It is contemplated that the present embodiments may be used to deliver other therapeutic agents or other biologically active substances including but not limited to: amino acids, anabolics, analgesics and antagonists, anesthetics, anthelmintics, anti-adrenergic agents, anti-asthmatics, anti-atherosclerotics, antibacterials, anticholesterolics, anti-coagulants, antidepressants, antidotes, anti-emetics, anti-epileptic drugs, anti-fibrinolytics, anti-inflammatory agents, antihypertensives, antimetabolites, antimigraine agents, antimycotics, antinauseants, antineoplastics, anti-obesity agents, anti-Parkinson agents, antiprotozoals, antipsychotics, antirheumatics, antiseptics, antivertigo agents, antivirals, bacterial vaccines, bioflavonoids, calcium channel blockers, capillary stabilizing agents, coagulants, corticosteroids, detoxifying agents for cytostatic treatment, contrast agents (like contrast media, radioisotopes, and other diagnostic agents), electrolytes, enzymes, enzyme inhibitors, gangliosides and ganglioside derivatives, hemostatics, hormones, hormone antagonists, hypnotics, immunomodulators, immunostimulants, immunosuppressants, minerals, muscle relaxants, neuromodulators, neurotransmitters and nootropics, osmotic diuretics, parasympatholytics, para-sympathomimetics, peptides, proteins, respiratory stimulants, smooth muscle relaxants, sympatholytics, sympathomimetics, vasodilators, vasoprotectives, vectors for gentherapy, viral vaccines, viruses, vitamins, and the like. In this example, the composition delivery element18is an expandable balloon having a porous surface25to which the composition layer24is applied, although other composition delivery elements, such as an expandable catheter, or a stent may be utilized. In another example, the composition delivery element18may be microbubbles filled with the composition that are delivered to the body region through the lumen19of the first longitudinal member12, by way of example. In another example, as shown inFIG.7, the composition delivery element18comprises a plurality of expandable ribs with the composition located thereon. Referring now again more specifically toFIGS.1and5, the composition delivery element18, such as a balloon, includes one or more raised elements28located on the surface25thereof. The raised elements28are configured to simultaneously score or cut the body region, such as an occlusion, so that a composition can more readily diffuse into the area into which the composition delivery element18is inserted. The raised elements28may comprise longitudinal or circumferential elements located on the composition delivery element18. In one example, the raised elements28have a triangular cross section, although other configurations may be utilized. The raised elements28are constructed of a metal or a polymer, by way of example, although other materials may be utilized. The composition layer24may be applied directly to the raised elements28of the composition delivery element18. In this example, the raised elements28are coupled directly to the composition delivery element18. Alternatively, referring now toFIG.8, the raised elements28may be coupled directly to the first longitudinal member12, although other configurations may be utilized. An example of a method for enhanced delivery of a composition to a body region of a patient utilizing radiofrequency energy will now be described with reference toFIGS.1-8. First, the longitudinal member12including the composition delivery element18with the composition layer24located on the surface25is delivered to the body region of the patient to be treated. The body region may be various regions in the body such as organs, body lumens or cavities, such as various ducts or vessels, blood vessels, grafts, glands. In one example, the body region may be an area in the body including an occlusion or a tumor that requires treatment. The composition layer24may be coated or imbedded on the surface25of the composition delivery element18, although in other examples the composition layer24may be located on the raised elements protruding from the surface25of the composition delivery element18, such as an expandable balloon. Once located in the body region, the composition delivery element18may be expanded to apply the composition layer24to the body region. The composition is a therapeutic agent or a pharmaceutical compound. Non-limiting examples of the compositions that may be utilized with the composition delivery device include a thrombolytic agent, a fibrinolytic enzyme, a thrombin inhibitor, an antiplatelet agent, an anticoagulant, an anti-restenotic agent, or an anti-cancer agent, although other therapeutic agents or pharmaceutical compounds may be delivered using the composition delivery device10. Next, the first electrode14(1) and the second electrode14(2) coupled to the radiofrequency energy source16are directed to the location proximate to the body region. In one example, the longitudinal member12has electrodes14(1) and14(2) located thereon, as shown inFIGS.1and5, such that the electrodes14(1) and14(2) are delivered simultaneously with the longitudinal member12. In another example, as shown inFIG.2, the electrodes14(1) and14(2) are delivered on second longitudinal member13that is configured to be inserted into the lumen19of the first longitudinal member12to be delivered proximate to the body region of the patient. In this example, the electrodes14(1) and14(2) are directed to the body region after delivery of the composition delivery element18. In yet another example, as shown inFIG.3, the electrodes14(1) and14(2) are directed separately to the body region through the lumen19of the first longitudinal member12on the second longitudinal member13and the third longitudinal member23, which are independent, non-overlapping guidewires or catheters, respectively. In this example, the second longitudinal member13and the third longitudinal member23may be delivered to the body in the same direction or in opposition directions, using an antegrade/retrograde approach, as described in U.S. Pat. No. 9,561,073, the disclosure of which is incorporated herein by reference in its entirety. As disclosed in U.S. Pat. No. 7,918,859 by the same inventors, which is incorporated herein in its entirety, in the controlled antegrade and retrograde tracking (CART) technique the retrograde approach takes advantage of an intercoronary channel. Such a channel may be an epicardial channel, an inter-atrial channel, an intra-septal channel (also referred to as septal collateral), or a bypass graft. The basic concept of the CART technique is to create a channel through an occlusion, preferably with limited dissections, by approaching the occlusion both antegradely and retrogradely. In a further example, a patch including one of the electrodes14(1) or14(2) is placed on the patient's skin proximate the body region of the patient to be treated. The patch is placed in close proximity to the body region to allow for the bipolar arrangement between the electrodes14(1) and14(2). Next, radiofrequency energy is delivered from the radiofrequency energy source16to the electrodes14(1) and14(2) in modulated pulses. In one example, the radiofrequency energy source16provides modulated pulses having a pulse width between about 0.05 to about 500 microseconds, although modulated pulses having a pulse width of less than 0.05 microseconds or between 500 microseconds and 1 second may be employed. The radiofrequency energy source16may further provide the modulated pulses in packets having between 2 and 10 pulses, by way of example only. In another example, the modulated pulses are grouped into bursts having a burst width between 100 ms to 1 s and an interval between each burst between 1 ms to 100 ms, by way of example only. The delivery of the modulated pulses may be gated using an electrocardiogram (ECG) or another waveform signal obtained from the body of the patient. In one example, a third electrode14(3) shown inFIG.7may be located on a patch15placed outside of the body region and electrically coupled to the electrodes14(1) and14(2). In yet another example, a third electrode may be located near the body region in order to measure impedance based on the delivery of the radio frequency energy or in another example the third electrode14(3) on the patch15can be used with one of electrodes14(1) or14(2). The impedance measurements may then be utilized to optimize the delivery of the radiofrequency energy. The radiofrequency energy source16provides the radiofrequency energy at a voltage between 400V to 4000V, although voltages less than 400V may be utilized in some examples. In one example, the incident intensity of the radiofrequency energy in the body region is between about 0.1 Joules to 5 Joules per square millimeter. In one example, the radiofrequency energy is delivered until an electrical limit, such as 100 Ohms, is met, although other electrical limits may be employed. The radiofrequency energy source16provides radiofrequency energy at a level that produces a delivery condition in the body region that enhances delivery of the composition, such as cavitation, microjets, shockwaves, electrical stimulation, or a chemical reaction. In one example, the radiofrequency energy source16provides energy to generate shockwaves having an instantaneous magnitude between 0.1 MPa to 20 MPa. In another example, the radiofrequency energy source16provides energy to generate one or more regions of cavitation bubbles in the body region having a diameter between 1 μm and 10 mm. The cavitation bubbles may be formed from the composition delivered to the body region using the composition delivery device10. The delivery of radiofrequency energy provides for prolonged delivery of the composition and imbedding of the composition within the body region to provide enhanced treatment. The radiofrequency signal can be adjusted using a number of modifications to the pulse such as by shortening or lengthening the pulse duration or adjusting the pulse period. As an example, by shortening the pulse duration to the micro or nanosecond range, a stronger mechanical effect can be obtained inducing stronger mechanical effects (i.e. deeper injection or imbedding) of the composition into the body region. A deeper imbedding of the composition is likely to result in a longer duration of the composition within the body region enabling a more durable effect from the composition. By way of example, the delivery of radiofrequency energy may be utilized to provide a mechanical force that enhances diffusion of the composition into the body region. Alternatively, the radiofrequency energy may be employed to cause impacts on the body region itself, such as vasodilation, increased cell permeability, or reversible electroporation that increase the effectiveness of the delivery of the composition to the body region. By way of example, the method may be utilized to treat on occlusion. The radiofrequency energy is applied between the two electrodes14(1) and14(2) generating a plasma and modifying the surrounding plaque or occlusion or vessel wall utilizing the effects of the plasma generation, such as cavitation or shockwaves. The composition is delivered to the occlusion, which has now become more amenable to diffusion or delivery of the composition due to the effects of the plasma generation, thus enhancing the delivery of the composition into the vessel wall. The delivery of the radiofrequency energy to the vessel wall or occlusion can induce vasodilation, alter cell permeability, or electroporation or the like to enhance the delivery of the composition. By adjusting the radiofrequency signal, the composition can be delivered deeper into the vessel wall, thus allowing the composition to remain within the vessel wall for a prolonged period of time and improving the durability of the composition within the vasculature. In another example, the electrodes14(1) and14(2) are placed on the same device as the composition, which allows for simultaneous modification of the surrounding tissue and delivery of radiofrequency energy to enhance delivery of the composition. In this example, the composition delivery element18, such as a balloon catheter, has the composition layer24placed on the outside surface25of the balloon. The electrodes14(1) and14(2) are located inside the composition delivery element18as either an attachment to the first longitudinal member12as shown inFIG.1, or delivered through the lumen19of the first longitudinal member12as shown inFIGS.2and3. The radiofrequency energy is then delivered and the effects of the radiofrequency energy are transmitted through the composition delivery element18, such as a balloon, to the composition layer24and the vessel wall enhancing delivery of the composition to the vessel wall. Another exemplary method for enhanced delivery of a composition to a body region of a patient, such as an occlusion, utilizing radiofrequency energy will now be described with reference toFIGS.9A-9C. In this example, electrodes14(1) and14(2) are directed to the occluded area in the vessel on the second longitudinal member13and the third longitudinal member23prior to delivery of the composition to the body area, as shown inFIG.9A. Radiofrequency energy is then applied as set forth above. The application of radiofrequency energy generates a plasma and modifies the surrounding plaque or occlusion or vessel wall utilizing the effects of the plasma generation, such as cavitation or shockwaves, as shown inFIG.9B. The electrodes14(1) and14(2) are then removed from the body region. Next, the composition is delivered to the occlusion using composition delivery element18as shown inFIG.9C. The occlusion has become more amenable to diffusion or delivery of the composition due to the effects of the plasma generation, thus enhancing the delivery of the composition into the vessel wall. The delivery of the radiofrequency energy to the vessel wall or occlusion can induce vasodilation, alter cell permeability, or electroporation or the like to enhance the delivery of the composition. By adjusting the radiofrequency signal, the composition can be delivered deeper into the vessel wall, thus allowing the composition to remain within the vessel wall for a prolonged period of time and improving the durability of the composition within the vasculature. EXAMPLE Preclinical work (FIG.11) has shown that at very high voltages, the effect of plasma-mediated ablation using radiofrequency energy within a nonoccluded vessel can result in effects that propagate into the vessel wall. In particular, medial dissections and/or hemorrhaging perivascularly can occur into the outer vessel wall. However, by altering the radiofrequency delivery settings, these effects can be controlled such that they enhance delivery of a composition into the vessel wall or occlusion without creating deleterious effects. Examples of alterations can include reducing the voltage or current levels, modifying the pulse period, modifying the pulse duration, or modifying the number of pulses delivered during radiofrequency delivery. As an example, in the case of an occlusion in a vessel wall, it has been shown that the use of voltages in the range of 1200V to 2000V can ablate tissue and create a channel through the occlusion in a very short period of time. The delivery of drugs or other compositions would likely require less energy or a lower voltage as the objective is not to create a channel but to enhance the delivery of the drug into the vessel wall. Similarly, it has been shown that very short pulses (on the order of nano seconds) generally create larger mechanical forces (e.g. shockwaves) than longer pulses. It would be preferred to deliver enough mechanical force to enhance delivery of the drug or composition into the vessel wall without causing damage to the wall itself. Accordingly, as illustrated and described by way of the examples herein this technology provides more efficient and effective devices and methods for delivering a composition to a body region. The devices and methods of this technology allow the composition to remain within the body region site for an extended period of time to provide enhanced treatment. In particular, the use of cavitation, shockwaves, electroporation, or the like, generated by radiofrequency energy or other energy source aids in the delivery of the composition. This technology also advantageously provides an enhanced method for delivering a drug into a vessel wall or occlusion such that the drug remains within the targeted site for a longer period of time without leaving anything behind. Prolonged action of the drug within the targeted site can lead to improved outcomes (e.g. reduced reocclusion, restenosis, or revascularization rates) Having thus described the basic concept of the invention, it will be rather apparent to those skilled in the art that the foregoing detailed disclosure is intended to be presented by way of example only, and is not limiting. Various alterations, improvements, and modifications will occur and are intended to those skilled in the art, though not expressly stated herein. These alterations, improvements, and modifications are intended to be suggested hereby, and are within the spirit and scope of the invention. Accordingly, the invention is limited only by the following claims and equivalents thereto. | 27,354 |
11857749 | DETAILED DESCRIPTION OF THE DRAWINGS An adapter device (e.g., adapter devices110,410) for a tattoo machine (e.g.100,400) and accompanying methods (e.g. method1500) for utilizing the adapter device with a tattoo machine are disclosed. In particular, the adapter device may enable a tattoo machine to switch from a fully wireless or other configuration to a wired configuration, such as by removing a wireless battery pack from the tattoo machine and replacing the wireless battery pack with the adapter. In certain embodiments, the adapter may be fitted with a connector, such as, but not limited to, a RCA connector that may couple with a power cable that may be utilized to deliver power to the tattoo machine when the tattoo machine is connected to the adapter and the coupled power cable is connected to a power supply supplying the power. The power supply may be any device may connect to a power source, such as a wall socket or other power source, and which may be utilized to deliver power to the tattoo machine via the adapter. In certain embodiments, the adapter may include a female RCA connector attached on one end of the adapter, and, on the opposite end (or other desired location), the adapter may include a printed circuit board with custom designed plating that is configured to make contact with pins on a motor assembly of the tattoo machine so that power may be transferred to the tattoo machine via the adapter and from the power supply. An internal circuit of the printed circuit board may be configured to ensure that the power delivered to the motor of the tattoo machine via the power cable attached to the female RCA connector always has the correct polarity regardless of the input polarity. As shown inFIG.1A-Band referring also toFIGS.2A-2B-3A-B, embodiments of a tattoo machine100including a tattoo machine portion130and an adapter110is disclosed. The tattoo machine100may be utilized to apply tattoo ink onto the skin of a tattoo recipient, such as a person. In certain embodiments, the tattoo machine portion130of the tattoo machine100may include a grip131that a tattoo artist may grip while utilizing the tattoo machine100. Additionally, the tattoo machine portion130may include a motor140that may be utilized to power and actuate the various components of the tattoo machine100. The tattoo machine portion130may also include a receptacle135, which may be configured to receive a needle cartridge containing a needle(s) that may be utilized to deliver ink onto the skin of a tattoo recipient. Furthermore, the tattoo machine portion130may also include another receptacle137(seeFIGS.13A,13B,13C,13D,13E,13F,13G,13H,13I, and13J) that may be configured to couple with the adapter110. The motor140of the tattoo machine portion130may be utilized to drive the needle so that the ink may be applied onto the skin of the tattoo recipient. In certain embodiments, the adapter110of the tattoo machine100may serve as a housing that may include a connector112and a printed circuit board115. In certain embodiments, the connector112may be a female RCA connector, a ¼ Jack connector, a male RCA connector, a 9V connector, any type of connector, or a combination thereof. In this example, the connector112may be a connector that enables a RCA version of the cable150to couple to the connector112. The connector112may include a cylindrical shaped structure117(or other shape) that may be configured to couple with an end of a power cable150, which may, for example, include an RCA or other plug. The connector112may couple and connect with the power cable150(seeFIGS.13A,13B,13C,13D,13E,13F,13G,13H,13I, and13J), which may connect with a power supply160that may deliver power to the adapter110via the power cable150. In certain embodiments, the adapter110may include one or more grooves111on a second portion116, which may enable a user to securely grab onto the adapter110, such as when connecting the adapter110to the tattoo machine portion130. In certain embodiments, the printed circuit board115of the adapter110may be utilized to transfer power from a connected power cable150when the adapter110is connected to the tattoo machine portion130to the motor140of the tattoo machine100. In certain embodiments, the printed circuit board115may include an internal circuit that may be utilized to ensure that the power delivered to the motor140of the tattoo machine portion130has the correct polarity irrespective of the input polarity. In certain embodiments, the printed circuit board115of the adapter110may include a custom-designed plating that makes contact with pins on the motor140when the adapter110is connected to the tattoo machine portion130. In order to connect the adapter110to the tattoo machine portion130, a user may align a first portion118of the adapter110with the receptacle137of a tattoo machine portion130. The user may then insert the first portion118of the adapter110axially into the receptacle137. Once inserted, the user may twist the adapter, such as in a clockwise motion (or other suitable and/or desired motion). The twisting motion may cause one or more extruded features113(e.g. three extruded features or other number of extruded features) of the first portion118of the adapter110to contact one or more ledges114of the tattoo machine portion130. Once contact between the one or more ledges114and the one or more extruded features113is made, an o-ring (or other similar device) of the adapter110may be squeezed between the adapter110and the body of the tattoo machine portion130(via the receptacle137) such that a pulling force may be generated on each of the extruded features113to cause the adapter110to lock into place with the receptacle137of the tattoo machine portion130. The user may then connect one end of the power cable150to the power supply160and the other end155to the connector112. The power supply160may then provide power to the adapter110, which may then deliver the power to the motor140of the tattoo machine portion130so that the tattoo artist may utilize the tattoo machine100to apply ink to a tattoo recipient. In another embodiment, as shown inFIGS.4-12, another adapter410may be utilized with a tattoo machine400and a tattoo machine portion430. Much like tattoo machine100, the tattoo machine400may be utilized to apply tattoo ink onto the skin of a tattoo recipient. In certain embodiments, the tattoo machine400, the tattoo machine portion430, and the adapter410may include some or all of the same components as found in tattoo machine100, tattoo machine portion130, and/or adapter110. The tattoo machine portion430of the tattoo machine400may include a grip431that a tattoo artist may grab onto while utilizing the tattoo machine400. Additionally, the tattoo machine portion430may include a motor440that may be utilized to power and actuate the various components of the tattoo machine400. The tattoo machine portion430may also include a receptacle435, which may be configured to receive a needle cartridge containing any number of needles that may be utilized to deliver ink onto the skin of a user. Furthermore, the tattoo machine portion430may also include another receptacle437(similar to receptacle137) that may be configured to couple with the adapter410. The motor440of the tattoo machine portion430may be utilized to drive the needle so that the ink may be applied onto the skin of the tattoo recipient. In certain embodiments, the adapter410of the tattoo machine400may serve as a housing that may include a connector412and a printed circuit board415. The housing may be made of any suitable material including, but not limited to, aluminum, titanium, plastic (e.g. POM, ABS, etc.), any material, or any combination thereof. In certain embodiments, the connector412may be a female RCA connector, a ¼ Jack connector, a male RCA connector, a 9V connector, any type of connector, or a combination thereof. In certain embodiments, instead of having the cylindrical shaped structure117(or other shape) of adapter110, the adapter410may have a configuration to receive other types of plugs designs for different power cables150. The configuration may be a receptacle as shown inFIG.4A-Band/or any type of structure that can accommodate any type of plug design of a power cable. The connector412may couple and connect with the power cable150(seeFIGS.13A,13B,13C,13D,13E,13F,13G,13H,13I, and13J), which may connect with a power supply160that may deliver power to the adapter410via the power cable150. In certain embodiments, the adapter410may include one or more grooves411, which may enable a user to securely grab onto the adapter410, such as when connecting the adapter410to the tattoo machine portion430. In certain embodiments, the printed circuit board415of the adapter410may be utilized to transfer power from a connected power cable150when the adapter410is connected to the tattoo machine portion430to the motor440of the tattoo machine400. In certain embodiments, the printed circuit board415may include an internal circuit that may be utilized to ensure that the power delivered to the motor440of the tattoo machine portion430has the correct polarity, irrespective of the input polarity. In certain embodiments, the printed circuit board415of the adapter410may include a custom-designed plating that makes contact with pins on the motor440when the adapter410is connected to the tattoo machine portion430. Connecting the adapter410to the tattoo machine portion430may be similar to connecting adapter110to the tattoo machine portion130. In particular, in order to connect the adapter410to the tattoo machine portion430, a user may align a first portion418of the adapter410with the receptacle437of a tattoo machine portion430. The user may then insert the first portion418of the adapter410axially into the receptacle437. Once inserted, the user may twist the adapter, such as in a clockwise motion (or other suitable and/or desired motion). The twisting motion may cause one or more extruded features113of the first portion418of the adapter410to contact one or more ledges114of the tattoo machine portion430. Once contact between the one or more ledges114and the one or more extruded features113is made, an o-ring (or other similar device) of the adapter410may be squeezed between the adapter410and the body of the tattoo machine portion430(via the receptacle437) such that a pulling force may be generated on each of the extruded features113to cause the adapter410to lock into place with the receptacle437of the tattoo machine portion430. The user may then connect one end of the power cable150to the power supply160and the other end155to the connector412. The power supply160may then provide power to the adapter410, which may then deliver the power to the motor440of the tattoo machine portion430so that the tattoo artist may utilize the tattoo machine400to apply ink to a tattoo recipient. Referring now also toFIG.14, another embodiment of a tattoo machine500is schematically illustrated. The tattoo machine500may include any of the components of the tattoo machines100,400, along with any other desired components. In certain embodiments, the tattoo machine500may include a specialized grip531, which may include one or more grooves540(or dimples, notches, indentations, or structures). The grooves540may be utilized to enhance a user's grip onto the grip531, reduce the weight of the grip531and/or tattoo machine500, and tattoo machine ergonomics. AlthoughFIGS.1A-15illustrates specific example configurations of the various adapters110,410, tattoo machine portions130,140, and tattoo machines100,400, these devices may include any configuration of the components, which may include using a greater or lesser number of the components. For example, the adapters110,410, the tattoo machine portions130,140, the tattoo machines100,400, and/or any of the other components shown inFIGS.1A-14may include any number extruded features113, ledges114, receptacles137,437, connectors112,412, grips131,431, receptacle135,435, connectors112,412, motors140,440, printed circuit boards115,415, and/or any number of other components. Additionally, components of tattoo machine100may be utilized with components of tattoo machine400and vice versa. Additionally, the power cable150may be configured to connect with any type of power source, such as via a port/socket of the footswitch180, which may be connected to another power source. A user may use the footswitch180to control the voltage delivered to the tattoo machines100,400, such as by depressing pedals/buttons/controls on the footswitch180with the user's feet. Other intermediary devices instead of a footswitch180may also be utilized to deliver power to the tattoo machines100,400. Notably, as shown inFIG.15, an exemplary method1500for utilizing an adapter (e.g. adapter110,410) with a tattoo machine (e.g.100,400) is schematically illustrated. The method1500may include, optionally, at step1502, removing a battery pack, such as a wireless battery pack from a tattoo machine, such as tattoo machine100and/or400. At step1504, the method1500may include aligning a first portion of the adapter with a receptacle of the tattoo machine. The method1500may proceed to step1506, which may include inserting the first portion of the adapter axially into the receptable of the tattoo machine. At step1508, the method1500may include twisting the adapter until at least one extruded feature of the first portion of the adapter contacts a ledge of the tattoo machine. At step1510, the method1500may include determining if the at least one extruded feature has contacted the ledge of the receptacle of the tattoo machine. If not, the method1500may revert back to step1508until the at least one extruded feature has contacted the ledge of the tattoo machine. If so, the method1500may proceed to step1512, which may include locking the adapter onto the receptacle of the tattoo machine so that the adapter and the tattoo machine are combined. At step1514, the method1500may include connecting a first end of a power cable to a connector of the adapter (e.g. second portion416). At step1516, the method1500may include connecting a second end of the power cable to a power supply for delivering power to the tattoo machine via the adapter. At step1518, the method1400may include delivering the power to the tattoo machine via the adapter while ensuring a correct polarity for the power. A user may then use the operable tattoo machine to apply ink to the skin of a user. Notably, the method1500may further incorporate any of the features and functionality described herein. The illustrations of arrangements described herein are intended to provide a general understanding of the structure of various embodiments, and they are not intended to serve as a complete description of all the elements and features of apparatus and systems that might make use of the structures described herein. Other arrangements may be utilized and derived therefrom, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Figures are also merely representational and may not be drawn to scale. Certain proportions thereof may be exaggerated, while others may be minimized. Accordingly, the specification and drawings are to be regarded in an illustrative rather than a restrictive sense. Thus, although specific arrangements have been illustrated and described herein, it should be appreciated that any arrangement calculated to achieve the same purpose may be substituted for the specific arrangement shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments and arrangements of the invention. Combinations of the above arrangements, and other arrangements not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description. Therefore, it is intended that the disclosure not be limited to the particular arrangement(s) disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments and arrangements falling within the scope of the appended claims. The foregoing is provided for purposes of illustrating, explaining, and describing embodiments of this invention. Modifications and adaptations to these embodiments will be apparent to those skilled in the art and may be made without departing from the scope or spirit of this invention. Upon reviewing the aforementioned embodiments, it would be evident to an artisan with ordinary skill in the art that said embodiments can be modified, reduced, or enhanced without departing from the scope and spirit of the claims described below. | 16,712 |
11857750 | DETAILED DESCRIPTION Some embodiments of the invention are configured to accomplish long term dialysis access with the use of ports or gateways into the vascular system that do not comprise indwelling catheters. Some embodiments can advantageously eliminate central venous scarring and subsequent stenoses or occlusions. The risk of infection can also be mitigated due to the lack of an indwelling catheter within the vascular system. Currently, there are no commercially available devices that offer percutaneous long term dialysis access in this method without an indwelling catheter. Conventional surgically placed fistulae and grafts are sewn on to arteries and veins and subsequently do not have indwelling catheters within the system. However, one issue with these fistulae and grafts is that they thrombose quite often, thus requiring “declotting” or thrombectomy interventions. Another issue with these is that they develop other complications, such as outflow vein stenoses, pseudoaneurysms, and even infections. All of these place an enormous burden on the healthcare system for urgent or emergent repair. Some embodiments of the invention can eliminate this by employing one or more valves that seal the device from blood flow when the device is not in use for vascular access, such as dialysis. Additionally, if the device does get infected, which is much less likely than conventional catheters, the subsequent reaction can be much more tolerable than an indwelling infected line, which leads to a more robust immune response, sepsis, and possibly death. Some embodiments can be utilized in inpatient and outpatient facilities, including hospitals, ambulatory surgical centers, and outpatient dialysis centers. The devices can be utilized by nephrologists and vascular specialists including vascular surgeons and interventional radiologists, and advantageously improve patient satisfaction, cost containment, and improved outcomes. In some embodiments, a system includes a vascular and/or luminal access device with a low profile intra-vascular/intraluminal device. The vascular and/or luminal access device can have a low profile state or resting state. The vascular and/or luminal access device can expand to a desired diameter for use. The vascular and/or luminal access device can have an expanded or active state. In some embodiments, the access has an intraluminal component contiguous with or attached to the extraluminal/subcutaneous component. In some embodiments, intra-vascular elements/components may be catheter tubing or flexible shape memory material, metallic, plastic, or other blended materials such as nitinol and/or silicone. The intra-vascular elements/components can act as a gateway element including a lumen or guide (lumen-guide) for catheters to pass through. The gateway element or lumen-guide can act as a conduit for one or more conduits or other medical devices to pass though it to a desired point in the vessel or body lumen. The material of the lumen-guide is expandable, hence in resting state (lumen-guide without a catheter going through it) it has a fraction of the diameter of the active state (lumen-guide with one or more devices passing through it). Some embodiments can include three main features, although more or less features can be included in certain systems and methods. FIGS.1A-1Dschematically illustrates an embodiment of a luminal access system100. The luminal access system100can have any features of any system described herein. The luminal access system100can include a port102. The port102can be an external port. The port102can be under the skin of the patient. The port102can be an internal port. The port102can be above the skin of the patient. The port102can have a normally open state. The port102can have a normally closed state. In the illustrated embodiment, the port102is below the skin of the patient. The port102can include a lumen104. The port102can be positioned near the treatment site. The port102can be positioned near the vein to be treated. The port102can be positioned near the artery to be treated. The port102can be at or near the treatment site. The port can be within a distance of the treatment site, wherein the distance is 1 cm, 2 cm, 3 cm, 4 cm, 5 cm, 6 cm, 7 cm, 8 cm, 9 cm, 10 cm, 11 cm, 12 cm, 13 cm, 14 cm, 15 cm, 16 cm, 17 cm, 18 cm, 19 cm, 20 cm, between 1 cm and 10 cm, between 3 cm and 9 cm, between 1 cm and 5 cm, between 5 cm and 12 cm, or any range of two of the foregoing values. The luminal access system100can include a conduit110. The conduit110can be catheter tubing. The conduit110can be flexible shape memory material. The conduit110can comprise metal, plastic, or other blended materials such as nitinol and/or silicone. The conduit110can include a lumen112. The conduit110can connect directly or indirectly to the port102. The conduit104can have a short length. The conduit110can have a length of 1 cm, 2 cm, 3 cm, 4 cm, 5 cm, 6 cm, 7 cm, 8 cm, 9 cm, 10 cm, 11 cm, 12 cm, 13 cm, 14 cm, 15 cm, 16 cm, 17 cm, 18 cm, 19 cm, 20 cm, between 1 cm and 10 cm, between 3 cm and 9 cm, between 1 cm and 5 cm, between 5 cm and 12 cm, or any range of two of the foregoing values. The conduit110can have a diameter of 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mcm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, between 1 mm and 10 mm, between 4 mm and 6 mm, between 3 mm and 7 mm, or any range of two of the foregoing values. The conduit110can span the length between the port102and the treatment site. The conduit110can include a sidewall114. The luminal access system100can include a one-way valve120. The one-way valve120can be at the distal of the conduit110. The one-way valve120can be proximate the distal of the conduit110. The one-way valve120can be along the length of the conduit110. The one-way valve120can allow the flow of material in one direction but prevent the flow of material in another direction. The one-way valve120can allow passage in one direction but prevent passage in another direction. The one-way valve120can allow material to flow into the treatment site, but not out of the treatment site. The luminal access system100can include a gateway element130. The gateway element130can be an expandable shape memory fixture. The gateway element130can be cylindrical. The gateway element130can any other shape. The gateway element130can be coupled to an end of the conduit110. The gateway element130can include one or more anchoring elements132. The gateway element130can include a pair of anchoring elements132. The anchoring elements132can sandwich the vessel wall from both sides in order to secure the conduit110in place. The anchoring elements132can be positioned on opposite sides of the vessel wall. The vessel wall can be disposed between the anchoring elements132. The gateway element130can be attached to or otherwise associated with the outer diameter of the one or more conduits110. The gateway element130can house a length of the conduits110in a lumen of the gateway element130therethrough. In some embodiments, the gateway element130can include one or more of an intravascular component and an extravascular component. The anchoring elements132can be positioned on either side of the vessel. The anchoring elements132are configured to fix the conduit110in place to the blood vessel wall by “sandwiching” the blood vessel wall. The gateway element130can take any desired geometry sufficient to fixate the catheter to the blood vessel wall. In some embodiments, the gateway element130can take the form of a plurality of movable arms, hooks, or barbs. In some embodiments, the gateway element130can take the form of a plurality of movable arms, hooks, or barbs that can extend substantially orthogonal to, or at other angles with respect to the longitudinal axis of the conduit110. The gateway element130can be penetrating or non-penetrating with respect to the target vessel wall. The conduit110can include a tip116. The tip116of the conduit110can extend slightly into the vessel, vein, artery, or other treatment site. The tip116of the conduit110can extend such as about 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, or any range of two of the foregoing values, or other dimensions as described herein. The luminal access system100can include the port102, the conduit110, the one-way valve120at or proximate the distal end of the conduit, and a shape memory fixture or gateway element130that can be cylindrical or other shapes, and sandwiches the vessel wall from both sides in order to secure the catheter in place. Some embodiments can include an implantable port102or other gateway underneath the skin that can have a domed, bubble, or other geometry that can be easily palpable for access by a health care professional, such as dialysis nurses for example. The port102or gateway can be made, for example, of a synthetic polymer that is durable and resistant to multiple needle sticks and can be replaced with a minor surgical procedure as needed, such as, e.g., every 5-10 years. In some embodiments, the port102can be made of a self-sealing material such as silicone. The port102can be free-floating. The port102can be sutured or otherwise anchored under the skin. In some embodiments, the port102can be a removable port positioned outside of the skin/body, such as a removable mushroom cap-shaped port. The port102can be a removable port with a locking feature, such as screw threads or a snap feature, for example. Another feature of certain systems and methods include one, two, or more conduits110. Another feature of certain systems and methods include one, two, or more valves120per conduit110. The first valve120can be present, for example, at the luminal, e.g., vascular entry point configured so as not to allow blood flow when the device is not in use. The valve120can be present near or at the distal end of the conduit110, and proximate the luminal entry point or the tip116. The valve120could be of a variety of types, including but not limited to pinch, sliding, duckbill, or miter valves. A second valve120can be present, for example, at or near the proximal end of the conduit110, either outside the body or subcutaneous when the system is implanted. The conduit110can comprise a single fluid flow path. The conduit110can comprise a plurality (e.g., 2, 3, or more) of fluid flow paths (e.g., multiple conduits). The conduit110can include coaxial fluid flow paths. The conduit110can include non-coaxial fluid flow paths. For example, a first conduit110, e.g., fluid flow path can be configured for inflow into a lumen of the body, and a second conduit110, e.g., fluid flow path can be configured for outflow out of a lumen of the body (e.g., for hemodialysis applications). In some embodiments, each fluid flow path can comprise the same diameter. In some embodiments, one fluid flow path can have a larger diameter than another fluid flow path. In some embodiments, each conduit110can each comprise proximal and/or distal valves120. For example, an embodiment with two conduits110can include two valves120for each conduit for a total of four valves120. The conduits110can include luer lock or other mechanisms associated with the proximal end/valves. FIGS.2A-2Cschematically illustrates an embodiment of a luminal access system200. The luminal access system200can have any features of any system described herein. The luminal access system200can include an expandable and/or contractible gateway element250. The gateway element250can be, for example, a shape memory element. The gateway element250can be a nitinol fixture at the vascular entry site. The gateway element250can be designed in order to secure a conduit260to the blood vessel without the need for an open surgical anastomosis. The gateway element250can be configured to expand and contract. The gateway element250can be configured to radially expand and contract. The gateway element250can be configured to radially expand and contract about a midpoint or centerline. The gateway element250can be configured to radially expand and contract about an offset axis. The gateway element250can include a lumen252. The gateway element250can comprises a shape memory material. The term “shape memory material” is used herein to refer to materials which recover from a deformed shape to a pre-formed shape. The shape memory material can be, for example, a shape memory alloy, a shape memory steel alloy or shape memory polymer. In some embodiments, the shape memory material can be Nitinol. In other embodiments, the shape memory material can be a shape memory polymer. Shape-memory polymers can include, e.g. polyurethanes, polyethylene terephthalate (PET), polyethylene oxides (PEO) or block copolymers containing a silicone segment. The gateway element250can have a length of 1 cm, 2 cm, 3 cm, 4 cm, 5 cm, 6 cm, 7 cm, 8 cm, 9 cm, 10 cm, 11 cm, 12 cm, 13 cm, 14 cm, 15 cm, 16 cm, 17 cm, 18 cm, 19 cm, 20 cm, between 1 cm and 10 cm, between 3 cm and 9 cm, between 1 cm and 5 cm, between 5 cm and 12 cm, or any range of two of the foregoing values. The gateway element250can have a diameter of 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mcm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, between 1 mm and 10 mm, between 4 mm and 6 mm, between 3 mm and 7 mm, or any range of two of the foregoing values. The gateway element250can be attached to one or more conduits260. The gateway element250can be otherwise associated with one or more conduits260. The gateway element250can receive the outer diameter of the one or more conduits260. and The gateway element250can house a length of the conduits260in the lumen252of the gateway element250therethrough. The gateway element250can be a shape memory fixture. In some embodiments, the gateway element250can include one or more of an intravascular component and an extravascular component. The gateway element250can include an intravascular component. The gateway element250can include an extravascular component. The luminal access system200can include anchors or anchoring structures configured to fix the conduits260in place to the blood vessel wall by “sandwiching” the tissue, a vessel, and/or a subcutaneous tract. The luminal access system200can include any anchoring element as described herein. In some embodiments, the gateway element250can take the form of a generally tubular, such as a cylindrical shape. In some embodiments, the gateway element250can take the form of an hourglass-like shape with larger end diameters and a smaller diameter more centrally. The gateway element250can take any desired geometry sufficient to fixate the catheter to the tissue, the blood vessel wall, and/or a subcutaneous tract. In some embodiments, the gateway element250can take the form of aa plurality of movable arms, hooks, or barbs. In some embodiments, the gateway element250can take the form of a plurality of movable arms, hooks, or barbs that can extend substantially orthogonal to, or at other angles with respect to the longitudinal axis of the conduit260and/or gateway element250. The gateway element250can be penetrating or non-penetrating with respect to the tissue, target vessel wall, and/or the subcutaneous tract. In some embodiments, the conduit260can also comprise a shape memory material. In some embodiments, the gateway element250can be configured to be radially expanded actively or passively. The gateway element250could be radially expanded passively by introduction of larger catheters/sheaths/devices within the lumen252of the gateway element250. The gateway element250can be radially expanded passively by introduction of larger catheters/sheaths/devices within the conduits260. The gateway element250can be radially expanded via an external control element/knob incorporated into a hub of the proximal port270. The gateway element250can be radially expanded by a mechanical expansion mechanism. The gateway element250can be radially expanded by an inflatable balloon configured to exert a force on a sidewall of the gateway element250, and the like. The gateway element250can be radially expanded to allow for flow into and/or out of the conduits260within the gateway element250. The gateway element250can be radially expanded to allow other medical devices to pass through the gateway element250into the target vessel. When use is complete, in some embodiments, the other medical device or other expander can be removed and the gateway element250can contract to its unstressed smaller-diameter configuration. When use is complete, in some embodiments, the control element can be actuated to effect transformation of the gateway element250to the smaller diameter configuration. The gateway element250can have a normally closed or contracted state. The gateway element250can have a closed shape memory state. The gateway element250can prevent the flow of material when closed. The gateway element250can be actively expanded. The gateway element250can be passively expanded. The gateway element250can be expanded by insertion of the conduits260, a mechanical expander, or other medical tools. The gateway element250can be contracted by removal of the conduits260, a mechanical expander, or other medical tools. The gateway element250can be expanded by insertion of tools or other devices through the lumen252of the gateway element250. The gateway element250can be contracted by removal of tools or other devices through the lumen252of the gateway element250. In some embodiments, the blood vessel accessed is a vein or an artery. The vein could be, in some cases, an internal jugular vein, external jugular vein, superior vena cava, subclavian vein, brachiocephalic vein, axially vein, basilic vein, cephalic vein, brachial vein, inferior vena cava, iliac vein, or femoral vein. In some embodiments, the system can be positioned within a chamber of the heart, such as the right atrium, for example. In some embodiments, the system can be positioned near the treatment site. The system can be positioned to reduce the length the gateway element250. In some embodiments, only a very short segment of length of the distal end of the conduit(s)260and/or the gateway element250, such as the distal tip, resides within the target lumen long-term. The length of conduit260actually within the target lumen when implanted can be, for example, less than about 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, 2 mm, 1 mm, or less, or ranges including any two of the foregoing values. The length of conduit260actually within the target lumen when implanted can be, for examples, less than about 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or even less of the total axial length of the catheter, or ranges including any two of the foregoing values. The length of gateway element250actually within the target lumen when implanted can be, for example, less than about 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, 2 mm, 1 mm, or less, or ranges including any two of the foregoing values. The length of gateway element250actually within the target lumen when implanted can be, for examples, less than about 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or even less of the total axial length of the catheter, or ranges including any two of the foregoing values. In some embodiments, only the shape memory component of the gateway element250resides in the target lumen when not being used. In some embodiments, a shorter axial segment of conduit260resides in the target lumen when not being used (compared with the shape memory element). In some embodiments, the total axial length of the conduit(s)260and/or the gateway element250can be, for example, about, at least about, or no more than about 2 cm, 3 cm, 4 cm, 5 cm, 6 cm, 7 cm, 8 cm, 9 cm, 10 cm, 11 cm, 12 cm, or ranges including any two of the foregoing values. In some embodiments, the diameter of the conduit260and/or the gateway element250(in either an expanded or reduced configuration) can be, for example, about, at least about, or no more than about 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 25 mm, 30 mm, 35 mm, or more or less, or ranges including any two of the foregoing values. In some embodiments, the gateway element250can radially expand (or contract) by, for example, about, at least about, or no more than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 125%, 150%, 175%, 200%, or more or less, or ranges including any two of the foregoing values. In some embodiments, the gateway element250has a diameter that is about, or less than about 50%, 40%, 30%, 20%, 10%, 5%, 4%, 3%, 2%, 1%, or less of the diameter of the target vessel in its radially reduced and/or unstressed state, such that it has a minimal footprint in the target vessel when not being used. In some embodiments, the gateway element250and/or the conduit260can comprise one, two, or more therapeutic agents, such as drugs (e.g., coated to the distal end of the conduit). The drug could include, for example, an anti-thrombotic agent such as heparin, warfarin, fragmin, danadparoid, enoxaparin, tinzaparin, or fondaparinux. In some embodiments, the drug could include an antibiotic agent. In some embodiments, a diagnostic and/or therapeutic medical device can be attached or otherwise associated with the gateway element, such as a sensor and/or a drug delivery element, for example. FIG.2Aschematically illustrates an embodiment of the luminal access system200post-implantation. Illustrated are a proximal port270. The proximal port270tcan include a removable cap272. The luminal access system200can include a plurality of conduits260, each with valves280near each conduit's proximal end and distal end. The valve280can be a one-way valve. Each conduit260can have one or more valves280. The gateway element250can be a shape memory conduit. The proximal port270can be outside of the patient as shown, or partially or entirely subcutaneous in other embodiments. The cap272can be removable. The cap272can be a re-sealable barrier in other embodiments, such as subcutaneous embodiments, and accessed with aseptic techniques to ensure sterility. The gateway element250can span a subcutaneous tract between the skin surface (or above the skin surface) and the target lumen (e.g., a vascular lumen, such as a vein). The vein is also shown. The direction of blood flow can be downward as shown by the arrow. The conduits260can be cannulas that direct the flow of materials or tools. The top conduit260can be an arterial cannula. The bottom conduit260can be a venous cannula. The conduit260can have one or more valve280. The gateway element250can be a nitinol conduit. The luminal access system200can include one or more luer locks. The proximal port can include one or more luer locks. The proximal port270can be a removable port mushroom cap272. The proximal port can screw on and off. The skin of the patient is also shown. The gateway element250spans the subcutaneous tract. FIG.2Bschematically illustrates the luminal access system in use for hemodialysis, dialysis or other infusion. The cap272is removed. The luer lock through the proximal valves280breaks lock and creates a flow channel. The cap can be screwed on and off with a technique to maintain sterility. The conduits260are connected to luer lock tubing262. The conduit260are attached to tubing262through the proximal valves280. The top conduit260can be to dialysate, and the bottom conduit can be from dialysate. The arrows show the direction of flow. The luminal access system200can include the first conduit260for outflow (e.g., to dialysate), and the second conduit260for inflow (e.g., to dialysate), with luer lock or other tubing serving as the conduits. The gateway element250can be radially expanded passively or actively as noted above to allow flow to and/from the target vessel. The gateway element250can be radially contracted following use to occlude the subcutaneous tract. In some embodiments, the gateway element250can self-expand. In some embodiments, the gateway element250can self-contract. FIG.2Cschematically illustrates replacement of a malfunctioning or aged conduit260, while maintaining the gateway element250in place. This can also be utilized to introduce other medical devices or for urgent vascular access without necessarily replacing a conduit260. The gateway element250can be expanded as noted above. A guidewire290can be used to replace the conduit260. The guidewire290can be threaded through the target conduit260into the target vessel, the conduit260removed, a new conduit260(including one or more valves280as noted above) inserted over the guidewire290into the gateway element250, the guidewire290can be withdrawn, and the gateway element250can be transformed back to the radially reduced configuration to occlude the subcutaneous tract. The conduit260can have over the wire removal. The new conduit260can be introduced over the guide wire290. The gateway element250shifts to pack the dead space and becomes occlusive. In some embodiments, a luminal access system200may include a single, or a plurality of conduits260that can be used for therapeutic infusions (e.g., chemotherapy or other long-term infusion) and/or blood draws. FIG.3Aschematically illustrates another embodiment of a luminal access system300. The luminal access system300can have any features of any system described herein. The luminal access system300can include a gateway element350. The luminal access system300can include a single port370. The luminal access system300can include a plurality of cutaneous and/or subcutaneous ports370. The port370can be locate at a proximal end of the gateway element350. The gateway element350can serve as a conduit itself. The gateway element350can include one, two, three, or more discrete conduits within a lumen352of the gateway element350. At least part of the gateway element352(e.g., at least, or only, an intravascular segment) can include a radially contracted configuration as shown, which can passively or actively radially expand as previously described. In some embodiments, only about, at least about, or no more than about the distal-most 10 cm, 9 cm, 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3 cm, 2 cm, 1 cm, or more or less (or ranges including any two of the foregoing values) of the gateway element350is subject to radial change or expansion by about or at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, 100%, 125%, 150%, 175%, 200%, or more or less (or ranges including any two of the foregoing values). In some embodiments, a portion of the gateway element350is not subject to radial change or expansion. The gateway element350can serve as a vascular window. The luminal access system300can include an external component, hub, or port370. The gateway element350can be an expandable, intraluminal component. The gateway element350can be made of shape memory material. The gateway element350can be coated with non-thrombogenic material. The gateway element350can be coated with a polymer or silicon. The gateway element350can be expanded by insertion of a device through it. The gateway element350can be expanded by actuating the expanding mechanism at the external hub or port370. The gateway element350can have a length of 1 cm, 2 cm, 3 cm, 4 cm, 5 cm, 6 cm, 7 cm, 8 cm, 9 cm, 10 cm, 11 cm, 12 cm, 13 cm, 14 cm, 15 cm, 16 cm, 17 cm, 18 cm, 19 cm, 20 cm, between 1 cm and 10 cm, between 3 cm and 9 cm, between 1 cm and 5 cm, between 5 cm and 12 cm, or any range of two of the foregoing values. The gateway element350can have a diameter of 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mcm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, between 1 mm and 10 mm, between 4 mm and 6 mm, between 3 mm and 7 mm, or any range of two of the foregoing values. The gateway element350can act as a conduit for introduction of devices into the body or vasculature. The gateway element350can be radially expanded passively by introduction of larger catheters, sheaths, expander, and/or devices within the lumen352of the gateway element350. The gateway element350can be radially expanded via any mechanism described herein. The gateway element350can be radially expanded to allow other medical devices to pass through the gateway element350into the body or vessel. When use is complete, in some embodiments, the other medical device or other expander can be removed and the gateway element350can contract to its unstressed smaller-diameter configuration. The gateway element350can have a normally closed or contracted state. The gateway element350can be hollow. The gateway element350can include the lumen352as shown. In other embodiments, the gateway element350can be solid. The gateway element350can be a wire. The gateway element350can be fixated extravascularly. The gateway element350can be fixated to subcutaneous tissues. The gateway element350can be fixated outside to the skin. FIG.3Billustrates an embodiment of the gateway element350that includes a shape memory frame overlying at least a portion of the inner lumen352, which could be a conduit per se as previously described. The gateway element350can alternatively house discrete conduits within the inner lumen352, such as conduits260. In some embodiments, the inner lumen352is defined by the shape memory frame of the gateway element350without any separate inner layers of non-shape memory materials. The shape memory frame of the gateway element350can include interstices as shown. The inner lumen352could be made of non-shape memory materials, including silicone, polymers, plastic, PTFE, ePTFE, and other biocompatible catheter and graft materials, for example. Radial expansion of the shape memory frame of the gateway element350can occur passively or actively as previously described, with corresponding expansion of the inner lumen352. Following removal of a medical device placed within the inner lumen352to expand the gateway element350and/or actuation of a control element, the shape memory frame of the gateway element350can radially contract, in turn radially contracting the inner lumen352and decreasing the profile and/or inhibiting flow within the gateway element350. In some embodiments, the shape memory frame of the gateway element350extends radially outward of, and over an axial length of about, at least about, or no more than about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or more or less of the entire gateway element350, including ranges including any two of the foregoing values. FIG.3Cschematically illustrates a wall pattern of a shape memory frame of the gateway element350in an unstressed, radially contracted state, including longitudinal struts354interconnected by crossing struts356defining interstices358therebetween.FIG.3Dschematically illustrates the wall pattern ofFIG.3Cin an expanded configuration, illustrating the longitudinal struts354′ taking a sinusoidal pattern, intersecting crossing struts356′ and enlarged interstices358′ therebetween. Various other wall patterns can also be utilized depending on the desired clinical result. The gateway element350can include a shape memory frame that can be coated with, for example, a non-thrombogenic material such as a polymer, silicone, etc. The shape memory frame can overlie and at least partially overlap with an inner lumen as described elsewhere herein. Various other modifications, adaptations, and alternative designs are of course possible in light of the above teachings. Therefore, it should be understood at this time that within the scope of the appended claims the invention may be practiced otherwise than as specifically described herein. It is contemplated that various combinations or subcombinations of the specific features and aspects of the embodiments disclosed above may be made and still fall within one or more of the inventions. Further, the disclosure herein of any particular feature, aspect, method, property, characteristic, quality, attribute, element, or the like in connection with an embodiment can be used in all other embodiments set forth herein. Accordingly, it should be understood that various features and aspects of the disclosed embodiments can be combined with or substituted for one another in order to form varying modes of the disclosed inventions. Thus, it is intended that the scope of the present inventions herein disclosed should not be limited by the particular disclosed embodiments described above. Moreover, while the invention is susceptible to various modifications, and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should be understood, however, that the invention is not to be limited to the particular forms or methods disclosed, but to the contrary, the invention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the various embodiments described and the appended claims. Any methods disclosed herein need not be performed in the order recited. The methods disclosed herein include certain actions taken by a practitioner; however, they can also include any third-party instruction of those actions, either expressly or by implication. For example, actions such as “inserting a needle through a subcutaneous port” includes “instructing the inserting a needle through a subcutaneous port.” The ranges disclosed herein also encompass any and all overlap, sub-ranges, and combinations thereof. Language such as “up to,” “at least,” “greater than,” “less than,” “between,” and the like includes the number recited. Numbers preceded by a term such as “approximately”, “about”, and “substantially” as used herein include the recited numbers (e.g., about 10%=10%), and also represent an amount close to the stated amount that still performs a desired function or achieves a desired result. For example, the terms “approximately”, “about”, and “substantially” may refer to an amount that is within less than 10% of, within less than 5% of, within less than 1% of, within less than 0.1% of, and within less than 0.01% of the stated amount. | 34,329 |
11857751 | Like reference numerals refer to like parts throughout the several views of the drawings. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT As represented in the accompanying drawings, the present invention is directed to a closure assembly, generally indicated as10. With initial reference toFIGS.1to4, the closure assembly10is illustrated in a first embodiment and comprises a tip cap12including an access opening14and a closed oppositely disposed end16. When operatively disposed in an intended manner, the tip cap12is positioned in enclosing relation to a discharge port100of a medical dispenser102. The versatility of the closure assembly10is such that it can be used to close the discharge port of different types of medical dispensers. However, for purposes of clarity, the medical dispenser102, represented throughout at leastFIGS.1-4, is a prefilled syringe, and may include an oral syringe. As such, the discharge port100includes, but is not necessarily limited to, a nozzle104, a flow channel105within the nozzle104and a terminal opening106formed in the outer end of the nozzle104, through which the contents of the syringe102pass, upon exiting the interior of the medical dispenser or syringe102. In the partially assembled, operative disposition ofFIG.1, the tip cap12is not necessarily disposed in direct sealing engagement with the discharge port100. Further, one feature of the tip cap12is interiorly dimensioned to accommodate any one of a plurality of discharge ports, which have a sufficiently smaller dimension to fit within the interior of the tip cap12. Therefore, the tip cap12is dimensioned to define a removable, slip-fit attachment to the discharge port100. Further, the tip cap12is preferably formed of a material having sufficient flexibility to be disposed, minimally deformed and/or forced into sealing engagement with the discharge port100, once it is positioned in the operative disposition ofFIGS.1,3and4. Moreover, the flexibility of the tip cap12should be sufficient to allow it to be “squeezed” inwardly as schematically illustrated by arrows200representing a squeezing force, into sealing engagement with the exterior of the discharge port100, when the outer clamping or deformation force200is applied to the exterior of the tip cap12. In order to establish a fluid sealing connection between the inner surface of the tip cap12and the outer surface of the discharge port100and/or nozzle104, the material from which the tip cap12is formed may also be accurately described as “elastomeric”. The “elastomeric” capabilities of the tip cap12facilitate it being squeezed or at least minimally deformed inwardly into the aforementioned fluid sealing engagement with the exterior of the discharge port100, concurrent to the exterior clamping force200being exerted on the exterior of the tip cap12. As such, the fluid sealing engagement between the tip cap12and the discharge port100of the medical dispenser102may be more specifically and accurately described as the inner surface of the tip cap12being disposed in a forced and/or clamped, fluid sealing engagement with the exterior surface of the discharge port100. As set forth above, a related feature of the embodiment ofFIGS.1-4includes its structural dimensioning to have a sufficient interior dimension to be used with and disposed in sealing engagement with discharge ports of different lesser dimensions. The flexibility and/or elastomeric capabilities of the tip cap12further enhance its versatile use, by further facilitating it being mounted on discharge ports100of different smaller dimensions. Therefore, the tip cap12is removably mounted, by virtue of a slip-fit attachment, as represented inFIG.1, in enclosing relation to any one of a possible plurality of discharge ports having a lesser outer dimension, than the interior dimension of the tip cap12. Therefore, the removable slip-fit attachment of the tip cap12on the discharge port100and/or nozzle104thereof is facilitated because of the above noted preferred dimensioning as well as its flexible, elastomeric characteristics. Accordingly, in order to establish the inwardly directed, squeezing and/or clamping force200on the exterior of the tip cap12, the closure assembly10of the present invention includes a retainer. As represented inFIGS.2-4, one embodiment of the retainer is generally indicated as20and may include a substantially clamshell-like structural configuration. Moreover, the clamshell structuring of the retainer20includes two segments22and24pivotally or movably connected by a hinge segment26therefore, the retainer segments22and24may be selectively disposed from the open position ofFIG.2, to the closed position as represented inFIGS.3and4. As should be apparent, when in the open orientation ofFIG.2, the retainer20may be disposed in surrounding, enclosing relation to the exterior of the tip cap12, concurrent to the tip cap12disposed in surrounding relation to the discharge port100. When operatively disposed, the retainer may then be selectively positioned in the closed orientation ofFIGS.3and4. Additional structural features of the retainer20are represented in at leastFIG.2and include a clamping structure25comprising at least one rib member27. The rib member27includes a plurality of at least two clamping rib sections28. Each of the clamping rib sections28is formed on the interior surface of a different one of the two retainer segments22and24, in substantially opposing relation to one another. Further, each of the two clamping rib sections28extend outwardly from the respective interior surfaces of the retainer segments22and24and are movable therewith between the open and closed orientations. As further represented inFIG.2, each clamping rib section28includes an irregular surface configuration28′. Also, the retainer20includes a locking connection or fixtures30and30′ which are cooperatively structured to fixedly engage one another and thereby maintain and lock the retainer20in the closed orientation. Also, when in the closed orientation the retainer20includes an open end defined by the open ends29of the retainer segments22and24. As a result, when in the locked, closed orientation access to the tip cap12, while it is enclosing the discharge port12, cannot be accomplished without a breaking, damaging or destroying the retainer20. Maintenance of the retainer20in the closed orientation may be further facilitated by a ramp and recess structure32and34respectively formed on the different retainer segments22and24. With primary reference toFIGS.3and4, when in the locked, closed orientation, the retainer20exerts the aforementioned inwardly directed squeezing and/or clamping force200on the exterior of the tip cap12. Such a squeezing or clamping force200may be facilitated by structuring the clamping ribs28to define an opening, in which the tip cap12is disposed, having a lesser dimension than that of the access opening29of the retainer20, when in the closed orientation, as clearly represented. Due to the removable, slip-fit connection between the tip cap12and the discharge port and/or nozzle104, access to the contents of the medical dispenser102can only be effectively accomplished by removing the discharge port100from the interior of the tip cap12and the retainer20while the tip cap remains within the retainer. This is accomplished by exerting a separating, pulling force on the medical dispenser102or exterior of the retainer20, or both. However, upon removal of the discharge port100through the access opening29of the retainer and access opening14of the tip cap12, the squeezing and/or clamping force200will continue to be exerted on the exterior of the tip cap12and a capturing of the tip cap12within the retainer20, as represented inFIG.4. This continued exertion of the squeezing and/or clamping force200on the tip cap12will result in an additional inward deformation of the tip cap20and at least a partially closing orientation of the access opening14of the tip cap12. As a result, reinsertion of the discharge port100will be prevented due to the additional inward deformation of the tip cap12and/or closing orientation of the access opening14as clearly represented inFIG.4. Therefore, the tip cap12is disposed in an insertion blocking position, which prevents reinsertion of the discharge port into the interior of the tip cap12. As represented in at leastFIGS.5and6, yet another embodiment of the present invention includes a closure assembly40including a tip cap42comprising an access opening44and an oppositely disposed closed end46. Further, the tip cap42includes an elongated sealing stem48including a free end48′ and a base48″, wherein the base48″ is fixedly or integrally secured to an interior of the closed-end46. The sealing stem48further includes an exterior sealing surface50comprising a progressively increasing outer diameter extending from and between the free end48′ and the base48″ thereof. As a result, a fluid sealing engagement between the tip cap42and the discharge port100of the associated medical dispenser102is accomplished by an insertion of the free end48′ of the sealing stem48into the interior of the flow path105of the discharge port100. The continued advancement of the nozzle104of the discharge port100along the length of the sealing stem48and outer sealing surface50, from the free end48′ towards the base48″, will result in sealing engagement therebetween. In more specific terms, as the sealing stem48advances into the nozzle104through the flow path105, a portion of an exterior of the sealing surface50will eventually come into sealing engagement with a substantially correspondingly dimensioned portion of the discharge port100, such as the terminal opening106. Further, the progressively increasing outer diameter of the exterior sealing surface50of the sealing stem48may be more specifically defined by a plurality of sealing segments52,54,56, etc., collectively disposed along the length of the sealing stem48. It is emphasized that the number of sealing segments52,54,56, etc. may vary in order to increase the versatility of the tip cap42, at least in terms of establishing a fluid sealing engagement with discharge ports of different sizes, configurations, categories, etc. In addition, each of the plurality of sealing segments52,54,56, etc. preferably has a progressively larger outer diameter than the next adjacent, preceding sealing segment, which is closer to the free end48′ of the sealing stem48. Therefore, as the sealing stem48passes into the interior of the flow channel105of the discharge port100, the terminal opening106or other portion of the discharge port100will eventually engage a substantially correspondingly dimensioned one of the plurality of sealing segments52,54,56, etc. When so aligned, the aforementioned fluid sealing engagement between the outer sealing surface50of the sealing stem48and the discharge port100will be established. Therefore, the operative disposition of the tip cap42relative to the discharge port100is its disposition in surrounding substantially enclosing relation to at least a portion of the nozzle104and terminal opening106, as clearly represented inFIG.5. As represented inFIG.6, the closure assembly40of this embodiment may also include structural additions including an outer cover60. The cover60is operatively disposed in enclosing, surrounding relation to the tip cap42and may include an access opening62and a closed end64. Further, the cover60may be structured to have tamper evident characteristics. More specifically, a tab68is frangibly or otherwise removably connected to the cover60, as at70. In cooperation there with, a tether assembly generally indicated as80inFIG.7, may be concurrently disposed in interconnecting relation to the body102′ of the medical dispenser102and the cover60. In more specific terms, the tether assembly80includes an elongated high strength tether82having one end82′ connected to an attachment structure84. The opposite end of the elongated tether82is connected to the cover60via direct attachment to the tab68. The attachment structure84may assume a variety of different structural and operative features which facilitate a fixed, generally non-removable attachment to the body102′ of the medical dispenser102. Further, the attachment structure84may have a fixed, locking connector as at end84′ and/or be adhesively attached to the exterior surface of the body102′ of the medical dispenser102. Also, the length of the tether82relative to the dispositions of the attachment member84and closure assembly40limits or restricts removal of the cover60from the tip cap42without a breaking, cutting, or other destructive removal of the tether82and/or the attachment member84. However, as set forth above, one end82″ of the tether82is removably connected to the cover60via the frangible or removably connected tab68. Due to the high strength material of the tether82and the fixed attachment of the attachment member84to the body102′ of the medical dispenser102, attempted access to the tip cap42and the contents of the medical dispenser102will most probably result in a breakage of the frangible connection70. This, in turn, will result in a disconnection of the tab68and the tether82from the cover60. Such breakage, disconnection or removal of the tab68will provide a clear indication of attempted tampering and/or authorized access to the closure assembly40and contents of the medical dispenser102. Since many modifications, variations and changes in detail can be made to the described preferred embodiment of the invention, it is intended that all matters in the foregoing description and shown in the accompanying drawings be interpreted as illustrative and not in a limiting sense. Thus, the scope of the invention should be determined by the appended claims and their legal equivalents. | 13,844 |
11857752 | DETAILED DESCRIPTION Embodiment of FIGS.1-23 Referring now to the drawings and particularly toFIG.1an injection port assembly is shown and generally designated by the number30. The injection port assembly30may also be referred to as an intermittent needleless connector30. The injection port assembly30includes a body32including a first mating structure34and the second mating structure36configured to be coupled to the first mating structure34. Each of the first and second mating structures34and36may be a separate integrally molded plastic part. The body32has a central body axis38extending from a distal body end40defined on the first mating structure34to a proximal body end42defined on the second mating structure36. The first mating structure34includes an annular wall44defining an open proximal end46of the first mating structure34facing toward the proximal body end42. A male luer connection48includes an axial passage50extending from a distal end40of the male Luer connection which is coincident with the distal end40of the body30. The open proximal end46may also be referred to as a first mating structure proximal end46. Annular wall44may also be referred to as an outer wall44and extends distally past a base52and includes an internal thread45concentric with the male luer connection48. The base52is centered on the body axis38and at least partially blocks the axial passage50. As best seen inFIG.7a plurality of circumferentially spaced ribs54,56,58and60extend from the annular wall44to the base52and define a plurality of transverse passages62,64,66and68between the circumferentially spaced ribs. The transverse passages are communicated with the axial passage50of the male luer connection48. The transverse passages may also be described as bypassing the base52to communicate an inner cylindrical surface108of the first mating structure34with the axial passage50of the male luer connection48. The base52may also be described as spanning the body axis38and being supported from the outer wall44. The base52may also be described as being located axially between the open proximal end46of the first mating structure34and the axial passage50of the male luer connection48. The axial passage50has an inside diameter51. The base52has a base outside diameter53substantially equal to the inside diameter51of the axial passage50of the male luer connection48. The use of the multiple transverse passages62,64,66and68provides a combined flow path from the open proximal end46to the axial passage51that is relatively unrestricted. The passages62,64,66and68have a combined cross-sectional flow area at least as great as, and preferably greater than, the cross-sectional area of the axial passage51. Also the passages62,64,66and68are preferably sloped in a range of from 40 to 60 degrees relative to the longitudinal axis38. In this manner the flow path through the passages62,64,66and68does not restrict the flow of fluids through the injection port assembly30, thus providing what may be referred to as a high fluid flow injection port assembly. The flow path is non-tortuous and the passages62,64,66and68are free of dead ends or spaces that are difficult to flush of blood and other fluids. The second mating structure36includes a female luer connection70configured to receive a male luer fitting72(seeFIGS.1and2). The second mating structure36has an interior71communicating the female luer connection70with the open proximal end46of the first mating structure34. The upper end of the second mating structure36carries an external thread75that can be engaged with a luer-lock connector (not shown). A flexible valve member76is mounted on the base52of the first mating structure34and has a proximal valve end portion78configured to be sealingly received in the female luer connection70of the second mating structure36when the flexible valve member76is in a closed position as seen inFIG.1. The flexible valve member76is configured to be displaced relative to the central body axis38upon entry of the male luer fitting72into the female luer connection70to thereby place the male luer fitting72in communication with the interior71of the second mating structure36. The first mating structure34includes a centering recess80defined in the base52and facing the proximal body end42. The flexible valve member76includes a distal end82having a central protrusion84received in the centering recess80. As is best seen inFIGS.3and4each of the ribs54,56,58and60has a proximal end face such as54f,56f,60fsloping distally from a radially outer end of the rib to a radially inner end of the rib attached to the base52, so that the proximal end faces of the ribs define a tapered guide86for guiding the distal end82of the flexible valve member76into engagement with the base52. The second mating structure36includes an annular radially inner distally facing step88. The open proximal end46of the first mating structure34abuts the distally facing step88of the second mating structure36when the first and second mating structures34and36are coupled together as shown for example inFIGS.1and2. One of the distally facing step88of the second mating structure36and the open proximal end46of the first mating structure34includes a groove90, and the other of the distally facing step88of the second mating structure36and the open proximal end46of the first mating structure34includes an annular ridge92received in the annular groove90to provide a seal between the first and second mating structures34and36. The ridge92may be sized slightly larger than the groove90, and the second mating structure36may have sufficient flexibility about the groove90so that a somewhat resilient mating occurs between the ridge92and groove90. The first mating structure34may also include a radially outer proximally facing step94. An external thread96may be located between the first mating structure proximal end46and the radially outer proximally facing step94. A first annular ratchet portion98may be located between the external thread96and the radially outer proximally facing step94. The second mating structure36includes the previously mentioned distally facing step88and a second mating structure distal end100. An internal thread102may be located between the second mating structure distal end100and the radially inner distally facing step88. A second ratchet portion104may be located between the internal thread102and the second mating structure distal end100. As best seen inFIG.15A, the first annular ratchet portion may include four external ratchet teeth98A,98B,98C and98D. And as best seen inFIG.8, the second annular ratchet portion104may include four internal ratchet teeth104A,104B,104C and104D. The first and second mating structures34and36may be coupled together by engagement of the internal thread102with the external thread96, such that the first and second annular ratchet portions98and104prevent disengagement of the internal thread102from the external thread96after the first and second mating structures34and36are coupled together. The threads96and102provide a threaded connection between the first and second mating structures34and36. The first and second ratchet portions98and104provide a ratchet lock configured to prevent unthreading of the threaded connection after the first and second mating structures34and36are coupled together by the threaded connection. The threaded connection96,102may provide a seal to prevent passage of any fluid that may pass the seal between groove90and ridge92. Additionally, and optionally, an O-ring seal106may be provided between the proximally facing step94and the distal end100. Such an O-ring seal106is schematically illustrated inFIG.2. As best seen in the enlarged view ofFIG.6, the first mating structure34includes an inner cylindrical surface108extending distally from the open proximal end46. The inner cylindrical surface108has a first inner diameter110. The axial passage50of the male luer connection48has a second inner diameter51smaller than the first inner diameter110. The transverse passages62,64,66and68are partially frusto-conical in shape tapering from the first inner diameter110to the second inner diameter51. The details of the flexible valve member76are best seen inFIGS.19-23. The proximal end portion78of flexible valve member76is configured to be sealingly received in the female luer connection70of the second mating structure36. Below the proximal end portion78is a segmented stop surface112configured to abut lower taper73of the second mating structure36to prevent the flexible valve member76from being pushed out of the second mating structure36due to internal pressure. The segmented stop surface may include four segments as seen inFIG.23, separated by gaps such as114. Below segmented stop surface112a relatively large lateral notch116is formed in flexible valve member. Notch116is designed to cause the flexible valve member76to collapse in an asymmetrical manner as schematically represented inFIG.2when the male luer fitting72pushes downward on the flexible valve member76. This causes the flexible valve member76to be displaced laterally relative to the longitudinal axis38when the flexible valve member76is moved from its closed position ofFIG.1to its open position ofFIG.2. The lowermost portion of flexible valve member76tapers at118to the distal end82and the centering protrusion84. The injection port assembly30may be assembled from the first mating structure34, second mating structure36and flexible valve member76substantially as follows. The flexible valve member76may be placed in the second mating structure36with the proximal end portion of the flexible valve member76adjacent or received in the female luer connection70substantially as shown inFIG.1. Then the external threads98of the first mating structure34may be engaged with the internal threads102of the second mating structure36and the threaded connection made up until the ridge92sealingly engages the groove90and the distal end100of second mating structure36bottoms out on the proximally facing step94of the first mating structure34. The ratchet lock provided by the first and second ratchet portions98and104will prevent the threads from disengaging. The first and second annular ratchet portions98and104are preferably arranged such that the second mating structure36bottoms out on the proximally facing step94of the first mating structure34just as the ratchet teeth have reached an engagement position as shown inFIG.8. During the assembly of the first and second mating portions34and36the tapered guide86formed by the sloping faces of the ribs will guide the distal end portion82of the flexible valve76toward the base52so that the central protrusion84is received in the centering recess82. The use of the injection port assembly30is best illustrated inFIGS.1and2. InFIG.1the injection port assembly is shown with the flexible valve member76in a closed position. A male luer fitting72is shown above the injection port assembly30in a position just prior to engaging the flexible valve member76. InFIG.2, the male ler fitting72has been moved downward and engaged with the upper end of the flexible valve member76to displace the flexible valve member76relative to the central body axis38upon entry of the male luer fitting72into the female luer connection70thereby placing the male luer fitting72, and particularly the interior thereof, in communication with the interior71of the second mating structure36. Embodiment of FIGS.24-38 FIGS.24-38illustrate a second embodiment of an injection port assembly generally designated by the numeral130. The injection port assembly130differs from the injection port assembly30in two primary ways. First the manner in which the first and second mating structures are connected together has been changed to a welded connection. Second the design of the flexible valve member has been modified. Referring now to the drawings and particularly toFIG.24an injection port assembly is shown and generally designated by the number130. The injection port assembly130may also be referred to as an intermittent needleless connector130. The injection port assembly130includes a body132including a first mating structure134and the second mating structure136configured to be coupled to the first mating structure134. Each of the first and second mating structures134and136may be a separate integrally molded plastic part. The body132has a central body axis138extending from a distal body end140defined on the first mating structure134to a proximal body end142defined on the second mating structure136. The first mating structure134includes an annular wall144defining an open proximal end146of the first mating structure134facing toward the proximal body end142. A male luer connection148includes an axial passage150extending from a distal end140of the male luer connection which is coincident with the distal end140of the body132. The open proximal end146may also be referred to as a first mating structure proximal end146. Annular wall144may also be referred to as an outer wall144and extends distally past a base152and includes an internal thread145concentric with the male luer connection148. The base152is centered on the body axis138and at least partially blocks the axial passage150. As best seen inFIG.30a plurality of circumferentially spaced ribs154,156,158and160extend from the annular wall144to the base152and define a plurality of transverse passages162,164,166and168between the circumferentially spaced ribs. The transverse passages are communicated with the axial passage150of the male luer connection148. The transverse passages may also be described as bypassing the base152to communicate an inner surface208of the first mating structure134with the axial passage150of the male luer connection148. The base152may also be described as spanning the body axis138and being supported from the outer wall144. The base152may also be described as being located axially between the open proximal end146of the first mating structure134and the axial passage150of the male luer connection148. The axial passage150has an inside diameter151. The base152has a base outside diameter153substantially equal to the inside diameter151of the axial passage150of the male luer connection148. The use of the multiple transverse passages162,164,166and168provides a combined flow path from the open proximal end146to the axial passage150that is relatively unrestricted. The passages162,164,166and168have a combined cross-sectional flow area at least as great as, and preferably greater than, the cross-sectional area of the axial passage150. Also the passages162,164,166and168are preferably sloped in a range of from 40 to 60 degrees relative to the longitudinal axis138. In this manner the flow path through the passages162,164,166and168does not restrict the flow of fluids through the injection port assembly130, thus providing what may be referred to as a high fluid flow injection port assembly. The flow path is non-tortuous and the passages162,164,166and168are free of dead ends or spaces that are difficult to flush of blood and other fluids. The second mating structure136includes a female luer connection170configured to receive a male luer fitting72(seeFIGS.24and25). The second mating structure136has an inner wall169defining an interior171communicating the female luer connection170with the open proximal end146of the first mating structure134. The upper end of the second mating structure136carries an external thread175that can be engaged with a luer-lock connector (not shown). A flexible valve member176is mounted on the base152of the first mating structure134and has a proximal valve end portion178configured to be sealingly received in the female luer connection170of the second mating structure136when the flexible valve member176is in a closed position as seen inFIG.24. The flexible valve member176is configured to be displaced relative to the central body axis138upon entry of the male luer fitting72into the female luer connection170to thereby place the male luer fitting72in communication with the interior171of the second mating structure136. The first mating structure134includes a centering recess180defined in the base152and facing the proximal body end142. The flexible valve member176includes a distal end182having a central protrusion184received in the centering recess180. As is best seen inFIG.29each of the ribs154,156,158and160has a proximal end face such as154f,156f,160fsloping distally from a radially outer end of the rib to a radially inner end of the rib attached to the base152, so that the proximal end faces of the ribs define a tapered guide186for guiding the distal end182of the flexible valve member176into engagement with the base152. The second mating structure136includes an annular radially inner distally facing step188. The open proximal end146of the first mating structure134abuts the distally facing step188of the second mating structure136when the first and second mating structures134and136are coupled together as shown for example inFIGS.24and25. The second mating structure136may also include a cylindrical inner surface300located between the second mating structure distal end200and the radially inner distally facing step188. The distal end200of the second mating structure136may also include a radially outwardly extending lower end face304. The first mating structure134may also include a radially outer proximally facing step194and a cylindrical outer wall surface302located between the proximal end146and the radially outer proximally facing step194. The injection port assembly130may be assembled from the first mating structure134, second mating structure136and flexible valve member176substantially as follows. The flexible valve member176may be placed in the second mating structure136with the proximal end portion of the flexible valve member176adjacent or received in the female luer connection170substantially as shown inFIG.24. Then the cylindrical outer wall surface302of the first mating structure134is closely received in the cylindrical inner surface300of the second mating structure136until the radially outwardly extending lower end face304of the distal end200of the second mating structure136abuts the radially outer proximally facing step194of the first mating structure134. During this assembly the tapered lower end314of the flexible valve member176is guided by guide186into engagement with the base152, so that center protrusion184is received in centering recess180. The assembly is then placed in a sonic welding machine and sonic energy is applied to cause the first and second mating structures134and136to be sonically welded together along the interface between surfaces300and302and along the engagement of the radially outwardly extending lower end face304of the distal end200of the second mating structure136with the radially outer proximally facing step194of the first mating structure134. Any weld slag or other debris generated during the sonic welding operation may be received in an annular groove306which is formed in the radially outer proximally facing step194of the first mating structure134. As best seen inFIG.29, the first mating structure134includes an inner surface208extending distally from the open proximal end46. The inner surface208has a first inner diameter210at its upper end. The axial passage150of the male luer connection148has a second inner diameter151smaller than the first inner diameter210. The transverse passages162,164,166and168are partially frusto-conical in shape tapering from the first inner diameter210to the second inner diameter151. The details of the flexible valve member176are best seen inFIGS.32-38. The proximal end portion178of flexible valve member176is configured to be sealingly received in the female luer connection170of the second mating structure136. Below the proximal end portion178is a segmented stop surface212configured to abut lower taper173of the second mating structure136to prevent the flexible valve member176from being pushed out of the second mating structure136due to internal pressure. The segmented stop surface may include four segments as seen inFIG.38, separated by gaps such as214. The flexible valve member176includes an axially extending main body portion310which is preferably cylindrical in shape having a main body portion diameter312. A tapered distal end portion314extends distally from the main body portion310and includes the distal end182and the protrusion184. A tapered proximal portion316extends proximally from the main body portion310and joins the proximal end portion178. The flexible valve member176has an axial length318. Proximal end portion178has an axial length320. Tapered proximal portion316has an axial length322. Main body portion310has an axial length or main body portion length324. Tapered distal end portion314has an axial length326. The main body portion length324may be at least one-half the axial length318of the flexible valve member176. The axial length322of the tapered proximal portion316may be greater than the main body portion diameter312, and preferably may be greater than 125% of the main body portion diameter312. The tapered proximal portion316may taper from the main body portion diameter312at its junction with main body portion310to a minimum outside diameter328less than 60% of the main body portion diameter312. The flexible valve member176includes a plurality of stabilizing fins330,332,334and336extending laterally, and preferably radially, outward from the main body portion310toward the interior wall169of the second mating structure136. As best seen inFIG.34the fins may extend along a fin length338which is less than the axial length324of the main body portion310. The flexible valve member176is constructed from a resilient elastomeric material such that the flexible valve member176can deflect as shown inFIG.25when engaged by the male luer fitting72, and can rebound back to its original shape to reseal against the female luer connection170when the male luer fitting72is withdrawn. The use of the injection port assembly130is best illustrated inFIGS.24and25. InFIG.24the injection port assembly is shown with the flexible valve member176in a closed position. A male luer fitting72is shown above the injection port assembly130in a position just prior to engaging the flexible valve member176. InFIG.25, the male luer fitting72has been moved downward and engaged with the upper end of the flexible valve member176to displace the flexible valve member176relative to the central body axis138upon entry of the male luer fitting72into the female luer connection170thereby placing the male luer fitting72, and particularly the interior thereof, in communication with the interior171of the second mating structure136. The function of the flexible valve member176when engaged by the male luer fitting72to move the flexible valve member176from the closed position ofFIG.24to the open position ofFIG.25is generally as follows. The stabilizing fins330-336keep the main body portion310centered in the body132even as the flexible valve member176begins to axially compress as the male luer fitting72begins to push downwardly on the proximal valve end portion178. Because the tapered proximal portion316has the smallest cross-section and is relatively long, the tapered proximal portion316will ultimately buckle and be displaced laterally relative to the center axis138as is schematically represented inFIG.25. When the tapered proximal portion316buckles the male luer fitting72will be in fluid communication with the interior171of the second mating structure136and can then introduce fluid into or withdraw fluid from the interior171. Thus it is seen that the apparatus and methods of the present invention readily achieve the ends and advantages mentioned as well as those inherent therein. While certain preferred embodiments of the invention have been illustrated and described for purposes of the present disclosure, numerous changes in the arrangement and construction of parts and steps may be made by those skilled in the art, which changes are encompassed within the scope and spirit of the present invention as defined by the appended claims. | 24,244 |
11857753 | DETAILED DESCRIPTION Embodiments of the present disclosure pertain to a disinfection cap for connection to and disinfection of a medical connector, including threaded connectors. In one or more embodiments, the connectors are male luer connectors or female luer connectors. The disclosure aims to provide a mechanism capable of disinfecting both the lumen of open luers and the corresponding IV connector while minimizing additional steps in medical administration. It is contemplated that the disinfection cap disclosed herein can be utilized with male or female threaded connectors. The disclosure aims to provide a mechanism to disinfect an IV needleless connector during syringe use, therefore saving the clinician time and reducing work steps. The disclosure aims to reducing the number of steps required in preventing contamination of VAD devices. With respect to terms used in this disclosure, the following definitions are provided. As used herein, the use of “a,” “an,” and “the” includes the singular and plural. As used herein, the term “catheter related bloodstream infection” or “CRBSI” refers to any infection resulting from the presence of a catheter or IV line. As used herein, the term “Luer connector” refers to a connection collar that is the standard way of attaching syringes, catheters, hubbed needles, IV tubes, etc. to each other. The Luer connector consists of male and male interlocking tubes, slightly tapered to hold together better with even just a simple pressure/twist fit. Luer connectors can optionally include an additional outer rim of threading, allowing them to be more secure. The Luer connector male end is generally associated with a flush syringe and can interlock and connect to the male end located on the vascular access device (VAD). A Luer connector comprises a distal end, a proximal end, an irregularly shaped outer wall, a profiled center passageway for fluid communication from the chamber of the barrel of a syringe to the hub of a VAD. A Luer connector also has a distal end channel that releasably attaches the Luer connector to the hub of a VAD, and a proximal end channel that releasably attaches the Luer connector to the barrel of a syringe. As used herein, the term “syringe” refers to a simple pump-like device consisting of a plunger rod that fits tightly in a barrel or tube. The plunger rod can be pulled or advanced along inside the barrel, allowing the syringe to take in and expel a liquid or gas through an opening at the open end of the barrel. As used herein, the term “medical device” refers to common medical devices having threaded or interlocking connections, the connections having corresponding mating elements. By way of example but not limitation, a syringe has a male threaded connection which releasably interlocks with a secondary medical device such as a male luer connection of a catheter, an IV line and the like. The threaded connection includes a lumen defining a fluid path surrounded by a protruding wall having the threaded means for attaching to the secondary medical device. As would be readily appreciated by skilled artisans in the relevant art, while descriptive terms such as “thread”, “taper”, “tab”, “wall”, “top”, “side”, “bottom” and others are used throughout this specification to facilitate understanding, it is not intended to limit any components that can be used in combinations or individually to implement various aspects of the embodiments of the present disclosure. The matters exemplified in this description are provided to assist in a comprehensive understanding of exemplary embodiments of the disclosure. Accordingly, those of ordinary skill in the art will recognize that various changes and modifications of the embodiments described herein can be made without departing from the scope and spirit of the disclosure. Also, descriptions of well-known functions and constructions are omitted for clarity and conciseness. Before describing several exemplary embodiments of the disclosure, it is to be understood that the disclosure is not limited to the details of construction or process steps set forth in the following description. The disclosure is capable of other embodiments and of being practiced or being carried out in various ways. Referring now to the drawings, wherein like reference numerals designate identical or corresponding parts throughout the several views, embodiments of the present disclosure are described as follows. Referring toFIG.1, the present disclosure includes a disinfection system100comprising a syringe110having a threaded connector such as a luer connector114, a disinfection tip150which is disposed at least partially within the luer connector114of the syringe110and an IV connector130which advances the disinfection tip150further into the luer connector114of the syringe as the IV connector130is threaded into the threaded connection of the syringe110; the disinfection tip150being advanced in a proximal direction. In one or more embodiments, the disinfection tip150is fully disposed within the luer connector114. In one or more embodiments, a disinfectant or antimicrobial agent102(hereinafter “disinfectant102,” not shown) is retained in a volume between the luer connector114and the disinfection tip150, defining a disinfectant chamber124when the disinfection tip150is at least partially disposed within the luer connector114. In one or more embodiments, the disinfection tip150is fully disposed within the luer connector114. In one or more embodiments, the disinfectant102is a fluid or gel. In an exemplary implementation of the embodiments of present disclosure, the disinfection tip150includes integrated threads or tabs, and other features in any and all combinations allowing it to interface with a threaded fitting of a medical device. In preferred embodiments, the disinfection tip150interfaces with a male Luer fitting. Exemplary configurations for couplers, fittings, ports and adapters may include commercially available luer locks, luer slip ports, locking ports, threaded connections, interlocking connection or generally other common medical device fitting known in the art. Referring toFIG.2, the syringe110includes a conical base112disposed on the distal end of the barrel of the syringe110. A luer connector114is distally disposed on the conical base112, the luer connector including a tapered tip116and an integrally formed outer collar120. The tapered tip116extends from the conical base112of the syringe and has a substantially conical shape. The outer collar120of the syringe110includes a plurality of threads122for engaging a plurality of threads138of the IV connector130. A lumen118is disposed within the tapered tip116, extending through the tapered tip116and the conical base112, the lumen opening being in fluid communication from the barrel of the syringe110to the IV connector130which connects to the luer connector114by a preferably threaded connection. Finally, a cavity is defined between the tapered tip116and the outer collar120, the cavity defining a volume in which disinfectant102is retained. In further embodiments, the syringe includes a flat base. In further embodiments, the integrally formed outer collar120lacks threads, in which secondary attachment devices are retained by a press-fit, interference fit or an interlocking push and twist-lock fit. In one or more embodiments in which the outer collar120lacks threads, the luer connector114is connected to the IV connector130by an interference fit between the lumen134of the IV connector130and the luer connector114of the syringe110. In one or more embodiments include any device having a luer or threaded connector, by way of example, a sample collection container such as a VACUTAINER®, provided by Becton Dickinson and Company. The sample collection container including a threaded or slip fit luer connector. As depicted inFIGS.3,8and9, in one or more embodiments, the distal portion of the IV connector130includes an IV needleless connector, a catheter, a rubber tube and the like. The IV connector130includes a cylindrical body132having a lumen134(not shown) disposed on the proximal end of the cylindrical body. The lumen is covered by a valve136which is pierced or opened by the tapered tip116of the syringe110, allowing for fluid communication from the barrel of the syringe110through the lumen118of the syringe110to the lumen134of the IV connector130. In one or more embodiments, the valve136is a diaphragm having a slit or a cross-shape slit which remain closed when not pierced or opened by the tapered tip116or a needle. An illustration of the IV connector130as part of a greater IV line or catheter device is depicted inFIG.3. It is understood that the illustration of the IV connector130is not representative of the distal portion of the IV connector130. As depicted inFIGS.5and6, the disinfection tip150comprises a substantially cylindrical outer housing152having and outer wall154, a distal wall162and a proximal surface160. The outer wall154includes a plurality of threads156for threadedly engaging the plurality of threads122of the syringe110. An aperture157extends a length L1from the proximal surface160to the distal wall162, defining a cavity158and an inner wall159. The distal wall162includes a concentrically placed opening164defining an inner rim166, the circumference of opening164being smaller than circumference of the cavity158defined by the aperture167. In one or more embodiments, the inner rim166is at a right angle relative to the distal wall162. In one or more embodiments, the inner rim166is rounded or chamfered. The diameter/circumference of opening164of the inner rim166configured to mate with the tapered tip116of the syringe110. From the inner rim166extends an inner housing168, the inner housing168extending in a proximal direction from the inner rim166at least partially a length L2of the outer housing152. The inner housing168is substantially cylindrical in shape, and the inner housing168includes an inner proximal surface172, an inner sidewall174and an outer sidewall175. The outer sidewall175, the inner wall159and the distal wall162of the outer housing152define a distal chamber176. In one or more embodiments, the inner proximal surface172is conical in shape, conforming to the corresponding conical shape of the tapered tip116of the syringe110. In one or more embodiments, the inner proximal surface172is flat and at a right angle with the inner housing168. In further embodiments, the inner proximal surface172is rounded or chamfered as to allow for greater conformity with the conical base112of the syringe. The inner sidewall174of the inner housing168and the tapered tip116of the syringe110form a liquid tight seal in which the tapered tip116abuts the inner sidewall174. In one or more embodiments, the liquid tight seal between the inner sidewall174of the inner housing168and the tapered tip116of the syringe110is facilitated with an interference fit. The interference fit deforms the inner sidewall174of the inner housing168in a radial direction as the disinfection tip150is further inserted in a proximal direction. In one or more embodiments, the inner sidewall174of the inner housing168is contoured to not deform as the disinfection tip150is further inserted in a proximal direction. Referring toFIG.6, at least one jet orifice178is radially disposed on the inner rim166of the distal wall162. As shown inFIG.6, the at least one jet orifice178is disposed within the inner housing168and transverses the inner sidewall174to outer sidewall175. A jet orifice inlet180of the at least one jet orifice178is in fluid communication with the distal chamber176allowing for fluid to pass from the distal chamber176through a jet orifice channel to a jet orifice outlet182. In the preferred embodiment, the channel is at an acute angle with relation to the distal wall162of the outer housing152, thus directing fluid from the distal chamber176in a distal direction towards the center of the outer housing152. The distal chamber176, the cavity158and the jet orifice178are in fluid communication with one another. As shown inFIGS.7and8, the disinfection tip150is first disposed at least partially within the luer connector114of the syringe110. In one or more embodiments, the disinfection tip150is fully disposed within the luer connector114. The disinfectant102is retained in the disinfectant chamber124, the disinfection chamber124being between the luer connector114and the disinfection tip150. As the IV connector130is threaded into the luer connector114of the syringe110in a proximal direction, the IV connector130further guides the disinfection tip150into the luer connector114in a proximal direction through the transference of axial force in the proximal direction and through the torqueing of the plurality of threads138of the IV connector130into the plurality of threads122of the syringe110. In one or more embodiments, the distal wall162of the disinfection tip150is configured to optimize torque transfer. In one or more embodiments, the distal wall162is smooth in order to limit torque coupling during unthreading of the IV connector130from the luer connector114. In one or more embodiments, the distal wall162has a rough or textured surface to promote torque coupling. In one or more embodiments, the distal wall162has friction enhancing materials or coatings to promote torque coupling. In one or more embodiments, the distal wall162has at least one radial spline configured to engage with the IV connector130. In one or more embodiments, the distal wall162has at least one gear tooth configured to engage with a corresponding tooth of the IV connector130, the at least one gear tooth configured to promote torque coupling. In one or more embodiments, the distal wall162includes a plurality of radial peaks, in which an incline of the peak is at a right angle with the distal wall162while a decline of the peak is at an acute angle with the distal wall162, wherein the incline allows for a feature of the IV connector130to advance the disinfection tip150in the direction of the incline, while the decline prohibits opposite direction of advancement, the direction of advancement being the same direction in which the IV connector130is threaded onto the luer connector114of the syringe110. As the proximal surface160of the disinfection tip150is advanced further towards the conical base112of the syringe110, the volume of the disinfectant chamber124is decreased, causing an increase in pressure of the disinfectant chamber124. Due to the incompressible nature of liquids, the increase in pressure causes the disinfectant102to follow the path of least resistance, traveling through the at least one jet orifice178, ejecting the liquid in the direction of the at least one jet orifice178, thereby disinfecting both the luer connector114and the IV connector130. The disinfectant102will tend not to ingress into the lumen118of the syringe110or the lumen of the IV connector130due to the interference fit between the tapered tip116of the syringe110and the lumen of the IV connector130, as per ISO594-2 standards. Due to the tapered tip116extending beyond the outer collar120of the syringe110, the interference fit is engaged before the increase in pressure of the disinfectant chamber124causes the disinfectant102to eject from the at least one jet orifice178. As the disinfection tip150is advanced even further in the proximal direction, the disinfectant102, having disinfected the luer connector114and the IV connector130, evacuates from the luer connector114through a distal end of the outer collar120of the syringe110into the atmosphere. Further evacuation of the disinfectant102is facilitated by a tolerance gap between the plurality of threads138of the IV connector130and the plurality of threads122of the syringe110. Disinfectant102evacuates through the tolerance gap and into the atmosphere from the distal end of the outer collar120of the syringe110. Such tolerance gap is known in the art and is specified under ISO594-2 standards. A length of the disinfection tip150is defined by the distance from the proximal surface160to the distal wall162. The length is sized to allow for at least one of the plurality of threads138of the IV connector130to sufficiently engage the plurality of threads122of the syringe110when the disinfection tip150is in a fully threaded position. The fully threaded position is reached when the proximal surface160of the disinfection tip150abuts or nearly abuts the conical base112of the syringe110. In one or more embodiments, the integrally formed outer collar120of the syringe110, the plurality of threads122of the syringe110and the tapered tip116of the syringe110are configured to fully accommodate the disinfection tip150while still allowing the standard syringe luer thread depth as required by ISO594-2 standards. Thus, the integrally formed outer collar120of the syringe110, the plurality of threads122of the syringe110and the tapered tip116of the syringe110are longer than the features of a common syringe by at least the length of the disinfection tip150, wherein the disinfection tip150may be in the fully threaded position while still permitting the IV connector130to sufficiently thread into the luer connector114in compliance with ISO594-2 standards. Thus, instead of disinfecting the luer connector114and the IV connector130individually, the present disclosure enables a practitioner merely has to thread the IV connector130into the luer connector114. The disinfectant is dispensed or ejected due to the increase in pressure, bathing both the luer connector114and the IV connector130. Furthermore, because the length of the disinfection tip150allows for the disinfection tip150to remain fully threaded into the luer connector114of the syringe110during engagement of the IV connector130and further administration of the medical procedure, the practitioner does not have to take any additional steps in disinfecting the connection. Thus, instead of individually disinfecting the luer connector114and the IV connector130individually, or even removing the means of disinfection, the practitioner merely has to thread the IV connector130into the luer connector114of the syringe and the disinfection system100can be normally used. In further embodiments, the surface of the distal wall162of the disinfection tip150also defines an engagement surface where a peelable seal is secured. In one or more embodiments, the disinfection tip150can include the peelable seal covering the opening164of the disinfection tip150and the at least one jet orifice178to seal the disinfectant102within the disinfectant chamber124of the syringe110and the disinfection tip150prior to use of the syringe110and the disinfection tip150. The peelable seal minimizes entry of potential particulate hazard and also provides a substantially impermeable enclosure for the disinfection tip150, provides a leak prevention and protection enclosure, protects the contents of the disinfectant chamber124of the syringe110and the disinfection tip150prior to use of the syringe110and the disinfection tip150and/or maintains a sealed, sterilized environment. The peelable seal provides a sufficient seal at a range of temperatures, pressures, and humidity levels. The disinfection tip150is designed to be compatible in interacting with the disinfectant102. In one or more embodiments, the disinfectant102includes variations of alcohol or chlorhexidine. In one or more embodiments, the disinfectant102includes variations of alcohol or chlorhexidine. In one or more embodiments, the disinfectant102is selected from the group consisting essentially of isopropyl alcohol, ethanol, 2-propanol, butanol, methylparaben, ethylparaben, propylparaben, propyl gallate, butylated hydroxyanisole (BHA), butylated hydroxytoluene, t-butyl-hydroquinone, chloroxylenol, chlorohexidine, chlorhexidine diacetate, chlorohexidine gluconate, povidone iodine, alcohol, dichlorobenzyl alcohol, dehydroacetic acid, hexetidine, triclosan, hydrogen peroxide, colloidal silver, benzethonium chloride, benzalkonium chloride, octenidine, antibiotic, and mixtures thereof. In a specific embodiment, the disinfectant102comprises at least one of chlorhexidine gluconate and chlorhexidine diacetate. In one or more embodiments, the disinfectant102is a fluid or a gel. In one or more embodiments the disinfection tip150can be deformable and is of polypropylene, polyethylene or TPE material. In further embodiments, the syringe110, disinfection tip150and/or IV connector130are made from any of a number of types of plastic materials such as polycarbonate, polypropylene, polyethylene, polyethylene terephthalate, polylactide, acrylonitrile butadiene styrene or any other moldable plastic material used in medical devices. In one or more embodiments, the syringe110, disinfection tip150and/or IV connector130comprises a polypropylene or polyethylene material. In one or more embodiments, the IV connector130may be selected from the group consisting essentially of needle-free connectors, catheter luer connectors, stopcocks, and hemodialysis connectors on primary IV gravity sets, secondary IV gravity sets, extension sets, and infusion or syringe pump sets. In one or more embodiments, the male connector may be selected from the group consisting essentially of needle-free connectors, catheter luer connectors, stopcocks, and hemodialysis connectors. While the present disclosure has been shown and described with reference to certain exemplary embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the embodiments of the present disclosure. Also, the inner and/or the outer housing of the cap can be single shot molded, or made by other suitable process. Furthermore, any of the features or elements of any exemplary implementations of the embodiments of the present disclosure as described above and illustrated in the drawing figures can be implemented individually or in any combination(s) as would be readily appreciated by skilled artisans without departing from the spirit and scope of the embodiments of the present disclosure. In addition, the included drawing figures further describe non-limiting examples of implementations of certain exemplary embodiments of the present disclosure and aid in the description of technology associated therewith. Any specific or relative dimensions or measurements provided in the drawings other as noted above are exemplary and not intended to limit the scope or content of the inventive design or methodology as understood by artisans skilled in the relevant field of invention. Other objects, advantages and salient features of the disclosure will become apparent to those skilled in the art from the details provided, which, taken in conjunction with the annexed drawing figures, disclose exemplary embodiments of the disclosure. Reference throughout this specification to “one embodiment,” “certain embodiments,” “one or more embodiments” or “an embodiment” means that a particular feature, structure, material, or characteristic described in connection with the embodiment is included in at least one embodiment of the disclosure. Thus, the appearances of the phrases such as “in one or more embodiments,” “in certain embodiments,” “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily referring to the same embodiment of the disclosure. Furthermore, the particular features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments. Although the disclosure herein has provided a description with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present disclosure. It will be apparent to those skilled in the art that various modifications and variations can be made to the method and apparatus of the present disclosure without departing from the spirit and scope of the disclosure. Thus, it is intended that the present disclosure include modifications and variations that are within the scope of the appended claims and their equivalents. | 24,318 |
11857754 | DESCRIPTION OF THE PREFERRED EMBODIMENT Although the disclosure hereof is detailed and exact to enable those skilled in the art to practice the invention, the physical embodiments herein disclosed merely exemplify the invention which may be embodied in other specific structures. While the preferred embodiment has been described, the details may be changed without departing from the invention, which is defined by the claims. Turning first toFIG.1, a first embodiment10of a closure container according to the present invention is shown. The closure container10preferably comprises a single injection-molded piece having a first casing member100hingedly attached to a second casing member200by at least one hinge12(seeFIG.2), which may be a living hinge. The first casing member100may generally be formed along a longitudinal length between and including a first end102opposite a second end104, an outer surface106, a peripheral edge portion116(FIG.2), a fastener118, and an inner surface132(FIG.2). The outer surface106of the first casing member100extends from the first end102to the second end104and to the peripheral edge portion116. The outer surface106has a planar portion108with a window110preferably provided therein and a plurality of catches112projecting therefrom. Each catch112preferably has an L-shape profile and extends outward from the planar portion108, whereby an arm114of the L-shape is spaced from and substantially parallel with the planar portion108of the outer surface106, and all of the catches112are oriented preferably in the same direction. The fastener118is flexibly connected at or near the peripheral edge portion116of the first casing member100opposite the hinge12. The fastener118has a width120, a thickness122, an exterior surface124, an interior surface126, and a tamper-evident pull-tab130. A barb128projects from the interior surface126distal to the outer surface106of the first casing member100. The tamper-evident pull-tab130preferably extends substantially perpendicular from the fastener118between the barb128and the outer surface106of the first casing member100. The tamper-evident pull-tab130is preferably offset from the exterior surface124of the fastener118in a direction away from the container10when the fastener118is in an engaged position, as discussed further below. The inner surface132of the first casing member100can be seen inFIGS.2and3. The inner surface132extends from the first end102to the second end104and to the peripheral edge portion116, and preferably has an at least substantially planar portion134. As shown here, a bridge136with a notch138projects from the planar portion134of the inner surface132near the first end102to or near the peripheral edge portion116. A retainer140extends from the planar surface134to or near the peripheral edge portion116and comprises a first wall142, with a first wall notch144, and a second wall146, with a second wall notch148, substantially parallel to the first wall142. A plurality of dosing ribs152project from the planar portion134to or near the peripheral edge portion116and are spaced between the second end104and the second wall146of the retainer140. Each dosing rib152has a notch154, an innermost side156(hidden), and an outermost side158. The spacing between the dosing ribs152relates to the predetermined dosage provided in a syringe50(FIG.2) to be contained within the closure container10. The preferable dosing amounts for which the ribs152will be spaced are 0.25 mL, 0.5 mL, 0.75 mL, and 1.0 mL, but other dosing amounts are contemplated. The second casing member200may be seen inFIGS.2and3as well. The second casing member200has a first end202opposite a second end204, an outer surface206, a peripheral edge portion216, and an inner surface232. The outer surface206of the second casing member200extends from the first end202to the second end204and to the peripheral edge portion216. The outer surface206preferably has an at least substantially planar portion208with a plurality of holes260(FIG.5) therein which are sized, positioned, and configured to be mateable with the catches112of the first casing member100of another closure container10. As shown inFIGS.10and11, the outer surface206of the second casing member200has a recess262with a width264slightly greater than the width120of the fastener118and a depth266preferably similar to the thickness122of the fastener118. A slot268sized and configured to receive the barb128of the fastener118is provided within the recess268. Looking back toFIGS.2and3, the inside surface232of the second casing member200is shown. The inside surface232of the second casing member200is preferably substantially similar to the inside surface132of the first casing member100. As shown here, the inner surface232extends from the first end202to the second end204and to the peripheral edge portion216, and preferably has a planar portion234. As shown here, a bridge236with a notch238projects from the planar portion234of the inner surface232near the first end202to or near the peripheral edge portion216. A retainer240extends from the planar portion208to or near the peripheral edge portion216and comprises a first wall242, with a first wall notch244, and a second wall246, with a second wall notch248, substantially parallel to the first wall242. The first wall242is spaced apart from the second wall246a distance250. A plurality of dosing ribs252project from the planar portion234of the inner surface232to or near the peripheral edge portion216and are spaced between the second end204and the second wall246of the retainer240. Each dosing rib252has a notch254, an innermost side256, and an outermost side258. The spacing between the dosing ribs252relates to the predetermined dosage provided in a syringe50(FIG.2) to be contained within the closure container10. The preferable dosing amounts for which the ribs252will be spaced are 0.25 mL, 0.5 mL, 0.75 mL, and 1.0 mL, however, other dosing amounts are contemplated. Additionally or alternatively, the dosing ribs152of the first casing member100may be staggered from the dosing ribs252of the second casing member200to provide more dosing options while still providing secure support of the syringe50and the plunger52. Additionally or alternatively, the first casing member100or the second casing member200may not contain the respective dosing ribs, retainer, or the bridge; instead being configured simply to cover the other casing member200,100. Looking back toFIG.1and also toFIGS.4-9, the closure container10is depicted in from various views with the syringe50positioned within the container10and the fastener118engaged with the second casing member200. As shown, when the container10is in a closed position, the fastener118preferably resides substantially within the recess262, with the barb128received within the slot268. The material from which the closure container10is formed is preferably initially transparent. The window110is preferably formed by covering the area in which the window110will be located, treating at least the outer surfaces106,206of the first casing member100and the second casing member200, respectively, to decrease the transparency of those surfaces, and removing the covering to reveal the window110. The treatment may be performed by any process now known or later discovered, including but not limited to, chemical etching, mechanical etching (e.g., sand blasting), or during the molding process using textured dies. Continuing to look atFIG.1, a syringe50can be viewed through the window110in a pre-set dosage configuration, ready for use. The window110is preferably located at least radially outward from the barrel64of the syringe50to provide a care provider with a view of the syringe50and preferably the dosage amount provided in the barrel64without having to open the closure container10. Directing attention toFIGS.16-19, the installation of the syringe50into the container10is shown.FIG.16illustrates the syringe50with a predetermined dosage provided in the barrel64prior to placement within the second casing member200; however, the syringe50may be placed within the first casing member100as well, as shown inFIG.17. Looking toFIG.17, with reference toFIG.16, the flange60of the syringe50is placed within the retainer140of the first casing member100with a portion of the barrel64received by the notch144of the first wall142and another portion of the barrel64received by the notch138of the bridge136. Preferably, the distance150between the first and second walls142,146of the retainer140(FIG.10) is preferably slightly greater than the thickness62of the syringe flange60. The top54of the plunger52has a topside surface56and an underside surface58. When installed within the container10, the underside surface58of the syringe top54preferably resides against or near the outermost side158of the respective dosing rib152. The placement of the flange60within the retainer140and the top54against the dosing rib152reduces the likelihood that the syringe50will be accidentally discharged prior to use. FIG.18illustrates the closing of the container10with the first and second casing members100,200rotating about the hinge12(FIG.17) and adjoining the first casing member peripheral edge portion116(FIG.17) with the second casing member peripheral edge portion216(FIG.17). The barrel64of the syringe50is thereby also received within the bridge notch238, the retainer240, and the respective dosing rib notch254of the second casing member200(seeFIG.17). Looking toFIGS.19and20, the engagement of the fastener118is shown. The fastener118is wrapped around the outside surface206of the second casing member200within the recess262. The barb128is engageably received within the slot268to retain the fastener118in the engaged position. When the time comes for the syringe50to be removed from the container10, the health care personnel will pull the tamper-evident pull-tab130away from the container10which will tear through the fastener118and sever the fastener's connection between the first and second casing members100,200, thus allowing the container10to be opened and the syringe50to be removed. Removal of the tamper-evident pull-tab130permanently detaches at least a portion of the fastener118from the first casing member100when pulled to gain access to the syringe50. Therefore, tampering with the fastener118or the tamper-evident pull-tab in an attempt to gain access to the syringe50will be visibly noticeable by a tear in the fastener118. FIGS.21and22demonstrate how multiple containers10A,10B,10C may be stacked one on top of the other. As shown in greater detail inFIG.22, a mateable stacking interaction between a catch112A and a hole260B is shown. The interaction allows the containers10A,10B to be removably interlocked. The catch112A, along with the other three catches (not shown), of the first container10A are inserted within the holes260B of the second container10B and the containers10A,10B, are slid in opposite directions relative to one another to place the arm114A of the first container10A adjacent to the inner surface232B of the second container second casing member200B. These actions are depicted by the dashed lines inFIG.21. FIG.23illustrates a second embodiment20of the closure container according to the present invention. The closure container20has tabs470projecting from the planar portion408of the second casing member outer surface406and apertures390(FIG.24) provided through the planar portion308of the first casing member outer surface306. The apertures390are alignable and mateable with the tabs470of a corresponding closure container20. Each tab470has a width472(FIG.24), an inward face476, and an outward face480. The tabs470preferably extend substantially perpendicular away from the outside surface planar portion408and comprise a protuberance478, or similarly shaped protrusion, on the inward face476at or near the distal end portion482(FIG.25) of each tab470. Alternatively, it is contemplated that the protuberance478may protrude from the outward face480. The apertures390have a width392and an abutting surface396. The width392of the apertures390is preferably slightly greater than the width472of the tabs470. FIGS.24and25demonstrate how multiple containers20A,20B,20C may be stacked by inserting the tabs470B of a second container20B within the apertures390A of a first container20B. This action is depicted by the dashed lines inFIG.24. In this fashion, stacking of these embodiments20require only a singular directional movement, rather than the compound movement that may be utilized to stack cases according to the first embodiment10. FIG.25more closely illustrates the interaction between a tab470B of the second container20B is received within an aperture390of the first container20A to provide a releasable connection between the two containers20A,20B. Preferably, the inner face476B of the tab470B is substantially flush with the abutting surface396A of the aperture390A, whereby the protuberance478B of the tab470B is in contact with the planar portion334A of the first casing member inner surface332A and the first container's second casing member outer surface planar portion308A is flush with the second container's first casing member outer surface planar portion408B. The foregoing is considered as illustrative only of the principles of the invention. Furthermore, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described. While the preferred embodiment has been described, the details may be changed without departing from the invention, which is defined by the claims. | 13,720 |
11857755 | The foregoing and other objects, features, and advantages of the invention will be apparent from the following more particular description of preferred embodiments herein, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, with emphasis instead being placed upon illustrating the embodiments, principles, concepts, etc. DETAILED DESCRIPTION AND FURTHER SUMMARY OF EMBODIMENTS Now, more specifically,FIG.1is an example diagram illustrating association management and fluid delivery management in a medical environment according to embodiments herein. As shown, medical environment100includes network190(which may include a packet-switched network, the Internet, WiFi™ network, etc.), association management resource140, information system165, domain150-1, domain150-2, etc. Each of the domains150(e.g., domain150-1, domain150-2, etc.) in medical environment100can represent a location in medical environment100in which fluid is delivered to a corresponding recipient. A fluid delivery domain can represent a hospital room, a person's home, etc. In this non-limiting example embodiment, assume that caregiver106configures fluid delivery system125-1(such as first pump) to deliver fluid from source120-1to recipient108. Assume math the caregiver106configures fluid delivery system125-2(such as a second pump) to deliver fluid from source120-2to recipient108. Recipient108in this example is patient John Smith. Note that domain150-1further includes communication interface145-1. In one embodiment, each of the medical devices in domain150-1has the ability to communicate with communication interface145-1. In this example embodiment, each of the fluid delivery systems125is communicatively coupled to communication interface145-1via a respective communication link (such as a wired communication link, wireless communication link etc.). In this non-limiting example embodiment, communication link128-1supports communications between fluid delivery system125-1and communication interface145-1; communication link128-2supports communications between fluid delivery system125-2and communication interface145-1; communication link128-3supports communications between fluid delivery system125-3and communication interface145-1; communication link128-4supports communications between management device160-1and communication interface145-1; and so on. Each of the communication links128can be a hardwired or wireless link. Any suitable protocol can be employed to communicate RF and/or hardwired communications between each of the devices and communication interface145-1over a respective communication link. In one embodiment, each of the communication links128supports communications in accordance with the WiFi™ protocol. As further shown, communication interface145-1supports communications126-1through network190to any of one or more remotely located resources such as association management resource140, information system165, etc. In a reverse direction, communication interface145-1receives communications126-2from the one or more remotely located resources in network190. Communication interface145-1forwards the received communications126-2to the appropriate resource (such as a medical device) in domain150-1. Accordingly, each of the one or more resources such as fluid delivery system125-1, fluid delivery system125-2, fluid delivery system125-3(such as third fluid pump), management device160-1, etc., is able to communicate with any of one or more resources located in medical environment100through communication interface145-1and over network190. In one embodiment, each of the devices or systems in medical environment100is assigned a corresponding unique network address. Via client-server type communications, each of the devices or systems in the medical environment is able to communicate with a respective remotely located resource. For example, using a network address of the association management resource140in respective generated data packets, any of the medical devices located in medical environment100are able to transmit the generated data packets to association management resource140. In a reverse direction, the association management resource140can include a network address of a corresponding target medical device in generated data packets to forward such communications to the target medical device. In one non-limiting example embodiment, the resources in medical environment100(such as each of the fluid delivery systems125, management device160-1, association management resource140, etc.) communicate amongst each other via a HyperText Transfer Protocol (HTTP) type protocol. By way of non-limiting example, the resources can communicate via using secure HTTP (i.e., HTTPS), ensuring that communications and the connections between the association management resource140and the fluid delivery systems are secure and that messages are fully encrypted. As shown, and as previously discussed, embodiments herein include an association management resource140. In accordance with one embodiment, and along the other functions, the association management resource140collects information (such as medical information122) associated with different resources in the medical environment100from one or more resources. As its name suggests, the association management resource140manages associations. By way of non-limiting example, based on received data, the association management resource140produces and manages association information185stored in repository180. As its name suggests, the association information185managed by association management resource140keeps track of associations amongst the different entities in medical environment100. In accordance with yet further embodiments, each of the entities in the medical environment100is assigned a corresponding unique value. For sake of illustration, assume that caregiver106is assigned to the unique value CGVR106; fluid delivery system125-1is assigned the unique value FDD313; fluid delivery system125-2is assigned a unique value FDD432; fluid delivery system125-3is assigned the unique value FDD566; domain150-1in medical environment100is assigned the unique value LOC277; domain150-2in medical environment100is assigned a unique value LOC278; and so on. Each of the domains150in medical environment100can include similar resources as domain150-1. As further discussed below, association management resource140produces and manages association information185to keep track of associations between the different resources or entities in medical environment100. Note that associations can change over time. For example, the association management resource140can receive communications from any resource in medical environment100(such as information system165, domain150-1, domain150-2, etc.) indicating to create one or more new associations. Additionally, in addition to receiving communications to create new associations, the association management resource140can receive communications indicating to terminate one or more associations. Thus, the state of association information185stored in repository180changes over time. By further way of a non-limiting example, the association management resource140can be configured to implement a set of association rules142to manage respective associations between entities in medical environment100. In one embodiment, these rules142help automate the association and disassociation of entities. For example, a rule may state that when two medical devices are associated, they also share the same patient and location associations. Thus, the rules142can specify how to create associations. Association rules142may be defined for the entire institution (medical environment100) or may be domain or device type specific. This enable rules for an intensive care unit to differ from rules used in an operating room. Use of different rules would also allow, for example, association rules between two infusion pumps to differ from those between an infusion pump and a patient monitor. FIG.2is an example diagram illustrating association information according to embodiments herein. As shown in this example, the association information185-1indicates associations (as represented by a line) between different types of entities in the medical environment100. Each node inFIG.2represents a corresponding entity or resource in or associated with medical environment100. Further note that management of the associations amongst the different entities can be achieved in any number of ways. For example, the association management resource140can employ any suitable resource such as pointers, tables, mappings, etc., can be used to indicate the associations amongst the different entities. Associations can be created continuously over time. For example, in one embodiment, association management resource140is configured to constantly search network194for information related to entities located in medical environment100. In the example embodiment shown, the association management resource140receives medical information122-1from information system165-1; the association management resource receives medical information122-2from information system165-2; and so on. Medical information122can be any suitable type of information. For example, the medical information can be patient information, billing information, physician information, medication order information (such as one or more prescription drug orders), caregiver information, location information, etc. Recall that each of the entities in medical environment100is assigned a unique value. Based on information received from one or more resources in medical environment100, the association management resource140creates association information185-1to indicate current associations amongst different entities or resources located in medical environment100. Note that medical environment100is not limited to a corresponding location such as a hospital. Medical environment100can include any resource, entity, etc., that is related to patient care. In this example, via respective caregiver-patient association lines inFIG.2, association information185-1indicates that: caregiver CGVR106(caregiver106) has been assigned to care for patients Jane Doe and John Smith; caregiver CGVR188is not assigned to care for anyone; and so on. Thus, associations in the association information185can indicate assignments. Further in this example, via respective medicine-patient association lines, association information185-1indicates that: fluid-based drug RX29has been prescribed to Jane Doe; fluid-based drugs RX24and RX36have been prescribed to John Smith; and so on. As previously discussed, the association management resource140can be configured to receive association information from any suitable resource. In one embodiment, the association management resource140receives medical information122-1from information system165-1indicating that a physician has prescribed fluid-based drugs RX24and RX36to John Smith. Based on receipt of this medical information (medication order information), the association management resource140creates the association lines between medication order drugs RX24and RX36and John Smith. Yet further in this example, via the respective patient-location association lines, association information185-1indicates that: patient Jane Doe resides in a respective domain LOC299(such as a first hospital room); patient John Smith resides in domain LOC277(such as a second hospital room); patient James Henry resides in domain LOC267(such as a third hospital room); and so on. James Henry has been assigned to caregiver CGVR103. Still further in this example embodiment, via respective domain-building association lines, association information185-1indicates that: the domain assigned LOC299is located on the second floor of building345; the domain assigned LOC277is located on the second floor of building345; the domain assigned LOC267is located on the second floor of building345; the domain assigned LOC269is located on the second floor of building345; the domain assigned LOC269is located on the second floor of building345; and so on. As may be expected, certain associations in the association information185are static. That is, location LOC299(such as a first room in a hospital) will always reside in the second floor of building345; location LOC277(such as a second room in a hospital) will always reside in the second floor building345; location LOC267(such as a third room in a hospital) will always reside in the second floor building345; and so on. Other associations are temporary. For example, caregiver CGVR106may be temporarily assigned to care for John Smith and Jane Doe during a first shift. When switching over to a second shift, the caregiver CGVR188may be assigned to care for Jane Doe and John Smith instead of caregiver CGVR106. In such an instance, in response to detecting this change, the association management resource140would create a respective association between caregiver CGVR188and each patient Jane Doe and John Smith. Additionally, the association management resource140may terminate an association between caregiver CGVR106and Jane Doe and John Smith. Yet further in this example embodiment, the respective pump-patient association lines, association information185-1indicates that: the fluid delivery system assigned the unique value FDD983has been assigned for use by Jane Doe. In response to detecting that a caregiver such as caregiver CGVR106currently dispenses medication order RX29prescribed to Jane Doe using the fluid pump FDD983, the association management resource140produces an association line between the medication order RX29and the fluid delivery system FDD983. The association line between the prescribed drug RX29and fluid delivery system FDD983indicates that the fluid delivery system FDD983is being used or has been assigned to deliver the prescribed drug RX29to patient Jane Doe. Using the association information185-1, it is possible to identify the status of fluid deliveries as well as assignments of different medical devices to different patients. In other words, the associations enable one to identify different types of information associated with medical care. For example, via the associations in association information185-1presented inFIG.2, the corresponding user is able to identify that caregiver CGVR106has been assigned to care for patient Jane Doe and that caregiver CGVR106has configured pump FDD983to deliver medication order RX29to Jane Doe. As previously discussed, the association management resource140creates associations between the different entities as specified by association information185based on input. For example, the association management resource140can be a computer server running on a local area network. The association management resource140is capable of communicating with medical devices/information systems connected either directly or wirelessly to that network190. By further way of a non-limiting example, the server exposes one or more communication services. These services utilize one or more communication mechanisms. For example, one service may be capable of communicating using RESTful web services while another, performing the same function, may support SOAP based web services. Each communication service is capable supporting one or more functions, including but not limited to, registering, modifying and/or unregistering clinical associations and returning association details to those that request that information. As previously discussed, the association information185can be configured to maintain a history of associations made over time such that it is possible to view prior existing associations between entities at a given snapshot in time. In one embodiment, the association management resource140produces the association information185to keep track of the history of the associations made over time. The retrieval of the history information from association information185stored in repository180, a respective user is able to keep track the occurrence of different types of events. All maintained associations can be made available to medical devices or any component capable of interacting through the server communication services. As shown in the association information185-1inFIG.2, note that there is currently no association between John Smith and any of the fluid delivery systems located in domain150-1. In this example embodiment, the association management resource140has not receiving information indicating that fluid delivery system125-1, fluid delivery system125-2, and fluid delivery system125-3reside in domain150-1(LOC277). In one embodiment, each of the fluid delivery systems can be configured to occasionally or periodically broadcast information indicating the presence at a particular location. In such an instance, a nearby communication interface at the location (such as communication interface145-1) may receive the communication and forward the location information to association management resource140. Accordingly, based on the received location information in corresponding entity, the association management resource140can create an association between each of the fluid delivery systems and a corresponding location in which the fluid delivery system resides. Alternatively, note that a caregiver may be required to operate a corresponding fluid delivery system to create a new association between the fluid delivery system and a location in which the fluid delivery system resides. Thus, association of a respective medical device (such as a fluid delivery system) can be automated or required that a caregiver manually associated a respective fluid delivery system with a location. Referring again toFIG.1, in this example embodiment, assume that there currently is no association between any of the fluid pumps (fluid delivery systems125) in domain150-1and a corresponding recipient108such as patient John Smith. Assume in this example that caregiver106(assigned the unique value CGVR106) receives notification that the medication orders RX24and RX25need to be administered to recipient108. The notification can be received on any suitable medical device. In one embodiment, the caregiver106receives the notification on medical device160-1assigned to and operated by the caregiver106. To associate respective one or more fluid delivery systems to recipient to administer the medication orders, the caregiver106initiates communications with association management resource140. For example, the caregiver106inputs association information to association management resource140to indicate the fluid delivery system125-1and fluid delivery system125-2are being assigned to John Smith. Supplying the association information to association management resource140can be achieved in any suitable manner. In one embodiment, the caregiver106provides the input (association information) associating the fluid delivery system125-1to John Smith through a graphical user interface of fluid delivery system125-1. In response to receiving the input, the fluid delivery system125-1communicates the pump-patient association information over communication link128-1to communication interface145-1. Communication interface145-1further communicates the input over network190to association management resource140. The association management resource140receives the input generated by the caregiver106and updates the corresponding association information185-2as shown inFIG.3to indicate that the fluid delivery system125-1(FDD313) has been assigned for use by recipient108(John Smith). In this example embodiment, as shown inFIG.3, in response to receiving the input notification from the caregiver106(CGVR106) that the fluid delivery system125-1(FDD313) has been assigned for use by recipient108(John Smith), the association management resource140creates a new patient-pump association310-1between recipient108(John Smith) and fluid delivery system125-1(FDD313). For further sake of illustration, assume that the caregiver106operates in graphical user interface of fluid delivery system125-2. In one embodiment, the caregiver106(CGVR106) provides the input (association information) associating the fluid delivery system125-2to John Smith through fluid delivery system125-2(FDD432). In response to receiving this further input from the caregiver106, the fluid delivery system125-2(FDD432) communicates this new pump-patient association information over communication link128-2to communication interface145-1. Communication interface145-1further communicates the input over network190to association management resource140. The association management resource140receives the input generated by the caregiver106and updates the corresponding association information185-2as shown inFIG.3. In this example embodiment, as shown inFIG.3, in response to receiving the input notification from the caregiver106that the fluid delivery system125-2(FDD432) has been assigned for use by recipient108(John Smith), the association management resource140creates a new patient-pump association310-2between recipient108(John Smith) and fluid delivery system125-2(FDD313). Note that the notification generated by caregiver106indicating assignment of the fluid delivery system125-1(FDD313) for use by recipient108(John Smith) can be submitted from any suitable resource. For example, as discussed above, the respective caregiver106can operate a respective graphical user interface of a corresponding fluid delivery system to communicate the association information to association management resource140. However, note that in accordance with further embodiments, the caregiver106can operate a graphical user interface of management device160-1to input the association information to association management resource140. In this latter instance, the management device160-1transmits the association information received from the caregiver106over communication link128-4to communication interface145-1. Communication interface145-1communicates the association information through network190to association management resource140. In a manner as previously discussed, the association management resource140utilizes the received information to create the association between the patient John Smith and the one or more fluid delivery systems. Accordingly, via generation of association information from any suitable resource, embodiments herein can include creating an association between a medical device and a corresponding entity such as a patient in the medical environment100. Creating the associations310-1and310-2between the fluid delivery systems and the patient is useful because it enables a corresponding caregiver106to more efficiently operate the fluid delivery systems assigned to recipient108(John Smith). For example, subsequent to making association between the recipient108and the fluid delivery systems, using respective graphical user interfaces of the fluid delivery systems125, the operator (caregiver106) of the fluid delivery systems can initiate a search for information associated with the recipient108(John Smith) to obtain useful information. For further sake of illustration, assume that the caregiver106provides input to a corresponding graphical user interface of the fluid delivery system125-1to transmit a request for information associated with an entity such as recipient108from fluid delivery system125-1over the network190to the association management resource140. In response to receiving the request, the association management resource140searches a repository for medical information associated with the entity to which the fluid delivery system has been assigned. In this example flow delivery system125-1has been assigned to recipient108(John Smith). The caregiver106may be interested and retrieving information regarding prescribed drugs prescribed to recipient108(John Smith). In such an instance, via communications through fluid delivery system125-1or management device160-1, the query from the caregiver106to association management resource140would indicate that the caregiver106would like information about one or more different drugs prescribed to the corresponding recipient108(John Smith). In response to receiving the query, the association management resource140accesses association information185shown inFIG.3to identify that John Smith has been assigned use of fluid delivery system125-1(FDD313) and fluid delivery system125-2(FDD432) by caregiver106. Additionally, via the association information185, the association management resource140identifies that medication orders RX24and RX36both have been assigned to recipient108(John Smith). In one embodiment, the association management resource140initiates retrieval of medical information (such as medication order information) associated with medication orders RX24and RX36from repository180or other suitable resource. In one embodiment, medication order information associated with a respective medication order can be stored as one or more retrievable objects for retrieval and viewing by the respective caregiver. The medication order information in a respective retrievable object can indicate parameters such as a type of fluid were type of drug to be delivered to the corresponding patient, a rate at which the fluid will be delivered to the corresponding patient, a time when the fluid should be dispensed to the corresponding patient, etc. Subsequent to retrieval of the medical information or object, the association management resource140initiates transmission of the medical information over the network190to fluid delivery system125-1. In accordance with associations identified by association management resource140, fluid delivery system125-1initiates display of the medical information associated with medication orders RX24and/or RX36on a respective graphical user interface displayed on a display screen of fluid delivery system125-1for viewing by caregiver106. Accordingly, association of the fluid delivery system to a corresponding patient enables the caregiver to easily retrieve information (such as medication order information) associated with the corresponding patient. Note that association of the fluid delivery systems to a corresponding patient is shown by way of non-limiting example. As previously discussed, embodiments herein can include use of a medical device to create any suitable types of associations. For example, further embodiments herein can include associating a fluid delivery system (fluid pump) with any suitable entity such as a location, one or more other medical devices, another fluid pump, a caregiver, etc. As discussed above, creation of an association makes it possible for a respective caregiver to retrieve and view related medical information associated with the entity to which the medical device has been assigned. FIG.4is an example diagram illustrating creation of associations amongst different entities in a medical environment according to embodiments herein. In this example embodiment, assume that the recipient108(John Smith) has recently been transported into domain150-1. Accordingly, association information185-3does not yet indicate an association between John Smith and corresponding domain150-1(LOC277). Assume that the association management resource140receives notification that John Smith has been moved into domain150-1. In response to receiving notification that the recipient108(John Smith) has been moved into domain150-1, the association management resource140updates the association information185-3inFIG.4to include association410to indicate that the patient John Smith now resides in domain150-1(LOC277). The notification that the recipient108has been moved into domain150-1can be received from any suitable resource. For example, in one embodiment the caregiver106can operate management device160-1to notify association management resource140that the recipient108now resides in domain150-1. In accordance with an alternative embodiment, information system165can be configured to keep track of the location of each of the patients in the medical environment100. In such an embodiment, the information system165can be configured to forward the location information (medical information) associated with the recipient108to the association management resource140. Further in this example embodiment, assume that the association management resource140receives input from each of the fluid delivery systems125indicating their location. Thus, in this example, the association information185-3managed by association management resource140indicates that: fluid delivery system125-1(FDD313) is available and associated with domain150-1(LOC277); fluid delivery system125-2(FDD432) is available and associated with domain150-1(LOC277); fluid delivery system125-3(FDD566) is available and associated with domain150-1(LOC277), and so on. Because the fluid delivery systems125-1,125-2, and125-3are not currently assigned for use by a particular patient, the association information185-3indicates that such fluid delivery systems are available. Thus, in addition to managing associations amongst each of the different entities in medical environment100, the association management resource140can be configured to maintain status information associated with each of the entities as well. Assume further in this example embodiment that the caregiver106operates fluid delivery system125-1(FDD313) to transmit association information to association management resource140. As previously discussed, the fluid delivery system125-1transmits the association information (associating the fluid delivery system125-1to recipient108) over communication link128-1to communication interface145-1. Communication interface145-1further communicates the association information generated by caregiver106(or other suitable resource) to association management resource140. In response to receiving the association information, the association management resource140updates the association information185-4as shown inFIG.5to indicate the new association510-1between the fluid delivery system125-1(FDD313) to recipient108(John Smith). That is, the new association510-1indicates that the fluid delivery system125-1(FDD313) has been assigned for use by recipient108(John Smith). Assume further in this example embodiment that the caregiver106operates fluid delivery system125-2(FDD432) to transmit association information to association management resource140. As previously discussed, the fluid delivery system125-2transmits the association information (associating the fluid delivery system125-2to recipient108) over communication link128-2to communication interface145-1. Communication interface145-1further communicates the association information generated by caregiver106to association management resource140. In response to receiving the association information, the association management resource140updates the association information185-4inFIG.5to indicate the new association510-2between the fluid delivery system125-1(FDD313) and recipient108(John Smith). In a manner as previously discussed, association of the fluid delivery systems with one or more entities in the medical environment100makes it easy for the caregiver106or other user to retrieve information associated with the interconnected entities. Each node in the association information185can include status information associated with the respective entity. For example, as previously discussed, association information185includes node representing John Smith. The node representing John Smith can include an object such as one or more files or documents associated with John Smith. The information in the object associated with John Smith can indicate information such as an age of the patient, gender of the patient, medical history, nature of an injury, allergies, etc. In other words, the object assigned to John Smith can include any useful information that would be helpful for providing care to John Smith while he resides in medical environment100. In a similar manner, the node associated with a respective caregiver can indicate useful information such as a name of the caregiver, the current location of the caregiver, the title of the caregiver such as whether the caregiver is a nurse or doctor, contact information of the caregiver, etc. As previously discussed, because the fluid delivery systems have been associated with the different entities in the medical environment100, the fluid delivery systems can be used to retrieve useful information. For example, a user in domain150-1can provide commands to a corresponding graphical user interface of fluid delivery system125-1to retrieve and display useful information on a respective display screen of the fluid delivery system125-1. Assume that the user of the fluid delivery system125-1generates a command to retrieve personal information associated with the recipient108(John Smith) to which the fluid delivery system125-1has been assigned. In such an instance, the user initiates transmission of the command to the association management resource140to retrieve the personal information about recipient108(John Smith). In response to receiving the command, the association management resource140retrieves the object assigned to the node John Smith in the association information185and forwards it to the fluid delivery system125-1for display on a corresponding display screen. Accordingly, the associations make it possible to retrieve useful information associated with the recipient108. FIG.6is an example diagram illustrating creation of associations between different entities in a medical environment according to embodiments herein. Assume in this example embodiment that the patient John Smith has been moved into domain150-1(LOC277) and that the caregiver106receives notification that John Smith requires administration of multiple medication orders including RX24and RX25. Assume further that the fluid delivery systems125-1,125-2, and125-3, are initially located in a room (LOC269) other than domain150-1(LOC277) where they are needed. The caregiver106realizes that she will need to retrieve fluid delivery systems in order to administer the medication orders assigned to John Smith. In one embodiment, to search for availability of fluid delivery systems, the caregiver106operates management device160-1and generates query620to learn of the availability of fluid delivery systems on floor two of building345. The caregiver106forwards the query to association management resource140. In response to receiving the query620, the association management resource140analyzes association information185-5and identifies that fluid delivery system125-1(FDD313), fluid delivery system125-2(FDD432), and fluid delivery system125-3(FDD566) are all located in a nearby room (LOC269) with respect to domain150-1(LOC277). The association management resource140transmits this information for display on management device160-1for viewing by caregiver106. Based on such information, indicating that available fluid delivery systems are located at location LOC269, the caregiver106walks to the hospital room (LOC269) to move fluid delivery system125-1(FDD313) and fluid delivery system125-2(FDD432) into domain150-1. As shown inFIG.7, in response to detecting movement of the fluid delivery systems125-1and fluid delivery system125-2into domain150-1, the association management resource140can receive updates indicating that the fluid delivery systems have been moved into domain150-1(LOC277). In response to detecting this condition (that fluid delivery system125-1and fluid delivery system125-2have been moved into domain150-1), as shown inFIG.7, the association management resource140updates association information185-6, creating an association between the fluid delivery system125-1(FDD313) and domain150-1(LOC277); the association management resource140creates an association between the fluid delivery system125-to (FDD432) and domain150-1(LOC277). Even though the fluid delivery system125-1and125-2have been moved into domain150-1, the association management resource140can be configured to maintain the status of these fluid delivery systems as being available because they have not yet been assigned to a corresponding patient. Further in this example embodiment, assume that the caregiver106produces and transmits association information to association management resource140indicating that fluid delivery system125-1and fluid delivery system125-2have been assigned for use by recipient108(John Smith). In such an instance, and in response to receiving the notification of new associations to be created, the association management resource140creates new association710-1to indicate that the fluid delivery system125-1(FDD313) has been assigned for use by recipient108(John Smith); the association management resource140creates new association710-2to indicate that the fluid delivery system125-2(FDD432) has been assigned for use by recipient108(John Smith). In a manner as previously discussed, subsequent to creating the associations, the respective fluid delivery system and or other management device can be used to retrieve useful information associated with the interrelated entities. FIG.8is an example diagram illustrating proximity association according to embodiments herein. Conventional medical devices typically operate independently and autonomously from one another even when those devices are connected to the same patient. As part of the setup of each device, a clinician or caregiver identifies both the location of the device and the patient association. In the event that multiple medical devices exist at a bedside, the same, time consuming association process must be performed with each device in order to associate the medical device with the other devices or patient. In other words, conventional methods require that the caregiver operate each of the devices independently to associate that device with a particular patient or other entity. According to embodiments herein, given the existence of the association management resource140, devices (such as fluid delivery systems125, medical device160-1, etc.) may associate with a device designated as a master device, form a group and inherit the location and patient associations of that master device. This significantly reduces the overall setup time of each subsequent device and reduces the probability of error during that process. As further discussed below, creation of a group of medical devices can be achieved in any suitable manner. Proximity association as described herein enables medical devices to form associations with one another through a few simple user interactions. For example, using a wireless communication, such as Bluetooth, Near Field Communication (RFC), RFID or similar near distance RF technology, etc., a medical device such as a fluid delivery system (master device) can be configured to transmit an invitation to nearby devices to join it in a group. Any available devices within range of this master device respond to the transmission, giving users and devices the option to join the group. For those that accept the invitation to join the group, an association is created between the two devices and the associated patient and location of the master device are synchronized with those joining the group. In one embodiment, although user interaction is required to initiate the formation of a group from one device and confirm membership in a group on another device, interactions can be straightforward and minimal. As part of the formation of the group, a personal area or piconet network is formed between the devices and the patient and location associations maintained by the master device is synchronized with each new group member. In accordance with more particular embodiments herein as shown in medical environment800ofFIG.8, proximity association can include a system made up of one or more medical devices825and association management resource140(such as a clinical association server). In this non-limiting example embodiment, each of the medical devices825can be configured to include a wireless transceiver (transmitter and receiver). For example, medical device825-1includes a transceiver to communicate with any other medical devices in medical environment800; medical device825-2includes a transceiver to communicate with any other medical devices in medical environment800; medical device825-3includes a transceiver to communicate with any other medical devices in medical environment800; medical device825-4includes a transceiver to communicate with any other medical devices in medical environment800; medical device825-5includes a transceiver to communicate with any other medical devices in medical environment800; and so on. From any medical device, a user may initiate the formation of a new group. The device from which an operator such as a caregiver initiates formation of the new group is referred to herein as the master device. In this example embodiment, assume that the medical device825-1is the master device. To initiate a group, the master device transmits a broadcast message to other medical devices located in the medical environment800. In one embodiment, the broadcast message is transmitted as an RF signal within domain150-1. In accordance with further embodiments, as a possible alternative to communicating the RF broadcast signal directly to the other medical devices, note that the medical device825-1can be configured to communicate with the association management resource140to identify nearby medical devices. In response to receiving a message from the medical device825-1that the operator would like to create a new grouping, the association management resource140can be configured to communicate over network190and communication interface145-1to medical devices825-2,825-3,825-4, etc., in domain150-1to indicate that the caregiver106might to create the new grouping. Accordingly, the other non-master medical devices in domain150-1can receive the invitation to join the new grouping in a number of different ways. For example, the medical devices in domain150-1can receive a communication directly from the master medical device825-1or receive notification from the association management resource140. Any medical device that receives the invitation and is available can join the group. For example, when a device receives the invitation message generated by master medical device825-1, the medical device receiving the invitation message prompts the user (via a respective notification on a display screen of the receiving device) to acknowledge or reject the group invitation on its local user interface for viewing by a caregiver. Thus, in this example embodiment, the display screen of medical device825-2displays a message that a nearby master medical device825-1generated a corresponding invitation to join a group; the display screen of medical device825-3displays a message that a nearby master medical device825-1generated a corresponding invitation to join a group; the display screen of medical device825-4displays a message that a nearby master medical device825-1generated a corresponding invitation to join a group; and so on. The visual prompt displayed on each of the medical devices receiving the broadcast message from medical device825-1indicates that medical device825-1has initiated formation of a medical device grouping. The visual prompt can indicate patient and location information associated with a particular patient for which the association is being created. Display of the visual prompt on each of the medical devices receiving the broadcast message gives the caregiver the option to join the group. More specifically, assume that the caregiver would like medical device825-1, medical device825-6, and medical device825-2, to be part of the grouping. Because the medical device825-1initiated the broadcast message inviting other medical devices to possibly join the group, medical device825-1is already part of the new grouping. To add medical device825-6to the grouping, the operator (such as caregiver106) in domain150-1provides input to the graphical user interface displayed on display screen of medical device825-6indicating that medical device825-6has joined the new grouping. To add medical device825-2to the grouping, the operator provides input to the graphical user interface displayed on display screen of medical device825-2indicating that medical device825-2has joined the new grouping. In one embodiment, in response to receiving input that the operator would like a respective medical device included in the new grouping, the respective medical device transmits a message to the other medical devices or association management resource140indicating that it has joined the new grouping. Each of the medical devices can be configured to display a listing of the current members of the new grouping. In accordance with further embodiments, the user reviews the members of the group from any device in the group and can optionally remove itself or other members from the group. When a device joins a group, it connects to a local network such as piconet network of the master device. It then inherits the patient and location associated with the master medical device825-1. Thus, if the master medical device825-1has been associated with recipient108(John Smith), then each of the medical devices825-6and825-2become associated with the recipient108(John Smith). By way of non-limiting example, once complete, the devices can be configured to notify association management resource140of its association with the group and its associated patient and location information. In a manner as previously discussed, the association management resource140creates and stores the associations amongst the medical devices and the new grouping. The association information is stored centrally and available to other devices in the system via the association management resource140. FIG.9is an example diagram of a flowchart illustrating formation of a group and creation of associations amongst one or more medical devices according to embodiments herein. In processing block910a flowchart900, the caregiver106optionally associates the master medical device825-1with corresponding location and/or patient information. In processing block915, the caregiver106operates the master medical device825-1to form a new grouping. In processing block920, the master medical device825-1forms a new grouping, shares his location and patient association information and broadcast a corresponding invitation to other potential members. In response to receiving a command to form a grouping, the medical device825-1(such as a first fluid delivery system) or association management resource140initiates communication with a set of one or more medical devices located in a vicinity of the medical device825-1(first fluid delivery system). In processing block925, each of the medical devices that receive the invitation initiates display of a query on a corresponding display screen of a medical device asking the user whether or not the device should be included in the new grouping. In one embodiment, each of the medical devices activates a prompt indicating that the respective medical device displaying the prompt can be programmed to join a group including the fluid delivery system. In processing block930, the caregiver provides input to each of the medical devices that are to be included in the new grouping. In processing block935, the medical devices that accept the invitation to join the group assume the associations of the group members. In processing block940, the caregiver106optionally reviews the new grouping and removes any medical devices that were incorrectly added to the new grouping. Note again that creation of the grouping amongst multiple medical devices can be performed in any suitable way. For example, in accordance with another embodiment, and with reference again toFIG.1, the caregiver106can operate fluid delivery system125-1in order to learn of other fluid delivery systems located in a corresponding vicinity. In this example embodiment assume that in response to transmitting a query to association management resource140, association management resource140transmits a response to fluid delivery system125-1indicating that fluid delivery system125-2and fluid delivery system125-3are also located within domain150-1based on the association information185. Accordingly, the association management resource140can provide notification to an operator (caregiver106) of the fluid delivery system125-1that fluid delivery system125-2and fluid delivery system125-3are available in a vicinity of the fluid delivery system125-1. Via input into a graphical user interface of the fluid delivery system125-1, the caregiver106can select delivery system125-2and fluid delivery system125-3in order to form a respective grouping. Assume that the fluid delivery system125-1communicates a request to form this new grouping to association management resource140. Assume further in this example that the request indicates that the fluid delivery system125-1would like to form a group including fluid delivery system125-1and fluid delivery system125-2. In response to receiving the request to form the new grouping, the association management resource140associates the fluid delivery system125-1and fluid delivery system125-2. The association management resource140records the association between the fluid delivery system125-1and the fluid delivery system125-2. FIG.10is an example diagram illustrating a patient association according to embodiments herein. When a new grouping of medical devices has not yet been associated with a patient, embodiments herein include creating an association between a selected patient and each medical device in the new grouping at a time when the selected patient is assigned for the first time to any of the medical devices in the newly formed grouping. In accordance with one embodiment, at the time of associating the new grouping of medical devices with a patient, a notification will be sent via wide area wireless technology, such as WiFi™, to the other devices in the group, indicating that the association now exists. This gives the user the option of accepting it or opting out of the group. Once a group has an associated patient, that patient association with the respective medical device cannot be changed. Changing the patient association with a respective medical device in the group will cause that device to be disassociated from the group. This avoids the possibility that a respective medical device (or new grouping of medical devices) will be inadvertently assigned to multiple patients. As shown flowchart1000, in processing block1010, the user associates a device in the group with a new patient. In processing block1015, a respective medical device determines whether a patient association already exists with a particular medical device. If so, processing continues at processing block1020. If not processing continues at processing block1025. In processing block1020, in response to detecting that the corresponding medical device is already associated with a patient, the medical device removes itself from the grouping and produces a corresponding notification. In processing block1025, in response to detecting that the corresponding medical device is currently not associated with a particular patient, and that the user associates the corresponding medical device with a new patient, the corresponding medical device associates itself with the news patient. In processing block1030, the corresponding medical device notifies other medical devices in the group of the association with the new patient. In processing block1035, each of the medical devices in the grouping that receives the notification of the association between the corresponding medical device and new patient updates their association to the new patient as well. Thus, when a single medical device in the grouping updates its association with a particular new patient, each of the other medical devices in the grouping updates their association with the new patient as well. FIG.11is an example diagram illustrating location association according to embodiments herein. Initially, the newly established grouping of medical devices may not be associated with a particular location. When a group of medical devices has no location association, this association will be set the first time any device in that group forms a respective association with location. In one embodiment, at the time of associating one of the medical devices and the grouping to a location, a notification is sent by the association management resource140via a wide area wireless technology, such as Wi-Fi™, to each medical device in the group. This causes each of the medical devices to update location association. Thus, when one of the medical devices in the grouping becomes associated with a particular location, all of the medical devices in the group become associated with the particular location. Note that a group's location association can be changed at any time. Doing so will result in a notification being sent by the association management resource140via a wide area wireless technology, such as Wi-Fi™, to each device in the group and cause each device to update its location. As further shown in flowchart1100ofFIG.11, in processing block1110, the caregiver106or other suitable resource associates a given medical device in the new grouping with a new location. In processing block1115, the caregiver106operates the given medical device to associate the given medical device with the new location. In processing block1120, the given medical device notifies all members of the newly formed group of the location change. In processing block1125, in response to receiving the notification from the given medical device, each medical device in the grouping changes its location association to the location as indicated by the association management resource140. Thus, association of one of the medical devices in the grouping to a corresponding location causes each of the other members in the grouping to be associated with the corresponding location. As previously discussed, one embodiment herein includes transmitting appropriate information to the association management resource140to indicate the creation of the new associations. In one embodiment, when the caregiver106exits the group formation utility on the master device, the device ceases to transmit and all devices disconnect. However, their association with the group remains intact. As previously discussed, each of the medical devices can be configured to provide the ability to disassociate itself with the respective group it has joined. A device will also automatically be removed from a group if a user attempts to form a new group from that device or associates the device with a different patient. Proximity Association Extensions 1. Embodiments herein can include creating state or programmed settings information for each of the medical devices in a respective grouping. In one embodiment, a respective medical device produces state information associated with the respective medical device. The respective medical device forwards the state information to association management resource140for storage in repository180. Any of the members in the grouping can communicate with the association management resource140to learn of the settings associated with the other medical devices. Thus, each of the medical devices in the grouping can be made aware of settings associated with other medical devices in the grouping. 2. In accordance with another embodiment, a grouping may include a first fluid delivery system and a second fluid delivery system assigned for use by the same patient. As previously discussed, the association management resource140can be configured to store settings information associated with each of the fluid delivery systems. The second fluid delivery system can be configured to communicate with the association management resource140to learn that the first fluid delivery system has been configured to deliver the same medicine as the second fluid delivery system. In such an instance, assuming that the infusion of the same drug from multiple different fluid delivery systems is a mistake, the second fluid delivery system (and/or first fluid delivery system) can be configured to generate a warning (such as an audible or visual warning) of the condition. The caregiver then takes corrective action. 3. In a similar vein, the second fluid delivery system can be configured to issue a warning notification to the caregiver106if the drug the second fluid delivery system is about to deliver is incompatible with a drug being delivered from the first fluid delivery system. In a similar vein, the second fluid delivery system can be configured to issue a warning notification to the caregiver106if the drug the second fluid delivery system is about to deliver results in a dangerous interaction with the drug being delivered from the first fluid. 4. Using information retrieved in #1 and knowledge of a scheduled order or order set, an unused but associated infusion device may prompt the user to allow it to auto-program itself to support a next scheduled treatment. 5. Using information retrieved in #1, an infusion device may issue a warning if the total fluid volume being infused into a respective patient is unsafe. 6. Any device in the group may disassociate with the group without impacting the remaining associations in the group. This includes the master device from where the grouping was first initiated. Disassociation of a respective member device from the group can be caused by the device being reset, power cycled, or re-associated with a new patient. 7. As previously discussed, if a group has been formed without a patient association, a new patient association can be created from any single device in the group and synchronized across all devices in the group via the association management resource140. Further Examples of Grouping Creation and Management FIG.21is an example diagram illustrating associations amongst resources according to embodiments herein. Note that each of the medical devices825as previously discussed inFIG.8can be a fluid delivery system. As indicated by association information185-21inFIG.21, the medical device825-1(FDD314), medical device825-6(FDD433), and medical device825-2(FDD567) are currently available for use. That is, they are not associated with any patient. Assume that caregiver106creates a respective grouping in any of the manners as discussed above. As previously discussed, the caregiver106can operate medical device825-1(FDD314) as a master device to initiate creation of a corresponding grouping. Assume that the caregiver106selects medical device825-2(FDD567) and medical device825-6(FDD433) for inclusion in the new grouping. As shown inFIG.22, in response to receiving notification from the master medical device or the slave medical devices, the association management resource140creates a new association850-1to indicate the association between the medical device825-1(FDD314) and medical device825-6(FDD433). In this example embodiment, in response to learning that medical device825-2is also to be included in the group, association management resource140also creates association850-2to indicate that medical device825-2is part of the grouping. For example, the association management resource140creates new association850-2to indicate the association between medical device825-6(FDD433) and medical device825-2(FDD567). As indicated by association850-1and association850-2in association information185-22, it is known that medical device825-1(FDD314), medical device825-6(FDD433), and medical device825-2(FDD567) are all part of the same grouping. After creating a corresponding grouping of related medical devices, the association management resource140can receive further input from the corresponding caregiver106indicating to associate the grouping of medical devices (FDD314, FDD433, and FDD567) with a corresponding patient's such as John Smith. In response to receiving such input, the association management resource140updates the association information185-23as shown inFIG.23to indicate that the new grouping of medical devices has been associated with recipient108(John Smith). As previously discussed, association of any medical device in the grouping with a corresponding patient results in the whole grouping of medical devices being associated with the corresponding patient. Thus, when the association management resource140receives notification that medical device825-1(FDD314) has been assigned by the caregiver106to John Smith, the association management resource140creates an association between each of the medical devices in the grouping and John Smith as shown. In addition to or as an alternative to associating the grouping (FDD314, FDD433, and FDD567) with a corresponding patient, the association management resource140can receive input from the caregiver106to associate this new grouping with a corresponding location. Assume that the caregiver106associates the new grouping of medical devices with domain150-1(LOC277). In response to receiving such input, the association management resource140updates the association information185-24as shown inFIG.24to indicate that the grouping of medical devices has been associated with domain150-1(LOC277). As previously discussed, association of any medical device in the grouping with a corresponding location results in the whole grouping of medical devices being associated with the corresponding location. Thus, when the association management resource140receives notification that medical device825-1(FDD314) has been assigned by the caregiver106to domain150-1(LOC277), the association management resource140creates an association between each of the medical devices in the grouping and domain150-1(LOC277). FIG.12is an example diagram illustrating census-based association according to embodiments herein. Most healthcare enterprises use information systems to track admissions, discharges and transfers across the enterprise. Information systems operating within clinical units across the enterprise can typically both consume ADT (Admit-Discharge-Transfer) messages from the healthcare enterprise and transmit them back to the enterprise when an ADT is initiated from that system. As a device operating within that enterprise, having knowledge of where a patient resides helps that device simplify the association of patients to those devices. Embodiments herein include a way to provide a medical device1260(such as management device160-1, fluid delivery system125-1, would delivery system125-2, etc.) with knowledge of admission, discharge, and transfer information can help facilitate this association process. FIG.13is an example diagram illustrating census-based association according to embodiments herein. As shown in the flowchart1300, the association management resource can be configured to receive location information associated with one or more entities in the medical environment100. The association management resource140collects location data indicating where each of multiple patients resides in the medical environment100. The association management resource140then stores the associations (such as location data) in repository180. As previously discussed, each of the associations (such as location data) associates a respective patient with a corresponding location in the medical environment in which the respective patient resides. As previously discussed inFIG.2, association information185-1indicates that John Smith resides that location LOC277(such as domain150-1), Jane Doe resides at location LOC299, James Henry resides at location LOC267, etc. For sake of illustration, in processing block1310, the association management resource140receives messages from information system165. By way of non-limiting example, the information system165can include a healthcare enterprise system that generates messages indicating a location of different entities. In one embodiment, the association management resource140receives ADT messages from the information system165. In processing block1315, the association management resource140extracts patient identification information, location information, demographic information, etc., from the messages received from information system165. In processing block1320, the association management resource140stores the received patient information in repository180as association information185. In processing block1325, in a manner as previously discussed, assume that a corresponding medical device1260is aware of its current location. The medical device forwards the location information (i.e., it's current location) to association manager resource140. Further in a manner as previously discussed, in processing block1330, the corresponding user operates a respective medical device1260such as a fluid delivery system, management device160-1, etc., to initiate association of the medical device1260with a corresponding patient. Assume that the user requests to associate the medical device1260with a corresponding patient. This can include providing input command to the medical device1260. In response to receiving the request, the medical device1260transmits a communication to association manager resource140to learn of the patients that are within a vicinity of the current location of the medical device1260. Assume that the association management resource140receives input indicating that the current location of the medical device1260is in a vicinity of floor2, building345. Based on association information185-1inFIG.2, the association manager resource140detects that Jane Doe, John Smith, and James Henry are present within a vicinity of the medical device. The association manager resource140generates a list including these names (i.e., identities of patients) and forwards the list of identities of the patients to the medical device1260. In processing block1335, the medical device1260receives the listing of names including Jane Doe, John Smith, and James Henry. The medical device1260initiates display of the listing of these names on a respective display screen of the medical device1260to indicate patients that were side in a vicinity of the current location of the medical device1260. In processing block1345, the user of the medical device1260selects a particular patient (such as John Smith) from the list to associate the medical device1260with the particular patient. In processing block1350, the medical device1260communicates the selection of the particular patient John Smith from the list to association management resource140. In a manner as previously discussed, the association management resource140then creates a new association between the medical device1260and the particular patient John Smith. In accordance with further embodiments, after creating a new association between medical device1260(such as management device160-1, fluid delivery system125-1, fluid delivery system125-2, etc.), the operator of the medical device1260can generate a query to association management resource140to learn of different medication orders that have been assigned to a particular patient John Smith. The caregiver106operating the medical device1260initiates transmission of a communication from the medical device1260to the association management resource140to learn of any medication order drugs that have been assigned for delivery to John Smith. The association management resource140receives the inquiry as transmitted over the network190from an operator of the medical device1260to association management resource140. As mentioned, the inquiry requests medication order drug information assigned to the particular patient John Smith. In response to receiving the inquiry, the association management resource140searches the association information185stored in repository180for the medication order drug information assigned to the particular patient John Smith. The association management resource140transmits the medication order drug information (associated with RX24and RX36) over the network190to the operator of the medical device. The medical device1260initiates display of the medication order drug information on a display screen of the medical device for viewing by the respective caregiver106. Note again that retrieval of the medication order drug information associated with John Smith is shown by way of non-limiting example only. Subsequent to creating the association between the medical device1260and a corresponding patient (or other entity), the operator of the medical device1260can obtain other types of information associated with the corresponding patient such as a doctor that has been assigned to the patient, the history of medical information associated with the patient, etc. FIG.14is an example diagram illustrating use of a management device to manage medical care according to embodiments herein. Mobile devices ranging from laptops to cell phones are increasingly becoming the primary productivity tool of care providers throughout the healthcare enterprise. The same devices (such as management device160-1) therefore become the ideal host for software applications enabling care providers to associate themselves with their patients and associate their patients with connected medical devices. The management device160-1can be any suitable type of computing device such as a smartphone, scanner, PDA, tablet computer, laptop computer, etc. Recall that management device160-1is disparately located with respect to fluid delivery systems or other medical devices located in the medical environment100. In one embodiment, the caregiver106stores the management device160-1in their pocket when moving from one location to another. Management device160-1executes management application1440. Execution of management application1440enables the caregiver to define or create associations as part of their normal care workflow. The management application1440can be configured to perform any suitable type of operations such as receiving input from a corresponding caregiver106operating the management device160-1, providing notifications to the corresponding caregiver106, communicating with association management resource140, and so on. As previously discussed, the caregiver106can operate management device160-1in order to associate itself with a corresponding patient. For example as previously discussed, the management device160-1can be configured to transmit its corresponding location information to association management resource140. Using association information185, the association management resource140forwards the listing of patients in a nearby vicinity of the management device160-1to management device160-1for display on display screen130. If desired, the caregiver106can provide input indicating which of the patients the caregiver106is going to provide care. Another way of associating a particular caregiver to a patient is to scan a corresponding barcode1420associated with the patient. For example, assume that caregiver106has already created an association with Jane Doe and Sidney Green indicating that the caregiver106will be providing care to these patients. The caregiver106can operate the management device and scan the barcode1420associated with John Smith to add John Smith as a patient cared for by caregiver106. In response to scanning the barcode1420, the management device160-1adds John Smith to the displayed list of patients that are cared for by the corresponding caregiver106. In accordance with further embodiments, in response to scanning of the barcode1420, the application1440transmits an identity of the scanned patient to association management resource140. The association management resource140updates the association information185to indicate that the caregiver106is now assigned to provide care to patient John Smith. As previously discussed, updating of the association information185can include creating an association between caregiver106(CGVR106) and John Smith. After creating the associations between the caregiver and a set of patients such as Jane Doe, Sidney Green, and John Smith, the caregiver160-1can operate the management device160-1to determine which patients are assigned to the caregiver106. For example, the caregiver106can generate a message from management device160-1to association management resource140to learn of any patients that are assigned to the caregiver106. The association management resource140transmits the list to management device160-1for display to caregiver106. Accordingly, the association management resource140can be configured to: receive a communication transmitted over the network190from the management device160-1(mobile device) operated by the caregiver106, the communication requesting a listing of patients assigned to the caregiver; analyze the association information185identifying a set of patients assigned to the caregiver; and in response to receiving the second communication, transmit a reply message over the network190to the management device160-1operated by the caregiver106, the reply message indicating the set of patients assigned to the caregiver106. FIG.15is an example diagram illustrating use of a caregiver's management device to associate one or more fluid delivery systems with a corresponding patient according to embodiments herein. Subsequent to associating patient John Smith to the caregiver106, the caregiver106can operate the management device160-1to identify any medical devices that have been assigned to the corresponding patient John Smith. For example, the caregiver106can operate management device160-1to communicate over network190with the association management resource140and retrieve a listing of any medical devices (such as fluid pumps) that have been assigned to the corresponding patient John Smith. The patient John Smith can be selected from the display screen130inFIG.14listing patients Jane Doe, Sidney Green, and John Smith. The association management resource140receives the communication transmitted over the network190from the management device160-1operated by the caregiver106. The communication indicates selection of a particular patient such as John Smith. In response to receiving the communication from management device160-1for any medical devices assigned to John Smith, the association management resource140transmits a message over the network190to the management device160-1operated by the caregiver160-1. The reply message from the association management resource140includes a listing of medical devices such as fluid delivery systems assigned to the particular patient John Smith. In this example embodiment, assume that the association management resource140indicates that fluid delivery system125-1(FDD313) and fluid delivery system125-2(FDD432) both have been assigned for use by John Smith. As shown inFIG.15, the management device160-1initiates display of the different fluid pumps assigned for use by John Smith. As further shown inFIG.15, the caregiver106operating management device160-1can be configured to scan barcode1520located on the fluid delivery system125-3. Scanning of the barcode1520indicates that the caregiver106like to add the fluid delivery system125-3(FDD566) for use by John Smith. The management device160-1communicates this information to association management resource140. In response to assigning the fluid delivery system125-3to the patient John Smith, the management device160-1initiates display of the identity of the fluid delivery system125-3(FDD566) on the corresponding display screen130of management device160-1to indicate that the fluid delivery system125-3is now assigned for use by John Smith. FIG.16is an example diagram illustrating use of a caregiver operated management device to dissociate a fluid delivery system with a corresponding patient according to embodiments herein. As shown, the management device160-1displays the different fluid delivery systems that have been assigned for use by John Smith. For example, fluid delivery system125-1(FDD313), fluid delivery system125-2(FDD432), and fluid delivery system125-3(FDD566) have been assigned for use by John Smith. In response to receiving selection of delete symbol1620displayed on display screen130of management device160-1, management device160-1communicates with association management resource140to delete a respective association between delivery system125-3(FDD566) and John Smith. Association management resource140receives the communication and updates the association information185to indicate that the association between fluid delivery system125-3(FDD566) and John Smith has been terminated. The association management resource140communicates the termination of the association to management device160-1. Subsequent to terminating the association, the management device160-1updates its corresponding display screen to indicate that only fluid delivery system125-1(FDD313) and fluid delivery system125-2(FDD432) are assigned for use by patient John Smith. FIG.17is an example diagram illustrating use of association information to facilitate delivery of multiple fluid-based drugs to a patient using multiple fluid delivery systems according to embodiments herein. In accordance with embodiments herein, medical devices that are involved in the delivery of a medication benefit from having access to the order for that medication over network190. For example, after an association is created between a patient and a device, the patient's order (such as a object specifying parameters of delivering a medication order) may be forwarded from association management resource140over network190to the respective medical device that is assigned to deliver the medication order fluid to a corresponding recipient. The following states illustrate settings of corresponding fluid delivery systems during the process of assigning different fluid-based drugs by a particular fluid delivery system. The process of receiving input from the different fluid delivery systems and display of corresponding notification information makes it easier for a corresponding caregiver to safely administer different drugs from multiple fluid pumps. State1700-1 Assume in this example embodiment that the caregiver106operates the fluid delivery system125-1to identify medication order medication assigned for delivery to patient John Smith. In such an instance, the caregiver106operates fluid delivery device125-1to transmit a query to association management resource140to learn of medication order medication prescribed to patient John Smith. In one embodiment, the query from the caregiver106includes a request for a listing of medicine prescribed to the patient John Smith. In response to receiving the query, the association management resource140searches the association information185and repository180for medication orders assigned to John Smith. Association management resource140analyzes the association information185and determines that medication order RX24and RX36have been assigned to John Smith. The association management resource140transmits a message (including medical information) to fluid delivery system125-1. The medical information in the message received by fluid delivery system125-1indicates that John Smith has been assigned medication order drugs RX24and RX36. Fluid delivery system125-1initiates display of a notification on display screen130-1of fluid delivery system125-1that both RX24and RX36are to be administered to patient John Smith. Assume in this example that the caregiver106operating the fluid delivery system125-1selects medication order RX24for delivery by fluid delivery system125-1. Selection of medication order RX24can include touching a display of a symbol RX24on the display screen of fluid delivery system125-1. In one embodiment, in response to receiving selection of the symbol RX24on the display screen of the fluid delivery system125-1, the fluid delivery system125-1transmits a message to association management resource140to indicate that the fluid delivery system125-1has been selected to deliver the medication order RX24to patient John Smith. In response to receiving the input, and in a manner as previously discussed, the association management resource140creates a new association between fluid delivery system125-1(FDD313) and node RX24in association information185to indicate that the medication order RX24is being administered by the fluid delivery system125-1. State1700-2 In response to receiving input indicating that fluid delivery system125-1has been selected to deliver medication order RX24to the patient John Smith, the fluid delivery system125-1presents a notification on a respective display screen of fluid delivery system125-1that medication order RX24has been assigned for delivery by fluid delivery system125-1. If desired, as shown, the display screen130-1of fluid delivery system125-1can further indicate that medication order RX36is still outstanding. For example, the message “NON YET ADMINISTERED” or other visual indicator implies that medication order RX36has not yet been assigned for delivery by a particular fluid delivery system. State1700-3 Further embodiments herein can include providing notification to fluid delivery system125-2that the corresponding medication order RX24is being delivered to the recipient108(John Smith) via fluid delivery system125-1(FDD313). For example, in one embodiment, the fluid delivery system125-2receives notification from association management resource140or other suitable resource that the fluid delivery system125-1has been assigned to administer the medication order RX24to patient John Smith. In response to receiving such notification, the fluid delivery system125-2initiates display of a message on display screen130-2indicating that the medication order RX24is being delivered on remote fluid delivery system125-1(FDD313). Accordingly, via the notification displayed on fluid delivery system125-2, the caregiver106is able to determine that the medication order RX36has not yet been assigned for delivery by a respective fluid pump. Assume that the carrier106provides input to fluid delivery system125-2indicating selection of medication order RX36for delivery to the patient via fluid delivery system125-2. In one embodiment, the caregiver106touches the symbol labeled RX36on display screen fluid delivery system125-2in order to assign delivery system125-2for delivery of the medication order RX36. In response to receiving the assignment of medication order RX36to fluid delivery system125-2, the fluid delivery system125-2communicates with the association management resource140. In response the notification, the association management resource140creates an association between medication order RX36and the fluid delivery system125-2(FDD432) to indicate that fluid delivery system125-2has been configured to deliver the medication order RX36. Accordingly, via this newly created association, association management resource140tracks that the fluid delivery system125-2has been assigned to deliver medication order RX36. State1700-4 In response to the assignment of delivering medication order RX36on fluid delivery system125-2, the fluid delivery system125-2updates its corresponding display screen130-2to indicate that medication order RX36has been assigned for delivery on fluid delivery system125-2. State1700-5 Further embodiments herein can include providing notification to fluid delivery system125-1that the fluid delivery system125-2has been assigned to deliver medication order RX36to recipient108(John Smith). Fluid delivery system125-1can be configured to receive the notification from any suitable resource such as from fluid delivery system125-2or from association management resource140to update display screen130-1. Further embodiments herein can include receiving feedback from each of the fluid delivery systems indicating a status of delivering a corresponding medication order. For example, during the course of delivering medication order RX24, the fluid delivery system125-1can be configured to continuously communicate status information back to association management resource140regarding progress of delivering the medication order RX24to patient John Smith. In a similar manner, during the course of delivering medication order RX36, the fluid delivery system125-2can be configured to continuously communicate status information back to association management resource140regarding progress of delivering the medication order RX36to patient John Smith. Feedback from a respective fluid delivery system can include information such as a time when the medication order is administered, amounts of the medication order that have not yet been delivered to a corresponding patient, etc. In one embodiment, the caregiver106operates the medical device160-1to retrieve the status information associated with delivery of the medication order drugs from association management to resource140. Accordingly, from a remote location, the carrier106can monitor attributes of the fluid delivery systems125-1and125-2. FIG.18is an example diagram illustrating authentication and authorization of a user of a fluid delivery system according to embodiments herein. User authentication and authorization can be managed centrally within a healthcare enterprise. Information system165can include technology such as Microsoft's Active Directory, to manage user accounts (which include details on a user's credentials), roles, permissions, etc. In one embodiment, information system165includes an enterprise user management system. The association management resource140(clinical association server) is capable of interacting with an enterprise user management system and using that system to authenticate and authorize a user attempting to log into one of its connected medical devices. Optionally, the medical device operated by a respective caregiver is capable of interacting directly with an enterprise user management system and using that system to authenticate and authorize a user attempting to log into itself. As a more specific example, assume that caregiver106would like to log onto fluid delivery system125-1. In one embodiment, the fluid delivery system125-1initiates a challenge to a caregiver106operating the fluid delivery system to provide appropriate authentication information (such as username and password information) to operate the fluid delivery system125-1. In response to receiving input from a caregiver106desiring to log onto fluid delivery system125-1, the fluid delivery system125-1transmits the login request (such as username and password information) S inputted by the caregiver106to association management resource140. Association management resource140forwards the login request to information system165(such as an enterprise user management system). Thus, in response to the challenge, the information system165receives (such as login request) over the network190from the caregiver106. As mentioned, the login requests can include authentication information (such as username and password) to operate fluid delivery system125-1. The information system165or other suitable resource verifies the authentication information received from the fluid delivery system125-1. Subsequent to verifying the authentication information provided by the caregiver106in the login request, the information system165transmits a login response (such as a command) to association management resource140. The association management resource140forwards the login response to fluid delivery system125-1. The login response (such as a command) enables (e.g., unlocks) the fluid delivery system125-1, enabling the caregiver to perform operations as discussed herein such as deliver fluid to a patient using the fluid delivery system125-1. In accordance with further embodiments, and as previously discussed, after the caregiver106has logged in and is enabled to operate fluid delivery system125-1, the caregiver106can further communicate with association management resource140in order to associate the fluid delivery system125-1to the caregiver106. In other words, as previously discussed, the caregiver106can provide input specifying an identity of the caregiver106to the association management resource140. The association management resource140then modifies association information185to create an association between the caregiver106and the fluid delivery system125-1. In one embodiment, medical device (fluid delivery system125-1) has the ability to cache previously authenticated users, and optionally utilize that cache to authenticate users when the server is unable to provide user authentication and/or authorization services. Thus, the user can be authenticated without having to communicate over network190with a remote resource such as information system165or association management resource140. As mentioned, medical device (such as fluid system125-1) provides the logged in user the ability to indicate their association with the medical device and the patient being treated. In one embodiment, after an association has been established between a caregiver106and the corresponding medical device (such as a fluid delivery system), all data generated by a respective fluid delivery system, such as medical alarms, can be tagged with an identity of the caregiver106. This information is optionally routed to the caregiver106for display on medical device160-1. FIG.19is an example block diagram of a computer device for implementing any of the operations as discussed herein according to embodiments herein. In one embodiment, fluid delivery system100includes a computer system750to execute association management resource140, management application1440, etc. As shown, computer system750of the present example includes an interconnect711, a processor713(such as one or more processor devices, computer processor hardware, etc.), computer readable storage medium712(such as hardware storage to store data), I/O interface714, and communications interface717. Interconnect711provides connectivity amongst processor713, computer readable storage media712, I/O interface714, and communication interface717. I/O interface714provides connectivity to a repository780and, if present, other devices such as a playback device, display screen, input resource792, a computer mouse, etc. Computer readable storage medium712(such as a non-transitory hardware medium) can be any hardware storage resource or device such as memory, optical storage, hard drive, rotating disk, etc. In one embodiment, the computer readable storage medium712stores instructions executed by processor713. Communications interface717enables the computer system750and processor713to communicate over a resource such as network190to retrieve information from remote sources and communicate with other computers. I/O interface714enables processor713to retrieve stored information from repository180. As shown, computer readable storage media712is encoded with controller application140-1(e.g., software, firmware, etc.) executed by processor713. Controller application140-1can be configured to include instructions to implement any of the operations as discussed herein. During operation of one embodiment, processor713(e.g., computer processor hardware) accesses computer readable storage media712via the use of interconnect711in order to launch, run, execute, interpret or otherwise perform the instructions in association management application140-1stored on computer readable storage medium712. Execution of the association management application140-1produces processing functionality such as association management process140-2in processor713. In other words, the association management process140-2associated with processor713represents one or more aspects of executing association management application140-1within or upon the processor713in the computer system750. Those skilled in the art will understand that the computer system750can include other processes and/or software and hardware components, such as an operating system that controls allocation and use of hardware resources to execute association management application140-1. In accordance with different embodiments, note that computer system may be any of various types of devices, including, but not limited to, a wireless access point, a mobile computer, a personal computer system, a wireless device, base station, phone device, desktop computer, laptop, notebook, netbook computer, mainframe computer system, handheld computer, workstation, network computer, application server, storage device, a consumer electronics device such as a camera, camcorder, set top box, mobile device, video game console, handheld video game device, a peripheral device such as a switch, modem, router, or in general any type of computing or electronic device. In one non-limiting example embodiment, the computer system850resides in fluid delivery system100. However, note that computer system850may reside at any location or can be included in any suitable resource in network environment100to implement functionality as discussed herein. Functionality supported by the different resources will now be discussed via flowcharts inFIG.20. Note that the steps in the flowcharts below can be executed in any suitable order. FIG.20is a flowchart2000illustrating an example method according to embodiments. Note that there will be some overlap with respect to concepts as discussed above. In processing block2010, the association management resource140receives input over a network190. The input associates fluid delivery system125-1to an entity located in a medical environment100in which the fluid delivery system125-1is operated. In processing block2020, the association management resource140records an association between the fluid delivery system125-1and the entity as indicated by the received input. In processing block2030, the association management resource140initiates transmission of medical information associated with the entity over the network to fluid delivery system125-1. Note again that techniques herein are well suited for use in management of fluid delivery systems. However, it should be noted that embodiments herein are not limited to use in such applications and that the techniques discussed herein are well suited for other applications as well. Based on the description set forth herein, numerous specific details have been set forth to provide a thorough understanding of claimed subject matter. However, it will be understood by those skilled in the art that claimed subject matter may be practiced without these specific details. In other instances, methods, apparatuses, systems, etc., that would be known by one of ordinary skill have not been described in detail so as not to obscure claimed subject matter. Some portions of the detailed description have been presented in terms of algorithms or symbolic representations of operations on data bits or binary digital signals stored within a computing system memory, such as a computer memory. These algorithmic descriptions or representations are examples of techniques used by those of ordinary skill in the data processing arts to convey the substance of their work to others skilled in the art. An algorithm as described herein, and generally, is considered to be a self-consistent sequence of operations or similar processing leading to a desired result. In this context, operations or processing involve physical manipulation of physical quantities. Typically, although not necessarily, such quantities may take the form of electrical or magnetic signals capable of being stored, transferred, combined, compared or otherwise manipulated. It has been convenient at times, principally for reasons of common usage, to refer to such signals as bits, data, values, elements, symbols, characters, terms, numbers, numerals or the like. It should be understood, however, that all of these and similar terms are to be associated with appropriate physical quantities and are merely convenient labels. Unless specifically stated otherwise, as apparent from the following discussion, it is appreciated that throughout this specification discussions utilizing terms such as “processing,” “computing,” “calculating,” “determining” or the like refer to actions or processes of a computing platform, such as a computer or a similar electronic computing device, that manipulates or transforms data represented as physical electronic or magnetic quantities within memories, registers, or other information storage devices, transmission devices, or display devices of the computing platform. While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present application as defined by the appended claims. Such variations are intended to be covered by the scope of this present application. As such, the foregoing description of embodiments of the present application is not intended to be limiting. Rather, any limitations to the invention are presented in the following claims. | 98,043 |
11857756 | Throughout the drawings, like reference numbers should be understood to refer to like elements, features and structures. DETAILED DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENTS As will be appreciated by one skilled in the art, there are numerous ways of carrying out the examples, improvements, and arrangements of a metering system in accordance with embodiments of the present invention disclosed herein. Although reference will be made to the illustrative embodiments depicted in the drawings and the following descriptions, the embodiments disclosed herein are not meant to be exhaustive of the various alternative designs and embodiments that are encompassed by the disclosed invention, and those skilled in the art will readily appreciate that various modifications may be made, and various combinations can be made, without departing from the invention. Although various persons, including, but not limited to, a patient or a healthcare professional, can operate or use illustrative embodiments of the present invention, for brevity an operator or user will be referred to as a “user” hereinafter. Although various fluids can be employed in illustrative embodiments of the present invention, for brevity the liquid in an injection device will be referred to as “fluid” hereinafter. Illustrative embodiments in accordance with the present invention are depicted inFIGS.1-30. In an illustrative embodiment according to the present invention, a metering system is provided for use in a wearable insulin infusion patch. For example, in illustrative embodiments of the present invention, the metering system is part of a larger fluidics sub-system that includes a flexible reservoir for storing insulin and a cannula assembly for delivering the insulin into sub-cutaneous tissue. The metering system draws a small dose of fluid from the reservoir and then pushes it down the cannula line and into the patient. The fluid dose is small relative to the reservoir volume, such that many pump strokes are required to completely empty the reservoir. FIG.1shows a diagram of an architecture of a patch pump100in accordance with an exemplary embodiment of the present invention. The patch pump100includes a fluidics sub-system120, an electronics sub-system140and a power storage sub-system160. The fluidics sub-system120includes a fill port122in fluid communication with a reservoir124. The reservoir124is adapted to receive fluid from a syringe, through the fill port. The fluidics sub-system120further includes a volume sensor126mechanically coupled to the reservoir124. The volume sensor126is adapted to detect or determine the fluidic volume of the reservoir. The fluidics sub-system120further includes a metering subsystem130, which includes an integrated pump and valve system132mechanically coupled to a pump and valve actuator134. The integrated pump and valve system132is in fluid communication with the reservoir124of the fluidics sub-system120, and is actuated by the pump and valve actuator134. The fluidics sub-system120further includes a cannula mechanism having a deployment actuator128mechanically coupled to a cannula129. The deployment actuator128is adapted to insert the cannula129into a user. The cannula129is in fluid communication with the integrated pump and valve system132of the metering sub-system130. The fluidics sub-system120further includes an occlusion sensor136mechanically coupled to a fluid pathway between the cannula129and the integrated pump and valve system132. The occlusion sensor136is adapted to detect or determine an occlusion in the pathway between the cannula129and the integrated pump and valve system132. The electronics sub-system140includes volume sensing electronics142electrically coupled to the volume sensor126of the fluidics sub-system120, a pump and valve controller144electrically coupled to the pump and valve actuator134of the metering sub-system130, occlusion sensing electronics146electrically coupled to the occlusion sensor136of the fluidics sub-system120, and optional deployment electronics148electrically coupled to the cannula129of the fluidics subsystem. The electronics sub-system140further includes a microcontroller149electrically coupled to the volume sensing electronics142, the pump and valve controller144, the occlusion sensing electronics146, and the deployment electronics148. The power storage sub-system160includes batteries162or any other electrical power source known in the art. The batteries162can be adapted to power any element or electronic component of the patch pump100. FIG.2shows the layout of fluidic and metering system components of a patch pump200in accordance with an exemplary embodiment of the present invention. The patch pump200includes a metering sub-system230, control electronics240, batteries260, a reservoir222, a fill port224and a cannula mechanism226. The elements of patch pump200are substantially similar to and interact substantially similarly to the elements of illustrative patch pump100that are referred to by similar reference numbers. FIG.3is an exploded view of a metering sub-system300of a patch pump in accordance with an exemplary embodiment of the present invention. The metering sub-system300includes a DC gear motor302mechanically coupled to a pump piston304disposed within a pump casing306. The pump piston304is mechanically coupled to a pump housing308by a coupling pin310. The metering sub-system300further includes a pump seal312between the pump piston304and the pump housing308. The metering sub-system300further includes port seals314on a seal carriage316disposed within a valve housing318. In an exemplary embodiment of the present invention, the output shaft320of the DC gear motor can rotate 360° in either direction. The pump piston304can rotate 360° in either direction and can translate by about 0.050 inches. The pump housing308can rotate 180° in either direction. The pump casing306, the port seals314, the seal carriage316and the valve housing318are preferably stationary. The metering sub-system300includes a positive displacement pump with integrated flow control valve & mechanical actuator and drive system. The pump includes a piston304and rotationally actuated selector valve. The metering system pulls a precise volume of insulin from a flexible reservoir into a pump volume321formed between the piston304and the pump housing308(seeFIG.5), and then expels this insulin volume through a cannula into a patient's subcutaneous tissue, administering insulin in small, discrete doses. The pump stroke creates positive and negative pressure gradients within the fluid path to induce flow. The stroke and internal diameter of the pump volume determine the nominal size and accuracy of the dose. The fluid control valve is actively shuttled between the reservoir and cannula fluid ports at each end of the pump stroke to alternately block and open the ports to ensure that fluid flow is unidirectional (from the reservoir to the patient) and that there is no possibility of free flow between the reservoir and the patient. FIG.4is an assembly view of the metering sub-system300according to an exemplary embodiment of the present invention. Also illustrated are a motor to piston coupling322, a piston to pump housing coupling324, a reservoir port326and a cannula port328. FIG.5is a cross-sectional view of the metering sub-system300of an exemplary embodiment of the present invention. As illustrated, a pump volume321is formed between the piston and the pump housing308. The pump housing includes a side port330that alternates in orientation between the reservoir port326and the cannula port328as the motor302reciprocates the pump, as will be described in greater detail below. In operation, an illustrative cycle of a metering system according to the present invention includes 4 steps: a 180° pump intake (counterclockwise) (when viewing from the pump toward the motor); a 180° valve state change (counterclockwise); a 180° pump discharge (clockwise); and a 180° valve state change (clockwise). A complete cycle requires a full rotation (360°) in each direction. FIG.6Ais an isometric view, andFIG.6Bis a cross-section view of the metering sub-system300in a starting position. In the starting position, the pump piston304is fully extended, the pump housing blocks the cannula port flow path at the cannula port328, and the reservoir port326is open to the side port330of the pump housing308, and a rotational limit sensor332is engaged. Pump housing308includes a helical groove334which receives coupling pin310. Piston304is in sliding engagement with pump housing308such that as piston304rotates within pump housing308(by rotational force of the motor302), coupling pin310slides along helical groove334to force piston304to translate axially with reference to pump housing308. In this embodiment, the helical groove334is formed into pump housing308and provides for 1800 of rotation for coupling pin310. FIG.7Ais an isometric view, andFIG.7Bis a cross-section view of the metering sub-system300during an intake stroke. The DC motor302turns the pump piston304, which is driven along the helical groove334(rotating and translating) of the pump housing308via the coupling pin310. The pump piston304translates toward the DC motor302, drawing fluid into the increasing pump volume321. During the intake stroke, friction between the seals and the outside diameter of the pump housing308is preferably be high enough to ensure that the pump housing308does not rotate. The pump housing308is stationary, while the pump volume321is expanding. The cannula port328is blocked, while the reservoir port326is open to fluid flowing into the expanding pump volume321. There is a sliding engagement between the motor302and the pump piston304. FIG.8Ais an assembly view,FIG.8Bis a detail view, andFIG.8Cis a cross-section view of the patch pump during a valve state change after an intake stroke. Torque is transmitted from the drive shaft of the motor302, to the pump piston304, and then to the pump housing308via the coupling pin310. Once the coupling pin310rotates to the end of the helical groove334, further rotation of motor302causes the coupling pin310to rotate pump housing308and pump piston304together as a unit without relative axial translation. The side port330on the pump housing308rotates between the reservoir port326and the cannula port328. Surface tension of the pump housing308side port330holds the fluid in the pump volume321. The pump housing side port330moves out of alignment with the reservoir port326and into alignment with the cannula port328over the next 180° rotation of the motor302. In between, both the cannula port328and the reservoir port326are blocked. The coupling pin310is at the end of the helical groove334and transmits torque to the pump housing308. The coupling pin310locks the pump piston304and the pump housing308together to prevent relative axial motion between the two components. The pump piston304and the pump housing308therefore rotate as a unit and do not translate relative to each other. The pump housing308rotates while the pump volume321is fixed and the pump piston304rotates. The seals314, the seal carriage and the valve housing318are preferably stationary. FIG.9Ais an assembly view, andFIG.9Bis a cross-section view of the metering sub-system in an intake travel stop position, ready to infuse. As illustrated, the side port330of the pump housing308is aligned with the cannula port328, the pump volume321is expanded, and the reservoir port326is blocked. The rotational limit sensor332is engaged by a feature on the rotating pump housing308. The motor302, the pump piston304, and the pump housing308are stationary. FIG.10Ais an assembly view, andFIG.10Bis a cross-section view of the metering sub-system300during a discharge stroke. At the end of the intake stroke the pump housing308engages the limit switch332, which causes the DC motor302to switch directions. Accordingly, the motor302turns the piston304and drives the coupling pin310down the helical groove334of the pump housing308, causing the piston304to translate axially. The pump piston304translates axially away from the DC motor302, pushing fluid from the pump volume321and out of the cannula port328to the cannula. During the discharge stroke, friction between the seals314and the outside diameter of the pump housing308is preferably high enough to ensure that the pump housing308does not rotate. The cannula port328is open to fluid flowing out of the collapsing pump volume321. The reservoir port326is blocked. The pump housing308is stationary while the pump volume321is collapsing and the pump piston304rotates and translates in a helical motion. The motor is slidingly connected to the piston304to accommodate the translation motion of the piston as it rotates in the helical groove334. FIG.11Ais an assembly view,FIG.11Bis a detail view, andFIG.11Cis a cross-section view of the metering sub-system300during a valve state change after a discharge stroke. Torque is transmitted from the drive shaft of the motor302, to the pump piston304, and then to the pump housing308via the coupling pin310. The pump housing308and pump piston304rotate as a unit with no relative axial motion. The side port330on the pump housing308rotates between the reservoir port326and the cannula port328, both of which are blocked during the rotation. Surface tension of the pump housing308side port330holds the fluid in the pump volume321. The coupling pin310locks the pump piston304and the pump housing308together to prevent relative axial motion between the two components. Therefore, the pump piston304and the pump housing308rotate as a unit and do not translate relative to each other. The pump housing308rotates while the pump volume321is fixed. The seals314, the seal carriage and the valve housing318are preferably stationary. FIG.12Ais an assembly view, andFIG.12Bis a cross-section view of the metering sub-system300after a pump cycle is complete. The pump mechanism (piston304) is fully extended, completing the pump cycle. The rotational limit sensor332is engaged to reverse the motor302and begin the pump cycle again. The cannula port328is blocked, while the reservoir port326is open to the flow path from the reservoir. In the foregoing exemplary embodiment, the pump piston both rotates and translates, the pump housing rotates, and the valve housing is stationary. However, it should be appreciated that in other embodiments, the system may be configured so that the pump piston rotates, the pump housing both rotates and translates, and the valve housing translates, or any other combination of motions causing the pump volume to increase and decrease, and a port in communication with the pump volume to move from alignment with the reservoir port to alignment with the cannula port. In the foregoing exemplary embodiment, the pump stroke and valve state change are configured with 180° rotational actuation from the motor. However, it should be appreciated that any suitable angle may be selected for the segments of the pump cycle. In the foregoing exemplary embodiment, there is an atmospheric break between the cannula and reservoir ports during the valve state change. However, it should be appreciated that in other embodiments, the seals may be configured, or additional seals may be added, to eliminate the atmospheric break and seal the pump and valve system during the state change. In the foregoing exemplary embodiment, a DC gear motor is used to drive the pump and valve. However, in other embodiments, any suitable drive mechanism may be provided to drive the pump and valve. For example, solenoids, nitinol wire, voice coil actuators, piezo motors, wax motors, and/or any other type of motor known in the art can be used to drive the pump. In the foregoing exemplary embodiment, the pump uses full discharge strokes. However, it should be appreciated that in other embodiments, a system with sequential incremental discharge strokes may be used to dispense finer doses. In the foregoing exemplary embodiment, the pump uses on/off limit switches to determine the state of the system at the limits of rotational travel. However, it should be appreciated that in other embodiments, other sensors with the capability to determine intermediate states, such as an encoder wheel and optical sensor, may be used to improve the resolution of the sensing scheme. It should be appreciated that the internal diameter of the pump may be adjusted to change the nominal output per cycle. In the foregoing exemplary embodiment, the pump uses elastomeric O-ring seals. However, it should be appreciated that other arrangements may also be used. For example, fluid seals may be molded directly onto the seal carriage, other elastomeric seals such as quad rings could be used, or other seal materials such as Teflon or polyethylene lip seals are used. In alternate embodiments of the invention, the motion of the pump can be used to initiate or trigger the deployment of the cannula. In the foregoing exemplary, the system advantageously uses a bi-directional actuation. The motor rotation is reversed to alternate between intake and discharge strokes. This provides a safety feature that prevents runaway in the event of a malfunctioning motor. The motor must reciprocate in order for the pump to continue delivering medication from the reservoir. However, it should be appreciated that in other embodiments, the metering system is designed to use a unidirectional actuator. In the foregoing exemplary embodiment, the system uses a pouch reservoir with two flexible walls. However, in other embodiments, the reservoir can be formed in any suitable manner, including with one rigid and one flexible wall. FIG.13is an exploded view of a metering sub-system1300for a patch pump in accordance another illustrative embodiment of the present invention. The metering sub-system1300includes a motor and gearbox assembly1302and a pump assembly1304. FIG.14is an exploded view of the pump assembly1304. The pump assembly1304includes a piston1306mechanically coupled to a sleeve1308through a coupling pin1310, within a pump manifold1312. The pump assembly1304further includes port seals1314, a plug1316, a sleeve rotational limit switch1318and an output gear rotational limit switch1320. The piston1306rotates a total of 196° in either direction and can translate by about 0.038 inches. The sleeve1308and the plug1316rotate together (as a pair) 56° in either direction. The pump manifold1312and the port seals1314are stationary. FIG.15is an exploded view of the motor and gearbox assembly1302. The motor and gearbox assembly1302includes a gearbox cover1322, compound gears1324, an output gear1326, axles1328, a gearbox base1330, a motor pinion gear1332and a DC motor1334. FIGS.16A-16Dillustrate the assembly and operation of the piston1306, sleeve1308and coupling pin1310.FIG.16Aillustrates the piston1306, which includes a press fit hole1338which receives the coupling pin1310, as well as a piston seal1340, which tightly seals the piston within the sleeve1308. Sleeve1308includes a helical groove1342. Piston1306is pressed axially into sleeve1308, and then coupling pin1310is press fit into hole1338through the helical groove1342. This provides operation similar to the above described embodiment, where rotation of the piston1306causes axial translation of the piston1306relative to the sleeve1308due to interaction of the coupling pin1310and the helical groove1342.FIG.16Billustrates the piston1306, sleeve1308and coupling pin1310assembled, with coupling pin1310shown at the lower end of helical groove1342.FIG.16Cillustrates the axial stroke length1344of the piston1306relative to the sleeve1308as a result of the helical groove1342.FIG.16Dillustrates tapered faces1346that are preferably provided at the ends of the helical groove1342to center the coupling pin1310within the groove1342. FIG.17Aillustrates assembly of the plug1316with sleeve1308. As shown, plug1316includes a key1346, and a seal1348. Seal1348provides a tight fit for the plug within sleeve1308. Sleeve1308is provided with a recess1350adapted to receive key1346. The key1346locks plug1316in rotational engagement with sleeve1308. The plug1316is pressed against the end face of the (advanced) piston1306during assembly in order to minimize air in the pump chamber. Friction between seal1348and the inner surface of sleeve1308retain the plug1316axially. With appropriate selection of seal diameters, squeeze, and materials, the plug1316can also serve as an occlusion or overpressure sensor. Pump pressures greater than the threshold value will cause the plug1616to move axially and disengage with the sleeve rotational limit switch1318. Friction holds the plug1316in position against pressures below a desired threshold.FIGS.17B and17Cillustrate axial movement of the piston1306within sleeve1308.FIG.17Billustrates the piston1306in a first state with minimal or no pump volume between piston1306and plug1316. As shown, coupling pin1310is abutted against the lowest end of helical groove1342.FIG.17Cillustrates the piston1306in a second state with maximum pump volume1352between piston1306and plug1316. As shown, coupling pin1310is abutted against the highest end of helical groove1342. FIGS.18A-18Dillustrate the assembly of the sleeve1308into manifold1312. As illustrated inFIG.18A, manifold1312includes port seals1314to seal a reservoir port1354and a cannula port1356, respectively. A small side hole1358(SeeFIG.17B) on the sleeve rotationally shuttles back and forth between the two ports, which are 56 degrees apart. As shown inFIG.18B, sleeve1308includes a tab1360, and manifold1312includes a corresponding slot1362to permit sleeve1308to be assembled into the manifold1312.FIG.18Cillustrates a manifold window1364provided in the manifold. Tab1360is received within and travels in window1364when the sleeve1308is assembled into manifold1312. Tab1360and window1364interact to permit sleeve1308to rotate between two positions while preventing axial translation of the sleeve1308relative to the manifold1312. Sleeve1308rotates between a first position in which side hole1358is aligned with the reservoir port1354and a second position in which the side hole1358is aligned with the cannula port1356.FIG.18Dillustrates the sleeve1308assembled into the manifold1312, with tab1360located within manifold window1364. FIG.19is a cross section of the assembled metering system. As illustrated, port seals1314are face seals which are compressed between the sleeve1308OD and recessed pockets in the manifold1312. As also illustrated, tab1360is located within manifold window1364, and side hole1358is shown in transition between the reservoir port1354and the cannula port1356. Output gear1326includes a cam feature1366that engages rotational limit switch1320to signal the end of rotational movement of the piston1306and sleeve1308in either direction. FIGS.20A-20Eare cross-section views illustrating rotation of the sleeve1308within manifold1312to move the side hole from alignment with reservoir port1354to alignment with cannula port1356.FIG.20Aillustrates side hole1358aligned with the reservoir port1354. While in this position, piston1306moves away from plug1316to fill volume1352with fluid from the reservoir.FIG.20Billustrates the sleeve1308as it begins to rotate towards the cannula port1356. In this position, the side hole1358is sealed by the seal1314on the reservoir port1354. For this reason, the seal1314and the side hole1358diameter are preferably selected such that seal1314covers the opening of the side hole1358.FIG.20Cillustrates the side hole1358of sleeve1308between the seal1314of the reservoir port1354and the seal1314of the cannula port1356. In this position, neither seal1314blocks the side hole1358, but surface tension of the liquid holds the liquid in the pump chamber.FIG.20Dillustrates the side hole1358rotated further to a position where the seal1314of the cannula port1356covers the opening of the side hole1358. Finally,FIG.20Eillustrates the side hole1358rotated into alignment with the cannula port1356. While in this position, the piston1306translates axially to reduce the volume1352, forcing the fluid out of the cannula port1356and to the cannula. FIGS.21A-21Cillustrate operation of the limit switches. As shown inFIG.21A, plug1316includes a cam feature1368that interacts with limit switch1318. As the sleeve1308and plug1316rotate, the cam feature1368causes metal flexures of limit switch1318to come into contact with one another, until the plug1316has fully rotated to the next position. A bump1370in one of the flexures rests in the cam feature1368as illustrated inFIG.21Cwhen the plug1316is in either end point of the plug rotation. The limit switch1318opening and closing each rotation cycle signals that the plug1316remains in proper alignment with the limit switch1318. Under overpressure or occlusion conditions, increased pressure will cause plug1316to slide out from sleeve1308, and out of alignment with the limit switch1318. Thus, overpressure conditions are detected. Limit switch1320is engaged by cam feature1366of output gear1326at each end of the rotation cycle. This signals the motor1334to reverse directions. With two metal flexures, as illustrated, it is not possible to determine from the limit switch which rotation cycle was completed. However, as will be appreciated, a third flexure would permit the direction of engagement to be determined. FIGS.22A-22Cillustrate the assembly of the motor and gearbox1302with the pump assembly1304. As illustrated inFIGS.22A and22B, motor and gearbox1302includes an opening1372to receive rotational limit switch1320. In this manner, output gear1326, which is internal to the gearbox housing, can access and engage the flexures of limit switch1320. Motor and gearbox1302also includes an axial retention snap1374so that the pump assembly1304may be snap-fit to the motor and gearbox1302. Motor and gearbox1302includes a rotational key1376within a pump-receiving socket1378to receive pump assembly1304and to prevent rotation of the pump assembly1304relative to the motor and gearbox1302. Output gear1326includes a slot1380(FIG.22B) adapted to receive a tab1382(FIG.22C) provided on the piston1306. When assembled, tab1382is received into slot1380so that the output gear1326can transmit torque to the piston1306. As the output gear1326rotates, the pump piston tab1382both rotates and slides axially in the slot. Metal spring flexures on the motor connections and limit switches are used to make electrical contact with pads on a circuit board during final assembly. In operation, the pump cycle of the above described embodiment includes five steps. First, an approximately 120° pump discharge (counterclockwise when viewing from the pump toward the gearbox); a 56° valve state change (counterclockwise); a 140° pump intake (clockwise); a 56° valve state change (clockwise); and an approximate 20° jog (counterclockwise) to clear the limit switch. A total pump cycle requires 196 degrees of output gear rotation in each direction. FIGS.23A-30Cillustrate a pump cycle. For the sake of clarity, only the output gear1326of the gearbox assembly1302is shown in the figures. FIG.23Aillustrates a starting position. As shown, the cam1366of output gear1326is not in contact with rotational limit switch1320, such that the flexures are not in contact with one another. The pump piston1306is retracted, as shown by the position of the coupling pin1310within helical groove1342inFIG.22C. In this position, sleeve1308blocks the reservoir flow path, the cannula port1356is open to the side hole1358of the sleeve1308, and the rotational limit sensor1320and the sleeve sensor1318(SeeFIG.23B) are both open. FIGS.24A and24Billustrate the metering sub-system during a discharge stroke. The output gear1326turns the pump piston1306in a first rotational direction (see arrow inFIG.24B), which is driven along the helical path of the helical groove1342in the sleeve1308via the coupling pin1310(SeeFIG.24A). The pump piston1306translates away from the gearbox while rotating, expelling fluid from the pump chamber1352and out of the cannula port1356. During the discharge stroke, friction between the port seals1314and the outside diameter of the sleeve1308should be high enough to ensure that the sleeve1308does not rotate during this portion of the cycle. FIGS.25A-25Cillustrate the metering sub-system during a valve state change after a discharge stroke. As shown inFIG.25A, after coupling pin1310reaching the distal end of helical groove1342, torque continues to be transmitted from the output gear1326, to the pump piston1306, and to the sleeve1308via the coupling pin1310. The sleeve1308and pump piston1306rotate as a unit with no relative axial motion. The side hole1358(not shown inFIGS.25A-25C) on the sleeve1308moves between the reservoir port1354and the cannula port1356. Tab1360moves in the direction shown by the arrow within the window1364of manifold1312. As shown inFIG.25B, sleeve limit switch1318is closed by the cam surface of plug1316. FIGS.26A and26Bshow the metering sub-system in a discharge rotational stop position. The side hole1358(not shown inFIG.26A or26B) of the sleeve is aligned with the reservoir port1354, the pump volume1352is collapsed, and the cannula port1356is blocked. Plug1316in a stop position, and sleeve limit switch1318is open. Output gear cam1366contacts rotational limit switch1320to signal the end of the rotation, such that output gear1326stops to reverse direction. FIGS.27A and27Bshow the metering sub-system during an intake stroke. The output gear1326turns the pump piston1306in the direction shown by the arrow inFIG.27B. The piston1306is translated axially relative to the sleeve1308due to interaction of the coupling pin1310within the helical groove1364. The pump piston1306translates toward the gearbox, pulling fluid from the reservoir into the pump chamber1352. During the intake stroke, friction between the seals and the outside diameter of the sleeve1308should be high enough to ensure that the sleeve1308does not rotate relative to the manifold1312. FIGS.28A to28Cshow the metering sub-system during a valve state change after an intake stroke. Coupling pin1310reaches the upper end of helical groove1342, motor1302continues to deliver torque, causing the sleeve1308and piston1306to rotate together. Tab1360on sleeve1308moves in the direction shown in the arrow inFIG.28Awithin the window1364in manifold1312. Cam surface1368of plug1316closes sleeve limit switch1318as plug1316rotates together with sleeve1308. The sleeve1308and pump piston1306rotate as a unit with no relative axial motion. During this rotation the side hole1358of the sleeve1308moves between the reservoir port1354and the cannula port1356. FIGS.29A and29Bshow the metering sub-system in an intake rotational stop position. In this position, the side hole1358of sleeve1308is aligned with the cannula port1356, the pump volume1352is expanded, and the reservoir port1354is blocked. Cam1366of output gear1326engages rotational limit switch1320to signal that rotation is complete. Motor1302stops to reverse direction. Sleeve limit switch1318is open. FIGS.30A-30Cshow the metering sub-system after a pump cycle is complete. The output gear cam1366is jogged off of the rotational switch1320and ready to start another cycle. FIGS.31A-31Cillustrate another metering system3100aaccording to an exemplary embodiment of the present invention.FIG.31Ashows the motor and gearbox assembly3101as well as a modified pump assembly3100. The motor and gearbox assembly3101is substantially similar to the motor and gearbox assembly illustrated and described above in connection withFIGS.13-30C. FIG.32is an exploded view of the pump assembly3100. The pump assembly3100includes a pump manifold3102, a port seal3104, a seal retainer3106, a piston3108which rotates ±196° and translates axially ±0.038″, a coupling pin3110, a sleeve3112with conductive pads, and a sleeve rotational limit switch3114having flexure arms3128. The sleeve3112with conductive pads rotates ±56° as illustrated. The pump assembly3100includes three flexure arms3128that operate as a rotational travel limit switch3114. The rotational travel limit switch3114will be described in further detail below. The rotational travel limit switch3114senses the position of the sleeve3112directly, rather than sensing the position of the output gear. This allows for more precise angular alignment of the sleeve3112with respect to the manifold3102and cannula port. FIGS.33A-33Billustrates the assembly of the piston3108into the sleeve3112. In this embodiment an internal wall3113in the sleeve3112forms the end face of the pump chamber. Features on the piston sleeve are designed with tolerances to minimize the gap between the end face of the piston3108and the face of the internal wall3113of the sleeve. FIGS.34A-34Eillustrates the assembly of sleeve3108into the manifold3102. As illustrated the port seal3104, the seal retainer3106, and the sleeve3112are inserted into the manifold3102. A small side hole3115(SeeFIG.34E) on the sleeve3112rotationally shuttles back and forth between a reservoir port and a cannula port, which are preferably 56 degrees apart. The sleeve3112is inserted past a retention tab3116(SeeFIG.34D) in the manifold3102and is then rotated into position to prevent axial travel. Because this embodiment prevents or minimizes axial movement of the plug, occlusion sensing by axial movement of the plug is typically not provided. FIG.35illustrates a cross section of the sleeve3112and manifold3102assembly taken through the port seal3104and through the axes of side ports to the manifold3102. The side ports to the manifold3102include the cannula port3118and reservoir port3120. The port seal3104is a face seal, which is compressed between the sleeve3112outer diameter and a recessed pocket in the manifold3102. FIGS.36A-36Care cross sections through the axes of the side ports as the sleeve3112rotates from the reservoir port3120to the cannula port3118, to illustrate the valve state change. In the initial position shown inFIG.36A, the sleeve side hole3115is open to the reservoir port3120. In this position the cannula port3118is blocked. In the intermediate position shown inFIG.36B, the sleeve side hole3115is blocked by the port seal3104during the transition. In the final position shown inFIG.36C, the sleeve side hole3115is open to the cannula port3118. In this position the reservoir port3120is blocked. FIGS.37a-37D illustrates the operation for the sleeve rotational limit switch3114. A three contact switch design allows the patch system to distinguish between the two rotational limits via switch input signals rather than through tracking the sleeve's angular orientation via software. Manifold3102preferably includes manifold mounting posts3122. The switch contacts3114are bonded to the posts3122with adhesive, ultrasonic welding, heat stake, or any other suitable bonding method. Sleeve3112includes conductive pads3124on the end of sleeve3112. These may be printed or over-molded metal inserts, or may be provided by any other suitable means. Sleeve rotational limit switch3114includes a plastic over-mold3126for spacing and mounting features for the flexures. Sleeve rotational limit switch3114also includes three metal flexures3128. Manifold3102is provided with alignment slots3130, which receive the flexures3128. In a first position, shown inFIG.37B, the side hole3115on the sleeve3112is aligned to the cannula port3118. In this position, a conductive pad3124on the sleeve3112bridges the center and right contacts3128a,3128b. In the middle position, shown inFIG.37C, the side hole3115on sleeve3112is midway between ports3118and3120. In this position, both sides of the switch3114are open. In the final position, shown inFIG.37D, the side hole3115on sleeve3112is aligned to reservoir port3120. In this position, conductive pad3124on the sleeve3112bridges the center and left contacts,3128b,3128c. The pump described above has a modified operating sequence. The operating sequence is substantially the same as that described above, with the exception that the 20° back jog is no longer required. The back jog is not required with the three contact switch design described above and a complete pump cycle consists of the following four segments. First, there is an approximately 140° pump discharge, which is counterclockwise when viewing from the pump toward the gearbox. Second, there is a 56° valve state change, which is also counterclockwise. Third, there is an 140° pump intake, which is clockwise. Fourth, there is a 56° valve state change clockwise. The total pump cycle requires 196 degrees of output gear rotation in each direction. FIGS.38A and38Billustrate an exploded view of another version of the pump assembly with elastomeric port and piston seals over-molded onto the manifold and pump piston respectively. This version of the pump functions in a manner substantially identical to the one described above, but has fewer discrete components and is easier to assemble. Over-molding seals directly onto the manifold and piston reduces the number of dimensions contributing to seal compression, allowing for tighter control and less variability in seal performance. FIG.39Aillustrates an exploded view of a pump assembly3900with an alternative rotational limit switch design. This version of the pump assembly includes a two contact design for the sleeve rotational limit switch. With this design, the pump would properly jog backwards at the end of a pump cycle so that the contact switch3902would be open in the rest state. As illustrated inFIG.39B, in a first position the side hole3115on the sleeve is aligned to the cannula port. In this position, a first rib3904on sleeve forces the contracts closed. In a mid-position shown inFIG.39C, the side hole3115on sleeve is midway between ports, and neither rib3904,3906touches the contact switch3902so it is open. In a third position shown inFIG.39D, the side hole3115on the sleeve is aligned to the reservoir port. In this position, a second rib3906on sleeve again forces the contact switch3902closed. FIG.40is an exploded view of another exemplary embodiment of a metering assembly4000. This embodiment shares substantial similarities with the embodiments described above so the following description focuses on the differences. Metering assembly4000includes a sleeve4002having a helical groove4004, a plug4006, seals4008, plunger4010, coupling pin4012, manifold4014, port seal4016, and flexible interlock4018.FIG.41illustrates the metering assembly in assembled form. Seals4008are preferably formed of an elastomeric material, and are unitary in construction. One seal4008is mounted onto plug4006, and the other seal4008is mounted onto plunger4010. Plug4006is preferably fixed into sleeve4002by gluing, heat sealing, or any other suitable means. An end face of the plug forms one surface of the pump volume. Plunger4010is inserted into sleeve4002, and coupling pin4012is press fit into the plunger4010and extends into helical groove4004to provide axial translation of the plunger4010as it is rotated by the motor (not shown). An end face of the plunger4010forms an opposing surface of the pump volume. Port seal4016is preferably a single molded piece of elastomeric material. This embodiment reduced the number of parts, and improves manufacturability.FIG.42is a cross section of the assembled metering assembly. FIGS.43A-43Cillustrate the interaction of the interlock4018with the sleeve4002. As shown inFIG.41, interlock4018is mounted onto manifold4014at either end of interlock4018. As shown inFIG.43A, an end face of sleeve4002includes a detent4020that is adjacent to a bump4022of the interlock4018when the metering assembly is in a first position (side hole aligned with reservoir pump). Under certain conditions, such as back pressure, it is possible that friction between the piston4010and the sleeve4008is sufficient to cause the sleeve to rotate before the plunger4010and coupling pin4012reach either end of the helical groove4004. This could result in an incomplete volume of liquid being pumped per stroke. In order to prevent this situation, interlock4018prevents sleeve4002from rotating until the torque passes a predetermined threshold. This ensures that piston4010fully rotates within sleeve4008until the coupling pin4012reaches the end of the helical groove4004. Once the coupling pin hits the end of the helical groove4004, further movement by the motor increases torque on the sleeve beyond the threshold, causing the interlock to flex and permit the detent4020to pass by the bump4022. This is illustrated inFIG.43B. At the completion of rotation of the sleeve4008such that the side hole is oriented with the cannula port, the detent4020moves past the bump4022in interlock4018. This is illustrated inFIG.43C. FIG.44illustrates a cross section of another exemplary embodiment of a metering system4400. The metering system4400includes a modified sleeve4402that has a face4404forming one surface of the pump volume. This embodiment eliminates the need for a plug as in the previous embodiment, and simplifies manufacturing. FIG.45illustrates another exemplary embodiment having a modified sleeve4500and switching mechanism4502.FIG.46is a perspective view of the modified sleeve4500, which includes a detent4504similar to the sleeve described above to interact with an interlock (not shown). Switch mechanism4502includes a limit switch arm4506adapted to rotate in either direction away from its neutral position. Sleeve4500includes a switching lever (actuator arm)4508adapted to interact with the limit switch4506as the sleeve4500rotates.FIG.47illustrates how limit switch4506rotates about an axis. Switch mechanism4502provides electrical signals to indicate the position of limit switch4506.FIG.48is a top view illustrating sleeve4500rotated to an orientation where limit switch4506has rotated to its maximum angle (alpha) from the neutral position. Further rotation of the sleeve causes the limit switch4506to be free of actuator arm4508and to return to its neutral position. This change in orientation of the switch arm indicates the end of the rotation of sleeve4500in one direction, and causes the rotational metering pump to reverse.FIG.49is a side elevation view oriented towards the sleeve face, illustrating the same interaction between limit switch4506and actuator arm4508.FIG.50is a side elevation view, showing sleeve4500and switching mechanism4502incorporated into a patch pump, together with interlock collar4510. FIG.51Aillustrates the relative angular positions of the limit switch4506and actuator arm4508. Alpha a is the angle of the limit switch4506. Beta13is the angle of the rotating sleeve and actuating arm.FIG.51Billustrate the relative change d(α)/d(β) vs. β. Reversal is preferably triggered at β=33°. As illustrated, as actuating arm4608rotates, it pushes limit switch4506away from the neutral position (α=0°). When actuating arm angle β reaches approximately 30β the actuating arm4508clears the limit switch4506, and limit switch4506returns to neutral (α=0°), thereby initiating a reversal of the rotational pump. The same procedure occurs in reverse as the sleeve4508rotates in the other direction. Accordingly, the sleeve reciprocates back and forth. Although only a few illustrative embodiments of the present invention have been described in detail above, those skilled in the art will readily appreciate that many modifications are possible in the illustrative embodiments, and various combinations of the illustrative embodiments are possible, without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention. | 43,955 |
11857757 | DETAILED DESCRIPTION Provided herein are systems and methods for delivering fluid to a patient. For example, medication such as insulin may be delivered transcutaneously using patch pumps that are user-friendly, environmentally-friendly, lower cost, discreet, less prone to errors, and/or that provide precise, repeatable doses of medication. As another example, the patch pump may incorporate components for rapid occlusion detection. Accessories for applying the patch pump to the patient's skin and managing the patch pump also are provided. In a preferred embodiment, the system includes a wearable insulin pump having a patch-style form factor for adhesion to a user's body surface. The systems and methods described herein may be used to deliver medication including, but are not limited to, insulin, antibiotics, nutritional fluids, total parenteral nutrition or TPN, analgesics, morphine, hormones or hormonal drugs, gene therapy drugs, anticoagulants, analgesics, cardiovascular medications, AZT or chemotherapeutics. The types of medical conditions that the systems and methods might be used to treat include diabetes, cardiovascular disease, pain, chronic pain, cancer, ADDS, neurological diseases, Alzheimer's Disease, ALS, Hepatitis, Parkinson's Disease or spasticity. Preferably, the systems and methods are optimized for transcutaneous delivery of insulin to users with diabetes including Type I Diabetes Mellitus patients. Referring toFIG.1, an exemplary medication infusion system including a patch pump for delivering medication is described. InFIG.1, components of the system are not depicted to scale on either a relative or absolute basis. Medication infusion system10may include applicator100, cannula200, pump300, cap400, cartridge500, charging system600, and/or software application700. Preferably, applicator100, cannula200, cap400, and cartridge500are disposable components that may be replaced approximately every 3-10 days and/or once the pre-filled cartridge is empty, while pump300is reusable and may last for an extended period of time, e.g., approximately 2-4 years. As such, pump300may be used with many different applicators, cannulas, caps, and pre-filled cartridges. Such a configuration is expected to promote sanitary use of the system, as the components exposed to the patient and the insulin are disposable, while reducing costs for components containing more expensive electronics, e.g., pump300, charging system600, and/or software application700, which may be used repeatedly. In a preferred embodiment, system10includes a second pump, such that the wearer may charge the second pump while using the first pump and vice versa. In this manner, the wearer will always have a pump that is charged and ready to be used once the cartridge of the pump in use is empty. Further, this system is designed to reduce waste while reducing the number of times the wearer is required to insert a new cannula. Medication infusion system10may be used to apply cannula200and a pad to a wearer and to deliver medication through cannula200via a patch pump coupled to the pad. Applicator100is configured to apply an adhesive pad to the wearer and, upon actuation, to insert cannula200into the wearer. The pad is configured to be secured to the wearer for a period of time, e.g., at least 3 days, 7-10 days, and then may be replaced by a similar pad using a similar applicator. The pad may include a pad skeleton having one or more locking mechanisms that are configured to couple the pad to applicator100for insertion of cannula200or to the assembled pump for delivery of medication. Applicator100may include an internal component configured to support an insertion mechanism designed to insert cannula200through the skin of the wearer via rotational movement and to guide and orient cannula200during insertion. Preferably, applicator100is designed to suppress noise during insertion. The insertion mechanism may include an applicator needle configured to pierce the wearer's skin and a biasing member, which may be coupled to one or more links configured to interact with cannula200and the applicator needle. Upon actuation by the wearer, the insertion mechanism preferably rotates and applies a distal force on cannula200and the applicator needle within cannula200, such that cannula200is inserted through the wearer's skin. Cannula200may include a proximal cannula head configured to couple to one or more locking mechanisms on the pad skeleton and, at the same time, uncouple applicator100from the pad skeleton. The insertion mechanism further may be configured to continue rotating to withdraw the applicator needle from cannula200and to store the applicator needle within the applicator after cannula200is inserted. Cannula200is designed to receive medication doses from a patch pump and to deliver the medication through one or more apertures. The one or more apertures may be disposed at the distal tip and/or along the elongated shaft of cannula200such that the medication is delivered along the length of elongated shaft. Preferably, the apertures are arranged and oriented such that the medication is delivered only below the derma layer of skin. Cannula200may include a cannula head having a self-sealing septum configured to support and guide the applicator needle during insertion of cannula200and the outflow needle of cap400during delivery of medication. In some embodiments, cannula200may be designed to change the location at which medication is delivered to the patient via the aperture(s) over time without repositioning cannula200in the patient's skin. Such a design is expected to extend the life of cannula200within the patient, allowing transcutaneous implantation for around 10 days or more. Further, such design may reduce the risk of cannula occlusion. In some embodiments, cannula200may include one or more biodegradable materials disposed within the lumen and/or the apertures of cannula200that are configured to dissolve over a period of several days, thereby opening new apertures over time through which medication is delivered via the cannula. Pump300is designed to pump medication from cartridge500through the microdosing system, through a transcutaneous portion, and into the wearer. The transcutaneous portion preferably includes a cannula inserted into the wearer's skin, the cannula configured to be fluidically coupled to a needle and having one or more apertures beneath the outer skin layer for delivery of the dose of medication. Pump300is designed to be removably coupled to cap400and the pad to form a patch pump, which is configured to deliver doses of medication through cannula200transcutaneously to the patient. The pump-cap assembly advantageously provides precise, repeatable microdoses of medication to the wearer. Pump300preferably is designed to be used for an extended period of time, e.g., over 1 year and more preferably up to 2-4 years, and may be manufactured to include a minimal number of parts. For example, in order to lower the cost of the patch pump, pump300may include less than 15 parts. After a cartridge of medication is used, a battery within pump300is charged and, after charging, the cartridge and cap may be removed and discarded, leaving pump300ready to be used again with a new cartridge and a new cap. Pump300may include a motor disposed within the pump housing and may be configured to move a pusher towards a plunger of cartridge500such that insulin is advanced through an inflow needle of cap400and to a microdosing system designed to measure and deliver predetermined doses of medication. Pump300preferably includes a controller disposed within the pump housing for controlling operation of pump300. For example, the controller may store instructions that, when executed, cause pump300to perform the operations described herein. In some embodiments, the controller of pump300may include a two processor architecture to, for example, to enhance the security of the pump. The first processor may control pumping while the second processor communicates data to and from the pump via a wireless chip. Advantageously, the first and second processors may be operatively de-coupled such that communication of data from outside the pump, handled by the second processor, does not interfere with the pump-related workings executed by the first processor. By isolating the pump processing from the external communication processing, security of the pump is enhanced. Pump300further may include one or more sensors designed to sense information associated with operation of pump300and/or physiological information associated with the wearer. The controller receives information from the sensor(s) and may adjust the algorithms associated with the pump based on such information. Additionally or alternatively, the controller may cause an alert based on the information from the sensor(s) to be issued. In some embodiments, pump300includes one or more skin sensors that detect skin of the wearer. The controller may cause the pump motor to activate only if a skin sensor on the skin-facing side of the pump housing detects skin. Pump300further may include a locking mechanism to lock pump300to cap400and the controller further may only unlock the pump after pump300reaches a predetermined state (e.g., the battery is charged and/or the pusher is reset to a home position). The controller further may monitor one or more sensors disposed within, on, or separate from the pump housing and alert the wearer via a vibration motor, an LED(s) of a user interface of the pump housing, a sound generator, or a mobile application based on the information sensed by the sensors. The sensors may include a contact sensor configured to detect a position of pumping components within the pump housing, a sensor configured to monitor the function of cap400, (e.g., to detect an occlusion in the dosing pathway, such as within the microdosing system of cap400or within the cannula), a position sensor configured to detect a position of a cam plate within the microdosing system of cap400, a pressure sensor configured to detect the pressure within cartridge500, a photoplethysmography sensor configured to detect a wearer's heart rate or other physiologic parameters, an accelerometer, a temperature sensor, a pressure sensor, a humidity sensor, an optical sensor to detect the insulin concentration in the cartridge via a specific marking on the cartridge that indicates the insulin concentration, and/or a continuous glucose monitoring sensor. Cap400preferably receives medication from cartridge500moved into tubing of cap400as a result of pumping by pump300. Further, cap400may deliver predetermined doses of the medication through an outflow needle, into cannula200, and to the wearer. Cap400preferably is designed to be replaced after the cartridge is empty or when the temperature sensor detects a temperature exceeding a predetermined temperature threshold, the temperature indicating that the insulin was damaged due to long exposure at a high temperature. Preferably, cap400is also manufactured to include a minimal number of parts, such as 15 parts, in order to lower the cost of cap400. Cap400may include a microdosing system configured to measure and deliver the predetermined doses of medication. The microdosing system may be configured to only deliver the predetermined dose of medication upon initialization of the microdosing system, for example, once the controller determines, based on information from the sensor, that the pressure within cartridge500is within a predetermined range. The microdosing system may include a dosing tube having a flattened portion configured to hold the predetermined dose, a cam plate coupled to a cam shaft, the cam plate having one or more raised surfaces, and/or a lever system configured to transition between a raised position and a lowered position upon contact with the raised surfaces of the cam plate when the cam shaft is rotated. Cap400further may include locking mechanisms configured to lock cap400to pump300and/or to the pad skeleton. Cartridge500is an enclosed container designed to hold the medication for infusion into the patient. Cartridge500may be a commercially available insulin container such as the NovoRapid PumpCart available from Novo Nordisk A/S of Bagsværd, Denmark. Cartridge500preferably is pre-filled with a plurality of doses of medication such as insulin. The patch pump is designed such that when cartridge500is inserted into the pump patch, the cartridge500is completely encased by pump300and cap400. Cartridge500may include a cartridge cap through which is disposed an inflow needle of cap400. Cartridge500further may include a flexible plunger configured to be advanced towards the cartridge cap, responsive to pumping by pump300. As the plunger is displaced, insulin is delivered to a microdosing system of cap400, which in turn delivers predetermined doses of medication to the wearer one at a time. Once cartridge500is empty, it may be replaced by a similar pre-filled cartridge. Charging system600is configured to charge one or more batteries within pump300, e.g., via respective inductive coils disposed within the housing of a charger and pump300. The charger is delivered with a USB-C to USB-A cable. The cable may be plugged into a standard USB-A socket (e.g. on an adapter put into a conventional wall electrical socket, on a computer, or in public transport), for charging components within the charger to permit charging pump300. Software application700is designed to cause a computer (e.g., smartphone, laptop, desktop, tablet, smartwatch, etc.) to communicate data with pump300and display information on the pump to a wearer in a user-friendly manner. Software application700may cause the computer to securely exchange data between two or more pumps that are used by a single wearer. Software application700preferably receives data from the second processor of pump300and may cause the computer to transmit such data to a second pump while pump300is charging. Software application700further may cause the computer to transmit to the patch pumps data indicative of the wearer's activity level and this data may be used to modify how the wearer is alerted and/or when the doses of medication are delivered. Referring now toFIG.2, exemplary attachment zones for the patch pump and an optional external sensor, such as a continuous glucose monitoring sensor are illustrated. Attachment zones12illustrate several locations on the wearer's body where the applicator may attach the adhesive pad and insert the cannula and to which the patch pump is secured. For example, the patch pump may be secured to the upper arms, abdomen, or thighs of the wearer. As will also be understood by one of ordinary skill in the art, the patch pump may be secured to other locations on the wearer. The patch pump also may be operatively coupled to an optional continuous glucose monitoring sensor, which may transmit data to a controller of the patch pump, which data may be used to adjust the time of insulin delivery or the amount of each dose. Preferably, the patch pump receives data from continuous glucose monitoring sensor14, which is configured to be attached within attachment zones12. Exemplary continuous glucose monitors include sensors commercially available from DexCom, Abbott, Eversense, Indigo, or Biolinq. The sensed glucose levels may be used to adjust the dosing cycles. For example, the patch pump may include an algorithm configured to determine when to deliver insulin to the wearer. The algorithm may recalculate the time of delivery depending upon the sensed glucose level such that the wearer's glucose level remains within a safe range. For example, if the wearer's glucose levels fall below a predetermined threshold, the controller may cause the patch pump to stop delivering insulin for a period of time. Or, if the wearer's glucose levels rise above a certain level, the controller may cause the patch pump to deliver a microdose of insulin. In addition, responsive to the sensed glucose levels, the algorithm may adjust the amount of insulin in the dose. For example, a standard dose of insulin may include the amount of insulin delivered over eight dosing cycles. If the wearer's glucose levels fall below a predetermined threshold, the controller may cause the patch pump to deliver a smaller dose of insulin than the standard dose, for example by permitting only 4 dosing cycles or 0 dosing cycles (stopping the pump). Further, as described above, software application700may receive information from the continuous glucose monitoring sensor or other monitoring systems, for example, sensed glucose levels, information about patient food intake, and/or information about patient's activity levels (e.g., due to exercising, playing sports). This information may be transferred to the patch pump via the communication circuitry and the processor of the pump and the patch pump may respond to the transferred information, causing the patch pump to adjust the timing and/or amount of each dose. In this manner, the pump is modular and interchangeable with many continuous glucose monitoring sensors or other monitoring systems, making the pump “universal.” Advantageously, the patch pump described herein may be used with a minimal amount of external monitoring while still being effective at delivering accurate microdoses of medication at levels to treat the wearer. The inclusion of sensors within the patch pump, such as the PPG sensor and a sensor for determining activity level, may result in less external monitoring systems, which can be beneficial for the wearer. For example, in one embodiment, the patch pump may only be used with a commercially available CGM sensor. Applicator, Pad, and Method for Inserting Cannula Referring now toFIGS.3A and3B, perspective and exploded views of an exemplary pad and applicator are described. Applicator100may transcutaneously apply a cannula, upon actuation by a user, which is designed to deliver doses of medication (e.g., insulin) from a patch pump configured to be removably coupled to the cannula. Advantageously, applicator100further may apply a pad that is adhered to the wearer's skin and then coupled to the patch pump. For example, actuation of applicator100may both insert the cannula and cause the cannula to be locked to the adhesive pad in a single actuation. Further, applicator100may include internal components designed to minimize noise during the actuation process. For example, applicator100may avoid clicks and/or hard stops that make audible noises during insertion of the cannula. In a pre-actuation state, applicator100may be coupled to pad102as shown inFIG.3A. For example, applicator100may be coupled to pad102via pad skeleton104of pad, which is disposed on a first surface of pad102. Skin-safe pad adhesive105may be disposed on a second, skin-facing surface of pad102such that the pump-pad assembly may be attached to a wearer for a period of time, for example, 3-5 days, 3-10 days, or 10 days or more. One or more release liners103may be attached to pad adhesive105until pad102is ready to be secured to the wearer. Pad skeleton104may be a frame with a shape designed to surround the pump-cap assembly so as to securely couple the adhesive pad to the pump-cap for wearing by the patient. Pad skeleton104may be designed to removably couple portions of pad102to applicator100in the pre-actuation state. For example, pad skeleton104may have one or more attachment mechanisms to lock pad102to applicator100and unlock upon actuation of applicator100. Advantageously, the attachment mechanisms also may lock the cannula to pad102after actuation. As depicted inFIG.3A, pad skeleton104may have pad attachments106at a first end of pad102and pad back clip108at a second end of pad102. Pad attachments106and pad back clip108may interact with applicator100or a patch pump to lock the pad to applicator100or the patch pump. Pad attachments106may include at least two arms that protrude upwards from the pad and away from the skin surface of the wearer. Each arm may have an opening (e.g., slot) to receive extensions from the applicator during pre-actuation and extensions from the cannula post-actuation. Thus, the arms, which may have a U-shape, and openings may be used to lock to both the applicator and the cannula. Pad skeleton104may also include pad clips holes107disposed on the sides of pad skeleton104. Pad clips holes107may be a hole or receptacle sized and shaped to interact with a corresponding feature of the pump-cap assembly such that the pump-cap assembly may be locked to the pad. Further, pad102may include pad opening109to allow direct sensing of the wearer's skin by one or more sensors of the pump. For example, the skin sensor(s) and/or the PPG sensor(s) may be positioned at pad opening109when the pump is coupled to the pad. Applicator100may include applicator housing110and actuator112. Applicator housing110is configured to house the mechanisms for inserting the cannula. After insertion of the cannula, internal component114is designed to withdraw and safely store the needle used to pierce the wearer's skin. Actuator112, upon actuation, causes the cannula to be transcutaneously inserted into the wearer's skin. Actuation of actuator112also may unlock applicator100from pad102. Actuation of actuator112also may lock the transcutaneously inserted cannula into pad102. For example, actuation of applicator100may insert the cannula transcutaneously, unlock the applicator from the pad, and lock the cannula to the pad in a single actuation. Actuator112may release the internal mechanism disposed within applicator housing110when actuated by the wearer, thus causing the cannula to advance through the wearer's skin. Actuator112may be a button configured to be pressed by the wearer as illustrated, or may be a lever, snap, knob, or the like. The mechanism for inserting the cannula may include internal component114, biasing member116, and links118and120, which are disposed within applicator housing110, and are configured to advance cannula200through pad102and into the wearer's skin. The mechanism may further include applicator needle150, which is configured to be disposed within cannula200during insertion and withdrawn from cannula200after insertion. Self-sealing septum224may be disposed within the cannula head of cannula200in order to support and guide applicator needle150and minimize backflow out of cannula200. Referring now toFIGS.4A and4B, cross-sectional perspective and side views of the applicator and pad are described. Applicator100may include one or more attachment mechanisms that are configured to interact with corresponding features of pad skeleton104to lock applicator100to pad102. These locking mechanisms may help retain applicator100locked to pad102when cannula200is inserted into the skin of the wearer. For example, applicator100may include one or more back pad couplers122, which may be coupled to pad back clip108at the second end of pad102. Back pad couplers122may be extensions that extend out from the applicator housing to couple with the pad skeleton. As described further below, applicator100also may be coupled to pad102via pad attachments106and may be uncoupled from pad102at the same time that cannula200is fully inserted into the wearer and locked to pad102. Internal component114supports the insertion mechanisms for inserting the cannula and, after insertion, withdrawing the needle disposed within the cannula. Internal component114may be coupled to applicator housing110at an angle. Preferably, internal component114is disposed at the angle (e.g., 30-60° angle, 40-50° angle, 45° angle) such that cannula200is inserted into the skin of the wearer at the same angle. Internal component114may be configured to position the tip of cannula200near pad102, between pad attachments106, in a pre-deployed state, as shown inFIG.4B. The insertion mechanisms supported by internal component may include biasing member116and links118and120. Biasing member116may be disposed at the proximal end of internal component114and preferably is a spring that may be coupled to one or more links that interact with cannula200. For example, as described further with respect toFIGS.7A-7D, biasing member116may be coupled to link118, link118may be coupled to link120, and link120may be coupled to cannula200. Actuator112may be disposed above internal component114, such that, when actuator112is pressed towards the skin by the wearer, a force also is applied to internal component114. Actuator112may include one or more activation ribs113, which are configured to engage with corresponding protrusions115disposed on the top of a lower portion of internal component114. Activation ribs113preferably are curved such that when a force is applied to actuator112by the wearer, the force applied to internal component114is perpendicular to the angle at which internal component114is disposed within applicator housing110. Activation ribs113reorient the force to be perpendicular to the internal component, such that friction is reduced, providing smoother insertion of the cannula without a stick-slip effect. Activation ribs113also allow a longer stroke upon activation, which results in more reliable insertion of the cannula. Referring now toFIGS.5A and5B, the internal components of the applicator are described. Internal component114may be injection molded to form a single piece of material and may be configured to fold in half, as depicted inFIG.5B, such that the internal component is sized and shaped to fit within the applicator housing. Internal component114may include upper portion132and lower portion134connected via hinge136. This configuration reduces the number of parts of the applicator, which contributes to a reduction in costs. Internal component114preferably includes a channel and one or more guiding mechanisms that are configured to help guide the cannula during insertion. An accurate location of insertion helps ensure that insulin is only delivered below the dermal layer of the wearer's skin. Upper portion132may include an upper portion of channel126and lower portion134may include a corresponding lower portion of channel126such that, when upper portion132is folded on top of lower portion134, the upper and lower portions of channel126form a complete channel. Channel126preferably is sized and shaped such that the cannula can move through the channel toward the wearer's skin. To ensure accurate control of the cannula as it moves through channel126, additional guiding mechanisms may guide the cannula on its insertion path. For example, the lower portion of channel126further may include one or more ledges128configured to interact with corresponding features of the cannula when the cannula is advanced in a distal direction. Advantageously, such ledges128ensure that cannula is inserted into the wearer's skin at a particular orientation, which may be helpful for aligning radially spaced apertures in the cannula within the wearer's skin. Further, the guiding mechanisms may extend into channel126to contact and guide cannula on the insertion path during insertion. For example, the cannula further may be guided by guiding arm140disposed on upper portion132and guiding arm138disposed on lower portion134. As described in further detail below, the cannula may have clips and wings sized and shaped to interact with ledges128and guiding arms138and140such that the cannula is advanced into the skin of the wearer in a substantially linear direction and with minimal rotation. Internal component114(e.g., at lower portion134) further may include blocking mechanism130, which is configured to interact with the biasing member and links such that, in an initial state, blocking mechanism130prevents rotation of the links. Attachment pad couplers124may interact with corresponding locking mechanisms of the pad skeleton to lock the applicator to the pad. For example, attachment pad couplers124may be coupled to the pad attachments at the first end of the pad. Attachment pad couplers124may be extensions (e.g., arms) that extend toward the pad. Further, attachment pad couplers124preferably are flexible such that contact from the cannula moves attachment pad couplers124away from the position that locks the applicator to the pad during cannula delivery. Referring now toFIG.6, operation of the internal component and mechanism for inserting the cannula is described. InFIG.6, internal component114is shown in a pre-assembled state. Lower portion134may include axis146around which link118is designed to rotate. Biasing member116extends around and along axis146. Biasing member116biases link118to rotate about axis118. Prior to actuation, blocking mechanism130contacts and holds link118in place. Upon actuation by the wearer, blocking mechanism130moves relative to link118such that blocking mechanism130no longer contacts link118, thereby allowing force applied by biasing member116to cause one or more links to rotate and advance the cannula and needle distally, through the skin of the wearer. Link118may be coupled to biasing member116such that link118cannot move relative to biasing member116. In a pre-deployed state, biasing member116may be biased in a direction (e.g., clockwise) such that link118applies a force to blocking mechanism130in a different direction (e.g., opposite, counterclockwise). Link120may be coupled to link118via joint142and applicator needle150may be coupled to link120via joint144. In a pre-deployed state, joint144may be disposed adjacent to cannula interface148and applicator needle150may be positioned within a lumen of cannula200. Applicator needle150may be sized and shaped such that the distal end of applicator needle150extends past the distal end of cannula200. Applicator needle150may have an angled tip that is configured to minimize the risk of hitting pad skeleton104or applicator housing110during insertion of cannula200. Cannula200may be disposed within channel126and may be configured to slide in a distal direction along ledges128, through channel126, and through the skin of the wearer. Referring now toFIGS.7A-7D, operation of the mechanism and steps for inserting the cannula are described. The applicator is configured to insert cannula200via rotational movement of the insertion mechanism of the applicator. This rotational movement provides several benefits over the mechanisms employed in previously known devices, including, for example, minimizing hard stops, thus reducing the noise of the applicator.FIG.7Adepicts the applicator in a pre-deployed state. Pad102is partially cut near the location of insertion of cannula200inFIGS.7A-7Dto better show how cannula200and applicator needle150are deployed. Biasing member116is biased in a clockwise direction and blocking mechanism130is disposed in a position that prevents link118, which is coupled to biasing member116, from moving in a counterclockwise direction. As will also be understood by one of ordinary skill in the art, biasing member116may instead be biased in a counterclockwise direction such that, upon actuation, link118rotates in a clockwise direction. The applicator may include a needle configured to pierce the skin of the wearer, and to provide a path for cannula200to advance through the skin. Alternatively, as described further below, a portion of cannula200may instead be used to pierce the wearer's skin. Applicator needle150may be disposed within the lumen of cannula200and may extend from cannula head204, through elongated shaft202, and past cannula tip218. In the pre-deployed state, cannula head204preferably is disposed at the proximal end of channel126such that cannula200is disposed entirely within applicator housing110. Cannula200may include one or more clips206disposed on cannula head204, which are configured to guide cannula200in a substantially linear direction. Clips206may extend outward from cannula and may be two wings disposed on either side of cannula head204and sized and shaped to slide along ledges128. Preferably, in the pre-deployed state, cannula tip218is disposed near pad102, between pad attachments106, such that clips206may be coupled to pad attachments106advancement of cannula200. FIG.7Bdepicts the applicator in a partially-deployed state, wherein cannula200is inserted into the skin of the wearer, but applicator needle150is not yet withdrawn. Upon actuation of actuator112, a downward force is applied to internal component114, which causes lower portion134to deflect. The downward force on blocking mechanism130transitions blocking mechanism130to a position beneath link118such that link118is able to freely rotate. Because biasing member116is biased in a clockwise direction and is coupled to link118, link118then rotates about axis146in a counter-clockwise direction. The rotation of link118causes link120, which is coupled to link118via joint142, to move distally and apply a distal force to applicator needle150and cannula200. Applicator needle150and cannula200are configured to move in a distal direction through channel126such that the distal end of applicator needle150pierces the skin of the wearer and at least a portion of cannula200is inserted. Preferably, clips206are disposed on cannula head204such that clips206slide along ledges128, guiding cannula200and applicator needle150in a substantially linear direction. As described further below, when cannula200is inserted, the proximal end of cannula200preferably is coupled to one or more pad attachments disposed on the pad skeleton in order to lock cannula200to the pad. At the same time that cannula200is coupled to the pad skeleton, the applicator may be uncoupled from pad skeleton in a single actuation. InFIG.7C, the applicator is depicted in a fully-deployed state, wherein cannula200is inserted into the skin of the wearer and applicator needle150is withdrawn. After cannula200is inserted, biasing member116may continue to apply a force to link118such that link118continues to rotate in a counter-clockwise direction, forcing link120to move in a proximal direction. Preferably, cannula200remains coupled to the pad skeleton and applicator needle150remains coupled to link120via joint144such that cannula200and applicator needle150are separated. As link120moves in a proximal direction, applicator needle150is withdrawn from cannula200and into the applicator, at least a portion of cannula200remaining in the wearer's skin. The withdrawal of applicator needle150into the applicator ensures the needle is stored in a safe, remote place. Referring toFIG.7D, the applicator is depicted in a fully-deployed state, wherein applicator needle150is stored within applicator housing110, biasing member116is completely unloaded, and the rotation of link118is stopped. Links118and120and applicator needle150may stop rotating without contacting any surfaces. Internal component114may include one or more stopping zones that are configured to allow slowing of the rotation of links118and120. For example, internal component114may include upper stopping zone152and lower stopping zone154. Upper stopping zone152may be positioned at the proximal end of internal component114, where joint142is configured to stop rotating when biasing member116is completely unloaded. Lower stopping zone154may be distal to upper stopping zone152, where joint144is configured to stop rotating when biasing member116is completely unloaded. Referring now toFIG.8, operation of the lower stopping portion when the applicator withdraws the needle is described. To further reduce the noise from inserting the cannula, lower stopping portion154may clamp joint144between two surfaces to help slow the rotation of link120and applicator needle150. As shown inFIG.6, the biasing member, links118and120, and applicator needle150are disposed between upper portion132and lower portion134. Upper portion132and lower portion134may each have a sloped section that narrows the space between the upper and lower portion. When joint144reaches lower stopping portion154, joint144becomes clamped between upper portion132and lower portion134, such that link120and applicator needle150are prevented from continuing to rotate. With respect toFIGS.9A and9B, an exemplary pad for attaching the pump to a wearer is described. Pad102is attached to the wearer and is configured to support the applicator, the patch pump, and the cannula. Pad102comprises a first surface, on which pad skeleton104is attached, and a second, skin-facing surface that includes pad adhesive105that is safe to apply to skin. Pad adhesive105is configured to secure the pad to the wearer for a period of at least 3-10 days and preferably is strong enough to hold the patch pump on the wearer during the wearer's normal, daily motions including showering, swimming, and other outdoor activities. One or more release liners103may be attached to pad adhesive105until pad102is ready to be secured to the wearer.FIG.9Bshows release liners103, which have been partially cut at the location of cannula insertion. Pad skeleton104is configured to couple pad102to the applicator for insertion of the cannula and to the patch pump for delivery of the medication. Pad skeleton104may include one or more locking mechanisms configured to lock the applicator, the pump-cap assembly, and/or the cannula to pad skeleton104. For example, pad skeleton104may include pad attachments106at a first end of pad102, pad back clip108at a second end of pad102, and one or more pad clips holes107at one or more sides of pad102. Referring now toFIGS.10A-10F, further details of the applicator, pad, and cannula are described. The applicator and pad may be configured to both insert the cannula and cause the cannula to be locked to the pad in a single actuation. Preferably, pad102, which is shown as partially cut inFIGS.10A,10B, and10Dto better show how cannula200and applicator needle150are deployed, includes one or more locking mechanisms that may be configured to lock to either the applicator, cannula, and/or the pump-cap assembly. For example, pad102may include pad attachments106, as described above, and the applicator may include flexible attachment pad couplers124, which are configured to fit within one or more slots of pad attachments106. In the pre-deployed state, attachment pad couplers124are disposed within the slots of pad attachments106such that the applicator is coupled to pad102via pad skeleton104, as shown inFIG.10A. Upon actuation by the wearer, the cannula is configured to advance distally, through the skin of the wearer. As shown inFIG.10C, cannula200may include one or more clips206disposed on cannula head204and configured to interact with channel126of the applicator and guide cannula200in a substantially linear direction during insertion. Cannula head204may further include one more wings207configured to protrude towards the wearer's skin and to interact with guiding arm138to order to prevent cannula200from rotating around the longitudinal axis of cannula200during and after insertion. As described below with respect toFIGS.12A and12B, control of the orientation of the cannula in the wearer's skin is important to ensure precise delivery of medication through the aperture(s). Clips206preferably are also configured to function as a locking mechanism. For example, clips206may be one or more protrusions disposed on a first and second side of cannula head204. In the deployed state, clips206may be disposed within the slots of pad attachments106such that the cannula is coupled to pad102via pad skeleton104, as shown inFIG.10B. This single actuation both locks the cannula to pad102and pushes attachment pad couplers124away from the slots of pad attachments106, unlocking the applicator to pad102. Once the attachment pad couplers124are uncoupled to pad attachments106, the applicator may be removed from the wearer's skin, leaving pad102and the cannula in place, as shown inFIGS.10D-10F. In order to maintain the proper orientation of the cannula, wings207are preferably sized and shaped to fit between two pad attachments106, as shown inFIG.10E, and clips206are preferably sized and shaped to fit within the slots of pad attachments106, as shown inFIG.10F. Pad skeleton104may further include angled interface101, which may be disposed between pad attachments106and shaped to have an interface at the angle the cannula is inserted such that angled interface101engages with cannula head204in the deployed state. Ensuring a proper fit of cannula200to pad skeleton104prevents rotation or other movement of the cannula after insertion, resulting in accurate delivery of medication. After the applicator is removed, the pump-cap assembly may be coupled to the pad-cannula assembly via pad clips holes107. Referring now toFIG.11A, further aspects of the applicator, pad, and cannula are described. InFIG.11A, the applicator is depicted in a partially-deployed state, wherein the cannula is inserted into the skin of the wearer, but applicator needle150is not yet withdrawn. The distal end of applicator needle150may be disposed distal to cannula tip218and the proximal end of applicator needle150may be coupled to link120. Applicator needle150preferably is inserted through the septum of the cannula and extends past the distal end of the cannula. Septum224is a self-sealing material designed to seal the proximal region of the cannula, such as silicone, and minimizes backflow out of the cannula. Septum224may be disposed within cannula head204and supports and guides applicator needle150such that the needle is withdrawn in a substantially linear direction. Applicator needle150may be coupled to link120, which interacts with applicator interfaces220and222disposed on cannula head204and configured to provide smooth and continuous contact with link120during insertion of the cannula. After the cannula is inserted, cannula head204of the cannula may be locked to pad attachments106, as shown inFIG.10B. Elongated shaft202of the cannula extends from pad attachments106, past pad skeleton104, through pad102, and into the skin of the wearer. Depending on the type of medication inserted (e.g., insulin), the cannula may be inserted such that apertures208,210,212, and214and cannula tip218are disposed below the dermal layer of skin. With respect toFIG.11B, interengagement of the pad and an exemplary patch pump is described. After the cannula is deployed and is coupled to pad102via pad attachments106, as shown inFIG.10B, the applicator is removed from pad102. A patch pump constructed in accordance with the principles of the present invention, which preferably includes a disposable cap and a reusable pump, is coupled to pad102to deliver medication via the cannula. For example, the patch pump may include a housing that is configured to lock to pad skeleton104such that the patch pump is secured to the wearer during the wearer's normal, daily motions. The patch pump may include outflow needle408, which is in fluid communication with the cannula and to deliver a predetermined dose of medication from a cartridge to the cannula responsive to pumping at the patch pump. Outflow needle408preferably is configured to pierce septum224of cannula head204such that the distal end of outflow needle408is disposed below septum224and medication flows into elongated shaft202, rather than back into the patch pump, for transcutaneous delivery to the wearer via one or more apertures of the cannula. Further, as illustrated, the entirety of cannula head204may be designed to stay above the skin line and remain external to the patient while elongated shaft202is transcutaneous. Cannula for Delivering Medication Referring now toFIGS.12A and12B, an exemplary cannula for delivering medication is described. Cannula200may be injection molded from a single piece of material, which is preferable to extrusion in order to reduce the risk of kinking of cannula200. Cannula200preferably is made from a material that is insulin compatible and flexible and includes cannula head204, cannula tip218, and elongated shaft202. Cannula head204is disposed at the proximal end of cannula200and configured to interact with the applicator needle and the needle through which the medication is delivered. Cannula tip218is disposed at the distal end of cannula200and may include distal aperture216for delivering medication. Elongated shaft202may extend between cannula head204and cannula tip218and may include one or more apertures for delivery of medication. Elongated shaft202may increase in diameter towards cannula head204and the wearer's skin surface, to mitigate the risk that the delivered medication travels proximally along the outside surface of the cannula to the dermal layer or the surface of the skin. This conical shape may also reduce the risk of kinking of cannula200. Elongated shaft202also may have one or more apertures disposed along the elongated shaft in any configuration. Preferably the apertures are disposed such that medication is delivered only below the dermal layer of the skin. As depicted inFIG.12A, cannula200may include aperture210and aperture214, disposed distal to aperture210, which are oriented towards the skin surface of the wearer. As shown inFIG.12B, cannula200also may include aperture208and aperture212, which are oriented away from the skin surface of the wearer. As will also be understood by one of ordinary skill in the art, the cannula may be configured such that the apertures are axially oriented relative to a different target infusion area within the wearer. Cannula head204may include one or more applicator interfaces that are configured to interact with link120to permit rotational movement of the cannula during insertion of the cannula into the skin of the wearer. For example, applicator interface220may be disposed on the side of cannula head204that is farthest away from the skin surface of the wearer. Applicator interface220may be a rounded, convex protrusion, which interacts with a corresponding rounded, concave receptacle of link120. Cannula head204also may include applicator interface222, which may be disposed on the opposite side of the cannula head, the side closest to the skin surface of the wearer. Applicator interface222may be a rounded, concave receptacle, which interacts with a corresponding rounded, convex protrusion of link120. The rounded shapes of applicator interfaces220and222and the corresponding features of link120are designed such that link120maintains smooth and continuous contact with cannula head204during insertion of cannula200into the wearer's skin. Cannula head204also may include one or more clips206configured to guide cannula200in a substantially linear direction. Clips206may be any component of cannula head204that is configured to interact with the channel of the internal component of the applicator during insertion of cannula200into the wearer's skin. For example, clips206may be one or more wings disposed on a first and second side of cannula head204and sized and shaped to slide along the ledges of the channel. Clips206alternatively may be receptacles disposed on cannula head204and configured to slide along corresponding protrusions of the channel. Cannula head204may further include wings207, which may be configured to interact with the guiding arm to order to prevent cannula200from rotating around the longitudinal axis of cannula200during and after insertion. Preferably, wings207are configured to protrude towards the wearer's skin and the guiding arm and are sized and shaped such that the guiding arm fits between the two wings. Clips206and wings207are designed to control orientation of the cannula during delivery and insertion. Because the apertures along the shaft of the cannula may be radially and longitudinally offset from one another, control of the orientation of the cannula in the wearer's skin is important to ensure precise delivery of medication through the aperture(s). Thus, clips206and wings207ensure axial orientation in a target direction of the apertures. Referring toFIGS.13A and13B, alternative embodiments of the distal end of the cannula are described. InFIG.13A, cannula tip218has an angled tip for inducing curvature in the cannula during insertion. Preferably, the cannula is curved towards the surface of the skin, which permits the cannula to have a greater length without being inserted too deep within the wearer's skin. The greater the length of the cannula, the more apertures that may be positioned along elongated shaft202, which may extend the life of the cannula. Further, the angled tip may be oriented such that the distal portion of the angled tip is configured to be oriented nearer the skin surface than the proximal portion of the angled tip. FIG.13Bdepicts an alternative embodiment of the distal end of the cannula, which includes one or more knife blades226, which are configured to reduce the pain from insertion of the cannula and maintain the preferred axial orientation of the cannula during and after insertion. Knife blades226may extend proximally from cannula tip218along a portion of elongated shaft202. Knife blades226have sharpened edges to facilitate piercing the skin and insertion of the distal end of the cannula. Preferably, two knife blades disposed on opposing sides of the cannula shaft, adjacent to the distal end, may be employed. Turning toFIG.14A, an embodiment of a cannula having multiple apertures is described. The apertures are preferably arranged in a configuration that ensures the medication is delivered to the appropriate location within the wearer's skin. The multiple apertures also may be arranged such that medication is delivered along the length of elongated shaft202. The cannula may include cannula head204, cannula tip218, and elongated shaft202. Cannula head204may include septum224, which is configured to both support the applicator needle during insertion of the cannula into the wearer's skin and to support the needle of the patch pump during delivery of the medication. The applicator needle is disposed through septum224during the insertion of the cannula into the wearer's skin. The cannula may have several apertures for delivery medication, such that medication is delivered only below the dermal layer of skin. Distal aperture216may be disposed at cannula tip218and four apertures may be disposed along elongated shaft202. Apertures208and212are disposed on the side of elongated shaft202oriented away from the skin surface of the wearer and apertures210and214are disposed on the side of elongated shaft202oriented towards to the skin surface of the wearer. Aperture208may be the proximal most aperture such that medication delivered through aperture208is delivered in the direction away from the skin surface of the wearer. This configuration of apertures mitigates the risk of delivering medication into the derma layer of the wearer's skin. Delivery below the dermal layer of skin is particularly important for insulin delivery in order to ensure stable absorption. As described above, clips206and wings207may be used to ensure a desired orientation of cannula shaft during and after insertion to align the apertures in the desired manner. With respect toFIGS.14B-14E, alternative embodiments of cannula comprising biodegradable materials are described. The use of biodegradable materials within the cannula expands the insulin infusion area and volume over time. One of the main issues with previously known cannula is the risk of occlusion, which occurs when insulin reacts with fat. The typical life of a cannula with a single aperture at the distal end (e.g., distal aperture216) is about 3-4 days. The addition of biodegradable materials that dissolve to open additional apertures over time may extend the life of the cannula to at least 7-10 days. The greater the life of the cannula, the fewer times the wearer is required to insert a new cannula into their skin at a different location and the less waste created from used cannulas. The biodegradable materials may either be disposed within the lumen of the cannula (“lumen plug”) or within the apertures of the cannula (“aperture plug”) such that medication may still travel through the lumen and distal aperture216. The biodegradable materials preferably have fast degradation rates, e.g., several days. Exemplary biodegradable materials include: polysaccharide-based materials; salt; silk; hyaluronic acid (HA); polyethylene glycol (PEG); saturated aliphatic polyesters: poly(lactic acid) (PLA), polyglycolide (PGA), combination thereof (poly(lactide-co-glycolide), PLGA); polyanhydrides. The cannula ofFIG.14Bincludes two types of lumen plugs in an initial state. First biodegradable material230and second biodegradable material232may be disposed within elongated shaft202and block one or more apertures. First biodegradable material230may have a shorter dissolution time than second biodegradable material232. For example, first biodegradable material230may have a dissolution period of 2-3 days and second biodegradable material232may have a dissolution period of 4-6 days. First biodegradable material230preferably is disposed distal to the proximal-most aperture (e.g., aperture208) such that, in the initial state, medication may be delivered through the proximal-most aperture. First biodegradable material230may block one or more apertures along elongated shaft. For example, first biodegradable material230preferably blocks aperture210but does not block apertures212or214or distal aperture216. As shown inFIG.14C, after first biodegradable material230dissolves, aperture210is opened and second biodegradable material232remains disposed within the lumen of the cannula. Second biodegradable material232may be disposed distal to first biodegradable material230and preferably blocks apertures212and214and distal aperture216. After second biodegradable material232dissolves, all of the apertures of the cannula may be opened. Over time, the apertures through which medication is initially delivered may become occluded due to the reaction between the delivered insulin and the fat. However, the dissolution of the biodegradable materials at varying times mitigates this issue by periodically opening new apertures. In the cannula plug embodiment ofFIGS.14B and14C, a modified applicator needle and method for inserting the cannula may be necessary. For example, the applicator needle may be shortened such that it does not extend through any biodegradable material. If the applicator needle does not extend past the distal tip218, the distal-most cannula plug, second biodegradable material232, preferably is configured to have a sharp distal end that is configured to pierce the wearer's skin. With respect toFIGS.14D and14E, a cannula having two types of aperture plugs in an initial state is described. Third biodegradable material234and fourth biodegradable material236may be disposed within the apertures on elongated shaft202such that medication may still travel through the lumen and distal aperture216, which remains unblocked. Third biodegradable material234may have a shorter dissolution time than fourth biodegradable material236. For example, third biodegradable material234may be similar to first biodegradable material230and may have a dissolution period of 2-3 days. Fourth biodegradable material236may be similar to second biodegradable material232and may have a dissolution period of 4-6 days. Third biodegradable material234preferably is disposed within apertures212and214and fourth biodegradable material236preferably is disposed within apertures208and210. As the delivered insulin reacts with fat, potentially occluding distal aperture216and apertures212and214, fourth biodegradable material236will dissolve, opening apertures208and210. As will also be understood by one of ordinary skill in the art, the cannula may include only one biodegradable material or may include more than two biodegradable materials. In the lumen plug embodiment, the biodegradable materials may be configured to block one or more apertures. In the aperture plug embodiment, the biodegradable materials may be configured to block different apertures than illustrated. As will also be understood, biodegradable materials may have a dissolution period of 0-10 days, and the choice of biodegradable material may depend upon the configuration of the biodegradable materials and the number of different types of biodegradable materials incorporated into the cannula. Reusable Patch Pump and Disposable Cap for Delivering Medication Referring now toFIGS.15A and15B, perspective views of an exemplary patch pump and pump-cap assembly constructed in accordance with the principles of the present invention are described. The patch pump is configured to attach to the adhesive pad secured to the wearer and to deliver doses of medication through the inserted cannula. The patch pump preferably includes a reusable pump, a disposable cap, a disposable pre-filled cartridge of medication, and a pad. The pump is configured to be used for several years, thus reducing waste as well as the cost of the system. The user preferably may own two reusable pumps, which allows the user to recharge the first pump while wearing and receiving medication from the second pump. As described above, the first pump may communicate data to or from the second pump, so as to provide continuity of insulin infusion when one pump is changed out for the other pump. The wearer may alternative using two pumps such that one pump is the center of the configuration data system controlling, among other things, the insulin delivery process, the heart rate measurement process, the glucose measurement process, the authentication of the pumps to each other, and the authentication of the user's smartphone, the authentication of the user, and the authentication of the physician. At any given time no or only one pump is active. The pumps share their configuration data when possible, either directly with the other pump or via a file temporarily stored in the patient's smartphone. The data may be secured by encryption and authenticated by a signature, both operations using the best standards in the field. The data may be transferred from the active pump to the non-active pump. Preferably, only the active pump can change the configuration via instructions given by the wearer or the physician. The patch pump may include pump300preferably designed to be used for an extended period of time (e.g., 2-4 years), and cap400preferably designed to be replaced after a much shorter period of time (e.g., 3-5 days). The patch pump also may include a pre-filled cartridge of medication, such as cartridge500, which may be filled during manufacturing or by the wearer prior to inserting cartridge500into the pump. For example, the wearer may pre-fill several cartridges configured to last one month and store the pre-filled cartridges in the fridge until the cartridge are to be used. The patch pump may be configured such that the pre-filled cartridges may be inserted into the patch pump as soon as the cartridges are removed from the fridge. For example, the patch pump may complete an initialization process, described further below, which reduces the formation of bubbles within the cartridge. Preferably, the wearer need not wait a certain period of time (e.g., 20 minutes) before inserting the cartridge into the patch pump. Cartridge500may include a cartridge cap through which an inflow needle of cap400is disposed and a plunger, disposed at the opposite end and configured to be advanced toward the cartridge cap to deliver insulin. Cartridge500is configured to be inserted into the patch pump such that cartridge500is completely enclosed within the patch pump. For example, cartridge500may be inserted first into pump300such that a portion of cartridge500remains outside of pump housing302. Cap400then may be coupled to cartridge500such that an inflow needle disposed within cap400pierces the cartridge cap of cartridge500. While still maintaining inflow needle within cartridge500, cap400then may be rotated relative to pump300to lock cap400to pump300, thereby coupling the cap-pump assembly to the pad and the pump. Pump300may include a motor disposed within pump housing302, the motor configured to move a pusher coupled to the plunger of cartridge500such that insulin is advanced through an inflow needle of cap400and to a microdosing system designed to measure and deliver predetermined doses of medication. The same motor may simultaneously activate the plunger of the cartridge and the microdosing system, for example, via a gearbox. Doses of medication may be delivered to the user responsive to operation of a processor, in accordance with programming stored in memory associated with the processor or specifically when requested by the user, e.g., using a suitable wireless application on the user's smartphone. The processor may be configured to monitor one or more sensors and modify operation of pump300or alert the wearer based on information sensed by one or more sensors. Cap400is configured to receive medication from cartridge500and deliver predetermined doses of the medication through an outflow needle, into cannula200, and to the wearer. Cap400preferably includes a microdosing system configured to measure and deliver the predetermined doses of medication. Cap400further may include locking mechanisms configured to lock cap400to pump300such that cartridge500is completely enclosed within pump housing302and cap housing402in a closed and locked position. Cap400may include additional locking mechanisms configured to lock the pump-cap assembly to the pad. For example, cap400may include one or more cap clips403, which may be sized and shaped to fit within one or more pad clips holes disposed on the pad skeleton. The pump-cap assembly may be unlocked from the pad by pressing unclipping buttons405, which preferably are configured to deflect cap clips403such that cap clips403may be removed from the pad clips holes. This method of locking and unlocking the pump-cap assembly to the pad ensures that the patch pump will remain in place during the wearer's daily motions and is convenient for the wearer to secure and remove the pump-cap assembly. For example, the wearer preferably can clip/unclip the pump-cap assembly from the pad using one hand, even if the patch pump is secured to a difficult to reach area of the body, such as the back of the arm. Referring toFIG.16, the lower side of the assembled patch pump is described. The patch pump includes pump housing bottom305, which is the lower side, or skin-facing side, of the pump that is oriented toward the wearer's skin. Pump housing bottom305may be coupled to pump housing302, which is an upper side of the pump that is oriented away from the wearer's skin. Pump housing bottom305may have a slight concavity such that the patch pump maintains contact with the wearer's skin. The patch pump preferably includes reusable pump300having pump housing302and disposable cap400having cap housing402, which are coupled together with the pad to form the patch pump. Cap400further may include connection cavity404, sized and shaped to receive the pad attachments and cannula head, which protrude from the pad and lock the cannula to the pad, when the patch pump is locked to the pad. Connection cavity404may house an outflow needle that is configured to interact with the cannula. Cap400may include one or more cap clips403, which may be coupled to one or more unclipping buttons405that may be pressed to unlock the pump-cap assembly from the pad. Preferably, the cap includes two unclipping buttons405disposed on each side of the cap, each unclipping button405having two cap clips403that are sized and shaped to fit within the pad clips holes disposed on the pad skeleton, thereby allowing lateral clipping. Pump300may include a photoplethysmography sensor configured to determine the wearer's heart rate or other physiologic parameters, which may be used to adjust the delivery of medication from pump300to the wearer, as described in U.S. Pat. No. 11,241,530 to Fridez et al. and PCT International Application No. PCT/IB2021/060766, the entire contents of each of which are incorporated herein by reference. For example, using physical activity level, or a determination that the wearer is sleeping or awake, a small change may be made in an algorithm that controls an amount or rate of insulin injection, which could significantly influence blood glucose level. The patch pump controller also could use heart rate, as determined by the photoplethysmography sensor, to implement a sport mode, for example, that permits a slightly higher glucose target to decrease the risk of hypoglycemia after physical exertion. The photoplethysmography sensor may be electrically coupled to a circuit board disposed within pump300and may be disposed within photoplethysmography sensor frame304, which is disposed on the skin-facing side of pump housing302. Photoplethysmography sensor frame304may extend through a pad opening in the pad attached to the wearer. The skin-facing side of pump housing302preferably is configured to include one or more protrusions such that the photoplethysmography sensor maintains contact with the wearer's body surface during motion, while also reducing cross talk between emitters and detectors and from ambient light impinging upon the photoplethysmography sensor. For example, the skin-facing side of pump housing302may include optional rib308, configured to protrude from pump housing302to block light. Rib308may surround bump310, which houses the photoplethysmography sensor. Bump310preferably protrudes farther from pump housing302than rib308, such that bump310maintains contact with the wearer's skin while ensuring that the contact force of bump310does not apply excessive pressure to the wearer's skin or cause tissue necrosis. The photoplethysmography sensor is designed to generate a strong photoplethysmography signal suitable for heart rate monitoring and pulse oximetry and may include one or more LEDs and one or more detectors. The photoplethysmography sensor may include an exemplary multi-chip photoplethysmography package suitable for use in the patch pump, for example, the SFH 7072 BIOFY® Sensor device commercially available from OSRAM Opto Semiconductors GmbH, Regensburg, Germany. The multi-chip photoplethysmography package may include red, infrared, and green LEDs, an infrared cut detector to detect reflected light from green LEDs, and a broadband detector to detect reflected light from red and infrared LEDs. Preferably, the red LED has a centroid wavelength of 655 nm, the infrared LED has a centroid wavelength of 940 nm and the green LEDs have a centroid wavelength of 530 nm. The LEDs and detectors are set in a ceramic package that includes one or more light barriers configured to reduce optical crosstalk between the LEDs and detectors. As is well known in the photoplethysmography art, green LEDs are commonly used in monitoring heart rate in wearables in view of their good signal-to-noise ratio and resistance to motion artifact, while the combination of red and infrared LEDs provides accurate monitoring of blood oxygen saturation. Suitable algorithms are known in the art for processing photoplethysmographic signals generated with red and infrared LEDs and green LEDs to reduce the effects of motion noise, including frequency domain analysis and Kalman filter analysis techniques. Alternatively, infrared-red LEDs may be used, instead of the green LEDs, to compute heart rates for wearers having darker skin complexions. As will also be understood by one of ordinary skill in the art, more or fewer LEDs advantageously could be employed in the photoplethysmography sensor. Photoplethysmography sensor frame304preferably includes one or more transparent windows306and a layer, forming bump310. Photoplethysmography sensor frame304may comprise a sturdy biocompatible plastic or rubber material that may have one or more openings. Windows306may consist of a clear plastic material having low absorptivity for light at the wavelengths of the LEDs and may be configured to mate with the openings of photoplethysmography sensor frame304to provide a smooth exterior surface for bump310. The layer preferably is a closed cell foam or similar compressible material against which the photoplethysmography sensor is urged against the layer into contact with windows306. Photoplethysmography sensor frame304and the layer preferably are matte black or gray to reduce light scattering of light reflected from tissue through windows306. Window306may be a single thin window <0.5 mm thick or, alternatively may include more than one window. Heart rate signals generated by the photoplethysmography sensor may be used by the controller to modulate infusion of insulin from the patch pump. Preferably, the photoplethysmography sensor periodically measures the wearer's heart rate, e.g., once every minute, 2½ minutes or five minutes, and computes a heart rate and a quality measure for the computed heart rate. The quality measure may be used to determine whether to adjust insulin delivery to better maintain the stability of the wearer's blood glucose level. In addition, the heart rate data may be used to compute an activity intensity level, similar to that employed in physical activity monitors, such as resting, passive behavior, and low, medium and high levels. Such an activity level could be used to adjust parameters of the insulin delivery algorithm to permit a “sport mode” that adjusts insulin delivery to reduce the risk of hypoglycemia during, and especially after, engaging in vigorous or sports activities. The heart rate also could be evaluated to determine whether the wearer is asleep or awake. For example, when a wearer is asleep, the parameters of the infusion algorithm used in the controller could be switched to a sleep mode. This sleep mode may allow fine-tuning of the wearer's glucose level to allow provide better sleep well and improve time in a targeted glucose range. Such adjustments are expected to be possible because while sleeping, the wearer does not eat, is not physically active, and is not physically or emotionally stressed. Determination that a wearer is asleep or awake additionally could be based on, or confirmed by, data from an accelerometer. Accelerometer outputs also could be analyzed to assess where the patch pump is being worn by the user, and to determine body orientation. The sleep/wake information also may be analyzed to provide a quality measure of the measurement, and thus allow the infusion algorithm employed by the controller to have a good degree of confidence regarding its insulin delivery adjustments. The output of the photoplethysmography sensor also may be used to validate that the patch pump is adequately adhered to the wearer's skin to allow insulin injection, as described further below. If, for example, patch pump includes a capacitive circuit for continuously detecting that the pump is adhered to a wearer's skin, the photoplethysmography sensor could provide confirmation that the pump is located on the wearer's skin. Referring now toFIG.17, internal components of an exemplary pump are described. For example, pump300may include within pump housing302and pump housing bottom305the following components: coil312, circuit board314, sensor316, battery318, sensor320, mechanical coupling322, gearbox324, sound generator326, pump motor328, vibration motor330, cartridge holder332, and/or pusher335(which may include screw334, nut336, bendable rod338, and/or cartridge contactor340). Pump300may include housing having one or more separate pieces that are configured to couple together to enclose the internal components of the pump. Preferably, pump300includes a minimal number of parts such that the cost of the pump is reduced. For example, pump300may include pump housing302coupled to pump housing bottom305, which may include photoplethysmography sensor frame304. Pump housing302preferably has a cavity to receive a portion of a pre-filled cartridge. When coupled to the cap housing, the combined housings preferably fully enclose the cartridge. Pump housing302may include plethysmography sensor frame304and pump housing back342, which may be disposed on the end of pump housing302that does not lock with the cap. Pump housing302also may include a dry zone seal and/or one or more dry zone vents, which are configured to separate wet and dry zones of the pump such that the electrical components in the dry zone are isolated from the wet zone and do not contact any fluid and/or to permit humidity and gas to escape the housing such that pressure may equilibrate. In addition, cartridge holder332may separate the protected wet zone from the dry zone and may include one or more O-rings to seal off the zones when a cartridge is disposed within the pump-cap assembly. Coil312is electrically coupled to battery318. Coil312may include a magnetic shielding and preferably receives energy from outside pump housing302to charge battery318of pump300. For example, a corresponding coil in charging system600may transfer energy to coil312to charge battery318. The coils may be inductive coils. Circuit board314permits electrical connection between electrical components within pump housing302. Circuit board has a controller with one or more processors to execute programmed instructions stored in memory to cause motor328to deliver the medication to the wearer and to monitor one or more sensed parameters generated by sensors (e.g., sensors316or320) disposed within or external to pump housing302. Sensor316is designed to sense information associated with operation of microdosing system410and to send the information to the controller for processing. Sensor316may, for example, monitor the microdosing function and sense information indicative of the presence of a cap, the status of a cap, and/or an occlusion in the dosing pathway, as described in detail below. Battery318is a rechargeable battery to power the pump. Battery318has a capacity sufficient to permit pump300to pump all the medication from the cartridge to the wearer with a single charge. Battery318may be disposed within the housing and may be charged by a charger via a coil with the charger and coil312within pump300. Sensor320is designed to sense information associated with operation of pump300and to send the information to the controller for processing. Sensor320may, for example, sense information indicative of the pressure within the cartridge of medication, as described below. Mechanical coupling322is designed to couple with a corresponding portion in the cap of the patch pump to translate motion from pump motor328into components of the cap, for example, for microdosing. Mechanical coupling322further may be used for locking pump housing302to the cap housing. Mechanical coupling322is coupled to the output from gearbox324such that mechanical coupling322may rotate at a reduced ratio as compared to rotation directly output by pump motor328. Gearbox324may be coupled to motor328, pusher335, and/or mechanical coupling322such that rotation of the gears with gearbox324causes delivery of a predetermined dose of medication to the wearer. As motor328turns when activated, gearbox324causes a corresponding movement at mechanical coupling322and at pusher335. Gearbox324incorporates gears to change the ratio of movement pump shaft rotations of pump motor328to generated sufficient torque to drive mechanical coupling322and pusher335. For example, gearbox324may utilize gearing that reduces movement generated by pump motor328to movement generated by mechanical coupling at a reduction ratio. The reduction ratio may be greater than 10:1, such as 68.42:1. Advantageously, a single pump motor may be used to both push medication out of the cartridge and move the microdosing system to generate the microdose of medication. For example, the single pump motor may simultaneously (1) advance the piston with micro-steps and (2) activate the microdosing system at every pump cycle. Sound generator326, responsive to instructions from the controller, generates an audible sound via a buzzer to the wearer. For example, sound generator326may generate the audible sound if there is an error with the pump or a sensed physiological parameter is beyond a predetermined threshold. Motor328may be coupled to vibration motor330, which may be operatively coupled to the controller. The controller may cause the vibration motor to vibrate to alert the wearer based on a sensed parameter by a sensor, which may be operatively coupled to the controller. Preferably the controller is configured to cause vibration motor330to vibrate when the sensed parameter falls outside a predetermined threshold stored in memory. In addition, the controller may cause vibration motor330to vibrate based on the controller's determination that an error has occurred associated with operation of the patch pump based on the sensed parameter. Alternatively, the controller may be configured to cause vibration motor330to vibrate based on the time. For example, the vibration motor may vibrate once every three days to provide regular alerts to the user. The sensors operatively coupled to the controller may include a sensor configured to sense a pressure within a cartridge, a sensor configured to detect an occlusion in a dosing pathway, a sensor configured to sense the temperature or humidity within the patch pump, a sensor configured to monitor glucose levels of the wearer, a photoplethysmography sensor configured to sense the wearer's heart rate or physiologic parameters, or a sensor configured to sense the wearer's activity level. These sensed parameters may indicate whether the patch pump is running properly, whether the medication is stored at a safe temperature, and whether the wearer's physiologic parameters are at a safe level. Preferably, the controller is configured to cause vibration motor330to vibrate when the pressure within the cartridge falls outside a predetermined pressure range, when the wearer's glucose level falls outside a predetermined glucose level range, when the wearer's heart rate or physiologic parameters fall outside a predetermined photoplethysmographic threshold, and/or when the wearer's activity level is outside a predetermined threshold. The controller also may be configured to cause vibration motor330to vibrate when the sensor detects information indicative of an occlusion or only when the sensor twice detects information indicative of an occlusion. Additionally or alternatively, the wearer may be alerted via sound generator326, a user interface having LEDs, which also may be disposed within pump300, or a mobile application. Pusher335is designed to push, responsive to movement from pump motor328, on an end of the cartridge. Preferably, pusher335pushes on a flexible plunger within the cartridge to move medication out of the cartridge during dosing. Pusher335also may push the plunger of the cartridge to increase pressure in the cartridge without moving medication to the wearer, for example, during pump initialization. Pusher335may include screw334, nut336, bendable rod338, and/or cartridge contactor340. Screw334is coupled to pump motor328, e.g., via gearbox324. Screw334may be a worm screw. Responsive to rotational movement at pump motor328, screw334rotates in a corresponding manner (e.g., at a geared ratio). Movement of screw334causes nut336to move along screw334. Screw334may include a threaded screw and nut336may include a threaded nut that moves along the screw responsive to rotation of the screw. Bendable rod338is coupled to nut336and moves as nut336moves. Bendable rod338may curve in an approximately 180 degree angle to cause equal and opposite movements between nut336and cartridge contactor340. Cartridge contactor340is designed to contact the cartridge and move the plunger of the cartridge responsive to movement of pump motor328. Cartridge contactor340may have a flange that contacts an outer surface of the plunger at a non-insulin-contacting end. Cartridge contactor340also may have an extension with a smaller diameter than the flange that extends into the inner part of the plunger. In this manner, cartridge contactor may have a top hat shape. Referring now toFIG.18, further aspects of the patch pump, are described. The skin-facing side of the patch pump is configured to interact with the pad and the cannula such that the patch pump is secured to the wearer and predetermined doses of medication are delivered to the wearer. Circuit board314, having photoplethysmography sensor346, may be disposed within pump300and may be configured to cause the motor to pump the medication from the cartridge to the outflow needle408, which is configured to pierce the cannula. Outflow needle408may be disposed within connection cavity404. Connection cavity404preferably is disposed on the skin-facing side of cap400and may be sized and shaped to receive the proximal region of the cannula (e.g., cannula head) such that outflow needle408can be coupled in fluid communication with the cannula to deliver the microdoses of medication. Connection cavity404may be sized and shaped to receive pad attachments, which protrude from the pad and lock the cannula to the pad, when the patch pump is locked to the pad. The patch pump further may include a portion configured to hold a pre-filled cartridge of medication and preferably does not include a reservoir to hold multiple doses of medication separate from the pre-filled cartridge. Turning toFIGS.19A and19B, an illustrative embodiment of a circuit board is described. Circuit board314preferably is disposed on flexible substrate356that can bend and fold to fit within the pump housing. Circuit board314includes electrical components and permits electrical coupling between the controller and the various electrical components. One or more electrical components and/or circuits may perform some of or all the roles of the various components described herein. Although described separately, as will be understood by one of ordinary skill in the art, the electrical components need not be separate structural elements. For example, a processor and wireless communication chip may be embodied in a single chip. In addition, while the one or more processor is described as having memory, a memory chip may be separately provided. Circuit board314may include sensor316, sensor320, sensor connector321, sensor344, sensor connector345, photoplethysmography sensor346, sensor348, skin detector350, processor352, sensor354, flexible substrate356, skin detector358, controller360, motors driver362, processor364, wireless communication chip366, user interface368, sensor369, wireless antenna370, battery and wireless charging management372, accelerometer374, and/or programming connectors376. Controller360is disposed within the pump housing for controlling operation of pump300. For example, the controller may store instructions that, when executed, cause pump300to perform the operations described herein. Controller360preferably includes electrical components coupled on circuit board314. Controller360may include one or more general purpose processors, digital signal processors (DSP), application specific integrated circuits (ASIC), field programmable gate arrays (FPGA) or other programmable logic devices, discrete gate or transistor logic, discrete hardware components, or any suitable combination thereof designed to perform the functions described herein. A processor also may be implemented as a combination of computing devices, e.g., a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration. The controller may contain memory and/or be coupled, via one or more buses, to read information from, or write information to, memory. The memory may include processor cache, including a multi-level hierarchical cache in which different levels have different capacities and access speeds. The memory also may include random access memory (RAM), other volatile storage devices, or nonvolatile storage devices. The storage devices can include, for example, hard drives, optical discs, flash memory, and Zip drives. The processor, in conjunction with firmware/software stored in the memory may execute an operating system, such as, for example, Windows, Mac OS, Unix or Solaris 5.10. The processor also executes software applications stored in the memory. In one non-limiting embodiment, the software comprises, for example, Unix Korn shell scripts. In other embodiments, the software may be programs in any suitable programming language known to those skilled in the art, including, for example, C++, PHP, or Java. In some embodiments, controller360may include two dedicated processors to increase the security of the patch pump. Processor352may manage delivery of the medication and may monitor of one or more sensors that may detect sensed parameters that effect the algorithm for delivery. Processor364may manage the communications to and from the patch pump. Processor352may be an autonomous, real time state machine that executes class C software. Processor364may execute class B software. Preferably, processor352is configured such that it cannot receive data from outside the patch pump. For example, any communication from the wearer's mobile device or from an external continuous glucose monitoring sensor must be received by processor364. This configuration protects processor352, and thus the delivery of medication, from any disruption by an external device. Processor352may be configured to execute first programmed instructions stored in a first memory to cause the pump motor to pump the medication towards the transcutaneous portion, to monitor sensed parameters generated by at least one sensor, and to monitor the battery life of the battery. For example, processor352may monitor sensed parameters generated by a sensor configured to sense a pressure within the cartridge, a sensor configured to detect an occlusion in the dosing pathway, a sensor configured to detect the wearer's skin, a sensor configured to detect the position of the pusher to indicate that the cartridge may be replaced, or a sensor configured to detect the position of the cam to indicate the status of a dosing cycle. The first programmed instructions may cause one or more components of the pump to move based on the sensed parameters. For example, the first programmed instructions may cause the motor to push the medication in the cartridge towards the transcutaneous portion only when a sensor detects the wearer's skin on the skin-facing side of the pump. The first programming instructions also may cause the cam shaft of the microdosing system to stop rotating when a sensor indicates that a dosing cycle is complete. Further, the first programming instructions may lock or unlock the pump, for example, when a first processor determines that the pusher is in the home position or when the first processor determines that the battery has been sufficiently charged to a predetermined state. Processor364may be configured to execute second programmed instructions stored in a second memory to communicate data to and from the patch pump via the wireless communication chip. The communicated data may include data indicative of a battery life of the rechargeable battery or data indicative of the wearer's hear rate and physiologic parameters, which may be detected by a photoplethysmography sensor. Preferably, the second programmed instructions also use an algorithm to calculate when to deliver the doses of medication and may adjust the calculation based on the data received. Wireless communication chip366is configured to transmit information, such as signals indicative of the sensed parameters, locally and/or to a remote location such as a server. Wireless communication chip366is configured for wireless communication over a network such as the Internet, a telephone network, a Bluetooth network, and/or a WiFi network using techniques known in the art. Wireless communication chip366may be a communication chip known in the art such as a Bluetooth chip and/or a WiFi chip. Wireless communication chip366may include a receiver and a transmitter, or a transceiver, for wirelessly receiving data from, and transmitting data to a remote computing device. In some embodiments, the remote computing device may be a mobile computing device that provides the system with a user interface; additionally or alternatively, the remote computing device is a server. In embodiments configured for wireless communication with other devices, wireless communication chip366may prepare data generated by processor364for transmission over a communication network according to one or more network standards and/or demodulates data received over a communication network according to one or more network standards. Wireless communication chip366may be coupled to wireless antenna370for sending and receiving information. Wireless antenna370may include Bluetooth antenna configured to transmit or receive signals in accordance with established standards and protocols, such as Bluetooth and/or BLE. In some embodiments, wireless antenna370may be the only means for the patch pump to transfer data. In some embodiments, pump300may communicate externally as described in WO 2020/008016 or WO 2020/008017, the entire contents of each of which are incorporated herein by reference. User interface368may be used to receive inputs from, and provide outputs to, the wearer. Illustratively, user interface368may alert the wearer when the pressure within the cartridge is outside of a predetermined range or when an occlusion is detected or when the wearer's glucose level, heart rate, or physiologic parameters are outside a predetermined range. User interface368may be coupled to processor364. User interface368may include a touchscreen, LED matrix, other LED indicators, or other input/output devices for receiving inputs from, and providing outputs to, the wearer. Alternatively, user interface368is not provided on the patch pump, but is instead provided on a remote computing device communicatively connected to the patch pump via wireless communication chip366. User interface368also may be a combination of elements on the patch pump and a remote computing device. User interface368may be configured to adjust the strength of the LEDs based on sensed parameters from sensor369. Sensor369may be a light sensor configured to detect whether the patch pump is disposed in a bright or dark environment. For example, processor352may be configured to adjust user interface368such that the strength of the LED is decreased when it is dark and is increased when it is light. Battery and wireless charging management372is configured to recharge the battery within the pump and to ensure the safety of the battery. Battery and wireless charging management372may communicate with the charging system to charge the battery and may protect against high voltage or high current which may damage the battery. Further, battery and wireless charging management372may be configured to efficiently charge the battery and generate adequate electrical tension for circuit board314. Programming connectors376may be provided for installing firmware in the on-board memory of the controller attached to circuit board314. For example, programming connectors376may be used to flash the firmware of the pump and may be used during development to output the signals of the sensors to determine whether circuit board314is working properly. Programming connectors376may be removed after programming, during the manufacturing of the pump. Motors driver362may be used to supply current to both the vibration motor and the pump motor. Controlling the power supply to the motors can have a significant effect on the noise, power consumption, and torque of the motors. Circuit board314also may include one or more sensors configured to sense conditions within the patch pump or external to the patch pump, for example, the wearer's physiologic parameters. For example, circuit board314may include sensors316,320,344,346,348,350,354,358,369, and/or374. The sensor(s) preferably are electrically coupled to controller360(e.g., at processor352) for monitoring and processing the information from the sensor(s). Sensor316is configured to sense information indicative of an occlusion in the dosing pathway, such as within the microdosing system or within the cannula. Sensor316preferably is electrically coupled to controller360such that sensed signals are sent to controller360for processing and detecting an occlusion. Sensor316may be located adjacent to the microdosing system but within the pump. In some embodiments, sensor316is a hall-effect sensor configured detect movement of a magnet disposed on a lever of the microdosing system. Sensor320may sense information indicative of the pressure within the cartridge. Sensor320preferably is electrically coupled to controller360such that the sensed signals are sent to controller360for processing and detecting the pressure within the cartridge. Sensor320may be located adjacent to the pusher and may be coupled to circuit board314via sensor connector321. Sensor connector321permits electrical coupling between sensor320and components on circuit board314, such as the controller. In some embodiments, sensor320is configured to detect the force applied to the pusher and includes a strain gauge configured to measure deformation, for example, by measuring a change in electrical resistance. Controller360processes this information to determine pressure within the cartridge. Sensor344may sense information indicative of the status of a dosing cycle. Sensor344preferably is electrically coupled to controller360such that sensed signals are sent to controller360for processing and detecting whether a dosing cycle is completed. Sensor344may be located adjacent to the microdosing system but within the pump and may be coupled to circuit board314via sensor connector345. Sensor connector345permits electrical coupling between sensor344and components on circuit board314, such as the controller. In some embodiments, sensor344detects oscillations of signals that are generated by a ferromagnetic blade that may be coupled to the cam plate. In some embodiments, a dosing cycle corresponds to a ½ turn of the cam so sensor344senses whether the ½ turn has occurred. Photoplethysmography sensor346is configured to sense the wearer's heart rate or other physiologic parameters. Photoplethysmography sensor346preferably is electrically coupled to controller360(e.g., to processor352of controller360) such that the sensed parameters are sent to controller360for processing and detecting whether the wearer's heart rate or other physiologic parameters are outside a predetermined range. Photoplethysmography sensor346may be located on circuit board314such that is disposed on the skin-facing side of the patch pump, preferably within a window of the patch pump. Sensor348may sense information indicative of the position of the pusher, which may be indicative of the battery life of the rechargeable battery, whether a new cartridge may be inserted, and/or whether the patch pump may be unlocked. Sensor348preferably is electrically coupled to controller360such that the sensed position is sent to controller360for processing and detecting the position of the pusher. For example, sensor348may indicate that a component of the pusher is at the end-of-stroke. Sensor348may be located adjacent to the pusher. In a preferred embodiment, sensor348is an electrical contact sensor that senses the position of the pusher based on whether a component (e.g., nut336) of the pusher has contacted the sensor. Sensor348may include one or more contacting pins that are configured to contact one or more contacting blades responsive to force applied on the contacting blades by the pusher. For example, the nut of the pusher may contact the blades at the end-of-stroke, causing the blades to move to contact the contacting pins. The contacting pins may be coupled to the circuit board via a conductor (e.g., illustratively a spring) such that when the one or more contacting pins contact the one or more contacting blades, a circuit is completed, which sends an electrical signal to controller360. Skin detector350senses information indicative of whether the patch pump is touching skin. Controller360may cause the motor to run only if skin detector350detects skin. Skin detector350preferably is electrically coupled to controller360such that sensed signals are sent to controller360for processing and detecting whether the patch pump is secured to a pad, held by the wearer, or not touching skin. Skin detector350may be located on the skin-facing side of the patch pump such that it detects whether the skin-facing side of the patch pump is touching skin. In some embodiments, skin detector350measures capacitance. Sensor354is configured to sense information indicative of the temperature and humidity in the patch pump. Sensor354preferably is electrically coupled to controller360such that sensed signals are sent to controller360for processing and detecting whether the temperature and humidity are within respective predetermined ranges. If outside the predetermined range(s), an alert may be generated using the vibration motor, the sound generator, and/or a communication sent to the software application. In some embodiments, the pump may include a second skin detection sensor. Similar to skin detector350, skin detector358senses information indicative of whether the patch pump is touching skin. Skin detector358preferably is electrically coupled to controller360such that sensed signals are sent to controller360for processing and detecting whether the patch pump is secured to a pad, held by the wearer, or not touching skin. Skin detector358may be located on the opposite side of the patch pump such that is detects whether the opposite side of the patch pump is touching skin. In some embodiments, skin detector358measures capacitance. Controller360may cause the motor to run only if skin detector350detects skin and skin detector358does not detect skin. If both skin detector350and skin detector358detect skin, it may indicate that the wearer is holding the patch pump. In such a case, the patch pump should not deliver medication. Sensor374is configured to sense information indicative of the wearer's activity level. Sensor374also may be configured to sense information indicative of the location of the patch pump on the wearer's body. Sensor374preferably is electrically coupled to controller360such that sensed signals are sent to controller360for processing and detecting the wearer's activity level. Sensor374may be an accelerometer that measures the movement of the wearer. Referring now toFIGS.20A-20B, operation of the exemplary patch pump is described, in whichFIG.20Acorresponds to positions of the pump components when the cartridge is full of medication andFIG.20Bcorresponds to positions of the pump components when the cartridge is empty. The pump motor may be disposed within the pump housing and may be configured to be coupled to a pusher and a cam (e.g., a circular cam) via a gearbox. Preferably, the pump motor is configured to move the pusher towards the cartridge to move the medication within the cartridge into an inflow needle within the cap. At the same time that the pusher is advancing, the cam disposed within the cap is configured to rotate to deliver a predetermined dose of medication to the cannula inserted into the wearer's skin. Pusher335may include screw334, which may be coupled to gearbox324and configured to rotate upon rotation of one or more gears with gearbox324. Nut336may be coupled to screw334such that rotation of screw334causes nut336to move along screw334. Nut336may be coupled to a first end of bendable rod338and a second end of bendable rod338may be coupled to cartridge contactor340, which is configured to contact plunger502of cartridge500. Upon rotation of screw334in a first direction, nut336is configured to move away from gearbox324such that bendable rod338applies a force to cartridge contactor340, causing at least a portion of plunger502to move within cartridge500. Upon rotation of screw334in a second direction, opposite the first direction, nut336is configured to move towards gearbox324, such that bendable rod338and cartridge contactor340move away from the cap of cartridge500. Bendable rod338may also be referred to as a curved piston. InFIG.20A, pusher335is depicted in a home position, when cartridge500is full of medication. In the home position, nut336may be disposed adjacent to the location where screw334is coupled to the gearbox324. InFIG.20B, pusher335is depicted in a delivery position, after cartridge500has delivered medication. Preferably, after all or substantially all of the medication within cartridge500has been delivered, the battery of pump300should be recharged. Upon reaching a predetermined state in the charging cycle, pusher335is configured to return to the home position. For example, the controller, upon sensing that the battery has reached the predetermined state (e.g., a predetermined time before full charge, such as 20 minutes), will cause pump motor328to rewind thereby transitioning the pump back from the empty position ofFIG.20Bto the full position ofFIG.20A. In some embodiments, the pump and the cap will not unlock until the battery is sufficiently charged and the pump is in the home position. Gearbox324preferably rotates screw334in the second direction such that cartridge contactor moves away from plunger502. Nut336may continue moving along screw334towards gearbox324until it reaches a contact sensor, as described below. Upon sensing contact with nut336, screw334is configured to reverse directions to rotate in the first direction such that nut336is advanced a short distance away from gearbox324and a small space is created between nut336and the contact sensor. Resetting pusher335to the home position permits a new, pre-filled cartridge500to be inserted into the patch pump. Plunger502is a movable end of cartridge500and is configured to seal cartridge500such that medication does not leak from the cartridge. Plunger502preferably includes a flexible, elastomeric material that is able to deform when a substantial force is applied. Plunger502may be configured to flex based on the pressure within cartridge500such that the pressure is maintained within a predetermined range. Ensuring the pressure remains within the predetermined range helps ensure the accuracy of each dose of medication, as described below. For example, plunger502may be configured to compress or deform when the pressure within cartridge500is over 800 or 1000 mbar. For example, plunger502may be configured to advance into the cartridge a predetermined distance such as 3-4 um, preferably 3.7 um, after each push from pusher335. Further, plunger502may include a first end that is configured to contact pusher335and a second end that is configured to contact the medication within cartridge500. A risk with using an elastomeric plunger is the “stick-slip effect,” whereby the plunger does not move due to sticking until a force applied to the first end exceeds a displacement needed for a dose of medication. Once the force overcomes the stick, the plunger may travel too far, resulting in an inaccurate dose. By pressurizing the cartridge prior to delivering microdoses, as described herein, the pump reduces the stick-slip effect by providing a counterforce via the pressurized medication on the pushing force caused by the pusher on the cartridge. As a result, the portion of the plunger of the cartridge contacting the medication does not move further than the distance needed to expel the desired volume of medication of the microdose, thereby ensuring enhanced accuracy of microdose volumes of medication. The counterforce from the pressurized medication also may cause the flexible plunger to compress while pumping a microdose. By advancing the piston a micro-step at each delivery of a dose via the microdosing system, pressure in the cartridge is maintained. This pressure within the cartridge varies only minimally due to stick-slip. Preferably, because the system is pressurized, stick-slip has minimal adverse effects on the volume of the microdoses. Advantageously, the patch pump may use this pressure to refill the microdosing system with equivalent amounts of insulin for every delivery cycle. For example, when the pressure within cartridge500is at a first pressure, pusher335may be configured to cause the first end of plunger502to move a first distance towards the cartridge cap and to deliver a first dose of medication. Pusher335also may be configured to cause the second end of plunger502to move a third distance towards the cartridge cap. When the pressure within cartridge500increases to a second pressure, pusher335may be configured to cause the first end of plunger502to move a second distance towards the cartridge cap to deliver a second dose of medication. Pusher335also may be configured to cause the second end of plunger502to move a fourth distance towards the cartridge cap. Preferably, pusher335is configured to advance the same distance every time screw334rotates. Plunger502may be configured so that each push from pusher335causes the first end of plunger502to move the same distance. Therefore, the first distance may be the same as the second distance. Plunger502further may be configured so that each push from pusher335causes the second end of plunger502to move a distance that depends upon the pressure within cartridge500. For example, when the pressure within cartridge500increases, the distance that second end of plunger502moves may decrease. Therefore, the third distance may be greater than the fourth distance. This adjustment by plunger502reduces the risk that the pressure within cartridge500will move outside the predetermined range of 600 mbar to 1000 mbar. Further, maintaining a consistent pressure within the cartridge500reduces the risk that volume of each dose of medication falls outside the predetermined volume of 0.08-1 uL, 0.2-0.6 uL, or 0.2 to 0.3 uL, preferably 0.25 uL±5%. Preferably, the volume of each dose of medication is within 5% of the volume of the other doses delivered to the wearer. The cap of patch pump preferably includes a microdosing system configured to measure and deliver the predetermined doses of medication. Preferably, pusher335, plunger502, and the microdosing system work together to ensure the accuracy of the doses of medication. At the same time that pusher335applies a force to plunger502, the microdosing system is configured to rotate to deliver medication to the wearer. The microdosing system may include a lever system comprising one or more levers configured to sequentially transition between a lowered position, wherein one or more levers contact a dosing tube such that medication cannot flow through the dosing, and a raised position, wherein one or more levers sequentially do not contact the dosing tube, such that medication is expelled from the dosing tube and to the wearer. The one or more levers may act as valves that either permit or prevent medication from flowing through the dosing tube. Preferably, the lever system is configured such that at least one lever is configured to be in a lowered position to close a portion of the dosing tube during the entire time the pump motor moves pusher335. With respect toFIG.20C, an arrangement of wet and dry zones within the patch pump is described. The patch pump may include isolated wet and dry zones to protect the electrical components from contacting any leaked medication or other fluids. The patch pump may include dry zone378that is configured to house the circuit board, motor, vibration motor, sound generator, battery, coil, gearbox, and one or more sensors. Dry zone378may be encapsulated to exclude moisture from reaching the components within the zone. Dry zone378may be encased in plastic and/or sealed via welding. One or more dry zone vents381may be disposed on the plastic housing of dry zone378such that humidity and gas may escape the housing and pressure may equilibrate. For example, dry zone vents381may be made of Gore-Tex®. Dry zone378may be separated from protected wet zone380and unprotected wet zone382via one or more sealing members, for example, dry zone seals379. Protected wet zone380may be configured to house the pusher and unprotected wet zone382may be configured to house the cartridge and the components of the cap including the needles and microdosing system. In addition, cartridge holder332may separate the protected wet zone from the dry zone and may include one or more O-rings to seal off the zones when a cartridge is disposed within the pump-cap assembly. Referring now toFIG.21A, further details of exemplary internal components of the patch pump are described. Circuit board314preferably is configured to have a flexible substrate that can bend and fold to fit to surround battery318, gearbox324, motor328, and vibration motor330within the pump housing. The components of circuit board314may be strategically positioned in particular locations relative to the corresponding components of the pump or cap. For example, photoplethysmography sensor346may be positioned on the skin-facing side of the pump patch so that photoplethysmography sensor346may detect the wearer's heart rate or other physiologic parameters. Sensor320, which is configured to detect a parameter indicative of the pressure within cartridge500, may be coupled to gearbox324and/or the pusher such that sensor320may detect the force applied to the pusher. Sensor320preferably is coupled to circuit board314via sensor connector321. Sensor316, which is configured to detect an occlusion in the dosing pathway, may be a hall-effect sensor. Preferably, sensor316is disposed adjacent to microdosing system410such that sensor316can detect the position of a magnet of microdosing system410based on proximity of the magnet to the hall-effect sensor. Sensor344, which is configured to determine the position of a cam plate of microdosing system410, may be coupled to gearbox324and disposed adjacent to microdosing system410and magnet396. Sensor344preferably is coupled to circuit board314via sensor connector345. Cartridge500is inserted into the patch pump such that the cartridge cap is disposed within the cap when the patch pump is locked. The longer the distance the medication must travel through before delivering the medication to the wearer, the higher the risk that an occlusion will form within the needles. Preferably, cartridge500is positioned as close as possible to microdosing system410and connection cavity404such that the lengths of inflow needle406and outflow needle408are as short as possible. With respect toFIGS.21B and21Cinternal components of the pump-cap assembly are shown with certain electrical components removed.FIG.21Bdepicts the components within the gearbox. Motor328, mechanical coupling322, and screw334are coupled to the gearbox. One or more dry zone seals379may be disposed between the gearbox and mechanical coupling322and/or screw334. Upon rotation of motor328, the gears within the gearbox rotate, causing mechanical coupling322to rotate. Mechanical coupling322is coupled to a cam shaft of microdosing system410such that rotation of mechanical coupling322causes the cam shaft to rotate, which in turn causes the lever system to deliver a predetermined dose of medication to the wearer. At the same time, the gears within the gearbox also cause screw334to rotate. Rotation of screw334causes nut336to move along screw334, preferably in the direction towards plunger502of cartridge500. FIG.21Cdepicts another view of the system. Inflow needle406and outflow needle408may be configured to have a short length in order to reduce the risk of occlusion. Inflow needle406preferably extends from the cartridge cap of cartridge500, around connection cavity404and to microdosing system410. Outflow needle408preferably extends from microdosing system410through connection cavity404, and into the cannula inserted into the wearer's skin. Coupled between the inflow and outflow needle is a dosing tube configured to hold the predetermined dose of medication. Turning now toFIGS.22A-22C, an exemplary contact sensor is described. The pump may include a sensor configured to detect the position of the pusher within the pump, which may indicate a state of the patch pump. The sensed position may be used to determine whether the pusher is positioned within the pump such that a new, pre-filled cartridge may be inserted into the patch pump. The sensed position further may be used to make sure that, when the pusher moves in the opposite direction to return to a home position, it does not stops moving before it reaches the pump housing. The sensed position also may be used to determine the battery level of the patch pump. As described below, until a sufficient battery level is reached, the pump may remain locked to the cap, preventing replacement of the emptied cartridge. InFIG.22A, exemplary contact sensor348, which may be an electrical contact sensor, is disposed within the pump and configured to detect the position of the pusher. For example, sensor348may include one or more contacting pins that are configured to contact one or more contacting blades coupled to the pusher. The contacting pins may be coupled to the circuit board via a conductor such that when the one or more contacting pins contact the one or more contacting blades, a circuit is completed, which indicates that the pusher is disposed in a starting position. The pusher may include screw334, nut336configured to move along screw334such that bendable rod338, which is coupled to nut336, pushes a cartridge contactor (not shown) to contact a plunger disposed within the cartridge. Upon movement of the pusher, the plunger is configured to advance into the cartridge such that medication is moved towards the inflow needle of the cap. After the cartridge is empty, the pusher moves in an opposite direction, away from the cartridge and back to the starting position. The position of the pusher may indicate that the pusher transitioned to a first position such that the cartridge is permitted to be removed and exchanged for a subsequent cartridge. One or more contacting blades390may be coupled to nut336. Sensor348preferably is disposed within pump housing302and adjacent to contacting blades390of the pusher. For example, sensor348may include one or more contacting pins386and388that are configured to contact contacting blade390when the pusher is positioned near the pump housing back such that a new, pre-filled cartridge may be inserted into the patch pump. Contacting pins386and388may be coupled to conductor384, which is configured to electrically connect contacting pins386and388to the circuit board. InFIG.22B, the contact sensor in a non-contacting position, wherein contacting blades390are not connected to contacting pins386and388. InFIG.22C, the contact sensor in a contacting position, wherein contacting blades390are connected to contacting pins386and388. Sensor348may be electrically coupled to a controller such that sensed signals are sent to the controller for processing and determining a state of the patch pump. For example, if sensor348detects that the pusher is in contact with contacting pins386and388, the controller may be configured to cause the pusher to move in an opposite direction to a home position, The controller further may be configured to monitor the battery level of the patch pump and unlock the pump and cap if both the battery level is at a sufficient level and sensor348senses contact with the pusher. Referring now toFIG.23A, aspects of the gearbox of the pump are described. Gearbox324is configured to cause simultaneous movement of the pusher and rotation of the microdosing system. One or more sensors may be disposed within gearbox324to determine the position of a cam plate within the microdosing system or the pressure within the cartridge. For example, as described below, the position of the cam plate may be used to validate that a dose of medication was properly delivered to the wearer or may be used to ensure that pump and cap remain locked together. Gearbox324may include a ferromagnetic blade that may be coupled to the cam plate and, upon rotation, may generate an oscillation of a signal that can be used to count the teeth on the ferromagnetic blade and accordingly whether the dosing cycle is complete. Gearbox324further may include a sensor that is configured to measure a force that is indicative of the pressure within the cartridge. Referring now toFIG.23B, an exemplary pressure sensor disposed within the pump is described. To ensure accurate doses of medication, the patch pump may be configured such that the pressure within the cartridge is maintained within a predetermined range. For example, the predetermined range may be between 600 mbar and 1000 mbar. A sensor may be coupled to a pusher and configured to measure the force on the pusher, which may be indicative of the pressure within the cartridge. For example, sensor320may include strain gauge394configured to measure deformation, for example, by measuring a change in electrical resistance. The pusher may include screw334having a first end, coupled to gearbox324and disposed adjacent to strain gauge394, and a second end, coupled to the cartridge. As the pressure within the cartridge increases, a greater force is applied to the pusher, and the pusher applies the same force to gearbox324at force application point392. The greater the force applied to the pusher, the greater the deformation of strain gauge394. Sensor320preferably is operatively coupled to a controller that may monitor the sensed pressure. The pressure within the cartridge must be increased until it falls within the predetermined range in order to ensure that the proper dose of medication is delivered to the wearer. Further the controller may be configured to alert the wearer when the pressure falls outside the predetermined range. For example, a pressure under 600 mbar may indicate that a cartridge is not disposed within the patch pump or that a cartridge was inserted incorrectly. A pressure over 1000 mbar may indicate that there is an occlusion within the cartridge cap, the inflow needle, and/or the cannula. In a preferred embodiment, the patch pump is configured to be “initialized” prior to pumping medication from the cartridge past the microdosing system and into the user. In this manner, the controller of the pump causes the pump to increase pressure within the cartridge into a predetermined range prior to delivering the first dose of medication from the cartridge to the wearer. By pressurizing the cartridge, the patch pump ensures that precise volumes of microdoses of medication and are consistently and predictably provided to the user, including the first dose of medication from the cartridge. Further, the initialization ensures that bubbles within the cartridge and the tubing connected thereto are reduced and that the formation of bubbles is reduced. Advantageously, the patch pumps described herein may be generally “bubble free.” With respect toFIG.24A, a graph showing the relationship between pressure and volume is described, whileFIGS.24B and24Cshow the relationship between the number of dosing cycles and the amount of medication delivered per cycle, without and with initialization.FIG.24Dshows the accuracy of the patch pump with and without the microdosing system andFIG.24Eshows a comparison of the percentage error of flow for the patch pump described herein and other commercially available pumps. Accurate dosing requires that the pressure within the cartridge remains within a predetermined range. As further explained below, the patch pump may include a microdosing system that is configured to measure and deliver a predetermined dose of medication. The microdosing system preferably includes a dosing tube with a flattened reservoir portion or compartment configured to hold a predetermined dose of medication. Because the reservoir portion is flexible, as the pressure of the medication increases, the reservoir portion expands more, allowing it to hold a greater volume of medication. Accordingly, pressure variations may result in delivery of inconsistent and inaccurate doses of the medication. This relationship is depicted inFIG.24A. Preferably, the pressure within the cartridge is between 600 mbar and 1000 mbar, and the ideal pressure is 800 mbar. When the pressure is at 800 mbar, the volume of medication is 0.25 ul, which is the preferred predetermined dose of medication. As the pusher advances towards the plunger of the cartridge, moving the plunger into the cartridge, the pressure within the cartridge builds. As the pressure builds to 800 mbar, the expected volume of the medication that would be held within the dosing tube—if the levers allowed medication to flow into the dosing tube—increases until it reaches the preferred dose of 0.25 ul. Preferably, the microdosing system is configured to complete an initialization process such that delivery of medication to the wearer is prevented until the pressure within the cartridge reaches the predetermined range (e.g., 250 mbar to 2000 mbar, 400 mbar to 1200 mbar, or 600 mbar to 900 mbar). If the microdosing system is configured to complete an initialization process such that delivery of medication to the wearer is prevented until the pressure within the cartridge reaches the predetermined range, the pressure increases at a faster rate than if the there is no initialization of the microdosing system. FIG.24Bdepicts what may occur if the microdosing system is configured to deliver medication prior to initialization. The first dosing cycle would deliver a first dose of medication having a much smaller volume than the preferred volume of 0.25 ul. The second dosing cycle would deliver a second dose of medication having a larger volume than the first dose of medication, but the volume would still be less than the preferred volume of 0.25 ul. As the dosing cycles continue, the pressure would slowly increase to the predetermined range and the volume of medication delivered would slowly reach the predetermined volume. However, the first doses that the wearer would receive would be less than the predetermined dose of medication. Preferably, as inFIG.24C, microdosing is disabled until the pressure is within 600 mbar and 1000 mbar, such that the volume of each dose of medication is within 5% of 0.25 ul. As the dosing cycles continue, the volume of each dose of medication should remain within 5% of the volume of the previous dose of medication. Referring now toFIG.24D, a graph showing the volume pumped per two microdoses over the total volume pump is described. Each data point represents two microdoses, each microdose preferably 0.25 uL. The measurements for the patch pump without the microdosing system shows that the system delivers accurate microdoses but with limited precision. In contrast, the measurements for the patch pump including the microdosing system is both accurate and precise. Referring now toFIG.24E, a graph showing the percentage error of flow measurements for the patch pump with and without microdosing and the percentage error of flow measurements for other commercially available pumps is described. The percentage error of flow corresponds to the precision of the pumps, a higher percentage error of flow indicating that the volume of each microdose has a greater variance and thus the pump is less precise. For each pump, the percentage error of flow decreases with each delivery of a microdose. As shown inFIG.24E, the patch pump described herein (“Sigi”) is as precise or more precise than other commercially available pumps. Referring now toFIG.24F, a schematic depiction of an exemplary pusher and microdosing system is described. Medication may be delivered from cartridge500, through inflow needle406, and into flattened dosing tube447. Upon rotation of the microdosing system, the medication may then be forced out of flattened dosing tube447, delivered through outflow needle408to cannula200, and inserted into the wearer. Preferably, microdosing system410and pusher335work together to maintain the pressure within cartridge500within a predetermined pressure range. For example, the strain of the plunger and the bendable rod of pusher335within cartridge500at one end and the levers of microdosing system410at the other end create a closed system in which the medication is disposed, the closed system helping maintain the pressure within the predetermined pressure range. The motor within the pump simultaneously advances the plunger and activates microdosing system410at each dosing cycle. Preferably, the plunger advances in microsteps (e.g., 3-4 um, preferably 3.7 um) at each dosing cycle such that the pressure within cartridge500varies only minimally due to the “stick-slip”effect that occurs at the elastomeric portion of the plunger. The patch pump uses the constant pressure to refill the reservoir of flattened dosing tube447with equivalent volumes of medication at every dosing cycle. Inflow needle406, outflow needle408, and dosing tube447are preferably made from materials compatible with insulin. For example, the inflow and outflow needles may be made of stainless steel and dosing tube447may be made of fluoropolymer tubing. Because the flow path for insulin may be directly from cartridge500into inflow needle406, then into dosing tube447, then into outflow needle, then into cannula200(which is also made from insulin compatible material), all materials in contact with the insulin are insulin compatible. With respect toFIG.25A, an exploded view an exemplary cap is described. For example, cap400may include within cap housing402and internal cap housing401the following components: cap clips403, unclipping buttons405, inflow needle406, outflow needle408, microdosing system410, cam shaft412, lever spring system413, lever system414, cam plate416, microdosing structure418, spring422, magnet428, tabs430, flattened dosing tube447, dosing tube support454, and/or prongs474. These components are described further herein. Referring now toFIG.25B, an exemplary microdosing system disposed within the cap, wherein an exemplary cam is in an initialization position, is described. The cap is configured to deliver medication from the cartridge to the wearer and preferably includes microdosing system410configured to measure and deliver the predetermined doses of medication. Preferably, microdosing system410is configured such that the insulin travels through a simple pathway designed for low shear stress, which avoids compromising the insulin. Microdosing system410may be configured to only deliver the predetermined dose of medication upon initialization of the microdosing system, when the pressure sensor, as described above, senses that the pressure within the cartridge is within the predetermined range. The initialization process helps ensure that the microdosing system accurately measures the predetermined doses of medication. The predetermined pressure range may depend upon the cartridge or medication used, but preferably is between 600 mbar and 1000 mbar. When the pressure sensor senses that the pressure is within the predetermined range, the processor, may be configured to execute programmed instructions stored in the memory to cause the microdosing system to move from an initialization position to a dosing position, such that medication may be delivered to the wearer. Microdosing system410is configured to provide for more accurate dosing and to reduce the noise from the delivery of the medication. Microdosing system410preferably is coupled to an inflow needle, which may extend from the cartridge to microdosing system410, and an outflow needle, which may extend from microdosing system410to the cannula. Coupled between the inflow and outflow needle is a dosing tube configured to receive the medication, the dosing tube having a flattened portion including a reservoir portion configured to hold the predetermined dose of medication. The reservoir portion may comprises one or more welded portions that help ensure that a predetermined volume of medication is delivered to the wearer. Microdosing system410further may include a cam, which is configured to rotate, and lever system414, which is configured to contact the dosing tube and release the predetermined dose of medication into the outflow needle upon interaction with the cam. The cam may be circular in shape to reduce the overall size of the cam and/or to permit two microdoses with a full 360 degree turn of the cam, although other shapes may be suitable. Lever system414may include one or more levers, each lever configured to be independently movable such that the movement of a first lever does not affect the position of a second lever. The cam may include cam shaft412, which is oriented in a first plane, and cam plate416, which is coupled to cam shaft412and oriented in a second plane, the second plane preferably orthogonal to the first plane. The cam plate may be circular in shape to reduce the overall size of the cam plate and/or to permit two microdoses with a full 360 degree turn of the cam plate, although other shapes may be suitable. Cam plate416may include a top surface having one or more raised surfaces that are configured to interact with one or more levers of lever system414upon rotation of cam shaft412such that the predetermined dose of medication is delivered to the wearer. The raised surface(s) may extend away from the circular portion of cam plate416, such as in a direction generally parallel to the longitudinal axis of the cam. Lever system414further may include magnet428, which is configured to be used to detect an occlusion in the dosing pathway. Microdosing system410further may include tabs430, which are configured to rotate upon actuation by the motor. Tabs430preferably are disposed at the end of cam shaft412such that tabs430may extend towards and interact with the pump. Additionally, tabs430may be configured to function as a locking mechanism. For example, tabs430may interact with the mechanical coupling of the pump such that the cap remains locked to the pump. The patch pump may be configured to remain locked until the pusher of the pump is reset in a home position and until the battery is sufficiently charged. Until a predetermined pressure range is detected within the cartridge, microdosing system410preferably remains in an initialization position, wherein cam plate416is disposed in a lowered position, as shown inFIG.25B. In the initialization position, cam plate416is separate from and not coupled to lever system414such that movement of cam plate416does not cause movement of lever system414. After the cap and the pump are locked together, cam shaft412is configured to rotate in a first direction while the pusher is advanced into the cartridge, causing the pressure within the cartridge to increase. Cam plate416may be configured to remain in the initialization position until the pressure within the cartridge is within a predetermined pressure range. To transition cam plate416to the dosing position, the direction of rotation may be reversed to a second direction, opposite of the first direction. Cam plate416may have a lower portion disposed below the top surface of cam plate416, the lower portion comprising an outer shaft that surrounds a lower shaft (e.g., cam shaft412). One or more wings may be disposed on the outer shaft such that wings420extend outwards at a slight angle, similar to a thread. In the initialization position, wings420interact with components of microdosing structure418such that cam plate416is prevented from transitioning from the lowered, initialization position to a raised, dosing position to contact lever system414. The components of microdosing structure418may include spring422, dampers424, and mating surfaces426. Spring422may be disposed on the top surface of microdosing structure418and may apply an upward force on cam plate416. Dampers424may include a plastic material that is configured to minimize the noise from the rotation of the circular cam. Dampers424also may act as a gripping mechanism on wings420when cam plate416transitions from the initialization position to the dosing position. Mating surfaces426may be configured to be positioned on microdosing structure418at a slight angle, similar to a thread, such that wings420may only transition to the dosing position when cam plate416rotates in a particular direction. Referring now toFIGS.25C-25F, further details of operation of the circular cam is described. As the pressure within the cartridge is increased to an optimal pressure, cam shaft416is rotated in a first direction, as depicted inFIG.25C. Spring422applies an upwards force on cam plate416such that wings420contact dampers424and mating surfaces426but the circular cam remains in a non-gripping position. After the pressure is determined to be within the predetermined pressure range, the direction of rotation of the circular cam is reversed to a second direction, as depicted inFIG.25D. The circular cam is transitioned to a gripping position wherein wings420are gripped between dampers424and mating surfaces426. As cam plate416continues to rotate and spring422continues to apply an upward force, wings420slide upwards through mating surfaces426, transitioning the circular cam to a sliding position, as depicted inFIG.25E. Wings420continue to slide between dampers424and mating surfaces426until wings420are disposed on top of microdosing structure418. In the last step of the initialization process, cam plate416shifts to the dosing position such that cam plate416contacts lever system414, as depicted inFIG.25F. The circular cam may be configured such that the transition from the initialization position to the dosing position is permanent and, once in the dosing position, the circular cam cannot return to the initialization position. InFIGS.26A and26B, the locations and functions of exemplary dampers and mating surfaces are described. Microdosing structure418may be configured to hold the circular cam in an initialization position until the pressure within the cartridge is within a predetermined range. Microdosing structure418may include dampers424and mating surfaces426, which are configured to interact with and grip the wings of the cam plate when the circular cam transitions from the initialization position to the dosing position. Mating surfaces426preferably are configured to have an angled interface that functions as a thread when the wings rotate upwards towards the lever system. Microdosing structure418also may be configured to minimize the noise from the rotation of the circular cam. For example, dampers424may be made from a flexible plastic material that is designed to minimize the sound from the contact between microdosing structure418and the top surface of cam plate416. Referring now toFIGS.27A and27B, details of a preferred microdosing system are described. Microdosing system410is configured to move a predetermined dose of medication towards an outflow needle and into the wearer's skin and may include a dosing tube, lever system414configured to contact the dosing tube, and a circular cam configured to rotate. The circular cam preferably includes a cam shaft and cam plate416, which, upon rotation of the cam shaft, is configured to interact with lever system414and deliver the predetermined dose of medication towards the wearer. Lever system414may be coupled to lever spring system413having one or more springs that are configured to keep the levers of lever system414in a lowered position. For example, microdosing system410may include first lever spring432coupled to a first lever, middle lever spring434coupled to a middle lever, and second lever spring436coupled to a second lever. Lever spring system413may be a single structure comprising one or more levers or may include separate structures, each structure comprising a lever. FIG.27Cdepicts the microdosing system with the lever system spaced apart to reveal the dosing tube. The lever springs are configured to provide a force on the lever system such that the levers of the lever system maintain contact with the dosing tube and the pressure from the levers prevents the medication from flowing through the dosing tube until intended. The lever springs preferably are disposed above corresponding sections of flattened dosing tube447, which is coupled to dosing tube support454. Flattened dosing tube447may include a flattened portion having three sections, dosing tube first portion448, dosing tube reservoir portion450, and dosing tube second portion452. Preferably, dosing tube reservoir portion450is a compartment between dosing tube first portion448and dosing tube second portion452, the compartment designed to hold a predetermined dose of medication. For example, first lever spring432may be disposed above dosing tube first portion448, middle lever spring434may be disposed above dosing tube reservoir portion450, and second lever spring436may be disposed above a dosing tube second portion452. With respect toFIG.27D, further details of the microdosing system are described. The lever system preferably includes first lever442, middle lever444, and second lever446, which are configured to contact the dosing tube and act as valves to either permit or prevent medication from flowing through the respective portion of the dosing tube. First lever442may be configured to be coupled to first lever spring432and to contact dosing tube first portion448. Middle lever444may be configured to be coupled to middle lever spring434and to contact dosing tube reservoir portion450. Second lever446may be configured to be coupled to second lever spring436and to contact dosing tube second portion452. Referring now toFIGS.28A and28B, details of the circular cam and lever system are described. Cam plate416is configured to interact with lever system414such that, upon rotation of cam plate416, the levers of lever system414move in a series of steps and deliver a predetermined dose of medication to the wearer. Cam plate416may include one or more rounded, raised surfaces that interact with corresponding rounded lever ramps on the levers of lever system414. The rounded surfaces ensure smooth movement between of the levers and may help mitigate the sound of the microdosing system. Each time a lever contacts the raised surfaces of cam plate416, the lever transitions from a lowered position to a raised position, allowing medication to flow through the corresponding section of the dosing tube. Cam plate416may include outer raised surfaces438and inner raised surfaces440, positioned radially outward of outer raised surfaces438. Outer raised surfaces438may be configured to contact the first lever ramp of first lever442and the second lever ramp of second lever446. Preferably, outer raised surfaces438are sized and shaped such that the outer raised surface may be disposed between the first lever ramp and the second lever ramp without contacting either the first lever ramp or the second lever ramp. Inner raised surfaces440may be configured to contact only the middle lever ramp of middle lever444. The raised surfaces on cam plate416may be configured such that a complete 360 degree rotation of cam plate416delivers two predetermined doses of medication towards the wearer. For example, inFIG.28A, cam plate416includes two outer raised surfaces438and two inner raised surfaces440, the second outer and inner raised surfaces mirror images of the first outer and inner raised surfaces. As will be understood by one of ordinary skill in the art, cam plate416may include more than two raised surfaces and may be configured such that a 360 degree rotation or a rotation of less than 180 degrees is required for delivery of a predetermined dose of medication. Turning toFIGS.29A-29C, operation of the lever system and exemplary dosing tube is described. The levers of lever system414are configured to transition between a lowered position, such that the levers sequentially contact the dosing tube to prevent medication from flowing through the dosing tube, and a sequentially raised position, to expel medication from the dosing tube to the wearer. Medication is delivered first through inflow needle406, which is configured to extend from the cartridge to a first end of the dosing tube, next though the dosing tube, and then through outflow needle408, which is configured to extend from a second end of the dosing tube to the cannula inserted into the wearer. The first end of the dosing tube is adjacent to first lever442and dosing tube first portion448. The second end of the dosing tube is adjacent to second lever446and dosing tube second portion452. Inflow needle406and outflow needle408preferably are coupled to the dosing tube such that the needles are disposed within the dosing tube, as shown inFIG.29B. For example, the outer diameter of inflow needle406and outflow needle408may be the same as or substantially similar to the inner diameter of the first and second ends of the dosing tube. FIG.29Cdepicts a close up of the levers and dosing tube. The dosing tube preferably is disposed on dosing tube support454, which is configured to provide a support for the dosing tube, which includes a flattened portion having three sections. Dosing tube first portion448is a first end of the flattened portion and may be disposed adjacent to first lever442such that, when first lever442is in a lowered position, medication is prevented from flowing from inflow needle406through dosing tube first portion448. Dosing tube second portion452is a second end of the flattened portion and may be disposed adjacent to second lever446such that, when second lever446is in a lowered position, medication is prevented from flowing through dosing tube second portion452and into outflow needle408. Dosing tube reservoir portion450is the middle portion that is substantially surrounded by one or more welded portions. Dosing tube reservoir portion450may be disposed adjacent to middle lever444such that, when middle lever444is lowered and second lever446is raised, medication is expelled from dosing tube reservoir portion450through dosing tube second portion452. Preferably, the levers are sized and shaped to correspond with the size and shape of the dosing tube portions. For example, first lever442and second lever446may contact only a small section of the flattened portion of the dosing tube. Middle lever444may contact a large section of the flattened portion of the dosing tube and may be sized and shaped such that, when middle lever444transitions from a raised position to a lowered position, substantially all the medication held within dosing tube reservoir portion450is expelled towards the wearer. Referring now toFIG.29D, further details of the microdosing system, are described. InFIG.29D, the lever system and lever springs are removed to reveal how the inflow and outflow needles are disposed within the pump housing. Inflow needle406preferably extends from the cartridge to the first end of the dosing tube. Inflow needle406may be configured to contact microdosing structure418and extend around connection cavity404of the cap housing. Outflow needle408preferably extends from the second end of the dosing tube, through connection cavity404, and into the cannula inserted into the wearer's skin. Turning toFIGS.30A-K, operation of microdosing system is described in an exemplary series of steps to deliver a predetermined dose of medication to the wearer. A predetermined dose of medication may be delivered upon rotation of the circular cam, which is configured to interact with the lever system. First lever442may include a first extended arm having first lever ramp456that is configured to contact the outer raised surfaces of cam plate416, middle lever444may include a middle extended arm having middle lever ramp458that is configured to contact the inner raised surfaces of cam plate416, and second lever446may include a second extended arm having second lever ramp460that is configured to contact the outer raised surfaces of cam plate416. Each extended arm may extend from the lever ramps to the dosing tube. Preferably, the lever ramps are configured to maintain smooth and continuous contact with the raised surfaces of cam plate416such that the noise from rotation of the circular cam is minimized. For example, the lever ramps may have a rounded shape and the raised surfaces may have a corresponding rounded shape. FIGS.30A and30Bshow the microdosing system in a first position, wherein first lever442, middle lever444, and second lever446are in a lowered position such that the levers are pressing down on the corresponding portions of the dosing tube and medication cannot flow past any of the levers. In the first position, none of the lever ramps contact the raised surfaces of the cam plate. FIGS.30C and30Dshow the microdosing system in a second position. Upon rotation of the cam plate, outer raised surface438contacts first lever ramp456, moving first lever442from a lowered position to a raised position. Middle lever444and second lever446remain in a lowered position such that medication can flow through dosing tube first portion448but cannot flow past dosing tube reservoir portion450. FIGS.30E and30Fshow the microdosing system in a third position. Upon further rotation of the cam plate, outer raised surface438remains in contact with first lever ramp456such that first lever442remains in a raised position and inner raised surface440contacts middle lever ramp458, moving middle lever444from a lowered position to a raised position. Second lever446remains in a lowered position such that medication can flow through dosing tube first portion448and into dosing tube reservoir portion450but cannot flow past dosing tube second portion452. In the third position, dosing tube reservoir portion450is configured to fill and expand with the predetermined dose of medication. FIGS.30G and30Hshow the microdosing system in a fourth position. Upon further rotation of the cam plate, outer raised surface438moves to a position between first lever ramp456and second lever ramp460such that outer raised surface438is not in contact with either first lever ramp456or second lever ramp460. Inner raised surface440remains in contact with middle lever ramp458such that middle lever444remains in a raised position. First lever442moves from a raised position to a lowered position and second lever446remains in a lowered position such that the predetermined dose of medication is held within dosing tube reservoir portion450and is unable to flow past dosing tube second portion452. FIGS.30I and30Jshow the microdosing system in a fifth position. Upon further rotation of the cam plate, outer raised surface438contacts second lever ramp460, moving second lever446from a lowered position to a raised position, and inner raised surface440remains in contact with middle lever ramp458such that middle lever444remains in a raised position. First lever446remains in a lowered position such that medication can flow through dosing tube second portion452to outflow needle408, but cannot flow back through dosing tube first portion448. FIGS.30K and30Lshow the microdosing system in a sixth position. Upon further rotation of the cam plate, outer raised surface438remains in contact with second lever ramp460such that second lever446remains in a raised position and inner raised surface440moves to a position past middle lever ramp456such that middle lever444moves from a raised position to a lowered position such that middle lever444applies pressure to dosing tube reservoir portion450, forcing the predetermined dose of medication past dosing tube second portion452and into outflow needle408. This step ensures the accuracy of the medication delivery and that all of the predetermined dose of medication is delivered to the wearer such that no medication remains in dosing tube reservoir portion450. FIG.31provides a schematic depiction of the series of steps configured to deliver the predetermined dose of medication to the wearer. As described with respect toFIGS.30A-Labove, the lever system includes lever ramps, which are configured to move the levers between a lowered position and a raised position upon contact with raised surfaces on the cam plate. Each lever is configured to contact a different portion of the dosing tube. Preferably, first lever442contacts dosing tube first portion448, middle lever444contacts dosing tube reservoir portion450, and second lever446contacts dosing tube second portion452. The steps depicted inFIG.31correspond with the steps shown inFIGS.30A-L. In the first position, first lever442, middle lever444, and second lever446are in a lowered position and contact the corresponding portions of the dosing tube such that the medication cannot flow through the dosing tube or past any of the levers. In the second position, first lever442moves to a raised position and middle lever444and second lever446remain in a lowered position such that medication may only flow through dosing tube first portion448. In the third position, first lever442remains in a raised position, middle lever444moves to a raised position, and second lever446remains in a lowered position such that medication may flow into dosing tube reservoir portion450, but not past second lever446. In the fourth position, first lever442moves to a lowered position, middle lever444remains in a raised position, and second lever446remains in a lowered position such that the predetermined dose of medication is measured within dosing tube reservoir portion450and cannot flow past either first lever442or second lever446. In the fifth position, first lever442remains in a lowered position, middle lever444remains in a raised position, and second lever446moves to a raised position such that predetermined dose of medication may flow from dosing tube reservoir portion450and through dosing tube second portion452. In the sixth position, first lever442remains in a lowered position, middle lever444moves to a lowered position, and second lever446remains in a raised position such that the all of the predetermined dose of medication is forced out of dosing tube reservoir portion450and through dosing tube second portion452towards the wearer. Following this step, the microdosing system returns to the first position wherein all of the levers are in a lowered position. Referring now toFIGS.32A and32B, an exemplary system for detecting an occlusion in the dosing pathway, from cartridge500to the location medication is delivered within the skin of the wearer, is described. An occlusion in the dosing pathway may occur within the dosing tube, within outflow needle408, or within the cannula. Fast detection of an infusion anomaly (e.g., an occlusion) in the dosing pathway allows the microdosing system to monitor the accuracy of the microdosing system and mitigates the risk that the wearer fails to receive a proper dose of medication. Pump300may include sensor316, which may be configured to confirm the accuracy of the microdosing system and that the predetermined dose of medication was delivered to the wearer. Sensor316preferably is configured to sense displacement of one or more levers, which may be indicative of whether there is an occlusion disposed within the dosing tube, within outflow needle408, or within the cannula. Sensor316may be electrically coupled to a controller such that sensed signals are sent to the controller for processing and detecting an occlusion. The controller may sense an occlusion if the sensed displacement is outside a threshold range, the determination based on the proximity of the magnet to the hall-effect sensor over time. For example, the controller may be configured to monitor whether the measured Hall-effect sensor values are within predetermined Hall-effect sensor value ranges that are expected for each step of the dosing cycle or if the measured Hall-effect sensor values change at a time it should remain the same. The controller may determine there is an occlusion based on one or more sensed signals. For example, detection of an occlusion may be based on sensed signals over more than one dosing cycles. Sensor316may also be used to determine whether the microdosing system is in the initialization position. For example, the controller may sense that the microdosing system is in the initialization position if the sensor does not sense any displacement of the one or more levers over a predetermined period of time. Further, sensor316may be used to determine whether the cap is coupled to the pump. The controller may confirm that the cap and pump are properly coupled together if sensor316senses that the one or more levers is disposed in a predetermined position. Alternatively or additionally, information sensed by sensor316may be used to determine a status of the cap, for example, whether the cap is “new” or “used.” For example, the when the cam plate moves from the initialization position to the dosing position, the magnet coupled to the lever system may move slightly towards the pump. Information from sensor316may be used to determine that the microdosing system has completed the initialization process and therefore the cap is “used.” Information sensed by sensor316may be used to determine if the cap is coupled to the pump. For example, if a magnetic field is not sensed by sensor316, the controller indicates that the cap is not coupled to the pump because the magnet in the cap is not being sensed. As such, the controller will not activate pumping until the cap is coupled to the pump. Further, the position of the magnet within the cap, as sensed by sensor316based on the strength of the magnetic field, may indicate the status of the cap. For example, if the magnetic field is within a predetermined range, the controller will indicate that the cap is in the initialization position. If the magnetic field is within a second predetermined range, the controller will indicate that the cap is in the dosing position. In some embodiments, the strength of the magnetic field is weaker when the cap is in the initialization position because the magnet is further from the pump. As the cap moves from the initialization position to the dosing position, the magnet is moved closer to the cap, thereby increasing the strength of the sensed magnetic field. As such, the second predetermined range may be higher than the first predetermined range to indicate that the pump is in the dosing position, as determined by the controller. FIGS.32A and32Bshow a simplified view of the microdosing system in two positions. Disposed within pump300is sensor316and cartridge500, which may be coupled to inflow needle406. Inflow needle406may be coupled to the dosing tube and the dosing tube may be coupled to outflow needle408. The lever system may include middle lever spring434, which may apply a force on middle lever444such that middle lever444remains in a lowered position adjacent to dosing reservoir portion450. At the opposite end of middle lever444, magnet428may be disposed. Magnet428may be positioned such that when middle lever444moves from a lowered position to a raised position, inFIG.32B, magnet428moves closer to sensor316. Sensor316preferably is a Hall-effect sensor that is configured to detect a magnetic field of a magnet disposed on the lever system. InFIG.32A, the dosing tube reservoir portion450is in a compressed state, such that no medication is disposed within dosing tube reservoir portion450. In the compressed state, middle lever444is positioned in a lowered position such that magnet428is disposed farther away from sensor316. The farther magnet428is away from sensor316, the smaller the Hall-effect value will be. InFIG.32B, when dosing tube reservoir portion450is in an expanded state, medication is disposed within dosing tube reservoir portion450. In the expanded state, middle lever44is positioned in a raised position such that magnet428is disposed closer to sensor316such that the Hall-effect value is greater than the Hall-effect value when dosing tube reservoir portion450is in the compressed state. Referring now toFIG.32C, the changing position of the magnet disposed on the middle lever of the microdosing system during a dosing cycle is described. In the first step, first lever442and middle lever444are in a raised position such that medication may flow into dosing tube reservoir portion450. After first lever442moves to a lowered position, second lever446moves to a raised position. A portion of the medication within dosing tube reservoir portion may flow into the outflow needle and thus middle lever444and magnet428may move a slightly farther away from the pump and sensor. In the third step, middle lever444moves to a lowered position such that a force is applied to dosing tube reservoir portion450. If there are no occlusions within the dosing tube or within the outflow needle or cannula, the remaining medication disposed within dosing tube reservoir portion450is forced into the outflow needle and middle lever444and magnet428move to a lowered position. In the last step, middle lever444and magnet428move to the farthest position away from the pump and sensor. FIGS.33A and33Bprovide schematic depictions of the series of steps configured to deliver the predetermined dose of medication to the wearer, wherein the dosing pathway is not occluded and the dosing pathway is occluded, are illustrated.FIG.33Ais similar toFIG.30, described above, and also includes arrows A and B pointing to two steps of the microdosing process. Arrow A is pointing to the sixth position of the microdosing system wherein middle lever444is configured to have moved from a raised position to a lowered position, thus forcing the predetermined dose of medication towards the wearer. Arrow B is pointing to the second position of the microdosing system wherein, first lever442is configured to have moved from a lowered position to a raised position, thus permitting medication to flow through dosing tube first portion448into dosing tube reservoir portion450. WhileFIG.33Adepicts proper operation of the microdosing system,FIG.33Bdepicts a scenario in which there is an occlusion in the dosing pathway. For example, the block may be disposed near dosing tube second portion452and outflow needle408such that medication can flow through a portion of the dosing tube but cannot reach the wearer. In another example, the block may be disposed within the cannula. InFIG.33B, arrow A is pointing to the sixth step, wherein middle lever444is configured to have moved to a lowered position such that predetermined dose of medication flows towards the wearer. However, dosing tube second portion452is blocked due to an occlusion in the dosing pathway, preventing the medication from flowing out of dosing tube reservoir portion450such that middle lever444is unable to move to a lowered position. In the next step, wherein the predetermined dose should be completely delivered to the wearer, second lever446is able to move to a lowered position, but the block prevents any delivery of medication. At arrow B, when the next dosing cycle starts, first lever442is configured to move to a raised position and middle lever444and second lever446are configured to remain in a lowered position. However, because the predetermined dose of medication was unable to move into outflow tube408, middle lever444is finally able to move to the lowered position, pushing the predetermined dose of medication back into the inflow tube. FIGS.33C and33Dillustrate the position of the magnet disposed on the middle lever of the microdosing system, wherein the dosing pathway is not occluded and wherein the dosing pathway is occluded. InFIG.33C, magnet428changes positions when the medication is delivered to the outflow needle. InFIG.33D, because there is an occlusion in the dosing pathway, for example, within the dosing tube, within the outflow needle, or within the cannula, middle lever444is not able to move to the lowered position and thus magnet428does not significantly change positions. By monitoring the value of a parameter(s) (e.g., the Hall-effect value), the sensor is able to determine the position of magnet428and middle lever444, these values indicating whether there is an occlusion in the dosing pathway. For example, if the magnet does not move at least a predetermined distance relative to the pump (e.g., away from the pump) during each microdosing cycle, the controller is able to determine an occlusion in the fluid flow path. InFIG.33D, the magnet does not move at least the predetermined distance away from the pump during a microdosing cycle, thereby indicating an occlusion. As such, the patch pump ensures real-time monitoring of each micro-dosing cycle resulting in ultrafast occlusion detection. Referring now toFIG.34, a graph showing Hall-effect sensor values over time when the dosing pathway is not occluded and when the dosing pathway is occluded is illustrated, and corresponds to the two situations presented inFIGS.33A and33B. At point A, in a non-occluded system, the middle lever would move to a lowered position such that the predetermined dose of medication was forced out of the dosing tube reservoir portion. When the middle lever moves to a lowered position, the magnet disposed at the end of the middle lever moves farther away from the hall-effect sensor and therefore the Hall-effect sensor value decreases. However, if there is a blockage within the dosing tube second portion, the outflow needle, or the cannula, middle lever would not be able to move to a lowered position and the position of the magnet would not either. The Hall-effect sensor value therefore would remain substantially the same. At point B, in a non-occluded system, the middle lever would have remained in a lowered position while the dosing cycle was beginning again. However, if the predetermined dose of medication was unable to deliver the medication from the dosing tube reservoir portion, the middle lever would have started in a raised position. As the first lever is moved to a raised position, the middle lever is able to move to the lowered position, forcing medication within the dosing tube reservoir portion to flow back into the inflow tube. Therefore, in an occluded system, at point B, the magnet disposed at the end of the middle lever moves farther away from the Hall-effect sensor such that the Hall-effect sensor value decreases. A controller may be operatively coupled to the sensor and may be configured to determine whether there is an occlusion in the dosing pathway. For example, the controller may be configured to monitor whether the measured Hall-effect sensor values are within predetermined Hall-effect sensor value ranges that are expected for each step of the dosing cycle or if the measured Hall-effect sensor values change at a time it should remain the same. If there is an occlusion, at point A, the measured Hall-effect sensor value may exceed the predetermined Hall-effect sensor value range for that step. At point B, the measured Hall-effect sensor value decreases while the predetermined Hall-effect sensor value remains the same. The controller may determine there is an occlusion based off of the measurements at point A, point B, or both point A and point B. Referring now toFIGS.35A-35D, an exemplary system configured to determine the position of the circular cam is described, whereinFIG.35Eis a graph showing signal strength over time as the circular cam rotates. Another way to validate that the predetermined doses of medication are properly delivered to the wearer and to ensure that the dosing cycle is fully completed is by determining the position of the cam plate. Monitoring of the position of the cam plate also helps the controller determine the absolute stopping position for each dosing cycle such that the controller can ensure that the patch pump remains locked, as described above. For example, a ferromagnetic blade having teeth may be coupled to the cam plate and, upon rotation, may generate an oscillation of a signal that can be used to count the teeth on the ferromagnetic blade. The generated oscillations may be used as an incremental sensor to determine the position of a cam plate and accordingly whether the dosing cycle is complete. Preferably, pump300includes circuit board314having sensor344disposed on one side of circuit board314and magnet396disposed on the other side of circuit board314and adjacent to sensor344. Pump300further may include gearbox324having ferromagnetic blade323. Ferromagnetic blade323may have a plurality of teeth and the plurality of teeth may include one or more gaps325. Gaps325may be spaced equally around ferromagnetic blade323and preferably align with the end of a dosing cycle. For example, one 360 degree rotation of cam plate416may complete two doses cycles. Ferromagnetic blade323may include two gaps325disposed opposite of each other and configured to align with the end of a dosing cycle. Sensor344preferably is electrically coupled to a controller such that sensed signals are sent to the controller for determining the position of cam plate416. Gaps325may create longer (dT1>dT2) and stronger (A1>A2) oscillations, as shown inFIG.35E. By monitoring the oscillations, and determining the position of cam plate416, the controller is able to determine the absolute stopping position for each dosing cycle. This determination also may help the controller ensure that the patch pump remains locked, as described above. With respect toFIGS.36A and36B, an exemplary tube flattening system before and after the dosing tube is flattened is described. The dosing tube preferably is made from a flexible polymer such that the levers of the lever system may apply pressure to the dosing tube, causing the dosing tube to deflect and prevent the medication from flowing through the dosing tube. The dosing tube preferably includes dosing tube reservoir portion450, which is designed to slightly expand such that the predetermined dose of medication is accurately measured. By monitoring the pressure within the cartridge and by measuring the predetermined dose of medication by volume, the accuracy of the dose is increased. Dosing tube reservoir portion450also may include welded portions that are configured to increase the accuracy of the volume within the reservoir. Tube flattening system800is configured to flatten dosing tube reservoir portion450. Tube flattening system800provides advantages over the methods of the prior art wherein the tube is blow molded and then flattened. One of the key benefits of this system is that it reduces the risk that the tubing walls within dosing tube reservoir portion450do not have a constant thickness and rigidity. Uniformity along the tubing walls helps ensure that each manufactured dosing tube reservoir portion450expands to the same size, thus ensuring that the predetermined doses of medication are similar among different devices. Tube flattening system800may include two or more raised portions802that are spaced apart such that unflattened dosing tube466may fit between a first and second raised portion without significant excess space remaining. Tube flattening system800further may include press806, which is configured to apply pressure onto unflattened dosing tube466to create a flattened dosing tube including dosing tube reservoir portion450, which is designed to hold a predetermined dose of medication. Preferably, press806moves from a raised position such that press806does not contact unflattened dosing tube466to a lowered position such that press806presses on unflattened dosing tube466until it reaches thickness guide804. Thickness guide804preferably is disposed on either side of unflattened dosing tube466and protrudes above lower portion808of tube flattening system800to a height that is substantially the same as the preferred thickness of dosing tube reservoir portion450. Turning toFIG.37, an exemplary welded dosing tube is described. To further ensure that the predetermined dose of the medication is accurate, dosing tube reservoir portion450may include welded portions468, which help define a specific volume to be filled with medication. Welded portions468also may increase the efficiency of the watertightness such that the levers can provide less pressure on the dosing tube while still preventing the medication from flowing towards the wearer. Welded portions468may be disposed on the outer portions of dosing tube reservoir portion450such that the medication may still flow through the dosing tube. Preferably, the dosing tube is welded onto dosing tube support454via laser welding. The dosing tube may be transparent to a laser and dosing tube support454may not be transparent to the laser. Dosing tube support454is configured to provide a support for the dosing tube during welding and also is configured to help position the dosing tube within the patch pump during assembly. Referring now toFIGS.38A-38C, exemplary mechanisms for locking the patch pump to the pad are described. The locking mechanisms preferably are configured such that the cap remains secured to the pump and the patch pump remains secured to the pad throughout the wearer's daily motions. InFIG.38A, the pump-cap assembly when the pump are locked together. The patch pump may include a pump having pump housing302and a cap having cap housing402and may be configured to house cartridge500. Cap housing402may include cap lock470and pump housing302may include pump housing lock398, configured to interact with cap lock470. The cap may be configured to couple to the pump via a twisting motion. For example, the cap may be placed onto the pump in a first position such that the inflow needle of the cap pierces the cartridge cap of cartridge500. The cap may then be rotated until cap lock470couples to pump housing lock398. InFIG.38Bthe pump-cap assembly and pad are locked together. In order to ensure that cartridge500remains within the patch pump and that the operation of the patch pump is not interrupted by the wearer, the patch pump is configured to couple to the pad such that the pump and cap cannot be uncoupled from each other until the patch pump is uncoupled from the pad. For example, cap housing402further may include pad interface472at a different edge of cap housing402. Cap lock470and pad interface472may be configured to interact with corresponding features of pad skeleton104. Once the patch pump is secured to the pad, the interaction between pad skeleton104, cap lock470and pump housing lock398ensure that the patch pump cannot be opened when disposed on the skin of the wearer. InFIG.38C, distortion that may occur if the pump-cap assembly and pad are not locked together is described. In particular, if the patch pump is not properly coupled to the pad, cap housing402may deform, causing the cap to uncouple from the pump. This unlocking could cause serious consequences for the wearer, and thus must be prevented. One way to prevent the unlocking is to lock the patch pump to the pad, as inFIG.38B. Referring now toFIGS.39A-39F, exemplary mechanisms for locking the cap to the pump are described. In addition to the locking mechanisms noted above, the cap and pump further may include a rotational locking mechanism disposed between pump housing302and cap housing402. This locking mechanism ensures that the wearer cannot uncouple the cap from the pump during delivery of medication. InFIGS.39A and39B, the cap may be placed onto the pump in an open, unlocked position such that the inflow needle of the cap pierces the cartridge cap of cartridge500. The pump may include tabs430, which are coupled to the microdosing system, and the cap may include mechanical coupling322, which is coupled to the gearbox. Both tabs430and mechanical coupling322are configured to rotate upon actuation of the gearbox. Preferably, in the closed position, tabs430are configured to be disposed within mechanical coupling322such that rotation of mechanical coupling322causes rotation of tabs430, which causes rotation of the circular cam described above. In the unlocked position, tabs430and mechanical coupling322may be disposed in a vertical position, perpendicular to the skin-facing side of the patch pump. After the inflow needle of the cap is disposed within cartridge500, the cap then may be rotated until the cap couples to the pump such that the pump and cap are in a closed, but unlocked position, as inFIG.39C. Tabs430are configured to protrude from cap housing402such that tabs430must be in the vertical position in order to either couple or uncouple the cap from the pump. For example, tabs430may be configured to move through channel303of pump housing302. Preferably, channel303is sufficiently narrow such that tabs430cannot travel through channel303when tabs430are in a horizontal position. After the cap is coupled to the pump, the controller may be configured to rotate mechanical coupling322such that mechanical coupling322and tabs430are in a locked position, as inFIG.39D. InFIGS.39E and39F, tabs430are in an unlocked position and a locked position, respectively. A microdosing system is disposed within the cap and is configured to measure and deliver a predetermined dose of medication. The microdosing system may include a dosing tube, circular cam, configured to rotate, and a lever system, configured to contact the dosing tube and release the predetermined dose of medication into an outflow needle. The circular cam may include a cam shaft and a cam plate coupled to the cam shaft. Preferably, the cam plate includes a top surface having one or more raised surfaces configured to interact with one or more levers of the lever system upon rotation of the cam shaft. Tabs430may be disposed at the end of the cam shaft such that tabs430may extend towards and interact with the pump. When the motor interacts with the gearbox, it causes both the pusher to move towards the plunger of the cartridge and mechanical coupling322to rotate, causing rotation of tabs430, which causes the microdosing system to deliver medication to the wearer. Preferably, a 180 degree rotation of mechanical coupling322delivers one dose of medication. Each dosing cycle may occur within a predetermined time period (e.g., 0.5 seconds) such that mechanical coupling322and tabs430are in the vertical position for a very limited amount of time such that the risk that the wearer may uncouple the cap and pump is reduced. In a preferred embodiment, tabs430are permitted to travel through channel303in a range of +−10 degrees from the vertical position. Upon each rotation of mechanical coupling322and tabs430, it may be possible to open the cap twice, each time for about 5 hundredths of a second. However, it may not be possible to open the cap when the pump-cap assembly is clipped to the pad because the cap lock secures the pump-cap assembly to the pad. Preferably, when the pump-cap assembly is not clipped to the pad, the skin detector does not detect the skin and the controller stops the pump such that mechanical coupling322and tabs430are disposed in a locked position and the wearer cannot unlock the pump-cap assembly. The patch pump may be configured to remain locked even after cartridge500is empty. Preferably, mechanical coupling322and tabs430remain in a locked position until the pusher of the pump is reset to the home position and until the battery is sufficiently charged. The controller may be configured to monitor the battery level of the patch pump and unlock the pump and cap if both the battery level is at a sufficient level and a sensor senses that the contacting blade of the pusher is in contact with the contacting pins. Referring now toFIGS.40A and40B, exemplary locking protrusions disposed on the cap and locking receptacles on the pump are described. Surrounding the cartridge, the cap may include one or more locking protrusions and the pump may include one or more corresponding locking receptacles configured to receive the locking protrusions. The locking protrusions and receptacles are configured to lock the cap to the pump such that the continuous force that the pusher places onto the cartridge does not uncouple the cap from the pump. Because the cartridge must remain pressurized in order to ensure accurate dosing, the cartridge may apply a considerable amount of force on the cap. Cap400may include one or more locking protrusions476configured to surround the region of cap400where inflow needle406pierces the cartridge cap of cartridge500. Pump300preferably includes one or more corresponding locking receptacles399, each locking receptacle399configured to engage a locking protrusion476. Locking protrusions476and locking receptacles399may be radially spaced surrounding the inflow needle, may be various sizes and shapes, and may be configured to lock to each other upon rotation of the cap from an open position to a closed position. Preferably, cap400includes at least three locking protrusions476and pump300includes at least three corresponding locking receptacles such that torque is minimized. Locking protrusions476may be configured to prevent the cap from rotating greater than 90 degrees. At least one locking protrusion476may include a first portion having a wide engagement slit and a second portion having a narrower engagement slit. Because the cap preferably is configured to be disposable and the pump preferably is configured to be reusable, the cap and pump may be designed such that the material of the pump housing has a greater creep resistance than the material of the cap housing. Therefore, if the force from the cartridge becomes too great, the cap may be designed to fail, or deform, before the pump fails or deforms. For example, the material of pump housing302may be different than the material of cap housing402. Additionally or alternatively, the material of pump housing302may have a greater thickness than the material of cap housing402. The same principle may apply to the pad. Because the pad preferably is configured to be disposable and the pump preferably is configured to be reusable, the pad and pump may be designed such that the material of the pump housing has a greater creep resistance than the material of the pad skeleton. With respect toFIG.41, a preferred embodiment of a cartridge is described. The patch pump may include a pre-filled cartridge that is configured to be inserted into the patch pump. Cartridge500may be filled during manufacturing or may instead be filled by the wearer prior to inserting cartridge500into the pump. For example, the wearer may pre-fill several cartridges configured to last one month and store the pre-filled cartridges in the fridge until the cartridge are to be used. Preferably the wearer may insert the pre-filled cartridges into the patch pump directly after removal from the fridge and need not wait a certain period of time (e.g., 20 minutes) before inserting the cartridge. Preferably, the pre-filled cartridge includes a movable end that is configured to interact with the pusher of the pump and a cap that is configured to interact with the inflow needle of the cap. For example, the wearer may insert cartridge500into the pump. Cartridge500may be sized and shaped such that when the pump and cap are coupled together, forming the patch pump, cartridge500is completely enclosed by the patch pump. Preferably, cartridge500contains insulin and is pre-filled with an amount of insulin that is sufficient for the wearer for at least three days. Cartridge500may be a commercially available insulin container such as the NovoRapid PumpCart available from Novo Nordisk A/S of Bagsværd, Denmark. Cartridge500further may include cartridge cap504, which may be disposed at a first end of cartridge500. Cartridge cap504may be configured to be inserted within the patch pump such that the inflow needle of the cap pierces cartridge cap504when the cap is coupled to the pump. Cartridge500further may include plunger502, which may be disposed at a second end of cartridge500, the second end opposite the first end, and may be configured to be inserted within the patch pump such that plunger502is disposed adjacent to the cartridge contactor of pusher. Upon movement of the cartridge contactor, plunger502preferably is configured to move towards cartridge cap504such that the medication with cartridge500is pushed into the inflow needle and towards the microdosing system of the cap. When cartridge500is emptied, the pusher may reset to an initial, home position and cartridge500may be removed and replaced with another pre-filled cartridge. Referring now toFIG.42, charging system600suitable for use with the pumps of the present invention is described and may be used to charge one or more batteries within the pump. Preferably, charging system600charges the battery via an inductive coil disposed within the housing of charger602and the pump. Charger602may be plugged into a conventional socket. via cable606or a cord with an AC or DC power converter. Charging system600also may include charger support frame604, which is configured to hold the pump while charging. Charger support frame604may be have a similar size and shape as the pad skeleton. Referring now toFIG.43A-G, illustrative screenshots of an exemplary mobile device and mobile application interfaces are described. The patch pump may be configured to communicate data to or from a mobile device running software application700such that the user may review the data and may activate the pump. Software application700may be a dedicated application or “app” and may be downloaded from an online store such as iTunes™ (Apple, Inc., Cupertino, Calif.), the App Store (Apple, Inc.), Google™ Play (Google, Inc., Mountain View, Calif), the Android™ Marketplace (Google, Inc.), Windows™ Phone Store (Microsoft Corp., Redmond, Wash.), or BlackBerry™ World (BlackBerry, Waterloo, Ontario, Canada). Preferably, software application700need only be downloaded once, although updates also may be downloaded. InFIG.43B, interface702permits the user to select which of various pumps to control, with one or more icons depicting a type of pump. The wearer may choose the icon identifying the pump that the wearer is using. Upon identification of the type of pump, software application700may display activation interface704, as inFIG.43C. Activation interface704may include an “activate”, “go”, “run”, “start”, or other similar button or icon that the wearer may press to activate the pump. After activation of the pump, the pump may complete an initialization process to increase the pressure within the cartridge until it is within a predetermined range, as described above. The wearer may view the status of the initialization process on initialization interface706, as inFIG.43D. Once the pump is activated, the wearer may wish to run a test to determine whether the pump is working properly. Software application700may display testing interface708, as inFIG.43E, which may include an icon that may be pressed by the wearer. Software application700may communicate with the pump that a delivery test should be run. For example, the delivery test may include delivery of one microdose of medication. Upon completing the test, the pump may communicate with software application700that the test was either successful or unsuccessful. If the pump ran properly during the test, test successful interface710will be displayed, as shown inFIG.43F, indicating that there were no issues. If the pump detected one or more issues during the test, test unsuccessful interface712will be displayed, as inFIG.43G. Because more than one dosing cycle may be necessary to detect an occlusion due to the flexibility of the cannula, the user may run multiple delivery tests. Testing interface708and interfaces710and712also may include icons allowing the wearer to choose the type of alarm that the pump may emit. For example, the wearer may choose a vibrate mode such that the pump silently alerts the wearer or the wearer may choose an audible mode. Software application700also may allow the user to input information regarding the type of cartridge that is inserted into the patch pump. For example, the cartridges that may be inserted into the patch pump may have different concentrations of medication. Each cartridge may have identification information such as concentration, volume, and/or manufacturer information that is readable by software application700. For example, the user may scan the identification information on the cartridge (e.g., QR code, RFID, color recognition) using the device's camera. Software application700may process an image obtained from the device's camera using, for example, image recognition software to determine the identification information on the cartridge and then may transmit this information to the controller. Alternatively, in some embodiments, the patch pump may automatically identify information on the cartridge (e.g., cartridge type, concentration, etc.) without user intervention. For example, the patch pump may automatically scan the identification information on the cartridge upon insertion of the cartridge into the pump using an optical sensor. The controller may use the identification information of the cartridge to modify the delivery of the medication. While various illustrative embodiments of the invention are described above, it will be apparent to one skilled in the art that various changes and modifications may be made therein without departing from the invention. The appended claims are intended to cover all such changes and modifications that fall within the true scope of the invention. | 186,533 |
11857758 | DETAILED DESCRIPTION OF THE INVENTION For the purpose of promoting an understanding of certain aspects of the invention, reference is made below to certain nonlimiting embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation to the scope of the invention is thereby intended. Furthermore, any dimensions or relative scaling within or among any of the drawings is by way of example and not to be construed as limiting. The following describes a drug delivery device capable of be implanted into a living body (hereinafter, “recipient”) and distributing a drug into the tissue or bloodstream of the recipient, in some cases instantly distributing the drug, as a result of the device being triggered or activated in response to an overdose, and in some cases automatically triggered or activated by the detection of an overdose. As used herein, the term “implantable” is understood to mean a device having an appropriate size, construction, and composition to be able to be surgically placed in a recipient and remain within that recipient over an extended period, for example, thirty days or more, and potentially for the life of the recipient in which it is implanted. Particular but nonlimiting examples of drugs that can be delivered include antidotes such as naloxone, known for its use in the treatment of overdoses due to opioids, though the device could be used to deliver a wide variety of drugs, including emergency drugs (e.g., epinephrine for allergic reaction) and slow-release drugs (e.g., naltrexone for drug recovery treatment). The triggering event used to trigger or activate the device can be based on one or more normal reactions of the human body that may be observable or measurable. For example, when an overdose occurs, the human body reacts with a sudden increase in temperature and other abrupt changes to normal body functions. These sudden changes can be automatically sensed and used to automatically trigger the device, or observed to enable the recipient or others to manually trigger the device. Because the device is already implanted in the recipient, the device is able to immediately release the drug into the recipient to diffuse the overdose before lethal effects occur. The drug delivery device can be configured for subcutaneous implantation via a minimally invasive surgical procedure. Through such a device, it may be possible to eliminate the symptoms and effects of an overdose altogether. FIGS.1and2schematically represent a drug delivery device10adapted to deliver an antidote to combat the effects of an overdose. The device10is represented inFIG.1as comprising a housing12that defines a fluid-tight chamber or reservoir18(not visible inFIG.1) within the device10that is capable of reliably containing a drug until its intended release from the device10. The reservoir18is represented inFIG.2as a single compartment that contains a single dose of a single drug, though it is within the scope of the invention to compartmentalize the reservoir18to enable it to contain multiple doses of one or more drugs. Drugs contained within the reservoir18may be in liquid form, solid (e.g., powder) form, or a combination thereof. The housing12is represented as having oppositely-disposed ends, each closed to define the reservoir18within the housing12. In the embodiment ofFIGS.1and2, a first end of the housing12has an opening that is closed with a permanent or persistent seal14, though it is foreseeable that the housing12could be fabricated so that the first end is closed by an integral wall of the housing12. The oppositely-disposed second end of the housing12has an opening22(not visible inFIG.1) that is closed with a temporary seal16(not visible inFIG.1), such that in combination the housing12, the seal14(if present), and the temporary seal16define the fluid-tight reservoir18. In any event, a drug within the reservoir18is not released unless, in the case of the particular embodiment shown inFIGS.1and2, the temporary seal16sufficiently degrades to allow the drug to exit the reservoir18through the opening22in the housing12. A heating element20(not visible inFIG.1) is incorporated into the housing12so as to be in thermal contact or communication with the temporary seal16, for example, embedded in the temporary seal16(FIG.2), or a tubular-shaped heating element within the reservoir18adjacent the persistent seal14(FIG.1) or adjacent the temporary seal16. In each case, physical degradation of the seal16is the result of the seal16being sufficiently heated to soften or melt to the extent that the drug is able to exit the reservoir18through the opening22that had been previously closed by the seal16. FIG.2schematically represents steps by which the drug delivery device10can be triggered to release a drug contained in its reservoir18. After the device10is subcutaneously implanted in a recipient, the device10remains dormant until such time as a physiological symptom of an overdose is observed or sensed, for example, as a result of an abrupt change in the recipient's body temperature as sensed by a temperature sensor (not shown) attached to or carried in proximity to the recipient's body. The detected or observed change serves as the basis for energizing the heating element20. The heating element20sufficiently heats the temporary seal16to cause the seal16to physically degrade, for example, melt, and become at least partially dislodged from the end of the housing12. The resulting opening22at the end of the housing12exposes the reservoir18, allowing or forcing the drug to exit the reservoir18. The heating element20may be heated to completely or only partially remove the seal16to regulate the release of the drug and, in some cases, heating may be discontinued to allow the seal16to resolidify and reseal the opening22. These aspects of the invention may be promoted by choosing materials for the seal16that exhibit changes in permeability or porosity in response to the thermal stimulus provided by the heating element20. Suitable materials for the temporary seal16include, but are not limited to, biocompatible thermosensitive polymers, for example, cross-linked polymers such as waxes that have melting points above the normal body temperature of the recipient (e.g., about 40 to about 42° C.), enabling the seal16to at least partially melt into liquid form at a temperature well above normal for the human body and yet sufficiently low to not damage the tissue in which the device10is implanted. The drug may be contained within the reservoir18under pressure, such that the drug is forcibly ejected from the reservoir18once the seal16has sufficiently degraded. The housing12and persistent seal14of the device10can be formed of materials having much higher melting or degradation temperatures than the seal16. As nonlimiting examples, the housing12may be in the form of a polytetrafluoroethylene (PTFE) tube and the seal14formed of a PTFE body placed in one end of the PTFE tube of the housing12. Alternatively, other materials can be used, or the housing12and seal14may be a unitary member formed of a single material. In one experimental embodiment, the housing12had a cylindrical shape with a length of about 10 mm and an outer diameter of about 4 mm to facilitate subcutaneous implantation of the device10. Examples of suitable devices for use as the heating element20include, but are not limited to, one or more ferrous (e.g., stainless steel) elements that can be heated by induction heating, and/or one or more ferrite elements with LC circuitry that enable the element to be heated by magnetic hysteresis. InFIG.2, the heating element20is represented as being subjected to an oscillating magnetic field generated by a radio frequency (RF) generator24, such that the heating element20can be wirelessly energized with RF waves at a resonant frequency of its circuitry.FIG.2generically represents the heating element20as inductively coupled to the generator24, for example, as a result of the heating element20being a stainless steel element.FIG.3represents an embodiment utilizing a ferrite heating element20, in which an impedance-matched primary and secondary coil design is used to achieve inductively coupled power transfer between circuitry of an RF generator (lefthand side ofFIG.3) and the LC circuitry (righthand side ofFIG.3) of the ferrite heating element20. The generator24may be in the possession of the recipient, a caregiver or emergency responders, or may be attached to or carried by the recipient. In any case, the generator24is utilized to externally generate an emission capable of wirelessly energizing the heating element20to heat the temporary seal16. On the basis of the above, the delivery device10is adapted to be implanted in a human recipient (or other living body) to deliver one or more drugs to the recipient by releasing the drug contained in the reservoir18as a result of the heating element20generating heat in response to means that will typically be located outside the recipient's body. In the case of an overdose, the heating element20is energized upon the detection of physiological indications that can be observed, sensed, or otherwise detected in the recipient. The device10can be implanted under the skin of an at-risk patient of opioid misuse to enable immediate delivery of an antidote to the patient. In some cases, the device10may be triggered by others, such as a caregiver or emergency responder, though it is also foreseeable that the patient may be able to trigger the device10without assistance. As previously noted, it is also foreseeable that one or more sensors can be utilized to provide feedback control to automatically release the drug when overdose is detected. In experiments leading to the present invention, a test drug (powdered acetaminophen) was placed in the reservoir of a drug delivery device configured similar to the representations ofFIGS.1and2and closed by a seal formed of a thermosensitive wax. The drug was released by melting the seal with heat generated by an inductively-coupled heating element. Spectrophotometric analysis was performed to measure the concentration of drug released. Results of the experiments evidenced that the experimental device was able to successfully diffuse the drug to the surroundings of the device when current was supplied to the heating element via a generator.FIG.4contains a calibration curve for acetaminophen and preliminary data. The concentrations of the diffused drug were found by comparing the data against the calibration curve of absorbance versus known concentrations. The spectrophotometer reading was obtained using λ=243 nm (maximum for acetaminophen). The data inFIG.4is presented as average±standard deviation, and the investigation showed that approximately 1 A was sufficient to melt the seal in a timely manner (less than 10 seconds). The device was determined to deliver a drug dose of about 2 to 5 mg. In another investigation, the time required to heat stainless steel heating elements sized for use in a device of the type represented inFIGS.1and2. The heating elements were inductively heated from a typical human body temperature of 37° C. to a temperature of 42° C., and observed with an infrared (IR) camera. The average time for the five heating elements was about 10 seconds. Preliminary in vivo investigations were also carried out to verify successful activation and passive diffusion of a drug from devices of the type represented inFIGS.1and2. For these investigations, incisions were made in the backs and down the necks of three male mice (C57BL). The skin was lifted and separated from the underlying tissue using forceps and surgical scissors, followed by implantation of the devices. Subcutaneous space was created within each incision to provide space surrounding each device for diffusion of indocyanine green (ICG) dye placed in the reservoirs of the devices. The mice were imaged every minute for forty minutes prior to activation of the devices, which were activated using a magnetic field generated by a coil placed above the skin of each mouse. The coil was supplied with 250 kHz 25 mVpp with a gain of 10 for sixty seconds to minimize the heating of the outer coil. The mice were then imaged for forty minutes post-activation. The normalized radiance values from fluorescent images of the mice are plotted inFIG.5, and evidence that no leakage occurred from the devices in the first forty minutes after implantation and prior to activation. Post-activation, the radiance of the drug signal exponentially increased and stabilized in about ten minutes, evidencing that the devices exhibited a burst release profile as a result of the rapid melting of their temporary seals, contrary to slow-release profiles usually observed with drug delivery implants. While the invention has been described in terms of particular embodiments and investigations, it should be apparent that alternatives could be adopted by one skilled in the art. For example, the drug delivery device10and its components could differ in appearance and construction from the embodiments described herein and shown in the drawings, functions of certain components of the device10could be performed by components of different construction but capable of a similar (though not necessarily equivalent) function, parameters such as temperatures and durations could be modified, and appropriate materials could be substituted for those noted. As such, it should be understood that the above detailed description is intended to describe the particular embodiments represented in the drawings and certain but not necessarily all features and aspects thereof, and to identify certain but not necessarily all alternatives to the embodiments and their described features and aspects. As a nonlimiting example, the invention encompasses additional or alternative embodiments in which one or more features or aspects of a particular embodiment could be eliminated or two or more features or aspects of different embodiments could be combined. Accordingly, it should be understood that the invention is not necessarily limited to any embodiment described herein or illustrated in the drawings, and the phraseology and terminology employed above are for the purpose of describing the illustrated embodiments and investigations and do not necessarily serve as limitations to the scope of the invention. Therefore, the scope of the invention is to be limited only by the following claims. | 14,573 |
11857759 | DETAILED DESCRIPTION The present disclosure is directed to devices used to monitor fluid levels in infusion devices, to determine whether the devices are maintaining proper flow rates and when the reservoirs need to be replenished. The monitoring devices use light sources and light sensors to determine the physical boundaries of the fluid being dispensed. Referring first toFIG.1, a system100is configured to monitor and control a fluid level in an infusion bag101. The infusion bag includes at an upper end of a main body an air vent102, an inlet103, and an injection port104. The main body of the infusion bag101is typically formed from a flexible plastic. Preferably, materials adaptable to3D printers are utilized. The bag may even be made from corn powder. Those skilled in the art will recognize that many materials are suitable for use in forming the infusion bag101. The air vent102provides a means for maintaining an appropriate air pressure in the body of the bag100so that fluid flow may occur properly. The inlet103provides the mechanism whereby the fluid being used in the infusion process is supplied to the infusion bag100. The injection port104allows a caregiver to inject additional required fluids into the infusion bag100. FIG.2illustrates the basic concept of the monitoring function of the infusion system. The infusion bag101is mounted between a light source mount201and a light sensor mount202. The light source mount201includes at least one light source203. The at least one light source203is positioned to direct light through the infusion bag100. The light is detected by one of at least two light sensors204. When fluid is present in the path of the light emitted from the light source203, the light is refracted by the fluid, so that it is detected by a first one of the light sensors204. If no fluid is present in the path of the emitted light, the light travels in a straight line and is detected by a second one of the light sensors204. By this mechanism, the system, using a plurality of light sources and sensors, can detect and track when the fluid level drops past a certain point. The system then triggers a warning and/or a report that the fluid has reached certain level. (More about this function follows below.) FIG.3shows another configuration for the sources and sensors of the system. It is important for the stationary system illustrated inFIG.3to have an array of light sources203, and an array of light sensors204. The light sources203are positioned on a first side of the infusion bag101. As the fluid level in the bag101drops, successive light sensors204will be activated. As each successive sensor204in the array is activated, the system detects and reports the drop of the fluid level in the infusion bag101. When the lowermost sensor204is activated, the system recognizes that the fluid needs to be replenished, and reports this situation to those individuals (generally nurses) monitoring the system100. The report may be in the form of a text message, a visual alert (graphic or text) on a monitor of the system, and/or an audible alarm. FIG.4shows a system400that employs a light bracket401with a movable arm402. The arm402moves up and down within the light bracket401, thereby changing the position of the light source/sensor pairs on the movable arm402. When the movable arm402reaches the bottom of its travel path, the system400recognizes that the fluid in the infusion bag101needs replenished, and reports the situation. Again, the report may be in the form of a text message, a visual alert (graphic or text) on a monitor of the system, and/or an audible alarm. Those skilled in the art will recognize that a plethora of mechanical systems may be utilized to move the light source/sensor pairs up and down within the expanse of the infusion bag101. Any such mechanism that allows the light source/sensor pairs to traverse the height of the infusion bag101will suffice. The system400will in various embodiments include a stationary base403that also includes at least one light source203and at least two light sensors204. The base403allows convenient monitoring of the bottom of the infusion bag101, where the fluid level is critical. An additional benefit to the system depicted inFIG.4is that the movement of the arm402can be used to physically trigger an alarm for the system as a backup to the light source and sensors that serve as the main detection mechanism. A contact switch positioned at or near the bottom of the bracket401may be triggered when the arm reaches the bottom of its travel path, thereby activating whatever alarm means have been chosen by the users. The duplicative detecting mechanisms make the system far more reliable than a system with only one mechanism, nearly foolproof. FIG.5is a schematic of the overall system for detecting and reporting fluid levels in an infusion device100. The light sources203and light sensors204are in two-way communication with a control system501. It is envisioned that in most installations of the system100, the control system501will be an integral part of an MCU (multipoint control unit) of a medical facility in which the system is installed. The control system501may include integrated circuits, CPU's, laptops, or any other kind of data processing system as may be chosen by the users. In various embodiments, the light sources203and sensors204are controlled by and send data via a wireless IOT (Internet of Things) network. Once data relative to the fluid level in the infusion bag is received in the control system501, whatever reporting is desired is available through a reporting module502. The reporting module502can generate time/fluid level date for each of the bags being utilized in the system. The reports, and particularly any warnings generated, can be monitored by the appropriate personnel, e.g. nurses. The nurses can receive the reports and warnings via any smart device, such as their phone, or a laptop or desk computer. The warning are triggered by predetermined conditions, such as fluid level, motion detected within the system, malfunction of hardware, etc. The reporting module can also trigger whatever alarms are desired within the system. Audible alarms, graphics, and written messages are all options. If desired by the user, a noise management module503may be installed in the system. Available options for the noise management module include means to detect motion of the bag unit itself, such as installing an accelerometer in physical contact with the bag itself. Those skilled in the art can envision multiple other methods of detecting motion in the bag. In a medical setting, two things can happen that interfere with the readings of the fluid level in the bag. First, patients or their family may touch the infusion device. This can lead to a large angle swing or motion of the infusion bag101. The infusion bag101should not have any acceleration, as any acceleration can interfere with the readings obtained from the light sensors204. The second phenomenon is that a small vibration generated due to movement of the patient may lead to vibration of the fluid in the drip bag. Since the methodology of the system relies on determining refraction through the fluid, movement of the fluid surface caused by a small amount of vibration of the fluid surface can lead to inaccurate readings from the light sensors204. Therefore, in the case of significant movement, the system can utilize the accelerometer readings to enable the system to rule out false readings due to movement of the device. For the second case of minor movement, a small vibration may lead to vibration in the light sources203and the light sensors204. If more than one light sensor204receives a signal from a given light source203, the system knows that this signal is due to movement of the device. The signal can therefore be discarded, and if desired, recorded in the reporting module502. An alarm may also be generated. These procedures, using devices such as an accelerometer and monitoring for false signals from the light sensors204, provide a method for the system to cross check and verify the signals received from the light sensors204. The technology disclosed herein addresses improved monitoring systems for fluid infusion devices. The corresponding structures, materials, acts, and equivalents of all means or step plus function elements in the claims below are intended to include any structure, material, or act for performing the function in combination with other claimed elements as specifically claimed. The description of the present disclosure has been presented for purposes of illustration and description, but is not intended to be exhaustive or limited to the present disclosure in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the present disclosure. Exemplary embodiments were chosen and described in order to best explain the principles of the present disclosure and its practical application, and to enable others of ordinary skill in the art to understand the present disclosure for various embodiments with various modifications as are suited to the particular use contemplated. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the technology. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprise” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. It will be understood that like or analogous elements and/or components, referred to herein, may be identified throughout the drawings with like reference characters. It will be further understood that several of the figures are merely schematic representations of the present disclosure. As such, some of the components may have been distorted from their actual scale for pictorial clarity. In the foregoing description, for purposes of explanation and not limitation, specific details are set forth, such as particular embodiments, procedures, techniques, etc. in order to provide a thorough understanding of the present invention. However, it will be apparent to one skilled in the art that the present invention may be practiced in other embodiments that depart from these specific details. Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” or “according to one embodiment” (or other phrases having similar import) at various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. Furthermore, depending on the context of discussion herein, a singular term may include its plural forms and a plural term may include its singular form. Similarly, a hyphenated term (e.g., “on-demand”) may be occasionally interchangeably used with its non-hyphenated version (e.g., “on demand”), a capitalized entry (e.g., “Software”) may be interchangeably used with its non-capitalized version (e.g., “software”), a plural term may be indicated with or without an apostrophe (e.g., PE's or PEs), and an italicized term (e.g., “N+1”) may be interchangeably used with its non-italicized version (e.g., “N+1”). Such occasional interchangeable uses shall not be considered inconsistent with each other. Also, some embodiments may be described in terms of “means for” performing a task or set of tasks. It will be understood that a “means for” may be expressed herein in terms of a structure, such as a processor, a memory, an I/O device such as a camera, or combinations thereof. Alternatively, the “means for” may include an algorithm that is descriptive of a function or method step, while in yet other embodiments the “means for” is expressed in terms of a mathematical formula, prose, or as a flow chart or signal diagram. While various embodiments have been described above, it should be understood that they have been presented by way of example only, and not limitation. The descriptions are not intended to limit the scope of the invention to the particular forms set forth herein. To the contrary, the present descriptions are intended to cover such alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims and otherwise appreciated by one of ordinary skill in the art. Thus, the breadth and scope of a preferred embodiment should not be limited by any of the above-described exemplary embodiments. | 13,253 |
11857760 | DETAILED DESCRIPTION The present disclosure more fully describes various embodiments with reference to the accompanying drawings. It should be understood that some, but not all embodiments are shown and described herein. Indeed, the embodiments may take many different forms, and accordingly this disclosure should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Like numbers refer to like elements throughout. Overview Described herein is a fluid sensor configured to characterize and monitor the fluid within a fluid delivery conduit. In an example implementation, a fluid sensor as discussed herein may be utilized to monitor fluid in tubes utilized in a medical environment (e.g., blood flow tubes, fluid delivery tubes, and/or the like). The fluid sensor discussed herein may be configured to utilize non-invasive ultrasonic technology to detect the presence of air bubbles within a tube. Such configurations are capable of point and continuous sensing, able to detect small bubbles, efficient with respect to power consumption, durable, compatible with a variety of tubing materials, and less sensitive to particle accumulation. The fluid sensor of certain embodiments described herein exhibits the aforementioned advantages, while further comprising components that enable both low-cost production and a decreased sensor footprint. Critically, a minimized sensor footprint may, in certain applications (e.g., medical infusion), enable monitoring at a point of entry into a patient's body, which may result in a more accurate dosage delivery. As described herein, the fluid sensor may detect pressure changes within the tube, which may be caused by, for example, an occlusion causing a decrease or increase in fluid pressure within the tube due to a blockage within the tube (which may be detected in light of either an increase or a decrease in pressure within the tube depending on whether the blockage is upstream or downstream from the sensor). The sensor may also detect bubbles, which as described herein encompass a volume of gas having a surface defined as an interface between the gaseous fluid (within the interior of the bubble) and a liquid fluid (at least partially surrounding the exterior of the bubble). A fluid sensor in accordance with various embodiments may be configured as described in co-pending U.S. application Ser. No. 16/370,099, filed Mar. 29, 2019, which is incorporated herein by reference in its entirety. Fluid sensors as discussed herein comprise both a pressure sensor and an ultrasonic transmitter, and characterize the flow in a tube positioned between the pressure sensor and the ultrasonic transmitter by measuring the in-line fluid pressure and detecting in-line air bubbles. The fluid sensor further comprises a housing configured receive at least a portion of a fluid delivery conduit, and to house the pressure sensor and the ultrasonic transmitter. Within the housing, the pressure sensor is positioned on one side of the fluid delivery conduit and the ultrasonic transmitter is positioned across from the pressure sensor on an opposite of the tubing; the two elements are aligned so as to face one another such that the ultrasonic transmitter emits ultrasonic signals through the fluid delivery conduit and into the face of the pressure sensor. To ensure the accuracy of the pressure sensor output, the portion of the fluid delivery conduit enclosed within the housing may be compressed such that at least a portion of the face of the pressure sensor is in contact with the wall of the fluid delivery conduit. In particular embodiments, at least substantially all of the face of the pressure sensor is in contact with the wall of the fluid delivery conduit. Alternatively, the pressure sensor and the ultrasonic transmitter may be positioned adjacent to one another on the same side of the fluid delivery conduit. The two elements may be aligned so as to face into the fluid delivery conduit in substantially the same direction such that the ultrasonic transmitter may emit ultrasonic signals through the fluid delivery conduit and into a reflector element positioned to reflect the emitted signals back through the fluid delivery conduit and into the face of the pressure sensor. The pressure sensor may comprise a pressure sensing element, which may, for example, be embedded in a coupling gel or some other force transmitting member such that low frequency, pressure-related signals detected as occurring within the tube (e.g., caused by occlusion) are sensed by the pressure sensing element as the gel transmits the signal from the tube (e.g., from the surface of the tube in contact with a surface of the force transmitting member). Such a configuration allows for the ultrasonic transmitter to emit high frequency signals through the tube and through the gel before reaching the pressure sensing element, thereby enabling the sensor's bubble detection functionality. The fluid sensor of certain embodiments detects AC and DC signal components of a signal transmitted from the ultrasonic transmitting member to characterize the in-line flow: the DC component is utilized to detect changes in pressure within the tube (e.g., which may be caused by occlusion), while the AC component is utilized for the bubble detection. In various embodiments, the fluid sensor may perform a Fast Fourier Transform (FFT) to convert the pressure sensor output signal into the frequency domain. The fluid sensor of certain embodiments determines the strength of the output signal at the ultrasonic transmitter frequency and, understanding the characteristics of a signal during both a baseline fluid-in-tube condition and an air-in-tube condition, correlates a more pronounced signal at a frequency of interest (e.g., the drive frequency) to the presence of an in-line bubble. As designed, the fluid sensor effectively reduces error rate by utilizing a dual sensor configuration (i.e. the simultaneous AC and DC signal components) to be used to compensate for inaccurate variations in the sensor's reading resulting from drifts in the acoustic baseline due to unwarranted changes in contact force (e.g., tubing deformation, temperature change, fluid pressure, etc.). Housing/Sensor Construction As shown inFIGS.1-3, the fluid sensor10comprises a housing100. The housing100defines the exterior of the fluid sensor10and may have a height, length, and a width, wherein the length of the housing100is defined by the distance between a first end and a second end. As illustrated inFIG.1, the housing may further comprise a channel113extending from the first end of the housing100to the second end and configured to receive and secure at least a portion of a fluid delivery conduit. Housing100may be configured to enclose both the pressure sensor200and the ultrasonic transmitter300within the interior portion of the housing. The pressure sensor200and the ultrasonic transmitter300are each coupled to an interior portion of the housing110and are spaced apart within the interior portion of the housing110to define a gap114between the two elements. In various embodiments, the width of the gap114may be substantially equal to the width of the channel113and may run parallel to (and/or coextensive with) at least a portion of the channel113. The pressure sensor200and the ultrasonic transmitter300of the illustrated embodiment are aligned within the housing100so as to face one another; that is, the emitting face of the ultrasonic transmitter301should be facing toward the receiving face of the pressure sensor201such that high frequency waves generated by the ultrasonic transmitter300and emitted from the emitting face of the ultrasonic transmitter301travel towards the receiving face of the pressure sensor201. In such an exemplary configuration, the pressure sensor200and the ultrasonic transmitter300may be arranged to face a direction perpendicular to the length of the channel113, and may define at least a portion of the channel113. In various embodiments, the fluid delivery conduit may have a length, and a diameter, and may comprise an outer circumferential wall, an inner circumferential wall, and a wall thickness extending between the outer circumferential wall and the inner circumferential wall; and an interior channel within the inner wall configured to direct the flow of fluid from one location to a second location. The fluid delivery conduit may comprise a resilient material (e.g., a silicone material, a polyvinyl chloride material, and/or the like). The housing100may be configured to receive at least a portion of a fluid delivery conduit120through the channel. A portion of fluid delivery conduit120may extend from a first end of the housing111to a second end of the housing112. The fluid delivery conduit120may be positioned within the channel113such that it runs parallel to and intersects the gap114. In such a configuration, at least a portion of the fluid delivery conduit120is between the pressure sensor200and the ultrasonic transmitter300. In such an exemplary configuration, the pressure sensor200and the ultrasonic transmitter300may be arranged to face a direction perpendicular to the length of the fluid delivery conduit120. Further, the pressure sensor200and the ultrasonic transmitter300may be centered at the same position along the length of the fluid delivery conduit such that the gap114between the two elements is substantially perpendicular to the length of the fluid delivery conduit. As described above and as illustrated inFIGS.2-4, at least a portion of the fluid delivery conduit120may be positioned between and adjacent to the pressure sensor200and the ultrasonic transmitter300such that when the ultrasonic transmitter300emits signals (e.g., high frequency ultrasonic signals) in the direction of the pressure sensor200, the signals pass through a cross-section of the fluid delivery conduit120. The housing100may be adjustably configured such that the width of the gap114between the pressure sensor200and the ultrasonic transmitter300may be smaller than the diameter of fluid delivery conduit120, thereby causing a compression force to be applied to a portion of the outer wall of the fluid delivery conduit120secured within the gap114. The compression force may be applied in a direction perpendicular to the length of the fluid delivery conduit120such that the outer wall of the fluid delivery conduit120is pressed against the receiving face of the pressure sensor201. In such an exemplary configuration, the applied compression force may be sufficient to cause at least substantially all of the receiving face of the pressure sensor201to be engaged by the compressed outer wall of the fluid delivery conduit120. In various embodiments, the compression force may be user-defined and/or dependent on one or more characteristics of the fluid delivery conduit120such as, for example, wall thickness, material type, outer diameter, inner diameter, and any other characteristic of the fluid delivery conduit120. In various embodiments, the fluid sensor10may be further configured to monitor a compressive force applied to a portion of the fluid delivery conduit120positioned between the receiving face of the pressure sensor201and the ultrasonic transmitter300(e.g., using an ancillary pressure sensor). The measured compressive force applied to the portion of the fluid delivery conduit120may be utilized in certain embodiments to calibrate pressure sensor200readings of pressure within the fluid delivery conduit120. In other embodiments, the fluid sensor10may be separately calibrated for pressure sensor200readings of pressure within the fluid delivery conduit120. In some embodiments, the fluid sensor10may be connected to a power supply130configured to receive power and power the fluid sensor. As non-limiting examples, the power supply130may comprise one or more batteries, one or more capacitors, one or more constant power supplies (e.g., a wall-outlet), and/or the like. In some embodiments, as shown inFIG.2, the power supply130may comprise an external power supply positioned outside of the housing100and configured to deliver alternating or direct current power to the fluid sensor10. Further, in some embodiments, as illustrated inFIG.3, the power supply130may comprise an internal power supply, for example, one or more batteries, positioned within the housing100. In various embodiments, power may be supplied to controller140to enable distribution of power to the various components described herein. In some embodiments, each of the components of the fluid sensor10may be connected to controller140(e.g., for electronic communication), which may be configured to facilitate communication and functional control therebetween. In various embodiments, the controller140may comprise one or more of a processor, memory, a communication module, an on-board display150, and signal analysis circuitry. For example, the controller140may comprise a driving circuit and a signal processing circuit. In various embodiments, the controller140may be configured to power the pressure sensor200and/or receive an output signal from the pressure sensor200. In various embodiments, the controller140may be configured to power the ultrasonic transmitter300and/or transmit a drive signal to the ultrasonic transmitter300. In various embodiments, as shown inFIGS.3and4, the controller may be configured to transmit output signals out to external components via universal serial bus (USB) or any other wired connection. In various embodiments, an on-board display may be configured to display a variety of signals transmitted from or received by the controller140, and/or the like. In various embodiments, the controller may be embodied as a single chip (e.g., a single integrated-circuit chip) configured to provide power signals to both the pressure sensor200and the ultrasonic transmitter300, to receive and process the output signal from the pressure sensor200, and/or to compensate for any detected changes in environmental factors such as, for example, temperature, flow, or pressure within the fluid delivery conduit120. Such a configuration may be desirable to minimize production costs and reduce the physical footprint of the fluid sensor10. As described above and as will be appreciated based on this disclosure, various embodiments may be configured in various forms including with portions of the fluid sensor10shown inFIG.5being remote from the apparatus. In various embodiments, all of the components necessary to characterize the flow through a fluid delivery conduit120may be integrated into a single housing100. In various embodiments, the controller140may be configured to communicate with a variety of external devices via Bluetooth™ Bluetooth Low Energy (BTLE), Wi-Fi™, or any other wireless connection. As shown inFIG.5, the controller may be configured so as to enable wireless communication within an Internet-of-Things (IoT) network500to a variety of wirelessly enabled devices (e.g., a user mobile device501, a server502, a computer503, and/or the like). In various embodiments, the controller140may comprise signal analysis circuitry, which may be configured to perform frequency based analysis of a pressure sensor output signal to determine whether a bubble is present within the fluid delivery conduit120. For example, the signal analysis circuitry may receive the pressure sensor output signal and perform a Fast Fourier Transform (FFT) to observe a signal representation in the frequency domain. In various embodiments, the signal analysis circuitry may be configured to analyze the transformed data and further to detect a bubble in the fluid delivery conduit120based at least in part on, for example, one or more of the measured strength of the signal at the known ultrasonic transmitter drive frequency, a signal contrast ratio between a measured signal and a baseline fluid-in-tube condition to an in-line bubble, and a signal-to-noise ratio of the transformed data at the ultrasonic transmitter drive frequency. In various embodiments, the transformed data may indicate a distinguishably higher signal strength at the ultrasonic transmitter drive frequency during an air-in-tube condition compared to the signal strength at the ultrasonic transmitter drive frequency during a fluid-in-tube condition. In various embodiments, the measured signal strength value may vary based on, for example, one or more of fluid delivery conduit120size, fluid delivery conduit120material, ultrasonic signal strength, signal amplifier gain, and any other applicable parameter specific to the implemented embodiment. In various embodiments, an air-in-tube condition may be detected by comparing the signal-to-noise ratio of the transformed data in an air-in-tube condition to that of the transformed data in a fluid-in-tube condition at the ultrasonic transmitter drive frequency. For example, a high signal contrast ratio may be indicative of the presence of a bubble within the tube. In various embodiments, a signal contrast ratio of between 2 and 5 (e.g., 3) may be measured when comparing the aforementioned respective transformed data. As described herein, when the fluid sensor10detects a signal contrast ratio as described above at the ultrasonic transmitter drive frequency with a value of at least 1 kHz, the controller140may be configured to determine that a bubble is present in the fluid delivery conduit120. In various embodiments, the signal analysis circuitry may further comprise a bandpass filter configured to isolate one or more signals of interest within a particular band of frequencies. In various embodiments, the bandpass filter range may be centered at the drive frequency of the ultrasonic transmitter and may be configured to allow a range of frequencies between, for example, within 500 Hz above and/or below the drive frequency to be received (e.g., a 1 kHz band). In various embodiments, the bandpass filter may be used to selectively distinguish the signal at the ultrasonic transmitter drive frequency from the noise present within the signal. In certain embodiments, the bandpass filter may sufficiently isolate the drive frequency of the ultrasonic transmitter that characteristics of the output signal (e.g., in the time-domain) may be utilized to detect the presence of a bubble within the fluid delivery conduit. For example, signal amplitude, detected presence (or absence) of a signal at the drive frequency, and/or the like may be utilized to determine whether a bubble is present within the fluid delivery conduit. It should be understood that the bandpass filter may be embodied as hardware and/or software. In various embodiments, the signal analysis circuitry may further comprise a signal amplifier configured to increase the strength of the pressure sensor output signal. In various embodiments, the signal amplifier may be used to strengthen the pressure sensor output signal so as to ensure that the signal at the ultrasonic transmitter drive frequency may be detected by the signal analysis circuitry. The use of the term “circuitry” as used herein with respect to components of the fluid sensor10therefore includes particular hardware configured to perform the functions associated with respective circuitry described herein. Of course, while the term “circuitry” should be understood broadly to include hardware, in some embodiments, circuitry may also include software for configuring the hardware. For example, in some embodiments, “circuitry” may include processing circuitry, storage media, network interfaces, input-output devices, and other components. In some embodiments, other elements of the controller140may provide or supplement the functionality of particular circuitry. For example, the processor may provide processing functionality, memory may provide storage functionality, and communication module may provide network interface functionality, among other features. Pressure Sensor As shown inFIGS.1-4, the fluid sensor10may comprise a pressure sensor200. The pressure sensor may be embodied as a pressure sensor such as that described in U.S. Patent Publ. No. 2018/0306659, which is incorporated herein by reference in its entirety. In various embodiments, the pressure sensor200may comprise a printed circuit board210, a pressure sensing element220, a sidewall240, and a force transmitting member250. As described above, the pressure sensor may be positioned within the housing100and coupled to an interior portion of the housing100. The pressure sensor200may further comprise a receiving face201, which may be, for example, either a flat, convex, or concave surface. The pressure sensor may be arranged such that the receiving face201is aligned with and facing the emitting face of the ultrasonic transmitter301. The receiving face of the pressure sensor201may be spaced apart from the emitting face of the ultrasonic transmitter301at a distance defining the gap114. The substrate210of the pressure sensor200may be any type of printed control board (PCB), a ceramic substrate, or other suitable substrate configuration. In some embodiments, the substrate210may be a thick film printed ceramic board, however other circuit board configurations may be utilized in other embodiments. In one example, the substrate210may be made, at least in part, of FR 4 laminate and/or other material. In various embodiments, the substrate210may have one or more electronic components thereon and/or pads for connecting to electronic components of a device in which the pressure sensor200may be inserted or with which the pressure sensor200may be used. In one example, the substrate210may include an application specific integrated circuit (ASIC) that may be attached to the substrate210. Such an ASIC may be electrically connected to the substrate210via wire bonds, bump bonds, electrical terminals, and/or any other suitable electrical connections. Additionally or alternatively, the substrate210may include one or more conductive pads for engaging circuitry and/or electronic components in communication with a remote processor or the like. Further, the substrate210may include one or more processing electronics and/or compensation circuitry (e.g., which may or may not include an ASIC). Such processing electronics may be electrically connected to terminals of the pressure sensing element220, an ASIC (if present), and/or electrical terminals to process electrical signals from the pressure sensing element220and/or to transfer outputs from the pressure sensing element220to electronic components of one or more devices used in conjunction with the pressure sensor200. In some instances, the substrate210may include circuitry that may be configured to format one or more output signals provided by the pressure sensing element220into a particular output format. For example, circuitry of the substrate210(e.g., circuitry on one or more of sides of the substrate210) may be configured to format the output signal provided by pressure sensing element220into a ratio-metric output format, a current format, a digital output format and/or any other suitable format. In some cases, the circuitry of the substrate210may be configured to regulate an output voltage. Circuitry on the substrate210for providing a ratio-metric (or other) output may include traces and/or other circuitry that may serve as a conduit to test pads, and/or for providing the ratio-metric (or other) output to one or more electrical terminals facilitating electrical connections with electronic components of one or more devices used with the pressure sensor200. The pressure sensing element220of the pressure sensor200may be configured in any manner and may have a first side221(e.g., a front side) and a second side222(e.g., a back side). In some cases, the pressure sensing element220may include a micro-machined pressure sense die that includes a sense diaphragm. In various embodiments, the pressure sensing element220may be back-side mounted on the substrate210with the second side of the pressure sensing element222facing the substrate210and may be configured to perform top-side sensing (e.g. sensing with the first side of the pressure sensing element221). In a pressure sensing element220configuration, the top-side sensing may be when a sensed media either directly or indirectly (e.g., through the force transmitting member250or other intermediary) interacts with a top side of the pressure sensing element221. Back-side mounting the pressure sensing element220to the substrate210may facilitate creating a robust pressure sensor200because any sensed media acting on the pressure sensing element220may act to push the pressure sensing element220against the substrate210. Although the pressure sensing element220may be described herein as being back-side mounted to the substrate210, it is contemplated that the pressure sensing element220may be mounted relative to the substrate210in one or more other configurations. For example, the pressure sensing element220may be front side mounted or mounted in any other suitable manner. Further, the pressure sensing element220may be electrically connected to the substrate210in one or more manners. In various embodiments, wire bonds230may be utilized to electrically connect the pressure sensing element220to the substrate210. The wire bonds230may have a first end connected to a bond pad of the pressure sensing element220and another end connected to a bond pad of the substrate210. Additionally or alternatively, the pressure sensing element220may be electrically connected to the substrate210via bump bonds and/or in any other suitable manner. The sidewall240of the pressure sensor200may extend from a first end241to a second end242. In various embodiments, the sidewall240may entirely or at least partially circumferentially surround and/or enclose the pressure sensing element220, wire bonds230, bond pads, the force transmitting member250, and/or other components of the pressure sensor200. The sidewall240may have a cross-section substantially circular or any other suitable shape. The sidewall240may be connected to the substrate210such that the second end of the sidewall242may face the substrate210and the first end of sidewall240may be spaced away from the substrate210. In some cases, the sidewall240may be attached to at least a portion of the substrate210to provide additional structural integrity to the pressure sensor200. The first end of the sidewall241may be positioned substantially adjacent the receiving face of the pressure sensor201and may at least partially define an opening from the first end of the sidewall241to the pressure sensing element220(e.g., a reservoir defined by the sidewall240). The sidewall240may be made from any type of material. In one example, the sidewall240may be made from a plastic, a metal, a ceramic and/or any other suitable material. In various embodiments, the force transmitting member250of the pressure sensor200may comprise a first end and a second end, wherein the first end may be configured to entirely engage a portion of the outer wall of the fluid delivery conduit120positioned within the gap114and the second end may be configured to interact with the pressure sensing element220. The force transmitting member250may fill or at least partially fill the opening and/or reservoir of the sidewall240. In various embodiments, the force transmitting member250may be configured to facilitate transferring a force interacting with the first end of the force transmitting member250to the pressure sensing element220. In such an exemplary configuration, the force experienced by the pressure sensing element220may arise due to a change in pressure within the fluid delivery conduit120caused by a pressure change event (e.g., occlusion) and may result in a shift in the DC signal produced by the pressure sensor200. The force transmitting member250may be formed from one or more layers of material. For example, the force transmitting member250may be formed from one layer of material, two layers of material, three layers of material, four layers of material, five layers of material, or other number of layers of material. The force transmitting member250may be made from any suitable material. In various embodiments, the force transmitting member250may comprise a dielectric material, a non-compressible material, a biocompatible material, colored material, non-colored material, and/or one or more other types of material. Further, in various embodiments the force transmitting member250may comprise a gel (e.g., a fluoro-silicone gel), a resilient material such as a cured silicone rubber or silicone elastomer, a cured liquid silicone rubber, an oil and/or any other suitable material. In various embodiments, the force transmitting member250may include a biocompatible material such as, for example, a cured silicone elastomer, that is medically safe to directly contact medicines or the like that are to be provided to a patient. In various embodiments wherein the force transmitting member250comprises a gel, the pressure sensor may further comprise a membrane configured to cover the entirety of the opening at the first end of the sidewall240so as to contain the gel within the cavity. In various embodiments, the pressure sensor200may be electronically connected to the controller140such that the controller140transmits a power signal to the pressure sensor200. In various embodiments, the pressure sensor200may be powered at a voltage of between 1.5 volts and 15 volts (e.g., 5 volts). The pressure sensor200may be configured to, upon sensing both a pressure sensor signal created by a pressure differential within the fluid delivery conduit120and a high frequency ultrasonic waves from the ultrasonic transmitter300, transmit an output signal comprising both an AC component and a DC component to the controller140. Ultrasonic Transmitter As shown inFIGS.1-4, the fluid sensor10may comprise an ultrasonic transmitter300, which, in various embodiments, may be coupled to the interior portion of the housing110. The ultrasonic transmitter300may define an emitting face301and may be arranged such that the emitting face301is aligned with and facing the receiving face of the pressure sensor201. The emitting face of the ultrasonic transmitter301may be spaced apart from the receiving face of the pressure sensor201at a distance defining the gap114. As illustrated inFIGS.3and4, the ultrasonic transmitter300may be configured to generate and emit an ultrasonic signal in a direction substantially perpendicular to the emitting face301, through the fluid delivery conduit120, and towards the receiving face of the pressure sensor201such that the signal may be detected by the pressure sensing element220. As is generally understood in the art, the ultrasonic transmitter300may, in various embodiments, comprise an ultrasonic generator and an ultrasonic transducer. In various embodiments, the ultrasonic transducer may be, for example, a piezoelectric ultrasonic transducer. A piezoelectric ultrasonic transducer may comprise, for example, a ceramic disc (e.g., PIC255) and wrap-around electrodes configured to establish an electrical connection at a favorable position within the transducer assembly. In various embodiments, the ultrasonic transducer may have a diameter of between 2 mm and 15 mm (e.g., between 5 mm and 10 mm) and may have a thickness of between 0.5 mm and 4 mm (e.g., between 1 mm and 2 mm). In various embodiments, the ultrasonic transmitter300may be tuned for optimal interaction with and response by the pressure sensing element220. In various embodiments, the ultrasonic transmitter300may be electronically connected to the controller140such that the ultrasonic transmitter300may be powered by the controller140. The controller140may be configured to further supply the ultrasonic transmitter300with a fixed frequency drive signal generally in the form of an oscillating signal, such as a sine-wave, square wave, triangular wave, sawtooth wave, and/or the like. However, it should be understood that other signal shapes may be provided as discussed herein. In various embodiments, the drive signal sent from the controller140to the ultrasonic transmitter300may manifest as a voltage centered between 1.5 volts and 100 volts (e.g., 5 volts). The ultrasonic transmitter300may be configured to receive the signal from the controller140and emit high frequency ultrasonic waves through the emitting face301and across a portion of the fluid delivery conduit120such that it may be received by the pressure sensor200. Pressure Sensing As described herein, the fluid sensor10may be configured to detect occlusion (or other fluid pressure-changing events) within a fluid delivery conduit120by detecting a change in pressure within the fluid delivery conduit120. As shown inFIGS.2-4, the pressure sensor200of the fluid sensor10may be located within the interior of the housing110and arranged such that the receiving face of the pressure sensor201is at least substantially parallel and adjacent to a length of the channel113configured to receive and secure at least a portion of the fluid delivery conduit120. Similarly, the emitting face of the ultrasonic transmitter301may be positioned at least substantially parallel to both the receiving face of the pressure sensor201and the length of the channel113configured to receive and secure at least a portion of the fluid delivery conduit120. In such an exemplary configuration, the pressure sensor200(e.g., the receiving face of the pressure sensor200) engages a portion of the outer wall of the fluid delivery conduit120located within the interior portion of the housing110such that pressure within the fluid delivery conduit120may exert a force onto the receiving face of the pressure sensor201. The force exerted on the pressure sensor200may be detected by the force transmitting member250, which may be configured to transmit at least a portion (e.g., all) of the force to the pressure sensing element220. In various embodiments, the force transmitting member250may comprise, for example, a gel. As described above, the pressure sensing element220may be configured to receive high frequency signals (e.g., oscillating signals) emitted by the ultrasonic transmitter300. The signal emitted by the ultrasonic transmitter300is received by the pressure sensing element220after traveling through the fluid delivery conduit120. In various embodiments, an occlusion within the fluid delivery conduit may result in a change of pressure within the fluid delivery conduit120, and thus, a change in force being exerted on the inner wall of the fluid delivery conduit120and, in turn, a change in force being transmitted from the fluid delivery conduit120to the pressure sensor200. The change in force arising from a change in pressure within the fluid delivery conduit120may define a low frequency event received by and transmitted through the force transmitting member250such that it may be sensed by the pressure sensing element220. In various embodiments, a low frequency event experienced by the pressure sensing element220may be detected as a shift in signal detected by the pressure sensing element220(e.g., correlating to a DC shift). Such a change in the signal to the pressure sensing element220may manifest in a proportional DC shift experienced by the pressure sensor's output signal to the controller140. For example, when the fluid within the fluid delivery conduit120experiences occlusion, the resultant change in pressure leads to a change signal voltage output by the pressure sensing element, and thus, a vertical shift of the output signal. Accordingly, in various embodiments, the fluid sensor10may be configured to detect occlusion within a fluid delivery conduit120by receiving the emitted high frequency signal components from the ultrasonic transmitter300and correlating a detected variance in voltage (i.e. DC shifts) in the pressure sensor's resultant output signal to a blockage within the fluid delivery conduit120. In various embodiments, to ensure accuracy of the signal detected by the pressure sensing element220, both the receiving face of the pressure sensor201and the emitting face of the ultrasonic transmitter301may be positioned at least substantially parallel to and in contact with a portion of the outer wall of the fluid delivery conduit120secured within the channel113. As described above and as shown inFIGS.3and4, the fluid delivery conduit120may be compressed in the direction of the conduit's width such that at least substantially all of receiving face of the pressure sensor201is in contact with a portion of the outer wall of the fluid delivery conduit120. Such a configuration enables the entirety of the face of the force transmitting member250to be coupled to the surface of the fluid flowing through the fluid delivery conduit120for the purposes of sensing force, and prevents any undesirable force “leakage” that is transmitted away from the pressure sensing element220. In various embodiments, failure to essentially couple the pressure sensing element220to the fluid being sensed through the force transmitting member250, may result in the force transmitting member250receiving a distorted signal. Such a distortion may result in the fluid sensor10producing inaccurate readings. Bubble Detection As described herein, the fluid sensor10may be configured to detect the presence of an air bubble302within a fluid delivery conduit120by detecting a change in the signal (e.g., the oscillating signal component) emitted from the ultrasonic transmitter and received by the pressure sensor200. For example, the fluid sensor may be configured to detect the presence of an air bubble302within a fluid delivery conduit120by detecting a change in signal strength at a defined frequency received by the pressure sensor200. As described above and as shown inFIGS.3and4, the pressure sensor200of the fluid sensor10may be located within the interior of the housing110and arranged such that the receiving face of the pressure sensor201is at least substantially parallel to a length of the channel113configured to receive and secure at least a portion of the fluid delivery conduit120. Similarly, the emitting face of the ultrasonic transmitter301may be positioned at least substantially parallel to both the receiving face of the pressure sensor201and the length of the channel113such that the emitting face of the ultrasonic transmitter301and the receiving face of the pressure sensor201are spaced apart to define a gap114configured to accept the fluid delivery conduit120therein. In such an exemplary configuration, the ultrasonic transmitter300may be configured to receive a drive signal (e.g., an oscillating drive signal, such as an AC drive signal) from the controller140and to emit ultrasonic waves carrying the signal through the emitting face of the ultrasonic transmitter301, through the portion of the fluid delivery conduit120positioned within the gap114, and to the receiving face of the pressure sensor201. In various embodiments, wherein the force transmitting member250may be, for example, a gel, the gel may act as an incompressible fluid. The emitted signal may be sensed by the pressure sensing element220, which may be configured to subsequently transmit an output signal to the controller140indicative of the detected signal. As described above, the emitted signal may be embodied as an AC signal or another oscillating signal shape, centered on a voltage characterized by a DC shift in the drive signal. In an exemplary condition wherein there are no air bubbles present within the fluid delivery conduit120, as illustrated inFIG.3, substantially all of the waves emitted from the ultrasonic transmitter300are sensed by the pressure sensor200, resulting in a signal transmitted to the controller140that is indicative of an uninterrupted signal transmitted through the fluid delivery conduit120. Conversely, in an exemplary condition wherein at least one air bubble302is present within the fluid delivery conduit120, as illustrated inFIG.4, the air bubble302may interrupt the direct transmission of the emitted signal from the ultrasonic transmitter300to the pressure sensor200and may reflect and/or deflect at least a portion of the emitted signal, deflecting the portion of the signal away from the pressure sensing element220. In such an exemplary circumstance, the reflection of at least a portion of the emitted signal may result in a distorted signal received by the pressure sensing element220when represented in the time domain. When the air bubble302is present in the fluid delivery conduit120, the received signal, when presented in a frequency domain, may exhibit, for example, a pronounced signal at the drive frequency of the ultrasonic transmitter300. Accordingly, in various embodiments, the fluid sensor10may be configured to detect the presence of an air bubble302within a fluid delivery conduit120by monitoring the emitted high frequency signal from the ultrasonic transmitter300and correlating a more pronounced signal at the ultrasonic transmitter300drive frequency to the presence of a bubble302within the fluid delivery conduit120. Further, in various embodiments, the fluid sensor10may be further configured to determine specific characteristics about the detected bubble302such as, for example, its size, based on one or more of the distortions in the signal received by the pressure sensing element Signal Analysis As illustrated inFIGS.7and8, in various embodiments a Fast Fourier Transform (FFT) may convert the pressure sensor200output signal to transformed data represented in the frequency domain. In various embodiments, the FFT may be performed by either the controller140or an external computer in communication with the sensor10and configured to perform the FFT. In various embodiments, the transformed data may be indicative of the strength of the pressure sensor output signal across a frequency range. The transformed data in an air-in-tube condition490may be discernably different from the transformed data in an air-in-tube condition470at one or more frequencies, such as, for example, the ultrasonic transmitter300drive frequency. The transformed data in an air-in-tube condition, distinct from that in a fluid-in-tube condition, may comprise a distinguished signal at the frequency along the x-axis correlating to the ultrasonic transmitter300drive frequency. In various embodiments, an air-in-tube condition may be detected by comparing the signal-to-noise ratio of the transformed data in an air-in-tube condition to that of the transformed data in a fluid-in-tube condition at the ultrasonic transmitter drive frequency. In various embodiments, a signal contrast ratio of between 2 and 5 (e.g., 3) may be measured when comparing the aforementioned respective transformed data. As described herein, when the fluid sensor10detects a signal contrast ratio as described above at the ultrasonic transmitter drive frequency with a value of at least 1 kHz, the controller140may be configured to determine that a bubble is present in the fluid delivery conduit120. Further, in various embodiments, when the fluid sensor10detects a signal-to-noise ratio at the ultrasonic transmitter drive frequency of at least between 2 and 5 (e.g., 3), the controller140may be configured to determine that a bubble is present in the fluid delivery conduit120. In an alternative embodiment, a bandpass filter configured to facilitate bubble detection by isolating one or more signals of interest within a particular band of frequencies. The bandpass filter may be implemented to selectively distinguish the signal at the ultrasonic transmitter drive frequency from the noise present within the signal, thereby producing transformed data to be analyzed without performing a FFT. In various embodiments, the bandpass filter range may be centered at the drive frequency of the ultrasonic transmitter and may be configured to allow a range of frequencies between, for example, within 500 Hz above and/or below the drive frequency to be received (i.e. a 1 kHz band). In various embodiments, when the fluid sensor10detects a signal at the ultrasonic transmitter drive frequency, the controller140may be configured to determine that a bubble is present in the fluid delivery conduit120. Experimental Testing Experimental testing was conducted to verify the effectiveness of embodiments as described herein. Data was collected over the course of multiple trials using various combinations of embodiments described above. In the testing configuration, an exemplary fluid sensor used for testing was configured to be in electronic communication with both the pressure sensor controller and the ultrasonic transmitter controller. The pressure sensor controller was configured to transmit a power signal to the pressure sensor. Similarly, the ultrasonic transmitter controller was configured to transmit a power signal to the ultrasonic transmitter. The testing circuitry comprised a drive circuit configured to transmit a signal to the ultrasonic transmitter. The testing circuitry was further electronically connected to an oscilloscope configured to generate the drive signal and graphically display the output signal sensed by the pressure sensor. Example output signals460,480are shown inFIGS.7and8. FIG.6shows a close-up view of the fluid sensor10sensory components used in the exemplary testing configuration. The pressure sensor200is secured to the bottom surface of a vise, a configuration meant to recreate the mounting of the pressure sensor200within the interior portion of the housing110. Similarly, the ultrasonic transmitter300is secured relative to the top surface of the vise. In such a configuration, the pressure sensor200and the ultrasonic transmitter300are spaced apart so as to define a gap114configured to receive a portion of the fluid delivery conduit120. As shown inFIG.6, the testing configuration comprised the pressure sensor200and the ultrasonic transmitter300mounted to a vise so as to replicate the requisite compression applied to the fluid delivery conduit120when secured within the housing100of the fluid sensor10. As described above, the fluid delivery conduit120was compressed by the vise such that the entirety of the receiving face of the pressure sensor201was covered by at least a portion of the outer wall of the fluid delivery conduit120. The exemplary testing configuration utilized a fluid303flowing through the tube with deliberately injected air bubbles302present within the fluid delivery conduit120to enable analysis of the signal sensed by the pressure sensor200under conditions both with and without air bubbles302present within the fluid delivery conduit120. FIG.7shows a graphical representation of an example pressure sensor output signal460represented in the time domain and example transformed data470, both under baseline fluid conditions. As described above, the characteristics of the corresponding ultrasonic transmitter drive signal may be selected to produce a drive signal shape for use in conjunction with the specific testing circuitry. Here, the shape of the example ultrasonic transmitter drive signal is similar to that of a general sinusoidal AC signal. As illustrated inFIGS.7and8, the ultrasonic transmitter drive signal has a frequency selected to be above the normal hearing range of humans. For example, the drive frequency may be 20 kHz, although it should be understood that other frequencies may be utilized. The shape of the example pressure sensor output signal460,480—shown inFIGS.1and8—may vary from that shown therein, and generally correlates to a baseline fluid pressure within a fluid delivery conduit void of air bubbles. The example pressure sensor output signal460is centered around an axis which may represent a signal shift of, for example, 300 mV. Upon detection of a change in pressure, the pressure sensor output signal460may shift vertically to represent the change in pressure. A DC shift of the pressure sensor output signal460may correspond to a change in pressure within the fluid delivery conduit120due to, for example, occlusion. FIG.7further illustrates the resultant transformed data470after a FFT has been performed on the pressure sensor output signal460. Like the pressure sensor output signal460, the transformed data470is representative of a fluid-in-tube condition. As shown, an 98 μV signal, highlighted by exemplary axis A for reference, was measured at the 20 kHz ultrasonic transmitter drive frequency. FIG.8shows an exemplary distorted pressure sensor output signal wave sensed by the pressure sensor480and example transformed data, both distorted by the presence of a gas bubble within a fluid delivery conduit120. As described above, in a condition in which gas bubbles302are present within the fluid delivery conduit120, the output signal480may exhibit characteristics different from those of the output signal under normal baseline fluid conditions460. However, depending on, for example, the input signal characteristics, such differences may be hard to detect in various embodiments. Accordingly, as illustrated by the resultant air-in-tube transformed data490inFIG.8, a FFT was performed on the pressure sensor output signal480to represent the signal in the frequency domain. As shown inFIG.8, a 308 μN signal, highlighted by exemplary axis B for reference, was measured at the 20 kHz ultrasonic transmitter drive frequency. Notably, the signal measured at the 20 kHz ultrasonic transmitter drive frequency during an air-in-tube condition was significantly greater than the corresponding signal measured at the same frequency during a fluid-in-tube condition. In the exemplary test configuration described herein, the signal contrast ratio between the signal air-in-tube transformed data490(308 μV) and the signal fluid-in-tube transformed data470(98 μV) at 20 kHz was approximately 3:1. In various embodiments, such transformed data comprising such an exemplary strong signal strength at the ultrasonic transmitter drive frequency may indicate the presence of bubble within the fluid delivery conduit120. In various exemplary testing embodiments, a signal contrast ratio of, for example, approximately between 2 and 5 may be indicative of the presence of a bubble within the fluid delivery conduit120. As described herein, the fluid sensor10is configured so as to enable the simultaneous monitoring of both the AC and DC components of the pressure sensor output signal. Critically, such a configuration may effectively reduce the error rate of the sensor by compensating for unwarranted external forces that may affect the sensor's acoustic baseline and lead in inaccuracies. Such a shift of the sensor's acoustic baseline may be caused by factors such as, for example, tubing/plastic deformation, temperature change, and/or fluid pressure that result in an unwarranted change of contact force to the sensor. Configuring the components of the fluid sensor in such a way that enables the coupling of the AC and DC components enables the efficient and accurate characterization of flow within a fluid delivery conduit. CONCLUSION Many modifications and other embodiments will come to mind to one skilled in the art to which this disclosure pertains having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. Therefore, it is to be understood that the disclosure is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. | 51,974 |
11857761 | DETAILED DESCRIPTION The disclosed check valve incorporates a wiping extension. The wiping extension can unclog or dislodge particulate from the valve member to allow particulate to be removed from the check valve. By removing particulate from the check valve, the wiping extension can ensure fluid flow, reliable operation of the check valve and reduce contamination of medical fluid that passes through the check valve, avoiding the need to replace an IV set. The detailed description set forth below is intended as a description of various configurations of the subject technology and is not intended to represent the only configurations in which the subject technology may be practiced. The detailed description includes specific details for the purpose of providing a thorough understanding of the subject technology. However, it will be apparent to those skilled in the art that the subject technology may be practiced without these specific details. In some instances, well-known structures and components are shown in block diagram form in order to avoid obscuring the concepts of the subject technology. Like components are labeled with identical element numbers for ease of understanding. Reference numbers may have letter suffixes appended to indicate separate instances of a common element while being referred to generically by the same number without a suffix letter. While the following description is directed to the administration of medical fluid using the disclosed check valve, it is to be understood that this description is only an example of usage and does not limit the scope of the claims. Various aspects of the disclosed check valve may be used in any application where it is desirable to control flow of medical fluid and eliminate particulate within fluid devices. The disclosed check valve overcomes several challenges discovered with respect to certain conventional check valves. One challenge with certain conventional check valves is that particulates or other contaminants can accumulate within the check valve. In certain applications, the accumulation of particulates can prevent the reliable operation of the check valve. Because the accumulation of particulates may result in back flow through the check valve and prevent proper dosage through an IV set, the use of certain conventional check valves is undesirable. Therefore, in accordance with the present disclosure, it is advantageous to provide check valves as described herein that allow for particulates or other contaminants to be dislodged and/or removed from the check valve, increasing reliability, preventing back flow, and providing proper dosage to the patient. Further, the use of the check valves described herein can reduce the need to replace IV sets, minimizing clinical steps and reducing waste. Examples of check valves that can dislodge or remove particulates from within the check valve are now described. FIG.1illustrates a patient5receiving an infusion of a medical fluid through an optional IV pump30according to certain aspects of the present disclosure. In applications that utilize an IV pump, the IV pump30comprises a controller32and two pump modules34. An IV set20is connected between a container36of the medical fluid and the patient5. During operation, a check valve can control the flow of medical fluid to a patient5to prevent the back flow of medical fluid. For example, a check valve can allow the delivery of a first medical fluid (e.g., saline) and a second medical fluid (e.g., a drug) to a patient while preventing the back flow of either medical fluid during the administration of the first medical fluid and the second medical fluid. In some embodiments, the check valve can be disposed in between or in line with tubing of the IV set20. FIG.2illustrates a check valve assembly100according to certain aspects of the present disclosure. In the depicted example, the check valve assembly100controls the flow of medical fluid through the inlet tubing50and the outlet tubing60. During operation, a check valve110can allow fluid flow from the inlet tubing50to the outlet tubing60. Further, the check valve110can prevent or reduce back flow from the outlet tubing60to the inlet tubing50. In some embodiments, the outlet tubing60can direct flow toward the patient76via the patient flow path74of the outlet flow path70. As described herein, the check valve110can allow for particulates or other contaminants to be dislodged and/or removed from within the check valve110. In some embodiments, dislodged or removed particulates can be directed to a reservoir90in fluid communication with the check valve110. The reservoir90can be in fluid communication with the check valve110via the reservoir flow path72of the outlet flow path70. During the dislodging or removal of the particulates within the check valve110, the patient flow path74can be obstructed by a clamp82to prevent particulates from flowing toward the patient76. During normal operation of the check valve110(e.g., when particulate is not being removed), the reservoir flow path72can be obstructed by a clamp80to prevent the flow of medical fluid into the reservoir90and direct medical fluid toward the patient76. FIG.3illustrates a perspective view of the check valve110ofFIG.2.FIG.4illustrates a cross-sectional view of the check valve110ofFIG.2. With reference toFIGS.2-4, as described herein, the check valve110controls the flow of medical fluid between an inlet114and an outlet124. As illustrated, the check valve110receives fluid flow from inlet tubing50coupled to the inlet portion112. In the depicted example, the inlet portion112defines an inlet114that is in fluid communication with the inlet tubing50to receive fluid flow from a fluid source, such as a medical fluid container. In the depicted example, the inlet114defines an inlet lumen116to permit fluid communication with the inlet tubing50. In some embodiments, the inlet portion112can be formed from a polymer (rigid or soft), including, but not limited to, methylmethacrylate acrylonitrile butadiene styrene (MABS), styrene acrylonitrile (SAN), or polycarbonate. Flow received by the inlet114can be directed toward a valve body130to control the flow through the check valve110. As illustrated, the inlet portion112can be disposed adjacent to, or above the valve body130. During operation, fluid flow from the inlet portion112is received by the valve body130. The valve body130defines a valve cavity134to receive fluid flow from the inlet portion112and control the direction of the fluid flow through the check valve110. In the depicted example, the valve cavity134is in fluid communication with the inlet114of the inlet portion112. In some embodiments, the valve body130can be formed from a polymer, including, but not limited to, MABS, SAN, or polycarbonate. During operation, fluid from the valve cavity134is directed to the outlet tubing60coupled to the outlet portion122. The outlet portion122defines an outlet124that is in fluid communication with the outlet tubing60to allow fluid to pass downstream to a patient or another portion of the IV set. In the depicted example, the outlet124defines an outlet lumen126to permit fluid communication with the outlet tubing60. As can be appreciated, the outlet lumen126is in fluid communication with the valve cavity134to allow fluid to pass from the inlet portion112, through the valve body130, and through the outlet portion122. In some embodiments, the outlet portion122can be formed from a polymer, including, but not limited to, MABS, SAN, or polycarbonate. As illustrated, the outlet portion122can be disposed adjacent to, or below the valve body130. In the depicted example, the check valve110includes a valve member140to control the direction of flow through the valve cavity134. As illustrated, the valve member140is disposed within the valve cavity134to allow flow from the inlet portion112toward the outlet portion122and prevent or reduce flow from the outlet portion122toward the inlet portion112. In the depicted example, the valve member140is movable relative to the valve cavity134to allow flow from the inlet portion112toward the outlet portion122and/or to prevent or reduce flow from the outlet portion122toward the inlet portion112. For example, portions (e.g., edges) of the valve member140can move away from the walls of the valve cavity134to allow flow from the inlet portion112toward the outlet portion122. In the presence of back flow, portions of the valve member can move toward and/or engage and seal with the walls of the valve cavity to prevent or reduce flow from the outlet portion122toward the inlet portion112. Optionally, the valve member140can be deformable to move relative to the valve cavity134. For example, the valve member140can be configured to deform in response to the direction of flow. Therefore, the valve member140may deform to permit flow from the inlet portion112toward the outlet portion122and may deform to prevent or reduce flow from the outlet portion122toward the inlet portion112. In some embodiments, the valve member140can be formed from a deformable material such as silicone, or any other suitable material, including, phthalate- and latex-free materials. The valve member140may have any size and shape that may permit the valve member140to flex or bend under fluid pressure and permit forward flow of the fluid (from the inlet portion112to the outlet portion122) through the check valve110, and occlude reverse flow of the fluid (from the outlet portion122to the inlet portion112) through the check valve110. The valve member140may be a disk, plate, a diaphragm or similar, and may be square, rectangular, circular, elliptical, oblong, and the like. The shape and size of the valve member140is not limited to any particular shape or size. In some embodiments, the valve member140can be supported on a pedestal formed by one or more posts128. The posts128can be spaced apart to define a portion of the passageway within the valve cavity134. In some embodiments, the posts128can extend from the outlet portion122and into the valve cavity134. FIGS.5and6illustrate a cross-sectional view of the check valve110ofFIG.2during fluid flow operation. With reference toFIGS.2-6, during operation, fluid flow F may enter the check valve110via inlet tubing50coupled to the inlet114. The fluid flow F may flow through the inlet lumen116and into the valve cavity134. The valve member140permits the fluid flow F to pass through the valve cavity134. The fluid flow F can exit the check valve110through the outlet124. The outlet lumen126can direct the fluid flow F from valve cavity134to the outlet tubing60. As can be appreciated, the fluid flow F can be directed toward the patient. FIGS.7and8illustrate a cross-sectional view of the check valve110ofFIG.2during back flow operation. With reference toFIGS.2-4,7, and8, during operation, backflow B from the outlet tubing60is prevented from entering the inlet tubing50. In the event that backflow B enters the check valve110via the outlet tubing60coupled to the outlet124, the backflow B can flow into the lower portion of the valve cavity134. However, the valve member140prevents the backflow B from entering the upper portion of the valve cavity134, and in turn, the inlet portion112of the check valve110. As described herein, the valve member140can seal against the walls of the valve cavity134to prevent the backflow B from passing through the valve cavity134. FIG.9illustrates a perspective view of the check valve110ofFIG.2.FIG.10illustrates a cross-sectional detail view of the check valve110ofFIG.2. As described herein, during operation, contaminants, sediment, grit, or other particulate P can accumulate on the valve member140of the check valve110, causing undesirable operation of the check valve110. Advantageously, the check valve110allows for the particulate P to be cleared, dislodged, or otherwise removed from the valve member140and/or the check valve110generally to allow for proper operation of the check valve110and locking of the fluid line. In the depicted example, particulate P accumulated on the valve member140can be dislodged by a wiping extension150configured to extend toward the valve member140and dislodge particulate P disposed on a surface of the valve member140. In some embodiments, the wiping extension150can extend to contact the surface of the valve member140and skim or scrape the valve member140without damaging the surface of the valve member140. In some embodiments, the wiping extension150can be spaced apart from the surface of the valve member140to prevent contact with the valve member140but permit particulate P to be dislodged from the valve member140. As illustrated, the wiping extension150can extend from an upper portion of the valve cavity134and toward an upper surface of the valve member140. Optionally, the wiping extension150can extend downward from the valve body130of the check valve110and into the valve cavity134. During a clearing or dislodging operation, the wiping extension150can be moved relative to the valve member140to scrape, skim, wipe, or dislodge any accumulated particulate P from the valve member140. For example, the wiping extension150can be rotated relative to the valve member140to allow the wiping extension150to dislodge any particulate P from the valve member140. In the depicted example, the valve body130can be rotated to move or rotate the wiping extension150relative to the valve member140. In some embodiments, the valve body130can be rotated relative to the inlet portion112and/or the outlet portion122to allow the wiping extension150to rotate relative to the valve member140. Optionally, the inlet portion112and/or the outlet portion122can remain stationary relative the rotating valve body130. As illustrated inFIGS.4-8and10, the valve body130can include valve body lips131to engage with the inlet portion112and/or the outlet portion122. The valve body lips131can allow the valve body130to be coupled to the inlet portion112and/or the outlet portion122while allowing the valve body130to rotate relative to the inlet portion112and/or the outlet portion122. For example, an upper valve body lip131can engage with an inlet portion groove111of the inlet portion112to allow the valve body130to rotate relative to the inlet portion112. Further, the engagement of the upper valve body lip131with the inlet portion groove111can guide the rotation of the valve body130relative to the inlet portion112. Similarly, a lower valve body lip131can engage with an outlet portion groove121of the outlet portion122to allow the valve body130to rotate relative to the outlet portion122. The engagement of the lower valve body lip131with the outlet portion groove121can guide the rotation of the valve body130relative to the outlet portion122. In some embodiments, a clinician can rotate the valve body130of the check valve110to move the wiping extension150to dislodge or remove any particulate P from within the check valve110. The outer surface of the valve body130can include one or more protrusions132to allow the clinician to securely grasp and rotate the valve body130relative to the check valve110. Optionally, a motor or actuator can rotate the valve body130to move the wiping extension150dislodge or remove any particulate P within the check valve110. As can be appreciated, a clinician, motor, or actuator can move the valve body130and therefore the wiping extension150at a regular interval or in response to the accumulation of particulates P. As described herein, dislodged or removed particulates P can flow through the outlet124of the check valve110and into the outlet tubing60. In some applications, the dislodged particulates P can be collected in a reservoir90(as described with respect toFIG.2). FIG.11illustrates a cross-sectional view of the check valve110ofFIG.2. In some embodiments, the check valve110includes one or more seals160to prevent fluid leaks between the components of the check valve110. For example, the seals160can prevent fluid leaks between the interface of the inlet portion112and the valve body130and between the interface of the valve body130and the outlet portion122. In some embodiments, the seals160allow for the valve body130to rotate relative to the inlet portion112and/or the outlet portion122while maintain sealing engagement or otherwise a fluid-tight seal between the interfaces between the inlet portion112, the valve body130, and the outlet portion122. The seals160can be referred to as O-rings. The present disclosure is provided to enable any person skilled in the art to practice the various aspects described herein. The disclosure provides various examples of the subject technology, and the subject technology is not limited to these examples. Various modifications to these aspects will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other aspects. A reference to an element in the singular is not intended to mean “one and only one” unless specifically so stated, but rather “one or more.” Unless specifically stated otherwise, the term “some” refers to one or more. Pronouns in the masculine (e.g., his) include the feminine and neuter gender (e.g., her and its) and vice versa. Headings and subheadings, if any, are used for convenience only and do not limit the invention. The word “exemplary” is used herein to mean “serving as an example or illustration.” Any aspect or design described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other aspects or designs. In one aspect, various alternative configurations and operations described herein may be considered to be at least equivalent. A phrase such as an “aspect” does not imply that such aspect is essential to the subject technology or that such aspect applies to all configurations of the subject technology. A disclosure relating to an aspect may apply to all configurations, or one or more configurations. An aspect may provide one or more examples. A phrase such as an aspect may refer to one or more aspects and vice versa. A phrase such as an “embodiment” does not imply that such embodiment is essential to the subject technology or that such embodiment applies to all configurations of the subject technology. A disclosure relating to an embodiment may apply to all embodiments, or one or more embodiments. An embodiment may provide one or more examples. A phrase such an embodiment may refer to one or more embodiments and vice versa. A phrase such as a “configuration” does not imply that such configuration is essential to the subject technology or that such configuration applies to all configurations of the subject technology. A disclosure relating to a configuration may apply to all configurations, or one or more configurations. A configuration may provide one or more examples. A phrase such a configuration may refer to one or more configurations and vice versa. In one aspect, unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, including in the claims that follow, are approximate, not exact. In one aspect, they are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain. In one aspect, the term “coupled” or the like may refer to being directly coupled. In another aspect, the term “coupled” or the like may refer to being indirectly coupled. Terms such as “top,” “bottom,” “front,” “rear” and the like if used in this disclosure should be understood as referring to an arbitrary frame of reference, rather than to the ordinary gravitational frame of reference. Thus, a top surface, a bottom surface, a front surface, and a rear surface may extend upwardly, downwardly, diagonally, or horizontally in a gravitational frame of reference. Various items may be arranged differently (e.g., arranged in a different order, or partitioned in a different way) all without departing from the scope of the subject technology. All structural and functional equivalents to the elements of the various aspects described throughout this disclosure that are known or later come to be known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be encompassed by the claims. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims. No claim element is to be construed under the provisions of 35 U.S.C. § 112, sixth paragraph, unless the element is expressly recited using the phrase “means for” or, in the case of a method claim, the element is recited using the phrase “step for.” Furthermore, to the extent that the term “include,” “have,” or the like is used, such term is intended to be inclusive in a manner similar to the term “comprise” as “comprise” is interpreted when employed as a transitional word in a claim. The Title, Background, Summary, Brief Description of the Drawings and Abstract of the disclosure are hereby incorporated into the disclosure and are provided as illustrative examples of the disclosure, not as restrictive descriptions. It is submitted with the understanding that they will not be used to limit the scope or meaning of the claims. In addition, in the Detailed Description, it can be seen that the description provides illustrative examples and the various features are grouped together in various embodiments for the purpose of streamlining the disclosure. This method of disclosure is not to be interpreted as reflecting an intention that the claimed subject matter requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed configuration or operation. The following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separately claimed subject matter. The claims are not intended to be limited to the aspects described herein, but is to be accorded the full scope consistent with the language claims and to encompass all legal equivalents. Notwithstanding, none of the claims are intended to embrace subject matter that fails to satisfy the requirement of 35 U.S.C. § 101, 102, or 103, nor should they be interpreted in such a way. | 22,530 |
11857762 | DESCRIPTION Reference will now be made to implementations, examples of which are illustrated in the accompanying drawings. In the following description, numerous specific details are set forth in order to provide an understanding of the various described implementations. However, it will be apparent to one of ordinary skill in the art that the various described implementations may be practiced without these specific details. In other instances, well-known methods, procedures, components, circuits, and networks have not been described in detail so as not to unnecessarily obscure aspects of the implementations. There is a desire to monitor the fluid flow in infusion processes more accurately. Unregulated flow, such as over-infusion and under-infusion, of a therapeutic fluid occurs when there are variations between a target flow rate set at an infusion device and an actual flow rate of the therapeutic fluid through an IV administration set and infused to a patient. The devices and methods described herein provide an integrated IV administration set that incorporates electronic sensing and control of fluid flows. FIG.1depicts an example of an institutional patient care system100of a healthcare organization, according to aspects of the subject technology. InFIG.1, a patient care device (or “medical device” generally)12is connected to a hospital network10. The term patient care device (or “PCD”) may be used interchangeably with the term patient care unit (or “PCU”), either which may include various ancillary medical devices such as an infusion pump, a vital signs monitor, a medication dispensing device (e.g., cabinet, tote), a medication preparation device, an automated dispensing device, a module coupled with one of the aforementioned (e.g., a syringe pump module configured to attach to an infusion pump), or other similar devices. Each element12is connected to an internal healthcare network10by a transmission channel31. Transmission channel31is any wired or wireless transmission channel, for example an 802.11 wireless local area network (LAN). In some implementations, network10also includes computer systems located in various departments throughout a hospital. For example, network10ofFIG.1optionally includes computer systems associated with an admissions department, a billing department, a biomedical engineering department, a clinical laboratory, a central supply department, one or more unit station computers and/or a medical decision support system. As described further below, network10may include discrete subnetworks. In the depicted example, network10includes a device network41by which patient care devices12and other devices) communicate in accordance with normal operations. Additionally, institutional patient care system100may incorporate a separate information system server130, the function of which will be described in more detail below. Moreover, although the information system server130is shown as a separate server, the functions and programming of the information system server130may be incorporated into another computer, if such is desired by engineers designing the institution's information system. Institutional patient care system100may further include one or multiple device terminals132for connecting and communicating with information system server130. Device terminals132may include personal computers, personal data assistances, mobile devices such as laptops, tablet computers, augmented reality devices, or smartphones, configured with software for communications with information system server130via network10. Patient care device12comprises a system for providing patient care, such as that described in Eggers et al., which is incorporated herein by reference for that purpose. Patient care device12may include or incorporate pumps, physiological monitors (e.g., heart rate, blood pressure, ECG, EEG, pulse oximeter, and other patient monitors), therapy devices, and other drug delivery devices may be utilized according to the teachings set forth herein. In the depicted example, patient care device12comprises a control module14, also referred to as interface unit14, connected to one or more functional modules116,118,120,122. Interface unit14includes a central processing unit (CPU)50connected to a memory, for example, random access memory (RAM)58, and one or more interface devices such as user interface device54, a coded data input device60, a network connection52, and an auxiliary interface62for communicating with additional modules or devices. Interface unit14also, although not necessarily, includes a main non-volatile storage unit56, such as a hard disk drive or non-volatile flash memory, for storing software and data and one or more internal buses64for interconnecting the aforementioned elements. In various implementations, user interface device54is a touch screen for displaying information to a user and allowing a user to input information by touching defined areas of the screen. Additionally or in the alternative, user interface device54could include any means for displaying and inputting information, such as a monitor, a printer, a keyboard, softkeys, a mouse, a track ball and/or a light pen. Data input device60may be a bar code reader capable of scanning and interpreting data printed in bar coded format. Additionally or in the alternative, data input device60can be any device for entering coded data into a computer, such as a device(s) for reading a magnetic strips, radio-frequency identification (RFID) devices whereby digital data encoded in RFID tags or smart labels (defined below) are captured by the reader60via radio waves, PCMCIA smart cards, radio frequency cards, memory sticks, CDs, DVDs, or any other analog or digital storage media. Other examples of data input device60include a voice activation or recognition device or a portable personal data assistant (PDA). Depending upon the types of interface devices used, user interface device54and data input device60may be the same device. Although data input device60is shown inFIG.1to be disposed within interface unit14, it is recognized that data input device60may be integral within pharmacy system or located externally and communicating with pharmacy system through an RS-232 serial interface or any other appropriate communication means. Auxiliary interface62may be an RS-232 communications interface, however any other means for communicating with a peripheral device such as a printer, patient monitor, infusion pump or other medical device may be used without departing from the subject technology. Additionally, data input device60may be a separate functional module, such as modules116,118,120and122, and configured to communicate with controller14, or any other system on the network, using suitable programming and communication protocols. Network connection52may be a wired or wireless connection, such as by Ethernet, WiFi, BLUETOOTH, an integrated services digital network (ISDN) connection, a digital subscriber line (DSL) modem or a cable modem. Any direct or indirect network connection may be used, including, but not limited to a telephone modem, an MIB system, an RS232 interface, an auxiliary interface, an optical link, an infrared link, a radio frequency link, a microwave link or a WLANS connection or other wireless connection. Functional modules116,118,120,122are any devices for providing care to a patient or for monitoring patient condition. As shown inFIG.1, at least one of functional modules116,118,120,122may be an infusion pump module such as an intravenous infusion pump for delivering medication or other fluid to a patient. For the purposes of this discussion, functional module116is an infusion pump module. Each of functional modules118,120,122may be any patient treatment or monitoring device including, but not limited to, an infusion pump, a syringe pump, a PCA pump, an epidural pump, an enteral pump, a blood pressure monitor, a pulse oximeter, an EKG monitor, an EEG monitor, a heart rate monitor or an intracranial pressure monitor or the like. Functional module118,120and/or122may be a printer, scanner, bar code reader or any other peripheral input, output or input/output device. Each functional module116,118,120,122communicates directly or indirectly with interface unit14, with interface unit14providing overall monitoring and control of device12. Functional modules116,118,120,122may be connected physically and electronically in serial fashion to one or both ends of interface unit14as shown inFIG.1, or as detailed in Eggers et al. However, it is recognized that there are other means for connecting functional modules with the interface unit that may be utilized without departing from the subject technology. It will also be appreciated that devices such as pumps or patient monitoring devices that provide sufficient programmability and connectivity may be capable of operating as stand-alone devices and may communicate directly with the network without connected through a separate interface unit or control unit14. As described above, additional medical devices or peripheral devices may be connected to patient care device12through one or more auxiliary interfaces62. Each functional module116,118,120,122may include module-specific components76, a microprocessor70, a volatile memory72and a nonvolatile memory74for storing information. It should be noted that while four functional modules are shown inFIG.1C, any number of devices may be connected directly or indirectly to central controller14. The number and type of functional modules described herein are intended to be illustrative, and in no way limit the scope of the subject technology. Module-specific components76include any components necessary for operation of a particular module, such as a pumping mechanism for infusion pump module116. While each functional module may be capable of a least some level of independent operation, interface unit14monitors and controls overall operation of device12. For example, as will be described in more detail below, interface unit14provides programming instructions to the functional modules116,118,120,122and monitors the status of each module. Patient care device12is capable of operating in several different modes, or personalities, with each personality defined by a configuration database. The configuration database may be a database56internal to patient care device, or an external database37. A particular configuration database is selected based, at least in part, by patient-specific information such as patient location, age, physical characteristics, or medical characteristics. Medical characteristics include, but are not limited to, patient diagnosis, treatment prescription, medical history, medical records, patient care provider identification, physiological characteristics or psychological characteristics. As used herein, patient-specific information also includes care provider information (e.g., physician identification) or a patient care device's10location in the hospital or hospital computer network. Patient care information may be entered through interface device52,54,60or62, and may originate from anywhere in network10, such as, for example, from a pharmacy server, admissions server, laboratory server, and the like. Medical devices incorporating aspects of the subject technology may be equipped with a Network Interface Module (NIM), allowing the medical device to participate as a node in a network. While for purposes of clarity the subject technology will be described as operating in an Ethernet network environment using the Internet Protocol (IP), it is understood that concepts of the subject technology are equally applicable in other network environments, and such environments are intended to be within the scope of the subject technology. Data to and from the various data sources can be converted into network-compatible data with existing technology, and movement of the information between the medical device and network can be accomplished by a variety of means. For example, patient care device12and network10may communicate via automated interaction, manual interaction or a combination of both automated and manual interaction. Automated interaction may be continuous or intermittent and may occur through direct network connection52(as shown inFIG.1), or through RS232 links, MIB systems, RIF links such as BLUETOOTH, IR links, WLANS, digital cable systems, telephone modems or other wired or wireless communication means. Manual interaction between patient care device12and network10involves physically transferring, intermittently or periodically, data between systems using, for example, user interface device54, coded data input device60, bar codes, computer disks, portable data assistants, memory cards, or any other media for storing data. The communication means in various aspects is bidirectional with access to data from as many points of the distributed data sources as possible. Decision-making can occur at a variety of places within network10. For example, and not by way of limitation, decisions can be made in HIS server30, decision support48, remote data server49, hospital department or unit stations46, or within patient care device12itself. All direct communications with medical devices operating on a network in accordance with the subject technology may be performed through information system server30, known as the remote data server (RDS). In accordance with aspects of the subject technology, network interface modules incorporated into medical devices such as, for example, infusion pumps or vital signs measurement devices, ignore all network traffic that does not originate from an authenticated RDS. The primary responsibilities of the RDS of the subject technology are to track the location and status of all networked medical devices that have NIMs, and maintain open communication. FIG.2depicts an example an integrated administration set and an infusion pump, according to aspects of the subject technology. In some implementations, an administration set200includes an integrated flow stop system202. The integrated flow stop system202provides closed loop control and flow sensing, in addition to functioning as a mechanical flow stop device.FIGS.4A-4Cprovide different views of the integrated flow stop system202. IV administration sets are typically single-use disposable consumables. Thus, they generally do not contain sensors or other electronics that monitor or control fluid flows. In contrast, the integrated IV set200includes liquid sensing capabilities and closed loop flow control circuitry, enhancing the accuracy and efficiency for sensing of the flow rate directly at the administration set and improving overall control of flow rates based, at least in part, on the sensed values. A closed loop control system (or feedback control system) can automatically regulate a process variable to a desired set point with limited or, in some cases, no human interaction. The control circuitry in the integrated flow stop system202detects the flow rate of the infusion process by generating control messages to adjust one or more elements of a patient care device. A control message may be generated based on a set (e.g., desired) flow rate provided at an infusion pump in comparison to a detected flow rate for the infusion pump. A closed loop control system includes one or more feedback loops between its output values and its input values. A closed-loop control system can generate an error signal that reflects a difference between its output values (e.g., the flow rate measured by the flow sensor) and its reference input value (e.g., the set flow rate provided at the infusion pump), and the control message generated by the closed-loop control system is dependent on the output value. For example, the control signal sent by the control circuitry changes an operational parameter of the infusion pump in order to bring the measured flow rate as close as possible to the set (e.g. desired) flow rate. FIG.2depicts the administration set200coupled to a large volume pump (LVP)250. In some implementations, the administration set200is used with syringe pumps or other infusion pump systems. The LVP250includes a door252, an upper tubing fitment receptacle254, and a pumping mechanism256. The LVP250also includes a molded feature260having a shape complementary to a corresponding portion of the integrated flow stop system202. In this way, the molded feature260ensures a snug fit of the integrated flow stop system202when the IV administration set200is loaded into and engaged with the pump250. A first plurality of conductive connections258on the pump250(FIG.2depicts4different conductive connections) permits electricity and data to flow between the pump250and the integrated flow stop system202when the integrated IV administration set200is loaded into, and engaged with the pump250. Each of the conductive connections258may be formed of the same material or different material depending on the conductive path formed. For example, a conductive connection for power may be formed from a metal or other material for conducting electricity while a data connection may be formed from a metallic or fiber optic conductive material to form a data pathway. The pump250also includes a retainer264to secure the tubing214. The pump250includes an inter-unit interface (IUI) connector266. The IUI connector266establishes power and communications between the pump250and various attached modules. A receiving portion262in the pump250defines a slot into which a tubing fitment222of the integrated flow stop system202is loaded. The flow stop210is coupled to and positioned below the tubing fitment222. As explained in more details in reference toFIGS.4A-4C, the flow stop210is configured to slide between two positions. In a first position (the open position), the flow stop210lines up with the tubing fitment222(as shown inFIG.4B), and a flow of a fluid in the tubing214is not occluded. In a second position (the closed position), the flow stop210slides toward the tubing214, protruding from under the tubing fitment222, and mechanically clamps the tubing214to occlude the flow of the fluid. In some implementations, the flow stop210is in the open position when the administration set200is loaded into the pump250. During an infusion process, the door252is closed and the flow stop210stays in the open position to permit fluid flow. When the door252opens (e.g., accidentally) during the infusion process, the flow stop210automatically changes to the closed position, mechanically pinching the tubing214to prevent accidental discharge of the fluid. The integrated flow stop system202adds electronically controlled functionalities to the flow stop. In some implementations, upon loading the integrated administration set200into the pump250, the flow stop210is engaged (e.g., remains in the open position) and the plurality of conductive connections258interfaces to the corresponding conductive connections on the integrated flow stop system202. The conductive connections provide electrical power to an electronic flow sensor406(shown inFIG.4C) disposed within a housing450of the integrated flow stop system202, activating the electronic flow sensor406. In addition to conducting electricity, the plurality of conductive connections258also permits sensor data and/or control signals from the flow sensor406or closed loop control circuitry to be relayed to the pump250. For example, in some implementations, the control signals from the closed loop control circuitry change an operational parameter of the pumping mechanism256to cause a measured flow rate at the electronic flow sensor406to shift closer in value to the desired set flow rate programmed at the pump250. In some implementations, the integrated flow stop system202also includes non-volatile memory components configured to store identification information of the administration set200. For example, upon correct loading and engagement of the integrated flow stop system202into the pump250, data stored in the non-volatile memory component is read by the pump250. In some implementations, the memory components store information about how long the administration set200has been in use. For example, a circuitry (e.g., an electronic time counter) disposed in the integrated flow stop system202records the length offline over which the integrated flow stop system202receives electricity from the plurality of conductive connections258. In some implementations, the memory components also store flow rate data measured by the electronic flow sensor406. In some implementations, the integrated flow stop system202includes a wireless communication module. The flow rate data measured by the electronic flow sensor406is uploaded directly to a server system (e.g., of a hospital system) that monitors the operation of the pump250. In some implementations, the pump250stores flow rates values for different infusion fluid types, and modifies its operational parameters based on flow rates measured by the electronic flow sensor406. The pump250receives the measured flow rates relayed directly by the integrated flow stop system202or transmitted from the server system. In some implementations, the identification information stored on the non-volatile memory includes a manufacture date of the administration set, allowing the pump250to determine a shelf-life of the administration set that is being loaded into the pump250. Once conductive connections (e.g., through the plurality of conductive connections258) are established between the integrated flow stop system202and the pump250, the pump250can obtain shelf-life information from the administration set200. The shelf life information may identify an expiration date for the set after which the set should not be used. To ensure patient safety, the pump250can block infusion processes on an administration set that has exceeded the identified shelf-life. The identification information may include additional or alternative information regarding the use of the administration set200. For example, the identification information may include a maximum time of use for the administration set200. In such instances, the pump250can terminate an infusion process and/or sound an alarm when the administration set200has been in use for longer than the maximum time of use. This can help to minimize infection risks associated with over-extended use of the administration set. Other use information may include drug type(s) that can or cannot be infused with the administration set, pumps or pump modules that are compatible with the administration sets, or calibration values that can be used to improve an accuracy of the pressure sensing and an accuracy of flow delivery performance. In some implementations, additional information can be provided via the flow stop system202, such as whether the IV bag is empty and has no flow, whether there is an occlusion condition due to pressure building up and affecting the flow pattern. If the sear on the flow stop does not engage or engages in a manner that is not within specifications, unregulated flow can result. The flow stop systems described herein may be able to detect such conditions because the pump module is able to communicate with the flow stop. Incorporating electronic functionalities into the integrated flow stop system202allows easy association of the flow sensor (in a particular administration set) to the pump. For a pump having multi-channel infusion capabilities, automatically establishing a data channel between the pump and the flow sensor of each administration set (e.g., through the plurality of conductive connections258) minimizes errors (e.g., of associating the wrong flow rate with the wrong infusion channel) and reduces the need for manual checks of the administration set during loading or during an infusion process from a health care professional. In some implementations, the IV bag and set are prepared together by the pharmacy. An identification (“ID”) number can be associated with both the IV bag and the administration set. The ID number can be read by the pump and correlated to the medication, the flow rate, and volume to be administered to the patient. The pump can be programed based on these parameters without the need for a clinician to enter these values. In some implementations, such information can be provided by the integrated flow stop system202. In some implementations, the plurality of conductive connections258includes spring loaded pogo pin type connectors. In some implementations, conductive connections258are made from an elastomeric plastic conductor material. In some implementations, there is contactless transfer of power and/or data between the integrated flow stop system202and the pump250. The contactless transfer of power includes inductive coupling elements. For example, the pump250includes a transmitter device, driven by electric power from a power source to generate a time-varying electromagnetic field. The electromagnetic field transmits power across space to a receiver device in the integrated flow stop system202. The receiver device extracts power from the electromagnetic field and supplies it to an electrical load (e.g., the electronic flow sensor406and/or the control circuitry). The molded feature260in the housing of the pump250receives, centers, and locates the housing450(and the components such as the electronic flow sensor406) of the integrated flow stop system202, and ensures alignment of the flow stop210, and electrical contacts between the integrated flow stop system202and the pump250. At slow flow rates, the pump can create large relative changes in the flow rate even with minor deviations (e.g., a minor change in the flow rate constitutes a large percentage change when the flow rate is small). In other words, a small (absolute) changes in the flow rate results in a large percentage (e.g., relative) change. The large relative changes limit a dynamic range of flow rates that a flow sensor can reliably detect. In addition, regions close to the pumping mechanism256are often subjected to high noise factors (e.g., from the motor generating bursts of flow in the system). In some implementations, the system202is provided at an upper fitment region of the pump (e.g., upper tubing fitment receptacle254) above the pumping mechanism256, and the flow stop would not be part of the flow sensor. In such implementations, the administration set would have two separate fitments: one containing (a standalone) flow sensor and associated control circuitry, and the other (lower) fitment having the flow stop clamp. Placing the flow sensor and control circuitry near the upper tubing fitment receptacle254allows the flow rate to be measured at a region of the pump that has lower noise factors, yielding more accurate measurements. The lower noise factors also allow a dynamic range of the flow rate measurements to be improved. In some implementations, the flow sensor406measures a dynamic range of flow rates between 0.1 ml/hour to 999 ml/hour. Even thoughFIGS.2and3show insertion of the integrated flow stop system202at the lower region of the pump250, the administration set according to aspects of the subject technology can be inserted at other regions of the pump250. In some implementations, instead of the entire integrated flow stop system202being positioned (e.g., inserted) at the upper tubing fitment receptacle254, only the electronics contained in the housing450(e.g., the electronic flow sensor406, the control circuitry, the wireless communication module, the inductive coupling elements) are inserted (e.g., while encased in a housing) at the top. In such implementations, the tubing fitment222and the flow stop210are still inserted below the pumping mechanism256, similar to the configuration shown inFIG.2. In such a configuration, the components included in the upper tubing fitment may be conductive coupled to the flow stop210. In this way, resources such as power and data may be conducted via the flow stop210to the components included in the upper tubing fitment. A conductive path may be formed on or within a wall of the administration set or the conductive path may be wireless. In other words, the flow sensor may be part of the upper fitment and the electric power or communication may be part of the flow stop in lower fitment. FIG.3depicts an enlarged view of an integrated administration set and an infusion pump, according to aspects of the subject technology. In some implementations, a portion of the pump250receives the integrated administration set200. The molded feature260has a shape complementary to the housing450of the integrated flow stop system202. The plurality of vertically arranged conductive connections258is embedded in the pump housing, and interfaces with the conductive connections in the integrated flow stop system202(shown more clearly inFIGS.4A-4C).FIG.3depicts more clearly how the receiving portion262is to engage the pump side alignment region220of the tube fitment222. FIG.4Adepicts a first perspective view of an integrated flow stop system, according to aspects of the subject technology. As shown in a close up view of the integrated flow stop system202, the integrated flow stop system202includes a tubing fitment222, a housing450, and a flow stop210. The tubing fitment222includes a protrusion228that is configured to receive a tubing212. The integrated flow stop system202includes a flow stop210, The flow stop210includes a slider portion216. The flow stop210is movably mounted to the tubing fitment222, and positioned below the tubing fitment222. The slider portion216of the flow stop210is able to slide along a channel defined in the tubing fitment222. The flow stop210is a clamping device, or safety clamp, that prevents inadvertent free-flow of fluids in the tubing212when the administration set200is removed from infusion device. The slider portion216slides along a direction410annotated by a double arrow. When the slider portion216slides closer to a pump side alignment region220of the fitment222, the flow stop210is in an open position, which allows a fluid to flow through the tubing212from a top portion of the integrated flow stop system202to a tubing214connected to a lower portion of the integrated flow stop system202. When the slider portion216slides toward a tubing side region230of the fitment222, a rounded region224of a tear-shaped opening218moves away from the tubing214, so that the narrower region226of the flow step210engages the tubing214and mechanically constricts (e.g., pinches or clamps) the tubing214, occluding the flow of fluid in the tubing214. In this closed position, the edge portion230of the flow stop210extends beyond (e.g., sticks out) the tubing side region230of the fitment222, along the direction410. When the administration set200is properly loaded into (e.g., engaged with) and received by the pump250, the flow stop210in the administration set200is maintained in the open state where fluids can flow through the tubing214. When the infusion process is interrupted (e.g., by opening the door252of the pump250), the flow stop210shifts into the closed position, to prevent accidental discharge of the fluid while the infusion process is interrupted. For example, the door252may include a latching element that secures the door in place against the pump250. When the handle attached to the front face of the door252is lifted, this lifting action may release the latching element. In doing so, the change in position of the latching element may change the position of the flow stop210to the closed position. In some implementations, the opening of the door applies the force necessary to shift the flow stop210to the closed position. For example, a flange236may engage below the flow stop210. When the door252is opened, the flange will be pulled away from the pump250and flow stop210. As the flange leaves the pump250, it may slide the flow stop210into the closed position. Conventional administrative sets typically rely on flow sensors that external or that are built into the pump. Having a flow sensor incorporated into a flow stop allows for higher sensitivity in measuring different flow rates. The flow stop210may include a door-facing housing234. The door-facing housing234may additionally or alternatively include conductive connectors to couple with connectors affixed on the door252. The door-facing housing234may include electronic components to implement one or more of the features described, such as sensors, a microprocessor, memory, power, antenna, valve or valve controller (e.g., piezoelectric or electromagnetic controller), and/or fiber optics. In some implementations, the flow stop is on the downstream section of the pump so that the flow going to the patient is more accurately controlled for flow continuity. Monitoring the flow on the upstream side measures the intake flow rate. In some implementations, the intake is filled very rapidly to allow flow continuity downstream. It may thus be desirable to monitor the flow on the downstream section of the pump. Assuming that there are no leaks or restrictions from the pump down to the needle (e.g., site of fluid entry into the patient), the location of flow monitoring should not matter. Placing the flow sensor near, or in the pump reduces the lengths of conductive (e.g., electrical) leads. FIG.4Bdepicts a second perspective view of an integrated flow stop system, according to aspects of the subject technology. As shown, a flow stop210is in the open position. In the open position, the rounded region224of the tear-shaped opening218does not mechanically obstruct a flow of fluid in the tubing214. In the open position, an edge232of the flow stop210does not protrude beyond the tubing side region230of the tubing fitment222. FIG.4Cdepicts a third perspective view of an integrated flow stop system, according to aspects of the subject technology. A view of the integrated flow stop system202from the pump side shows a number of conductive connections402-ato402-ein a recessed portion404of the housing450of an upper part of the integrated flow stop system202. The fitment222forms the lower part of the system202. The recessed portion404allows easier alignment of the conductive connections to a corresponding receiving portion of conductive connections on the pump250. As shown inFIG.4C, the flow stop system202includes five conductive connections whereas the pump interface includes four (seeFIG.3, element258). The conductive connections may differ between the flow stop system202shown inFIG.4Cand the pump. This allows the flow stop system202to interface with a variety of different pumps and, as resources are available, increase the functionality provided thereby. In some instances, the flow stop system202may be inoperable without sufficient connectivity with the pump. In such instances, the flow stop system202may include a valve that remains closed to prevent fluid from infusing through the administration set. In such instances, the pump may receive a message from the flow stop system202disabling infusions through the pump until the administration set is changed. The housing450of the integrated flow stop system202includes one or more flow sensors. In some implementations, at least a portion of a flow sensor may be in contact with the fluid. In such implementations, the flow sensor may include a metering element in the fluid path that can move based on the rate of fluid moving along the fluid path. In some implementations, the inline pressure for differential pressure) of fluid along the fluid path or constricted fluid path may be measured to determine the flow rate. In some implementations, the fluid may not be in contact with the flow sensors. In some implementations, the flow sensor may include two components, one within the housing450and one within the door-facing housing234. An emission from one component may be read by the second component. A comparison between the emitted signal and the received signal may provide an indication of flow rate. In some implementations, the flow sensor may include an acoustic sensor. The acoustic sensor may detect the noise within the fluid line as the fluid is flowing past the sensor. The detected noise may be used to identify the flow rate. In some implementations, the acoustic sensor includes an ultrasonic method of flow sensing. In some implementations, the flow sensors operate based on calorimetric principles. For example, a static heating element and two temperature sensors are placed in the fluid path, and the flow rate is measured based on changes in the temperature profile of the fluid. Such flow sensors may be CMOS based. In some implementations, the flow sensors operate based on time-of-flight principles. Unlike static heaters, the heater based on time-of-flight principles is modulated and receivers both upstream and downstream of the heater receive the modulated signal. Based on the time of arrival of the modulated signal, the flow rate is determined. In some implementations, such flow sensors may be packaged as MEMS. In some implementations, electrical energy for powering the flow sensors are transmitted from the pump through the conductive connections402-ato the flow sensors. The flow sensors send data back to the pump250through one of the conductive connections. In some implementations, the conductive connections402-aand402-einclude pogo-pin type connectors. In some implementations, the conductive connections402-aand402-einclude elastomeric plastic conductor material. In some implementations, the conductive connections402-aand402-eform a conductive connection with an inductive power source housed within the pump. The inductive power source includes inductive coupling components configured to transfer power wirelessly from the pump to the electronic flow sensor. In such cases, the conductive connections need not be formed on an exposed surface of the housing450in the upper part of the integrated flow stop system202. In some implementations, the integrated flow stop system202includes wireless communication circuitry, allowing the administration set200to form a wireless association with the pump and/or a server system. In some implementations, the wireless association is formed automatically, without specific user input. Such wireless connectivity allows a server system to track locations of particular administration sets, and also allows the server system to receive information about flow rates of therapeutic treatments provided by different administration sets. The housing450in the upper part of the system202may also contain various circuitry that allows the pump to identify a particular administration set. Non-volatile memory in the circuit can store information regarding a manufacture date of the administration set200, allowing the pump to ascertain if the administration set200has exceeded a particular shelf-life. In some implementations, to ensure patient safety, the pump would not proceed with an infusion process when the pump reads from the non-volatile memory of the integrated flow stop system202that administration set200has exceeded its shelf-life. In some implementations, the administration set has degraded accuracy towards its end of life, and the pump would be able to obtain life-time information from the non-volatile memory of the administration set200. The integrated flow stop system202thus provides a smart sensor for the pump250. The pump is also able to record the usage time clocked on a particular administration set. In some implementations, when a patient is moved between different zones in a hospital (e.g., from the intensive care unit, to a general ward), the same administrative set is used/associated with different pumps, and the circuitry on the integrated flow stop system202provides information to the hospital system regarding a total duration of the therapeutic treatment. The circuitry contained within the housing450in the upper part of the integrated flow stop system202also includes closed loop flow control circuitry. In some implementations, the closed loop flow control circuit directly receives real-time data recorded by the flow sensors (or other sensors included in the flow stop such as a temperature sensor, a light sensor, a camera, a gyro sensor or accelerometer to identify if the set has been properly inserted by the user, a near-field communication (NFC) sensor for powering, communication and/or authentication of an authorized administration set, a Bluetooth Low Energy (BLE) beacon for asset tracking and for identifying active infusions and administration sets) and provides control signals to the pump250to alter a flow rate of the pump to achieve a desired therapeutic fluid flow rate profile for the infusion. In some implementations, the flow sensors include electrical capacitance sensors that measure flow based on the changes in dielectric caused by fluid flow. In some implementations, it may be desirable to provide measurements to the pump and allow the pump to assess and apply adjustments to achieve the target pumping conditions. Having the flow sensors provide real-time measured data to the close-loop flow control circuit contained within the housing450of the integrated flow stop system202minimizes or, in some cases, eliminates the need to transfer raw flow rate data to the pump and reducing latency between detecting the flow rate and the pump receiving, computing and adjusting a flow rate. In some implementations, the housing450of the integrated flow stop system202may include newer control circuitry and/or firmware, allowing even an older version of the pump to provide enhanced flow control or other fluid characteristic sensing based on the control circuitry in the administration set, without having the need to retrofit or modify the pump or to add and coordinate additional sensors. In some implementations, additional circuitry provides the capability of updating the flow stop firmware over the air so that algorithms can be enhanced to improve flow sensitivity without needing to reconfigure a pump that is already deployed in the field. In some implementations, older pumps that have mating connections can connect with a flow stop having corresponding conductive connections (e.g., electrically conductive connections and data conductive elements). In some implementations, the measured flow rate or other fluid characteristic data is stored on the administration set. In some implementations, the measured flow rate or other fluid characteristic data is stored in the system (e.g., on the pump, or on a server system (e.g., in a hospital system)). The pump includes flow rate values for different fluid types. By measuring the flow rate and controlling the flow rate in closed loop, right on the administration set, higher accuracy is achieved. The higher accuracy permits better predictions of the amount of therapeutic fluid that is going to be infused to the patient. The system250detects risks of unregulated flows (e.g. over-infusion, under-infusion) and preemptively corrects for any infusion rate errors. FIG.5Adepicts an example sensor system that is retrofitted to an infusion device, according to aspects of the subject technology. Instead of the integrated flow stop system202establishing electrical or data connections to a control module14(e.g., the pump250), a sensor wedge500has one or more sensor plugins502to couple one or more distinct administration sets (e.g.,508,510) infusing one or more fluids to a patient via an integrated flow stop system (similar to the flow stop system202described inFIGS.2-4D). In some implementations, various flow features can be integrated into the one or more sensor plugins502. In some implementations, sensor features are plugged into the wedge (as shown inFIG.5BandFIG.5C) or are included in (e.g., affixed to) the wedge (as shown inFIGS.5D and5E). When the sensor features are included in the sensor500, the administration sets (e.g.,508,510) can be loaded into the sensor plugin502for non-contact sensing (e.g., through the tubing without direct contact with the fluid). In some implementations, modules504and506may include different pumps, such as a large volume pump (LVP), a syringe pump, or an end-tidal CO2 monitor (EtCO2). In some implementations, the sensor plugins may be clamped externally to the administration set rather than couple with or be integrated into the administration sets. In this way, the sensor plugins may be reused for multiple infusions. In some implementations, the sensor plugins are integrated into the administration set and include one or more conductive coupling elements to connect with the sensor wedge. The control module14may include a user interface device54. The sensor wedge500can be retrofitted to pumps to provide sensing capabilities via the IUI connector266(shown inFIG.2). Data and power may be transferred via the IUI connector266. The sensor wedge may include similar circuitry as the flow stop such as a microprocessor, memory, power storage, antenna, sensors, etc. The sensor plugins may provide measurements to the sensor wedge500. As discussed, the sensor wedge may process the measurements and provide control messages to adjust the pump. In some implementations, the sensor wedge may forward sensor readings to the pump and allow the pump to assess the proper controls. In some implementations, the sensor wedge allows the flow sensor and the control circuitry to be located on the top tube fitment, instead of the lower fitment. FIG.5Bdepicts an example sensor system that includes a device having a port for receiving a flow sensor, according to aspects of the subject technology.FIG.5Bshows a view of one side of a wedge sensor520. The wedge sensor520has a housing522. In some implementations, the housing522has a first main surface524and a second main surface (not shown inFIG.513) parallel to the first main surface524. A processor of the wedge sensor520is located inside the housing522. Storage memory is also located inside housing522. The wedge sensor520includes a connection element528mounted on the first surface524of the housing522. In some implementations, the connection element528is an inter-unit interface connector configured to mate with the IUI connector on a pump module or a patient care unit (PCU). The connection element528includes a data conductive element to transfer data from the wedge sensor520to the pump module or the PCU. The connection element528also includes an electrically conductive element to transfer power. In some implementations, the connection element528receives power from the infusion device, and the data is transferred between the sensor system and the infusion device. In some implementations, the connection element528includes a mounting element to attach to a corresponding interface connector of the infusion device. In some implementations, the infusion device has a predetermined length, and the first surface524of the housing522has a length exceeding the predetermined length such that the first electronic flow sensor can extend from the first surface524under or above the infusion device. In some implementations, the inter-unit interface connector528includes a mounting element to attach to a corresponding interface connector of a first infusion device, and the second inter-unit interface connector534includes a second mounting element to attach to a corresponding interface connector of a second infusion device. In some implementation, power is received from the first infusion device, and data is transferred between the sensor system and the first infusion device. In some implementation, power received by the second inter-unit interface connector534includes at least a portion of the power received by inter-unit interface connector528, and is transmitted to the second infusion device. Data received by the second inter-unit interface connector534includes at least a portion of the data transferred between the sensor system and the first infusion device, and is transferred between the sensor system and the second infusion device. The wedge sensor520includes, on the first main surface524, an electronic flow sensor port526for receiving a flow sensor. In some implementations, the port522includes three pins as shown inFIG.5B, In some implementations, there may be more or fewer pins, depending on the power and data capabilities of the flow sensor. The port526is configured to receive flow information from a first electronic flow sensor of a first fluid line (e.g., from an administration set) that is coupled to it. The data conductive element, the electrically conductive element, and the electronic flow sensor port are coupled with the processor. A second connection element534(shown inFIG.5C) is mounted on the second surface of the housing522. In some implementations, the second connection element is similar to the connection element that is mounted on the first main surface524: it is configured to mate with the IUI connector on the pump module or PCU; it includes a second data conductive element to transfer second data from the wedge sensor520to the pump module or the PCU; and it includes a second electrically conductive element to transfer power. A second electronic flow sensor port536(shown inFIG.5C) is also mounted on the second main surface. In some implementations, the second electronic flow sensor port is similar to the electronic flow sensor port526that is mounted on the first main surface524: it is configured to receive flow information from a second electronic flow sensor of a second fluid line (e.g., from an administration set) that is coupled to it. The second data conductive element, the second electrically conductive element, and the second electronic flow sensor port are also coupled with the processor. In some implementations, a first portion530of the housing522has a height x that corresponds to height of the pump module. A second portion532of the housing522includes the port526, and has a height n. In some implementations, a sum of the height of the first portion530and a height of the second portion532exceeds the height of the pump module, providing clearance for the sensors. FIG.5Cdepicts an example sensor system configured to couple more than one sensors and more than one pump modules, according to aspects of the subject technology.FIG.5Cshows the coupling between the microprocessor in the wedge sensor520and various connectors and ports. In some implementations, the first RR connector528and the first electronic flow sensor port526, both of which are mounted to a first main surface524of the housing522are coupled to the microprocessor. The microprocessor in the wedge sensor520is also coupled to the second IUI connector534and the second electronic flow sensor port536, both of which are mounted to the second main surface of the housing522. Storage memory or other memory is also coupled to the microprocessor. In other words, the wedge sensor520includes two sensor ports (one on each side of the wedge sensor520) and is configured to be coupled to two PCUs (one on each side of the wedge). FIG.5Ddepicts an example sensor system, according to aspects of the subject technology.FIG.5Dshows a view of one side of a wedge sensor540. The wedge sensor540has a housing542. In some implementations, the housing542has a first main surface544and a second main surface (not shown inFIG.5D) parallel to the first main surface544. A processor of the wedge sensor540is located inside the housing542. Storage memory is also located inside housing542. The wedge sensor540includes a connection element548mounted on the first surface544of the housing542. In some implementations, the connection element548is an RI connector configured to mate with the MI connector on an infusion device (e.g., the pump module or PCU). The connection element548includes a data conductive element to transfer data from the wedge sensor540to the pump module or the PCU. The connection element548also includes an electrically conductive element to transfer power. In some implementations, the connection element548receives power from the infusion device, and the data is transferred between the sensor system and the infusion device. In some implementations, the connection element548includes a mounting element to attach to a corresponding interface connector of the infusion device. In some implementations, the infusion device has a predetermined length, and the first surface544of the housing542has a length exceeding the predetermined length such that the first electronic flow sensor can extend from the first surface544under or above the infusion device. In some implementations, the inter-unit interface connector548includes a mounting element to attach to a corresponding interface connector of a first infusion device, and the second inter-unit interface connector554includes a second mounting element to attach to a corresponding interface connector of a second infusion device. In some implementation, power is received from the first infusion device, and data is transferred between the sensor system and the first infusion device. In some implementation, power received by the second inter-unit interface connector554includes at least a portion of the power received by inter-unit interface connector548, and is transmitted to the second infusion device. Data received by the second inter-unit interface connector554includes at least a portion of the data transferred between the sensor system and the first infusion device, and is transferred between the sensor system and the second infusion device. An electronic flow sensor546affixed to the first main surface544is configured to measure flow information for a first fluid line coupled to it. The data conductive element, the electrically conductive element, and the first electronic flow sensor are coupled with the processor. A second connection element554(shown inFIG.5E) is mounted on the second surface of the housing552. In some implementations, the second connection element is similar to the connection element that is mounted on the first main surface554: it is configured to mate with the IUI connector on the pump module or PCU; it includes a second data conductive element to transfer second data from the wedge sensor550to the pump module or the PCU; and it includes a second electrically conductive element to transfer power. A second electronic flow sensor556(shown inFIG.5E) affixed to the second surface is configured to measure flow information for a second fluid line coupled to it. The second data conductive element, the second electrically conductive element, and the second electronic flow sensor port are also coupled with the processor. FIG.5Edepicts an example sensor system configured to couple more than one pump modules, according to aspects of the subject technology.FIG.5Eshows the coupling between the microprocessor in the wedge sensor540and various connectors and ports. In some implementations, the first IUI connector548and the first electronic flow sensor546, both of which are mounted to a first main surface544of the housing542are coupled to the microprocessor. The microprocessor in the wedge sensor540is also coupled to the second IUI connector554(mounted to the second main surface of the housing542) and the second electronic flow sensor556. Storage memory or other memory is also coupled to the microprocessor. In other words, the wedge sensor540includes two sensors (one on each side of the wedge sensor540) and is configured to be coupled to two PCUs (one on each side of the wedge). In one aspect, an integrated intravenous (IV) administration set includes a flow stop having a tubing fitment and a housing, the flow stop configured, in a first position, to prevent a flow of a fluid through a tubing, and in a second position, to permit the flow of the fluid through the tubing, the tubing fitment comprising a protrusion configured to receive a tubing. The IV administration set also includes an electronic flow sensor disposed within the housing, the electronic flow sensor configured to measure the flow of the fluid in the tubing, and one or more conductive connections configured within the housing and configured to provide electrical power to the electronic flow sensor. The flow stop is shaped to be loaded and engaged to a receptacle of an infusion device, and shaped to cause, when loaded and engaged, the one or more conductive connections to engage with a corresponding conductive connection provided by the infusion device to activate the electronic flow sensor based on a power flow from the infusion device. In some implementations, the integrated intravenous (IV) administration set further includes control circuitry is configured to send a control signal to the infusion device to modify a flow rate generated by a pumping mechanism of the infusion device. In some implementations, the electronic flow sensor further includes a data communication component. The one or more conductive connections is arranged on an exterior of the housing, and the infusion device is configured with a corresponding one or more conductive connections so that during use of the integrated IV administration set: the one or more conductive connections is in electrical contact with the corresponding one or more conductive connections, and the electronic flow sensor is in electrical communication to transmit data using the data communication component to the infusion device. In some implementations, the housing includes a recessed portion, and the one or more the conductive connections is vertically aligned within the recessed portion. In some implementations, the one or more conductive connections includes spring loaded pogo pin connectors. In some implementations, the one or more conductive connections includes an elastomeric plastic conductor material. In some implementations, the tubing fitment has a shape complementary to features molded into a housing of the infusion device so that the tubing fitment is configured to align the flow stop with respect to the infusion device when the integrated IV administration set is loaded and engaged to the infusion device. In some implementations, the integrated IV administration set further includes a wireless communication module. In some implementations, the integrated IV administration set is configured to wirelessly upload data measured by the electronic flow sensor to a server system that monitors an operation of the infusion device. In some implementations, the integrated IV administration set is configured to wirelessly transfer data measured by the electronic flow sensor to the infusion device. In some implementations, the one or more conductive connections include inductive coupling components configured for wireless power transfer from the infusion device to the electronic flow sensor. In some implementations, the integrated IV administration set further includes non-volatile memory components storing identification information of the integrated IV administration set. In some implementations, the non-volatile memory components store information about a manufacture date of the integrated IV administration set, and the infusion device is configured to check the identification information and the manufacture date of the integrated IV administration set prior to starting an infusion process. In some implementations, the non-volatile memory components store information that is transmitted to the infusion device, the information indicating how long the integrated IV administration set has been in used. In some implementations, the flow stop includes a slider component mounted to and positioned orthogonal to the tubing fitment. The slider component is configured to slide relative to the tubing fitment and engage a tubing connected to the tubing fitment to prevent a flow of fluid in the tubing when the IV administration set is removed from the infusion device and to allow the flow of fluid in the tubing when the IV administration set is loaded and engaged to the infusion device. In some implementations, the tubing fitment and the housing are configured to be received in a top portion of the infusion device, the top portion of the infusion device being above a pumping mechanism of the infusion device, and the flow stop is configured to be received in a bottom portion of the infusion device, the bottom portion of the infusion device being below the pumping mechanism of the infusion device. In some implementations, the flow sensor is configured to send a control signal to the infusion device after the integrated IV administration set has been in use for a predetermined period of time. In some implementations, the IV administration set further includes a processor configured to determine a duration of time the integrated IV administration set has been in use based on a length of time the integrated IV administration set receives electrical power from the infusion device through the one or more conductive connections. In another aspect, a sensor system includes a first plurality of conductive connections; a data port to receive data recorded by an electronic flow sensor of an integrated intravenous (IV) administration set, wherein the integrated IV administration set includes a second plurality of conductive connections configured to interface with the first plurality of conductive connections when the integrated IV administration set engages with the sensor system; and the sensor system is configured to provide control signals to an infusion device based on the data recorded by the electronic flow sensor to maintain a fluid flowing through the integrated IV administration set at a desired flow rate. Many of the above-described features and applications, may also be implemented as software processes that are specified as a set of instructions recorded on a computer readable storage medium (also referred to as computer readable medium), and may be executed automatically (e.g., without user intervention). When these instructions are executed by one or more processing unit(s) (e.g., one or more processors, cores of processors, or other processing units), they cause the processing unit(s) to perform the actions indicated in the instructions. Examples of computer readable media include, but are not limited to, CD-ROMs, flash drives. RAM chips, hard drives, EPROMs, etc. The computer readable media does not include carrier waves and electronic signals passing wirelessly or over wired connections. The term “software” is meant to include, where appropriate, firmware residing in read-only memory or applications stored in magnetic storage, which can be read into memory for processing by a processor. Also, in some implementations, multiple software aspects of the subject disclosure can be implemented as sub-parts of a larger program while remaining distinct software aspects of the subject disclosure. In some implementations, multiple software aspects can also be implemented as separate programs. Finally, any combination of separate programs that together implement a software aspect described here is within the scope of the subject disclosure. In some implementations, the software programs, when installed to operate on one or more electronic systems, define one or more specific machine implementations that execute and perform the operations of the software programs. A computer program (also known as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted languages, declarative or procedural languages, and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, object, or other unit suitable for use in a computing environment. A computer program may, but need not, correspond to a file in a file system. A program can be stored in a portion of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, sub programs, or portions of code). A computer program can be deployed to be executed on one computer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network. FIG.6is a conceptual diagram illustrating an example electronic system600for sensing and controlling liquid flows in infusion processes, according to aspects of the subject technology. Electronic system600may be a computing device for execution of software associated with one or more portions or steps of process600, or components and processes provided byFIGS.1-6, including but not limited to information system server30, or computing hardware within patient care device12. Electronic system600may be representative, in combination with the disclosure regardingFIGS.1-6. In this regard, electronic system600may be a personal computer or a mobile device such as a smartphone, tablet computer, laptop, PDA, an augmented reality device, a wearable such as a watch or band or glasses, or combination thereof, or other touch screen or television with one or more processors embedded therein or coupled thereto, or any other sort of computer-related electronic device having network connectivity. Electronic system600may include various types of computer readable media and interfaces for various other types of computer readable media. In the depicted example, electronic system600includes a bus608, processing unit(s)612, a system memory604, a read-only memory (ROM)610, a permanent storage device602, an input device interface614, an output device interface606, and one or more network interfaces616. In some implementations, electronic system600may include or be integrated with other computing devices or circuitry for operation of the various components and processes previously described. Bus608collectively represents all system, peripheral, and chipset buses that communicatively connect the numerous internal devices of electronic system600. For instance, bus608communicatively connects processing unit(s)612with ROM610, system memory604, and permanent storage device602. From these various memory units, processing unit(s)612retrieves instructions to execute and data to process in order to execute the processes of the subject disclosure. The processing unit(s) can be a single processor or a multi-core processor in different implementations. ROM610stores static data and instructions that are needed by processing unit(s)612and other modules of the electronic system. Permanent storage device602, on the other hand, is a read-and-write memory device. This device is a non-volatile memory unit that stores instructions and data even when electronic system600is off. Some implementations of the subject disclosure use a mass-storage device (such as a magnetic or optical disk and its corresponding disk drive) as permanent storage device602. Other implementations use a removable storage device (such as a floppy disk, flash drive, and its corresponding disk drive) as permanent storage device602. Like permanent storage device602, system memory604is a read-and-write memory device. However, unlike storage device602, system memory604is a volatile read-and-write memory, such a random access memory. System memory604stores some of the instructions and data that the processor needs at runtime. In some implementations, the processes of the subject disclosure are stored in system memory604, permanent storage device602, and/or ROM610. From these various memory units, processing unit(s)612retrieves instructions to execute and data to process in order to execute the processes of some implementations. Bus608also connects to input and output device interfaces614and606. Input device interface614enables the user to communicate information and select commands to the electronic system. Input devices used with input device interface614include, e.g., alphanumeric keyboards and pointing devices (also called “cursor control devices”). Output device interfaces606enables, e.g., the display of images generated by the electronic system600. Output devices used with output device interface606include, e.g., printers and display devices, such as cathode ray tubes (CRT) or liquid crystal displays (LCD). Some implementations include devices such as a touchscreen that functions as both input and output devices. Also, as shown inFIG.6, bus608also couples electronic system600to a network (not shown) through network interfaces616. Network interfaces616may include, e.g., a wireless access point (e.g., Bluetooth or WiFi) or radio circuitry for connecting to a wireless access point. Network interfaces616may also include hardware (e.g., Ethernet hardware) for connecting the computer to a part of a network of computers such as a local area network (“LAN”), a wide area network (“WAN”), wireless LAN, or an Intranet, or a network of networks, such as the Internet. Any or all components of electronic system600can be used in conjunction with the subject disclosure. These functions described above can be implemented in computer software, firmware or hardware. The techniques can be implemented using one or more computer program products. Programmable processors and computers can be included in or packaged as mobile devices. The processes and logic flows can be performed by one or more programmable processors and by one or more programmable logic circuitry. General and special purpose computing devices and storage devices can be interconnected through communication networks. Some implementations include electronic components, such as microprocessors, storage and memory that store computer program instructions in a machine-readable or computer-readable medium (also referred to as computer-readable storage media, machine-readable media, or machine-readable storage media). Some examples of such computer-readable media include RAM ROM, read-only compact discs (CD-ROM), recordable compact discs (CD-R), rewritable compact discs (CD-RW), read-only digital versatile discs (e.g., DVD-ROM, dual-layer DVD-ROM), a variety of recordable/rewritable DVDs DVD-RAM, DVD-RW, DVD+RW, etc.), flash memory (e.g., SD cards, mini-SD cards, micro-SD cards, etc.), magnetic and/or solid state hard drives, read-only and recordable Blu-Ray® discs, ultra density optical discs, any other optical or magnetic media, and floppy disks. The computer-readable media can store a computer program that is executable by at least one processing unit and includes sets of instructions for performing various operations. Examples of computer programs or computer code include machine code, such as is produced by a compiler, and files including higher-level code that are executed by a computer, an electronic component, or a microprocessor using an interpreter. While the above discussion primarily refers to microprocessor or multi-core processors that execute software, some implementations are performed by one or more integrated circuits, such as application specific integrated circuits (ASICs) or field programmable gate arrays (FPGAs). In some implementations, such integrated circuits execute instructions that are stored on the circuit itself. As used in this specification and any claims of this application, the terms “computer”, “server”, “processor”, and “memory” all refer to electronic or other technological devices. These terms exclude people or groups of people. For the purposes of the specification, the terms display or displaying means displaying on an electronic device. As used in this specification and any claims of this application, the terms “computer readable medium” and “computer readable media” are entirely restricted to tangible, physical objects that store information in a form that is readable by a computer. These terms exclude any wireless signals, wired download signals, and any other ephemeral signals. To provide for interaction with a user, implementations of the subject matter described in this specification can be implemented on a computer having a display device, e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor, for displaying information to the user and a keyboard and a pointing device, e.g., a mouse or a trackball, by which the user can provide input to the computer. Other kinds of devices can be used to provide for interaction with a user as well; e.g., feedback provided to the user can be any form of sensory feedback, e.g., visual feedback, auditory feedback, or tactile feedback; and input from the user can be received in any form, including acoustic, speech, or tactile input. In addition, a computer can interact with a user by sending documents to and receiving documents from a device that is used by the user; e.g., by sending web pages to a web browser on a user's client device in response to requests received from the web browser. Implementations of the subject matter described in this specification can be implemented in a computing system that includes a back end component, e.g., as a data server, or that includes a middleware component, e.g., an application server, or that includes a front end component, e.g., a client computer having a graphical user interface or a Web browser through which a user can interact with an implementation of the subject matter described in this specification, or any combination of one or more such back end, middleware, or front end components. The components of the system can be interconnected by any form or medium of digital data communication, e.g., a communication network. Examples of communication networks include a local area network (“LAN”) and a wide area network (“WAN”), an inter-network (e.g., the Internet), and peer-to-peer networks (e.g., ad hoc peer-to-peer networks). The computing system can include clients and servers. A client and server are generally remote from each other and may interact through a communication network. The relationship of client and server arises by virtue of computer programs running on the respective computers and having a client-server relationship to each other. In some implementations, a server transmits data (e.g., an HTML page) to a client device (e.g., for purposes of displaying data to and receiving user input from a user interacting with the client device). Data generated at the client device (e.g., a result of the user interaction) can be received from the client device at the server. As used herein a “user interface” (also referred to as an interactive: user interface, a graphical user interface or a UI) may refer to a network based interface including data fields and/or other control elements for receiving input signals or providing electronic information and/or for providing information to the user in response to any received input signals. Control elements may include dials, buttons, icons, selectable areas, or other perceivable indicia presented via the UI that, when interacted with (e.g., clicked, touched, selected, etc.), initiates an exchange of data for the device presenting the UI. A UI may be implemented in whole or in part using technologies such as hyper-text mark-up language (HTML), FLASH™, JAVA™, .NET™, C, C++, web services, or rich site summary (RSS). In some implementations, a UI may be included in a stand-alone client (for example, thick client, fat client) configured to communicate (e.g., send or receive data) in accordance with one or more of the aspects described. The communication may be to or from a medical device or server in communication therewith. As used herein, the terms “determine” or “determining” encompass a wide variety of actions. For example, “determining” may include calculating, computing, processing, deriving, generating, obtaining, looking up (e.g., looking up in a table, a database or another data structure), ascertaining and the like via a hardware element without user intervention. Also, “determining” may include receiving (e.g., receiving information), accessing (e.g., accessing data in a memory) and the like via a hardware element without user intervention. “Determining” may include resolving, selecting, choosing, establishing, and the like via a hardware element without user intervention. As used herein, the terms “provide” or “providing” encompass a wide variety of actions. For example, “providing” may include storing a value in a location of a storage device for subsequent retrieval, transmitting a value directly to the recipient via at least one wired or wireless communication medium, transmitting or storing a reference to a value, and the like. “Providing” may also include encoding, decoding, encrypting, decrypting, validating, verifying, and the like via a hardware element. As used herein, the term “message” encompasses a wide variety of formats for communicating (e.g., transmitting or receiving) information. A message may include a machine readable aggregation of information such as an XML document, fixed field message, comma separated message, JSON, a custom protocol, or the like. A message may, in some implementations, include a signal utilized to transmit one or more representations of the information. While recited in the singular, it will be understood that a message may be composed, transmitted, stored, received, etc. in multiple parts. In any implementation, data generated or detected can be forwarded to a “remote” device or location, where “remote,” means a location or device other than the location or device at which the program is executed. For example, a remote location could be another location (e.g., office, lab, etc.) in the same city, another location in a different city, another location in a different state, another location in a different country, etc. As such, when one item is indicated as being “remote” from another, what is meant is that the two items can be in the same room but separated, or at least in different rooms or different buildings, and can be at least one mile, ten miles, or at least one hundred miles apart. “Communicating” information references transmitting the data representing that information as electrical signals over a suitable communication channel (e.g., a private or public network). “Forwarding” an item refers to any means of getting that item from one location to the next, whether by physically transporting that item or otherwise (where that is possible) and includes, at least in the case of data, physically transporting a medium carrying the data or communicating the data. Examples of communicating media include radio or infra-red transmission channels as well as a network connection to another computer or networked device, and the Internet or including email transmissions and information recorded on websites and the like. Those of skill in the art would appreciate that the various illustrative blocks, modules, elements, components, methods, and algorithms described herein may be implemented as electronic hardware, computer software, or combinations of both. To illustrate this interchangeability of hardware and software, various illustrative blocks, modules, elements, components, methods, and algorithms have been described above generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the overall system. The described functionality may be implemented in varying ways for each particular application. Various components and blocks may be arranged differently (e.g., arranged in a different order, or partitioned in a different way) all without departing from the scope of the subject technology. It is understood that the specific order or hierarchy of steps in the processes disclosed is an illustration of example approaches. Based upon design preferences, it is understood that the specific order or hierarchy of steps in the processes may be rearranged. Some of the steps may be performed simultaneously. The accompanying method claims present elements of the various steps in a sample order, and are not meant to be limited to the specific order or hierarchy presented. The previous description is provided to enable any person skilled in the art to practice the various aspects described herein. The previous description provides various examples of the subject technology, and the subject technology is not limited to these examples. Various modifications to these aspects will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other aspects. Thus, the claims are not intended to be limited to the aspects shown herein, but is to be accorded the full scope consistent with the language claims, wherein reference to an element in the singular is not intended to mean “one and only one” unless specifically so stated, but rather “one or more.” Unless specifically stated otherwise, the term “some” refers to one or more. Pronouns in the masculine (e.g., his) include the feminine and neuter gender (e.g., her and its) and vice versa. Headings and subheadings, if any, are used for convenience only and do not limit the invention described herein. The term website, as used herein, may include any aspect of a website, including one or more web pages, one or more servers used to host or store web related content, etc. Accordingly, the term website may be used interchangeably with the terms web page and server. The predicate words “configured to”, “operable to”, and “programmed to” do not imply any particular tangible or intangible modification of a subject, but, rather, are intended to be used interchangeably. For example, a processor configured to monitor and control an operation or a component may also mean the processor being programmed to monitor and control the operation or the processor being operable to monitor and control the operation. Likewise, a processor configured to execute code can be construed as a processor programmed to execute code or operable to execute code. The term automatic, as used herein, may include performance by a computer or machine without user intervention: for example, by instructions responsive to a predicate action by the computer or machine or other initiation mechanism. The word “example” is used herein to mean “serving as an example or illustration.” Any aspect or design described herein as “example” is not necessarily to be construed as preferred or advantageous over other aspects or designs. A phrase such as an “aspect” does not imply that such aspect is essential to the subject technology or that such aspect applies to all configurations of the subject technology. A disclosure relating to an aspect may apply to all configurations, or one or more configurations. An aspect may provide one or more examples. A phrase such as an aspect may refer to one or more aspects and vice versa. A phrase such as an “implementation” does not imply that such implementation is essential to the subject technology or that such implementation applies to all configurations of the subject technology. A disclosure relating to an implementation may apply to all implementations, or one or more implementations. An implementation may provide one or more examples. A phrase such as an “implementation” may refer to one or more implementations and vice versa. A phrase such as a “configuration” does not imply that such configuration is essential to the subject technology or that such configuration applies to all configurations of the subject technology. A disclosure relating to a configuration may apply to all configurations, or one or more configurations. A configuration may provide one or more examples. A phrase such as a “configuration” may refer to one or more configurations and vice versa. | 84,163 |
11857763 | DETAILED DESCRIPTION Medicine delivery systems and methods provided herein may be used and performed, respectively, by a user, for example, a person with diabetes (PWD). The PWD may live with type 1, type 2, or gestational diabetes. In some cases, a user can be a healthcare professional or caregiver for a PWD. Methods and systems provided herein can use information from a glucose measurement device (e.g., a continuous glucose monitor) to have up-to-date blood glucose data (e.g., a plurality of blood glucose data points each hour) for the PWD in order to determine how to adjust basal insulin delivery rates. In some cases, methods and systems provided herein can use blood glucose data from both one or more continuous glucose monitors and one or more blood glucose meters. Methods and systems provided herein can be part of a hybrid closed-loop system (for example, where basal rates can be adjusted automatically and the PWD can manually enter or deliver a bolus). In some cases, methods and systems provided herein can be part of a fully closed-loop system (for example, where basal rates can be adjusted automatically and boluses can be delivered automatically). In some cases, “up-to-date” may mean less than 1 hour old, less than 30 minutes old, or less than 15 minutes old. Methods and systems provided herein can use a model to predict multiple future blood glucose levels for multiple different basal insulin delivery profiles or basal insulin delivery rates, and select one of the basal insulin delivery profiles or basal insulin delivery rates based on prediction of which profile or rate will approximate a target blood glucose level, or more specifically, select the profile that minimizes the differences between the predicted future blood glucose values and one or more target blood glucose values. In some cases, the profile that minimizes, lessons, or lowers variations from one or more target blood glucose levels in the future may be selected. The selected basal profile can then be delivered to the PWD at least until a process of evaluating different basal insulin delivery profiles or rates is repeated. In some cases, methods and systems provided herein can repeat a process of evaluating multiple different basal insulin delivery profiles or basal insulin delivery rates at a time interval that is less than the time interval for the plurality of future predicted blood glucose values. For example, in some cases, the time interval between evaluating and selecting from multiple different basal insulin delivery profiles or basal insulin delivery rates can be less than one hour while the plurality of future predicted blood glucose values can extend over a time interval of at least two hours into the future. In some cases of methods and systems provided herein, each of the evaluated basal insulin delivery profiles or rates can extend for a time interval greater than the time interval between evaluation processes. In some cases, methods and systems provided herein can evaluate insulin delivery profiles and rates that extend at least two hours into the future and predicted blood glucose values can also be predicted over a time interval that extends at least two hours into the future. In some cases, the profiles/rates and time interval of predicted future blood glucose values extends at least three hours into the future. In some cases, the profiles/rates and time interval of predicted future blood glucose values extends a period of time (e.g., at least four hours) into the future. In some cases, the profiles/rates and time interval of predicted future blood glucose values extends at least five hours into the future. As used herein, the term blood glucose level may include any measurement that estimates or correlates with blood glucose level, such as a detection of glucose levels in interstitial fluids, urine, or other bodily fluids or tissues. The different basal insulin delivery profiles or rates for each evaluation process can be generated using any suitable techniques. In some cases, multiple profiles or delivery rates are generated using one or more user-specific dosage parameters. In some cases, one or more users-specific dosage parameters can be entered by a user, calculated by information entered by a user, and/or calculated by monitoring data generated from the PWD (e.g., monitoring insulin delivery rates and blood glucose data while the PWD is using a pump in an open-loop mode). In some cases, methods and systems provided herein can modify user-specific dosage parameters over time based on one or more selected basal insulin delivery profiles or rates and/or other data obtained from the PWD. In some cases, the user-specific dosage parameters can be dosage parameters that are commonly used in the treatment of diabetes, such as average total daily insulin, total daily basal (TDB) insulin, average basal rate, insulin sensitivity factor (ISF), and carbohydrate-to-insulin ratio (CR). For example, in some cases, a PWD's average basal rate can be used to calculate multiple different basal insulin delivery profiles based on multiples or fractions of the average basal rate used over different intervals of time. In some cases, methods and systems provided herein can use time-interval-specific user-specific dosage parameters (e.g., a time-interval-specific baseline basal rate). In some cases, methods and systems provided herein can make adjustments to time-interval-specific user-specific dosage parameters for each time interval for where a delivered basal rate varies from a baseline basal rate for that time interval. In some cases, user-specific dosage parameters are specific for time intervals of two hours or less, one hour or less, thirty minutes or less, or fifteen minutes or less. For example, in some cases, methods and systems provided herein can store a baseline basal rate for the hour between 1 PM and 2 PM, and can adjust the baseline basal rate for that hour up if the method or system delivers more basal insulin during that time period and adjust the baseline basal rate down if the method or system delivers less basal insulin during that time period. In some cases, adjustments to user-specific dosage parameters can be based on a threshold variation and/or can be limited to prevent excessive adjustments to user-specific dosage parameters. For example, in some cases, a daily adjustment to a user-specific dosage parameter can be limited to less than 10%, less than 5%, less than 3%, less than 2%, or to about 1%. In some cases, an adjustment to a baseline basal rate is less than a difference between the amount of basal insulin actually delivered and the baseline basal for a specific period of time (e.g., if a baseline basal rate is 1 U/hour and systems or methods provided herein actually delivered 2U for the previous hour, the adjustment to any baseline basal rate based on that difference would be less than 1U/hour). Methods and systems provided herein can use any appropriate model to predict multiple future blood glucose values. In some cases, predictive models can use one or more current or recent blood glucose measurements (e.g., from a blood glucose meter and/or a continuous glucose monitor), estimates of rates of change of blood glucose levels, an estimation of unacted carbohydrates, and/or an estimation of unacted insulin. In some cases, predictive models can use one or more user-specific dosage parameters in predicting multiple blood glucose values over a future time interval for multiple different basal insulin delivery profiles or rates over that same future time interval. As discussed above, that future time interval can be at least two hours, at least three hours, or at least four hours, at least five hours, etc. User-specific dosage parameters, which can be time-interval-specific, can also be used in determining an estimation of unacted carbohydrates and/or an estimation of unacted insulin. In some cases, an estimation of unacted carbohydrates and/or an estimation of unacted insulin can use a simple decay function. In some cases, an estimate of unacted insulin can be determined using an Insulin On Board (IOB) calculation, which is common in the art of treating diabetes. In some cases, an IOB calculation used in a predictive model used in methods and systems provided herein can consider insulin delivered to the PWD during the delivery of a bolus. In some cases, the IOB calculation can additionally add or subtract to the IOB based on changes to the basal insulin delivery rate from a baseline basal rate. In some cases, an estimate of unacted carbohydrates can be determined using a Carbohydrates On Board (COB) calculation, which can be based on a decay function and announced meals. In some cases, predictive models used in methods and systems provided herein can also consider the non-carbohydrate components of a meal. In some cases, methods and systems provided herein can infer an amount of carbohydrates from an unannounced meal due to a spike in up-to-date blood glucose data. In some cases, predictive models used in methods and systems provided herein can additionally consider additional health data or inputs, which may indicate that the PWD is sick, exercising, experiencing menses, or some other condition that may alter the PWD's reaction to insulin and/or carbohydrates. In some cases, at least an IOB, a COB, an insulin sensitivity factor (ISF), and a carbohydrate-to-insulin ratio (CR) are used to predict future blood glucose values for each evaluated basal insulin delivery profile or rate. Methods and systems provided herein can set one or more blood glucose targets using any suitable technique. In some cases, a blood glucose target can be fixed, either by a user or preprogrammed into the system. In some cases, the target blood glucose level can be time interval specific (e.g., based on diurnal time segments). In some cases, a user can temporarily or permanently adjust the target blood glucose level. In some cases, methods and systems provided herein can analyze the variability of blood glucose data for specific days of the week and/or based on other physiological patterns and adjust the blood glucose targets for that individual based on the specific day of the week or based on other physiological patterns. For example, a PWD may have certain days of the week when they exercise and/or PWD may have different insulin needs based on a menses cycle. Methods and systems provided herein can evaluate each basal insulin delivery profile or rate to select the profile or rate that minimizes a variation from the one or more blood glucose targets using any appropriate method. In some cases, methods and systems provided herein can use a cost function to evaluate differences between the predicted blood glucose values for each basal insulin delivery profile or rate and blood glucose targets, potentially specified for a diurnal time segment. Methods and systems provided herein can then select a basal profile or rate that produces the lowest cost function value. Methods and systems provided herein can use any suitable cost function. In some cases, cost functions can sum the absolute value of the difference between each predicted blood glucose value and each blood glucose target. In some cases, cost functions used in methods and systems provided herein can use a square of the difference. In some cases, cost functions used in methods and systems provided herein can assign a higher cost to blood glucose values below the blood glucose target in order reduce the risk of a hypoglycemic event. In some cases, the cost function can include a summation of the absolute values of a plurality of predicted deviations, squared deviations, log squared deviations, or a combination thereof. In some cases, a cost function can include variables unrelated to the predicted blood glucose values. For example, a cost function can include a penalty for profiles that do not deliver 100% of the BBR, thus adding a slight preference to use 100% of BBR. In some cases, methods and systems provided herein can include a cost function that provides a slight preference to keep the existing basal modification for every other interval (e.g., a second 15 minute segment), which could reduce the variability in basal insulin delivery rates in typical situations, but allow for more critical adjustments. Methods and systems provided herein can receive various inputs from a user related to the delivery of basal insulin. In some cases, a user may input a fear of hypoglycemia (FHI) index. The FHI may indicate the preference for or reticence to experience certain blood glucose levels by the PWD. For example, the FHI may indicate that the PWD prefers “high” blood glucose levels (e.g., blood glucose levels above a threshold); or as another example, the FHI may indicate that the PWD is concerned about “going low” (e.g., blood glucose levels below a threshold). In some cases, the FHI may correspond to a threshold and an acceptable probability of crossing the threshold, including using the threshold to signify going high or using the threshold to signify going low, or both. In some cases, a probability of the PWD crossing the threshold may be determined and a baseline basal insulin rate may be modified to more closely align the acceptable probability of crossing the threshold with the actual probability of crossing the threshold. Additionally or alternatively, the FHI may be used in other ways in methods and systems of the present disclosure. For example, modification of the baseline basal insulin rate for a diurnal period may be modified one way for a high FHI and another way for a low FHI. As another example, multiple profiles of insulin delivery steps may use one set of possible steps for a high FHI, and another set of possible steps for a low FHI. Methods and systems provided herein can modify or alter an insulin delivery profile or rate in any number of ways. In some cases, a user may select a temporary override to indicate a user preference for a particular blood glucose level. For example, the PWD may indicate that they are going for a long drive and do not want to have their blood glucose levels drop below a certain level, and so may designate a target blood glucose level higher than their normal target blood glucose level, which may be set for a particular or indefinite length of time. In some cases, methods and systems provided herein may modify or otherwise select a new profile or rate from multiple profiles that corresponds to the blood glucose level from the temporary override. In some cases, methods and systems provided herein can permit a user to merely indicate a reduced tolerance for the risk of going low and can determine a temporary blood glucose level based on the variability of blood glucose data for that PWD for previous days (optionally for a particular diurnal time segment). Methods and systems provided herein can store a plurality of user-specific dosage parameters (e.g., BBR, CR, and ISF) as different values for a plurality of different diurnal time segments. As used herein, the term “diurnal time segments” may refer to periods of time during each day, such that the methods and systems will repeat use of each diurnal-specific user-specific dosage parameter during the same time on subsequent days if a stored diurnal-specific user-specific dosage parameter is not modified or change, thus the use of the stored diurnal-specific user-specific dosage parameter will wrap each day. Methods and systems provided herein, however, can be adapted to make daily (or more or less frequent) adjustments to each diurnal-specific user-specific dosage parameter based on the operation of the system. Methods and systems provided herein may additionally store settings or adjustments for specific days of the week or for other repeating cycles. After a basal insulin delivery profile or rate is selected, methods and systems provided herein can include the delivery of basal insulin to the PWD according to the selected basal insulin profile or rate for any suitable period of time. In some cases, methods and systems provided herein may supply basal insulin according to the selected basal insulin delivery profile or rate for a predetermined amount of time that may be less than the time interval of the evaluated basal insulin delivery profiles or rates. For example, methods and systems provided herein may analyze projected blood glucose values for basal insulin delivery profiles or rates that last over the next four hours but repeat the process of selecting a new basal insulin delivery profile or rate every fifteen minutes. In some cases, methods and systems provided herein can delay or suspend basal insulin delivery during the delivery of a bolus, which can be triggered by a user requesting a bolus. As used herein, “basal insulin delivery” has its normal and customary meaning within the art of the treatment of diabetes. Although basal rates are expressed as a continuous supply of insulin over time, basal insulin delivery may constitute multiple discrete deliveries of insulin at regular or irregular intervals. In some cases, methods and systems provided herein may only be able to deliver insulin in discrete fractions of a unit. For example, some insulin delivery devices can only deliver insulin in a dose that are an integer multiple of 0.05 units or 0.1 units. In some cases, a delivery of basal insulin can include a delivery of insulin at predetermined time intervals less than or equal to fifteen minutes apart or less, ten minutes apart or less, or five minutes apart or less. In some cases, the time interval between discrete basal insulin deliveries can be determined based on the basal insulin delivery rate (e.g., a basal rate of 1.0 units/hour might result in the delivery of 0.1 units every six minutes). As used herein, the term “bolus” has its normal and customary meaning with the art of the treatment of diabetes, and can refer to a bolus delivered in order to counteract a meal (i.e., a meal-time bolus) and/or to correct for elevated blood glucose levels (i.e., a correction bolus). Methods and systems provided herein can in some cases include multiple delivery modes. In some cases, methods and systems provided herein can monitor the presence of blood glucose using one or more blood glucose measuring devices or methods, control or monitor the dispensation of medicine, and determine and/or update the user-specific dosage parameters regardless of the operating mode. For example, possible operating modes could include closed-loop or hybrid closed-loop modes that automatically adjust basal rates based on continuous glucose monitoring data (CGM) and other user-specific dosage parameters, e.g., baseline basal rate (BBR), insulin sensitivity factor (ISF), and carbohydrate-to-insulin ratio (CR), modes that can use blood glucose monitor (BGM) data to update user-specific dosage parameters (e.g., BBRs, ISFs, and CRs) for different time blocks over longer periods of time, manual modes that require a patient to manually control the therapy program using an insulin pump, and advisory modes that recommend dosages for a PWD to inject using an insulin pen or syringe. By determining optimized control parameters that work across delivery modes, systems and methods provided herein can provide superior analyte control even when a PWD switches to a different delivery mode. For example, methods and systems provided herein may be forced to switch away from a hybrid closed-loop delivery mode that adjusts basal insulin delivery away from a BBR if a continuous glucose monitor malfunctions or the system otherwise loses access to continuous data. In some cases, data can be collected when the system is in an advisory or manual mode to optimize control parameters in preparation for a PWD to switch to a hybrid closed-loop system (e.gk, in preparation for a PWD to start use of a continuous glucose monitor (CGM) and/or an insulin pump). Methods and systems provided herein can include an insulin pump and at least one blood glucose measurement device in communication with the insulin pump. In some cases, the blood glucose measurement device can be a CGM adapted to provide blood glucose measurements at least every fifteen minutes. In some cases, methods and systems provided herein include a CGM adapted to provide blood glucose measurements at least every ten minutes. In some cases, methods and systems provided herein include a CGM adapted to provide blood glucose measurements every five minutes. Methods and systems provided herein additionally include a controller adapted to determine an amount of basal insulin for delivery to a PWD and memory to store multiple user-specific dosage parameters. In some cases, the controller can be part of an insulin pump. In some cases, a controller can be part of a remote device, which can communicate wirelessly with an insulin pump. In some cases, the controller can communicate wirelessly with a CGM. In some cases, methods and systems provided herein can additionally include a user interface for displaying data and/or receiving user commands, which can be included on any component of a system provided herein. In some cases, the user interface can be part of smartphone. In some cases, a user can input information on the user interface to trigger methods and systems provided herein to deliver a bolus of insulin. In some cases, methods and systems provided herein can use a blood glucose meter adapted to use a test strip as a blood glucose measurement device. In some cases, methods and systems provided herein can additionally include an insulin pen, which can optionally communicate wirelessly with a controller. Example Diabetes Management System FIG.1depicts an example diabetes management system10including a pump assembly15for insulin and a continuous glucose monitor50. As shown, the continuous glucose monitor50is in wireless communication with pump assembly15. In some cases, a continuous glucose monitor can be in wired communication with pump assembly15. In some cases not shown, a continuous glucose monitor can be incorporated into an insulin pump assembly. As shown, pump assembly15can include a reusable pump controller200that forms part of the pump assembly15. In some cases, reusable pump controller200is adapted to determine one or more basal delivery rates. In some cases, continuous glucose monitor50can act as a controller adapted to communicate basal delivery rates to pump assembly15. Pump assembly15, as shown, can include reusable pump controller200and a disposable pump100, which can contain a reservoir for retaining insulin. A drive system for pushing insulin out of the reservoir can be included in either the disposable pump100or the reusable pump controller200in a controller housing210. Reusable pump controller200can include a wireless communication device247, which can be adapted to communicate with a wireless communication device54of continuous glucose monitor50and other diabetes devices in the system, such as those discussed below. In some cases, pump assembly15can be sized to fit within a palm of a hand5. Pump assembly15can include an infusion set146. Infusion set146can include a flexible tube147that extends from the disposable pump100to a subcutaneous cannula149that may be retained by a skin adhesive patch (not shown) that secures the subcutaneous cannula149to the infusion site. The skin adhesive patch can retain the cannula149in fluid communication with the tissue or vasculature of the PWD so that the medicine dispensed through tube147passes through the cannula149and into the PWD's body. The cap device130can provide fluid communication between an output end of an insulin cartridge (not shown) and tube147of infusion set146. Although pump assembly15is depicted as a two-part insulin pump, one piece insulin pumps are also contemplated. Additionally, insulin pump assemblies used in methods and systems provided herein can alternatively be a patch pump. Continuous glucose monitor50(e.g., a glucose sensor) can include a housing52, a wireless communication device54, and a sensor shaft56. The wireless communication device54can be contained within the housing52and the sensor shaft56can extend outward from the housing52. In use, the sensor shaft56can penetrate the skin20of a user to make measurements indicative of the PWD's blood glucose level or the like. In some cases, the sensor shaft56can measure glucose or another analyte in interstitial fluid or in another fluid and correlate that to blood glucose levels. In response to the measurements made by the sensor shaft56, the continuous glucose monitor50can employ the wireless communication device54to transmit data to a corresponding wireless communication device247housed in the pump assembly15. In some cases, the continuous glucose monitor50may include a circuit that permits sensor signals (e.g., data from the sensor shaft56) to be communicated to the wireless communication device54. The wireless communication device54can transfer the collected data to reusable pump controller200(e.g., by wireless communication to the wireless communication device247). Additionally or alternatively, the system10may include another glucose monitoring device that may utilize any of a variety of methods of obtaining information indicative of a PWD's blood glucose levels and transferring that information to reusable pump controller200. For example, an alternative monitoring device may employ a micropore system in which a laser porator creates tiny holes in the uppermost layer of a PWD's skin, through which interstitial glucose is measured using a patch. In the alternative, the monitoring device can use iontophoretic methods to non-invasively extract interstitial glucose for measurement. In other examples, the monitoring device can include noninvasive detection systems that employ near IR, ultrasound or spectroscopy, and particular implementations of glucose-sensing contact lenses. In other examples, the monitoring device can include detection of glucose levels using equilibrium fluorescence detectors (e.g., sensors including a diboronic acid receptor attached to a fluorophore). Furthermore, it should be understood that in some alternative implementations, continuous glucose monitor50can be in communication with reusable pump controller200or another computing device via a wired connection. In some cases, continuous glucose monitor50can be adapted to provide blood glucose measurements for a PWD when in use for the PWD at regular or irregular time intervals. In some cases, continuous glucose monitor50can detect blood glucose measurements at least every thirty minutes, at least every fifteen minutes, at least every ten minutes, at least every five minutes, or about every minute. In some cases, continuous glucose monitor50can itself determine a basal delivery rate using methods provided herein and communicate that basal rate to the pump assembly15. In some cases, continuous glucose monitor50can transmit blood glucose measurement data to reusable pump controller200and reusable pump controller200can use methods provided herein to determine a basal delivery rate. In some cases, a remote controller can receive glucose data from continuous glucose monitor50, determine a basal delivery rate using methods provided herein, and communicate the basal rate to pump assembly15. Diabetes management system10may optionally include a blood glucose meter70(e.g., a glucose sensor). In some cases, blood glucose meter70can be in wireless communication with reusable pump controller200. Blood glucose meter70can take a blood glucose measurement using one or more test strips (e.g., blood test strips). A test strip can be inserted into a strip reader portion of the blood glucose meter70and then receive the PWD's blood to determine a blood glucose level for the PWD. In some cases, the blood glucose meter70is configured to analyze the characteristics of the PWD's blood and communicate (e.g., via a BLUETOOTH® wireless communication connection) the information to reusable pump controller200. In some cases, a user can manually input a glucose meter reading. The blood glucose meter70can be manually operated by a user and may include an output subsystem (e.g., display, speaker) that can provide the user with blood glucose readings that can be subsequently entered into the controller200or user interface to collect the data from an unconnected BGM into the system10. The blood glucose meter70may be configured to communicate data (e.g., blood glucose readings) obtained to reusable pump controller200and/or other devices, such as the mobile computing device60(e.g., a control device). Such communication can be over a wired and/or wireless connection, and the data can be used by system10for a number of functions (e.g., calibrating the continuous glucose monitor50, confirming a reading from the continuous glucose monitor50, determining a more accurate blood glucose reading for a bolus calculation, detecting a blood glucose level when the continuous glucose monitor50is malfunctioning). In some cases, the system10can further include a mobile computing device60that can communicate with the reusable pump controller200through a wireless and/or wired connection with the reusable pump controller200(e.g., via a BLUETOOTH® wireless communication connection or a near-field communication connection). In some cases, the mobile computing device60communicates wirelessly with other diabetes devices of system10. The mobile computing device60can be any of a variety of appropriate computing devices, such as a smartphone, a tablet computing device, a wearable computing device, a smartwatch, a fitness tracker, a laptop computer, a desktop computer, and/or other appropriate computing devices. In some cases (for example, where the reusable pump controller200does not determine a basal delivery rate), the mobile computing device60can receive and log data from other elements of the system10and determine basal delivery rates using methods provided herein. In some cases, a user can input relevant data into the mobile computing device60. In some cases, the mobile computing device60can be used to transfer data from the reusable pump controller200to another computing device (e.g., a back-end server or cloud-based device). In some cases, one or more methods provided herein can be performed or partially performed by the other computing device. In some cases, the mobile computing device60provides a user interface (e.g., graphical user interface (GUI), speech-based user interface, motion-controlled user interface) through which users can provide information to control operation of the reusable pump controller200and the system10. For example, the mobile computing device60can be a mobile computing device running a mobile app that communicates with reusable pump controller200over short-range wireless connections (e.g., BLUETOOTH® connection, Wi-Fi Direct connection, near-field communication connection, etc.) to provide status information for the system10and allow a user to control operation of the system10(e.g., toggle between delivery modes, adjust settings, log food intake, change a fear of hypoglycemia index (FHI), confirm/modify/cancel bolus dosages, and the like). Optionally, system10may include a bolus administering device80(e.g., a syringe, an insulin pen, a smart syringe with device communication capabilities, or the like) through which bolus dosages can be manually administered to a PWD. In some cases, a suggested dosage for a bolus to be administered using the bolus administering device80can be output to a user via the user interface of reusable pump controller200and/or the user interface of the mobile computing device60. In some cases, the bolus administering device80can communicate through a wired and/or wireless connection with reusable pump controller200and/or the mobile computing device60. In some cases, system10can allow users to input insulin deliveries made using a syringe or insulin pen. Operation of a Diabetes Management System FIG.2depicts an example method202for operation of a diabetes management system, such as system10depicted inFIG.1. As shown inFIG.2, a system can receive user inputs, such as user inputs at blocks251and252, which can be used to provide initial settings, such as one or more target blood glucose values that may be used or determined at block261and/or one or more user-specific dosage parameters that may be used or determined at block262. In some cases, user inputs at blocks251and252can be entered by a PWD, a caregiver for the PWD, or a healthcare professional. In some cases, user inputs at blocks251and252can be entered on a mobile computing device60, such as a smartphone. Based on the user-specific dosage parameters, the method202can generate multiple basal insulin delivery profiles and/or rates at block263. In some cases, the plurality of basal insulin delivery profiles and/or rates can be based upon one or more baseline basal rates. At block264, the method202can analyze each basal delivery profile or rate generated at block263based on variations of predicted future blood glucose values from one or more target blood glucose values (such as the target blood glucose values from block261) using blood glucose data from a continuous glucose monitor (CGM) or blood glucose meter (BGM), such as generated in block271. In some cases, the blood glucose data can be from the continuous glucose monitor50from the system10ofFIG.1. As will be discussed below, predicted blood glucose values for each generated basal delivery profile or rate can use user-specific dosage parameters (for example, those determined or otherwise adjusted at block262). Additionally, predicted blood glucose values can include inputs regarding previous dosages of insulin and/or food consumption (e.g., estimates of carbohydrates consumed). In some cases, predicted blood glucose values used at block264can consider data indicative of exercise, sickness, or any other physical state that might impact blood glucose levels in a PWD. Based on an analysis of a variation of predicted blood glucose levels performed at block264, a basal delivery profile or rate generated at block263can be selected at block265, and the system can deliver basal insulin according to that selected basal delivery profile or rate to the PWD for a select period of time at block272. In some cases, the pump assembly15of system10ofFIG.1can be used to deliver the insulin. In some cases, the blocks263,264,265, and272can each be conducted by reusable pump controller00of system10. In some cases, the blocks271,263,264, and265can all be conducted by continuous glucose monitor50of system10, with data regarding the selected delivery rate being sent to reusable pump controller200. In some cases, the blocks251,252,261,262,263,264, and265can all be conducted on mobile computing device60of system10ofFIG.1, with data regarding the selected delivery rate being sent to reusable pump controller200from the mobile computing device60. Methods and systems provided herein can additionally update or adjust user-specific dosage parameters at block262and can update or adjust the blood glucose targets at block261based on the selected basal delivery profiles and/or rates selected at block265or based on blood glucose data obtained at block271. In some cases, at block281, periods of time when a selected basal delivery was different from a baseline basal rate for that period of time can be detected. For these select periods of time (e.g., diurnal time segments), at block262the user-specific dosage parameters can be adjusted for that period of time. For example, if the selected basal delivery for a time block exceeds the baseline basal rate for that time block, at block262the system10can increase the baseline basal rate for that time block (e.g., a diurnal period) or some other related time block (such as the preceding diurnal period). For example, if the selected basal delivery from 2 PM to 3 PM exceeded the baseline basal rate for that time, the system10may increase the baseline basal rate for 2 PM to 3 PM or may adjust the baseline basal rate for 1 PM to 2 PM, 12 PM to 1 PM and/or 11 AM to 12 PM. In some cases, each adjustment to a baseline basal rate is less than the difference between the baseline basal rate and the selected basal delivery. In some cases, each adjustment can be a predetermined amount (e.g., baseline basal rate adjusted up or down by 0.5 units/hour, 0.3 units/hour, 0.1 units per hour) or percentage (e.g., 5%, 3%, 1%), which can limit the change to the user-specific dosage parameters due to an irregular event. At block283, the variability of blood glucose data can be analyzed to make adjustments to the blood glucose target(s) at block261. For example, at block283, a blood glucose data distribution can be determined for a diurnal period (e.g., between 1 AM and 2 AM) to determine a measure of dispersion of blood glucose values for the PWD during that diurnal period, and at block261adjustments can be made to the blood glucose target for that diurnal period, and/or adjacent periods, based on the measure of dispersion. Each of the processes discussed in regards toFIG.2are discussed at further length below. Setting Initial User-Specific Dosage Parameters Systems and methods provided herein can use multiple user-specific dosage parameters for a PWD in order to determine rates of basal insulin delivery and optionally amounts of bolus insulin delivery. In some cases, initial user-specific dosage parameters can be set by a healthcare professional. In some cases, data entered by a user (e.g., the PWD, the PWD's caregiver, or a health care professional) can be used to estimate one or more user-specific dosage parameters. For example,FIG.2depicts a method where a user enters at least one dosage parameter at block252. In some cases, multiple user-specific dosage parameters can be set for multiple diurnal time segments. In some cases, different user-specific dosage parameters can have diurnal time segments of the same length of time or different lengths of time. In some cases, an initial setting for each user-specific dosage parameter can be set at the same value for each diurnal time segment, but the user-specific dosage parameter for each diurnal time segment can be independently adjusted in the methods and systems provided herein. In some cases, users (e.g., health care professionals) can input different user-specific dosage parameter values for different diurnal time segments. Methods and systems provided herein can, in some cases, use user-specific dosage parameters that are commonly used in the treatment of diabetes. For example, methods and systems provided herein can ask a user to input one or more of an average Total Daily Dose (TDD) of insulin, a total daily basal (TDB) dose of insulin, an average basal rate (ABR) (which can be used as an initial baseline basal rate (BBR) in methods and systems provided herein), an insulin sensitivity factor (ISF), and/or a carbohydrate-to-insulin ratio (CR). In some cases, methods and systems provided herein can ask for a weight, age, or combination thereof of a PWD to estimate one or more user-specific dosage parameters. In some cases, methods and systems will store a BBR, an ISF, and a CR, which can each be set for multiple different time blocks over a repeating period of time (e.g., fifteen, thirty, sixty, or one hundred twenty minute diurnal periods). As will be discussed in further detail below, methods and systems provided herein can adjust user-specific dosage parameters for each of the diurnal periods in order to personalize the delivery of insulin for the PWD in order to minimize risks for the PWD. Methods and systems provided herein can ask for or permit a user to input a variety of different user-specific dosage parameters or dosage proxies to determine values for the initial settings of one or more user-specific dosage parameters and/or blood glucose targets. In some cases, the inputs can be limited to a Total Daily Basal (TDB) amount of insulin and a Fear of Hypoglycemia Index (FHI). In some cases, the inputs can be limited to a Total Daily Dose (TDD) amount of insulin and a FHI. In some cases, the TDB or TDD can be used determine the initial baseline basal rate (BBR), the initial carbohydrate-to-insulin ratio (CR), and the initial insulin sensitivity factor (ISF) based on mathematical relationships among and between for BBR, CR, ISF, TDB, and TDD. In some cases, a user can also set an initial ISF and CR. In some cases, a user (e.g., a health care professional) can optionally input any combination of BBR, CR, ISF, TDB, and TDD, and at least the initial BBR, initial CR, and initial ISF can be based on the values entered. For example, in some cases, a relationship between initial TDB, TDD, BBR, CR, and ISF can be expressed as follows: TDD [u/day]=2 x TDB [u/day]=1800/ISF [mg/dL/u or[mmol/u]=400/CR [g/u]=48 hours/day x BBR [u/hour]. In some cases, the mathematical equation used to estimate ISF, CR, and BBR can use non-linear relationships between BBR, ISF, and CR. Methods and systems provided herein can also make adjustments to user-entered user-specific dosage parameters prior to initial use. In some cases, methods and systems provided herein adjust user entered initial BBR, CR, and/or ISF values based on mathematical relationships among and between the initial BBR, CR, and ISF values. In some cases, if an entered ISF and an entered CR are outside of a predefined relationship between BBR, CR, and ISF, methods and systems provided herein will calculate a CR and an ISF that meets a predetermined relationship between BBR, CR, and ISF while minimizing a total change from the entered values for ISF and CR. In some cases, the predetermined relationship permits a range of CR values for each ISF value, permits a range of ISF values for each CR value, and permits a range of ISF and CR values for each BBR value. In some cases, the predetermined relationship represents a confidence interval for empirical data regarding relationships between basal rates, ISF, and CR values for a population of PWDs. In some cases, if an entered ISF, BBR, and/or CR are outside of a predefined relationship between BBR, CR, and ISF, methods and systems of the present disclosure may notify the user of the deviation from the predefined relationship. Additionally or alternatively, a healthcare provider override may be required to include ISF, BBR, and/or CR values outside of the predefined relationship as the initial user-specific dosage parameters. Setting Initial Blood Glucose Targets Initial blood glucose targets can be set or determined using any suitable technique. In some cases, blood glucose targets can be preprogrammed on memory within a system or device provided herein. In some cases, there can be a single blood glucose target preprogrammed into the system that does not change. In some cases, the diurnal time segments can each have a preprogrammed blood glucose target. In some cases, a user can program one or more blood glucose targets, which can be set differently for different periods of time. In some cases, a user can program the typical sleeping schedule, exercise schedule, and/or meal schedule for a PWD, and methods and systems provided herein can select lower blood glucose targets for sleep times and higher blood glucose targets around meal times and/or exercise times. In some cases, historical continuous glucose monitor data for the PWD prior to the PWD using the system can be used to set initial blood glucose targets (either for specific diurnal periods or for an entire day). In some cases, methods provided herein can have a PWD wear a CGM for a preliminary period of time (e.g., at least twenty-four hours, at least forty-eight hours, at least five days, or at least ten days) prior to allowing the methods and systems provided herein from delivering insulin at rates other than the BBR to detect blood glucose variability data for the PWD to set one or more initial blood glucose targets. In some cases, such as shown inFIG.2at block251, a user can enter a fear of hypoglycemia index (FHI), which can be used to determine and/or adjust blood glucose targets. An FHI can be represented to the user in a number of ways. In some cases, the FHI can be represented to the user as an aggressiveness index, which could be set at “prefer high,” “prefer low,” or “prefer moderate.” In some cases, the FHI can be represented to the user as a target blood glucose level or target average blood glucose level (e.g., 100 mg/dl, 120 mg/dl, or 140 mg/dl). In some cases, the FHI can be represented to the user as a target A1C level. In some cases, the FHI can be represented to the user as a probability of going above or below a certain threshold (e.g., a five percent chance of going below 80 mg/dl, or a three percent chance of going above 200 mg/dl). In these and other cases, a user interface may be generated with an interactive feature (e.g., radio buttons, check boxes, hyperlinked images/text, drop-down list, etc.) that a user can interact with to make a selection of the FHI. In some cases, the PWD may interact with the interface to select the FHI, and in some cases, the user can be a health care professional that selects the FHI. In some cases, each possible FHI value can correspond to a preprogrammed initial blood glucose target. For example, an FHI of “prefer high” might correspond to a preprogrammed initial blood glucose target of 140 mg/dl, an FHI of “prefer moderate” might correspond to a preprogrammed initial blood glucose target of 120 mg/dl, and an FHI of “prefer low” might correspond to a preprogrammed initial blood glucose target of 100 mg/dl. As will be discussed below, initial blood glucose targets can be adjusted over time based on data collected in methods and systems provided herein. Modes of Operation Methods and systems provided herein can in some cases include multiple delivery modes. In some cases, methods and systems provided herein can monitor the presence of blood glucose using one or more blood glucose measuring devices or methods, control or monitor the dispensation of insulin, and determine and/or update the user-specific dosage parameters regardless of the operating mode. For example, possible operating modes could include closed-loop or hybrid closed-loop modes that automatically adjust basal rates based on continuous glucose monitoring data (CGM) and other user-specific dosage parameters (e.g., BBR, ISF, and CR), modes that can use blood glucose monitor (BGM) data to update user-specific dosage parameters (e.g., BBRs, ISFs, and CRs) for different time blocks over longer periods of time, manual modes that require a patient to manually control the therapy program using an insulin pump, and advisory modes that recommend dosages for a user to inject using an insulin pen or syringe. By determining optimized control parameters that work across delivery modes, systems and methods provided herein can provide superior blood glucose control even when a PWD switches to a different delivery mode. For example, methods and systems provided herein may be forced to switch away from a hybrid closed-loop delivery mode that adjusts basal insulin delivery away from a BBR if a continuous glucose monitor malfunctions or the system otherwise loses access to continuous data, yet still use a personalized ISF and CR for calculating correction and/or mealtime bolus amounts. In some cases, data can be collected when the system is in an advisory or manual mode to optimize control parameters in preparation for a PWD to switch to a hybrid closed-loop system (e.g., in preparation for a PWD to start use of a continuous glucose monitor (CGM) and/or an insulin pump). In some cases, the use of a closed-loop delivery mode that adjusts basal insulin delivery away from a BBR may be prevented until a sufficient amount of current blood glucose data is available (e.g., the insulin delivery according to multiple profiles that can occur at blocks263,264,265, and272ofFIG.2may not occur until sufficient CGM and/or BGM data is collected at the block271ofFIG.2). In some cases, systems and methods provided herein can deliver insulin at the BBR rate for each diurnal period when insufficient blood glucose data is available. In some cases, methods and systems provided herein can switch between open-loop and closed-loop modes based on whether there are a predetermined number of authenticated blood glucose measurements from a continuous glucose monitor within a predetermined period of time (e.g., at least two authenticated blood glucose data points within the last twenty minutes). Automating Basal Insulin Delivery Systems and methods provided herein can automate basal insulin delivery based on one or more stored user-specific dosage parameters (e.g., BBR, ISF, CR), one or more blood glucose targets, and/or blood glucose data. The example method depicted inFIG.2depicts an example process of automating basal insulin delivery as blocks263,264,265, and272. Methods and systems provided herein can use a model predictive control system that projects multiple future blood glucose levels for a future time period for multiple possible basal insulin delivery profiles and/or rates over that future time period and determines which of the multiple possible basal insulin delivery profiles and/or rates will produce future blood glucose values that approximate one or more blood glucose targets. Methods and systems provided herein can produce improved control as compared to control algorithms that merely make adjustments to basal insulin delivery without evaluating multiple possible basal insulin delivery profiles or rates. In some cases, methods and systems provided herein can predict future blood glucose values at least two hours, or at least three hours, or at least four hours, or at least five hours into the future, which can adequately consider the long term impact of increasing or decreasing the basal insulin delivery relative to the BBR. After a rate or profile is selected, the rate or profile can be delivered for a predetermined delivery period of time (for example, the block272ofFIG.2) prior to repeating one or more of the steps in the process of selecting a new basal insulin delivery profile or rate. In some cases, this predetermined delivery period of time can be less than the length of time for the generated basal insulin delivery profiles and/or rates and less than the time period for which future blood glucose values were estimated, thus methods and systems provided herein can dynamically make changes to basal insulin delivery based on recent blood glucose data. For example, generating basal delivery profiles at block263may be repeated every fifteen minutes, and the period of time evaluated at block264may be a four hour window such that every fifteen minutes, a new four hour window of analysis for the basal delivery profiles is generated. In this way, each delivery action is based on a prediction not only of that action, but on how the prior delivery action is determined to impact blood glucose levels for four hours into the future. Generating Possible Basal Delivery Profiles and/or Rates for Evaluation Possible basal insulin delivery profiles and/or rates can be generated using any suitable technique. In some cases, each generated profile or rate can be based on user-specific dosage parameters. In some cases, each generated profile or rate can be based on one or more user-specific dosage parameters that are specific to a particular diurnal period. In some cases, each generated profile or rate is based on a predetermined relationship to a stored baseline basal rate (BBR), such as indicated at block263inFIG.2. In some cases, generated profiles and/or rates for analysis extend for at least two hours, at least three hours, or for at least four hours. In some cases, the generated profiles may extend for a day (e.g., twenty-four hours) or less. In some cases, each generated profile or rate includes basal insulin delivery rates based on predetermined multiples or fractions of one or more stored BBRs. In some cases, multiple insulin delivery profiles and/or rates are based on multiple diurnal-time-block-specific BBRs. In some cases, generated basal insulin delivery profiles each deliver insulin at a ratio of a BBR, such as an integer multiple of one or more stored BBRs (e.g., 1×BBR, 1×BBR, 2×BBR, and 3×BBR). In some cases, insulin delivery profiles can delivery insulin at ratios that may include both fractions and multiples of one or more stored BBRs (e.g., 0×BBR, 0.5×BBR, 1×BBR, 1.5×BBR, and 2×BBR). In some cases, generated basal insulin delivery profiles each deliver insulin at only multiples or fractions of between 0 and 3. In some cases, generated basal insulin delivery profiles each deliver insulin at only multiples or fractions of between 0 and 2. In some cases, multiple generated basal delivery profiles can include only deliveries of basal insulin at 0% of BBR, 100% of BBR, or 200% of BBR. In some cases, each generated basal delivery profile permutation has fixed future time periods. In some cases, different future time periods for permutations can have different lengths. In some cases, the number of generated basal delivery profiles or rates for evaluation is less than 100, less than 50, less than 30, less than 25, or less than 20. By limiting the number of evaluated preset permutations based on stored BBRs, methods and systems provided herein can limit an energy expenditure used to run a controller determining a basal delivery rate. In some cases, one or more of the profiles may include an inflection point between a first insulin delivery amount for a first portion of delivery actions and a second delivery amount for a second portion of delivery actions. For example, a profile may include an inflection point between 0% and 100% between 3.5 hours and 4 hours (e.g., for the portion before the inflection point, 0% of the BBR is delivered as the delivery action and for the portion after the inflection point, 100% of the BBR is delivered as the delivery action). As another example, another profile may include an inflection point between 100% and 200% between 1 hour and 1.5 hours (e.g., before the inflection point, 100% of the BBR is delivered as the delivery action and after the inflection point, 200% of the BBR is delivered as the delivery action). In some cases, each profile may be a permutation of including one inflection point (or no inflection point) between three possible delivery actions (e.g., 0%, 100%, 200%). In some cases, more than one inflection point may be used, yielding additional profiles. In some cases, the number of profiles may be fewer than thirty. In some cases, only three profiles are analyzed in order to select between whether to deliver 0%, 100%, or 200%. In some cases, the inclusion of additional profiles assuming no basal insulin or continuing supply of maximum basal insulin can allow the system to detect an approaching predicted hypoglycemic event or an approaching predicted hyperglycemic event, and additional profiles can be selected and recorded to detect situations where future decisions are not conforming to an expected profile. In some cases, methods and systems provided herein can continue to deliver insulin according to a selected profile after the select period of time in block272, including changes in basal delivery rates, if reliable up-to-date blood glucose data is lost. In other cases, methods and systems provided herein will revert to another mode or alarm and stop insulin delivery if reliable up-to-date blood glucose data is lost. In some cases, the range of possible values of the BBR for a given profile can be adjusted or modified depending on the FHI. For example, in some cases, if the FHI is “prefer low” (e.g., indicating a preference for the system to aggressively keep the PWD within range and not go high), the target blood glucose might be set around 100 mg/dl and the range for delivery may include 0%, 50%, 100%, 200%, and 300% BBR. As another example, if the FHI is “prefer high” (e.g., indicating that the PWD prefers to avoid hypoglycemic events even with a higher risk of hyperglycemic events), the target blood glucose might be set around 140 mg/dl and the range for delivery may include 0%, 100%, and 200% of BBR. Evaluating Generated Basal Delivery profiles and/or Rates Referring again toFIG.2, the evaluation of multiple generated basal insulin delivery profiles and/or rates includes projecting future blood glucose levels and comparing those to blood glucose targets. In some cases, multiple permutations may be generated and analyzed. Predicting Future Blood Glucose Values Systems and methods provided herein can use any suitable physiology model to predict future blood glucose values. In some cases, methods and systems provided herein can predict future blood glucose values using past and current carbohydrate, insulin, and blood glucose values. Systems and methods provided herein can in some cases estimate a first future blood glucose a model as depicted inFIG.3. In some cases, blood glucose can be approximated using two determinist integrating first order plus dead time (FOPDT) models for the effect of carbohydrates and insulin, combined with an autoregressive (AR2) disturbance model. Accordingly, blood glucose (BG) at time (t) can be estimated using the following equation: BGt=yt=BGct+BGit+BGdt=Gcct+Giit+Gdeat From the equation above, the first element may represent the effect on blood glucose due to carbohydrates: Gc=kc(1-ac)Bcdt(1-acB)(1-B) where: B is the backward shift operator such that BYt=Yt-1, B2Yt=Yt-2, BkYt=Yt−k kc=1SFCR is the carb gain (in units of mg/dl/g) ac=e-tsτc,where τcis the carb time constant (for example, approximately 30 min), and where ts is the sampling time (for example, a CGM may use a sampling time interval of every 5 min) cdt=floor (τdc/ts), where τdcis the carb dead time (for example, approximately 15 min)From the equation above, the second element may represent the effect on blood glucose due to insulin: Gi=ki(1-ai)Bidt(1-aiB)(1-B) whereki=−ISF is the insulin gain (in units of mg/dl/unit) ai=e-tsτi, where τiis the insulin time constant (for example, approximately 120 min) idt=floor (τdi/ts), where τdiis the insulin dead time (for example, approximately 30 min)From the equation above, the third element may represent the effect on blood glucose due to disturbances (e.g., the AR2 disturbance model).Gdeatand may be based on the following log-transformed AR2 model: ln(BGdtμ*)=a1ln(BGdtμ*)+a2ln(BGdt-2μ*)+at which when rearranged, yields: BGdt=BGdt−1a1BGdt−2a2π*(1−a1−a2)eat where, in some examples,at˜Normal (0, σa) and σa≈50%ln(σ*)1+a21-a2((1-a2)2)-a12 withπ*˜10Normal (2.09,0.08)and σ*˜10Normal (0.15,0.028) such thata1≈1.6442, a2≈−0.6493.Using the above notation, expansion of the initial equation for BGt may be represented by the equation: BGt=kc(1-ac)(1-acB)(1-B)ct-dtc+ki(1-ai)(1-aiB)(1-B)it-dti+BGdt-1a1BGdt-2a2μ*(1-a1-a2) Systems and methods provided herein can in some cases calculate an amount of insulin on board (JOB) and/or an amount of carbohydrates on board (COB) in order to predict future blood glucose values. IOB and COB represent the amount of insulin and carbohydrates, respectively, which have been infused and/or consumed but not yet metabolized. Knowledge of IOB and COB can be useful for a user of a method or system provided herein when it comes to bolus decisions to prevent insulin stacking, but knowledge of IOB and COB can also be used in methods and systems provided herein to predict future blood glucose values. IOB and COB represent the amount of insulin and carbohydrates, respectively, which have been infused and/or consumed but not yet metabolized. Knowledge of IOB can be useful in correcting bolus decisions to prevent insulin stacking. Knowledge of IOB and COB can be useful for predicting and controlling blood glucose. Both insulin infusion and carbohydrate consumption can involve dead time or transportation delay (e.g., it can take ten to forty minutes for insulin and/or carbohydrates to begin to affect blood glucose). During the period immediately after entering the body (e.g., during the dead time period), it can be beneficial to account for IOB and COB in any decisions such as bolusing. This can be called “Decision” IOB/COB. “Action” IOB/COB, on the other hand, can represent the insulin and/or carbohydrates available for action on blood glucose. In some cases, Decision IOB can be a displayed JOB, while Action IOB can be an IOB determined for use in selecting a basal delivery rate or profile in methods and systems provided herein. From the equations above, BGit=-ISF(1-ai)Bidt(1-aiB)(1-B)it-idt whereBYt=Yt−1, B2Yt=Yt−2, BkYt=Yt−k ai=e-tsτi,where τiis the insulin time constant (for example, approximately 120 min) idt=floor (τdi/ts), where τdiis the insulin dead time (for example, approximately 30 min) and where ts is the sampling time (for example, a CGM may use a sampling time interval of every 5 min)“Decision” IOB In some embodiments, Decision IOB at time (t) (IOB_Dt) may be calculated according to the following mathematical process: IOB_Dt=IOB_Dt-1-BGit-BGit-1-ISF+itor,alternatively,∇IOB_Dt=-∇BGit-ISF+it substituting the equation above for BGitinto the equation for IOB_Dtor ∇IOB_Dtyields IOBDt=1-aiB-(1-ai)Bidt1-(ai+1)B+aiB2itor,alternatively,∇IOB_Dt=-1-ai1-aiBit-idt+it “Action” IOB In some embodiments, Action IOB at time (t) (IOB_At) may be calculated according to the following mathematical process: IOB_At=11-aiBit-idt For an arbitrary series of insulin infusions, using an infinite series of expansions of 11-aiB′IOB_At may be represented by IOB_At=∑k=onaikit-k-idt Stated another way, BGit=-ISF(1-ai)1-BIOB_At The formula for COB, including Action COB and Decision COB, may be developed in a similar fashion, using the equation above related to Gc: Gct=kc(1-ac)Bcdt(1-acB)(1-B) Accordingly, future blood glucose data can be estimated using current or recent blood glucose data, data about when carbohydrates were consumed, and/or data regarding when insulin was and/or will be administered. Moreover, because evaluated insulin delivery profiles and/or rates include basal insulin delivery rates above and below the BBR, those insulin delivery rates above BBR can be added to the IOB calculation and insulin delivery rates below the BBR can be subtracted from the IOB. In some cases, a variation in a Decision IOB due to actual variations from BBR can be limited to positive deviations in order to prevent a user from entering an excessive bolus. Estimating Glucose Levels from Blood Glucose Data Referring back toFIG.1, continuous glucose monitor50and blood glucose meter70can both provide blood glucose data to system10. The blood glucose data, however, can be inaccurate. In some cases, continuous glucose monitor50can be replaced (or have sensor shaft56replaced) at regular or irregular intervals (e.g., every three days, every five days, every seven days, or every ten days). In some cases, data from blood glucose meter70can be used to calibrate the continuous glucose monitor50at regular or irregular intervals (e.g., every three hours, every six hours, every twelve hours, every day, etc.). In some cases, systems and methods provided herein can remind a user to change the continuous glucose monitor50or calibrate continuous glucose monitor50using blood glucose meter70based on data from continuous glucose monitor50and/or at regular intervals. For example, if the pattern of insulin delivery varies greatly from an earlier predicted pattern of insulin deliveries it may indicate that the continuous glucose monitor50requires maintenance and/or replacement. In some cases, methods and systems can determine an accuracy factor for blood glucose data from the continuous glucose monitor50based upon when the particular continuous glucose monitor sensor shaft56was first applied to the PWD and/or when the particular continuous glucose monitor50was last calibrated using blood glucose data from blood glucose meter70. In some cases, methods and systems provided herein make adjustments to future blood glucose targets based on a calculated accuracy factor for data from the continuous glucose monitor50in order to reduce a risk of hypoglycemia. In some cases, methods and systems provided herein can estimate the current blood glucose level as being a predetermined number of standard deviations (e.g., 0.5 standard deviation, one standard deviation, two standard deviations) below data received from continuous glucose monitor50based on the accuracy factor in order to reduce a risk of hypoglycemia. After continuous glucose monitor50is calibrated or replaced with a new continuous glucose monitor or has a new sensor shaft56installed, however, a discontinuity of reported glucose data from the continuous glucose monitor50can occur. In some cases, methods and systems provided herein, however, can use and report historical blood glucose values in selecting insulin basal rates and/or profiles. In some cases, methods and systems provided herein can revise stored and/or reported blood glucose levels based on data from one or more continuous glucose monitors in order to transition between different continuous glucose monitor sensors and/or to data produced after a calibration. In some cases, a continuous glucose monitor50can provide each blood glucose value with an estimated rate of change, and the rate of change information can be used to retrospectively adjust one or more historical estimated blood glucose values from data from a continuous glucose monitor50. For example, the rate of change of the pre-calibration reported blood glucose value may be used to determine an estimated post-calibration value assuming the same rate of change. A ratio of the post-calibration reported blood glucose value to the estimated post-calibration value can then be used to linearly interpolate multiple historical blood glucose values based on that ratio. In some cases, all readings between calibrations can be linearly interpolated. In some cases, data from a predetermined amount of time prior to a calibration can be linearly interpolated (e.g., fifteen minutes, thirty minutes, one hour, two hours, three hours, or six hours). Analyzing Variations from Targets Methods and systems provided herein can evaluate each future basal delivery profile by predicting blood glucose for the basal delivery profiles and calculating a variation index of the predicted blood glucose values from the target blood glucose values. Methods and systems provided herein can then select the profile of basal rate delivery actions that corresponds to the lowest variation index. The variation index can use a variety of different mathematical formulas to weight different types of variations. The variation index can be a cost function. In some cases, methods and systems provided herein can use a cost function that sums up squares of differences for the projected blood glucose values from target blood glucose values for multiple diurnal time segments. Methods and systems provided herein can use any suitable cost function. In some cases, cost functions can sum the absolute value of the difference between each predicted blood glucose value and each blood glucose target. In some cases, cost functions used in methods and systems provided herein can use a square of the difference. In some cases, cost functions used in methods and systems provided herein can use a square of the difference between the logs of each predicted blood glucose level and each corresponding blood glucose target. In some cases, cost functions used in methods and systems provided herein can assign a higher cost to blood glucose values below the blood glucose target in order reduce the risk of a hypoglycemic event. In some cases, a profile that has the lowest value of loss may be selected. In some cases, cost functions provided herein can include elements that additional bias of the selected profile toward a profile that maintains the previously administered basal rate and/or that delivers the baseline basal rate, which may prevent the system from changing delivery rates every time a basal delivery profile or rate is selected in block265, for example, seeFIG.2. In some cases, the cost function can square the difference between the log of the values in order to provide a higher cost for projected lows than projected highs. Selecting a Basal Insulin Delivery Profile or Rate Methods and systems provided herein can then select a basal profile or rate that produces the lowest cost function value. With reference toFIG.2, at block272insulin can then be delivered according to the selected profile for an amount of time. In some cases, the amount of time is a predetermined amount of time. In some cases, the predetermined amount of time is less than the time horizon for the estimated future blood glucose values and the length of time for the selected basal delivery profile. In some cases, the predetermined amount of time is ninety minutes or less, sixty minutes or less, forty-five minutes or less, thirty minutes or less, twenty minutes or less, fifteen minutes or less, ten minutes or less, or five minutes or less. After the period of time, the system can again repeat the operations at blocks263,264,265, and272to select and deliver a basal insulin for a subsequent period of time. Adjusting User-Specific Dosage Parameters Methods and systems provided herein can make adjustments to the user-specific dosage parameters. For example,FIG.2includes the block281for detecting time periods when an amount of delivered basal insulin is different from a BBR, which can then be used to adjust user-specific dosage parameters at block262. These updated user-specific dosage parameters can then be used to generate new basal delivery profiles at block263and used at block264to evaluate different basal delivery profiles. For example, for a BBR of 1.46 U/hour (associated with a TDB of 35 U/day), if a diurnal period under consideration is one hour and for the first forty-five minutes, insulin was delivered at a rate of 2.92 U/hour (e.g., 2× the BBR) and only the last fifteen minutes was delivered at a rate of 1.46 U/hour (e.g., 1× the BBR), user-specific dosage parameters for a related diurnal time period (e.g., that same hour on another day in the future, or a preceding diurnal time period on a day in the future) may be adjusted. In some cases, methods and systems provided herein can make adjustments for BBR, ISF, and/or CR for multiple diurnal periods based on variations in the insulin amounts actually delivered for that diurnal period compared to the baseline basal insulin rate for that diurnal period. In some cases, diurnal periods can have a same length of time as a predetermined length of time for the delivery of a selected insulin delivery. In some cases, a diurnal period can be greater than a predetermined length of time for the delivery of a selected insulin delivery, for example, multiple doses of insulin may be delivered during a single diurnal period. In some cases, a diurnal period can be fifteen minutes, thirty minutes, one hour, two hours, etc. In some cases, an actual delivery of insulin for a diurnal period must surpass a predetermined threshold above or below the BBR for that diurnal period in order for user-specific dosage parameters (e.g., BBR, ISF, CR) to be adjusted for that diurnal period. For example, diurnal periods can be one hour long, but each basal delivery profile can be delivered for fifteen minute time periods before methods and systems provided herein determine a new basal insulin delivery profile, and methods and systems provided herein can require that the total basal insulin delivery for the diurnal period be at least greater than 50% of the BBR to increase the BBR for that diurnal period or at 50% or less than the BBR to decrease the BBR for that diurnal period. Using the example from above, for a BBR of 1.46 U/hour, if a diurnal period under consideration is one hour and for the first forty-five minutes (e.g., three iterations of profile generation and delivery actions), insulin was delivered at a rate of 2.92 U/hour (e.g., 2× the BBR) and only the last fifteen minutes (e.g., one iteration of profile generation and delivery action) was delivered at a rate of 1.46 U/hour (e.g., 1× the BBR), the total amount delivered would be at 175% of the BBR for the one hour diurnal period, or an average ratio of 1.75× the BBR. In some cases, because the 175% exceeded 150% of the BBR, methods and systems of the present disclosure may adjust user-specific dosage parameters. As another example using the same 1.46 U/hour BBR and a two hour diurnal time period and delivery profiles reformulated every fifteen minutes, if the first forty-five minutes delivered no insulin (0× the BBR) and the last hour and fifteen minutes delivered 1.46 U/hour, the total amount delivered may be 62.5% of the BBR, or 0.625× of the BBR. In some cases, because the 62.5% did not drop below 50% of the BBR, methods and systems of the present disclosure may not adjust the user-specific dosage parameters and may maintain the user-specific dosage parameters for the particular diurnal period. An adjustment to the CR, ISF, and BBR can be any suitable amount. In some cases, the adjustment to the BBR is less than the difference between the delivered basal insulin and the previously programmed BBR. In some cases, a change to each user-specific dosage parameter (e.g., BBR, ISF, and CR) is at a predetermined percentage or value. For example, in some cases, each of BBR and ISF can be increased by 5%, 3%, or 1% and CR decreased by the same percent for every period where the amount of delivered basal insulin exceeds the BBR by at least 25%. In some cases, BBR and ISF can be decreased by 5%, 3%, or 1% and CR increased by the same percent for every period where the amount of delivered basal insulin exceeds the BBR by at least 25%. By setting each adjustment at a low level, methods and systems provided herein can eventually be personalized for the PWD without over adjusting the system based on an unusual day (e.g., to mitigate the risk of short term disturbances being mistaken for changes in physiological parameters). In some cases, the adjustment to CR, ISF, and BBR may be based on a relationship between CR, ISF, and BBR, rather than a fixed amount or percentage. In some cases, CR, ISF, and BBR can be adjusted based on a predetermined relationship between their log transformed values. In some cases, the adjustments to CR, ISF, and BBR may be performed independently. In these and other cases, systems and methods provided herein can monitor for variations in adjustments to CR, ISF, and/or BBR away from a relationship between CR, ISF, and BBR. In such cases, a notification may be provided to a user (e.g., the PWD or a health care provider) that the systems and methods of the present disclosure had adjusted one or more user-specific dosage guidelines outside of or away from a relationship between CR, ISF, and BBR. In some cases, systems and methods provided herein can update or adjust user-specific operating parameters for select time blocks every twenty-four hours. In some cases, diurnal periods can be updated dynamically (e.g., immediately after a basal delivery profile or rate is selected). In some cases, diurnal periods can be updated by reusable pump controller200, by mobile computing device60, or using a remote server in the cloud. In some cases, the length of diurnal periods can vary depending on the time of day (e.g., nighttime diurnal periods could be longer) or depending on the user-specific dosage parameter (e.g., BBRs might have fifteen minute diurnal periods while the CR and ISF might have one hour diurnal periods). In some cases, when performing an adjustment, a related diurnal period may be adjusted based on variation from the BBR for a given diurnal period. For example, if an adjustment were to be performed because delivery from 2 PM to 3 PM exceeded 150% of the BBR, an adjustment may be made to the user-specific dosage parameters for the same time on a different day in the future (e.g., 2 PM to 3 PM on the next day) or a preceding diurnal period on a different day in the future (e.g., 1 PM to 2 PM on the next day or 12 PM to 1 PM on the next day, etc.). In some cases, modifying a preceding diurnal period may adjust more appropriately for variations in BBR and/or other user-specific dosage parameters because of the delay of effect after delivery of insulin and/or the delay of effect after consumption of carbohydrates (e.g., if a PWD repeatedly goes high between 2 PM and 3 PM, the PWD may need additional insulin during the 1 PM to 2 PM hour). In some cases, systems and methods disclosed herein can smooth adjustments to user-specific dosage parameters in one diurnal period relative to other diurnal periods. For example, in some cases, a proposed adjustment to a BBR for a first diurnal period may be compared to one or more preceding diurnal periods and one or more following diurnal periods. If the proposed adjustment is a threshold amount different from one or more of the preceding or following diurnal period values, the proposed adjustment may be modified to avoid drastic jumps between diurnal periods. For example, if a preceding diurnal period had a BBR of 1.06 U/hour and the proposed adjustment was from a BBR of 1.4 U/hour to a BBR of 1.90 U/hour, the adjustment may be reduced to smooth the transition from the preceding diurnal time period. In some cases, the smoothing may include adjusting proceeding or following diurnal time periods in addition to the diurnal time period under consideration. In these and other cases, such adjustment may be performed once per day or at another periodic time such that following diurnal periods may have already occurred and the smoothing is not being performed based on projections. For example, the diurnal period from 1 PM to 2 PM may be analyzed for potential adjustment at 4 PM such that the diurnal periods from 11 AM to 12 PM and 12 PM to 1 PM and from 2 PM to 3 PM and 3 PM and 4 PM are available in considering any adjustment and/or smoothing to perform on the user-specific dosage parameters for the 1 PM to 2 PM diurnal period. In some cases, systems and methods disclosed herein can adjust user-specific dosage parameters in a diurnal period based on the FHI. For example, if the FHI is high (e.g., indicating a preference that the PWD not go low), the range for adjusting the BBR may be limited to a relatively small change (e.g., 0.5%, 1%, 1.5%, etc.). As another example, if the FHI is low (e.g., indicating that the PWD is not as concerned about going low), the range for adjusting the BBR may include a broader range of changes (e.g., up to a 5% change). Adjusting Blood Glucose Targets Methods and systems provided herein can make adjustments to the blood glucose targets. For example,FIG.2includes the block283for analyzing the variability of CGM and/or BGM data (e.g., data from the CGM 50 and/or the BGM 70 ofFIG.1), which can then be used to adjust blood glucose targets at the block261. In some cases, blood glucose targets are set for diurnal periods. In some cases, the diurnal periods for blood glucose targets are at least fifteen minutes long, at least thirty minutes long, at least one hour long, or at least two hours long. In some cases, blood glucose targets can have a constrained range. In some cases, blood glucose targets must be at least 80 mg/dL, at least 90 mg/dL, at least 100 mg/dL, at least 110 mg/dL, or at least 120 mg/dL. In some cases, blood glucose targets must be no greater than 200 mg/dL, no greater than 180 mg/dL, no greater than 160 mg/dL, no greater than 140 mg/dL, or no greater than 125 mg/dL. In some cases, a constrained range is between 100 mg/dL and 160 mg/dL. These updated blood glucose targets can then be used at block264to evaluate different basal delivery profiles. Updated blood glucose targets for a particular diurnal period can be based on historical blood glucose patterns for the PWD and the risk of hypoglycemia for the PWD over the course of a day. The updated blood glucose targets can also consider a set FHI. For example, based on an FHI selection, an initial blood glucose target at a conservative level (e.g., 120 mg/dl) can be set, and over the course of a period of days and/or weeks as more information is gained about variability patterns, the blood glucose target(s) can be adjusted. A slow adjustment can prevent the blocks283and261from overreacting to short term disturbances but still allow blood glucose target individualization to a PWD's lifestyle and habits over time. In some cases, methods and systems provided herein can also allow a user to temporarily or permanently adjust blood glucose targets by adjusting their fear of hypoglycemia index (FHI). In some cases, a user adjustment to FHI can result in blood glucose targets being temporarily or permanently adjusted to blood glucose targets based on the variability of CGM (and optionally BGM) data for multiple diurnal periods. In some cases, a user adjustment to FHI can add or subtract a predetermined value from a previously used blood glucose target (e.g., an adjustment from “prefer low” to “prefer medium” could add 20 mg/dL to each stored blood glucose target). In some cases, a temporary adjustment to FHI could analyze variability data for multiple time blocks and set a new blood glucose target for each diurnal period based on the variability data for that time block (e.g., an adjustment from “prefer low” to “prefer medium” could adjust the blood glucose target for each diurnal period from a level estimated to send the PWD below a threshold of 70 mg/dL about 5% of the time to a level estimated to send the PWD below a threshold of 70 mg/dL about 3% of the time). Allowing a PWD to change the FHI for temporary time periods or otherwise use some form of temporary override may allow a PWD to tell the system that the PWD is about to or is experiencing some activity or condition that might impact their blood glucose levels. For example, a PWD that is about to exercise might set a temporary FHI of “prefer high” to offset the risk that exercise will send the PWD low for that period of time. In some cases, a PWD might set a temporary FHI of “prefer low” if the PWD is feeling sick in order to offset the risk that the sickness will result in high blood glucose levels. In some embodiments, such a temporary override may be a separate setting or entry other than the FHI. In these and other cases, in addition to a preferred range (e.g., “high” or “low”), the user may be able to select a temporary override of a target blood glucose level or range (e.g., approximately 120 mg/dL or between 120 mg/dL and 200 mg/dL, etc.), or may select a particular activity or circumstance the PWD will participate in or is experiencing (e.g., exercising, sickness, menses, driving, etc.). In some cases, after a temporary override is input, methods and systems of the present disclosure can select a new profile to follow based on the profile more closely aligning with the temporary override. In these and other cases, a new set of profiles can be generated before selecting the new profile. Additionally or alternatively, after a temporary override is input, methods and systems of the present disclosure can temporarily modify the BBR. In some cases, after the BBR has been modified, a new set of profiles may be generated based on the temporarily modified BBR. In some cases a log of temporary overrides can be generated. For example, each time a user (e.g., the PWD) inputs an override, an entry can be created in the log that includes what override was selected, what starting and ending times, and/or what the reason for the override was. In these and other cases, the log can be periodically provided to a healthcare professional, for example, via email or some other electronic message. Additionally or alternatively, in some cases the log can be parsed for patterns. For example, the PWD may input a temporary override every Monday, Wednesday, and Friday from 6 PM to 7 PM when the PWD exercises. The log can be parsed to find such patterns of overrides. In these and other cases, methods and systems of the present disclosure can modify a BBR based on the patterns. Continuing the example, the BBR may be lowered for the diurnal period of 6 PM to 7 PM on Monday, Wednesday, and Friday because of a PWD repeatedly entering a temporary override during that diurnal period that the PWD is exercising and not to go low. Overall System Methods and systems provided herein can control basal insulin delivery over time and adjust basal user-specific dosage parameters and blood glucose targets for multiple diurnal periods to personalize the user-specific dosage parameters over time. For example,FIG.4illustrates various examples of user interfaces (e.g.,400,410,420, and430) displaying various aspects of the present disclosure. In some cases,FIG.4illustrates a simulation of a method provided herein, showing how methods and systems provided herein may generate a user interface400that may illustrate BBRs401, CRs402, ISFs403, and a blood glucose targets404set for multiple time blocks. For example, after a system (e.g., the system10ofFIG.1) has run on a PWD after thirty days, user-specific dosage parameters may be personalized based on adjustments made to the user-specific dosage parameters. For example, the user interface400may align the various user-specific dosage parameters over various diurnal periods throughout a day. For example, the BBR401may be higher around meal times (e.g., nine AM, twelve PM, and seven PM), and lower while the PWD is sleeping (e.g., eleven PM to five AM). As an additional example, the CR402and ISF403may follow a similar trajectory of variation as illustrated for the BBR401. In some cases, as illustrated in user interface410ofFIG.4, methods and/or systems of the present disclosure (including, for example, back-end computer systems) may monitor and/or track blood glucose levels over time. For example, the user interface410may illustrate glucose levels for one hundred eighty days, with a bar indicating the last thirty days. In some cases, when adjusting user-specific dosage parameters, methods and systems of the present disclosure may disregard readings older than thirty days, or may weight more recent readings more heavily than older readings. In some cases, the user interface420may include time aligned charts (including chart421, chart422, and chart423) that can show a six hour window of the timeline illustrated in user interface410. As illustrated inFIG.4, chart421depicts the current blood glucose values as well as the predictions that have been made over time for that particular delivery time. For example, once the “current” bar424is reached, there may have been multiple predictions made for each time segment. As the window extends further into the future, the number of predictions may be lower. The chart422illustrates the calculated IOB and the calculated COB for the PWD. The chart423indicates whether the method or system delivered 0% of the BBR, 100% of the BBR, or 200% of the BBR for fifteen minute time segments. As illustrated inFIG.4, the user interface430depicts a possible user interface for a PWD showing some data that may be displayed on a mobile device of a PWD (e.g., the mobile computing device60ofFIG.1). In some cases, only the data prior to the bar424(e.g., historic data) may be shown in the user interface430. In a first part431of the user interface430, historic blood glucose data can be displayed. In a second section432, announced meals and bolus insulin deliveries can be displayed. In a third section433, the rates of basal delivery can be displayed. The section433can differ from chart423by displaying the actual rates of basal delivery rather than a ratio of the rate delivered to the BBR. Section434can display a current blood glucose reading, a current IOB, and/or an indication of whether the system is automating. In some cases, more or less information can be displayed on the user interface430than illustrated inFIG.4. For example, the user interface430may include any of the information from the user interfaces400,410, and/or420in any combination. Additional Details about Example Pump Assembly FIGS.5A and5Bprovide additional details about example pump assembly15as discussed above in regards toFIG.1.FIG.5Bdepicts the details of example reusable pump controller200. Referring now toFIG.5A, disposable pump100in this embodiment includes a pump housing structure110that defines a cavity116in which a fluid cartridge120can be received. Disposable pump100also can include a cap device130to retain the fluid cartridge120in the cavity116of the pump housing structure110. Disposable pump100can include a drive system (e.g., including a battery powered actuator, a gear system, a drive rod, and other items that are not shown inFIG.5A) that advances a plunger125in the fluid cartridge120so as to dispense fluid therefrom. In this embodiment, reusable pump controller200communicates with disposable pump100to control the operation of the drive system. For example, in some cases, the reusable pump controller200can generate a message for the disposable pump100directing the disposable pump100to deliver a certain amount of insulin or deliver insulin at a certain rate. In some cases, such a message may direct the disposable pump100to advance the plunger125a certain distance. In some cases, not depicted, reusable pump controller200may include a user interface220to control the operation of disposable pump100. In some cases, disposable pump100can be disposed of after a single use. For example, disposable pump100can be a “one-time-use” component that is thrown away after the fluid cartridge120therein is exhausted. Thereafter, the user can removably attach a new disposable pump100(having a new fluid cartridge) to the reusable pump controller200for the dispensation of fluid from a new fluid cartridge. Accordingly, the user is permitted to reuse reusable pump controller200(which may include complex or valuable electronics, as well as a rechargeable battery) while disposing of the relatively low-cost disposable pump100after each use. Such a pump assembly15can provide enhanced user safety as a new pump device (and drive system therein) is employed with each new fluid cartridge. The pump assembly15can be a medical infusion pump assembly that is configured to controllably dispense a medicine from the fluid cartridge120. As such, the fluid cartridge120can contain a medicine126to be infused into the tissue or vasculature of a targeted individual, such as a human or animal patient. For example, disposable pump100can be adapted to receive a fluid cartridge120in the form of a carpule that is preloaded with insulin or another medicine for use in the treatment of Diabetes (e.g., Exenatide (BYETTA®, BYDUREON®) and liraglutide (VICTOZA®), SYMLIN®, or others). Such a fluid cartridge120may be supplied, for example, by Eli Lilly and Co. of Indianapolis, Ind. The fluid cartridge120may have other configurations. For example, the fluid cartridge120may comprise a reservoir that is integral with the pump housing structure110(e.g., the fluid cartridge120can be defined by one or more walls of the pump housing structure110that surround a plunger to define a reservoir in which the medicine is injected or otherwise received). In some embodiments, disposable pump100can include one or more structures that interfere with the removal of the fluid cartridge120after the fluid cartridge120is inserted into the cavity116. For example, the pump housing structure110can include one or more retainer wings (not shown) that at least partially extend into the cavity116to engage a portion of the fluid cartridge120when the fluid cartridge120is installed therein. Such a configuration may facilitate the “one-time-use” feature of disposable pump100. In some embodiments, the retainer wings can interfere with attempts to remove the fluid cartridge120from disposable pump100, thus ensuring that disposable pump100will be discarded along with the fluid cartridge120after the fluid cartridge120is emptied, expired, or otherwise exhausted. In another example, the cap device130can be configured to irreversibly attach to the pump housing structure110so as to cover the opening of the cavity116. For example, a head structure of the cap device130can be configured to turn so as to threadably engage the cap device130with a mating structure along an inner wall of the cavity116, but the head structure may prevent the cap device from turning in the reverse direction so as to disengage the threads. Accordingly, disposable pump100can operate in a tamper-resistant and safe manner because disposable pump100can be designed with a predetermined life expectancy (e.g., the “one-time-use” feature in which the pump device is discarded after the fluid cartridge120is emptied, expired, or otherwise exhausted). Still referring toFIG.5A, reusable pump controller200can be removably attached to disposable pump100so that the two components are mechanically mounted to one another in a fixed relationship. In some embodiments, such a mechanical mounting can also form an electrical connection between the reusable pump controller200and disposable pump100(for example, at electrical connector118of disposable pump100). For example, reusable pump controller200can be in electrical communication with a portion of the drive system (not shown) of disposable pump100. In some embodiments, disposable pump100can include a drive system that causes controlled dispensation of the medicine or other fluid from the fluid cartridge120. In some embodiments, the drive system incrementally advances a piston rod (not shown) longitudinally into the fluid cartridge120so that the fluid is forced out of an output end122. A septum121at the output end122of the fluid cartridge120can be pierced to permit fluid outflow when the cap device130is connected to the pump housing structure110. For example, the cap device130may include a penetration needle that punctures the septum121during attachment of the cap device130to the pump housing structure110. Thus, when disposable pump100and reusable pump controller200are mechanically attached and thereby electrically connected, reusable pump controller200communicates electronic control signals via a hardwire-connection (e.g., electrical contacts along electrical connector118or the like) to the drive system or other components of disposable pump100. In response to the electrical control signals from reusable pump controller200, the drive system of disposable pump100causes medicine to incrementally dispense from the fluid cartridge120. Power signals, such as signals from a battery (not shown) of reusable pump controller200and from the power source (not shown) of disposable pump100, may also be passed between reusable pump controller200and disposable pump100. Referring again toFIGS.1and5, the pump assembly15can be configured to be portable and can be wearable and concealable. For example, a PWD can conveniently wear the pump assembly15on the PWD's skin (e.g., skin adhesive) underneath the PWD's clothing or carry disposable pump100in the PWD's pocket (or other portable location) while receiving the medicine dispensed from disposable pump100. The pump assembly15is depicted inFIG.1as being held in a PWD' s hand5so as to illustrate the size of the pump assembly15in accordance with some embodiments. This embodiment of the pump assembly15is compact so that the PWD can wear the pump assembly15(e.g., in the PWD's pocket, connected to a belt clip, adhered to the PWD's skin, or the like) without the need for carrying and operating a separate module. In such embodiments, the cap device130of disposable pump100can be configured to mate with an infusion set146. In general, the infusion set146can be a tubing system that connects the pump assembly15to the tissue or vasculature of the PWD (e.g., to deliver medicine into the tissue or vasculature under the PWD's skin). The infusion set146can include a tube147that is flexible and that extends from disposable pump100to a subcutaneous cannula149that may be retained by a skin adhesive patch (not shown) that secures the subcutaneous cannula149to the infusion site. The skin adhesive patch can retain the cannula149in fluid communication with the tissue or vasculature of the PWD so that the medicine dispensed through the tube147passes through the cannula149and into the PWD's body. The cap device130can provide fluid communication between the output end122(FIG.5A) of the fluid cartridge120and the tube147of the infusion set146. In some embodiments, the pump assembly15can be pocket-sized so that disposable pump100and reusable pump controller200can be worn in the PWD's pocket or in another portion of the PWD's clothing. In some circumstances, the PWD may desire to wear the pump assembly15in a more discrete manner. Accordingly, the PWD can pass the tube147from the pocket, under the PWD's clothing, and to the infusion site where the adhesive patch can be positioned. As such, the pump assembly15can be used to deliver medicine to the tissues or vasculature of the PWD in a portable, concealable, and discrete manner. In some embodiments, the pump assembly15can be configured to adhere to the PWD's skin directly at the location in which the skin is penetrated for medicine infusion. For example, a rear surface of disposable pump100can include a skin adhesive patch so that disposable pump100can be physically adhered to the skin of the PWD at a particular location. In these embodiments, the cap device130can have a configuration in which medicine passes directly from the cap device130into an infusion set146that is penetrated into the PWD's skin. In some examples, the PWD can temporarily detach reusable pump controller200(while disposable pump100remains adhered to the skin) so as to view and interact with the user interface220. In some embodiments, the pump assembly15can operate during an automated mode to deliver basal insulin according the methods provided herein. In some cases, pump assembly15can operate in an open-loop mode to deliver insulin at the BBR. A basal rate of insulin can be delivered in an incremental manner (e.g., dispense 0.10 U every five minutes for a rate of 1.2 U per hour) according to a selected basal insulin delivery profile. A user can use the user interface on mobile computing device60to select one or more bolus deliveries, for example, to offset the blood glucose effects caused by food intake, to correct for an undesirably high blood glucose level, to correct for a rapidly increasing blood glucose level, or the like. In some circumstances, the basal rate delivery pattern may remain at a substantially constant rate for a long period of time (e.g., a first basal dispensation rate for a period of hours in the morning, and a second basal dispensation rate for a period of hours in the afternoon and evening). In contrast, the bolus dosages can be more frequently dispensed based on calculations made by reusable pump controller200or the mobile computing device60(which then communicates to reusable pump controller200). For example, reusable pump controller200can determine that the PWD's blood glucose level is rapidly increasing (e.g., by interpreting data received from the continuous glucose monitor50), and can provide an alert to the user (via the user interface220or via the mobile computing device60) so that the user can manually initiate the administration of a selected bolus dosage of insulin to correct for the rapid increase in blood glucose level. In one example, the user can request (via the user interface of mobile computing device60) a calculation of a suggested bolus dosage (e.g., calculated at the mobile computing device60based upon information received from the user and from reusable pump controller200, or alternatively calculated at reusable pump controller200and communicated back via the mobile computing device60for display to the user) based, at least in part, on a proposed meal that the PWD plans to consume. Referring now toFIG.5B, reusable pump controller200(shown in an exploded view) houses a number of components that can be reused with a series of successive disposable pumps100. In particular, reusable pump controller200can include control circuitry240(e.g., a control device) and a rechargeable battery pack245, each arranged in the controller housing210. The rechargeable battery pack245may provide electrical energy to components of the control circuitry240, other components of the controller device (e.g., a display device222and other user interface components, sensors, or the like), or to components of disposable pump100. The control circuitry240may be configured to communicate control or power signals to the drive system of disposable pump100, or to receive power or feedback signals from disposable pump100. The control circuitry240of reusable pump controller200can include one or more microprocessors241configured to execute computer-readable instructions stored on one or more memory devices242so as to achieve any of the control operations described herein. At least one memory device242of the control circuitry240may be configured to store a number of user-specific dosage parameters. One or more user-specific dosage parameters may be input by a user via the user interface220. Further, as described further below in connection withFIG.2, various user-specific dosage parameters can be automatically determined and/or updated by control operations implemented by the control circuitry240of reusable pump controller200. For example, the control circuitry240can implement a secondary feedback loop to determine and/or update one or more user-specific dosage parameters in parallel with the infusion pump system10operating in a closed-loop delivery mode. Whether determined automatically or received via the mobile computing device60(or via the user interface220of reusable pump controller200), the control circuitry240can cause the memory device242to store the user-specific dosage parameters for future use during operations according to multiple delivery modes, such as closed-loop and open-loop delivery modes. Additionally, the control circuitry240can cause reusable pump controller200to periodically communicate the user-specific dosage parameters to the mobile computing device60for future use during operations by the mobile computing device60or for subsequent communication to a cloud-based computer network. Such user-specific dosage parameters may include, but are not limited to, one or more of the following: total daily basal dosage limits (e.g., in a maximum number of units/day), various other periodic basal dosage limits (e.g., maximum basal dosage/hour, maximum basal dosage/six hour period), insulin sensitivity (e.g., in units of mg/dL/insulin unit), carbohydrate ratio (e.g., in units of g/insulin unit), insulin onset time (e.g., in units of minutes and/or seconds), insulin on board duration (e.g., in units of minutes and/or seconds), and basal rate profile (e.g., an average basal rate or one or more segments of a basal rate profile expressed in units of insulin unit/hour). Also, the control circuitry240can cause the memory device242to store (and can cause reusable pump controller200to periodically communicate out to the mobile computing device60) any of the following parameters derived from the historical pump usage information: dosage logs, average total daily dose, average total basal dose per day, average total bolus dose per day, a ratio of correction bolus amount per day to food bolus amount per day, amount of correction boluses per day, a ratio of a correction bolus amount per day to the average total daily dose, a ratio of the average total basal dose to the average total bolus dose, average maximum bolus per day, and a frequency of cannula and tube primes per day. To the extent these aforementioned dosage parameters or historical parameters are not stored in the memory device242, the control circuitry240can be configured to calculate any of these aforementioned dosage parameters or historical parameters from other data stored in the memory device242or otherwise input via communication with the mobile computing device60. FIG.6illustrates a flow diagram of an example method600of using insulin delivery profiles. The method600may be performed by any suitable system, apparatus, or device. For example, the system10, the pump assembly15, the mobile computing device60ofFIG.1, and/or a remote server may perform one or more of the operations associated with the method600. Although illustrated with discrete blocks, the steps and operations associated with one or more of the blocks of the method600may be divided into additional blocks, combined into fewer blocks, or eliminated, depending on the desired implementation. At block610, a set of insulin delivery profiles can be generated, each having a series of insulin delivery actions. For example, the pump assembly15may generate a series of potential delivery actions that may include permutations based on one or more potential inflection points in the delivery actions. At block620, a prediction can be made of future blood glucose levels for each of the delivery profiles. For example, the pump assembly15and/or the mobile computing device60ofFIG.1can generate a prediction of future blood glucose levels at various points in time if a particular profile is followed. Such prediction may be based on the effect of glucose, insulin, carbohydrates, and/or other disturbances projected for the blood glucose levels at the various points in time. At block630, a determination can be made as to variations from a target blood glucose level for each of the profiles. For example, the pump assembly15and/or the mobile computing device60ofFIG.1may compare the predicted blood glucose levels to a target blood glucose level for each of the various points in time. In some cases, the target blood glucose level may be constant and in other cases, the target blood glucose level may vary over time. In these and other cases, the variation may be measured as a distance between the target blood glucose level and the projected blood glucose level, or a square of the difference, etc., as described above. At block640, the profile that approximates the target blood glucose level can be selected. In some cases, the profile that minimizes variation from the target blood glucose level may be selected. For example, a cost function can be utilized and the profile with the lowest cost can be selected as the profile that approximates the target blood glucose level. At block650, insulin may be delivered based on the next action in the selected profile. For example, control circuitry240of the pump assembly15may send a message to the pump portion of the pump assembly to deliver insulin based on the next action in the selected profile. For example, a next action may indicate that the pump is to deliver 0×, 1×, or 2× of a BBR. The next action can be the first delivery action in the set of actions of the profile. In some cases, after the block650, the method600can return to the block610to generate another set of insulin delivery profiles, predict future blood glucose levels, determine variations from a target blood glucose level, etc. In some cases, the method600can be performed iteratively each time a PWD is to receive a dose of basal insulin. In these and other cases, the method600can routinely update delivery actions based on a repeatedly updated projection of the blood glucose levels of the PWD and the effect a particular delivery action may have on the blood glucose levels. In some cases, methods and systems provided herein can change modes if there is a lack of reliable CGM data at this point in time (e.g., the system can change modes to a mode where BBR is delivered and potentially provide notice that the system has exited the automation mode). Modifications, additions, or omissions may be made to the method600without departing from the scope of the present disclosure. For example, the operations of the method600may be implemented in differing order. Additionally or alternatively, two or more operations may be performed at the same time. Furthermore, the outlined operations and actions are provided as examples, and some of the operations and actions may be optional, combined into fewer operations and actions, or expanded into additional operations and actions without detracting from the essence of the disclosed embodiments. FIG.7illustrates a flow diagram of an example method700of adjusting insulin delivery rates. The method700may be performed by any suitable system, apparatus, or device. For example, the system10, the pump assembly15, the mobile computing device60ofFIG.1, and/or a remote server may perform one or more of the operations associated with the method700. Although illustrated with discrete blocks, the steps and operations associated with one or more of the blocks of the method700may be divided into additional blocks, combined into fewer blocks, or eliminated, depending on the desired implementation. At block710, insulin can be delivered over a diurnal time period. For example, the pump assembly15ofFIG.1can deliver insulin to a PWD based on a BBR for the diurnal time period. In some cases, the insulin may be actually delivered at multiple points in time throughout the diurnal time period as a ratio of the BBR, such as 0×, 1×, and 2×. At block720, variations between actual insulin delivered values and the BBR for the diurnal time period can be determined. For example, if the delivery actions throughout the diurnal time period deliver a ratio of the BBR, the actual delivery actions may be averaged over the diurnal time period to find an average ratio for the diurnal time period. In these and other cases, the actual insulin delivered values can be based on periodically projected blood glucose levels and the BBR. For example, a set of insulin delivery profiles can be generated and a delivery action selected as described in the present disclosure (e.g., as described inFIG.6). At block730, a determination is made as to whether the variations between the actual insulin delivered values and the baseline basal insulin rate exceeds a threshold. If the variations do exceed the threshold, the method700may proceed to the block740. If the variations do not exceed the threshold, the method700may proceed back to the block710. In some cases, the threshold may be based on a ratio of the baseline basal delivery rate. For example, the threshold may include that the average rate over the diurnal period be above 150% of the BBR or below 50% of the BBR for the actual delivery values over the diurnal time period. At block740, the baseline basal insulin rate can be adjusted for a related diurnal time period. For example, the BBR can be adjusted higher by a certain amount (e.g., 1%, 2%, or 5%) if the variations went above a threshold and can be adjusted lower by a certain amount (e.g., 1%, 2%, or 5%) if the variations went below a threshold. In some cases, the related diurnal time period can be the same block of time (e.g., if the variations exceeded the threshold during the 2 PM to 3 PM diurnal period, then the BBR from 2 PM to 3 PM of the next day may be adjusted) on another day in the future, and in some cases, the related diurnal time period can be a different time on another day (e.g., if the variations exceeded the threshold during the 2 PM to 3 PM diurnal period, then the BBR from 1 PM to 2 PM of the next day may be adjusted). In some cases, such an adjustment may be performed once per day for all the diurnal periods of that day. In some cases, the adjustment at block740can include smoothing of the adjustment. For example, a potential modification can be compared to the BBR of the preceding diurnal time period or the following diurnal time period, and may modify the adjustment to be closer to the other diurnal time periods. Additionally or alternatively, the BBR can be smoothed by comparing the potential modification to BBRs of the same time of day for preceding days to determine whether the potential modification may be responsive to an unusual day. In some cases the adjustment at block740can consider other factors. For example, the adjustment can be based on penalizing a modification that increases the probability of the PWD having a hypoglycemic event (e.g., by penalizing modifications that may increase the probability of the blood glucose levels of the PWD falling below a threshold low blood glucose level). In these and other cases, in addition to or in place of adjusting the BBR, other user-specific dosage guidelines can be adjusted. For example, ISF and CR can also be adjusted according to the present disclosure. In some cases, if BBR is adjusted higher, ISF may be adjusted higher by the same or an approximately proportional percentage amount and CR may be adjusted lower by the same or an approximately proportional percentage amount of the BBR. At block750, insulin may be delivered during the related diurnal time period based on the adjusted baseline basal insulin rate. For example, the insulin pump can deliver insulin based on the adjusted baseline basal insulin rate. In some cases, such delivery can include a control device (e.g., the control circuitry240ofFIG.5B) sending a message to the insulin pump to deliver insulin. Modifications, additions, or omissions may be made to the method700without departing from the scope of the present disclosure. For example, the operations of the method700may be implemented in differing order. Additionally or alternatively, two or more operations may be performed at the same time. Furthermore, the outlined operations and actions are provided as examples, and some of the operations and actions may be optional, combined into fewer operations and actions, or expanded into additional operations and actions without detracting from the essence of the disclosed embodiments. FIG.8illustrates a flowchart of an example method800of utilizing a fear of hypoglycemia index. The method800may be performed by any suitable system, apparatus, or device. For example, the system10, the pump assembly15, the mobile computing device60ofFIG.1, and/or a remote server may perform one or more of the operations associated with the method800. Although illustrated with discrete blocks, the steps and operations associated with one or more of the blocks of the method800may be divided into additional blocks, combined into fewer blocks, or eliminated, depending on the desired implementation. At block810, an interface can be displayed to a user to input an FHI. For example, an interface can be displayed on a mobile computing device (e.g., the mobile computing device60ofFIG.1) and/or to a terminal connected over a network such as the Internet to a remote server. In some cases, the user (e.g., a PWD or a healthcare professional) can be presented with an interactive feature from which the user can select the FHI. In these and other cases, the interface can include a variety of ways that the user can input the FHI, such as a preferred blood glucose level, a preferred probability of going above or below a certain threshold, a textual description of a blood glucose level (e.g., “prefer high”), etc. In these and other cases, the FHI can correspond to a threshold blood glucose level and an acceptable probability of crossing the threshold blood glucose level. For example, “prefer high” may designate a low threshold blood glucose level as 100 mg/dl, with a target blood glucose level of 150 mg/dl, and a high threshold blood glucose level of 220 mg/dl, and an acceptable probability of 5% for exceeding either the low or the high threshold values. At block820, a probability of a PWD crossing a threshold blood glucose level is calculated. For example, a calculation can be made as to how likely the PWD is to cross the threshold blood glucose level corresponding to the FHI. In these and other cases, the probability of crossing the threshold can also be compared to the acceptable probability of crossing the threshold. For example, if the FHI indicates that a 5% probability of exceeding a threshold is acceptable, the calculated probability of exceeding the threshold can be compared to the 5% acceptable probability. At block830, target blood glucose level can be modified to more closely align the probability of crossing the threshold with the FHI. For example, if the probability of dropping below a threshold is higher than the acceptable probability, the target blood glucose level may be adjusted higher such that the probability is closer to the acceptable probability. In some cases, the target blood glucose level can be adjusted such that the probability of crossing the threshold is the same as the acceptable probability. In these and other cases, the modification of the baseline basal insulin rate can also be based on the actual insulin delivered compared to the BBR for a diurnal period. For example, if four delivery actions occur during a diurnal time period and each of them deliver 2× the BBR, the BBR can be modified based on both the FHI and the 2× delivered. Continuing the example, if a user had selected a low FHI (e.g., the PWD is not as concerned about going low), the target blood glucose level can be changed by a large amount (e.g., between 0% and 5%) while if the user had selected a high FHI (e.g., the PWD is concerned about going low), the BBR can be changed be a smaller amount (e.g., between 0% and 2%). In these and other cases, the change amount can vary depending on whether it is adjusting up or down. For example, for a PWD that prefers high blood glucose levels, methods and systems of the present disclosure can use a larger change when adjusting the BBR upwards and a lower change when adjusting the BBR downwards. In some cases, increases to the target blood glucose level can be unconstrained, but decreases constrained to 5% or less, 3% or less, 2% or less, or 1% or less. At block840, insulin can be delivered based on the modified target blood glucose level. For example, a control device can determine insulin delivery profiles or rates based the target blood glucose level(s) using any suitable method, including the methods described above. In some cases, the delivery of insulin can be based off of one or more insulin delivery profiles that can be generated, and selecting one of the profiles that most closely approximates a target blood glucose level. In these and other cases, the actions of the delivery profiles can be a ratio of the modified BBR. For example, the delivery actions can include one of delivering 0×, 1×, or 2× the modified BBR. In some cases, the delivery actions of the delivery profiles can be based off of the FHI as well. For example, for a first FHI (e.g., the PWD is concerned about going low), the possible ratios used in the delivery actions of the profile can include 0×, 0.5×, 1× and 1.5× the BBR (e.g., for a PWD that prefers low), while for a second FHI, the possible ratios used in the delivery actions of the profile can include 0×, 1×, 2×, and 3× (e.g., for a PWD that prefers high). Modifications, additions, or omissions may be made to the method800without departing from the scope of the present disclosure. For example, the operations of the method800may be implemented in differing order. Additionally or alternatively, two or more operations may be performed at the same time. Furthermore, the outlined operations and actions are provided as examples, and some of the operations and actions may be optional, combined into fewer operations and actions, or expanded into additional operations and actions without detracting from the essence of the disclosed embodiments. FIG.9illustrates a flowchart of an example method900of utilizing a temporary override. The method900may be performed by any suitable system, apparatus, or device. For example, the system10, the pump assembly15, the mobile computing device60ofFIG.1, and/or a remote server may perform one or more of the operations associated with the method900. Although illustrated with discrete blocks, the steps and operations associated with one or more of the blocks of the method900may be divided into additional blocks, combined into fewer blocks, or eliminated, depending on the desired implementation. At block910, a set of insulin delivery profiles may be generated, each having a series of insulin delivery actions. For example, an electronic device (e.g., the pump assembly15, the mobile computing device60ofFIG.1and/or a remote server) may generate a set of profiles in accordance with the present disclosure. At block920, an input indicating a temporary override may be received. The temporary override can indicate a user-preferred blood glucose level for one or more diurnal periods. For example, a user (e.g., a PWD) may be presented with a field or other entry component where the user can enter a numerical blood glucose level for a set period of time. As another example, the user may be presented with multiple activities (e.g., exercising, driving a car for an extended period of time, etc.) and when the activity will be performed. As another example, the user may be presented with a series of textual descriptions of preferred blood glucose levels (e.g., “do not go low,” or “do not go high”). In these and other cases, the user may be limited in selecting a temporary override for a period of time some point in the future (e.g., at least thirty minutes in the future). At block930, a log of the temporary override can be generated. For example, the electronic device can record what was selected for the temporary override (e.g., a target blood glucose level, a particular activity, etc.), when, and/or for how long. In some cases, the log may be updated each time the user inputs a temporary override. At block940, a baseline basal insulin rate (BBR) can be temporarily modified based on the temporary override. For example, the BBR can be modified to more closely align the BBR with the user-preferred blood glucose level. For example, the BBR can be adjusted higher if the temporary override indicates a lower than normal blood glucose level. As another example, the BBR can be adjusted lower if the temporary override indicates a higher than normal blood glucose level. In some cases, the temporary override from the block920can be received and the BBR can be modified prior to generating the set of profiles, or the set of profiles can be updated after the temporary override is received and/or the BBR is modified. At block950, a determination can be made as to which profile from the set of profiles approximates the user-preferred blood glucose level during the diurnal period. For example, a predicted blood glucose level for various points in time can be projected based on each of the profiles. The variation from the user-preferred blood glucose level can be analyzed, for example, by accumulating the variation over time and finding the profile with the lowest variation from the user-preferred blood glucose level. In these and other cases, the profile that most closely approximates the user-preferred blood glucose level can be selected as the basis for delivery actions of insulin. At block960, insulin can be delivered based on the next action in the selected profile. For example, a given profile that was selected might have sixteen delivery actions spanning four hours, and the first of sixteen actions may be taken to deliver insulin. In some cases, the block960can include control circuitry or another control device generating a message to be provided to a pump to deliver insulin in accordance with the next action in the selected profile. At block970, the log can be periodically provided to a healthcare professional. For example, the log generated and/or updated at block930can be sent to a healthcare professional using email, text message, via an app, etc. such that the healthcare professional can review the overrides that have occurred for a PWD. At block980, the log can be parsed to determine if a pattern is present in the temporary overrides. For example, the PWD may input a temporary override every Monday, Wednesday, and Friday from 6 PM to 7 PM when they exercise. As another example, the PWD may input a temporary override Monday through Friday from 5:30 PM until 6:15 PM while the PWD drives home from work. The log can be parsed to find such patterns of overrides. At block990, the baseline basal insulin rate can be modified for a given diurnal period based on the pattern. Following the first example given at block980, methods and systems of the present disclosure can adjust the BBR for 6 PM to 7 PM on Monday, Wednesday and Friday based on the repeated overrides occurring at those times. Following the second example given at block980, methods and systems of the present disclosure can adjust the BBR from 5:30 PM to 6:15 PM Monday through Friday based on the repeated overrides for that span of time. Modifications, additions, or omissions may be made to the method900without departing from the scope of the present disclosure. For example, the operations of the method900may be implemented in differing order (e.g., the block920can be performed after the block910, and/or the blocks970and/or980can be performed any time after the block930). Additionally or alternatively, two or more operations may be performed at the same time. Furthermore, the outlined operations and actions are provided as examples, and some of the operations and actions may be optional (e.g., the blocks930,940,970,980, and/or990), combined into fewer operations and actions, or expanded into additional operations and actions without detracting from the essence of the disclosed embodiments. The embodiments described herein may include the use of a special-purpose or general-purpose computer including various computer hardware or software modules, as discussed in greater detail below. Embodiments described herein may be implemented using computer-readable media for carrying or having computer-executable instructions or data structures stored thereon. Such computer-readable media may be any available media that may be accessed by a general-purpose or special-purpose computer. By way of example, and not limitation, such computer-readable media may include non-transitory computer-readable storage media including Random-Access Memory (RAM), Read-Only Memory (ROM), Electrically Erasable Programmable Read-Only Memory (EEPROM), Compact Disc Read-Only Memory (CD-ROM) or other optical disk storage, magnetic disk storage or other magnetic storage devices, Flash memory devices (e.g., solid-state memory devices), or any other storage medium which may be used to carry or store desired program code in the form of computer-executable instructions or data structures and which may be accessed by a general-purpose or special-purpose computer. Combinations of the above may also be included within the scope of computer-readable media. Computer-executable instructions comprise, for example, instructions and data which cause a general-purpose computer, special-purpose computer, or special-purpose processing device (e.g., one or more processors) to perform a certain function or group of functions. Although the subject matter has been described in language specific to structural features and/or methodological acts, it is to be understood that the subject matter defined in the appended claims is not necessarily limited to the specific features or acts described above. Rather, the specific features and acts described above are disclosed as example forms of implementing the claims. As used herein, the terms “module” or “component” may refer to specific hardware implementations configured to perform the operations of the module or component and/or software objects or software routines that may be stored on and/or executed by general-purpose hardware (e.g., computer-readable media, processing devices, etc.) of the computing system. In some embodiments, the different components, modules, engines, and services described herein may be implemented as objects or processes that execute on the computing system (e.g., as separate threads). While some of the systems and methods described herein are generally described as being implemented in software (stored on and/or executed by general-purpose hardware), specific hardware implementations or a combination of software and specific hardware implementations are also possible and contemplated. In the present description, a “computing entity” may be any computing system as previously defined herein, or any modules or combination of modulates running on a computing system. Any ranges expressed herein (including in the claims) are considered to be given their broadest possible interpretation. For example, unless explicitly mentioned otherwise, ranges are to include their end points (e.g., a range of “between X and Y” would include X and Y). Additionally, ranges described using the terms “approximately” or “about” are to be understood to be given their broadest meaning consistent with the understanding of those skilled in the art. Additionally, the term approximately includes anything within 10%, or 5%, or within manufacturing or typical tolerances. All examples and conditional language recited herein are intended for pedagogical objects to aid the reader in understanding the disclosure and the concepts contributed by the inventor to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Although embodiments of the present disclosure have been described in detail, it should be understood that the various changes, substitutions, and alterations could be made hereto without departing from the spirit and scope of the disclosure. | 130,624 |
11857764 | While various embodiments are amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail. It should be understood, however, that the intention is not to limit the claimed inventions to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the subject matter as defined by the claims. DETAILED DESCRIPTION OF THE DRAWINGS The following detailed description should be read with reference to the drawings in which similar elements in different drawings are numbered the same. The drawings, which are not necessarily to scale, depict illustrative embodiments and are not intended to limit the scope of the invention. FIG.1depicts an embodiment of a medical device according to the disclosure. In this embodiment, the medical device is configured as a pump12, such as an infusion pump, that can include a pumping or delivery mechanism and reservoir for delivering medicament to a patient and an output/display44. The output/display44may include an interactive and/or touch sensitive screen46having an input device such as, for example, a touch screen comprising a capacitive screen or a resistive screen. The pump12may additionally or instead include one or more of a keyboard, a microphone or other input devices known in the art for data entry, some or all of which may be separate from the display. The pump12may also include a capability to operatively couple to one or more other display devices such as a remote display, a remote control device, a laptop computer, personal computer, tablet computer, a mobile communication device such as a smartphone, a wearable electronic watch or electronic health or fitness monitor, or personal digital assistant (PDA), a CGM display etc. In one embodiment, the medical device can be a portable insulin pump configured to deliver insulin to a patient. Further details regarding such pump devices can be found in U.S. Pat. No. 8,287,495, which is incorporated herein by reference in its entirety. In other embodiments, the medical device can be an infusion pump configured to deliver one or more additional or other medicaments to a patient. In a further embodiment, the medical device can be a glucose meter such as a BGM or CGM. FIG.2illustrates a block diagram of some of the features that can be used with embodiments of the present invention, including features that may be incorporated within the housing26of a medical device such as a pump12. The pump12can include a processor42that controls the overall functions of the device. The infusion pump12may also include, e.g., a memory device30, a transmitter/receiver32, an alarm34, a speaker36, a clock/timer38, an input device40, a user interface suitable for accepting input and commands from a user such as a caregiver or patient, a drive mechanism48, an estimator device52and a microphone (not pictured). One embodiment of a user interface is a graphical user interface (GUI)60having a touch sensitive screen46with input capability. In some embodiments, the processor42may communicate with one or more other processors within the pump12and/or one or more processors of other devices, for example, a continuous glucose monitor (CGM), display device, smartphone, etc. through the transmitter/receiver. The processor42may also include programming that may allow the processor to receive signals and/or other data from an input device, such as a sensor that may sense pressure, temperature or other parameters. FIGS.3A-3Bdepict another pump system including a pump102that can be used with embodiments. Drive unit118of pump102includes a drive mechanism122that mates with a recess in disposable cartridge116of pump102to attach the cartridge116to the drive unit118. Pump system100can further include an infusion set145having a connector154that connects to a connector152attached to pump102with tubing153. Tubing144extends to a site connector146that can attach or be pre-connected to a cannula and/or infusion needle that punctures the patient's skin at the infusion site to deliver medicament from the pump102to the patient via infusion set145. In one embodiment, pump102includes a processor that controls operations of the pump and, in some embodiments, may receive commands from a separate device for control of operations of the pump. Such a separate device can include, for example, a dedicated remote control or a smartphone or other consumer electronic device executing an application configured to enable the device to transmit operating commands to the processor of pump102. In some embodiments, processor can also transmit information to one or more separate devices, such as information pertaining to device parameters, alarms, reminders, pump status, etc. In one embodiment pump102does not include a display but may include one or more indicator lights174and/or one or more input buttons172. Pump102can also incorporate any or all of the features described with respect to pump12inFIG.2. Further details regarding such pumps can be found in U.S. Pat. No. 10,279,106 and U.S. Patent Publication Nos. 2016/0339172 and 2017/0049957, each of which is hereby incorporated herein by reference in its entirety. Pump12or102can interface directly or indirectly (via, e.g., a smartphone or other device) with a glucose meter, such as a blood glucose meter (BGM) or a continuous glucose monitor (CGM). Referring toFIG.4, an exemplary CGM system100according to an embodiment of the present invention is shown (other CGM systems can be used). The illustrated CGM system includes a sensor101affixed to a patient104that can be associated with the insulin infusion device in a CGM-pump system. The sensor101includes a sensor probe106configured to be inserted to a point below the dermal layer (skin) of the patient104. The sensor probe106is therefore exposed to the patient's interstitial fluid or plasma beneath the skin and reacts with that interstitial fluid to produce a signal that can be associated with the patient's blood glucose (BG) level. The sensor101includes a sensor body108that transmits data associated with the interstitial fluid to which the sensor probe106is exposed. The data may be transmitted from the sensor101to the glucose monitoring system receiver100via a wireless transmitter, such as a near field communication (NFC) radio frequency (RF) transmitter or a transmitter operating according to a “Wi-Fi” or Bluetooth® protocol, Bluetooth® low energy protocol or the like, or the data may be transmitted via a wire connector from the sensor101to the monitoring system100. Transmission of sensor data to the glucose monitoring system receiver by wireless or wired connection is represented inFIG.4by the arrow line112. Further detail regarding such systems and definitions of related terms can be found in, e.g., U.S. Pat. Nos. 8,311,749, 7,711,402 and 7,497,827, each of which is hereby incorporated by reference in its entirety. In an embodiment of a pump-CGM system having a pump12,102that communicates with a CGM and that integrates CGM data and pump data as described herein, the CGM can automatically transmit the glucose data to the pump. The pump can then automatically determine therapy parameters and deliver medicament based on the data. Such an automatic pump-CGM system for insulin delivery can be referred to as an artificial pancreas system that provides closed-loop therapy to the patient to approximate or even mimic the natural functions of a healthy pancreas. In such a system, insulin doses are calculated based on the CGM readings (that may or may not be automatically transmitted to the pump) and are automatically delivered to the patient at least in part based on the CGM reading(s). For example, if the CGM indicates that the user has a high blood glucose level or hyperglycemia, the system can automatically calculate an insulin dose necessary to reduce the user's blood glucose level below a threshold level or to a target level and automatically deliver the dose. Alternatively, the system can automatically suggest a change in therapy upon receiving the CGM data such as an increased insulin basal rate or delivery of a bolus, but can require the user to accept the suggested change prior to delivery rather than automatically delivering the therapy adjustments. If the CGM data indicates that the user has a low blood glucose level or hypoglycemia, the system can, for example, automatically reduce a basal rate, suggest to the user to reduce a basal rate, automatically deliver or suggest that the user initiate the delivery of an amount of a substance such as, e.g., a hormone (glucagon) to raise the concentration of glucose in the blood, automatically suggest that the user, e.g., ingest carbohydrates and/or take other actions and/or make other suggestions as may be appropriate to address the hypoglycemic condition, singly or in any desired combination or sequence. Such determination can be made by the infusion pump providing therapy or by a separate device that transmits therapy parameters to the infusion pump. In some embodiments, multiple medicaments can be employed in such a system as, for example, a first medicament, e.g., insulin, that lowers blood glucose levels and a second medicament, e.g., glucagon, that raises blood glucose levels. As with other parameters related to therapy, such thresholds and target values can be stored in memory located in the pump or, if not located in the pump, stored in a separate location and accessible by the pump processor (e.g., “cloud” storage, a smartphone, a CGM, a dedicated controller, a computer, etc., any of which is accessible via a network connection). The pump processor can periodically and/or continually execute instructions for a checking function that accesses these data in memory, compares them with data received from the CGM and acts accordingly to adjust therapy. In further embodiments, rather than the pump determining the therapy parameters, the parameters can be determined by a separate device and transmitted to the pump for execution. In such embodiments, a separate device such as the CGM or a device in communication with the CGM, such as, for example, a smartphone, dedicated controller, electronic tablet, computer, etc. can include a processor programmed to calculate therapy parameters based on the CGM data that then instruct the pump to provide therapy according to the calculated parameters. As is known in the art, a meal bolus alarm is an alarm that reminds the user to deliver a meal bolus during a predetermined time interval. For example, if the user typically eats breakfast between 7:00 am and 8:00 am, the user may set a missed meal bolus alarm/reminder for an interval between, e.g., 6:15 am and 8:00 am. In this example, an alarm sounds if a meal bolus is not delivered within this interval. Generally, the user can navigate the menu structure of an infusion pump and/or remote control for an infusion pump to a Missed Meal Bolus Reminder or Alarm setting. From there, the user can select a start time and an end time defining a period of time during which a meal is expected to be consumed for a reminder that is then stored in memory and can be turned on and off and/or set to be active on certain days. If the reminder or alarm is turned on and/or active on a given day, the pump and/or remote will detect whether or not a meal bolus was programmed and/or delivered during the programmed period of time. If a meal bolus is delivered, then the pump takes no further action. However, if no meal bolus is delivered by the programmed end time, the pump will automatically issue a missed meal bolus alarm reminder or alert to remind the user to deliver a meal bolus responsive to the expected meal. Further details regarding missed meal bolus alarms/reminders can be found in U.S. Pat. No. 8,690,856, which is hereby incorporated by reference herein in its entirety. Existing infusion pumps therefore can be programmed to alert the user if no bolus is given during a specified time window, but do so automatically if no bolus is delivered without detecting if the patient actually ate a meal such that the bolus is actually required. For example, a user may at times skip a usual meal for which a missed bolus alarm or reminder is programmed such that the alarm/reminder is not necessary. With missed meal bolus reminders or alerts as described above, the reminder/alert requiring the user to access the user's pump and/or remote control and clear the reminder/alert even when the user skipped a meal is an unnecessary hassle. Embodiments described herein seek to address this issue by leveraging CGM data such that the missed meal bolus alert is only triggered when glucose levels rise in response to consuming the meal within the programmed time window. Therefore, the alert is only provided when a meal is actually consumed and no bolus has been delivered. This further allows the user to be alerted sooner, i.e., as soon as glucose levels rise a predetermined amount or passed a predetermined threshold indicating consumption of a meal as opposed to only at the end of the programmed window. In one embodiment, software resident on the pump and/or a device for remotely controlling the pump reads and/or records the glucose level/status from the CGM at the start of the programmed meal window. During the meal window, the software continuously or periodically checks if the glucose level has risen by more than a certain threshold above the starting level. The threshold can be, for example, an amount above the starting level, a percentage above the starting level and/or a predetermined high glucose level threshold. In various embodiments, the detection threshold could be fixed, selected from a limited list of options, or completely user specified. The software alerts with a missed bolus alarm/reminder only if the glucose level has risen above the threshold and no bolus has been administered during the meal window. In various embodiments, the software can provide the alert when the threshold is reached before the end of the programmed time period or can be delayed until the end of the time period even after reaching the threshold in order to enable to user to still deliver the bolus within the programmed window. If the threshold has not been reached by the end of the programmed missed meal bolus window, the missed meal bolus alert/reminder is not provided to the user. This effectively provides an automatic cancellation of the missed meal bolus alarm based on the CGM data indicating no meal was consumed, which saves the user the inconvenience of having to address an unneeded alert. In various embodiments, the software can utilize other statistical measures alternatively and/or in addition to glucose level. For example, the software can analyze the glucose rate (e.g., in mg/dL/min) during the meal window and alert only when the glucose rate is above a threshold and/or analyze the change in glucose rate during the meal window and alert only when the glucose rate changes by a threshold. FIG.5depicts an embodiment of a method200of providing diabetes therapy that includes detecting un-bolused meals and modifying missed meal bolus alarms according to an embodiment. At step202programming for a missed meal bolus alarm for an infusion pump is received and stored. In embodiments, the alarm input can be received via a user interface of and stored via a memory of the infusion pump, a remote control device, etc. The method continues at step204when the beginning time for the programmed alarm is reached on a day for which the programmed alarm is turned on/active. During the programmed time window, the system monitors both whether or not a meal bolus is delivered with the pump at step206and the CGM data for the user at step208. At step210, the system determines if a meal bolus has been delivered with the pump. If so, at step212the missed meal bolus alarm is cancelled and no alarm is issued because a bolus corresponding to the scheduled meal was delivered. When no meal bolus has been delivered, the system at step214continually monitors the CGM data to determine if the CGM alarm threshold has been reached. If the CGM alarm threshold is reached and no meal bolus has been delivered, the missed meal bolus alarm is issued at step216. This can be done, for example, at the time the threshold is reached as indicated by the solid arrow inFIG.5or only after the programmed end time of the alarm window is reached at step218without a meal bolus being delivered as indicated by the dashed arrows inFIG.5. If the CGM alarm threshold is not reached when the alarm window ends at step218, the system reverts to step212and no missed meal bolus alarm is issued because the system has determined from the CGM data that no meal was consumed. As noted above, method200saves a user from the hassle and inconvenience of responding to unnecessary missed meal bolus alarms when no meal was consumed during a programmed meal window. In embodiments, the software can further automatically disable the missed meal bolus reminder if the glucose level goes below a low threshold and/or is dropping at a rate greater than a threshold. For example, if a user's glucose level is low, the carbohydrates consumed during the meal window may be needed to bring the user's glucose level up to a safer level and delivery of a meal bolus may drop the user's glucose level to a dangerously low level. By disabling the bolus reminder when a user's glucose level is below a certain predetermined threshold, delivery of such an unneeded bolus can be deterred. Although primarily described herein with respect to a processor of an infusion pump in communication with a CGM, it should be understood that some or all of the steps of the methods described herein can be performed by a processor of a remote control device including, for example, a consumer electronic device such as a smartphone or a dedicated remote controller, in communication with a CGM. For example, the remote control device may receive and store the missed meal bolus alarm, communicate with the CGM to receive CGM data and determine whether or not the missed meal bolus alarm should be issued. Such remote control device may communicate with the pump to determine if a bolus was delivered with the pump and/or the device may inherently know whether or not a bolus has been delivered by receiving the bolus programming at the remote control device and issuing an operating command to the pump to deliver the bolus. Although the embodiments herein are specifically described with respect to the delivery of insulin, delivery of other medicaments, singly or in combination with one another or with insulin, including, for example, glucagon, pramlintide, etc., as well as other applications are also contemplated. Device and method embodiments discussed herein may be used for pain medication, chemotherapy, iron chelation, immunoglobulin treatment, dextrose or saline IV delivery, treatment of various conditions including, e.g., pulmonary hypertension, or any other suitable indication or application. Non-medical applications are also contemplated. Also incorporated herein by reference in their entirety are commonly owned U.S. Pat. Nos. 6,999,854; 8,133,197; 8,287,495; 8,408,421 8,448,824; 8,573,027; 8,650,937; 8,986,523; 9,173,998; 9,180,242; 9,180,243; 9,238,100; 9,242,043; 9,335,910; 9,381,271; 9,421,329; 9,486,171; 9,486,571; 9,492,608; 9,503,526; 9,555,186; 9,565,718; 9,603,995; 9,669,160; 9,715,327; 9,737,656; 9,750,871; 9,867,937; 9,867,953; 9,940,441; 9,993,595; 10,016,561; 10,201,656; 10,279,105; 10,279,106 and 10,279,107. commonly owned U.S. Patent Publication Nos. 2009/0287180; 2012/0123230; 2013/0053816; 2014/0276419; 2014/0276420; 2014/0276423; 2014/0276569; 2014/0276570; 2016/0082188; 2017/0142658; 2017/0182248; 2017/0250971; 2018/0021514; 2018/0071454 and 2018/0193555 commonly owned U.S. patent application Ser. Nos. 16/266,471 and 16/380,475. Further incorporated by reference herein in their entirety are U.S. Pat. Nos. 8,601,465; 8,502,662; 8,452,953; 8,451,230; 8,449,523; 8,444,595; 8,343,092; 8,285,328; 8,126,728; 8,117,481; 8,095,123; 7,999,674; 7,819,843; 7,782,192; 7,109,878; 6,997,920; 6,979,326; 6,936,029; 6,872,200; 6,813,519; 6,641,533; 6,554,798; 6,551,276; 6,295,506; and 5,665,065. Various embodiments of systems, devices, and methods have been described herein. These embodiments are given only by way of example and are not intended to limit the scope of the claimed inventions. It should be appreciated, moreover, that the various features of the embodiments that have been described may be combined in various ways to produce numerous additional embodiments. Moreover, while various materials, dimensions, shapes, configurations and locations, etc. have been described for use with disclosed embodiments, others besides those disclosed may be utilized without exceeding the scope of the claimed inventions. Persons of ordinary skill in the relevant arts will recognize that the subject matter hereof may comprise fewer features than illustrated in any individual embodiment described above. The embodiments described herein are not meant to be an exhaustive presentation of the ways in which the various features of the subject matter hereof may be combined. Accordingly, the embodiments are not mutually exclusive combinations of features; rather, the various embodiments can comprise a combination of different individual features selected from different individual embodiments, as understood by persons of ordinary skill in the art. Moreover, elements described with respect to one embodiment can be implemented in other embodiments even when not described in such embodiments unless otherwise noted. Although a dependent claim may refer in the claims to a specific combination with one or more other claims, other embodiments can also include a combination of the dependent claim with the subject matter of each other dependent claim or a combination of one or more features with other dependent or independent claims. Such combinations are proposed herein unless it is stated that a specific combination is not intended. | 22,329 |
11857765 | DETAILED DESCRIPTION The following detailed description is merely illustrative in nature and is not intended to limit the embodiments of the subject matter or the application and uses of such embodiments. As used herein, the word “exemplary” means “serving as an example, instance, or illustration.” Any implementation described herein as exemplary is not necessarily to be construed as preferred or advantageous over other implementations. Furthermore, there is no intention to be bound by any expressed or implied theory presented in the preceding technical field, background, brief summary or the following detailed description. Exemplary embodiments of the subject matter described herein are implemented in conjunction with medical devices, such as portable electronic medical devices. Although many different applications are possible, the following description focuses on embodiments that incorporate a fluid infusion device (or infusion pump) as part of an infusion system deployment. For the sake of brevity, conventional techniques related to infusion system operation, insulin pump and/or infusion set operation, and other functional aspects of the systems (and the individual operating components of the systems) may not be described in detail here. Examples of infusion pumps may be of the type described in, but not limited to, U.S. Pat. Nos. 4,562,751; 4,685,903; 5,080,653; 5,505,709; 5,097,122; 6,485,465; 6,554,798; 6,558,320; 6,558,351; 6,641,533; 6,659,980; 6,752,787; 6,817,990; 6,932,584; and 7,621,893; each of which are herein incorporated by reference. That said, the subject matter described herein can be utilized more generally in the context of overall diabetes management or other physiological conditions independent of or without the use of an infusion device or other medical device (e.g., when oral medication is utilized), and the subject matter described herein is not limited to any particular type of medication. Generally, a fluid infusion device includes a motor or other actuation arrangement that is operable to linearly displace a plunger (or stopper) of a reservoir provided within the fluid infusion device to deliver a dosage of fluid, such as insulin, to the body of a user. Dosage commands that govern operation of the motor may be generated in an automated manner in accordance with the delivery control scheme associated with a particular operating mode, and the dosage commands may be generated in a manner that is influenced by a current (or most recent) measurement of a physiological condition in the body of the user. For example, in a closed-loop operating mode, dosage commands may be generated based on a difference between a current (or most recent) measurement of the interstitial fluid glucose level in the body of the user and a target (or reference) glucose value. In this regard, the rate of infusion may vary as the difference between a current measurement value and the target measurement value fluctuates. For purposes of explanation, the subject matter is described herein in the context of the infused fluid being insulin for regulating a glucose level of a user (or patient); however, it should be appreciated that many other fluids may be administered through infusion, and the subject matter described herein is not necessarily limited to use with insulin. Exemplary embodiments described herein generally relate to systems for modeling control parameters or variables in a manner that improves component performance, systemic performance, user experience, and/or the like, an in particular, in conjunction with operation of a medical device, such as, for example, operation of a sensing arrangement (or sensing device) to monitor a physiological condition in a body of a patient or operation of an infusion device delivering fluid influencing the physiological condition to the body of the patient. In this regard, the current values utilized for such parameters or variables may be determined dynamically or in real-time using the corresponding model to account for the current operational context experienced by the respective device. In exemplary embodiments, the parameter models are personalized and patient-specific, and rely on input variables indicative of the current operational context that have been identified as predictive or correlative to the value of that parameter based on historical data associated with the patient. In this regard, for each patient, the particular subset of input variables that are predictive or correlative to a particular parameter for that patient may be different from those of other patients. In one or more exemplary embodiments, patient-specific models are utilized to calculate or otherwise determine factors used to convert a measurement signal to a corresponding calibrated measurement value, such as a calibrated glucose measurement value. For example, the calibration factor used to convert from a measurement signal to a calibrated glucose measurement value may be determined based at least in part on one or more of a current location of the sensing arrangement (or sensor site location) on the body of the patient, the number or type of sensing arrangements being utilized, current measurements from other sensing arrangements, one or more current temporal variables (e.g., current time of day, day of week, month of year, etc.), one or more current environmental or geographic variables, patient demographics, and/or current patient variables (e.g., the patient's current weight, body mass index, or the like). Thus, the calibration factor may vary over time as dictated by different operational contexts, and in a unique patient-specific manner. Similarly, the amount of offset to be applied to the measurement signal before conversion may be determined dynamically or in real-time and in a patient-specific manner using a corresponding model. Additionally, in some embodiments, patient-specific models are utilized to generate user notifications, alerts or indications or generate graphical user interface (GUI) displays. For example, a patient-specific model may be utilized to determine one or more optimal or recommended times of day for the patient to calibrate a sensing arrangement and provide corresponding indications or guidance to the patient. Similarly, a patient-specific model may be utilized to determine one or more optimal or recommended sensor site locations on the body for the sensing arrangement and provide corresponding indications or guidance to the patient. In this regard, a sensor site (or site), site location, or variants thereof should be understood as referring to a distinct region of the body where a sensing arrangement may be attached, inserted, affixed, or otherwise located. It should also be noted that different sites may be associated with a common part of the body (e.g., the abdomen) while being physically distinguishable (e.g., different sides of the body, different quadrants or sectors of a body part, or the like). In some embodiments, patient-specific models are also utilized to calculate or otherwise determine one or more metrics indicative of the health or useful life of the sensing arrangement and provide corresponding indications or guidance to the patient. Additionally, in some embodiments, patient-specific models may be utilized to dynamically adjust one or more aspects of the control scheme being implemented by changing the values of control parameters or the like relied on by the control scheme. FIG.1depicts an exemplary embodiment of a patient management system100. The patient management system100includes an infusion device102that is communicatively coupled to a sensing arrangement104to obtain measurement data indicative of a physiological condition in the body of a patient, such as sensor glucose measurement values, as described in greater detail below in the context ofFIGS.5-10. In one or more exemplary embodiments, the infusion device102operates autonomously to regulate the patient's glucose level based on the sensor glucose measurement values received from the sensing arrangement104. In the illustrated embodiment, the infusion device102periodically uploads or otherwise transmits the measurement data (e.g., sensor glucose measurement values and timestamps associated therewith) to a remote device106via a communications network114, such as a wired and/or wireless computer network, a cellular network, a mobile broadband network, a radio network, or the like. That said, in other embodiments, the sensing arrangement104may be communicatively coupled to the communications network114to periodically upload or otherwise transmit measurement data to the remote device106via the communications network114independent of the infusion device102. WhileFIG.1depicts a single sensing arrangement104, in practice, embodiments of the system100may include multiple different sensing arrangements, which may be configured to sense, measure, or otherwise quantify any number of conditions or characteristics. For example, multiple instances of a glucose sensing arrangement104may be deployed for redundancy or other purposes (e.g., averaging or other statistical operations). In other embodiments, additional sensing arrangements104may be deployed to measure different physiological conditions of the patient, such as, for example, the patient's heart rate, oxygen levels, or the like. In exemplary embodiments, the infusion device102also uploads delivery data and/or other information indicative of the amount of fluid delivered by the infusion device and the timing of fluid delivery, which may include, for example, information pertaining to the amount and timing of manually-initiated boluses and associated meal announcements. Some examples of an infusion device uploading measurement and delivery data to a remote device are described in United States Patent Application Publication Nos. 2015/0057807 and 2015/0057634, which are incorporated by reference herein in their entirety. In addition to measurement and delivery data, various control parameter values of the sensing arrangement104and/or the infusion device102(e.g., calibration factors, sensitivity factors, and the like) may also be uploaded to the remote device106. The information uploaded to the remote device106by the infusion device102and/or the sensing arrangement104may also include operational context information, such as, for example, geographic location data associated with the infusion device102and/or the sensing arrangement104, data pertaining to environmental conditions (e.g., temperature, humidity, or the like) at the geographic location or in the vicinity of the infusion device102and/or the sensing arrangement104, and other data characterizing or describing the current operational context for the infusion device102and/or the sensing arrangement104. Additionally, current or updated patient data may be uploaded to the remote device106, such as, for example, the current weight of the patient, the height of the patient, the current body mass index of the patient, or the like. In some embodiments, activity or behavioral data for the patient may also be uploaded, such as, for example, indications of the type and duration of exercise or other activity undertaken by the patient. The uploaded information may also include gender information, age information, and other demographic information associated with the patient. The remote device106generally represents a computing system or another combination of processing logic, circuitry, hardware, and/or other components configured to support the processes, tasks, operations, and/or functions described herein. In this regard, the server106includes a processing system116, which may be implemented using any suitable processing system and/or device, such as, for example, one or more processors, central processing units (CPUs), controllers, microprocessors, microcontrollers, processing cores and/or other hardware computing resources configured to support the operation of the processing system116described herein. The processing system116may include or otherwise access a data storage element118(or memory) capable of storing programming instructions for execution by the processing system116, that, when read and executed, cause processing system116to perform or otherwise support the processes, tasks, operations, and/or functions described herein. For example, in one embodiment, the instructions cause the processing system116to create, generate, or otherwise facilitate an application platform that supports instances of an application using data that is stored or otherwise maintained by the database108. Depending on the embodiment, the memory118may be realized as a random access memory (RAM), read only memory (ROM), flash memory, magnetic or optical mass storage, or any other suitable non-transitory short or long term data storage or other computer-readable media, and/or any suitable combination thereof. In exemplary embodiments, the remote device106is coupled to a database108configured to store or otherwise maintain historical measurement data, historical delivery data, historical control parameter data, and other uploaded operational context or demographic information corresponding to such data in association with a patient associated with the infusion device102and/or the sensing arrangement104(e.g., using unique patient identification information). Additionally, the database108may store or otherwise maintain, in association with a particular patient, personalized and patient-specific control parameter models. In this regard, a control parameter model defines which input variables or parameters are to be factored in to calculate a resulting control parameter value along with relative weightings assigned to those respective inputs corresponding to how predictive or correlative the value of a respective model input value is to the control parameter value, as described in greater detail below in the context ofFIG.2. The remote device106generally represents an electronic device configured to analyze or otherwise monitor the measurement and delivery data obtained for the patient associated with the infusion device102and generate patient-specific control parameter models based on a respective patient's historical measurement, delivery, and control parameter data in conjunction with the historical operational context data and/or demographic data. In some embodiments, the remote device106also generates or otherwise facilitates a GUI display that is influenced by or otherwise reflects a control parameter value determined using a corresponding model. The GUI display may be presented on the remote device106or another electronic device110, alternatively referred to herein as a client device. In practice, the remote device106may reside at a location that is physically distinct and/or separate from the infusion device102, such as, for example, at a facility that is owned and/or operated by or otherwise affiliated with a manufacturer of the infusion device102. For purposes of explanation, but without limitation, the remote device106may alternatively be referred to herein as a server. The client device110generally represents an electronic device coupled to the network114, and in practice, the client device110can be realized as any sort of personal computer, mobile telephone, tablet or other network-enabled electronic device that includes a display device, such as a monitor, screen, or another conventional electronic display, capable of graphically presenting data and/or information provided by the server106along with a user input device, such as a keyboard, a mouse, a touchscreen, or the like, capable of receiving input data and/or other information from the user of the client device110. In one or more embodiments, a user, such as the patient, the patient's doctor or another healthcare provider, or the like, manipulates the client device110to execute a client application112that contacts the server106via the network114using a networking protocol, such as the hypertext transport protocol (HTTP) or the like. The client application112may be utilized by a user to access and view data stored in the database108via the server106, or otherwise receive information or indications pertaining to operations of the infusion device102and/or the sensing arrangement104. It should be appreciated thatFIG.1depicts a simplified representation of a patient management system100for purposes of explanation and is not intended to limit the subject matter described herein in any way. For example, in various embodiments, one or more of the devices102,104,106,108,110may be absent from the system100. For example, one or more of the infusion device102, the sensing arrangement104, or the client device110may be configured to perform the functionality described herein in the context of the remote device106and/or database108, in which case the remote device106and/or the database108may not be present in such an embodiment. FIG.2depicts an exemplary patient modeling process200suitable for implementation by a patient management system to develop a patient-specific control parameter model. The various tasks performed in connection with the patient modeling process200may be performed by hardware, firmware, software executed by processing circuitry, or any combination thereof. For illustrative purposes, the following description refers to elements mentioned above in connection withFIG.1. In practice, portions of the patient modeling process200may be performed by different elements of the patient management system100, such as, for example, the infusion device102, the sensing arrangement104, the server106, the database108, the client device110, the client application112, and/or the processing system116. It should be appreciated that the patient modeling process200may include any number of additional or alternative tasks, the tasks need not be performed in the illustrated order and/or the tasks may be performed concurrently, and/or the patient modeling process200may be incorporated into a more comprehensive procedure or process having additional functionality not described in detail herein. Moreover, one or more of the tasks shown and described in the context ofFIG.2could be omitted from a practical embodiment of the patient modeling process200as long as the intended overall functionality remains intact. The patient modeling process200begins by obtaining historical measurement data for the patient of interest and obtaining historical bolus data for the patient over the period corresponding to the historical measurement data (tasks202,204). For example, the infusion device102may periodically upload, to the server106via the network114, reference blood glucose measurement values obtained from the body of the patient (e.g., using a blood glucose meter or fingerstick device) along with bolus information including the timings and amounts of insulin delivered, including indications of whether a particular bolus is a meal bolus or otherwise associated with a meal. The bolus information may also include the amount of carbohydrates consumed, the type of meal, or the like. In this regard, in the absence of an explicit meal indication or announcement from the patient, the server106may automatically classify a bolus delivered as a meal bolus when a carbohydrate entry occurred within a threshold amount of time of the bolus being delivered (e.g., within 5 minutes). Additionally, the infusion device102(or alternatively, the sensing arrangement104) may periodically upload, to the server106, sensor glucose measurement values obtained from the body of the patient by the sensing arrangement104. In exemplary embodiments, the historical measurement values may also be stored in association with a current location of the sensing arrangement104(or sensor site location) on the body of the patient at the time the respective measurement values were obtained. The illustrated patient modeling process200also obtains demographic information or other clinically-relevant information associated with the patient (task206). Demographic information associated with the patient may be input or otherwise provided by the patient or another user to any one of the devices102,104,110in the system100and uploaded to the server106for storage in the database108in association with the patient. The demographic information may include, for example, the patient's height, weight, body mass index, age, ethnicity, residence information, or other information that may be utilized to classify the patient. In this regard, as demographic information associated with the patient changes (e.g., the patient gains or loses weight, ages, relocates, etc.), such updated demographic information may be uploaded or otherwise provided to the server106to update the patient's history stored in the database108. The demographic information may also be stored in association with a timestamp or other temporal information to facilitate analysis and establishing correlations with other data to generate patient-specific models, as described below. Other clinically-relevant information may be obtained and utilized, either in addition to or alternatively to the demographic information. Such clinically-relevant information may include, for example, the patient's medical history, the patient's medication or drug history, the patient's hospitalization or other treatment information and records, or the like. For purposes of explanation the subject matter is primarily described herein in the context of utilizing demographic information, but it should be appreciated that clinically-relevant information may be similarly utilized in an equivalent manner. In exemplary embodiments, the patient modeling process200continues by obtaining environmental and behavioral information associated with preceding operations of a sensing arrangement or infusion device (tasks208,210). In this regard, environmental and behavioral information concurrent to the measurement data, the delivery data, or potentially other data may be obtained and used to facilitate analysis of relationships between such data. The environmental information (e.g., temperature, humidity, and the like) may be received in any number of manners, such as, for example, via one or more environmental sensors integrated with the sensing arrangement104, the infusion device102, or the client device110, via the network114from a remote resource using geolocation information associated with any one of the sensing arrangement104, the infusion device102, or the client device110, or the like. Such environmental data may also be stored in association with a timestamp or other temporal information to facilitate analysis and establishing correlations with other data for generating patient-specific models, as described below. Similarly, behavioral information may be received in any number of manners. For example, in one embodiment, the patient may manipulate a user input device associated with any one of the devices102,104,110to provide an indication of the type, duration, and/or other characteristics of activities that the patient is, has, or will be engaged in, which, in turn, may be uploaded from the respective device102,104,110to the server106via the network114. In alternative embodiments, the behavioral information may be obtained from one or more sensing arrangements at the location of the patient, which may be either standalone sensing arrangements or integrated with any one of the devices102,104,110. For example, an accelerometer, pedometer, or similar device capable of sensing or otherwise detecting motion by the patient may be worn by the patient or integrated with any one of the devices102,104,110carried on or by the patient to provide measurements of the motion of the patient, which, in turn, may be uploaded to the server106via the network114. Similarly, a heart rate sensing arrangement or a similar sensing arrangement capable of sensing a physiological condition of the patient that is different from that measured by the sensing arrangement104to obtain measurements of a physiological condition correlative to activity by the patient. The behavioral data may also be stored in association with a timestamp or other temporal information to facilitate analysis and establishing correlations with other data for generating patient-specific models, as described below. The behavioral data may also include information such as the patient's usage of various sensor site locations (e.g., the sensor site location temporally associated with other pieces of data), the number or type of sensing arrangements being utilized by the patient, and potentially other aspects of the system100that are controlled, configured, or otherwise dictated by the patient. In exemplary embodiments, the patient modeling process200also obtains historical values for the parameter of interest to be modeled for the patient (task212). In this regard, the historical values for the parameter being modeled may also be uploaded to the server106via the network114by any one of the devices102,104,110. For example, when the parameter of interest is a calibration factor for converting a measurement signal output by a sensing element of the sensing arrangement104to a corresponding measurement value, each time the sensing arrangement104is calibrated, the sensing arrangement104and/or the infusion device102may upload or otherwise transmit the resulting calibration factor to the server106for storage in the database108as part of the patient's history. In addition to the calibration factor values, the sensing arrangement104and/or the infusion device102may also upload the reference measurement values (e.g., reference blood glucose measurement values obtained using a fingerstick device, a portable blood glucose measurement device, or the like) and corresponding measurement signal values used to calculate the calibration factor, along with corresponding timestamps or other temporal information to facilitate analysis and establishing correlations. In one or more embodiments, the server106stores or otherwise maintains, in the database108, one or more files or entries associated with the patient that maintains an association between the patient's historical sensor glucose measurement data, the patient's historical bolus and meal data, the patient's historical reference blood glucose measurements, the patient's current and/or past demographic information, the historical context information associated with operation of the patient's sensing arrangement104and/or infusion device102(e.g., historical environmental data, behavioral data, and the like), and historical values for the parameter of interest, along with timestamps or other temporal information associated with the respective pieces of historical data. It should be noted that the patient modeling process200may support modeling any number of parameters of interest, such that the database108may store historical values for any number of parameters or variables utilized by the sensing arrangement104and/or the infusion device102to support respective operation thereof. In this regard, one parameter of interest may be modeled as a function of other parameters or variables in addition to the historical measurement, delivery, and contextual data, and those parameters or variables themselves may also be modeled as a function of the historical measurement, delivery, and contextual data. Once a sufficient amount of historical data has been obtained by the server106and/or the database108, the patient modeling process200continues with determining a patient-specific model for a parameter of interest based on the patient's historical data. In one embodiment, the patient modeling process200requires that data for at least a minimum threshold number of days (or hours) has been uploaded to continue. In other embodiments, additional thresholds may be utilized to determine when modeling can occur, such as, for example, a minimum number of historical values for the parameter of interest or the like. Still referring toFIG.2, to obtain a model for a parameter of interest, the patient modeling process200identifies or otherwise determines a subset of the historical data that is predictive of or correlative to the historical values for the parameter of interest for that individual patient and generating a patient-specific model of the parameter of interest for that patient using that predictive subset of variables (tasks214,216). In this regard, in exemplary embodiments, the server106utilizes machine learning to determine which combination of historical sensor measurement data, historical delivery data, demographics data, environmental data, behavioral data, and other historical parameter data are most strongly correlated to or predictive of the contemporaneous historical values for the parameter of interest, and then determines a corresponding equation for calculating the value of the parameter of interest based on that subset of input variables. Thus, the model is capable of characterizing or mapping a particular combination of one or more of the current (or recent) sensor glucose measurement data, delivery data, demographic information, environmental conditions, patient behavior, and the like to a current value for the parameter of interest, and vice versa. Since each patient's physiological response may vary from the rest of the population, the subset of input variables that are predictive of or correlative to the parameter of interest for that patient may vary from other users. Additionally, the relative weightings applied to the respective variables of that predictive subset may also vary from other patient's who may have common predictive subsets, based on differing correlations between a particular input variable and the historical values of the parameter of interest for that particular patient. It should be noted that any number of different machine learning techniques may be utilized by the server106to determine what input variables are predictive of the parameter of interest for the current patient of interest, such as, for example, artificial neural networks, genetic programming, support vector machines, Bayesian networks, probabilistic machine learning models, or other Bayesian techniques, fuzzy logic, heuristically derived combinations, or the like. In one or more exemplary embodiments, only a subset of the historical data for the patient are used to develop the parameter model, with the remaining historical data being utilized by the patient modeling process200to test or otherwise validate the developed model (tasks218,220). For example, for the testing subset of the historical data, the server106applies the developed parameter model to the predictive variable values contemporaneous to or otherwise temporally associated with historical values for the modeled parameter, and then identifies or otherwise determines whether the model results are correlative to those historical values for the modeled parameter. In this regard, the server106compares the model-based parameter value calculated based on the predictive subset of historical data to the corresponding historical values for the modeled parameter and calculates or otherwise determines one or more metrics indicative of the performance of the model. For example, the server106may calculate or otherwise determine one or more correlation coefficient values associated with the developed model based on the differences between the model-based calculated parameter values and the corresponding historical values for the modeled parameter. When the performance metrics associated with the developed model are greater than a threshold or otherwise satisfy applicable validation criteria, the patient modeling process200stores or otherwise maintains the parameter model in association with the patient for use in subsequently determining values for that parameter (task222). For example, identification of the predictive variables for the patient for that particular parameter of interest along with the relative weightings or manner in which those predictive variables should be combined to calculate a value for the parameter of interest may be stored or otherwise maintained in the database108in association with a patient identifier assigned to or otherwise associated with the patient, the infusion device102and/or the sensing arrangement104. As described in greater detail below, the validated model may then be utilized to determine a current value for the parameter of interest in real-time based on the current values of the predictive variables for that parameter in lieu of or in addition to other techniques. For example, a calibration factor model may be utilized to calculate or otherwise determine a current calibration factor value in real-time instead of relying on a new reference blood glucose measurement from a fingerstick device, a portable blood glucose measurement device, or the like. In some embodiments, the model could also be utilized to continually and dynamically vary the value of the parameter of interest as the values for the predictive variables change during operation. Additionally, the model may be utilized to augment or otherwise adjust a parameter value over time. For example, the calibration factor may be calculated or otherwise determined as a function of the modeled calibration factor value and a calibration factor value determined using a reference blood glucose measurement, where the relative weighting applied to the modeled calibration factor value increases and the relative weighting applied to the reference calibration factor value decreases as the amount of time that has elapsed since the reference blood glucose measurement was obtained increases. In one or more embodiments, when the performance metrics associated with the developed model do not satisfy applicable validation criteria, the patient modeling process200discards the developed model and assigns or otherwise associates the patient with a broader population model (task224). In this regard, the population model may be developed by performing various aspects of the patient modeling process200across a plurality of different patients. For example, in one embodiment, a patient may be assigned or otherwise associated with a particular group of patients having one or more characteristics in common based on the demographic information associated with that patient, with a parameter model for that patient group being determined based on the aggregated historical data for the different patients of the group. In one or more embodiments, the patient modeling process200assigns or otherwise associates the patient with a patient group parameter model upon initialization of the patient within the patient management system100prior to accumulating sufficient historical data for developing a patient-specific model. It should be noted that in one or more embodiments, the patient modeling process200is performed repeatedly to dynamically update the model(s) substantially in real-time. For example, whenever new data becomes available from a particular source within a patient management system100, the patient modeling process200may be repeated to dynamically update the parameter model as appropriate. That said, in other embodiments, once a sufficient amount of data has been obtained, or the parameter model has stabilized (e.g., no changes over a certain number of successive iterations of the patient modeling process200), the parameter model may be persisted and the patient modeling process200may not be continually performed. FIG.3depicts an exemplary parameter determination process300suitable for implementation by one or more devices within a patient management system to calculate or otherwise determine a current value for a parameter in real-time using a patient-specific model for that parameter. The various tasks performed in connection with the parameter determination process300may be performed by hardware, firmware, software executed by processing circuitry, or any combination thereof. For illustrative purposes, the following description refers to elements mentioned above in connection withFIG.1. In practice, portions of the parameter determination process300may be performed by different elements of the patient management system100, such as, for example, the infusion device102, the sensing arrangement104, the server106, the database108, the client device110, the client application112, and/or the processing system116. It should be appreciated that the parameter determination process300may include any number of additional or alternative tasks, the tasks need not be performed in the illustrated order and/or the tasks may be performed concurrently, and/or the parameter determination process300may be incorporated into a more comprehensive procedure or process having additional functionality not described in detail herein. Moreover, one or more of the tasks shown and described in the context ofFIG.3could be omitted from a practical embodiment of the parameter determination process300as long as the intended overall functionality remains intact. Generally, the parameter determination process300is performed whenever it is desirable to update the value for a parameter used to control or otherwise influence operation of a device within a patient management system100, such as, for example, the sensing arrangement104or the infusion device102. Depending on the embodiment, the parameter determination process300may be initiated automatically or manually, and could be performed continually, periodically, or asynchronously (e.g., whenever a value of a predictive variable changes). While the parameter determination process300is described herein primarily in the context of use with a patient-specific parameter model, it should be appreciated that the parameter determination process300may be implemented in an equivalent manner or population parameter models and the subject matter described herein is not necessarily limited to a patient-specific model. The illustrated parameter determination process300begins by receiving or otherwise obtaining a patient-specific model for the parameter of interest (task302). For example, the sensing arrangement104or the infusion device102may download or otherwise obtain, from the server106via the network114, a patient-specific parameter model determined using the patient modeling process200(e.g., task222) for a parameter utilized by that respective device102,104. The parameter determination process300continues by obtaining the current values for the input variables identified by the obtained model as predictive or correlative to the parameter of interest for the patient and then calculating or otherwise determining a current value for the parameter based on the current input variable values using the obtained model (tasks304,306). In this regard, the obtained model indicates the input variables that are predictive of or correlative to the parameter of interest (e.g., task214) along with the weightings or manner in which those input variables should be combined to arrive at a value for the parameter of interest (e.g., task216). Thus, the sensing arrangement104or the infusion device102identifies the input variables for which values should be obtained, and then obtains the current, updated, or most recent values for those input variables from the appropriate source within the system100. Once the current input variable values are obtained, the sensing arrangement104or the infusion device102calculates or otherwise determines a current value for the parameter of interest as a function of those current input variable values in the manner indicated by the parameter model. For example, in one embodiment, the sensing arrangement104or the infusion device102calculates the current value for the parameter of interest as a weighted sum of the current input variable values, where the weightings applied to the respective input variable values are indicated by parameter model and correspond to the relative strength of the correlation or predictiveness of the respective input variable to the parameter value. In exemplary embodiments, the parameter determination process300continues by operating a respective device within the patient management system in accordance with the calculated parameter value or in a manner that is otherwise influenced by the calculated parameter value (task308). In this regard, the calculated value for the parameter may influence, for example, the output of the sensing arrangement104, the amount or rate of delivery of fluid by the infusion device102, the type or manner of alerts or user notifications generated by a respective device102,104,110, a GUI display presented on or by a respective device102,104,110, or the like. For example, referring toFIGS.1-3, in accordance with one embodiment, the parameter determination process300may be utilized to determine an expected calibration factor for determining a calibrated current measurement of the glucose level in the body of the patient based on output signals from the sensing element of the sensing arrangement104. For example, in one or more embodiments, a calibrated sensor glucose measurement (SG) is calculated using the following equation: SG=CF (isig−offset), where isig represents the measurement signal output by the sensing element of the sensing arrangement104, offset represents an amount of offset associated with the measurement signal, and CF represents the calibration factor for converting the measurement signal into a corresponding glucose measurement value. In one embodiment, the measurement signal (isig) is an electrical current having a magnitude correlative to the patient's glucose level and the offset (offset) represents the amount of background current within the measurement signal that is substantially independent of the patient's glucose level. The patient modeling process200may be performed to obtain historical calibration factor values (e.g., task212) for the patient determined based on reference blood glucose measurements along with other historical data contemporaneous or otherwise temporally related to those calibration factor values, and then determines an expected calibration factor model for the patient based on those historical calibration factor values and a subset of the historical data associated with the patient that are predictive of or correlative to the historical calibration factor values. For example, as described above, the model may indicate predictive variables for the calibration factor for the patient, such as, for example, the current sensor site location, the patient's current body mass index, the patient's gender, the current time of day, and the like. Continuing the example, the parameter determination process300may be performed by the sensing arrangement104to obtain the patient's calibration factor model from the server106and then calculate or otherwise determine the calibration factor value to be utilized in determining a calibrated sensor glucose measurement value as a function of the current sensor site location, the patient's current body mass index, the patient's gender, the current time of day, and the like in accordance with the relative weighting or manner of combination dictated by the patient's calibration factor model. Thus, rather than requiring a new fingerstick measurement, the sensing arrangement104may periodically update the calibration factor value using the calibration factor model, and then use the calculated calibration factor value to calculate a calibrated sensor glucose measurement value (SG) based on measurement signals from its sensing element, which are then transmitted, output, or otherwise provided to another device102,110. In this manner, the calibration factor model may influence the output provided by the sensing arrangement104, which, in turn, may influence operation of the infusion device102(e.g., by influencing delivery of fluid determined based on the current sensor glucose measurement value, suspending or resuming delivery based on the current sensor glucose measurement value, or the like) or influence GUI displays, alerts, or other user notifications generated by another device102,110based on the current sensor glucose measurement value. That said, in other embodiments, the parameter determination process300may be performed by the infusion device102, the remote device106, or the client device110to calculate an expected calibration factor value to be utilized to convert measurement signals received from the sensing arrangement104into calibrated sensor glucose measurement values at the respective device102,106,110. In one embodiment, the expected calibration factor model is used in conjunction with determining a calibration factor using a fingerstick measurement or other reference glucose value. For example, when a sensing arrangement104is initially inserted at a sensor site location, transients may undesirably influence the calibration factor value determined using a reference measurement value. Thus, the expected calibration factor may be dynamically calculated and used to normalize or otherwise adjust the calibration factor value determined using a reference measurement value to improve the accuracy of the calibration factor value utilized by the sensing arrangement104and/or the infusion device102. For example, the sensing arrangement104may dynamically calculate an updated calibration factor value as a weighted sum of the initial calibration factor value determined based on a reference measurement value and the expected calibration factor value based on the current values of the predictive variables for the patient's calibration factor, with the relative weightings varying over time in a manner that accounts for the behavior of the sensing arrangement104after insertion. As another example, the parameter determination process300may be utilized to determine an expected offset associated with the measurement signal for use in determining a calibrated current measurement of the glucose level in the body of the patient based on output signals from the sensing element of the sensing arrangement104. In this regard, the patient modeling process200obtains historical offset values (e.g., task212) for the patient determined based on reference blood glucose measurements along with other historical data contemporaneous or otherwise temporally related to those calibration factor values, and then determines an expected calibration factor model for the patient based on those historical offset values and a subset of the historical data associated with the patient that are predictive of or correlative to the historical offset values. For example, the model may indicate predictive variables for the offset value for the patient, such as, for example, the patient's current insulin sensitivity factor, the current sensor site location, and the like. In a similar manner as described above, the parameter determination process300may be performed by the sensing arrangement104to obtain the patient's measurement signal offset model from the server106and then calculate or otherwise determine the offset value to be utilized in determining a calibrated sensor glucose measurement value as a function of the current sensor site location, the patient's current insulin sensitivity factor, and the like in accordance with the relative weighting or manner of combination dictated by the patient's measurement signal offset model. In one embodiment, the current measurement signal offset value calculated using the patient's predictive variables according to the patient's measurement signal offset model influences calibration factor values determined based on a reference measurement, for example, by applying the calculated offset to the measurement signal(s) utilized in the calibration factor calculation. The calculated measurement signal offset value may also be utilized in conjunction with a calculated calibration factor value from the patient's expected calibration factor model to determine calibrated sensor glucose measurements values. In one or more embodiments, the parameter determination process300is utilized to determine a time-dependent expected offset associated with the measurement signal for use in determining a calibrated sensor glucose measurement. In this regard, the patient modeling process200determines a time-dependent expected offset model for the patient based on those historical offset values and an amount of time elapsed after sensor site insertion and potentially other historical data associated with the patient that are predictive of or correlative to the historical behavior of the historical offset values relative to the time of sensor site insertion. Thus, the parameter determination process300may be performed by the sensing arrangement104to obtain the patient's measurement signal offset model from the server106and then dynamically calculate or otherwise determine the offset value to be utilized in determining a calibrated sensor glucose measurement value as a function of the amount of time elapsed since insertion at the current sensor site location, the particular sensor site location, and potentially other predictive variables. As a result, the relationship between the calibrated sensor measurement value output by the sensing arrangement104and the measurement signals output by the sensing element of the sensing arrangement104may dynamically vary in a manner that accounts for the behavior of the sensing element over time after being inserted at the particular sensor site location. In other embodiments, the processes200,300are utilized to generate GUI displays or user notifications for the patient. For example, in one embodiment, the patient modeling process200may be performed to generate a model of the sensor accuracy and/or sensor stability as a function of an amount of time elapsed after sensor site insertion, the time since last calibration, the current sensor site location, behavioral patterns, and other predictive variables of sensor accuracy for the particular patient. Thereafter, upon insertion of the sensing arrangement104at a particular site location, the parameter determination process300may be performed by any one of the devices102,104,106,110in the system100to determine an amount of time after the sensor site insertion time for which the sensor accuracy or stability is at its maximum value using the model, the current sensor site location, and the current values for the other predictive variables of sensor accuracy or stability for the particular patient. In this regard, after identifying an amount of elapsed time that yields the best sensor accuracy or stability, the respective device102,104,106,110may calculate or otherwise determine a corresponding time of day when the patient should calibrate the sensing arrangement104(e.g., using a fingerstick or other reference measurement) and generate or otherwise provide indication of that optimal time for calibration. For example, the infusion device102or the client device110may generate or otherwise provide a graphical representation of the optimal calibration time on its respective display device. In one embodiment, the infusion device102or the client device110monitors the current time and automatically generates or otherwise provides a user notification or alert when the current time corresponds to the optimal calibration time determined using the model. In some embodiments, the optimal calibration time may be dynamically updated in response to changes in one or more predictive variable values. In one or more embodiments, historical values for sensor accuracy are calculated retrospectively by quantifying the performance or accuracy of previous calibrations based on the relationship between historical reference blood glucose measurement values and corresponding calibration factors. Modeling the sensor accuracy as a function of a subset of predictive variables, the parameter determination process300may be performed to estimate or otherwise determine a current sensor accuracy value using the model and provide a corresponding indication to replace the sensing arrangement when the current accuracy value falls below a replacement threshold. As another example, historical values for sensor sensitivity may be calculated based on changes in the historical calibration factor values over time. In this regard, increasing calibration factor values are indicative of decreasing sensitivity. By modeling the sensitivity values as a function of the characteristic impedance, time since insertion, and the like, the parameter determination process300may be performed to estimate or otherwise determine a current sensor sensitivity value using the model and provide a corresponding indication to replace the sensing arrangement when the current sensitivity value falls below a replacement threshold. As described above, by correlating predictive variables characterizing the operational context associated with the sensor calibration, such as the time of day, location, patient behavior or activity, or the like, with the resulting sensor accuracy, the best operational context for calibrations may be identified for a particular patient. Additionally, the sensor accuracy model may be utilized to identify the frequency or rate at which a particular patient should calibrate his or her sensing arrangement. For example, an individual patient's sensor accuracy model may indicate a relatively strong correlation between the sensor accuracy and the amount of time that has elapsed since the most recent calibration, such that that patient should recalibrate the sensing arrangement every 6 hours to achieve a desired likelihood of maintaining a sensor accuracy above a recalibration threshold value. Conversely, other patients may exhibit a lesser correlation between sensor accuracy and elapsed time since sensor calibration, and thus, can recalibrate the sensing arrangement at a lower frequency. Accordingly, the sensing arrangement104or the client device110may utilize the sensor accuracy model to calculate or otherwise determine a current sensor accuracy value and provide a corresponding indication to the patient recommending recalibration when the calculated value is less than the recalibration threshold value. Thus, the sensor accuracy model may be utilized to not only identify optimal times of day or other optimal operating contexts for calibrating the sensing arrangement, but also provide notifications or alerts on a periodic basis alerting the patient of a potential need to recalibrate in a manner that is unique to that particular patient. As another example, in one embodiment, the patient modeling process200may be performed to generate a model of the remaining usage life of the sensing arrangement104(or the sensing element associated therewith) as a function of current sensor glucose measurement values, the current sensor site location, the current environmental conditions and/or other predictive variables of sensor life for the particular patient. In this regard, the parameter determination process300may be periodically performed by any one of the devices102,104,106,110in the system100to determine an estimated amount of useful life remaining for the sensing arrangement104using the developed model of sensor usage life for the particular patient. The respective device102,104,106,110may generate or otherwise provide a graphical representation of the estimated remaining usage life to the patient. In one embodiment, in addition to the measurement signal, the sensing arrangement104obtains or otherwise provides a characteristic impedance associated with the sensing element and/or the sensing arrangement104. In such embodiments, the patient modeling process200may obtain historical values for the characteristic impedance and corresponding metrics for historical sensor performance (e.g., accuracy, sensitivity, or the like) and usage life and a model of the remaining usage life of the sensing arrangement104as a function of the characteristic impedance. The remaining usage life model may account for historical patterns in the characteristic impedance when sensor performance decreases or the sensor is terminated or replaced. In other embodiments, the remaining usage life model may account for other patterns in the patient's historical data contemporaneous to sensor performance decreases or sensor termination or replacement, such as, for example, historical calibration factor value patterns, measurement signal patterns, or the like. Additionally, the remaining usage life model may account for environmental conditions, patient demographics, sensor site locations or site rotation patterns, or other factors that are predictive of the remaining usage life for that particular patient. In another embodiment, the remaining usage life model is utilized to calculate or otherwise determine a value for an adjustment factor based on remaining usage life predictive variables for the patient, which, in turn, is utilized to influence or adjust the calculation of the remaining usage life based on the characteristic impedance. For example, in one embodiment, a linear equation may be utilized to extrapolate the characteristic impedance from the current value to a replacement value based on the gradient of the characteristic impedance, with the remaining usage life corresponding to the temporal difference between the current time and the future time associated with the extrapolated replacement value. In one embodiment, the remaining usage life for when the sensor should be replaced is calculated using the equation EISref-EIScurrent-EISrG, where EISrefrepresents a preceding value for the characteristic impedance, EIScurrentrepresents a current value for the characteristic impedance, EISrrepresents a replacement value for the characteristic impedance, and G represents the gradient of the characteristic impedance between the preceding value and the current value calculated by EIScurrent-EISreft, where t is the duration of time between the current and preceding values. In this regard, the adjustment factor determined using the remaining usage life model may be utilized to adjust any one of the terms in the equations for the remaining usage life and the gradient, either individually or collectively, in a manner that reduces the difference between the calculated remaining usage life and the actual remaining usage life. Expressed another way, the model may be utilized to tune or adjust the linear equation to improve the estimate of the sensor's remaining usage life using current values for predictive variables for the particular patient that define the current operational context for the sensing arrangement104. In other embodiments, the processes200,300are utilized to generate models that may be utilized to calculate control parameters or settings variables that dictate operations of the infusion device102or the sensing arrangement104. For example, in one embodiment, the patient modeling process200is performed to generate a model of tissue properties (or tissue resistance) associated with the sensing arrangement104and/or the infusion device102as a function of the current sensor site location, the current infusion site location, the current body mass index for the patient, the current characteristic impedance and/or other predictive variables of sensor life for the particular patient. The parameter determination process300may then be performed by the respective device102,104to calculate a current value for the tissue property based on current values for the predictive variables indicated by the patient's tissue property model, and then adjusting or altering operation of the respective device102,104based on the calculated tissue property value. For example, the sensing arrangement104may utilize the calculated tissue property value to identify the current sensor site location and/or adjust one or more parameters, such as the calibration factor, the offset, or the like, to obtain sensor glucose measurement value that accounts for the tissue property at the current sensor site location. In other embodiments, the infusion device102may utilize the calculated tissue property value to adjust or otherwise alter control parameters that influence the sensitivity or responsiveness of an autonomous control scheme implemented by the infusion device102improve regulation of the patient's glucose level in a manner that accounts for the tissue property at the current sensor site location. In yet other embodiments, any one of the devices102,104,106,110in the system100may utilize the calculated tissue property value to generate or otherwise provide GUI displays or other notifications for the patient. For example, based on the calculated tissue property value, the sensing arrangement104and/or the client device110may generate or otherwise provide an alert that notifies the patient to rotate the sensing arrangement from the current sensing arrangement104. In other embodiments, the calculated tissue property value(s) may be utilized to determine recommended sensor site locations or recommended sensor site rotation patterns and provide a corresponding guidance GUI display that informs the patient of the manner in which site locations could be utilized to improve performance. The calculated tissue property value(s) may also be utilized to identify the current sensor site location and adjust or otherwise modify control parameters to optimize performance for the current sensor site location. It should be noted that the above examples are provided primarily for purposes of illustration and are not intended to be limiting. In practice, the patient modeling process200may be performed to generate a model for calculating any parameter of interest based on any number or type of predictive variables identified based on historical values for the parameter of interest and those predictive variables. Likewise, the parameter determination process300may be performed to calculate an expected or likely value for a parameter of interest based on current values for the predictive variables using the model. In other words, the subject matter described herein is not intended to be limited to any particular subset of predictive input variables for the model or any particular parameter of interest to be calculated therefrom. Additionally, it should be appreciated that the processes200,300may be implemented in concert or concurrently to support modeling of any number of parameters of interest and calculating current values for such modeled parameters concurrently. It should also be noted that not only may the above processes200,300improve operations of the infusion device102and/or the sensing arrangement104in a manner that improves the glucose regulation achieved by the system100, the processes200,300may also improve the user experience by decreasing the number or frequency of affirmative actions that need to be performed by the patient to effectuate improved glucose regulation or otherwise maintaining the patient apprised of the current operations of the devices102,104and various means for improving performance. For example, the processes200,300may be utilized to model the patient's calibration factors, insulin sensitivity factors, or the like and allow those patient-specific factors to be calculated, estimated, or otherwise determined in a manner that obviates the need for the patient to manually obtain calibration measurements, manually input various values, or the like. Additionally, when the processes200,300is utilized to model remaining usage life of the sensing arrangement104, the patient may be apprised of the remaining usage life or the time of when the patient will need to replace, rotate, or otherwise modify the sensing arrangement104in advance of the need arising, thereby reducing frustration and inconvenience as well as facilitating an improved understanding of the current status or functionality of the sensing arrangement104. Similarly, providing guidance or recommendations for sensor site rotations based on calculated values from patient-specific models reduces the burden on the patient of determining when or how to rotate sensor sites and improves the patient's understanding and control of his or her sensor usage. FIG.4illustrates a computing device400suitable for use in a diabetes data management system in conjunction with the processes200,300ofFIGS.2-3described above. The diabetes data management system (DDMS) may be referred to as the Medtronic MiniMed CARELINK™ system or as a medical data management system (MDMS) in some embodiments. The DDMS may be housed on a server (e.g., server106) or a plurality of servers which a user or a health care professional may access via a communications network via the Internet or the World Wide Web. Some models of the DDMS, which is described as an MDMS, are described in U.S. Patent Application Publication Nos. 2006/0031094 and 2013/0338630, which is herein incorporated by reference in their entirety. While description of embodiments are made in regard to monitoring medical or biological conditions for subjects having diabetes, the systems and processes herein are applicable to monitoring medical or biological conditions for cardiac subjects, cancer subjects, HIV subjects, subjects with other disease, infection, or controllable conditions, or various combinations thereof. In various embodiments, the DDMS may be installed in a computing device in a health care provider's office, such as a doctor's office, a nurse's office, a clinic, an emergency room, an urgent care office. Health care providers may be reluctant to utilize a system where their confidential patient data is to be stored in a computing device such as a server on the Internet. The DDMS may be installed on a computing device400. The computing device400may be coupled to a display433. In some embodiments, the computing device400may be in a physical device separate from the display (such as in a personal computer, a mini-computer, etc.) In some embodiments, the computing device400may be in a single physical enclosure or device with the display433such as a laptop where the display433is integrated into the computing device. In various embodiments, the computing device400hosting the DDMS may be, but is not limited to, a desktop computer, a laptop computer, a server, a network computer, a personal digital assistant (PDA), a portable telephone including computer functions, a pager with a large visible display, an insulin pump including a display, a glucose sensor including a display, a glucose meter including a display, and/or a combination insulin pump/glucose sensor having a display. The computing device may also be an insulin pump coupled to a display, a glucose meter coupled to a display, or a glucose sensor coupled to a display. The computing device400may also be a server located on the Internet that is accessible via a browser installed on a laptop computer, desktop computer, a network computer, or a PDA. The computing device400may also be a server located in a doctor's office that is accessible via a browser installed on a portable computing device, e.g., laptop, PDA, network computer, portable phone, which has wireless capabilities and can communicate via one of the wireless communication protocols such as Bluetooth and IEEE 402.11 protocols. In the embodiment shown inFIG.4, the data management system416comprises a group of interrelated software modules or layers that specialize in different tasks. The system software includes a device communication layer424, a data parsing layer426, a database layer428, database storage devices429, a reporting layer430, a graph display layer431, and a user interface layer432. The diabetes data management system may communicate with a plurality of subject support devices412, two of which are illustrated inFIG.4. Although the different reference numerals refer to a number of layers, (e.g., a device communication layer, a data parsing layer, a database layer), each layer may include a single software module or a plurality of software modules. For example, the device communications layer424may include a number of interacting software modules, libraries, etc. In some embodiments, the data management system416may be installed onto a non-volatile storage area (memory such as flash memory, hard disk, removable hard, DVD-RW, CD-RW) of the computing device400. If the data management system416is selected or initiated, the system416may be loaded into a volatile storage (memory such as DRAM, SRAM, RAM, DDRAM) for execution. The device communication layer424is responsible for interfacing with at least one, and, in further embodiments, to a plurality of different types of subject support devices412, such as, for example, blood glucose meters, glucose sensors/monitors, or an infusion pump. In one embodiment, the device communication layer424may be configured to communicate with a single type of subject support device412. However, in more comprehensive embodiments, the device communication layer424is configured to communicate with multiple different types of subject support devices412, such as devices made from multiple different manufacturers, multiple different models from a particular manufacturer and/or multiple different devices that provide different functions (such as infusion functions, sensing functions, metering functions, communication functions, user interface functions, or combinations thereof). By providing an ability to interface with multiple different types of subject support devices412, the diabetes data management system416may collect data from a significantly greater number of discrete sources. Such embodiments may provide expanded and improved data analysis capabilities by including a greater number of subjects and groups of subjects in statistical or other forms of analysis that can benefit from larger amounts of sample data and/or greater diversity in sample data, and, thereby, improve capabilities of determining appropriate treatment parameters, diagnostics, or the like. The device communication layer424allows the DDMS416to receive information from and transmit information to or from each subject support device412in the system416. Depending upon the embodiment and context of use, the type of information that may be communicated between the system416and device412may include, but is not limited to, data, programs, updated software, education materials, warning messages, notifications, device settings, therapy parameters, or the like. The device communication layer424may include suitable routines for detecting the type of subject support device412in communication with the system416and implementing appropriate communication protocols for that type of device412. Alternatively or in addition, the subject support device412may communicate information in packets or other data arrangements, where the communication includes a preamble or other portion that includes device identification information for identifying the type of the subject support device. Alternatively, or in addition, the subject support device412may include suitable user-operable interfaces for allowing a user to enter information, such as by selecting an optional icon or text or other device identifier, that corresponds to the type of subject support device used by that user. Such information may be communicated to the system416, through a network connection. In yet further embodiments, the system416may detect the type of subject support device412it is communicating with and then may send a message requiring the user to verify that the system416properly detected the type of subject support device being used by the user. For systems416that are capable of communicating with multiple different types of subject support devices412, the device communication layer424may be capable of implementing multiple different communication protocols and selects a protocol that is appropriate for the detected type of subject support device. The data-parsing layer426is responsible for validating the integrity of device data received and for inputting it correctly into a database429. A cyclic redundancy check CRC process for checking the integrity of the received data may be employed. Alternatively, or in addition, data may be received in packets or other data arrangements, where preambles or other portions of the data include device type identification information. Such preambles or other portions of the received data may further include device serial numbers or other identification information that may be used for validating the authenticity of the received information. In such embodiments, the system416may compare received identification information with pre-stored information to evaluate whether the received information is from a valid source. The database layer428may include a centralized database repository that is responsible for warehousing and archiving stored data in an organized format for later access, and retrieval. The database layer428operates with one or more data storage device(s)429suitable for storing and providing access to data in the manner described herein. Such data storage device(s)429may comprise, for example, one or more hard discs, optical discs, tapes, digital libraries or other suitable digital or analog storage media and associated drive devices, drive arrays or the like. Data may be stored and archived for various purposes, depending upon the embodiment and environment of use. Information regarding specific subjects and patient support devices may be stored and archived and made available to those specific subjects, their authorized healthcare providers and/or authorized healthcare payor entities for analyzing the subject's condition. Also, certain information regarding groups of subjects or groups of subject support devices may be made available more generally for healthcare providers, subjects, personnel of the entity administering the system416or other entities, for analyzing group data or other forms of conglomerate data. Embodiments of the database layer428and other components of the system416may employ suitable data security measures for securing personal medical information of subjects, while also allowing non-personal medical information to be more generally available for analysis. Embodiments may be configured for compliance with suitable government regulations, industry standards, policies or the like, including, but not limited to the Health Insurance Portability and Accountability Act of 1996 (HIPAA). The database layer428may be configured to limit access of each user to types of information pre-authorized for that user. For example, a subject may be allowed access to his or her individual medical information (with individual identifiers) stored by the database layer428, but not allowed access to other subject's individual medical information (with individual identifiers). Similarly, a subject's authorized healthcare provider or payor entity may be provided access to some or all of the subject's individual medical information (with individual identifiers) stored by the database layer428, but not allowed access to another individual's personal information. Also, an operator or administrator-user (on a separate computer communicating with the computing device400) may be provided access to some or all subject information, depending upon the role of the operator or administrator. On the other hand, a subject, healthcare provider, operator, administrator or other entity, may be authorized to access general information of unidentified individuals, groups or conglomerates (without individual identifiers) stored by the database layer428in the data storage devices429. In embodiments of the subject matter described herein, the database layer428may store patient-specific parameter models, population group parameter models, and corresponding historical data for various potential input variables and parameters of interest from which such models may be derived. In the database layer428, for example, each user may store information regarding specific parameters that correspond to the user. Illustratively, these parameters could include target blood glucose or sensor glucose levels, what type of equipment the users utilize (insulin pump, glucose sensor, blood glucose meter, etc.) and could be stored in a record, a file, or a memory location in the data storage device(s)429in the database layer. The preference profiles may include various threshold values, monitoring period values, prioritization criteria, filtering criteria, and/or other user-specific values for parameters utilized to generate a snapshot GUI display on the display433or a support device412in a personalized or patient-specific manner. Additionally, data or information defining the parameter models associated with a particular individual may also be stored in a record, a file, or a memory location associated with that patient in the data storage device(s)429in the database layer. The DDMS416may measure, analyze, and track either blood glucose (BG) or sensor glucose (SG) readings for a user. In exemplary embodiments, the medical data management system may measure, track, or analyze both BG and SG readings for the user. Accordingly, although certain reports may mention or illustrate BG or SG only, the reports may monitor and display results for the other one of the glucose readings or for both of the glucose readings. The reporting layer430may include a report wizard program that pulls data from selected locations in the database429and generates report information from the desired parameters of interest. The reporting layer430may be configured to generate multiple different types of reports, each having different information and/or showing information in different formats (arrangements or styles), where the type of report may be selectable by the user. A plurality of pre-set types of report (with pre-defined types of content and format) may be available and selectable by a user. At least some of the pre-set types of reports may be common, industry standard report types with which many healthcare providers should be familiar. In exemplary embodiments described herein, the reporting layer430also facilitates generation of a snapshot report including a snapshot GUI display. In some embodiments, the database layer428may calculate values for various medical information that is to be displayed on the reports generated by the report or reporting layer430. For example, the database layer428, may calculate average blood glucose or sensor glucose readings for specified timeframes. In some embodiments, the reporting layer430may calculate values for medical or physical information that is to be displayed on the reports. For example, a user may select parameters which are then utilized by the reporting layer430to generate medical information values corresponding to the selected parameters. In other embodiments, the user may select a parameter profile that previously existed in the database layer428. Alternatively, or in addition, the report wizard may allow a user to design a custom type of report. For example, the report wizard may allow a user to define and input parameters (such as parameters specifying the type of content data, the time period of such data, the format of the report, or the like) and may select data from the database and arrange the data in a printable or displayable arrangement, based on the user-defined parameters. In further embodiments, the report wizard may interface with or provide data for use by other programs that may be available to users, such as common report generating, formatting or statistical analysis programs. In this manner, users may import data from the system416into further reporting tools familiar to the user. The reporting layer430may generate reports in displayable form to allow a user to view reports on a standard display device, printable form to allow a user to print reports on standard printers, or other suitable forms for access by a user. Embodiments may operate with conventional file format schemes for simplifying storing, printing and transmitting functions, including, but not limited to PDF, JPEG, or the like. Illustratively, a user may select a type of report and parameters for the report and the reporting layer430may create the report in a PDF format. A PDF plug-in may be initiated to help create the report and also to allow the user to view the report. Under these operating conditions, the user may print the report utilizing the PDF plug-in. In certain embodiments in which security measures are implemented, for example, to meet government regulations, industry standards or policies that restrict communication of subject's personal information, some or all reports may be generated in a form (or with suitable software controls) to inhibit printing, or electronic transfer (such as a non-printable and/or non-capable format). In yet further embodiments, the system416may allow a user generating a report to designate the report as non-printable and/or non-transferable, whereby the system416will provide the report in a form that inhibits printing and/or electronic transfer. The reporting layer430may transfer selected reports to the graph display layer431. The graph display layer431receives information regarding the selected reports and converts the data into a format that can be displayed or shown on a display433. In various embodiments, the reporting layer430may store a number of the user's parameters. Illustratively, the reporting layer430may store the type of carbohydrate units, a blood glucose movement or sensor glucose reading, a carbohydrate conversion factor, and timeframes for specific types of reports. These examples are meant to be illustrative and not limiting. Data analysis and presentations of the reported information may be employed to develop and support diagnostic and therapeutic parameters. Where information on the report relates to an individual subject, the diagnostic and therapeutic parameters may be used to assess the health status and relative well-being of that subject, assess the subject's compliance to a therapy, as well as to develop or modify treatment for the subject and assess the subject's behaviors that affect his/her therapy. Where information on the report relates to groups of subjects or conglomerates of data, the diagnostic and therapeutic parameters may be used to assess the health status and relative well-being of groups of subjects with similar medical conditions, such as, but not limited to, diabetic subjects, cardiac subjects, diabetic subjects having a particular type of diabetes or cardiac condition, subjects of a particular age, sex or other demographic group, subjects with conditions that influence therapeutic decisions such as but not limited to pregnancy, obesity, hypoglycemic unawareness, learning disorders, limited ability to care for self, various levels of insulin resistance, combinations thereof, or the like. The user interface layer432supports interactions with the end user, for example, for user login and data access, software navigation, data input, user selection of desired report types and the display of selected information. Users may also input parameters to be utilized in the selected reports via the user interface layer432. Examples of users include but are not limited to: healthcare providers, healthcare payer entities, system operators or administrators, researchers, business entities, healthcare institutions and organizations, or the like, depending upon the service being provided by the system and depending upon the embodiment. More comprehensive embodiments are capable of interacting with some or all of the above-noted types of users, wherein different types of users have access to different services or data or different levels of services or data. In an example embodiment, the user interface layer432provides one or more websites accessible by users on the Internet. The user interface layer may include or operate with at least one (or multiple) suitable network server(s) to provide the website(s) over the Internet and to allow access, world-wide, from Internet-connected computers using standard Internet browser software. The website(s) may be accessed by various types of users, including but not limited to subjects, healthcare providers, researchers, business entities, healthcare institutions and organizations, payor entities, pharmaceutical partners or other sources of pharmaceuticals or medical equipment, and/or support personnel or other personnel running the system416, depending upon the embodiment of use. In another example embodiment, where the DDMS416is located on one computing device400, the user interface layer432provides a number of menus to the user to navigate through the DDMS. These menus may be created utilizing any menu format, including but not limited to HTML, XML, or Active Server pages. A user may access the DDMS416to perform one or more of a variety of tasks, such as accessing general information made available on a website to all subjects or groups of subjects. The user interface layer432of the DDMS416may allow a user to access specific information or to generate reports regarding that subject's medical condition or that subject's medical device(s)412, to transfer data or other information from that subject's support device(s)412to the system416, to transfer data, programs, program updates or other information from the system416to the subject's support device(s)412, to manually enter information into the system416, to engage in a remote consultation exchange with a healthcare provider, or to modify the custom settings in a subject's supported device and/or in a subject's DDMS/MDMS data file. The system416may provide access to different optional resources or activities (including accessing different information items and services) to different users and to different types or groups of users, such that each user may have a customized experience and/or each type or group of user (e.g., all users, diabetic users, cardio users, healthcare provider-user or payor-user, or the like) may have a different set of information items or services available on the system. The system416may include or employ one or more suitable resource provisioning program or system for allocating appropriate resources to each user or type of user, based on a pre-defined authorization plan. Resource provisioning systems are well known in connection with provisioning of electronic office resources (email, software programs under license, sensitive data, etc.) in an office environment, for example, in a local area network LAN for an office, company or firm. In one example embodiment, such resource provisioning systems is adapted to control access to medical information and services on the DDMS416, based on the type of user and/or the identity of the user. Upon entering successful verification of the user's identification information and password, the user may be provided access to secure, personalized information stored on the DDMS416. For example, the user may be provided access to a secure, personalized location in the DDMS416which has been assigned to the subject. This personalized location may be referred to as a personalized screen, a home screen, a home menu, a personalized page, etc. The personalized location may provide a personalized home screen to the subject, including selectable icons or menu items for selecting optional activities, including, for example, an option to transfer device data from a subject's supported device412to the system416, manually enter additional data into the system416, modify the subject's custom settings, and/or view and print reports. Reports may include data specific to the subject's condition, including but not limited to, data obtained from the subject's subject support device(s)412, data manually entered, data from medical libraries or other networked therapy management systems, data from the subjects or groups of subjects, or the like. Where the reports include subject-specific information and subject identification information, the reports may be generated from some or all subject data stored in a secure storage area (e.g., storage devices429) employed by the database layer428. The user may select an option to transfer (send) device data to the medical data management system416. If the system416receives a user's request to transfer device data to the system, the system416may provide the user with step-by-step instructions on how to transfer data from the subject's supported device(s)412. For example, the DDMS416may have a plurality of different stored instruction sets for instructing users how to download data from different types of subject support devices, where each instruction set relates to a particular type of subject supported device (e.g., pump, sensor, meter, or the like), a particular manufacturer's version of a type of subject support device, or the like. Registration information received from the user during registration may include information regarding the type of subject support device(s)412used by the subject. The system416employs that information to select the stored instruction set(s) associated with the particular subject's support device(s)412for display to the user. Other activities or resources available to the user on the system416may include an option for manually entering information to the DDMS/MDMS416. For example, from the user's personalized menu or location, the user may select an option to manually enter additional information into the system416. Further optional activities or resources may be available to the user on the DDMS416. For example, from the user's personalized menu, the user may select an option to receive data, software, software updates, treatment recommendations or other information from the system416on the subject's support device(s)412. If the system416receives a request from a user to receive data, software, software updates, treatment recommendations or other information, the system416may provide the user with a list or other arrangement of multiple selectable icons or other indicia representing available data, software, software updates or other information available to the user. Yet further optional activities or resources may be available to the user on the medical data management system416including, for example, an option for the user to customize or otherwise further personalize the user's personalized location or menu. In particular, from the user's personalized location, the user may select an option to customize parameters for the user. In addition, the user may create profiles of customizable parameters. When the system416receives such a request from a user, the system416may provide the user with a list or other arrangement of multiple selectable icons or other indicia representing parameters that may be modified to accommodate the user's preferences. When a user selects one or more of the icons or other indicia, the system416may receive the user's request and makes the requested modification. FIG.5depicts one exemplary embodiment of an infusion system500that includes, without limitation, a fluid infusion device (or infusion pump)502(e.g., infusion device102), a sensing arrangement504(e.g., sensing arrangement104), a command control device (CCD)506, and a computer508, which could be realized as any one of the computing devices106,110,400described above. The components of an infusion system500may be realized using different platforms, designs, and configurations, and the embodiment shown inFIG.5is not exhaustive or limiting. In practice, the infusion device502and the sensing arrangement504are secured at desired locations on the body of a user (or patient), as illustrated inFIG.5. In this regard, the locations at which the infusion device502and the sensing arrangement504are secured to the body of the user inFIG.5are provided only as a representative, non-limiting, example. The elements of the infusion system500may be similar to those described in U.S. Pat. No. 8,674,288, the subject matter of which is hereby incorporated by reference in its entirety. In the illustrated embodiment ofFIG.5, the infusion device502is designed as a portable medical device suitable for infusing a fluid, a liquid, a gel, or other agent into the body of a user. In exemplary embodiments, the infused fluid is insulin, although many other fluids may be administered through infusion such as, but not limited to, HIV drugs, drugs to treat pulmonary hypertension, iron chelation drugs, pain medications, anti-cancer treatments, medications, vitamins, hormones, or the like. In some embodiments, the fluid may include a nutritional supplement, a dye, a tracing medium, a saline medium, a hydration medium, or the like. The sensing arrangement504generally represents the components of the infusion system500configured to sense, detect, measure or otherwise quantify a condition of the user, and may include a sensor, a monitor, or the like, for providing data indicative of the condition that is sensed, detected, measured or otherwise monitored by the sensing arrangement. In this regard, the sensing arrangement504may include electronics and enzymes reactive to a biological or physiological condition of the user, such as a blood glucose level, or the like, and provide data indicative of the blood glucose level to the infusion device502, the CCD506and/or the computer508. For example, the infusion device502, the CCD506and/or the computer508may include a display for presenting information or data to the user based on the sensor data received from the sensing arrangement504, such as, for example, a current glucose level of the user, a graph or chart of the user's glucose level versus time, device status indicators, alert messages, or the like. In other embodiments, the infusion device502, the CCD506and/or the computer508may include electronics and software that are configured to analyze sensor data and operate the infusion device502to deliver fluid to the body of the user based on the sensor data and/or preprogrammed delivery routines. Thus, in exemplary embodiments, one or more of the infusion device502, the sensing arrangement504, the CCD506, and/or the computer508includes a transmitter, a receiver, and/or other transceiver electronics that allow for communication with other components of the infusion system500, so that the sensing arrangement504may transmit sensor data or monitor data to one or more of the infusion device502, the CCD506and/or the computer508. Still referring toFIG.5, in various embodiments, the sensing arrangement504may be secured to the body of the user or embedded in the body of the user at a location that is remote from the location at which the infusion device502is secured to the body of the user. In various other embodiments, the sensing arrangement504may be incorporated within the infusion device502. In other embodiments, the sensing arrangement504may be separate and apart from the infusion device502, and may be, for example, part of the CCD506. In such embodiments, the sensing arrangement504may be configured to receive a biological sample, analyte, or the like, to measure a condition of the user. In various embodiments, the CCD506and/or the computer508may include electronics and other components configured to perform processing, delivery routine storage, and to control the infusion device502in a manner that is influenced by sensor data measured by and/or received from the sensing arrangement504. By including control functions in the CCD506and/or the computer508, the infusion device502may be made with more simplified electronics. However, in other embodiments, the infusion device502may include all control functions, and may operate without the CCD506and/or the computer508. In various embodiments, the CCD506may be a portable electronic device. In addition, in various embodiments, the infusion device502and/or the sensing arrangement504may be configured to transmit data to the CCD506and/or the computer508for display or processing of the data by the CCD506and/or the computer508. In some embodiments, the CCD506and/or the computer508may provide information to the user that facilitates the user's subsequent use of the infusion device502. For example, the CCD506may provide information to the user to allow the user to determine the rate or dose of medication to be administered into the user's body. In other embodiments, the CCD506may provide information to the infusion device502to autonomously control the rate or dose of medication administered into the body of the user. In some embodiments, the sensing arrangement504may be integrated into the CCD506. Such embodiments may allow the user to monitor a condition by providing, for example, a sample of his or her blood to the sensing arrangement504to assess his or her condition. In some embodiments, the sensing arrangement504and the CCD506may be used for determining glucose levels in the blood and/or body fluids of the user without the use of, or necessity of, a wire or cable connection between the infusion device502and the sensing arrangement504and/or the CCD506. In one or more exemplary embodiments, the sensing arrangement504and/or the infusion device502are cooperatively configured to utilize a closed-loop system for delivering fluid to the user. Examples of sensing devices and/or infusion pumps utilizing closed-loop systems may be found at, but are not limited to, the following U.S. Pat. Nos. 6,088,608, 6,119,028, 6,589,229, 6,740,072, 6,827,702, 7,323,142, and 7,402,153, all of which are incorporated herein by reference in their entirety. In such embodiments, the sensing arrangement504is configured to sense or measure a condition of the user, such as, blood glucose level or the like. The infusion device502is configured to deliver fluid in response to the condition sensed by the sensing arrangement504. In turn, the sensing arrangement504continues to sense or otherwise quantify a current condition of the user, thereby allowing the infusion device502to deliver fluid continuously in response to the condition currently (or most recently) sensed by the sensing arrangement504indefinitely. In some embodiments, the sensing arrangement504and/or the infusion device502may be configured to utilize the closed-loop system only for a portion of the day, for example only when the user is asleep or awake. FIGS.6-8depict one exemplary embodiment of a fluid infusion device600(or alternatively, infusion pump) suitable for use in an infusion system, such as, for example, as infusion device502in the infusion system500ofFIG.5or as infusion device102in the patient management system100ofFIG.1. The fluid infusion device600is a portable medical device designed to be carried or worn by a patient (or user), and the fluid infusion device600may leverage any number of conventional features, components, elements, and characteristics of existing fluid infusion devices, such as, for example, some of the features, components, elements, and/or characteristics described in U.S. Pat. Nos. 6,485,465 and 7,621,893. It should be appreciated thatFIGS.6-8depict some aspects of the infusion device600in a simplified manner; in practice, the infusion device600could include additional elements, features, or components that are not shown or described in detail herein. As best illustrated inFIGS.6-7, the illustrated embodiment of the fluid infusion device600includes a housing602adapted to receive a fluid-containing reservoir605. An opening620in the housing602accommodates a fitting623(or cap) for the reservoir605, with the fitting623being configured to mate or otherwise interface with tubing621of an infusion set625that provides a fluid path to/from the body of the user. In this manner, fluid communication from the interior of the reservoir605to the user is established via the tubing621. The illustrated fluid infusion device600includes a human-machine interface (HMI)630(or user interface) that includes elements632,634that can be manipulated by the user to administer a bolus of fluid (e.g., insulin), to change therapy settings, to change user preferences, to select display features, and the like. The infusion device also includes a display element626, such as a liquid crystal display (LCD) or another suitable display element, that can be used to present various types of information or data to the user, such as, without limitation: the current glucose level of the patient; the time; a graph or chart of the patient's glucose level versus time; device status indicators; etc. The housing602is formed from a substantially rigid material having a hollow interior1014adapted to allow an electronics assembly604, a sliding member (or slide)606, a drive system608, a sensor assembly610, and a drive system capping member612to be disposed therein in addition to the reservoir605, with the contents of the housing602being enclosed by a housing capping member616. The opening620, the slide606, and the drive system608are coaxially aligned in an axial direction (indicated by arrow618), whereby the drive system608facilitates linear displacement of the slide606in the axial direction618to dispense fluid from the reservoir605(after the reservoir605has been inserted into opening620), with the sensor assembly610being configured to measure axial forces (e.g., forces aligned with the axial direction618) exerted on the sensor assembly610responsive to operating the drive system608to displace the slide606. In various embodiments, the sensor assembly610may be utilized to detect one or more of the following: an occlusion in a fluid path that slows, prevents, or otherwise degrades fluid delivery from the reservoir605to a user's body; when the reservoir605is empty; when the slide606is properly seated with the reservoir605; when a fluid dose has been delivered; when the infusion pump600is subjected to shock or vibration; when the infusion pump600requires maintenance. Depending on the embodiment, the fluid-containing reservoir605may be realized as a syringe, a vial, a cartridge, a bag, or the like. In certain embodiments, the infused fluid is insulin, although many other fluids may be administered through infusion such as, but not limited to, HIV drugs, drugs to treat pulmonary hypertension, iron chelation drugs, pain medications, anti-cancer treatments, medications, vitamins, hormones, or the like. As best illustrated inFIGS.7-8, the reservoir605typically includes a reservoir barrel619that contains the fluid and is concentrically and/or coaxially aligned with the slide606(e.g., in the axial direction618) when the reservoir605is inserted into the infusion pump600. The end of the reservoir605proximate the opening620may include or otherwise mate with the fitting623, which secures the reservoir605in the housing602and prevents displacement of the reservoir605in the axial direction618with respect to the housing602after the reservoir605is inserted into the housing602. As described above, the fitting623extends from (or through) the opening620of the housing602and mates with tubing621to establish fluid communication from the interior of the reservoir605(e.g., reservoir barrel619) to the user via the tubing621and infusion set625. The opposing end of the reservoir605proximate the slide606includes a plunger617(or stopper) positioned to push fluid from inside the barrel619of the reservoir605along a fluid path through tubing621to a user. The slide606is configured to mechanically couple or otherwise engage with the plunger617, thereby becoming seated with the plunger617and/or reservoir605. Fluid is forced from the reservoir605via tubing621as the drive system608is operated to displace the slide606in the axial direction618toward the opening620in the housing602. In the illustrated embodiment ofFIGS.7-8, the drive system608includes a motor assembly607and a drive screw609. The motor assembly607includes a motor that is coupled to drive train components of the drive system608that are configured to convert rotational motor motion to a translational displacement of the slide606in the axial direction618, and thereby engaging and displacing the plunger617of the reservoir605in the axial direction618. In some embodiments, the motor assembly607may also be powered to translate the slide606in the opposing direction (e.g., the direction opposite direction618) to retract and/or detach from the reservoir605to allow the reservoir605to be replaced. In exemplary embodiments, the motor assembly607includes a brushless DC (BLDC) motor having one or more permanent magnets mounted, affixed, or otherwise disposed on its rotor. However, the subject matter described herein is not necessarily limited to use with BLDC motors, and in alternative embodiments, the motor may be realized as a solenoid motor, an AC motor, a stepper motor, a piezoelectric caterpillar drive, a shape memory actuator drive, an electrochemical gas cell, a thermally driven gas cell, a bimetallic actuator, or the like. The drive train components may comprise one or more lead screws, cams, ratchets, jacks, pulleys, pawls, clamps, gears, nuts, slides, bearings, levers, beams, stoppers, plungers, sliders, brackets, guides, bearings, supports, bellows, caps, diaphragms, bags, heaters, or the like. In this regard, although the illustrated embodiment of the infusion pump utilizes a coaxially aligned drive train, the motor could be arranged in an offset or otherwise non-coaxial manner, relative to the longitudinal axis of the reservoir605. As best shown inFIG.8, the drive screw609mates with threads802internal to the slide606. When the motor assembly607is powered and operated, the drive screw609rotates, and the slide606is forced to translate in the axial direction618. In an exemplary embodiment, the infusion pump600includes a sleeve611to prevent the slide606from rotating when the drive screw609of the drive system608rotates. Thus, rotation of the drive screw609causes the slide606to extend or retract relative to the drive motor assembly607. When the fluid infusion device is assembled and operational, the slide606contacts the plunger617to engage the reservoir605and control delivery of fluid from the infusion pump600. In an exemplary embodiment, the shoulder portion615of the slide606contacts or otherwise engages the plunger617to displace the plunger617in the axial direction618. In alternative embodiments, the slide606may include a threaded tip613capable of being detachably engaged with internal threads804on the plunger617of the reservoir605, as described in detail in U.S. Pat. Nos. 6,248,093 and 6,485,465, which are incorporated by reference herein. As illustrated inFIG.7, the electronics assembly604includes control electronics624coupled to the display element626, with the housing602including a transparent window portion628that is aligned with the display element626to allow the display626to be viewed by the user when the electronics assembly604is disposed within the interior1014of the housing602. The control electronics624generally represent the hardware, firmware, processing logic and/or software (or combinations thereof) configured to control operation of the motor assembly607and/or drive system608, as described in greater detail below in the context ofFIG.9. Whether such functionality is implemented as hardware, firmware, a state machine, or software depends upon the particular application and design constraints imposed on the embodiment. Those familiar with the concepts described here may implement such functionality in a suitable manner for each particular application, but such implementation decisions should not be interpreted as being restrictive or limiting. In an exemplary embodiment, the control electronics624includes one or more programmable controllers that may be programmed to control operation of the infusion pump600. The motor assembly607includes one or more electrical leads636adapted to be electrically coupled to the electronics assembly604to establish communication between the control electronics624and the motor assembly607. In response to command signals from the control electronics624that operate a motor driver (e.g., a power converter) to regulate the amount of power supplied to the motor from a power supply, the motor actuates the drive train components of the drive system608to displace the slide606in the axial direction618to force fluid from the reservoir605along a fluid path (including tubing621and an infusion set), thereby administering doses of the fluid contained in the reservoir605into the user's body. Preferably, the power supply is realized one or more batteries contained within the housing602. Alternatively, the power supply may be a solar panel, capacitor, AC or DC power supplied through a power cord, or the like. In some embodiments, the control electronics624may operate the motor of the motor assembly607and/or drive system608in a stepwise manner, typically on an intermittent basis; to administer discrete precise doses of the fluid to the user according to programmed delivery profiles. Referring toFIGS.6-8, as described above, the user interface630includes HMI elements, such as buttons632and a directional pad634, that are formed on a graphic keypad overlay631that overlies a keypad assembly633, which includes features corresponding to the buttons632, directional pad634or other user interface items indicated by the graphic keypad overlay631. When assembled, the keypad assembly633is coupled to the control electronics624, thereby allowing the HMI elements632,634to be manipulated by the user to interact with the control electronics624and control operation of the infusion pump600, for example, to administer a bolus of insulin, to change therapy settings, to change user preferences, to select display features, to set or disable alarms and reminders, and the like. In this regard, the control electronics624maintains and/or provides information to the display626regarding program parameters, delivery profiles, pump operation, alarms, warnings, statuses, or the like, which may be adjusted using the HMI elements632,634. In various embodiments, the HMI elements632,634may be realized as physical objects (e.g., buttons, knobs, joysticks, and the like) or virtual objects (e.g., using touch-sensing and/or proximity-sensing technologies). For example, in some embodiments, the display626may be realized as a touch screen or touch-sensitive display, and in such embodiments, the features and/or functionality of the HMI elements632,634may be integrated into the display626and the HMI630may not be present. In some embodiments, the electronics assembly604may also include alert generating elements coupled to the control electronics624and suitably configured to generate one or more types of feedback, such as, without limitation: audible feedback; visual feedback; haptic (physical) feedback; or the like. Referring toFIGS.7-8, in accordance with one or more embodiments, the sensor assembly610includes a back plate structure650and a loading element660. The loading element660is disposed between the capping member612and a beam structure670that includes one or more beams having sensing elements disposed thereon that are influenced by compressive force applied to the sensor assembly610that deflects the one or more beams, as described in greater detail in U.S. Pat. No. 8,474,332, which is incorporated by reference herein. In exemplary embodiments, the back plate structure650is affixed, adhered, mounted, or otherwise mechanically coupled to the bottom surface638of the drive system608such that the back plate structure650resides between the bottom surface638of the drive system608and the housing cap616. The drive system capping member612is contoured to accommodate and conform to the bottom of the sensor assembly610and the drive system608. The drive system capping member612may be affixed to the interior of the housing602to prevent displacement of the sensor assembly610in the direction opposite the direction of force provided by the drive system608(e.g., the direction opposite direction618). Thus, the sensor assembly610is positioned between the motor assembly607and secured by the capping member612, which prevents displacement of the sensor assembly610in a downward direction opposite the direction of arrow618, such that the sensor assembly610is subjected to a reactionary compressive force when the drive system608and/or motor assembly607is operated to displace the slide606in the axial direction618in opposition to the fluid pressure in the reservoir605. Under normal operating conditions, the compressive force applied to the sensor assembly610is correlated with the fluid pressure in the reservoir605. As shown, electrical leads640are adapted to electrically couple the sensing elements of the sensor assembly610to the electronics assembly604to establish communication to the control electronics624, wherein the control electronics624are configured to measure, receive, or otherwise obtain electrical signals from the sensing elements of the sensor assembly610that are indicative of the force applied by the drive system608in the axial direction618. FIG.9depicts an exemplary embodiment of a control system900suitable for use with an infusion device902, such as any one of the infusion devices102,502,600described above. The control system900is capable of controlling or otherwise regulating a physiological condition in the body901of a user to a desired (or target) value or otherwise maintain the condition within a range of acceptable values in an automated or autonomous manner. In one or more exemplary embodiments, the condition being regulated is sensed, detected, measured or otherwise quantified by a sensing arrangement904(e.g., sensing arrangement904) communicatively coupled to the infusion device902. However, it should be noted that in alternative embodiments, the condition being regulated by the control system900may be correlative to the measured values obtained by the sensing arrangement904. That said, for clarity and purposes of explanation, the subject matter may be described herein in the context of the sensing arrangement904being realized as a glucose sensing arrangement that senses, detects, measures or otherwise quantifies the user's glucose level, which is being regulated in the body901of the user by the control system900. In exemplary embodiments, the sensing arrangement904includes one or more interstitial glucose sensing elements that generate or otherwise output electrical signals (alternatively referred to herein as measurement signals) having a signal characteristic that is correlative to, influenced by, or otherwise indicative of the relative interstitial fluid glucose level in the body901of the user. The output electrical signals are filtered or otherwise processed to obtain a measurement value indicative of the user's interstitial fluid glucose level. In exemplary embodiments, a blood glucose meter930, such as a finger stick device, is utilized to directly sense, detect, measure or otherwise quantify the blood glucose in the body901of the user. In this regard, the blood glucose meter930outputs or otherwise provides a measured blood glucose value that may be utilized as a reference measurement for calibrating the sensing arrangement904and converting a measurement value indicative of the user's interstitial fluid glucose level into a corresponding calibrated blood glucose value. For purposes of explanation, the calibrated blood glucose value calculated based on the electrical signals output by the sensing element(s) of the sensing arrangement904may alternatively be referred to herein as the sensor glucose value, the sensed glucose value, or variants thereof. In exemplary embodiments, the infusion system900also includes one or more additional sensing arrangements906,908configured to sense, detect, measure or otherwise quantify a characteristic of the body901of the user that is indicative of a condition in the body901of the user. For example, in the illustrated embodiment, the infusion system900includes a heart rate sensing arrangement906that may be worn on or otherwise associated with the user's body901to sense, detect, measure or otherwise quantify the user's heart rate, which, in turn, may be indicative of exercise, stress, or some other condition in the body901that is likely to influence the user's insulin response in the body901. The measured heart rate values output by the heart rate sensing arrangement906may be utilized to calculate or otherwise quantify one or more characteristics of the user's heart rate. In some embodiments, the heart rate measurement data from the heart rate sensing arrangement906is utilized by processes200,300to develop a parameter model for calculating a current value of a parameter of interest for the user based at least in part on the current heart rate measurement value from the heart rate sensing arrangement906. While the illustrated embodiment depicts the heart rate sensing arrangement906as being realized as a standalone component worn by the user, in alternative embodiments, the heart rate sensing arrangement906may be integrated with the infusion device902or with another sensing arrangement904,908worn on the body901of the user. Additionally, the illustrated infusion system900includes an acceleration sensing arrangement908(or accelerometer) that may be worn on or otherwise associated with the user's body901to sense, detect, measure or otherwise quantify an acceleration of the user's body901, which, in turn, may be indicative of exercise or some other condition in the body901that is likely to influence the user's insulin response. In the illustrated embodiment, the acceleration sensing arrangement908is depicted as being integrated into the infusion device902, however, in alternative embodiments, the acceleration sensing arrangement908may be integrated with another sensing arrangement904,906on the body901of the user, or the acceleration sensing arrangement908may be realized as a standalone component that is worn by the user. The acceleration measurement data may be utilized to establish behavioral history of the user (e.g., when the user is exercising or awake versus at rest). In some embodiments, the acceleration measurement data from the acceleration sensing arrangement908is utilized by processes200,300to develop a parameter model for calculating a current value of a parameter of interest for the user based at least in part on the current acceleration measurement value from the acceleration sensing arrangement906or other current behavior or activities correlative to the current acceleration measurement value. In the illustrated embodiment, the pump control system920generally represents the electronics and other components of the infusion device902that control operation of the fluid infusion device902according to a desired infusion delivery program in a manner that is influenced by the sensed glucose value indicative of a current glucose level in the body901of the user. For example, to support a closed-loop operating mode, the pump control system920maintains, receives, or otherwise obtains a target or commanded glucose value, and automatically generates or otherwise determines dosage commands for operating an actuation arrangement, such as a motor932, to displace the plunger917and deliver insulin to the body901of the user based on the difference between a sensed glucose value and the target glucose value. In other operating modes, the pump control system920may generate or otherwise determine dosage commands configured to maintain the sensed glucose value below an upper glucose limit, above a lower glucose limit, or otherwise within a desired range of glucose values. In practice, the infusion device902may store or otherwise maintain the target value, upper and/or lower glucose limit(s), and/or other glucose threshold value(s) in a data storage element accessible to the pump control system920. The target glucose value and other threshold glucose values may be received from an external component (e.g., CCD506and/or computing device508) or be input by a user via a user interface element940associated with the infusion device902. In practice, the one or more user interface element(s)940associated with the infusion device902typically include at least one input user interface element, such as, for example, a button, a keypad, a keyboard, a knob, a joystick, a mouse, a touch panel, a touchscreen, a microphone or another audio input device, and/or the like. Additionally, the one or more user interface element(s)940include at least one output user interface element, such as, for example, a display element (e.g., a light-emitting diode or the like), a display device (e.g., a liquid crystal display or the like), a speaker or another audio output device, a haptic feedback device, or the like, for providing notifications or other information to the user. It should be noted that althoughFIG.9depicts the user interface element(s)940as being separate from the infusion device902, in practice, one or more of the user interface element(s)940may be integrated with the infusion device902. Furthermore, in some embodiments, one or more user interface element(s)940are integrated with the sensing arrangement904in addition to and/or in alternative to the user interface element(s)940integrated with the infusion device902. The user interface element(s)940may be manipulated by the user to operate the infusion device902to deliver correction boluses, adjust target and/or threshold values, modify the delivery control scheme or operating mode, and the like, as desired. Still referring toFIG.9, in the illustrated embodiment, the infusion device902includes a motor control module912coupled to a motor932(e.g., motor assembly607) that is operable to displace a plunger917(e.g., plunger617) in a reservoir (e.g., reservoir605) and provide a desired amount of fluid to the body901of a user. In this regard, displacement of the plunger917results in the delivery of a fluid that is capable of influencing the condition in the body901of the user to the body901of the user via a fluid delivery path (e.g., via tubing621of an infusion set625). A motor driver module914is coupled between an energy source918and the motor932. The motor control module912is coupled to the motor driver module914, and the motor control module912generates or otherwise provides command signals that operate the motor driver module914to provide current (or power) from the energy source918to the motor932to displace the plunger917in response to receiving, from a pump control system920, a dosage command indicative of the desired amount of fluid to be delivered. In exemplary embodiments, the energy source918is realized as a battery housed within the infusion device902(e.g., within housing602) that provides direct current (DC) power. In this regard, the motor driver module914generally represents the combination of circuitry, hardware and/or other electrical components configured to convert or otherwise transfer DC power provided by the energy source918into alternating electrical signals applied to respective phases of the stator windings of the motor932that result in current flowing through the stator windings that generates a stator magnetic field and causes the rotor of the motor932to rotate. The motor control module912is configured to receive or otherwise obtain a commanded dosage from the pump control system920, convert the commanded dosage to a commanded translational displacement of the plunger917, and command, signal, or otherwise operate the motor driver module914to cause the rotor of the motor932to rotate by an amount that produces the commanded translational displacement of the plunger917. For example, the motor control module912may determine an amount of rotation of the rotor required to produce translational displacement of the plunger917that achieves the commanded dosage received from the pump control system920. Based on the current rotational position (or orientation) of the rotor with respect to the stator that is indicated by the output of the rotor sensing arrangement916, the motor control module912determines the appropriate sequence of alternating electrical signals to be applied to the respective phases of the stator windings that should rotate the rotor by the determined amount of rotation from its current position (or orientation). In embodiments where the motor932is realized as a BLDC motor, the alternating electrical signals commutate the respective phases of the stator windings at the appropriate orientation of the rotor magnetic poles with respect to the stator and in the appropriate order to provide a rotating stator magnetic field that rotates the rotor in the desired direction. Thereafter, the motor control module912operates the motor driver module914to apply the determined alternating electrical signals (e.g., the command signals) to the stator windings of the motor932to achieve the desired delivery of fluid to the user. When the motor control module912is operating the motor driver module914, current flows from the energy source918through the stator windings of the motor932to produce a stator magnetic field that interacts with the rotor magnetic field. In some embodiments, after the motor control module912operates the motor driver module914and/or motor932to achieve the commanded dosage, the motor control module912ceases operating the motor driver module914and/or motor932until a subsequent dosage command is received. In this regard, the motor driver module914and the motor932enter an idle state during which the motor driver module914effectively disconnects or isolates the stator windings of the motor932from the energy source918. In other words, current does not flow from the energy source918through the stator windings of the motor932when the motor932is idle, and thus, the motor932does not consume power from the energy source918in the idle state, thereby improving efficiency. Depending on the embodiment, the motor control module912may be implemented or realized with a general purpose processor, a microprocessor, a controller, a microcontroller, a state machine, a content addressable memory, an application specific integrated circuit, a field programmable gate array, any suitable programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof, designed to perform the functions described herein. In exemplary embodiments, the motor control module912includes or otherwise accesses a data storage element or memory, including any sort of random access memory (RAM), read only memory (ROM), flash memory, registers, hard disks, removable disks, magnetic or optical mass storage, or any other short or long term storage media or other non-transitory computer-readable medium, which is capable of storing programming instructions for execution by the motor control module912. The computer-executable programming instructions, when read and executed by the motor control module912, cause the motor control module912to perform or otherwise support the tasks, operations, functions, and processes described herein. It should be appreciated thatFIG.9is a simplified representation of the infusion device902for purposes of explanation and is not intended to limit the subject matter described herein in any way. In this regard, depending on the embodiment, some features and/or functionality of the sensing arrangement904may implemented by or otherwise integrated into the pump control system920, or vice versa. Similarly, in practice, the features and/or functionality of the motor control module912may implemented by or otherwise integrated into the pump control system920, or vice versa. Furthermore, the features and/or functionality of the pump control system920may be implemented by control electronics624located in the fluid infusion device902, while in alternative embodiments, the pump control system920may be implemented by a remote computing device that is physically distinct and/or separate from the infusion device902, such as, for example, the CCD506or the computing device508. FIG.10depicts an exemplary embodiment of a pump control system1000suitable for use as the pump control system920inFIG.9in accordance with one or more embodiments. The illustrated pump control system1000includes, without limitation, a pump control module1002, a communications interface1004, and a data storage element (or memory)1006. The pump control module1002is coupled to the communications interface1004and the memory1006, and the pump control module1002is suitably configured to support the operations, tasks, and/or processes described herein. In exemplary embodiments, the pump control module1002is also coupled to one or more user interface elements1008(e.g., user interface630,940) for receiving user input and providing notifications, alerts, or other therapy information to the user. AlthoughFIG.10depicts the user interface element1008as being separate from the pump control system1000, in various alternative embodiments, the user interface element1008may be integrated with the pump control system1000(e.g., as part of the infusion device902), the sensing arrangement904or another element of an infusion system900(e.g., the computer508or CCD506). Referring toFIG.10and with reference toFIG.9, the communications interface1004generally represents the hardware, circuitry, logic, firmware and/or other components of the pump control system1000that are coupled to the pump control module1002and configured to support communications between the pump control system1000and the sensing arrangement904. In this regard, the communications interface1004may include or otherwise be coupled to one or more transceiver modules capable of supporting wireless communications between the pump control system920,1000and the sensing arrangement104,504,904or another electronic device106,110,400,412,506,508in a system100,400,500including the infusion device102,502,902. For example, the communications interface1004may be utilized to receive sensor measurement values or other measurement data from a sensing arrangement104,504,904as well as upload such sensor measurement values to a server106or other computing device110,400,412,508. In other embodiments, the communications interface1004may be configured to support wired communications to/from the sensing arrangement904. The pump control module1002generally represents the hardware, circuitry, logic, firmware and/or other component of the pump control system1000that is coupled to the communications interface1004and configured to determine dosage commands for operating the motor932to deliver fluid to the body901based on data received from the sensing arrangement904and perform various additional tasks, operations, functions and/or operations described herein. For example, in exemplary embodiments, pump control module1002implements or otherwise executes a command generation application1010that supports one or more autonomous operating modes and calculates or otherwise determines dosage commands for operating the motor932of the infusion device902in an autonomous operating mode based at least in part on a current measurement value for a condition in the body901of the user. For example, in a closed-loop operating mode, the command generation application1010may determine a dosage command for operating the motor932to deliver insulin to the body901of the user based at least in part on the current glucose measurement value most recently received from the sensing arrangement904to regulate the user's blood glucose level to a target reference glucose value. Additionally, the command generation application1010may generate dosage commands for boluses that are manually-initiated or otherwise instructed by a user via a user interface element1008. Still referring toFIG.10, depending on the embodiment, the pump control module1002may be implemented or realized with a general purpose processor, a microprocessor, a controller, a microcontroller, a state machine, a content addressable memory, an application specific integrated circuit, a field programmable gate array, any suitable programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof, designed to perform the functions described herein. In this regard, the steps of a method or algorithm described in connection with the embodiments disclosed herein may be embodied directly in hardware, in firmware, in a software module executed by the pump control module1002, or in any practical combination thereof. In exemplary embodiments, the pump control module1002includes or otherwise accesses the data storage element or memory1006, which may be realized using any sort of non-transitory computer-readable medium capable of storing programming instructions for execution by the pump control module1002. The computer-executable programming instructions, when read and executed by the pump control module1002, cause the pump control module1002to implement or otherwise generate the command generation application1010and perform tasks, operations, functions, and processes described herein. It should be understood thatFIG.10is a simplified representation of a pump control system1000for purposes of explanation and is not intended to limit the subject matter described herein in any way. For example, in some embodiments, the features and/or functionality of the motor control module912may be implemented by or otherwise integrated into the pump control system1000and/or the pump control module1002, for example, by the command generation application1010converting the dosage command into a corresponding motor command, in which case, the separate motor control module912may be absent from an embodiment of the infusion device902. FIG.11depicts an exemplary closed-loop control system1100that may be implemented by a pump control system920,1000to provide a closed-loop operating mode that autonomously regulates a condition in the body of a user to a reference (or target) value. It should be appreciated thatFIG.11is a simplified representation of the control system1100for purposes of explanation and is not intended to limit the subject matter described herein in any way. In exemplary embodiments, the control system1100receives or otherwise obtains a target glucose value at input1102. In some embodiments, the target glucose value may be stored or otherwise maintained by the infusion device902(e.g., in memory1006), however, in some alternative embodiments, the target value may be received from an external component (e.g., CCD506and/or computer508). In one or more embodiments, the target glucose value may be dynamically calculated or otherwise determined prior to entering the closed-loop operating mode based on one or more patient-specific control parameters. For example, the target blood glucose value may be calculated based at least in part on a patient-specific reference basal rate and a patient-specific daily insulin requirement, which are determined based on historical delivery information over a preceding interval of time (e.g., the amount of insulin delivered over the preceding 24 hours). The control system1100also receives or otherwise obtains a current glucose measurement value (e.g., the most recently obtained sensor glucose value) from the sensing arrangement904at input1104. The illustrated control system1100implements or otherwise provides proportional-integral-derivative (PID) control to determine or otherwise generate delivery commands for operating the motor910based at least in part on the difference between the target glucose value and the current glucose measurement value. In this regard, the PID control attempts to minimize the difference between the measured value and the target value, and thereby regulates the measured value to the desired value. PID control parameters are applied to the difference between the target glucose level at input1102and the measured glucose level at input1104to generate or otherwise determine a dosage (or delivery) command provided at output1130. Based on that delivery command, the motor control module912operates the motor910to deliver insulin to the body of the user to influence the user's glucose level, and thereby reduce the difference between a subsequently measured glucose level and the target glucose level. The illustrated control system1100includes or otherwise implements a summation block1106configured to determine a difference between the target value obtained at input1102and the measured value obtained from the sensing arrangement904at input1104, for example, by subtracting the target value from the measured value. The output of the summation block1106represents the difference between the measured and target values, which is then provided to each of a proportional term path, an integral term path, and a derivative term path. The proportional term path includes a gain block1120that multiplies the difference by a proportional gain coefficient, KP, to obtain the proportional term. The integral term path includes an integration block1108that integrates the difference and a gain block1122that multiplies the integrated difference by an integral gain coefficient, KI, to obtain the integral term. The derivative term path includes a derivative block1110that determines the derivative of the difference and a gain block1124that multiplies the derivative of the difference by a derivative gain coefficient, KD, to obtain the derivative term. The proportional term, the integral term, and the derivative term are then added or otherwise combined to obtain a delivery command that is utilized to operate the motor at output1130. Various implementation details pertaining to closed-loop PID control and determine gain coefficients are described in greater detail in U.S. Pat. No. 7,402,153, which is incorporated by reference. In one or more exemplary embodiments, the PID gain coefficients are user-specific (or patient-specific) and dynamically calculated or otherwise determined prior to entering the closed-loop operating mode based on historical insulin delivery information (e.g., amounts and/or timings of previous dosages, historical correction bolus information, or the like), historical sensor measurement values, historical reference blood glucose measurement values, user-reported or user-input events (e.g., meals, exercise, and the like), and the like. In this regard, one or more patient-specific control parameters (e.g., an insulin sensitivity factor, a daily insulin requirement, an insulin limit, a reference basal rate, a reference fasting glucose, an active insulin action duration, pharmodynamical time constants, or the like) may be utilized to compensate, correct, or otherwise adjust the PID gain coefficients to account for various operating conditions experienced and/or exhibited by the infusion device902. The PID gain coefficients may be maintained by the memory1006accessible to the pump control module1002. In this regard, the memory1006may include a plurality of registers associated with the control parameters for the PID control. For example, a first parameter register may store the target glucose value and be accessed by or otherwise coupled to the summation block1106at input1102, and similarly, a second parameter register accessed by the proportional gain block1120may store the proportional gain coefficient, a third parameter register accessed by the integration gain block1122may store the integration gain coefficient, and a fourth parameter register accessed by the derivative gain block1124may store the derivative gain coefficient. Referring toFIGS.9-11, in one or more embodiments, the parameter determination process300may be performed to calculate a value for a control parameter that influences operation of the infusion device902to deliver fluid to the patient. For example, in one embodiment one of more of the PID gain coefficients1120,1122,1124may be calculated or determined using a patient-specific model derived by the patient modeling process200, or alternatively, may be adjusted or scaled using an adjustment factor that is calculated or determined using a patient-specific model derived by the patient modeling process200. In other embodiments, the parameter determination process300may be performed to calculate a calibration factor value, an offset value, or another parameter value that influences the calibrated sensor glucose measurement value provided at input1104, which, in turn, influences the delivery commands generated by the control system1100, and thereby, the rate or amount of fluid delivered. Patient-specific models may also be used to determine delivery thresholds (e.g., to suspend, resume or otherwise modify delivery), alerting thresholds, or the like, which, in turn, influence the operation or behavior of the infusion device902. Again, it should be noted that the processes200,300may be utilized to calculate, adjust, modify, or otherwise determine any number of different potential control parameters utilized by the pump control module920,1002and/or the control scheme implemented thereby based on the current values for any number of different predictive variables. In some embodiments, one or more patient-specific parameter models are stored or otherwise maintained by the pump control system920,1000(e.g., in memory1006) to support the infusion device902performing the parameter determination process300substantially in real-time. FIG.12depicts an exemplary embodiment of an electronic device1200suitable for use as a sensing arrangement104,504,904in accordance with one or more embodiments. For purposes of explanation, but without limitation, the device1200may alternatively be referred to herein as a sensing device or a sensing arrangement. The illustrated sensing device1200includes, without limitation, a control module1202, a sensing element1204, an output interface1206, and a data storage element (or memory)1208. The control module1202is coupled to the sensing element1204, the output interface1206, and the memory1208, and the control module1202is suitably configured to support the operations, tasks, and/or processes described herein. The sensing element1204generally represents the component of the sensing device1200that is configured to generate, produce, or otherwise output one or more electrical signals indicative of a condition that is sensed, measured, or otherwise quantified by the sensing device1200. In this regard, the physiological condition of a user influences a characteristic of the electrical signal output by the sensing element1204, such that the characteristic of the output signal corresponds to or is otherwise correlative to the physiological condition that the sensing element1204is sensitive to. For example, the sensing element1204may be realized as a glucose sensing element that generates an output electrical signal having a current (or voltage) associated therewith that is correlative to the interstitial fluid glucose level that is sensed or otherwise measured in the body of the user by the sensing arrangement1200. One or more glucose independent diagnostic signals or values associated with the sensing element1204may also be obtained by the sensing device1200and stored and/or transmitted by the sensing device1200, such as, for example, electrochemical impedance spectroscopy (EIS) values or other measurements indicative of a characteristic impedance associated with the sensing element1204. Still referring toFIG.12, the control module1202generally represents the hardware, circuitry, logic, firmware and/or other component(s) of the sensing device1200that is coupled to the sensing element1204to receive the electrical signals output by the sensing element1204and perform various additional tasks, operations, functions and/or processes described herein. For example, in one or more embodiments, the control module1202implements or otherwise executes a data management application module1210that filters, analyzes or otherwise processes the electrical signals received from the sensing element1204to obtain a filtered measurement value indicative of the measured interstitial fluid glucose level. In some embodiments, data management application module1210may add or subtract an offset to/from the measured electrical signal, as described above. In the illustrated embodiment, a calibration application module1212utilizes a calibration factor value to convert the filtered measurement value from the data management application1210to a calibrated sensed glucose value (or sensor glucose value). In some embodiments, the control module1202also implements or otherwise executes a health monitoring application module1214that detects or otherwise identifies replacement or other maintenance with respect to the sensing element1204is desirable. Depending on the embodiment, the control module1202may be implemented or realized with a general purpose processor, a microprocessor, a controller, a microcontroller, a state machine, a content addressable memory, an application specific integrated circuit, a field programmable gate array, any suitable programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof, designed to perform the functions described herein. In this regard, the steps of a method or algorithm described in connection with the embodiments disclosed herein may be embodied directly in hardware, in firmware, in a software module executed by the control module1202, or in any practical combination thereof. In some embodiments, the control module1202includes an analog-to-digital converter (ADC) or another similar sampling arrangement that samples or otherwise converts the output electrical signal received from the sensing element1204into a corresponding digital measurement data value. In other embodiments, the sensing element1204may incorporate an ADC and output a digital measurement value. For purposes of explanation, the input to the data management application1210from the sensing element1204may alternatively be referred to herein as the unfiltered measurement value, which should be understood as referring to the digital value correlative to the interstitial fluid glucose level sensed by the sensing element1204. In one or more embodiments, the current of the electrical signal output by the sensing element1204is influenced by the user's interstitial fluid glucose level, and the input to the data management application1210is realized as an unfiltered current measurement value (or unfiltered current measurement signal). As described above, depending on the embodiment, the unfiltered measurement value may be output directly by the sensing element1204or converted based on an analog electrical output signal from the sensing element1204by an ADC of the control module1202. In exemplary embodiments, the control module1202includes or otherwise accesses the data storage element or memory1208. The memory1208may be realized using any sort of RAM, ROM, flash memory, registers, hard disks, removable disks, magnetic or optical mass storage, short or long term storage media, or any other non-transitory computer-readable medium capable of storing programming instructions, code, or other data for execution by the control module1202. The computer-executable programming instructions, when read and executed by the control module1202, cause the control module1202to implement or otherwise generate the applications1210,1212,1214and perform the tasks, operations, functions, and processes described in greater detail below. The output interface1206generally represents the hardware, circuitry, logic, firmware and/or other components of the sensing device1200that are coupled to the control module1202for outputting data and/or information from/to the sensing device1200to/from the infusion device902, the pump control system920, the remote device106, the client device110and/or the user. In this regard, in exemplary embodiments, the output interface1206is realized as a communications interface configured to support communications to/from the sensing device1200. In such embodiments, the communications interface1206may include or otherwise be coupled to one or more transceiver modules capable of supporting wireless communications between the sensing device1200and another electronic device (e.g., an infusion device502,902or another electronic device506,508in an infusion system500). Alternatively, the communications interface1206may be realized as a port that is adapted to receive or otherwise be coupled to a wireless adapter that includes one or more transceiver modules and/or other components that support the operations of the sensing device1200described herein. In other embodiments, the communications interface1206may be configured to support wired communications to/from the sensing device1200. In yet other embodiments, the output interface1206may include or otherwise be realized as an output user interface element, such as a display element (e.g., a light-emitting diode or the like), a display device (e.g., a liquid crystal display or the like), a speaker or another audio output device, a haptic feedback device, or the like, for providing notifications or other information to the user. In such embodiments, the output user interface1206may be integrated with the sensing arrangement904,1200(e.g., within a common housing) or implemented separately (e.g., user interface element940). It should be understood thatFIG.12is a simplified representation of a sensing device1200for purposes of explanation and is not intended to limit the subject matter described herein in any way. In this regard, althoughFIG.12depicts the various elements residing within the sensing device1200, one or more elements of the sensing device1200may be distinct or otherwise separate from the other elements of the sensing device1200. For example, the sensing element1204may be separate and/or physically distinct from the control module1202and/or the communications interface1206. Furthermore, althoughFIG.12depicts the applications1210,1212,1214as being implemented by the sensing device1200, in alternative embodiments, features and/or functionality of one or more of the applications1210,1212,1214may be implemented by or otherwise reside on the infusion device502,902or another device506,508within an infusion system500. For example, in some embodiments, the features and/or functionality of one or more of the applications1210,1212,1214may be implemented by the pump control system920. In one or more embodiments, the parameter determination process300may be performed to influence the output of the sensing device1200. For example, as described above, an offset value applied by the data management module1210and/or a calibration factor value applied by the calibration factor module1212may be calculated or determined using a patient-specific model for the respective parameter derived by the patient modeling process200, or alternatively, may be adjusted or scaled using an adjustment factor that is calculated or determined using a patient-specific model derived by the patient modeling process200. Thus, the resulting calibrated sensor glucose measurement value provided to the output interface1206and output by the sensing device1200may be influenced by a patient-specific parameter module as described above. In other embodiments, a remaining usage life model may be utilized by the health monitoring module1214to calculate or otherwise determine a remaining usage life and provide a corresponding indication to the patient via the output interface1206. In yet other embodiments, the health monitoring module1214may provide site rotation recommendations or other guidance to the patient via the output interface1206based on one or more parameter values calculated using a patient-specific parameter model. Again, it should be noted that the processes200,300may be utilized to calculate, adjust, modify, or otherwise determine any number of different potential parameters utilized by the sensing device1200based on the current values for any number of different predictive variables. In some embodiments, one or more patient-specific parameter models are stored or otherwise maintained by the sensing device1200(e.g., in memory1208) to support the sensing device1200performing the parameter determination process300substantially in real-time to dynamically adjust the value for one or more parameters. It should be noted that although the subject matter may be described herein primarily in the context of an infusion device delivering insulin to the body of a patient with diabetes to regulate the patient's glucose level for purposes of explanation, in practice, the subject matter is not limited to use with infusion devices, insulin, diabetes or glucose control, and the like. Rather, the subject matter may be implemented in an equivalent manner in the context of patient management systems that do not include an infusion device, for example, in systems with where patients self-administer injections, oral medications, or the like, in systems where a sensing arrangement is utilized to monitor any a physiological condition of a patient in a substantially continuous manner, or in the context of a patient with dysglycemia or another physiological condition being monitored that is influenced by meals or other behavioral events. Thus, the infusion device102may be absent from some embodiments of the patient management system100, in which case, the sensing arrangement104communicates with the server106and/or the client device110without reliance on the infusion device102as an intermediary. In one or more exemplary embodiments, the subject matter described herein is implemented in the context of operating a sensing device104,1200associated with a patient. In such embodiments, a control module1202of the sensing device104,1200obtains current operational context information associated with the sensing device, obtains a parameter model associated with the patient (e.g., from database108via the server106and network114), calculates a current parameter value based on the parameter model and the current operational context information, obtains one or more signals from a sensing element1204configured to measure a condition in a body of the patient, and provides an output, such as a calibrated measurement value, a user notification or alert, or the like, which is influenced by the calculated current parameter value and the one or more signals. In yet other embodiments, the subject matter described herein is implemented in the context of another electronic device in a patient management system100, such as a remote device106, a client device110, or an infusion device102, to develop a patient-specific model for a parameter of interest. In such embodiments, the respective device102,106,110obtains historical measurements of a condition in a body of the patient previously provided by a sensing device104, historical delivery information for fluid previously delivered to the body of the patient by the infusion device102, historical operational context information associated with preceding operation of one or more of the infusion device102and the sensing device104, and historical values for a parameter from one or more of the infusion device102and the sensing device104. A patient-specific model of the parameter of interest is determined based on relationships between the historical measurements, the historical delivery information, the historical operational context information and the historical values, and the patient-specific model is provided to one of the infusion device102, the sensing device104or the client device110, wherein subsequent operation of that respective device is influenced by the patient-specific model. For example, the patient-specific model may influence alerts, guidance, recommendations or other notifications generated by the respective device, or other outputs generated by the respective device, such as, for example, measurement values, fluid deliveries, and the like. For the sake of brevity, conventional techniques related to glucose sensing and/or monitoring, glucose regulation, modeling, machine learning, and other functional aspects of the subject matter may not be described in detail herein. In addition, certain terminology may also be used in the herein for the purpose of reference only, and thus is not intended to be limiting. For example, terms such as “first”, “second”, and other such numerical terms referring to structures do not imply a sequence or order unless clearly indicated by the context. The foregoing description may also refer to elements or nodes or features being “connected” or “coupled” together. As used herein, unless expressly stated otherwise, “coupled” means that one element/node/feature is directly or indirectly joined to (or directly or indirectly communicates with) another element/node/feature, and not necessarily mechanically. While at least one exemplary embodiment has been presented in the foregoing detailed description, it should be appreciated that a vast number of variations exist. It should also be appreciated that the exemplary embodiment or embodiments described herein are not intended to limit the scope, applicability, or configuration of the claimed subject matter in any way. For example, the subject matter described herein is not necessarily limited to the infusion devices and related systems described herein. Moreover, the foregoing detailed description will provide those skilled in the art with a convenient road map for implementing the described embodiment or embodiments. It should be understood that various changes can be made in the function and arrangement of elements without departing from the scope defined by the claims, which includes known equivalents and foreseeable equivalents at the time of filing this patent application. Accordingly, details of the exemplary embodiments or other limitations described above should not be read into the claims absent a clear intention to the contrary. | 158,817 |
11857766 | DESCRIPTION In a first aspect of the present invention, this problem is solved by a device for manually inserting a plunger-type stopper made of elastomer, which forms part of a plunger, into a syringe cylinder, comprising: a receptacle adapted to hold the syringe cylinder; a tubular barrel adapted to receive the plunger-type stopper therein; a holding device adapted to hold the barrel relative to the receptacle; and a moving device adapted to move the plunger-type stopper relative to the barrel; wherein the holding device comprises an actuation portion adapted to be manually actuated to displace the barrel relative to the plunger-type stopper. The device according to the invention enables a series of filled syringes (and other syringe-like cylindrical tubes such as cartridges, double-chamber cartridges, and double-chamber syringes) to be used from the quantity of 1. In addition, the device according to the invention can be used to fill a respective syringe aseptically and perfectly for different applications. This leads to a significant reduction in costs and time for the applications described so far. In particular, the device according to the invention allows a filling sequence of fully automated filling machines to be imitated, so that a later changeover from the small series to the actual series of drug production is possible without major conversions in this context, components of a filling machine can also be taken directly for the device according to the invention in order to achieve absolutely identical conditions for the properties of the syringe produced. For example, the barrel and plunger (see below) come into question here. By means of the device according to the invention, a respective plunger-type stopper can be set without the formation of excess pressure in the syringe cylinder, as a result of which, for example, product could be expelled unintentionally. In connection with the present invention, therefore, the term “pressure-free” stopper setting is also used. The plunger-type stoppers can thus be positioned with absolute precision, so that a desired and required “headspace” and uniformity can be obtained over an entire batch. Inert gases or other gases can be connected for settling gassing. In general, the device according to the invention can also be used and operated in an aseptic environment (from laboratory to isolator) along the entire development chain (formulation development, stability studies, toxicity studies, clinical studies, packaging change to life cycle management). Advantageously, at least all components which come into contact with parts of the syringe to be filled and/or the drug, in particular all components, of the device according to the invention are autoclavable. Furthermore, it can be advantageous that at least the holder and/or the barrel is/are designed in such a way that it/they can be replaced by a counterpart for a syringe of a different format. In this way it can be achieved, for example, that syringes of the formats 1 ml, 3 ml or 10 ml can be filled. In the device according to the invention, for example, an already filled syringe cylinder can first be arranged in the receptacle, then the syringe cylinder is displaced relative to the barrel in such a way that the end of the barrel associated with the drug is at a predetermined distance from the drug. Now, a plunger-type stopper can be displaced through the barrel, wherein gas disposed in the barrel between the plunger-type stopper and the drug can be expelled upon displacement of the plunger-type stopper in the barrel and can escape from the syringe cylinder between the barrel and the syringe cylinder without causing an overpressure to form in the syringe cylinder. When the plunger-type stopper is located at the end of the barrel adjacent to the drug, an operator of the device according to the invention actuates the actuation portion, thereby displacing the barrel relative to the plunger-type stopper and away from the drug. As this occurs, the plunger-type stopper expands such that it interacts with the syringe cylinder in a sealing manner. The finished syringe can now be removed from the device according to the invention. In a further development of the present invention, the actuation portion of the holding device may comprise a rocking device adapted to transfer a manual actuating force acting in a first direction, which has been input at a first end of the rocking device, to a lever force acting in a second direction at a second end of the rocking device arranged opposite to the first end, wherein the first direction may be substantially opposite to the second direction. Such a device may allow a small actuating force at one end to be converted into a comparatively larger displacement force at the other end, so that actuation of the actuation portion may be simplified. The rocking device can be designed as an elongated plate-like element. This can be a particularly simple and cost-effective design of the rocking device. Furthermore, the plate-like element may thereby have a first end adapted to be actuated by a finger and a second end arranged substantially opposite to the first end and which at least partially encloses the barrel. The plate-like element may therefore be arranged on the device according to the invention, in particular in such a way that it is readily accessible to a user so that the user can act on the first end of the plate-like element with his finger. Advantageously, the device may further comprise at least one support element to which the holding device and/or the displacement device are/is connected. Also, the device may further comprise a base plate which may advantageously be connected to the at least one support element. The at least one support element and the base plate can thus together form a frame on which the above-described parts of the device according to the invention can be supported. In particular, the receptacle can be attached to the base plate. In this way, the receptacle can be supported relative to the base plate and, for example, horizontal play of the receptacle relative to the base plate can be reduced or even avoided. The receptacle can be adjustable relative to the holding device and/or the displacement device, advantageously via at least one screw connection. This allows the syringe cylinder to be displaced in the device. Furthermore, the device according to the invention can thus be adapted to the filling of syringes with mutually different filling levels or different syringe formats. Advantageously, the holding device and/or the displacement device and/or the receptacle can be adjustable relative to one another, advantageously via at least one screw connection in each case. In this way, maximum flexibility can be achieved when producing the syringes and/or when adapting the device according to the invention to different syringe formats and/or filling levels. The barrel may further be adapted to be displaceable relative to the receptacle such that, in a predetermined position of its displacement path, it projects at least partially into an interior of a syringe cylinder arranged on the receptacle. Thus, the barrel with a plunger-type stopper arranged therein can be displaced into the syringe cylinder until the barrel is in the vicinity of a drug arranged in the syringe cylinder. In particular, the barrel can have a radially outwardly extending collar at one end. The barrel can thus be inserted into a corresponding holder, for example from above, and held in place due to the collar and the force of gravity. This may allow easy interchangeability of the barrel on the device according to the invention. Further, the receptacle configured to hold the syringe cylinder may include at least two parts. In this regard, the receptacle may include a first centering receptacle configured to hold a second centering receptacle and the second centering receptacle configured to hold the syringe cylinder, wherein the second centering receptacle is at least partially immersed in the first centering receptacle. The first centering receptacle may have a depth stop configured to limit the displacement path of the second centering receptacle. In other words, the displacement path of the second centering receptacle can be defined by the first centering receptacle. At its end essentially opposite the first centering receptacle, the second centering receptacle can have a holder for a syringe cylinder, which is advantageously designed in the shape of a hollow cylinder or in the form of a clamp. A respective syringe cylinder can then be inserted into this holder of the second centering receptacle either from above or engaged laterally, for example in a horizontal direction, if the receptacle is designed, for example, as an elastic clamp. At this point, the drug can already be present in the syringe cylinder or can only be filled into the holder of the second centering receptacle after the latter has been adjusted. Furthermore, the holding device set up to hold the barrel can at least partially enclose the barrel. In particular, partial enclosure can be such that the barrel is only accommodated in such a way that it can be displaced along its longitudinal extension. In this context, the holding device can be hollow-cylindrical in shape with a bore, preferably concentric with the center axis of the holding device, for receiving the barrel. In a further development of the present invention, the displacement device arranged for displacing the plunger-type stopper relative to the barrel may comprise a plunger guide arranged for aligning a plunger relative to the barrel, and the plunger arranged for displacing the plunger-type stopper relative to the barrel. The plunger can be designed here, for example, as a rod which can be displaced in particular parallel, advantageously coaxially, to a longitudinal center axis of the syringe cylinder. In this context, the displacement device can further comprise a plunger guide receptacle which is set up to hold the plunger guide. For example, the plunger guide can be designed as a slide bushing. Furthermore, the plunger guide or the plunger guide receptacle can be connected to the at least one support element, wherein the plunger guide can advantageously be directly or indirectly adjustable, advantageously via at least one screw connection. Again, divisibility of the plunger guide may allow the device according to the invention to be adapted to different syringe formats. Advantageously, the plunger can have a cylindrical section at the end facing the holding device, the outer diameter of which is smaller than a clear inner diameter of the barrel. This can allow the plunger to be inserted into the barrel in order to move the plunger-type stopper through the tube. An only slightly smaller diameter of this section of the plunger compared to the internal diameter of the barrel can prevent unintentional tilting of the plunger-type stopper in the barrel. The plunger may further comprise, at the end opposite the holding device, an advantageously radially outwardly extending head which is advantageously adapted to be manually actuated, advantageously with a finger, to displace the plunger-type stopper relative to the barrel. On the one hand, the head of the plunger may provide a sufficiently large actuation surface to allow an operator to manually displace the plunger. On the other hand, the head of the plunger may also serve as a weight to assist the operator in applying the force necessary to displace the plunger-type stopper through the barrel. In particular, the plunger may further comprise an advantageously adjustable depth stop adapted to define the end of the displacement path of the plunger-type stopper in the barrel by the displacement device. This can allow an operator, after the depth stop has been successfully adjusted and the syringe format/fill level remains the same, to displace the plunger to the limit without having to pay attention to the position of the plunger relative to the syringe cylinder. Once the plunger has reached its maximum displacement distance, the operator can actuate the actuation section, such as the rocking device, which releases the plunger-type stopper as described above. Further, the device may comprise a securing means adapted to prevent inadvertent displacement of the plunger-type stopper relative to the barrel, wherein the securing means is advantageously pivotally connected to the at least one support element, advantageously via at least one screw connection. Thus, the screw connection may prevent the securing device from pivoting in a fixed state and allow it to pivot in a released state. The securing device can also be equipped with an elastic element, such as a spring, so that the securing device automatically shifts from a release state, in which displacement of the plunger is permitted, to a securing state, in which displacement of the plunger is inhibited. In an advantageous embodiment of the device, the device may comprise:a base plate;a support element connected to the base plate;a receptacle advantageously attached to the base platecomprisinga first centering receptacle adapted to hold a second centering receptacle and advantageously having a depth stop, andthe second centering receptacle, which is adapted to hold the syringe cylinder;a tubular barrel adapted to receive the plunger-type stopper therein;a holding device advantageously attached to the support element, which is adapted to hold the barrel relative to the receptacle and which advantageously at least partially encloses the barrel, wherein the holding device comprises a rocking device configured as an elongated plate-like element adapted to displace the barrel relative to the plunger-type stopper, wherein the rocking device advantageously has a first end adapted to be actuated by a finger and a second end arranged substantially opposite to the first end and at least partially enclosing the barrel; anda displacement device comprising a plunger guide adapted to align a plunger relative to the barrel, wherein the plunger guide is advantageously directly or indirectly adjustable;the plunger which is adapted to displace the plunger-type stopper relative to the barrel and advantageously comprises a depth stop, and a plunger guide receptacle advantageously attached to the support element and adapted to hold the plunger guide; and optionally a securing means adapted to prevent inadvertent displacement of the plunger-type stopper relative to the barrel, wherein the securing means is advantageously pivotally connected to the at least one support element. With respect to this particular embodiment of the present invention, reference is made to the descriptions given for the corresponding individual features. In a second aspect, the present invention relates to a method for manually inserting a plunger-type stopper of elastomer forming part of a plunger into a syringe cylinder in a fluid-tight manner, comprising the steps of:inserting the plunger-type stopper into a tubular barrel;inserting the syringe cylinder into a receptacle set up for this purpose;displacing the plunger-type stopper within the barrel to a predetermined position; anddisplacing the barrel relative to the plunger-type stopper by means of manual actuation of an actuation portion of a displacement device. Already at this point it should be pointed out that all advantages, features and effects mentioned with respect to the device according to the invention are also applicable to the method according to the invention and vice versa. Thus, also the method according to the invention allows to produce small series of syringes filled with a drug (and other syringe-like cylindrical tubes such as cartridges, double-chamber cartridges and double-chamber syringes) from a quantity of 1 while maintaining series conditions. In this case, the plunger-type stopper can be arranged in the predetermined position inside the syringe cylinder. This means that the plunger-type stopper can be arranged in the predetermined position both inside the barrel and inside the syringe cylinder. After the plunger-type stopper reaches the predetermined position within the barrel and syringe cylinder, the barrel may be displaced relative to the plunger-type stopper to a further position wherein the plunger-type stopper fully emerges from the barrel and expands to contact an inner surface of the syringe cylinder. In this way, the plunger-type stopper interacts with the syringe cylinder in a sealing manner. The method according to the invention may further comprise the step of filling the syringe cylinder and optionally closing a syringe head before the syringe cylinder is inserted into the receptacle. This step of filling the syringe cylinder with a drug may be performed at a section of the device according to the invention set up for this purpose, or at a section separate from the device according to the invention. Filling can be carried out, for example, by means of a pipette or semi-automatic filling, advantageously in a sterile environment, such as in an isolator. According to the invention, it is possible to place all the equipment required for filling syringe cylinders on the one hand and for stoppering on the other hand in an isolator. This means that both filling and stoppering can be performed in a sterile environment. Furthermore, the method may comprise the step of arranging the barrel in a holding device before the plunger-type stopper is inserted into the barrel. In this way, the holding device can be used to interchangeably connect different barrels. The method may further comprise the step of displacing the receptacle with the syringe cylinder to a predetermined position prior to displacing the plunger-type stopper within the barrel, wherein the end of the barrel facing the syringe cylinder is at least partially within the syringe cylinder in the predetermined position of the syringe cylinder. In such an embodiment of the method according to the invention, the holding device may remain fixed with the barrel, for example relative to a frame to which the holding device is connected, whereas the syringe cylinder may be displaced to the predetermined position via the barrel. The predetermined position of the receptacle with the syringe cylinder can be achieved by placing the receptacle against a depth stop mounted in the receptacle. This can prevent the syringe cylinder from being displaced beyond the predetermined position relative to the barrel, which in turn can prevent the barrel from coming into contact with the drug. Prior to displacing the plunger-type stopper within the syringe cylinder, the receptacle with the syringe cylinder and the barrel can be adjusted so that they are substantially coaxial with each other. This allows the barrel and syringe cylinder to be moved relative to each other without contacting each other, which could contaminate an inner wall of the syringe cylinder, for example. Further, the displacement of the plunger-type stopper within the barrel may be effected by a displacement device adapted to displace the plunger-type stopper relative to the barrel. In this case, a displacement direction of the displacement device may be substantially parallel or coaxial to a longitudinal center axis of the barrel and/or the syringe cylinder. In particular, the displacement of the plunger-type stopper within the barrel can be effected by applying, advantageously manually, a compressive force to a plunger which forms part of the displacement device and which is adapted to displace the plunger-type stopper relative to the barrel. As already described with reference to the device according to the invention, the plunger can displace the plunger-type stopper through the barrel in particular in such a way that the plunger-type stopper maintains a desired orientation relative to the barrel, i.e., an unintentional tilting of the plunger-type stopper can be prevented. In this case, the predetermined position of the plunger-type stopper can advantageously be achieved by arranging a depth stop arranged on the plunger against a plunger guide. Here, too, a depth stop can prevent the plunger-type stopper from being displaced beyond the predetermined position. Advantageously, the displacement of the barrel relative to the plunger-type stopper can be effected by means of manually exerting an actuating force acting in a first direction, advantageously with a finger, on a first end of a rocking device, whereby a lever force acting in a second direction is transmitted to the barrel at a second end of the rocking device, which is arranged substantially opposite to the first end and which advantageously at least partially encloses the barrel, wherein the first direction is arranged substantially opposite to the second direction. This allows the barrel to be displaced out of its holding device such that it moves away from the syringe cylinder, releasing the plunger-type stopper so that it expands and comes into contact with the syringe cylinder. At the latest after removal of the finished syringe, the barrel can be displaced back to its original position in its holding device, for example due to gravity or due to a new plunger-type stopper being inserted into the barrel. In this case, the displacement of the barrel relative to the plunger-type stopper can be achieved by means of(i) holding the plunger-type stopper in the predetermined position within the syringe cylinder by means of exerting a holding force on the plunger-type stopper, advantageously via a fixable plunger which constitutes part of the displacement device and which is adapted to displace the plunger-type stopper relative to the barrel and which advantageously rests against a plunger guide with a depth stop arranged thereon, and(ii) exerting a compressive force, advantageously with a finger, on a first end of an elongated plate-like element, thereby transmitting to the barrel, at a second end arranged opposite the first end and at least partially enclosing the barrel, a lever force whose direction is substantially opposite to the compressive force,so that the plunger-type stopper completely emerges from the barrel and expands in such a way that it comes into contact with an inner surface of the syringe cylinder. As mentioned above, a plunger-type stopper in a syringe cylinder can thus be brought close to a filling level of a drug arranged in the syringe cylinder without creating an overpressure in the syringe cylinder, which can, for example, expel drug from the syringe cylinder. In an advantageous embodiment of the method according to the invention, the method may comprise the following steps of:inserting the plunger-type stopper into a tubular barrel;inserting an advantageously filled syringe cylinder into a receptacle adapted thereto comprising a first centering receptacle adapted to hold a second centering receptacle and the second centering receptacle adapted to hold the syringe cylinder;displacing the second centering receptacle with the syringe cylinder to a predetermined position within the first centering receptacle, wherein the predetermined position is advantageously achieved by placing the second centering receptacle against a depth stop mounted in the first centering receptacle;arranging the barrel with the plunger-type stopper in a holding device;optionally, adjusting the receptacle with the syringe cylinder and the barrel so that they are aligned substantially coaxially with each other;releasing a securing device which is arranged to prevent unintentional displacement of the plunger-type stopper relative to the barrel;displacing the plunger-type stopper within the barrel by exerting, advantageously manually, a compressive force on a plunger adapted to displace the plunger-type stopper relative to the barrel, wherein the plunger-type stopper, which is arranged at the end of the plunger-type stopper opposite to the plunger, is displaced to a predetermined position by means of the compressive force exerted on the plunger, wherein the predetermined position of the plunger-type stopper is advantageously achieved by placing a depth stop arranged on the plunger against a plunger guide; anddisplacing the barrel relative to the plunger-type stopper by holding the plunger-type stopper in the predetermined position inside the syringe cylinder by exerting a holding force on the plunger-type stopper via the plunger, which advantageously rests against the plunger guide with the depth stop; and exerting a compressive force, advantageously with a finger, on a first end of an elongated plate-like element, whereby at a second end, which is arranged opposite to the first end and at least partially encloses the barrel, a lever force is transmitted to the barrel, the direction of which is substantially opposite to the compressive force, wherein the plunger-type stopper completely emerges from the barrel and expands such that it comes into contact with an inner surface of the syringe cylinder. With reference to the above description of the method according to the invention and the device according to the invention concerning the individual features of this embodiment, this embodiment can represent a particularly simple realization for producing very small series of syringes filled with drugs, also of different syringe formats, while maintaining series conditions. InFIG.1, an embodiment of the device according to the invention is generally designated by the reference sign10. The device10comprises a base plate12as a bottom plate on which the device10stands. Connected to the base plate12is a support element14, which is formed here as a square tube which is welded to a cover16at its end opposite the base plate12. A syringe receptacle18is also connected to the base plate12via two screws20in the embodiment shown inFIG.1. The connection of the syringe receptacle18to the base plate12allows here a displacement of the syringe receptacle18along an axis X towards or away from the support element14. The syringe receptacle18includes a first centering receptacle22adapted to receive a second centering receptacle24, wherein the second centering receptacle24is in turn adapted to receive a syringe cylinder (not shown). The second centering receptacle24is displaceable in the first centering receptacle22along an axis Y, wherein a screw26connected to the second centering receptacle24and engaging the first centering receptacle22forms a depth stop26and allows adjustment of the two centering receptacles22,24relative to each other in a desired position. Along the direction Y, a holding device28is screwed to the support element14above the second centering receptacle24in such a way that the holding device28can be displaced along the axis X relative to the support element14when the screw connection is loosened. The holding device28has a central through-bore into which a barrel30is inserted. The barrel30includes a collar32at its end of the tube portion opposite the second centering receptacle24, the collar32extending radially outwardly from the tube portion of the barrel30. On the one hand, the collar32defines a predetermined position of the barrel30relative to the holding device28. On the other hand, an actuation portion34engages with the collar32and at least partially surrounds the barrel30between the collar32and the holding device28. The actuation portion34is designed here as a plate-like rocking device, which is supported here on the holding device28via an adjusting screw36, via which a pretension or an inclination of the actuation portion34relative to the holding device28or the barrel30can be adjusted, so that an actuation of the actuation portion34at its end38opposite to the barrel30, for example by a finger pressure of a user, in the Y-direction inFIG.1downwards causes a lifting of the barrel30in the Y-direction inFIG.1upwards. In the Y-direction inFIG.1above the holding device28, a plunger guide receptacle40is connected to the support element14, which is also displaceable and adjustable relative to the support element14along the X-axis. Connected to the plunger guide receptacle40is a plunger guide42, in which a plunger44is displaceably arranged along the Y-direction. The section of the plunger44facing the barrel30has an outer diameter which is smaller than an inner diameter of the barrel30, so that the plunger44can dip into the barrel30. At a predetermined, in particular adjustable, position of the plunger44, a depth stop46is connected thereto, which can come into contact with the plunger guide42in such a way that a displacement of the plunger in the Y-direction beyond a position defined by the depth stop46is prevented. At its end opposite the barrel30, the plunger44has a pressure head48which serves as a gripping surface for an operator. InFIG.1, it can be seen that a securing device50is engaged with the print head48, which prevents a displacement of the plunger44, in particular from the position shown inFIG.1along the Y-direction downwards. The embodiment of the securing device50shown inFIG.1is adapted to be pivoted about the Y-axis to release displacement of the plunger44. In the following, the method according to the invention in one possible embodiment will be briefly described again with reference to the device10according to the invention. First, a plunger-type stopper is inserted into the barrel30using, for example, tweezers. Then, a syringe cylinder filled with a drug is inserted into the second centering receptacle24. The second centering receptacle24is now displaced upward in the direction Y inFIG.1until further displacement is limited by the depth stop26. In this position, the screw26is tightened so that the relative position of the second centering receptacle24to the first centering receptacle22is fixed. In this condition, the barrel30is immersed in the syringe cylinder. Next, the securing device50is pivoted to the side so that the plunger44can be displaced downward in the Y-direction until the depth stop46rests against the plunger guide42. While an operator maintains a pressure on the plunger48, the operator presses on the first end38of the actuation portion34in the Y-direction from top to bottom, at least partially displacing the barrel30upwardly out of the syringe cylinder. This releases the plunger-type stopper, which continues to be held in position relative to the syringe cylinder by the plunger44, allowing it to expand to engage the syringe cylinder in a sealing manner. Subsequently, the plunger44and the second centering receptacle24are moved back to their initial positions and the syringe cylinder provided with the plunger-type stopper can be removed from the device10. The following items are subject matter of the invention. It is noted that the following items may be combined in any order and in any combination or sub-combination with one another: Example embodiments of the invention can be achieved by a device (10) for manually inserting a plunger-type stopper made of elastomer forming part of a plunger into a syringe cylinder, comprising:a receptacle (18) adapted to hold the syringe cylinder;a tubular barrel (30) adapted to receive the plunger-type stopper in its interior;a holding device (28) adapted to hold the barrel (30) relative to the receptacle (18); anda displacement device (40,42,44,46,48) adapted to displace the plunger-type stopper relative to the barrel (30);wherein the holding device (28) comprises an actuation portion (34) adapted to be manually actuated to displace the barrel (30) relative to the plunger-type stopper. The device (10) can be characterized in that the actuation portion (34) of the holding device (28) comprises a rocking device (34) adapted to transfer a manual actuating force acting in a first direction, which has been input at a first end of the rocking device (34), into a lever force acting in a second direction at a second end of the rocking device (34) arranged opposite to the first end, wherein the first direction is substantially opposite to the second direction. The device (10) can be characterized in that the rocking device (34) is designed as an elongated plate-like element. The device (10) can be characterized in that the plate-like element (34) has a first end (38) adapted to be actuated by a finger and a second end disposed substantially opposite the first end (38) and which at least partially encloses the barrel (30). The device (10) can be characterized in that it further comprises at least one support element (14) to which the holding device (28) and/or the displacement device (40,42,44,46,48) are/is connected. The device (10) can be characterized in that it further comprises a base plate (12) advantageously connected to the at least one support element (14) according to item5. The device (10) can be characterized in that the receptacle (18) is attached to the base plate (12). The device (10) can be characterized in that the receptacle (18) is adjustable relative to the holding device (28) and/or the displacement device (40,42,44,46,48), advantageously via at least one screw connection (26). The device (10) can be characterized in that the holding device (28) and/or the displacement device (40,42,44,46,48) and/or the receptacle (18) can be adjusted relative to one another, advantageously by means of at least one screw connection (26) in each case. The device (10) can be characterized in that the barrel (30) is further adapted to be displaceable relative to the receptacle (18) such that, in a predetermined position of its displacement path, it projects at least partially into an interior of a syringe cylinder arranged on the receptacle (18). The device (10) can be characterized in that the barrel (30) has a radially outwardly extending collar (32) at one end. The device (10) can be characterized in that the receptacle (18) arranged for holding the syringe cylinder comprises at least two parts. The device (10) can be characterized in that the receptacle (18) comprises a first centering receptacle (22) adapted to hold a second centering receptacle (24) and the second centering receptacle (24) adapted to hold the syringe cylinder, wherein the second centering receptacle (24) dips at least partially into the first centering receptacle (22). The device (10) can be characterized in that the first centering receptacle (22) has a depth stop (26) which is adapted to limit the displacement path of the second centering receptacle (24). The device (10) can be characterized in that the second centering receptacle (24) has, at its end substantially opposite the first centering receptacle (22), a holder for a syringe cylinder, which is advantageously of hollow-cylindrical or clamp-like design. The device (10) can be characterized in that the holding device (28) adapted to hold the barrel (30) at least partially encloses the barrel (30). The device (10) can be characterized in that the holding device (28) is designed in the shape of a hollow cylinder with a bore, preferably concentric with the center axis of the holding device (28), for receiving (18) the barrel (30). The device (10) can be characterized in that the displacement device (40,42,44,46,48) arranged to displace the plunger-type stopper relative to the barrel (30) comprises a plunger guide (42) adapted to align a plunger (44) relative to the barrel (30) and the plunger (44) adapted to displace the plunger-type stopper relative to the barrel (30). The device (10) can be characterized in that the displacement device (40,42,44,46,48) further comprises a plunger guide receptacle (40) adapted to hold the plunger guide (42). The device (10) can be characterized in that the plunger guide (42) or the plunger guide receptacle (40) are connected to the at least one support element (14), wherein the plunger guide (42) is advantageously adjustable directly or indirectly, advantageously via at least one screw connection. The device (10) can be characterized in that the plunger (44) has a cylindrical portion at the end facing the holding device (28), the outer diameter of which is smaller than a clear inner diameter of the barrel (30). The device (10) can be characterized in that the plunger (44) further comprises, at the end opposite the holding device (28), an advantageously radially outwardly extending head (48) adapted to be manually actuated, advantageously with a finger, to displace the plunger-type stopper relative to the barrel (30). The device (10) can be characterized in that the plunger (44) further comprises an advantageously adjustable depth stop (46) adapted to define the end of the displacement path of the plunger-type stopper in the barrel (30) by the displacement device (40,42,44,46,48). The device (10) can be characterized in that the device (10) further comprises a securing means (50) adapted to prevent inadvertent displacement of the plunger-type stopper relative to the barrel (30), wherein the securing device (50) is advantageously pivotally connected to the at least one support element (14), advantageously via at least one screw connection. The device (10) can include a base plate (12); a support element (14) connected to the base plate (12); a receptacle (18) advantageously attached to the base plate (12), including a first centering receptacle (22) adapted to hold a second centering receptacle (24) and advantageously having a depth stop (26), and the second centering receptacle (24) adapted to hold the syringe cylinder, a tubular barrel (30) adapted to receive the plunger-type stopper in its interior; a holding device (28) advantageously attached to the support element (14), which is adapted to hold the barrel (30) relative to the receptacle (18) and which advantageously at least partially encloses the barrel (30), wherein the holding device (28) comprises a rocking device (34) configured as an elongated plate-like element, which is adapted to displace the barrel (30) relative to the plunger-type stopper, wherein the rocking device (34) advantageously has a first end (38) adapted to be actuated by a finger and a second end which is arranged substantially opposite the first end (38) and which at least partially encloses the barrel (30), and a displacement device (40,42,44,46,48) comprising a plunger guide (42) adapted to align a plunger (44) relative to the barrel (30), wherein the plunger guide (42) is advantageously directly or indirectly adjustable, the plunger (44) is adapted to displace the plunger-type stopper relative to the barrel (30) and advantageously comprises a depth stop (46), and a plunger guide receptacle (40) advantageously attached to the support element (14) and adapted to hold the plunger guide (42); and optionally a securing device (50) adapted to prevent inadvertent displacement of the plunger-type stopper relative to the barrel (30), wherein the securing device (50) is advantageously pivotally connected to the at least one support element (14). Example embodiment of the present invention can include a method for manually inserting a plunger-type stopper made of elastomer forming part of a plunger into a syringe cylinder in a fluid-tight manner, comprising the steps of:inserting the plunger-type stopper into a tubular barrel (30);inserting the syringe cylinder into a receptacle (18) set up for this purpose;displacing the plunger-type stopper within the barrel (30) to a predetermined position; anddisplacing the barrel (30) relative to the plunger-type stopper by means of manual actuation of an actuation portion (34) of a displacement device (40,42,44,46,48). The method can be characterized in that the plunger-type stopper is arranged in the predetermined position inside the syringe cylinder. The method can be characterized in that after the plunger-type stopper reaches the predetermined position within the barrel (30) and the syringe cylinder, the barrel (30) is displaced relative to the plunger-type stopper to a further position, wherein the plunger-type stopper fully emerges from the barrel (30) and expands such that it contacts an inner surface of the syringe cylinder. The method can include the step of filling the syringe cylinder and optionally closing a syringe head before inserting the syringe cylinder into the receptacle (18). The method can include the step of placing the barrel (30) in a holding device (28) before inserting the plunger-type stopper into the barrel (30). The method can include the step of displacing the receptacle (18) with the syringe cylinder to a predetermined position prior to displacing the plunger-type stopper within the barrel (30), wherein the end of the barrel (30) facing the syringe cylinder is at least partially within the syringe cylinder in the predetermined position of the syringe cylinder. The method can be characterized in that the predetermined position of the receptacle (18) with the syringe cylinder is achieved by placing the receptacle (18) against a depth stop (26) mounted in the receptacle (18). The method can be characterized in that prior to displacing the plunger-type stopper within the barrel (30), the receptacle (18) with the syringe cylinder and the barrel (30) are adjusted to be substantially coaxially aligned. The method can be characterized in that the displacement of the plunger-type stopper within the barrel (30) is effected by a displacement device (40,42,44,46,48) adapted to displace the plunger-type stopper relative to the barrel (30). The method can be characterized in that the displacement of the plunger-type stopper within the barrel (30) is effected by exerting, advantageously manually, a compressive force on a plunger (44) which constitutes part of the displacement device (40,42,44,46,48) and which is adapted to displace the plunger-type stopper relative to the barrel (30). The method can be characterized in that the predetermined position of the plunger-type stopper is advantageously achieved by arranging a depth stop (46) arranged on the plunger (44) against a plunger guide (42). The method can be characterized in that the displacement of the barrel (30) relative to the plunger-type stopper is effected by means of manual exertion of an actuating force acting in a first direction, advantageously with a finger, on a first end (38) of a rocking device (34), as a result of which a lever force acting in a second direction is transmitted to the barrel (30) at a second end of the rocking device (34), which is arranged substantially opposite the first end (38) and which advantageously at least partially encloses the barrel (30), wherein the first direction is substantially opposite the second direction. The method can be characterized in that the displacement of the barrel (30) relative to the plunger-type stopper is achieved by means of holding the plunger-type stopper in the predetermined position within the syringe cylinder by means of exerting a holding force on the plunger-type stopper, advantageously via a fixable plunger (44) which constitutes part of the displacement device (40,42,44,46,48) and which is adapted to displace the plunger-type stopper relative to the barrel (30) and which advantageously rests against a plunger guide (42) with a depth stop (46) arranged thereon, and exerting a compressive force, advantageously with a finger, on a first end (38) of an elongated plate-like element (34), thereby transmitting to the barrel (30), at a second end arranged opposite the first end (38) and at least partially surrounding the barrel (30), a lever force whose direction is substantially opposite to the compressive force, so that the plunger-type stopper emerges completely from the barrel (30) and expands so that it comes into contact with an inner surface of the syringe cylinder. The method can be characterized in that the method comprises the following steps of:inserting the plunger-type stopper into a tubular barrel (30);inserting an advantageously filled syringe cylinder into a receptacle (18) adapted thereto comprising a first centering receptacle (22) adapted to hold a second centering receptacle (24) and the second centering receptacle (24) adapted to hold the syringe cylinder;displacing the second centering receptacle (24) with the syringe cylinder to a predetermined position within the first centering receptacle (22), wherein the predetermined position is advantageously achieved by placing the second centering receptacle (24) against a depth stop (26) mounted in the first centering receptacle (22);arranging the barrel (30) with the plunger-type stopper in a holding device (28);optionally, adjusting the receptacle (18) with the syringe cylinder and the barrel (30) so that they are aligned substantially coaxially with each other;releasing a securing device (50) adapted to prevent inadvertent displacement of the plunger-type stopper relative to the barrel (30);displacing the plunger-type stopper within the barrel (30) by exerting, advantageously manually, a compressive force on a plunger (44) adapted to displace the plunger-type stopper relative to the barrel (30), wherein the plunger-type stopper, arranged at the end of the plunger-type stopper opposite to the plunger (44), is displaced to a predetermined position by means of the compressive force exerted on the plunger (44), wherein the predetermined position of the plunger-type stopper is advantageously achieved by placing a depth stop (46) arranged on the plunger (44) against a plunger guide (42); anddisplacing the barrel (30) relative to the plunger-type stopper by holding the plunger-type stopper in the predetermined position within the syringe cylinder by exerting a holding force on the plunger-type stopper via the plunger (44), which advantageously rests against the plunger guide (42) with the depth stop (46), and exerting a compressive force, advantageously with a finger, on a first end (38) of an elongated plate-like element (34), thereby transmitting to the barrel (30), at a second end arranged opposite the first end (38) and at least partially enclosing the barrel (30), a lever force whose direction is substantially opposite to the compressive force, wherein the plunger-type stopper completely emerges from the barrel (30) and expands to contact an inner surface of the syringe cylinder. | 46,479 |
11857767 | DETAILED DESCRIPTION OF THE DISCLOSURE Certain terminology is used in the following description for convenience only and is not limiting. For example, the words “lower,” “bottom,” “upper” and “top” designate directions in the drawings to which reference is made. The words “inwardly,” “outwardly,” “upwardly” and “downwardly” refer to directions toward and away from, respectively, the geometric center of the injector, and designated parts thereof, in accordance with the present disclosure. Unless specifically set forth herein, the terms “a,” “an” and “the” are not limited to one element, but instead should be read as meaning “at least one.” The terminology includes the words noted above, derivatives thereof and words of similar import. It should also be understood that the terms “about,” “approximately,” “generally,” “substantially” and like terms, used herein when referring to a dimension or characteristic of a component of the invention, indicate that the described dimension/characteristic is not a strict boundary or parameter and does not exclude minor variations therefrom that are functionally similar. At a minimum, such references that include a numerical parameter would include variations that, using mathematical and industrial principles accepted in the art (e.g., rounding, measurement or other systematic errors, manufacturing tolerances, etc.), would not vary the least significant digit. Referring to the drawings in detail, wherein like numerals indicate like elements throughout, there is shown inFIGS.1-9Ban injector, generally designated10, in accordance with an embodiment of the present disclosure. In the illustrated embodiment, the injector10takes the form of a wearable injector (patch injector), such as, for example, without limitation, a wearable drug injector, but the disclosure is not so limited. As should be understood by those of ordinary skill in the art, the injector10generally includes a body11. The body11includes a main housing12having a first surface14configured to contact a skin surface of a user (not shown), e.g., a patient, the first surface14having an opening14atherein. In the illustrated embodiment, the first surface14defines a base surface of the injector main housing12, but the disclosure is not so limited. The main housing12also includes a second surface16opposing the first surface14. In the illustrated embodiment, the second surface16defines a top, external surface of the injector main housing12, but the disclosure is not so limited. As shown inFIGS.2-3, a needle hub18, constructed, for example, from a polymeric or metal material, combinations thereof, or the like, is movably mounted within the main housing12of the injector body11and an injection needle20is supported by the movable needle hub18in a manner well understood by those of ordinary skill in the art. In the illustrated embodiment, the needle hub18and the injection needle20are axially translatable (or otherwise displaceable) in the direction of axis A (FIG.2) extending substantially perpendicularly to the first surface14, between a retracted position (FIG.2), wherein at least a tip20aof the injection needle20is contained within the injector main housing12, and an injection position (FIG.3), wherein at least the tip20aof the injection needle20protrudes from the injector main housing12through the opening14a. As should be understood by those of ordinary skill in the art, however, the axis A may be positioned at angles other than 90° relative to the first surface14. As also should be understood, the injection needle20may be movably mounted within the injector main housing12via mechanisms other than the needle hub18. In some embodiments, a depressible activation button assembly22, constructed, for example, from a polymeric or metal material, combinations thereof, or the like, may be movably mounted to the injector main housing12and operatively connected to the injection needle20. The activation button assembly22may be translatable, i.e., depressible, along a button axis B (FIG.2) from an unactuated position (FIGS.1,2) to an actuated position (FIG.3) in a manner well understood by those of ordinary skill in the art, to activate the injector10. In one embodiment, the button axis B may be parallel to the axis A, but the disclosure is not so limited. Activation of the injector10includes, for example, driving the injection needle20from the retraction position to the injection position thereof to perform an injection. A biasing member24may be operatively connected with the activation button assembly22and the injection needle20(FIGS.2,3), but the disclosure is not so limited. As one alternative example, the biasing member24may be connected with the second surface16and the injection needle20. The biasing member24is stabilized in a stored energy state in the unactuated position of the activation button assembly22(FIG.2) and released into an energy releasing state, when the activation button assembly22is translated into the actuated position thereof (FIG.3), to drive the injection needle20along the direction of axis A from the retracted position thereof to the injection position thereof. As should be understood by those of ordinary skill in the art, the stored energy state of the biasing member24is a state in which the biasing member24stores at least some potential energy. The energy releasing state of the biasing member24is a state of the biasing member24in which the biasing member24releases at least some of the previously stored potential energy from the stored energy state. In one embodiment, the biasing member24may take the form of a coil spring mounted between the needle hub18and the activation button assembly22, i.e., the spring24abuts the activation button assembly22at one end and abuts the needle hub18at an opposing end. In the energy storing state, the coil spring24is at least partially compressed. In the energy releasing state, the coil spring24expands (relative to the at least partially compressed energy storing state) to drive the needle hub18and the injection needle20into the injection position thereof. As should be understood by those of ordinary skill in the art, however, the biasing member24may alternatively take the form of other members capable of storing and releasing energy. Non-limiting examples include other springs (e.g., torsion or leaf springs), elastic bands, and the like. Alternatively, the biasing member24may take the form of an electromechanical or pneumatic actuator configured to apply a translational force onto the injection needle20when the activation button assembly22is depressed into the actuated position thereof. The injector body11further includes a cartridge door26movably, e.g., pivotably, mounted to the injector main housing12, between an open position (not shown) and a closed position (FIG.1). As shown inFIG.4A, the cartridge door26includes a proximal open end26aand an interior pathway26bfor receiving (in the open position of the door) one of a plurality of differently dimensioned cartridges28therein, e.g., at least a first cartridge28′ or a differently dimensioned second cartridge28″ e.g., radially different, (as will be described in further detail below, see, e.g.,FIGS.8A-9B). As should be understood, a cartridge28usable with the injector10includes a reservoir28acontaining a substance (not shown), e.g., medicament, to be dispensed from the injector10through the injection needle20, and having a first, distal opening sealed by a pierceable septum29in a manner well understood by those of ordinary skill in the art. The cartridge door26further includes a coupler26cmounted within the interior pathway26b. In the illustrated embodiment, the coupler26ctakes the form of a cartridge piercing needle26c, but the disclosure is not so limited. As shown schematically inFIGS.8A-9B, the cartridge piercing needle26cis fluidly connected to the injection needle20in a manner well understood by those of ordinary skill in the art, e.g., via a flexible tube (partially shown inFIGS.4B,5) extending from the piercing needle26cto the injection needle20. In the illustrated embodiment, the cartridge piercing needle26cis positioned proximate a closed, distal end of the interior pathway26b, opposite the proximal open end26a(FIGS.4A,8A-9B). The cartridge piercing needle26cextends inwardly into the interior pathway26band terminates at a tip of the needle26c, positioned to face and align with the pierceable septum29of the cartridge28when the cartridge28is inserted into the cartridge door26. The cartridge piercing needle26cis configured to fully penetrate the pierceable septum29of the cartridge28to fluidly connect the substance within the cartridge28with the injection needle20when the cartridge28is sufficiently inserted into the interior pathway26band/or when the injector10is activated. As shown inFIGS.4-5, at least one adapter collar30,30′ is mountable within the interior pathway26b(in an orientation generally transverse to the cartridge insertion path). The adapter collar30,30′ is configured, i.e., sized and dimensioned, to receive any cartridge28usable with the injector10therethrough upon insertion of the cartridge28into the interior pathway26b, and configured to engage a portion of a particularly dimensioned corresponding cartridge28to stabilize the cartridge28within the interior pathway26b. In one configuration, as shown best inFIGS.6A-6B, the adapter collar30includes a disk32and a plurality of angularly spaced ribs34projecting radially inwardly into the interior pathway26bfrom the disk32. In the illustrated embodiment, the adapter collar30includes three ribs34generally equally angularly spaced apart about the interior of the disk32, but the disclosure is not so limited. The ribs34are substantially equally sized, dimensioned and configured to engage and stabilize the corresponding cartridge28in a position aligned, e.g., substantially co-axially, with the cartridge piercing needle26c. In one configuration, as shown inFIGS.6A-6B, one or more of the ribs34each includes a first segment34aprojecting primarily radially inwardly from the disk32, a second segment34bprojecting primarily distally (i.e., toward the cartridge piercing needle26c) from the first segment34aand a third segment34cprojecting primarily radially inwardly from the second segment34b. The first and third segments34aand34cmay also be slightly angled distally and/or be distally flexible upon engagement of the ribs34with a cartridge28to better align the cartridge28with the cartridge piercing needle26c. As should be understood by those of ordinary skill in the art, however, the ribs34may be employed in alternative configurations capable of performing the function of the ribs34described herein. In some embodiments, the adapter collar30may also include a plurality of angularly spaced apart cantilevered fingers36projecting from the disk32. In the illustrated embodiment, the adapter collar30includes three fingers36generally equally angularly spaced apart about the interior of the disk32, but the disclosure is not so limited. As shown inFIGS.4A,4B and6A, the fingers36are oriented in a radially inwardly projecting, closed position when unbiased by a cartridge28, i.e., when a cartridge28has not been advanced past the fingers36. The fingers36are dimensioned, such that the fingers36cover the cartridge piercing needle26cwhen in the closed position. For example, the fingers36may extend radially inwardly proximate to the central axis of the disk32. Thus, in the closed position thereof, the fingers36assist in preventing contact between the cartridge piercing needle26cand a user's hands/fingers (or other of a user's body parts), and, therefore, assist in preventing needle stick injuries. As shown inFIGS.5and6B, the cantilevered fingers36are deflectable distally and radially outwardly (generally at the interface between the finger36and the disk32) relative to one another into an open position exposing the cartridge piercing needle26c, upon advancement of a cartridge28beyond the disk32. That is, the cartridge28deflects the fingers36into the open position thereof upon advancement of the cartridge28beyond the position of the fingers36in the closed position thereof, exposing the cartridge piercing needle26cto penetrate the septum29of the cartridge28. In one configuration, as shown inFIGS.6A-6B, one or more of the fingers36each include a first segment36aprojecting primarily radially inwardly from the disk32. The interface between the first segment36aand the disk32may define, for example, a living hinge having a natural bias to orient in the closed position in the absence of an external force by a cartridge28. A second segment36bprojects primarily distally from the first segment36aand a third segment36cprojects primarily radially inwardly from the second segment36b. A fourth segment36dmay project further radially inwardly and also project proximally from the third segment36cto provide additional vertical clearance above the cartridge piercing needle26c. One or more of the segments36a-36dmay also define living hinges at the respective interfaces therebetween to provide additional flexibility to the fingers36. As should be understood, the lengths of the segments36a-dbehave as moment arms for the deflection of the fingers36. Accordingly, the lengths of the segments36a-dmay be configured to generally set the advancement force required by a cartridge28to deflect the fingers36from the closed position to the open position thereof. As also should be understood by those of ordinary skill in the art, the fingers36may be employed in alternative configurations capable of performing the function of the fingers36described herein. FIGS.7A-7Billustrate an alternative configuration of the adapter collar30′. This configuration is similar to that of the configuration ofFIGS.6A-6B, and, therefore, the description of certain similarities between the configurations ofFIGS.7A-7BandFIGS.6A-6Bmay be omitted herein for the sake of brevity and convenience, and, therefore, is not limiting. One difference of the adapter collar30′ over the adapter collar30(as shown in the figures) is the addition of a frangible, i.e., intentionally breakable, member38connecting the cantilevered fingers36′ to one another in the closed position thereof. In the illustrated embodiment, the frangible member38takes the form of a frangible ring, but the disclosure is not so limited. As shown best inFIG.7A, the frangible ring38includes at least one scored segment38a, e.g., a scored segment38abetween each cantilevered finger36′, defining the intentionally breakable segment(s) of the ring38(FIG.7B). As should be understood by those of ordinary skill in the art, the scored segments38aof the frangible ring38define a pre-set breaking force of the frangible ring38, which must be exceeded to separate and disconnect the ring38in order to separate and disconnect the fingers36′ from one another and deflect the fingers36′ from the closed position to the open position thereof. As should be understood, the fingers36of the adapter collar30may also be joined by frangible members similar to the frangible member38joining the fingers36′ of the adapter collar30′. In one configuration of the adapter collar30′, one or more of ribs34′ takes the form of a generally arcuate member extending radially inwardly and distally from the disk32, having a convex surface thereof facing toward the central axis of the disk32, but the disclosure is not so limited. Additionally, or alternatively, one or more of the cantilevered fingers36′ defines a generally S-shaped curvilinear contour, extending radially inwardly and distally from the disk32(assisting in cartridge28lead in), but the disclosure is not so limited. As shown best inFIGS.4A-5, at least one adapter collar30,30′ is mounted within the interior pathway26b. In one configuration, the adapter collar30,30′ may be removably mounted within the interior pathway26b(intentionally removable without damaging the collar30,30′ and/or the interior pathway26b). For example, the interior pathway26bmay include a radially inwardly extending annular lip40projecting from the sidewall of the interior pathway26b, or radially inwardly extending lip segments40projecting from the sidewall of the interior pathway26bangularly spaced (in substantially the same plane) about the sidewall, upon which the adapter collar30,30′ may be supported. Alternatively, or additionally, the adapter collar30,30′ may be mounted within the interior pathway26bvia a friction fit with the sidewall of the interior pathway26b. In one embodiment, the adapter collar30,30′ may include mounting slot32ain the disk32thereof, for receiving the annular lip segments40. As should be understood by one those of ordinary skill in the art, however, the adapter collar30,30′ may be removably mounted within the interior pathway26bvia any of numerous mounting means currently known, or that later become known. Alternatively, an adapter collar30,30′ may be permanently (i.e., non-removable without damaging the collar30,30′ and/or the interior pathway26b) mounted within the interior pathway26bor integrally formed with the interior pathway26b. For injectors10having more than one adapter collar30,30′ mounted within the interior pathway26bthereof (as will be discussed in further detail below), the adapter collars30,30′, may be integrally, permanently or removably mounted therein, or any combination thereof. In use, an injector10includes at least one adapter collar30,30′ mounted within the interior pathway26b, corresponding to a cartridge28intended for use with the injector10(FIGS.4A,4B). The cartridge28is inserted into the interior pathway26bvia the proximal open end26athereof and advanced through the adapter collar30,30′ and into engagement with the cartridge piercing needle26c(FIG.5), i.e., piercing the septum29. The adapter collar30,30′ is configured (via the size and dimension of the ribs34,34′) to engage a portion of the corresponding cartridge28to stabilize the cartridge28within the interior pathway26band align, e.g., substantially co-axially, the cartridge28with the cartridge piercing needle26c. In configurations where the adapter collar30,30′ includes the cantilevered fingers36,36′, the fingers36,36′ protect the user against inadvertent needle stick injuries from the cartridge piercing needle26cin the closed position. During insertion of the cartridge28into the interior pathway26b, the cartridge28engages and deflects the fingers36,36′ into the open position thereof upon advancement beyond the fingers36,36′ and into engagement with the cartridge piercing needle26c(FIG.5). In some embodiments, the injector10may be configured to be usable with cartridges28of different sizes. For example, as shown schematically, inFIGS.8A-9B, the injector10may be configured for use with at least two differently dimensioned cartridges: a first cartridge28′ and a second cartridge28″. Accordingly, the interior pathway26bis sized, e.g., in diameter, to receive either of the first cartridge28′ or second cartridge28″. In one exemplary non-limiting embodiment, the interior pathway26cmay include at least two of the adapter collars30,30′ mounted therein (two of the adapter collars30,30′ shown inFIGS.8A,8B). As shown in the non-limiting example ofFIGS.8A and8B, the first cartridge28′ may define a radially larger distal portion relative to the distal portion of the second cartridge28″, and the second cartridge28″ may define a radially larger proximal portion relative to the proximal portion of the first cartridge28′. A first adapter collar30,30′, therefore, is mounted distally within the interior pathway26crelative to the second adapter collar30,30′. The first, distal adapter collar30,30′ is sized and positioned within the interior pathway26bto permit advancement of either one of the first cartridge28′ or the second cartridge28″ therethrough upon insertion of that cartridge into the interior pathway26b. As shown inFIG.8B, the first, distal adapter collar30,30′ is sized and positioned, however, to only engage a distal portion of the first cartridge28′ to stabilize the first cartridge28′ within the interior pathway26b, and align the first cartridge28′ with the cartridge piercing needle26c. That is, the ribs34,34′ of the first, distal adapter collar30,30′ are sized and dimensioned to engage the distal portion of the first cartridge28′, without interfering with the smaller distal portion of the second cartridge28″ if the second cartridge28″ was to be utilized with the injector10. Similarly, the second, proximal adapter collar30,30′ is also sized and positioned within the interior pathway26bto permit advancement of either one of the first cartridge28′ or the second cartridge28″ therethrough upon insertion of that cartridge into the interior pathway26b. Conversely, however, as shown inFIG.8A, the second, proximal adapter collar30,30′ is sized and positioned to only engage a proximal portion of the second cartridge28″ to stabilize the second cartridge28″ within the interior pathway26b, and to align the second cartridge28″ with the cartridge piercing needle26c. That is, the ribs34,34′ of the second, proximal adapter collar30,30′ are sized and dimensioned to engage the proximal portion of the second cartridge28″, without interfering with the first cartridge28′ if the first cartridge28′ was to be utilized with the injector10. Therefore, in the embodiment ofFIGS.8A,8B, the second cartridge28″ is not obstructed by either of the adapter collars30,30′ mounted within the interior pathway26b, and the first cartridge28′ is also not obstructed by either of the adapter collars30,30′ mounted within the interior pathway26b. Either of the two cartridges28′,28″ is usable with the injector10, however, as either cartridge28′,28″ may be stabilized within the interior pathway26band aligned with the cartridge piercing needle26c. In some embodiments, some of the adapter collars30,30′ mounted within the interior pathway26b, such as, for example, the distal-most adapter collar, may include the plurality of angularly spaced apart cantilevered fingers36,36′ projecting from the disk32to assist in preventing contact between a user's hands/fingers (or other of a user's body parts) and the cartridge piercing needle26c, and, therefore, assist in preventing needle stick injuries. Alternatively, all or none of the adapter collars30,30′ mounted within the interior pathway26bmay include the cantilevered fingers36,36′. In an alternative exemplary non-limiting embodiment, as shown inFIGS.9A, and9B, the interior pathway may include solely the distal adapter collar30,30′ as shown inFIGS.8A and8B, configured in like manner as the distal adapter collar30,30′ described with respect toFIGS.8A and8Bto stabilize the first cartridge28′ within the interior pathway26b, and to align the first cartridge28′ with the cartridge piercing needle26c(FIG.9B). Conversely, the interior pathway26bitself, i.e., the internal features thereof, may be configured to stabilize the second cartridge28″ within the interior pathway26b, and to align the second cartridge28″ with the cartridge piercing needle26c(FIG.9A). For example, without limitation, the interior pathway26bmay be dimensioned or include a cartridge cradle, a cartridge track, combinations thereof, or the like (not shown) to receive and stabilize the cartridge28in the interior pathway26b. In one configuration, the injector10may be provided as a kit with a plurality of adapter collars30,30′ removably mountable within the interior pathway26b. The interior pathway26bmay be configured to receive any one of multiple different dimensioned cartridges28, i.e., sized and dimensioned to receive the largest of those cartridges28. Each adapter collar30,30′ provided may be configured, i.e., sized and dimensioned, for use with a corresponding one of the multiple differently dimensioned cartridges28, to engage a portion of the corresponding cartridge28(with the ribs34,34′ thereof) to stabilize the cartridge28within the interior pathway26band align the cartridge28with the cartridge piercing needle26c. Alternatively, or additionally, adapter collars30,30′ provided may be configured to account for variations between cartridges28due to manufacturing tolerances. Accordingly, a user may mount a particular adapter collar30,30′ within the interior pathway26bto enable usage of the injector10with the respective corresponding cartridge28prior to inserting the corresponding cartridge28into the interior pathway26b. It will be appreciated by those skilled in the art that changes could be made to the embodiments described above without departing from the broad inventive concept thereof. It is understood, therefore, that this invention is not limited to the particular embodiments disclosed, but it is intended to cover modifications within the spirit and scope of the present invention, as set forth in the appended claims. | 24,977 |
11857768 | DETAILED DESCRIPTION The presently disclosed subject matter is described with specificity to meet statutory requirements. However, the description itself is not intended to limit the scope of this patent. Rather, the inventors have contemplated that the claimed subject matter might also be embodied in other ways, to include different steps or elements similar to the ones described in this document, in conjunction with other present or future technologies. Moreover, although the term “step” may be used herein to connote different aspects of methods employed, the term should not be interpreted as implying any particular order among or between various steps herein disclosed unless and except when the order of individual steps is explicitly described. FIG.1illustrates the filtered needle assembly100in exploded perspective form. Introduced inFIG.1are: the needle and connector portion110and a filtering needle cap200, which includes a seal plug300, and a filter400. The needle and connector portion110has a proximal end114which may be in the form of a hub118. The hub118may be adapted to work with a Luer fitting sometimes called a Luer Taper. Luer fittings include those known as Luer-Lock and Luer-Slip (sometimes slip tip). While various Luer fittings are very common connections for medical devices, the teachings of the present disclosure are not limited to any specific fitting as other connections could be used. Frequently, but not always, the connection between the hollow needle150and the hub118is augmented by an adhesive component. Such an adhesive component is conventional and not a point of focus for the present disclosure. Thus, details of this adhesive component are not provided. The adhesive component may be considered a part of the hub118for the purposes of this disclosure and the claims that follow. The hollow needle150is secured to the hub118of the needle and connector portion110. The hollow needle150has a distal tip154that is fluid communication with a needle lumen156. As discussed below, this application teaches sealing around a distal portion158of the hollow needle150. The distal portion158includes the distal tip154but also a nearby portion of the hollow needle150so that the distal tip154extends beyond the sealed portion of the distal portion158of the hollow needle150. The filtering needle cap200has a filter needle cap body250with a distal portion204which is open, and a proximal end208which is also open. The filtering needle cap200also has a seal plug300and a filter400which are inserted into the open distal portion204of the filter needle cap body250during assembly. FIG.2is a side and front perspective view of filtered needle assembly100which allows a view of the filter400within the distal end of the filtered needle assembly100. A distal portion of the hub118is designed to be secured within the open proximal end208of the filtering needle cap200. FIG.3is a cross section of filtered needle assembly100.FIG.3shows that the distal tip154of the hollow needle150may be inserted distally into the open proximal end208of the filtering needle cap200and advanced through the proximal chamber212. As the distal tip154moves distally, the cross section of the proximal chamber212diminishes via inwardly sloped walls216. Eventually, the distal tip154reaches an annular shoulder220that limits the proximal movement of the seal plug300. The annular shoulder220is the proximal end of the distal chamber230. FIG.4is a cross section of a side view of the seal plug300. Seal plug300has a distal end304that is originally closed but later punctured by the distal tip154of the hollow needle150. The seal plug300has a proximal face308with an opening312to a hollow interior316that is initially closed at the distal end306. Optionally, the diameter320of most of the hollow interior316is greater than the outer diameter of the hollow needle150so the distal tip154(FIG.3) of the hollow needle150can traverse most of the hollow interior316without resistance. The annular proximal face308has a series of hemispheric protrusions330which make contact with the annular shoulder220of the filtering needle cap200. These hemispheric protrusions330assist in ejecting the molded parts from the mold. The seal plug300has a first rib ring344and a second rib ring348. A careful observer will note that in this instance, the first rib ring344is not the same shape as the second rib ring348. Both rib rings (344and348) have a maximum outer diameter346that is larger than outer diameter336. The maximum outer diameter346of the rib rings (344and348) is larger than the inner diameter236of distal chamber230(FIG.3). Thus, when seal plug300is loaded into the distal chamber230before the addition of the filter400, a holding tool can be used to push the seal plug300proximally as the rib rings (344and348) compress to fit within inner diameter236of distal chamber230. This compression fit retains the seal plug300in proximity to the annular shoulder220at the proximal end of the distal chamber230. The holding power of this compression fit is not sufficient to resist force imposed by a distal tip154of a hollow needle150if the hollow needle150is advanced distally. The hollow needle150pushes the seal plug300distally away from the annular shoulder220at the proximal end of the distal chamber230. Use of a Holding Tool. While a wide range of holding tools could be used to move the seal plug300proximally within the distal chamber230, a holding tool with an open midline may be used to retain the seal plug300against the annular shoulder220at the proximal end of the distal chamber230as the distal tip154of the hollow needle150is pushed against the initially closed distal end306of the hollow interior316of the seal plug300. With an appropriate holding tool holding the seal plug300against the annular shoulder220at the proximal end of the distal chamber230, sufficient force can be applied to the hollow needle150to drive the distal tip154through the remainder of seal plug300and out the distal end304of the seal plug300so that a seal is formed around distal portion158(FIG.3) of the hollow needle150. After removing the holding tool and inserting the filter400, one has a filtered needle assembly100as shown inFIG.2andFIG.3. Additional Views of Seal Plug. FIG.5provides a front side perspective view of seal plug300. Visible in this view are distal end304, first rib ring344and second rib ring348. The circle visible at the distal end304is simply a flat portion of the domed distal end304. FIG.6provides a rear side perspective view of seal plug300. Visible in this view are proximal face308, opening312, a portion of hollow interior316, and the set of hemispheric protrusions330. Also visible in this view are first rib ring344and second rib ring348 Process for Use. FIG.7illustrates process1000for loading a syringe with a liquid payload through a filtered needle assembly100. Step1004—Add Filtered Needle Assembly to Syringe. The filtered needle assembly100such as shown inFIG.2is secured to the end of a syringe (not shown) or other fitting by engagement with the hub118at the proximal end114of the needle and connector portion110. Step1008—Optional—Remove Outer Cap. Often, the filter needle assembly100is shipped with an outer cap (not shown here). The outer cap is removed. Note this step is optional as in some instances the filter needle may be delivered in sterile packaging such as a blister pack without an outer cap. In many instances the filter needle assembly will be delivered with the needle and connector portion110factory inserted into the filtering needle cap200and with the outer cap covering a portion of the filtering needle cap200. In order to minimize the chances that the filtering needle cap200will be separated from the needle and connector portion110when intending to merely remove the outer cap, the components may be designed so that the force needed to remove the filtering needle cap200from the needle and connector portion110may be significantly more than the force needed to remove the outer cap from the filtering needle cap200. In this context, significantly more would include at least double. The difference in required force may be achieved by having different degrees of interference fits, or use of different materials or surface treatments. Other ways of increasing or decreasing the requisite removal force will be apparent to those of skill in the art. Step1012—Draw Payload into Syringe. The filter element400is immersed in an ampoule or suitable receptacle for a liquid payload such as a pharmaceutical or other liquid. As the syringe plunger is withdrawn in a known manner, the liquid payload is drawn up in order to fill the syringe through a pathway through:the filter element400;the distal chamber230; andthe interior of the hollow needle150that extends beyond the seal plug300into the distal chamber230. The suction force for drawing up the liquid payload is confined to the pathway by the seal plug300which substantially seals the distal chamber230. The seal plug300prevents the flow of air in a distal direction from entering the distal chamber230from along the outer perimeter of the hollow needle150such that the syringe may effectively draw in liquid payload. As the syringe is loaded, any debris in the receptacle initially holding the liquid payload is precluded by the filter element400from entry into the distal chamber230. Step1016—Remove Filtered Needle Assembly from Syringe. Once the syringe is loaded, the filtering needle cap200is removed from the needle and connector portion110by sliding the filtering needle cap200distally until the distal tip154of the hollow needle150is free of the filtering needle cap200. The filtering needle cap200may then be discarded along with any debris captured in the filter400. Step1020—Loaded Syringe is Ready for Use. The syringe is loaded with the desired amount of liquid payload which has been filtered as the liquid passed through filter400. The distal tip154of the hollow needle150is exposed and ready for use. Depending on the application, the distal tip154of the hollow needle150may be inserted as appropriate into a patient's body, to a port with a septum for use with IV therapy, or to some other location. Process for Precluding Second Use. FIG.8illustrates process2000for precluding loading second syringe with a previously used filtered needle assembly100. Step2004—Load a syringe with a liquid payload through a filtered needle assembly100including a filtering needle cap200as described in process1000but do not discard the filtering needle cap200after removing the hollow needle150from the filtering needle cap200. Step2008—Insert a distal tip of a hollow needle into the open proximal end of the filtering needle cap200. This distal tip of a hollow needle may be the same distal tip of the hollow needle used in process1000or may be a new distal tip of a new hollow needle attached to a new syringe. Step2012—Advance the distal tip of the hollow needle through the proximal chamber of the filtering needle cap and into the hollow interior316of the seal plug300. Step2016—Continue to advance the distal tip of the hollow needle distally. Step2020—Contact the distal tip154of the hollow needle150with the seal plug300. As the opening formed by forcing the first distal tip of the first hollow needle across the seal plug300while the seal plug300was precluded from distal movement by an appropriate holding tool has substantially closed after withdrawal of the hollow needle from the seal plug300, there is resistance even if the second distal tip154is perfectly aligned with the prior path taken by the first distal tip154. Step2024—Push the seal plug300distally within the distal chamber without traversing the seal plug300. As the force needed to penetrate and traverse the seal plug is greater than the friction force holding the seal plug300adjacent to the annular shoulder220by the compression fit of the rib rings (344and348) within the distal chamber230, the continued distal movement of the distal tip154of the hollow needle150pushes the seal plug300distally within the distal chamber without traversing the seal plug300. SeeFIG.9which shows an enlarged partial cross section of the filter needle assembly100after a distal tip154of a hollow needle150has pushed against the seal plug300while not held by a holding tool. The seal plug300has slid distally within distal chamber230. Step2028—Fail to easily draw in liquid payload through filter400as the distal tip154of the needle150has not traversed the seal plug300. It is possible that some liquid payload may eventually be drawn through the prior needle path in the seal plug300but it is likely that air from the proximal end of the filter needle assembly100would travel down to the distal tip154of the hollow needle150as the distal tip is on the proximal side of the seal and nothing would block air from entering the distal tip and satisfying the suction pull from the syringe body. This would not be a satisfactory process and the staff member would not try this a second time. Thus the design precludes making a habit of loading second syringe with a previously used filtered needle assembly100as the hollow needle displaces rather than traverses the seal plug and does not work well to obtain liquid payload. The process set forth above precludes insertion of a second hollow needle connected to a second syringe to draw up a second payload liquid. In this context, the filtering needle cap200cannot recognize that the inserted hollow needle150is the same hollow needle150that was recently withdrawn from the filtering needle cap200. Once the hollow needle150is removed from the filtering needle cap200, the hollow needle becomes a stranger and thus a second hollow needle connected to a second syringe seeking to obtain a second liquid payload. The process would work the same when a different hollow needle was inserted. That hollow needle would also be treated as a prohibited second hollow needle. Process for Assembling a Filtered Needle Assembly. FIG.10sets forth the key steps in the process3000to assemble a filtered needle assembly100. Step3004—Obtain: the needle and connector portion110, a filtering needle cap body25, a seal plug300, and a filter400. Step3008—Push the seal plug300into the open distal end of the filtering needle cap body250and continue moving the seal plug300until the seal plug rests against the annular shoulder220at the end of the proximal chamber212. Step3012—Hold the seal plug while the distal tip traverses the seal plug. More specifically, hold the seal plug300against the annular shoulder with a holding tool that has an open midline while advancing the distal tip154of the hollow needle150all the way into the hollow interior316of the seal plug300and then push the distal tip154through the remaining portion of the seal plug300while the seal plug300is precluded from distal movement by the holding tool so that the distal tip154extends beyond the distal end304of the seal plug300and into the empty midline of the holding tool. Step3016—Remove the holding tool from the distal portion204of the filtering needle cap after the distal end of the hollow needle extends beyond the distal end of the seal plug. Step3020—Insert the filter400into the distal end of the filtering needle cap body250. The filter may be held in position by various methods known to those of skill in the art including adhesives, compression fit, and others. Step3024—Creating a sealed and sterilized package with the filtered needle assembly100inside the package. Details Choice of Filter Element. One design criterion for choice of a filter element on the distal end of the filtering needle cap versus a filter element contained internal in the filtering needle cap is whether collection of abnormal components within the liquid payload is relevant to the application. While all filter elements may be used to remove shards of glass, in some instances it may be useful to use a filter element on the distal end of the filtering needle cap as this distal surface will concentrate certain types of abnormal components. For example, some pharmaceuticals may partially crystalize from age or handling. While a small amount of crystallization may be tolerated, an unusual amount of crystallization may indicate that the pharmaceutical should be discarded rather than used. Likewise, some pharmaceuticals may have a small amount of sediment in the reservoir of the pharmaceutical such as an ampoule, but if a large amount of sediment appears on the outer surface of the filter element, the excessive sediment may indicate that the pharmaceutical is too old or has been compromised by handling. The filter elements may be sintered filters which have a number of tortuous internal channels for liquid payload to traverse while capturing debris. Extending the thickness of the filter increases the distance that the liquid payload must travel but it also increases the number of possible paths for the liquid payload to travel. Thus, for some range of thicknesses, increasing the thickness decreases the overall resistance to flow. One well-known vendor in the field of sintered filter material is the Porex Corporation located in Fairburn Georgia and at www.Porex.com (spaces inserted to avoid a live link). Material for Plug. The choice of the material for use in the plug will be a design choice and may be influenced by the type of needle being used and the geometry of the plug and other components. The material will need to be compatible with the liquids to be filtered, planned sterilization process, and desired shelf life. One suitable material is 50 durometer Chlorobutyl which is available from a number of vendors. Retention of the Filter Element. In some of the examples set forth above, the filter element was retained by protrusions or detents that extended into the filter element to secure the filter element. Adhesives may be used to secure the filter element. Many designers may prefer a protrusion or other form of interference fit as the use of adhesives might cause adhesives to enter possible flow paths for liquid payload and thus partially impair the filter element. Those of skill in the art will recognize that other attachment methods may be used such at an ultrasonic bond, spin welding, heat welding, and press fit. Likewise, other suggested connections between components have been provided to provide a suitable example and those of skill in the art will recognize the many options for connecting two components together. The teachings of this present disclosure are not limited to any particular connection method for joining components unless specifically recited in the claims that follow. Needle Types. The various figures discussed in connection with this disclosure have uniformly shown sharp distal ends for the needles. These needles have beveled tips. Sharp ended hypodermic needles are particularly adapted for injecting fluids directly into the body of the patient. In many instances, the liquid payload is not delivered directly into the patient but is instead delivered to a bag of fluids used in intravenous therapy (IV therapy). A drip of liquid is provided into a vein of the patient to slowly provide a desired treatment. The IV fluids are typically in a bag. Ports with a self-sealing septum may be used to add pharmaceuticals to the liquid being provided in IV therapy. While a sharp tipped needle may be used to deliver a liquid payload through a septum, some prefer using a blunt tip needle. A blunt tip needle reduces the risk of a needle stick to the medical personnel and may be less damaging to the septum. While the variation of needle tips and the best uses for each type of needle tip are beyond the scope of the present disclosure, nothing in this present disclosure limits the teachings to applications with sharp point needles. Blunt tip needles will have openings on their distal portions and one of skill in the art can adapt the geometries of the filtering needle cap if needed to accommodate the geometry of various types of blunt tip needles. Connection to the Hub. The examples in this disclosure referenced a distal end of a syringe engaging with the hub118. This may be the most common interaction with the filter needle, but the teachings of this disclosure could be employed where there is a combination of components rather than a syringe. For some specific reasons, there may be a series of components including check valves, tubing, a syringe, or even a replacement for a syringe that may controllably intake and discharge liquid payload through the needle. The present disclosure may be used as long as there is an appropriate connection between the filtered needle and the remaining components via the distal fluid fitting of the remaining components. Sterilization Choices. Those of skill in the art will recognize that the filtering needle cap with or without an outer cap may be sterilized prior to provision to the medical facility. Those of skill in the art will recognize that there are many different processes such as electron beam processing, gamma ray sterilization, or ethylene oxide gas. Those of skill in the art will recognize that medical devices may be adapted for use with a particular sterilization process to maximize effectiveness and throughput. The teachings of the present disclosure may be adapted for use with a variety of sterilization techniques and thus this aspect of the examples was not highlighted or discussed. Optional Use of Outer Cap. As noted above, some applications may not use the outer cap but package the needle and connector portion along with the filtering needle cap in packaging such as a blister pack. The packaging would maintain the sterility of the items and would preclude even sterilized debris from becoming entrained in the filtering needle cap. Outer caps are well known to those of skill in the art. FIG. 1 of U.S. Pat. No. 9,669,164 shows an outer cap as element12.FIG.1is incorporated by reference. Alternatives and Variations. Locations of the filter400. While the figures used in the present disclosure show a filter400wholly within the distal end of the filtering needle cap200, this is not required in order to enjoy the benefits of the seal plug300. U.S. Pat. No. 9,669,164 to Carr et al. for Filtering Needle Cap Having a Sleeve Sealing Around a Needle shows a range of suitable locations for the filter. The '164 patent is incorporated by reference in its entirety. Number of Rib Rings. The example set forth above had a seal plug300with two rib rings344and348. One of skill in the art will appreciate that the number of rib rings could be one, two, or more than two. What is needed is an ability to push the seal plug300into a slightly smaller diameter as the seal plug300deforms to fit and this compression fit increases the amount of force necessary to move the seal plug300but does not raise the required level sufficiently to allow a distal tip154of a hollow needle150to be driven through a seal plug300without the use of a holding tool. Holding Tool. FIG.11provides a perspective view of holding tool500, the filter needle cap body250and the seal plug300. The holding tool504has a distal end508and a proximal end504which is inserted into the open distal portion204of the filter needle cap body250and then used to push and hold the seal plug300against the annular shoulder220(FIG.3). While the seal plug300is held against the annular shoulder220, the distal tip154of the hollow needle150(FIG.3) may be forced to penetrate and transit the distal end304(FIG.4) of the seal plug300. The proximal end504of the holding tool500needs a concavity of sufficient depth to receive the distal end of the hollow needle150that extends beyond the distal end304of the seal plug300. One way to form this concavity is to have a holding tool500that is a hollow cylinder with an open midline from the proximal end504to the distal end508. But this is not required. The opening at the proximal end504may end somewhere within the holding tool500. The proximal end504of the holding tool may be a set of two or more fingers that hold the seal plug300against the annular shoulder220and provide adequate room for the distal end of the hollow needle150. Those of skill in the art can work with the present disclosure to come up with a variety of holding tools in keeping with the purpose of the tool. One of skill in the art will recognize that some of the alternative implementations set forth above are not universally mutually exclusive and that in some cases additional implementations can be created that employ aspects of two or more of the variations described above. Likewise, the present disclosure is not limited to the specific examples or particular embodiments provided to promote understanding of the various teachings of the present disclosure. Moreover, the scope of the claims which follow covers the range of variations, modifications, and substitutes for the components described herein as would be known to those of skill in the art. Where methods and/or events described above indicate certain events and/or procedures occurring in a certain order, the ordering of certain events and/or procedures may be modified. Additionally, certain events and/or procedures may be performed concurrently in a parallel process, when possible, as well as performed sequentially as described above. The legal limitations of the scope of the claimed invention are set forth in the claims that follow and extend to cover their legal equivalents. Those unfamiliar with the legal tests for equivalency should consult a person registered to practice before the patent authority which granted this patent such as the United States Patent and Trademark Office or its counterpart. | 25,863 |
11857769 | Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set out herein illustrate exemplary aspects of the disclosure, and such exemplifications are not to be construed as limiting the scope of the disclosure in any manner. DETAILED DESCRIPTION The following description is provided to enable those skilled in the art to make and use the described embodiments contemplated for carrying out the invention. Various modifications, equivalents, variations, and alternatives, however, will remain readily apparent to those skilled in the art. Any and all such modifications, variations, equivalents, and alternatives are intended to fall within the spirit and scope of the present invention. For purposes of the description hereinafter, the terms “upper”, “lower”, “right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, “lateral”, “longitudinal”, and derivatives thereof shall relate to the invention as it is oriented in the drawing figures. However, it is to be understood that the invention may assume various alternative variations, except where expressly specified to the contrary. It is also to be understood that the specific devices illustrated in the attached drawings, and described in the following specification, are simply exemplary embodiments of the invention. Hence, specific dimensions and other physical characteristics related to the embodiments disclosed herein are not to be considered as limiting. Referring toFIGS.1-16, a drug delivery system10according to one aspect of the present invention includes a drive assembly12, a container14, a valve assembly16, and a needle actuator assembly18. The drive assembly12, the container14, the valve assembly16, and the needle actuator assembly18are at least partially positioned within a housing20. The housing20includes a top portion22and a bottom portion24, although other suitable arrangements for the housing20may be utilized. In one aspect, the drug delivery system10is an injector device configured to be worn or secured to a user and to deliver a predetermined dose of a medicament provided within the container14via injection into the user. The system10may be utilized to deliver a “bolus injection” where a medicament is delivered within a set time period. The medicament may be delivered over a time period of up to 45 minutes, although other suitable injection amounts and durations may be utilized. A bolus administration or delivery can be carried out with rate controlling or have no specific rate controlling. The system10may deliver the medicament at a fixed pressure to the user with the rate being variable. The general operation of the system10is described below in reference toFIGS.1-16with the specifics of the drive assembly12, needle actuator assembly18, and other features of the system10, discussed below in connection withFIGS.17-93. Referring again toFIGS.1-16, the system10is configured to operate through the engagement of an actuation button26by a user, which results in a needle28of the needle assembly18piercing the skin of a user, the actuation of the drive assembly12to place the needle28in fluid communication with the container14and to expel fluid or medicament from the container14, and the withdrawal of the needle28after injection of the medicament is complete. The general operation of a drug delivery system is shown and described in International Publication Nos. 2013/155153 and 2014/179774, which are hereby incorporated by reference in their entirety. The housing20of the system10includes an indicator window30for viewing an indicator arrangement32configured to provide an indication to a user on the status of the system10and a container window31for viewing the container14. The indicator window30may be a magnifying lens for providing a clear view of the indicator arrangement32. The indicator arrangement32moves along with the needle actuator assembly18during use of the system10to indicate a pre-use status, use status, and post-use status of the system10. The indicator arrangement32provides visual indicia regarding the status, although other suitable indicia, such an auditory or tactile, may be provided as an alternative or additional indicia. Referring toFIGS.4-6, during a pre-use position of the system10, the container14is spaced from the drive assembly12and the valve assembly16and the needle28is in a retracted position. During the initial actuation of the system10, as shown inFIGS.7-9, the drive assembly12engages the container14to move the container14toward the valve assembly16, which is configured to pierce a closure36of the container14and place the medicament within the container14in fluid communication with the needle28via a tube (not shown) or other suitable arrangement. The drive assembly12is configured to engage a stopper34of the container14, which will initially move the entire container14into engagement with the valve assembly16due to the incompressibility of the fluid or medicament within the container14. The initial actuation of the system10is caused by engagement of the actuation button26by a user, which releases the needle actuator assembly18and the drive assembly12as discussed below in more detail. During the initial actuation, the needle28is still in the retracted position and about to move to the extended position to inject the user of the system10. During the use position of the system10, as shown inFIGS.10-12, the needle28is in the extended position at least partially outside of the housing20with the drive assembly12moving the stopper34within the container14to deliver the medicament from the container14, through the needle28, and to the user. In the use position, the valve assembly16has already pierced a closure36of the container14to place the container14in fluid communication with the needle28, which also allows the drive assembly12to move the stopper34relative to the container14since fluid is able to be dispensed from the container14. At the post-use position of the system10, shown inFIGS.13-15, the needle28is in the retracted position and engaged with a pad38to seal the needle28and prevent any residual flow of fluid or medicament from the container14. The container14and valve assembly16may be the container14and valve assembly16shown and described in International Publication No. WO 2015/081337, which is hereby incorporated by reference in its entirety. Referring toFIGS.15A-15C, the pad38is biased into the pad as the needle actuator body96moves from the use position to the post-use position. In particular, the pad38is received by a pad arm122having a cam surface124that cooperates with a cam track126on the bottom portion24of the housing20. The pad arm122is connected to the needle actuator body96via a torsion bar128. The cam surface124is configured to engage the cam track126to deflect the pad arm122downwards thereby allowing the pad38to pass beneath the needle28before being biased upwards into the needle28. The torsion bar128allows the pad arm122to twist about a pivot of the needle actuator body96. The pad38may be press-fit into an opening of the pad arm122, although other suitable arrangements for securing the pad38may be utilized. Referring toFIGS.1-33, the drive assembly12according to one aspect of the present invention is shown. As discussed above, the drive assembly12is configured to move the container14to pierce the closure36of the container14and also to move the stopper34within the container14to dispense fluid or medicament from the container14. The drive assembly12shown inFIGS.17-33is configured to engage and cooperate with a spacer assembly40received by the stopper34of the container14. The spacer assembly40includes a spacer42and a spacer holder44. The spacer holder44is received by the stopper34and the spacer42is received by the spacer holder44. The spacer holder44includes a first threaded portion46that engages a corresponding threaded portion of the stopper34, although other suitable arrangements may be utilized. The spacer42also includes a threaded portion48that engages a corresponding second threaded portion50of the spacer holder44for securing the spacer42to the spacer holder44, although other suitable arrangements may be utilized. The drive assembly12is configured to dispense a range of predetermined fill volumes of the container14while maintaining the functional features of the system10described above, including, but not limited to, retraction of the needle28after the end of the dose and providing an indication of the status of the system10while also minimizing abrupt engagement of the stopper34by the drive assembly12. The drive assembly12is configured to dispense a plurality of discrete fill volume ranges by utilizing a plurality of sizes of the spacers42. In one aspect, twelve fill volume ranges and twelve spacer42sizes are provided. In one aspect, the length of the spacer42is changed to accommodate different fill volumes in the container14. Alternatively, a single size spacer42may be utilized with a plurality of fill volumes in the container14accommodated by utilizing a plurality of shims that are received by the spacer42. Referring toFIGS.17-26, the drive assembly12includes a first plunger member52, a second plunger member54received by the first plunger member52, a first biasing member56, a second biasing member58, a plunger actuation member60, and an index member62. The first plunger member52is moveable from a pre-use position (shown inFIG.18), to a use position (shown inFIG.19), to a post-use position (shown inFIG.20) with the first plunger member52configured to engage the spacer assembly40and move the stopper34within the container14to dispense medicament from the container14. The first plunger member52is configured to move axially. The second plunger member54and the first plunger member52form a telescoping arrangement with the second plunger54configured to move axially after the first plunger member52moves a predetermined axial distance. The movement of the first and second plunger members52,54is provided by the first and second biasing members56,58, which are compression springs, although other suitable arrangements for the biasing members56,58may be utilized. The first biasing member56is received by the second plunger member54and is constrained between the plunger actuation member60(and index member62) and a first spring seat64of the second plunger member54. The second biasing member58is positioned radially inward from the first biasing member56and received by the second plunger member54. The second biasing member58is constrained between a second spring seat66of the second plunger member54and the first plunger member52. The second biasing member58is configured to bias the first plunger52member towards the container14from the pre-use position, to the use position, and to the post-use position. The first biasing member56is configured to bias the second plunger member54towards the container14, which, in turn, biases the first plunger member52towards the container14from the pre-use position, to the use position, and to the post-use position. More specifically, the second biasing member58is configured to drive the first plunger member52against the spacer assembly40or stopper34to move the container14into engagement the valve assembly16thereby piercing the closure36of the container14and placing the container14in fluid communication with the needle28. The first biasing member56is configured to move the stopper34within the container14to dispense the medicament within the container14. The second biasing member58has a different spring constant than the first biasing member56. In particular, the second biasing58member is stiffer than the first biasing member56to provide a high force for piercing the closure36of the container14while the first biasing member56provides a lower force for dispensing as appropriate for the viscosity of the fluid or medicament within the container14. Referring again toFIGS.17-26, the plunger actuation member60has an annular portion68and a spindle portion70. The plunger actuation member60is rotationally moveable relative to the first plunger member52between a first rotational position and a second rotational position spaced from the first rotational position. The first rotational position may be 15 degrees from the second rotational position, although other suitable positions may be utilized. The annular portion68includes a drive surface72including a plurality of gears74, although other suitable arrangements may be utilized for the drive surface72. The spindle portion70includes an actuator locking surface76configured for engagement and release from a plunger locking surface78of the first plunger member52. The plunger locking surface78includes a plurality of projections80configured to be received by a plurality of slots or cutouts81defined by the actuator locking surface76. As shown inFIGS.18and23, in the first rotational position of the plunger actuation member60, the plurality of projections80and the plurality of slots or cutouts81are out of alignment such that the plunger actuation member80is engaged with the first plunger member52to prevent movement of the first and second plunger members52,54with the first and second biasing members56,58biasing the first and second plunger members52,54away from the plunger actuation member60. As shown inFIGS.19and24, in the second rotational position of the plunger actuation member60, the plurality of projections80and the plurality of slots or cutouts81are aligned with each other such that the plunger actuation member60is disengaged with the first plunger member52to allow movement of the first and second plunger members52,54thereby starting the dispensing process from the container14. Referring toFIGS.7and33, the drive surface72of the plunger actuation member60is configured to be engaged by a portion of the needle actuator assembly18. After engagement of the actuator button26and release of the needle actuator assembly18, which is discussed in more detail below, the needle actuator assembly18moves within the housing20from the pre-use position, to the use position, and to the post-use position. During the initial movement of the needle actuator assembly18, a portion of the needle actuator assembly18engages the drive surface72of the plunger actuation member60to move the plunger actuation member60from the first rotational position to the second rotational position. As shown inFIG.33, an angled blade portion82of the needle actuator assembly18engages the drive surface72of the plunger actuation member60to cause rotation of the plunger actuation member60. Referring toFIGS.11,13, and26, the second plunger member52includes a plurality of coded projections84with a preselected one of the plurality of coded projections84configured to engage a restriction member86of the system10. As discussed in more detail below, the restriction member86cooperates with the needle actuation assembly18and restricts movement of the needle actuator assembly18from the use position to the post-use position until a predetermined end-of-dose position of the stopper34is reached. In one aspect, the restriction member86is configured to restrict axial movement of the needle actuation assembly18from the use position through engagement between the restriction member86and a portion of the needle actuation assembly18. Such engagement between the restriction member86and the needle actuation assembly18is released by rotation of the restriction member86when the stopper34reaches the end-of-dose position. During the use position of the needle actuator assembly18, the restriction member86is biased in a rotational direction with the rotation of the restriction member86being prevented through engagement between the restriction member86and one of the plurality of coded projections84of the second plunger member54. The plurality of coded projections84may be axial ribs of varying length, although other suitable arrangements may be utilized. Each coded projection84defines a point at which the restriction member86is able to rotate thereby releasing the needle actuator assembly18. The smooth portion of the second plunger member52may also provide a further “code” for determining when the system10transitions to the end-of-dose position. As discussed above, the indicator arrangement32moves with different portions of the indicator arrangement32visible through the indicator window30as the system10moves from the pre-use, use, and post-use or end-of-dose positions. More specifically, the indicator arrangement32engages a portion of the restriction member86and moves along with the restriction member86through the various stages of the system10to provide an indication to the user regarding the state of the system10. During assembly of the system10, the dosage of the container14is matched with a specific spacer42having a set length and a corresponding one of the plurality of coded projections84is aligned with the restriction member86. Accordingly, as discussed above, the container14may be provided with a plurality of dosage volumes with each volume corresponding to a specific spacer42and coded projection84. Thus, even for different dosage volumes, the system10is configured to inject the needle28into the user to deliver a dose of medicament from the container14, retract the needle28after the end of the dose, and provide an indication of the status of the system10while minimizing abrupt engagement of the stopper34by the drive assembly12. In particular, the size of the stopper34may be selected to minimize the distance between the first plunger member52and the spacer assembly40and does not require the use of damping. Referring toFIGS.27-33, a drive assembly12A according to a further aspect of the present invention is shown. The drive assembly12A shown inFIGS.27-33is similar to and operates in the same manner as the drive assembly12shown inFIGS.17-26and described above. In the drive assembly ofFIGS.27-33, however, the first plunger member52is received by the second plunger member54and extends from the second plunger member54during axial movement from the pre-use position to the use position. Further, the first plunger member52includes an extension portion88configured to engage the second plunger member54after the first plunger member52moves predetermined axial distance such that the first and second plunger members52,54move together. The first and second biasing members56,58engage and act on the first and second plunger members52,54in the same manner as the drive assembly12ofFIGS.17-26. Referring toFIGS.27-32, the index member62is positioned about the first and second plunger members52,54and includes a plurality of ratchet teeth90configured to engage a flexible tab92positioned on the bottom portion24of the housing20. When the drive assembly12,12A is installed into the bottom portion24of the housing20, the engagement of the ratchet teeth90of the index member62with the flexible tab92of the housing20provide a one-way rotation of the index member62. The index member62is configured to rotate to align one of the coded projections84of the second plunger member52with the restriction member86based on the dosage volume and spacer42size as discussed above. The index member62may provide the drive assembly12,12A with24rotational positions of which 12 may have unique dose values associated with them. Referring toFIGS.1-16and34-40B, the needle actuator assembly18according to one aspect of the present invention is shown. The needle actuator assembly18includes a needle actuator body96having guide surfaces98, a needle shuttle102having cam surfaces104, and the needle28received by the needle shuttle102and configured to be in fluid communication with the container14as discussed above. The needle actuator body96is generally rectangular with the guide surfaces98protruding radially inward. The needle shuttle102is received within the needle actuator body96. As described above, the needle actuator body96is moveable within the housing20from a pre-use position (shown inFIGS.4-6), an initial actuation position (FIGS.7-9), a use position (FIGS.10-12), and a post-use position (FIGS.13-15). The needle actuator body96is biased from the pre-use position to the post-use position via an extension spring106, although other suitable biasing arrangements may be utilized. The needle actuator body96is released and free to move from the pre-use position to the use position upon engagement of the actuator button26, which is discussed in more detail below. The needle actuator body96moves from the use position to the post-use position after rotation of the restriction member86as discussed above in connection withFIGS.17-33. Referring toFIGS.34-40B, the needle shuttle102is moveable along a vertical axis between a retracted position where the needle28is positioned within the housing20and an extended position where at least a portion of the needle28extends out of the housing20. The needle shuttle102is configured to move between the retracted position and the extended position through engagement between the guide surfaces98of the needle actuator96and the cam surfaces104of the needle shuttle102. The cam surfaces104are provided by first and second cam members108,110, with the first cam member108spaced from the second cam member110. The housing20includes a guide post112having recess configured to receive a T-shaped projection114on the needle shuttle102, although other shapes and configurations may be utilized for the guide post112and T-shaped projection114. The needle shuttle102moves along the guide post112between the retracted and extended positions. The guide post112is linear and extends about perpendicular from the housing20, although other suitable arrangements may be utilized. The guide surfaces98of the needle actuator body86are non-linear and each include a first side116and a second side118positioned opposite from the first side116. As discussed below, the guide surfaces98of the needle actuator body96cooperate with the cam members108,110of the needle shuttle102to move the needle shuttle102vertically between the retracted and extended positions as the needle actuator body96moves axially from the pre-use position to the post-use position. The needle shuttle102also includes a shuttle biasing member120configured to engage the housing20or the actuator button26. In particular, the shuttle biasing member120engages the housing20or actuator button26and provides a biasing force when the needle actuator body96is transitioning from the use position to the post-use position. When the needle actuator body96is fully transitioned to the post-use position, the cam members108,110of the needle shuttle102are disengaged from the guide surfaces98of the needle actuator body96and the shuttle biasing member120biases the needle shuttle102downward such that the needle28engages the pad38, as discussed above. As discussed above in connection withFIGS.1-16, however, the pad38may also be biased into the needle28rather than biasing the needle shuttle102downwards via the shuttle biasing member120. The needle actuator body96may interact with the actuator button26to prevent the actuator button26from popping back up until the post-use position is reached, which is discussed below in more detail. Referring toFIGS.37A-40B, in a pre-use position (FIG.37A), the needle shuttle102is in the retracted position with the cam members108,110spaced from the guide surface98of the needle actuator body96. As the needle actuator body96moves to the use position (FIGS.37B and38A), the second cam member110of the needle shuttle102engages the second side118of the guide surfaces98to move the needle shuttle102from the retracted position to the extended position. During the transition from the use position to the post-use position of the needle actuator body96(FIG.37C), the first cam member108of the needle shuttle102is engaged with the first side116of the guide surfaces98to move the needle shuttle102from the second position to the first position. After the needle actuator body96is fully transitioned to the post-use position (FIGS.37D and38B), the shuttle biasing member120biases the needle shuttle102downward as the cam members108,110disengage from the guide surfaces98of the needle actuator body96with the needle28engaging the pad38. The transition of the needle actuator body96and the corresponding position of the needle shuttle102is also shown inFIGS.39-40B. The interaction between the actuator button26and the needle actuator body96is discussed in detail in connection withFIGS.65A-67. Referring toFIGS.41-64, a drug delivery system200according to a further embodiment is shown. The system200includes a housing202having an upper housing204and a lower housing206. The housing has a proximal end205and a distal end207. The upper housing204has a status view port208so that a user can view the operating status of the system200. The system200also includes a valve assembly212, a tube214fluidly connecting the valve assembly214with a patient needle215that is disposed in a proximal end of a needle arm216. A spring218biases a needle actuator220distally. As shown inFIGS.42-46, the system200additionally includes a container or medicament container222with a stopper224movably disposed therein, although the stopper224is omitted from various figures to aid clarity. Preferably, the distal end of the medicament container222has a septum assembly228that is spaced apart from the valve assembly212prior to actuation of the device222, as best shown inFIG.47. For manufacturing purposes, using one size for a medicament container is often desirable, even if multiple fill volumes or dosages are contemplated for use with the container. In such cases, when medicament containers are filled, the differing fill volumes result in different positions of the stopper. To accommodate such different stopper positions, as well as accommodate manufacturing differences of the stoppers, aspects of the present invention include a bespoke or custom spacer226disposed in a proximal end of the container222, proximal to the stopper224. In other words, the bespoke spacer226provides an option that allows dispensing of a range of manufacturer-set pre-defined fill volumes by selection of different spacers226, and reduces or eliminates the need for assembly configuration operations. The size of the spacer226can be employed to account for under-filled volumes of the container222, and provide a consistent bearing surface at the proximal end of the container. The spacer226is selected from a plurality of different size spacers226to occupy space from a proximal end of the stopper224to a proximal end of the container222. According to one embodiment, as shown inFIGS.45-47, the spacer226is selected to be substantially flush with the proximal end of the container222. Additionally, according to one embodiment, the spacer226has a “top hat” shape, which includes a central column230and a distal flange232, as best shown inFIG.45. Returning toFIGS.44-47, the system200also includes a drive assembly234for displacing the container222distally to establish the fluid connection between the container222and the patient needle215, as well as dispensing the medicament from the container222. In more detail, the drive assembly234includes an inner spring236disposed within a central plunger238, an outer plunger240, an outer spring242disposed between the central plunger238and the outer plunger240, a telescoping member244, and a release gate246. Preferably, the inner spring236has a greater spring constant than the outer spring242, and is therefore, stronger or stiffer than the outer spring242. The inner spring236is disposed inside the central plunger238, and pushes between a spring flange248in the lower housing (best shown inFIG.46) and the central plunger238, which bears directly on the proximal end of the spacer226subsequent to device activation. The outer spring242is disposed inside outer plunger240, and pushes between a proximal external flange250of the central plunger238and a distal internal flange252of the outer plunger240. Thus, the inner and outer springs236and242are nested, and can provide a more compact drive assembly (and thus, a more compact system200) than employing a single spring. According to one aspect, the inner spring236acts only to displace the container222to establish the fluid connection with the patient needle215, and the outer spring242acts only to subsequently dispense the medicament from the container222. According to another aspect, the inner spring236acts to displace the container222to establish the fluid connection with the patient needle215, and also acts to begin dispensing the medicament from the container222, and the outer spring242acts to complete dispensing the medicament. In a further aspect, the inner spring236causes the initial piercing of the container222with the outer spring242completing the piercing and dispensing of the medicament from the container222. As shown inFIGS.44-47, and as subsequently described in greater detail, the outer plunger240includes a pair of proximal flanges or feet254that each have a slanted surface that interacts with a corresponding slanted surface (or surfaces) on the release gate to retain and subsequently release the power module subsequent to actuation of the device200. As best shown inFIGS.46and47, as initially assembled, the container222is disposed in clearance from the drive assembly234and the valve assembly212. A lateral flange256on the needle actuator220axially retains the medicament container222, and the needle actuator220prevents the release gate246from displacing laterally. According to one embodiment, a spring (not shown) biases the needle actuator220distally, but the actuation button210(and/or its associated assembly) prevents distal displacement of the needle actuator220prior to actuation of the device200. A status bar258is disposed on the needle actuator220, and has a top surface that is visible through the status view port208. According to one embodiment, the top surface of the status bar has a plurality of colors or patterns, and when the device is in a pre-actuated state, a first color or pattern, such as yellow, is visible through the status view port208. FIGS.48-52are top views of the system200illustrating the operation of events at and subsequent to actuation of the system200. InFIG.47, a user slides the actuation button210proximally and then displaces the button210vertically into the housing202, thereby freeing the needle actuator220to displace distally under the influence of the spring (omitted for clarity). As shown inFIG.49, as the needle actuator displaces distally, tracks260on the needle actuator220interact with lateral bosses262on the needle arm216to insert the patient needle215. Preferably at this stage, the proximal end of the needle actuator220has not yet cleared the release gate246, and thus, the drive assembly234has not yet been released. But the lateral flange256has displaced distally and therefore, the container222is unrestrained. Subsequently, as shown inFIGS.50and51, with continued distal displacement, the proximal end of the needle actuator220clears the release gate246(thereby releasing the drive assembly234). The needle actuator220comes to temporarily rest against a feature on a rotatable release flipper264, driving the release flipper264against an outrigger266(best shown inFIGS.44and59) of the telescoping member244. The needle actuator220remains in this position until the medicament has been dispensed. In this position, preferably, a second color or pattern of the status bar258, such as green, is visible through the status view port208. At this stage, the force of the springs236and242and the interaction of the angled surfaces of the proximal flanges or feet254with the corresponding angled surface (or surfaces) on the release gate246causes the release gate246to displace laterally, thereby freeing the outer plunger240from restraining interaction with the release gate246. Up to this point, the outer plunger240has been restraining the central plunger238. Referring toFIGS.52and53(the inner spring236is omitted fromFIG.52for clarity), the stiff inner spring236distally drives central plunger238to contact the spacer226. Because the medicament container222is filled with a substantially incompressible fluid, the continued distal displacement of the central plunger238distally displaces the spacer226, the stopper224, and the container222relative to the housing202. This distal displacement causes the septum assembly228to be pierced by the valve assembly212, establishing fluid communication between the container222and the patient needle215. The central plunger238travels distally until its proximal external flange250(best shown inFIG.59) contacts a flange on the lower housing206, thereby limiting the “piercing travel.” Preferably, another flange on the lower housing206and/or the lateral flange256of the needle actuator220limits distal travel of the container222. Subsequently, because the inner spring236can no longer distally displace the central plunger238, the lighter outer spring242distally displaces the outer plunger240relative to the central plunger238to contact the distal flange232of the spacer226, as shown inFIGS.54and55. As subsequently described in greater detail, preferably, the contact between the outer plunger240and the spacer226is damped to minimize the impact force. Further expansion of the outer spring242distally displaces the outer plunger240to dispense the medicament. As shown inFIGS.56and57, as the outer spring242continues to expand and distally displace the outer plunger240, upon a predetermined distal displacement of the outer plunger240relative to the telescoping member244, an external feature or flange268of the outer plunger240interacts with an internal distal feature or flange270of the telescoping member244to “pick up” the telescoping member244. This ensures that further distal displacement of the outer plunger240causes corresponding distal displacement of the telescoping member244. This paired distal displacement continues until the end of the medicament dispensing. As previously noted, the outrigger266is disposed on the telescoping member244. The axial length of the outrigger and the distal travel of the telescoping member144controls the timing of the disengagement of the outrigger266with the release flipper264. As shown inFIGS.58and59, at the end of medicament dispensing, the proximal end of the outrigger266bypasses the release flipper264. This allows the release flipper264to rotate out of engagement with the needle actuator220(FIG.60), and allows the needle actuator220to continue its distal displacement and withdraw the patient needle215(FIG.61). At this stage, another color or pattern of the status bar258, such as red, is visible through the status view port208, signifying that the device200has completed operation. As previously noted, the contact between the outer plunger240and the spacer226, as illustrated inFIGS.62and63, is preferably damped to minimize the impact force. The highest level of energy dissipation is desirable for under-filled syringes containing viscous fluid, as the outer spring242will be stiffer to provide desired dispense rates. The lowest level of energy dissipation is desirable for maximum-filled syringes containing low-viscosity fluid, as the outer spring can be less stiff to provide desired dispense rates. Various methods can be employed to adjust damping levels, such as air damping, or closed-cell foam damping. As another method of damping the impact force,FIG.64illustrates an embodiment of a spacer226in which one or more axial interface ribs272are circumferentially arrayed about the central column230of the spacer226. In this embodiment, the outer plunger240must drive past the interference ribs272, which provide frictional resistance to the distal displacement of the outer plunger240relative to the spacer226. The frictional force created by the interference between interference ribs272and the outer plunger240is independent of plunger speed. Preferably, the frictional force does not exceed the minimum dispense spring load, to avoid stalling weaker springs. The interference can be tuned to give the desired level of frictional resistance. For different fluid viscosities, there can be different sizing (axial and/or radial) of the interference ribs272. This could mean a bespoke or custom spacer for each viscosity and fill-level combination, or, depending on the number of springs required for a viscosity range, there can be a number of tined positions, whereby the spacer can be set to a particular position for a particular modular spring (the position have had the interference/damping tuned for that particular spring load/viscosity scenario). Referring toFIGS.65A-69, an actuator button arrangement280for actuating the system10according to one aspect of the present invention is shown. The actuator button arrangement280includes the actuator button26, a button spring284, and a needle actuator body286. The needle actuator body286may be similar to the needle actuator bodies96,220discussed above and configured to move within the housing20to transition the needle shuttle102or needle28between retracted and extended positions. As shown inFIG.69, the actuator button26includes a user interface portion288for interacting with a user. Preferably, the user interface portion288is about 22 mm long and about 10 mm wide, although other suitable dimensions may be utilized. The actuator button26includes two pairs of lockout arms290,292that interact with button contacting surfaces294,296on the needle actuator body286prior to device actuation to prevent the needle actuator body286from rocking upward. As shown inFIG.65H, an overlap between the needle actuator body286and the housing20prevents premature actuation. Referring toFIG.66, the button spring284includes a first bearing surface298and a second bearing surface300spaced from the first bearing surface298, and a cantilevered central spring arm302surrounded by a pair of outer arms304that are joined by the first bearing surface298. The actuation button arrangement280is configured to provide one or more of the following features, which are discussed in more detail below: one-way axial displacement or sliding of the actuator button26; transverse movement (raised and depressed positions) of the actuator button26where the actuator button26remains depressed during the use position of the needle actuator body286; and lockout of the actuator button26in the post-use position of the needle actuator body286such that the button26is in the raised position and cannot be depressed by a user. To actuate the system10using the actuator button26, the user first slides the user interface portion288in a first axial direction, shown as being to the right inFIGS.65G and65H. The user may be required to slide the user interface portion288about 10 mm or about 8 mm, although other suitable distances may be utilized. Moving the actuator button26axially moves the lockout arms290,292to clear the button contact surfaces294,296on the needle actuator body286to allow movement of the actuator button26from the raised position to the depressed position. As the user distally slides the user interface portion288, the central spring arm302of the button spring284rides over a spring arm306bearing surface on the housing20while the first and second bearing surfaces298,300engage first and second bearing ramps308,310on the housing20. The forces on the button spring284are balanced through the engagement with the spring arm bearing surface306and the first and second bearing ramps308,310to provide a smooth axial displacement or sliding of the actuator button26. As the actuator button26and the button spring284reach the end of their axial sliding travel, the central spring arm302and the first bearing surface298pass the end of a respective stops312,314to prevent the actuator button26from sliding backward to its original position, as shown inFIG.65H. Further, when the actuator button26and the button spring284reach the end of their axial sliding travel, the user engages the user interface portion288to move the actuator button26downward to its depressed position. The actuator button26may be depressed about 2 mm and the minimum force required to depress the actuator button26is about 3 N, and most preferably, about 2.8 N, although other suitable distances and minimum forces may be utilized. As the user depresses the user interface portion288, shown inFIGS.65A and65B, the actuator button26rotates the needle actuator body286to release the needle actuator body286thereby allowing the needle actuator body286to move from the pre-use position to the use position. As shown inFIG.65B, as the needle actuator body286travels to the use position, the lockout arms290,292run along the underside of the button contact surfaces294,296to prevent the actuator button26springing upward. After the medicament has been delivered and as the needle actuator body286is transitioning from the use position to the post-use position, shown inFIG.65C, the lockout arms290,292are disengaged from the button contact surfaces294,296allowing the actuator button26to spring back up under the influence of the button spring284. Once the needle actuator body286fully transitions to the post-use position, shown inFIG.65D, the actuator button26has finished moving from the depressed position to the raised position due to the biasing force of the button spring284. When the needle actuator body286is in the post-use position, a spring arm316on the needle actuator body286engages the actuator button26to prevent the actuator button26from moving to the depressed position while axial movement is still restricted by the engagement of the spring arm302with the stops312,314. Thus, the actuator button26is locked after delivery of the medicament is complete to provide a clear indication between a used system and an unused system. Furthermore, if the user holds down the actuator button26during dispensing of the medicament, proper dosing and needle retraction will still complete, but the actuator button26will not spring back up to the raised position until the button26is released. In one aspect, the button spring284is made of plastic. The button spring284may also be a pressed metal spring could be used instead, although any other suitable material may be utilized. Referring toFIGS.68A-68G, rather than providing a separate actuator button26and button spring284, the spring may be provided integrally with the button26. More specifically, an actuator button320according to a further aspect of the present invention includes an integral spring arm322. The actuator button320also includes lockout arms324, retention arms326, and a rear pivot328. As shown inFIGS.68D and68E, the spring arm322engages prongs330in the top portion22of the housing20. During transition of the system10from the pre-use position to the use position, the spring arm322slides past a detent of the prongs330providing an axial spring force. The end of the spring arm322engages a portion of the top portion22of the housing20to provide the vertical spring force as the spring arm322deflects. The actuator button320is configured to a fluid motion between the sliding and depression movements of the button320even though two separate motions are occurring, which is similar to the operation of the button26discussed above. During transition between the pre-use position and the use position, the button320pivots about the rear pivot328with the retention arm326engaging a portion of the needle actuator body286thereby maintaining a depressed position of the button320until the end-of-dose position is reached in a similar manner as actuator button26. The lockout arms324deflect inwards and engages a portion of the needle actuator body286as the needle actuator body286moves to the end-of-dose position thereby preventing further movement of the actuator button320in a similar manner as the actuator button26discussed above. Aspects of the present invention provide improvements over previous button designs. For example, the actuation button arrangement280provides multiple surfaces to hold the needle actuator body286in place against a needle actuator spring106prior to actuation, thereby reducing the likelihood of premature actuation during a drop impact. The actuation button arrangement280physically prevents the needle actuator body286from moving prior to actuation by holding it in a tilted (locked) state in such a way that the surfaces have no room to separate and pre-activate. In addition, button slide forces of the actuation button arrangement280are controlled more precisely by utilizing a flexing arm rather than using a simple bump detent. This permits longer sliding strokes of the button26with better force control, resulting in a more ergonomically effective design. Further, the actuation button arrangement280causes the button26to pop back out at the end of injection, giving the user an additional visual, audible, and tactile indication that the medicament delivery is completed. According to one aspect, the fluid delivery volume of the system10is determined by the end position of a plunger relative to a point inside the housing regardless of actual fill volume, container inner diameter, and stopper starting position and length. The dosing accuracy variability can be significant because the tolerances of the factors above can be quite large. Aspects of the present invention allow for the elimination of some or all of these tolerances from the dosing equation, resulting in a more precise and less variable injection volume of medicament. Referring toFIGS.70A-70G, a spacer assembly400for use in connection with a drive assembly according to one aspect of the present invention is shown. Elements in a chain of tolerances in the stopper spacer assembly400include a thickness (A) of a flange402of an inner plunger404, an internal length (B) of an outer plunger406between an internal proximal end408and an internal shoulder410, and an initial offset distance (C1) between the inner plunger flange402and the internal proximal end408of the outer plunger. This initial offset distance (C1) is preferably greater than a gap distance (C2) between outer plunger406and the proximal end of the medicament barrel412. The chain of tolerances in the stopper spacer assembly400also includes the internal barrel diameter (D). Once assembled, the stopper spacer414and the outer plunger406are unique for a given medicament volume. FIGS.70B-70Gillustrate operation of the stopper spacer assembly400. As shown inFIG.70B, when the system is actuated, the both inner and outer plungers404and406are released. An outer spring416pushes the outer plunger406into the barrel412, compressing damping material418, and an inner spring420. The stopper422does not yet mover relative to the barrel412due to the fluid column of medicament. Next, as shown inFIG.70C, the outer spring416distally displaces the outer plunger406and the barrel412to open a valve (not shown) at the distal end of the barrel412that establishes fluid communication with the needle (not shown). Due to the incompressibility of the liquid medicament, the stopper422cannot displace relative to the barrel412until the valve is opened and the fluid path to the patient needle is established. Subsequently, as shown inFIGS.70D and70E, the inner spring420displaces the inner plunger404, the stopper spacer414, and the stopper422, to dispense the fluid. FIG.70Fillustrates the end of medicament delivery when the proximal flange402of the inner plunger404contacts the internal shoulder410of the outer plunger406, thereby ceasing displacement of the inner plunger404(and the stopper spacer414and stopper422) relative to the medicament barrel212and stopping the flow of medicament. According to one aspect, as shown inFIG.70G, the cessation of displacement of the inner plunger404relative to the medicament barrel412triggers an end-of-dose indicator for the system. Referring toFIGS.71and72, a collapsible spacer assembly430includes a forward spacer portion432secured to a stopper434, an inner plunger436, a rear spacer portion438, and a rotating shuttle440. The inner plunger436can translate relative to the forward spacer portion432, but not rotate relative thereto. Similarly, the rear spacer portion438can also move axially relative to the forward spacer portion432, but not rotate relative to the forward spacer portion432. As subsequently described in greater detail, the rotating shuttle440first rotates, and subsequently translates. According to one aspect, forward spacer portion432is fixedly secured to the stopper434. One skilled in the art will understand that many methods can be employed to secure the forward spacer portion432to the stopper434, for example, adhesive, mechanical fasteners, or any other suitable arrangement. Preferably, the forward spacer portion432includes threads that engage mating threads in the stopper434. When the stopper spacer assembly430is screwed into the stopper434, an axial load is applied through access openings442in the rear spacer portion438. This force can be used to push the stopper434forward, applying pressure to the fluid medicament. This pressure causes the front (distal) face of the stopper434to deflect and press proximally, pushing back on the rear spacer portion438and rotating the rotating shuttle into its “as assembled” condition. In other words, when a medicament barrel is filled with medicament and the system's plunger is applying axial force to the medicament via the spacer assembly430, the distal face of the stopper434is deformed by the pressure of the medicament. During medicament delivery, pressure is applied by a drive assembly (via the plunger) to the rear spacer portion438, which in turn applies a rotational torque to the rotating shuttle440via helical faces444of the rear spacer portion438. But the stopper deformation from the medicament provides a rearward or proximal force on the inner plunger436, which prevents rotation of the rotating shuttle440. According to one aspect, an axial reaction load on the inner plunger436can be increased by increasing the length of the inner plunger436. Once the medicament delivery is complete, as shown inFIG.73, the pressure on the stopper434decreases, thereby permitting the distal end of the inner plunger436to displace distally. This distal displacement permits the rotating shuttle440to rotate. The continued axial force applied by the drive assembly rotates and distally displaces the rotating shuttle440due to interaction of the helical faces444in the rear spacer portion438with corresponding cam-faced arms446of the rotating shuttle440. According to one aspect, this final movement of the rotating shuttle440causes the drive assembly to trigger needle retraction. Referring toFIGS.74and75, a restriction member452according to one aspect of the present invention is disposed with the drive assembly. The restriction member452governs the timing of the final displacement of the needle actuator bodies96,220subsequent to the completion of the medicament dose. Instead of rotating about a fixed post, the restriction member452floats freely. Once a plunger displaces sufficiently distally for a gap to align with the restriction member452(as shown inFIGS.74and75), the restriction member452displaces laterally into the gap because of the force of the spring on the needle actuator96,220and the angled face454on the rear of the arm of the restriction member174that engages the needle actuator body (best shown inFIG.75). Once the restriction member no longer retains the needle actuator body96,220, the needle actuator body96,220is free to complete the axial movement to the post-use position. Further, as shown inFIG.75, the restriction member452is biased onto the rear of the barrel portion of the container14, which minimizes the tolerance chain of the various components and improves dose accuracy. Referring toFIGS.76-78, a spacer assembly460according to a further aspect of the present invention is shown. The spacer assembly460shown inFIGS.76-78allows for the removal of the effect of manufacturing tolerance build up through adjustment of the spacer assembly thereby allowing each system to inject the same amount of medicament. As shown inFIG.77, the spacer assembly460includes a stopper462and a stopper spacer464. The stopper spacer464includes a fixed spacer piece or fixed spacer466that is fixedly connected with the stopper462, and an adjustable spacer piece or adjustable spacer468that is rotationally displaceable in one direction relative to the fixed spacer466. One skilled in the art will understand that many methods can be employed to secure the fixed spacer466to the stopper462, for example, adhesive, mechanical fasteners, or any other suitable arrangement. Preferably, the fixed spacer466includes one or more external threads that engage one or more mating threads in the stopper462. According to one aspect, the adjustable spacer468has a distal stem with an external thread470. The distal stem thread470engages an internal thread472in the fixed spacer466(best shown inFIG.78) to rotationally control axial displacement of the adjustable spacer468relative to the fixed spacer466. As shown inFIGS.76and77, the fixed spacer466includes radially spaced detents474and the adjustable spacer468includes a spring detent arm476, the free end of which engages a selected one of the detents474to prevent rotation and axial displacement of the adjustable spacer468toward the fixed spacer466. The free end of the spring detent arm476is shaped to pass over the detents474in one direction, thereby permitting rotation and proximal axial displacement of the adjustable spacer468away from the fixed spacer466. Despite variations in the dimensions of stoppers and containers, the adjustable spacer468can be adjusted relative to the fixed spacer466to provide a consistent axial length of the stopper assembly460. As shown inFIG.78, once the container is filled, an axial load, such as a load that would be encountered when installed in the system10,200, can be applied to the adjustable spacer468(and thus, the fixed spacer466and the stopper462). Once the axial load is applied, the adjustable spacer468can be proximally backed out to ensure a consistent gap478between the proximal end of a medicament barrel480and the proximal face of the adjustable spacer468, thereby accounting for variations in the medicament barrel glass and the compressibility of any entrapped air. In other words, the spacer assembly460allows the adjustable spacer468to have a predetermined set position relative to the container14independent of the variables of the container14and stopper length. Accordingly, the start position of the spacer assembly460is a predetermined distance from the container14and the end position of the spacer assembly460is also a predetermined distance from the container14such that the travel of the stopper462is defined by the effective length of the plungers52,54of the drive assembly12. Referring toFIGS.79and80, a base column482and a cap484of an automatically adjusting spacer486according to one aspect of the present invention is shown. The base column482includes a base portion488and an axially extending column490. According to one embodiment, the base column482includes a plurality of columnar protrusions491that each have a plurality of ratchet teeth492disposed on a proximal portion thereof. A locking barb493is disposed at the proximal end of each of the plurality of ratchet teeth492. The cap484is hollow, and a distal end of the cap484includes one or more axial springs494. According to one aspect, the axial springs494are bent, cantilevered arms formed during molding of the cap484. According to another aspect, a separate biasing member, such as a compression spring can be employed in the automatically adjusting spacer486. When assembled with the base column482, the springs494engage the base portion488and maintain an initial spacing between the base column482and the cap484. According to one aspect, the springs494are omitted. The cap484also includes a plurality of flexible cantilevered arms or tabs496, which each have a free proximal portion with a plurality internal of ratchet teeth497. The proximal end of each flexible tab496includes a foot498. FIG.81Billustrates the cap of the automatically adjusting spacer deployed within a proximal recess of a stopper494at a proximal portion of a medicament barrel. The base column482is assembled into the hollow cap484with the base portion482engaging the stopper494and the feet498disposed outside the proximal end of the barrel. In operation, as shown inFIGS.81A and81B, the cap484displaces distally relative to the base column482(as well as the stopper494and the barrel) until the proximal end of the cap484is flush with the end of the medicament barrel. This action causes the feet498to engage the internal surface of the barrel and displace radially inward, thereby forcing the ratchet teeth492into locking engagement with the ratchet teeth497. The locking barb493, the engagement of the ratchet teeth492and497, and the engagement of the feet498with the internal surface of the barrel prevents the displacement of the cap484relative to the base column482. Thus, the automatically adjusting spacer486can accommodate differences in stoppers, barrel diameters, and medicament fill volumes, to automatically provide a bearing surface flush the proximal end of the medicament barrel. One aspect of the present invention is a spacer assembly486that is situated against the stopper in the container within the system. The spacer design is such that its effective length can be adjusted in order to allow the dispensing of a precise quantity of medicament. The length adjustment is intended to compensate for manufacturing tolerances within the container, the fill volume, and especially the stopper length, which can add up to ⅓ of the variability in a delivered dose using a non-adjustable spacer. The spacer length can be adjusted through several techniques, depending on the specific aspect. The spacer length can be self adjusting based on its location to the back of the container, it can be adjusted by assembly equipment at the time of final assembly of the primary container into the subassembly, and it can be made an integral part of the stopper and adjusted as a subassembly prior to filling. The adjustable spacer486allows a more precise volume of fluid to be injected compared to a non-adjustable stopper. Referring toFIGS.82-87, a drive assembly500for a drug delivery system according to one aspect of the present invention is shown. The drive assembly500includes an actuation button506, a container508, a needle actuator assembly510, an actuation release or flipper512, a lead screw514, and a plunger516. The lead screw includes a drum portion518with external radially-protruding vanes520, and, as best shown inFIGS.84and85and subsequently described in greater detail, a screw thread portion522. Prior to activation, as best shown inFIGS.83and86one end513of the actuation release512engages one of the vanes520to prevent rotation of the lead screw514. According to one aspect, as shown inFIGS.84-86, the screw thread portion522of the lead screw514engages internal threads of a nut524connected with the plunger516. According to another aspect, the nut and its internal threads are integrally formed with the plunger as a unitary structure. Additionally, a constant force spring526is received within the drum portion518and biases the lead screw514in a rotational direction. According to one aspect, the spring526is secured to the base cover504. According to another aspect, as shown inFIGS.84-86, a drive assembly housing528is disposed within the system and the spring526is secured to the power pack housing528. Unlike a helical spring, such as a compression spring, which has a force profile proportional to its displacement, the constant force spring526and the like maintain a relatively flat or even force profile over a long working length. The even force profile advantageously provides an injection force that is proportional to the spring force. This will provide a flat or even injection force, and thus, a substantially constant injection rate for the medicament. Although the spring526is illustrated inFIG.86as having only two turns of material, one skilled in the art will appreciate that fewer or greater numbers of turns can be employed. Preferably, an assembler winds the spring526when the drive assembly500is assembled, and the spring526is stored in the wound position until the time of actuation. Upon actuation of the system, the needle actuator assembly510is released to axially displace (to the right inFIGS.82-85) from the pre-use position to the post-use position under the influence of a biasing member530(best shown inFIG.83). During this displacement, the needle actuator assembly510bears against a second end532of the actuation release512and rotates the release512counter-clockwise, as shown inFIG.87. This counter-clockwise rotation of the actuation release512frees the first end513thereof from engagement with the vane520. Subsequent to the disengagement of the first end513from the vane520, the spring526unwinds and drives rotation of the lead screw514, which, in combination with the nut524, advances the plunger514to dispense the medicament. As the lead screw514is rotating, the rotation of the drum portion518and the vanes520is visible through a window534in the housing. This window534indicates progress of the screw in a way that is much more apparent than viewing the linear movement of the stopper536in the container508. In fact, this rotational movement is many times more sensitive than the linear movement. One skilled in the art will appreciate that the exact amount of advantage or increase depends on the pitch of screw thread portion522of the lead screw514, the diameter of the drum portion518, and number of vanes520on the drum portion518. Referring toFIGS.88-93, a drive assembly600for a drug delivery system according to a further aspect of the present invention is shown. The drive assembly600acts to store a spring's mechanical energy and to activate it when triggered. The drive assembly600includes a medicament barrel601, a stopper602slidably disposed in the barrel601, a first valve plunger603, a second valve plunger604, a first revolve nut605, and a second revolve nut606. The drive assembly600also includes a rotary indicator607, a locking element608, a constant force spring609disposed within the rotary indicator607, and an actuation release or flipper610. The drive assembly600is at least partially disposed within a housing611that can be assembled into a drug delivery system. The constant force spring609is contained between the housing611and the rotary indicator607within a drum portion616of the rotary indicator607. The drive assembly's inactive state is such that energy is applied by uncoiling the spring609and harnessing this energy geometrically with the housing611, rotary indicator607, and actuation release610. When the drive assembly600is deactivated, the spring recoils and translates the mechanical energy into rotational motion of the rotary indicator. The telescoping multi-part plunger is oriented along a force axis between the medicament barrel601and the rotary indicator607. The rotary indicator607features a threaded shaft618. According to one aspect, the threads are dual lead, and are either square or rectangular in nature. The multi-part telescoping plunger includes a two-part threaded nut (first revolve nut605and second revolve nut606) and a two-part plunger (first valve plunger603and second valve plunger604). The second revolve nut606is a threaded shaft that mates with the rotary indicator607and first revolve nut605and features matching threads on its inner and outer surfaces (internal and external threads, respectively) to mate with them. The second revolve nut606also has a circular collar620(best shown inFIG.92) on its proximal end that bottoms down on the second valve plunger604. The second revolve nut606is free to spin along the force axis. The first revolve nut605is also a threaded shaft that features threads on its inner diameter corresponding to the external threads of the second revolve nut606to mate with the second revolve nut606. According to one aspect, on one end, the first revolve nut605has a hexagonal collar that press fits on the first valve plunger603to fixedly connect the first valve plunger603with the first revolve nut605. In the drive assembly600, the first revolve nut is not free to rotate and will only translate when the power module subassembly is actuated. The second valve plunger604is a hollow cylindrical component with a small collar622on its distal end, a large collar624on its proximal end, and an extended L-shaped arm626(best shown inFIG.93) protruding from the large proximal collar624. According to one embodiment, the small collar622is discontinuous and features four leaf cantilevered arms or leaf springs623that allow the collar to bend and mate with the first valve plunger603. The inner surface of the second valve plunger604has an undercut through its length terminating at its proximal end a radially inward protruding shelf628of the large collar624. The shelf628engages the second revolve nut606within the telescoping assembly. The first valve plunger603attaches to the stopper602and is also a hollow cylindrical component that mates with the second valve plunger604. More specifically, the first valve plunger603features a cylindrical protrusion630on its distal end to mate with the stopper602. According to one aspect, as best shown inFIG.89, four thru slots632are disposed on the proximal quadrants of the first valve plunger603to mate with the leaf springs or arms623and small collar portion622of the second valve plunger604. Both the first and second valve plungers603and604are free to slide. Telescoping is achieved when the constant force spring609recoils and the rotary indicator607starts spinning. The threaded attachment between the rotary indicator607and the second revolve nut606causes second revolve nut606to rotate. But because the second revolve nut606is threaded to the first revolve nut605, which cannot rotate and experiences resistance to distal translation due to the pressure caused by medicament in the barrel601, the second revolve nut606will displace proximally and bottom out on the second valve plunger's radially inward protruding shelf628. The second valve plunger604is prevented from displacing proximally by the housing611. Subsequently, and with continued rotation of the rotary indicator607, because the second revolve nut606is threaded with the first revolve nut605(which cannot rotate) the first revolve nut605translates distally to push the first valve plunger603(and the stopper602) to dispense medicament from the barrel601. The first valve plunger603displaces distally relative to the second valve plunger604until the small collar sections622(respectively disposed on the distal ends of the leaf springs or arms623of the second valve plunger604) engage the corresponding proximal ends of the slots632of the first valve plunger603. This locks the relative position of the first and second valve plungers603and604, with continued rotation of the rotary indicator607, both valve plungers translate distally while also pushing the second revolve nut along (because of its proximal engagement with the shelf624). The initial and final positions of the telescoping plunger, and thus the medicament dose, are controlled by the rectangular thread form of the threaded shaft618of the rotary indicator607, a threaded shaft on the drum portion616of the rotary indicator607, and a stepped pin that acts as the locking element608. According to one aspect, threaded shaft on the drum portion616of the rotary indicator607is single lead, and because the rest of the components in the telescoping chain have dual lead threads, the axial travel of the other threaded components is twice the axial travel of the lock608relative to the rotary indicator. According to one embodiment, the lock608is cylindrical and features a domed tip on one end and a cylindrical collar on the other. The threads on the exterior of the rotary indicator's drum portion616along with a slot and undercut636at the bottom of the housing611captures the lock608in place, allowing it to slide parallel to the force axis. Thus, as the spring609is released and the rotary indicator607turns, the lock608translates as well and creates a positive stop when the distal end of the thread on the exterior of the rotary indicator's drum portion616is reached. One benefit of aspects of the drive assembly600include the use of a constant force spring609, the mechanical energy of which is converted into substantially constant linear force to the medicament in the barrel601. In turn, this creates a uniform medicament delivery rate. Another benefit is that employing the telescoping plunger driven by a thread form, the drive assembly can create in-line space savings of up to 0.75 inches compared to other plunger designs. Additionally, the drive assembly provides a controlled medicament dose through an initial and final mechanical constraint within the same component. As previously noted, other drug delivery systems utilize a compressed coil spring, which exerts a maximum force at actuation that eventually decreases as the spring expands. A decreasing force at the plunger translates into variable medicament delivery time and medicament exit pressure. By using a constant force spring, the force exerted on the plunger is constant from the beginning to the end of the dosage. In addition, the distance a coil spring has to travel in addition to the length of a static plunger that needs translate inside the drug container can create a long assembly. In contrast, in embodiments of the present invention, the constant force spring is contained radially and does not require any additional space before or after activation. Furthermore, the aspects of the telescoping plunger allow that the plunger length of the can be significantly reduced in comparison to the length of a static plunger. Previous drug delivery systems have variable dose accuracy performance because the mechanical components enabling the drug delivery create a geometric dependence by bottoming down on the container, which cannot be fabricated with tight tolerances. Some embodiments of the present invention create a control to the start and end times of the translating plunger via a thread form in the rotary indicator and the use of the constant force spring. The drive assembly creates a space saving geometry in addition to well-controlled time, volume and pressure for the drug delivery device, which translates to a more attractively compact and precise drug delivery device. Some aspects of the drive assembly implement three rotating threaded shafts to create a linear space savings of about 0.75 inch. In other aspects, the same concept can be employed using two rotating threaded shafts and result in a space savings of about 0.5 inch. Some aspects of the present invention convert the rotational energy of a constant force spring to a translational force motion of a plunger. Referring toFIGS.94-100, a spacer assembly660according to a further aspect of the present invention is shown. The spacer assembly660is similar to the spacer assembly460discussed above and shown inFIGS.76-78and operates in a similar manner to achieve similar advantages. The spacer assembly660includes a fixed spacer666and an adjustable spacer668. The fixed spacer666is configured to be received by the stopper462with lugs670engaging the stopper462to secure the fixed spacer666within the stopper462, although other suitable securing arrangements, such as threads, may be utilized. The fixed spacer666includes interior threads672that receive exterior threads678of the adjustable spacer668. The fixed spacer666includes a plurality of detents674positioned on a helical portion of the fixed spacer666. The adjustable spacer668includes a spring detent arm676that engages one of the detents674to prevent rotation and axial displacement of the adjustable spacer668relative toward the fixed spacer666. The spring detent arm676is shaped and configured to pass over the detents674in one direction to allow rotation and axial displacement of the adjustable spacer668away from the fixed spacer666. The adjustable spacer668may be initially secured to the fixed spacer666via the threads672,678by applying a force to the top of the spring detent arm676, which biases the spring detent arm676away from the detents674to allow the spacers666,668to be secured to each other. Accordingly, in the same manner as discussed above in connection with spacer assembly460, the adjustable spacer is free to rotate in one axial direction to adjust the length of the spacer assembly660. Referring again toFIGS.94-100, the spacer assembly660further includes a shim680configured to be received and secured to the adjustable spacer668. Rather than providing a plurality of sizes of adjustable spacers468,668, a plurality of shim680sizes can be provided to accommodate a plurality of different fill volumes within the container14. The shim680may be secured to the adjustable spacer668via a connector682extending from the shim680that is received by the adjustable spacer668using a snap-fit, although other suitable securing arrangements may be utilized. A center portion684of the fixed spacer666is configured to be engaged while the adjustable spacer668is rotated relative to the fixed spacer666to prevent rotation of the fixed spacer666along with the adjustable spacer268. The center portion684of the fixed spacer666is accessible through an opening in the shim680. Elements of one disclosed aspect can be combined with elements of one or more other disclosed aspects to form different combinations, all of which are considered to be within the scope of the present invention. While this disclosure has been described as having exemplary designs, the present disclosure can be further modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the disclosure using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this disclosure pertains and which fall within the limits of the appended claims. | 74,788 |
11857770 | DETAILED DESCRIPTION For the purposes of promoting an understanding of the principles of the present disclosure, reference will now be made to the embodiments illustrated in the drawings, and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended. The present disclosure relates to sensing systems for medication delivery devices. In one aspect, the sensing system is for determining the amount of a dose delivered by a medication delivery device based on the sensing of relative rotational movement between a dose setting member and an actuator of the medication delivery device. The sensed relative angular positions or movements are correlated to the amount of the dose delivered. In a second aspect, the sensing system is for determining the type of medication contained by the medication delivery device. By way of illustration, the medication delivery device is described in the form of a pen injector. However, the medication delivery device may be any device which is used to set and to deliver a dose of a medication, such as an infusion pump, bolus injector or an auto injector device. The medication may be any of a type that may be delivered by such a medication delivery device. Devices described herein, such as a device10, may further comprise a medication, such as for example, within a reservoir or cartridge20. In another embodiment, a system may comprise one or more devices including device10and a medication. The term “medication” refers to one or more therapeutic agents including but not limited to insulins, insulin analogs such as insulin lispro or insulin glargine, insulin derivatives, GLP-1 receptor agonists such as dulaglutide or liraglutide, glucagon, glucagon analogs, glucagon derivatives, gastric inhibitory polypeptide (GIP), GIP analogs, GIP derivatives, oxyntomodulin analogs, oxyntomodulin derivatives, therapeutic antibodies and any therapeutic agent that is capable of delivery by the above device. The medication as used in the device may be formulated with one or more excipients. The device is operated in a manner generally as described above by a patient, caregiver or healthcare professional to deliver medication to a person. An exemplary medication delivery device10is illustrated inFIGS.1-4as a pen injector configured to inject a medication into a patient through a needle. Pen injector10includes a body11comprising an elongated, pen-shaped housing12including a distal portion14and a proximal portion16. Distal portion14is received within a pen cap18. Referring toFIG.2, distal portion14contains the reservoir or cartridge20configured to hold the medicinal fluid of medication to be dispensed through its distal outlet end during a dispensing operation. The outlet end of distal portion14is equipped with a removable needle assembly22including an injection needle24enclosed by a removable cover25. A piston26is positioned in reservoir20. An injecting mechanism positioned in proximal portion16is operative to advance piston26toward the outlet of reservoir20during the dose dispensing operation to force the contained medicine through the needled end. The injecting mechanism includes a drive member28, illustratively in the form of a screw, axially moveable relative to housing12to advance piston26through reservoir20. A dose setting member30is coupled to housing12for setting a dose amount to be dispensed by device10. In the illustrated embodiment, dose setting member30is in the form of a screw element operative to spiral (i.e., simultaneously move axially and rotationally) relative to housing12during dose setting and dose dispensing.FIGS.1and2illustrate the dose setting member30fully screwed into housing12at its home or zero dose position. Dose setting member30is operative to screw out in a proximal direction from housing12until it reaches a fully extended position corresponding to a maximum dose deliverable by device10in a single injection. Referring toFIGS.2-4, dose setting member30includes a cylindrical dose dial member32having a helically threaded outer surface that engages a corresponding threaded inner surface of housing12to allow dose setting member30to spiral relative to housing12. Dose dial member32further includes a helically threaded inner surface that engages a threaded outer surface of sleeve34(FIG.2) of device10. The outer surface of dial member32includes dose indicator markings, such as numbers that are visible through a dosage window36to indicate to the user the set dose amount. Dose setting member30further includes a tubular flange38that is coupled in the open proximal end of dial member32and is axially and rotationally locked to dial member32by detents40received within openings41in dial member32. Dose setting member30may further include a collar or skirt42positioned around the outer periphery of dial member32at its proximal end. Skirt42is axially and rotationally locked to dial member32by tabs44received in slots46. Further embodiments described later shown examples of the device without a skirt. Dose setting member30therefore may be considered to comprise any or all of dose dial member32, flange38, and skirt42, as they are all rotationally and axially fixed together. Dose dial member32is directly involved in setting the dose and driving delivery of the medication. Flange38is attached to dose dial member32and, as described later, cooperates with a clutch to selectively couple dial member32with a dose button56. Skirt42provides a surface external of body11to enable a user to rotate the dial member32for setting a dose. Skirt42illustratively includes a plurality of surface features48and an annular ridge49formed on the outer surface of skirt42. Surface features48are illustratively longitudinally extending ribs and grooves that are circumferentially spaced around the outer surface of skirt42and facilitate a user's grasping and rotating the skirt. In an alternative embodiment, skirt42is removed or is integral with dial member32, and a user may grasp and rotate dose button56and/or dose dial member32for dose setting. In the embodiment ofFIG.4, a user may grasp and rotate the radial exterior surface of one-piece dose button56, which also includes a plurality of surface features, for dose setting. Delivery device10includes an actuator50having a clutch52which is received within dial member32. Clutch52includes an axially extending stem54at its proximal end. Actuator50further includes dose button56positioned proximally of skirt42of dose setting member30. In an alternative embodiment, dose setting member30may include a one-piece dose button without the skirt, such as, for example, shown inFIGS.14,18,19, and22. Dose button56includes a mounting collar58(FIG.2) centrally located on the distal surface of dose button56. Collar58is attached to stem54of clutch52, such as with an interference fit or an ultrasonic weld, so as to axially and rotatably fix together dose button56and clutch52. Dose button56includes a disk-shaped proximal end surface or face60and an annular wall portion62extending distally and spaced radially inwardly of the outer peripheral edge of face60to form an annular lip64there between. Proximal face60of dose button56serves as a push surface against which a force can be applied manually, i.e., directly by the user to push actuator50in a distal direction. Dose button56illustratively includes a recessed portion66centrally located on proximal face60, although proximal face60alternatively may be a flat surface. Similarly, the alternative one-piece dose button, such as shown inFIG.22, may include a recessed portion66centrally located on proximal face60or alternatively may be a flat surface. A bias member68, illustratively a spring, is disposed between the distal surface70of button56and a proximal surface72of tubular flange38to urge actuator50and dose setting member30axially away from each other. Dose button56is depressible by a user to initiate the dose dispensing operation. Delivery device10is operable in both a dose setting mode and a dose dispensing mode. In the dose setting mode of operation, dose setting member30is dialed (rotated) relative to housing12to set a desired dose to be delivered by device10. Dialing in the proximal direction serves to increase the set dose, and dialing in the distal direction serves to decrease the set dose. Dose setting member30is adjustable in rotational increments (e.g., clicks) corresponding to the minimum incremental increase or decrease of the set dose during the dose setting operation. For example, one increment or “click” may equal one-half or one unit of medication. The set dose amount is visible to the user via the dial indicator markings shown through dosage window36. Actuator50, including dose button56and clutch52, move axially and rotationally with dose setting member30during the dialing in the dose setting mode. Dose dial member32, flange38and skirt42are all fixed rotationally to one another, and rotate and extend proximally of the medication delivery device10during dose setting, due to the threaded connection of dose dial member32with housing12. During this dose setting motion, dose button56is rotationally fixed relative to skirt42by complementary splines74of flange38and clutch52(FIG.2), which are urged together by bias member68. In the course of dose setting, skirt42and dose button56move relative to housing12in a spiral manner from a “start” position to an “end” position. This rotation relative to the housing is in proportion to the amount of dose set by operation of the medication delivery device10. Once the desired dose is set, device10is manipulated so the injection needle24properly penetrates, for example, a user's skin. The dose dispensing mode of operation is initiated in response to an axial distal force applied to the proximal face60of dose button56. The axial force is applied by the user directly to dose button56. This causes axial movement of actuator50in the distal direction relative to housing12. The axial shifting motion of actuator50compresses biasing member68and reduces or closes the gap between dose button56and tubular flange38. This relative axial movement separates the complementary splines74on clutch52and flange38, and thereby disengages actuator50, e.g., dose button56, from being rotationally fixed to dose setting member30. In particular, dose setting member30is rotationally uncoupled from actuator50to allow back-driving rotation of dose setting member30relative to actuator50and housing12. The dose dispensing mode of operation may also be initiated by activating a separate switch or trigger mechanism. As actuator50is continued to be axially plunged without rotation relative to housing12, dial member32screws back into housing12as it spins relative to dose button56. The dose markings that indicate the amount still remaining to be injected are visible through window36. As dose setting member30screws down distally, drive member28is advanced distally to push piston26through reservoir20and expel medication through needle24(FIG.2). During the dose dispensing operation, the amount of medicine expelled from the medication delivery device is proportional to the amount of rotational movement of the dose setting member30relative to actuator50as the dial member32screws back into housing12. The injection is completed when the internal threading of dial member32has reached the distal end of the corresponding outer threading of sleeve34(FIG.2). Device10is then once again arranged in a ready state or zero dose position as shown inFIGS.2and3. The start and end angular positions of dose dial member32, and therefore of the rotationally fixed flange38and skirt42, relative to dose button56provide an “absolute” change in angular positions during dose delivery. Determining whether the relative rotation was in excess of 360° is determined in a number of ways. By way of example, total rotation may be determined by also taking into account the incremental movements of the dose setting member30which may be measured in any number of ways by a sensing system. Further details of the design and operation of an exemplary delivery device10may be found in U.S. Pat. No. 7,291,132, entitled Medication Dispensing Apparatus with Triple Screw Threads for Mechanical Advantage, the entire disclosure of which is hereby incorporated by reference herein. Another example of the delivery device is an auto-injector device that may be found in U.S. Pat. No. 8,734,394, entitled “Automatic Injection Device With Delay Mechanism Including Dual Functioning Biasing Member,” which is hereby incorporated by reference in its entirety, where such device being modified with one or more various sensor systems described herein to determine an amount of medication delivered from the medication delivery device based on the sensing of relative rotation within the medication delivery device. The dose detection systems described herein use a sensing component and a sensed component attached to members of the medication delivery device. The term “attached” encompasses any manner of securing the position of a component to another component or to a member of the medication delivery device such that they are operable as described herein. For example, a sensing component may be attached to a member of the medication delivery device by being directly positioned on, received within, integral with, or otherwise connected to, the member. Connections may include, for example, connections formed by frictional engagement, splines, a snap or press fit, sonic welding or adhesive. The term “directly attached” is used to describe an attachment in which two components, or a component and a member, are physically secured together with no intermediate member, other than attachment components. An attachment component may comprise a fastener, adapter or other part of a fastening system, such as a compressible membrane interposed between the two components to facilitate the attachment. A “direct attachment” is distinguished from a connection where the components/members are coupled by one or more intermediate functional members, such as the way dial member32is coupled inFIG.2to the dose button56by a clutch52. The term “fixed” is used to denote that an indicated movement either can or cannot occur. For example, a first member is “fixed rotationally” with a second member if the two members are required to move together in rotation. In one aspect, a member may be “fixed” relative to another member functionally, rather than structurally. For example, a member may be pressed against another member such that the frictional engagement between the two members fixes them together rotationally, while the two members may not be fixed together absent the pressing of the first member. Various sensor systems are contemplated herein. In general, the sensor systems comprise a sensing component and a sensed component. The term “sensing component” refers to any component which is able to detect the relative position of the sensed component. The sensing component includes a sensing element, or “sensor”, along with associated electrical components to operate the sensing element. The “sensed component” is any component for which the sensing component is able to detect the position and/or movement of the sensed component relative to the sensing component. For the dose delivery detection system, the sensed component rotates relative to the sensing component, which is able to detect the angular position and/or the rotational movement of the sensed component. For the dose type detection system, the sensing component detects the relative angular position of the sensed component. The sensing component may comprise one or more sensing elements, and the sensed component may comprise one or more sensed elements. The sensor system is able to detect the position or movement of the sensed component(s) and to provide outputs representative of the position(s) or movement(s) of the sensed component(s). A sensor system typically detects a characteristic of a sensed parameter which varies in relationship to the position of the one or more sensed elements within a sensed area. The sensed elements extend into or otherwise influence the sensed area in a manner that directly or indirectly affects the characteristic of the sensed parameter. The relative positions of the sensor and the sensed element affect the characteristics of the sensed parameter, allowing a microcontroller unit (MCU) of the sensor system to determine different rotational positions of the sensed element. Suitable sensor systems may include the combination of an active component and a passive component. With the sensing component operating as the active component, it is not necessary to have both components connected with other system elements such as a power supply or MCU. Any of a variety of sensing technologies may be incorporated by which the relative positions of two members can be detected. Such technologies may include, for example, technologies based on tactile, optical, inductive or electrical measurements. Such technologies may include the measurement of a sensed parameter associated with a field, such as a magnetic field. In one form, a magnetic sensor senses the change in a sensed magnetic field as a magnetic component is moved relative to the sensor. In another embodiment, a sensor system may sense characteristics of and/or changes to a magnetic field as an object is positioned within and/or moved through the magnetic field. The alterations of the field change the characteristic of the sensed parameter in relation to the position of the sensed element in the sensed area. In such embodiments the sensed parameter may be a capacitance, conductance, resistance, impedance, voltage, inductance, etc. For example, a magneto-resistive type sensor detects the distortion of an applied magnetic field which results in a characteristic change in the resistance of an element of the sensor. As another example, Hall effect sensors detect changes in voltage resulting from distortions of an applied magnetic field. In one aspect, the sensor system detects relative positions or movements of the sensed elements, and therefore of the associated members of the medication delivery device. The sensor system produces outputs representative of the position(s) or the amount of movement of the sensed component. For example, the sensor system may be operable to generate outputs by which the rotation of the dose setting member during dose delivery can be determined. MCU is operably connected to each sensor to receive the outputs. In one aspect, MCU is configured to determine from the outputs the amount of dose delivered by operation of the medication delivery device. The dose delivery detection system involves detecting relative rotational movement between two members. With the extent of rotation having a known relationship to the amount of a delivered dose, the sensor system operates to detect the amount of angular movement from the start of a dose injection to the end of the dose injection. For example, a typical relationship for a pen injector is that an angular displacement of a dose setting member of 18° is the equivalent of one unit of dose, although other angular relationships are also suitable. The sensor system is operable to determine the total angular displacement of a dose setting member during dose delivery. Thus, if the angular displacement is 90°, then 5 units of dose have been delivered. One approach for detecting the angular displacement is to count increments of dose amounts as the injection proceeds. For example, a sensor system may use a repeating pattern of sensed elements, such that each repetition is an indication of a predetermined degree of angular rotation. Conveniently, the pattern may be established such that each repetition corresponds to the minimum increment of dose that can be set with the medication delivery device. An alternative approach is to detect the start and stop positions of the relatively moving member, and to determine the amount of delivered dose as the difference between those positions. In this approach, it may be a part of the determination that the sensor system detects the number of full rotations of the dose setting member. Various methods for this are well within the ordinary skill in the art, and may include “counting” the number of increments to assess the number of full rotations. The sensor system components may be permanently or removably attached to the medication delivery device. In an illustrative embodiment, as least some of the dose detection system components are provided in the form of a module that is removably attached to the medication delivery device. This has the advantage of making these sensor components available for use on more than one pen injector. In some embodiments, a sensing component is mounted to the actuator and a sensed component is attached to the dose setting member. The sensed component may also comprise the dose setting member or any portion thereof. The sensor system detects during dose delivery the relative rotation of the sensed component, and therefore of the dose setting member, from which is determined the amount of a dose delivered by the medication delivery device. In an illustrative embodiment, a rotation sensor is attached, and rotationally fixed, to the actuator. The actuator does not rotate relative to the body of the medication delivery device during dose delivery. In this embodiment, a sensed component is attached, and rotationally fixed, to the dose setting member, which rotates relative to the actuator and the device body during dose delivery. The sensed component may also comprise the dose setting member or any portion thereof. In an illustrative embodiment, the rotation sensor is not attached directly to the relatively rotating dose setting member during dose delivery. Referring toFIG.5, there is shown in diagrammatic form a dose delivery detection system80including one example of a module82useful in combination with a medication delivery device, such as device10. Module82carries a sensor system, shown generally at84, including a rotation sensor86and other associated components such as a processor, memory, battery, etc. Module82is provided as a separate component which may be removably attached to the actuator. Dose detection module82includes a body88attached to dose button56. Body88illustratively includes a cylindrical side wall90and a top wall92, spanning over and sealing side wall90. By way of example, inFIG.5upper side wall90is diagrammatically shown having inwardly-extending tabs94attaching module82to dose button56. Dose detection module82may alternatively be attached to dose button56via any suitable fastening means, such as a snap or press fit, threaded interface, etc., provided that in one aspect module82may be removed from a first medication delivery device and thereafter attached to a second medication delivery device. The attachment may be at any location on dose button56, provided that dose button56is able to move any required amount axially relative to dose setting member30, as discussed herein. Examples of alternative attachment elements for module82are shown inFIGS.15,23and37described later. During dose delivery, dose setting member30is free to rotate relative to dose button56and module82. In the illustrative embodiment, module82is rotationally fixed with dose button56and does not rotate during dose delivery. This may be provided structurally, such as with tabs94ofFIG.5, or by having mutually-facing splines or other surface features on the module body88and dose button56engage upon axial movement of module82relative to dose button56. In another embodiment, the distal pressing of the module provides a sufficient frictional engagement between module82and dose button56as to functionally cause the module82and dose button56to remain rotationally fixed together during dose delivery. Top wall92is spaced apart from face60of dose button56and thereby provides a cavity96in which some or all of the rotation sensor and other components may be contained. Cavity96may be open at the bottom, or may be enclosed, such as by a bottom wall98. Bottom wall98may be positioned in order to bear directly against face60of dose button56. Alternatively, bottom wall98if present may be spaced apart from dose button56and other contacts between module82and dose button56may be used such that an axial force applied to module82is transferred to dose button56. In another embodiment, module82may be rotationally fixed to the one-piece dose button configuration, such as shown inFIG.22. In an alternate embodiment, module82during dose setting is instead attached to dose setting member30. For example, side wall90may include a lower wall portion100having inward projections102that engage with skirt42in a position underneath ridge49. In this approach, tabs94may be eliminated and module82effectively engages the proximal face60of dose button56and the distal side of annular ridge49. In this configuration, lower wall portion100may be provided with surface features which engage with the surface features of skirt42to rotationally fix module82with skirt42. Rotational forces applied to housing82during dose setting are thereby transferred to skirt42by virtue of the coupling of lower wall portion100with skirt42. Module82is disengaged rotationally from skirt42in order to proceed with dose delivery. The coupling of lower wall portion100with skirt42is configured to disconnect upon distal axial movement of module82relative to skirt42, thereby allowing skirt42to rotate relative to module82during dose delivery. In a similar fashion, module82may be coupled with both dose button56and skirt42during dose setting. This has the advantage of providing additional coupling surfaces during rotation of the module in dose setting. The coupling of the module82to the skirt42is then released prior to dose injection, such as by the axial movement of module82relative to skirt42as dose delivery is being initiated, thereby allowing dose setting member30to rotate relative to module82during dose delivery. In certain embodiments, rotation sensor86is coupled to side wall90for detecting a sensed component. Lower wall portion100also serves to reduce the likelihood that a user's hand inadvertently applies drag to dose setting member30as it rotates relative to module82and housing12during dose delivery. Further, since dose button56is rotationally fixed to dose setting member30during dose setting, the side wall90, including lower wall portion100, provide a single, continuous surface which may be readily grasped and manipulated by the user during dose setting. When the injection process is initiated by pressing down on the dose detection module82, dose button56and dose setting member30are rotationally fixed together. Movement of module82, and therefore dose button56, a short distance, for example less than 2 mm, releases the rotational engagement and the dose setting member30rotates relative to module82as the dose is delivered. Whether by use of a finger pad or other triggering mechanism, the dose detection system is activated before the dose button56has moved a sufficient distance to disengage the rotational locking of the dose button56and the dose setting member30. Illustratively, the dose delivery detection system includes an electronics assembly suitable for operation of the sensor system as described herein. Electronics assembly is operably connected to the sensor system to receive outputs from one or more rotational sensors. Electronics assembly may include conventional components such as a processor, power supply, memory, microcontrollers, etc. contained for example in cavity96defined by module body88. Alternatively, at least some components may be provided separately, such as by means of an external device such as a computer, smart phone or other device. Means are then provided to operably connect the external controller components with the sensor system at appropriate times, such as by a wired or wireless connection. An exemplary electronics assembly120comprises a flexible printed circuit board (FPCB) having a plurality of electronic components. The electronics assembly comprises a sensor system including one or more rotation sensors86operatively communicating with a processor for receiving signals from the sensor representative of the sensed relative rotation. The electronics assembly further includes the MCU comprising at least one processing core and internal memory. One example of an electronics assembly schematic is shown inFIG.46. The system includes a battery, illustratively a coin cell battery, for powering the components. The MCU includes control logic operative to perform the operations described herein, including detecting a dose delivered by medication delivery device10based on a detected rotation of the dose setting member relative to the actuator. In one embodiment, the detected rotation is between the skirt42and the dose button56of a pen injector. The MCU is operative to store the detected dose in local memory (e.g., internal flash memory or on-board EEPROM). The MCU is further operative to wirelessly transmit and/or receive a signal representative of the detected dose to a paired remote electronic device, such as a user's smartphone, over a Bluetooth low energy (BLE) or other suitable short or long range wireless communication protocol. Illustratively, the BLE control logic and MCU are integrated on a same circuit. Further description of the electronics arrangement is described further below. Much of the sensing electronics is contained in the cavity96. However, the rotation sensor may be positioned in a variety of locations in order to sense the relative movement of the sensed component. For example, the rotation sensor may be located within cavity96, within body88but outside of the cavity96, or in other locations of the body, such as on lower wall portion100. The only requirement is that the rotation sensor be positioned to effectively detect the rotational movement of the sensed component during dose delivery. In some embodiments, the rotation sensor is integral to the device10. One or more sensed elements are attached to the dose setting member30. In one aspect, the sensed elements are directly attached to skirt42of the dose setting member. Alternatively, sensed elements may be attached to any one or more of the dose setting components, including the dial member, flange and/or skirt. The only requirement is that the sensed element(s) be positioned to be sensed by the rotation sensor during relative rotational movement during dose delivery. In other embodiments, the sensed component comprises the dose setting member30or any portion thereof. Further illustrative embodiments of a dose delivery detection system80are provided inFIGS.6-13. The embodiments are shown in somewhat diagrammatic fashion, as common details have already been provided with respect toFIGS.1-5. In general, each embodiment includes similar components of the dose detection module82, including a body88having a cylindrical upper wall90and a top wall92. Each embodiment also includes a lower wall100, although it will be appreciated that variations on these components, including the absence of lower wall100, are within the scope of the disclosure. Other parts common to the earlier descriptions herein include an electronics assembly120contained within cavity96of module body88, dose button56, dose setting member32and device housing12. Further, in each embodiment the dose detection module82is diagrammatically shown as being attached to the annular side wall62of dose button56, although alternative forms and locations of attachment may be used. For example, dose detection module82may be attached to dose button56and releasably attached to skirt42in some embodiments. Also, dose detection module82may be attached to one-piece dose button, such as shown inFIGS.22and35. Each example also demonstrates the use of a particular type of sensor system. However, in some embodiments the dose detection system includes multiple sensing systems using the same or different sensing technologies. This provides redundancy in the event of failure of one of the sensing systems. It also provides the ability to use a second sensing system to periodically verify that the first sensing system is performing appropriately. In certain embodiments, as shown inFIG.6, attached to top wall92of module82is a finger pad110. Finger pad110is coupled to top wall92, which is in turn attached to upper side wall90. Finger pad110includes a ridge114which extends radially inward and is received within circumferential groove116of wall component92. Groove116allows a slight axial movement between finger pad110and wall component92. Springs (not shown) normally urge finger pad110upwardly away from wall component92. Finger pad110may be rotationally fixed to wall component92. Axial movement of finger pad110in the distal direction toward module body88as the injection process is initiated may be used to trigger selected events. One use of finger pad110may be the activation of the medication delivery device electronics upon initial pressing and axial movement of the finger pad110relative to the module body88when dose injection is initiated. For example, this initial axial movement may be used to “wake up” the device, and particularly the components associated with the dose detection system. In one example, module82includes a display for indication of information to a user. Such a display may be integrated with finger pad110. MCU may include a display drive software module and control logic operative to receive and processed sensed data and to display information on said display, such as, for example, dose setting, dosed dispensed, status of injection, completion of injection, date and/or time, or time to next injection. In the absence of a finger pad, the system electronics may be activated in various other ways. For example, the initial axial movement of module82at the start of dose delivery may be directly detected, such as by the closing of contacts or the physical engagement of a switch. It is also known to activate a medication delivery device based on various other actions, e.g., removal of the pen cap, detection of pen movement using an accelerometer, or the setting of the dose. In many approaches, the dose detection system is activated prior to the start of dose delivery. Referring toFIGS.6-8, dose detection module82operates using a magnetic sensing system84. Two magnetic sensors130are positioned on lower wall portion100(illustratively the inside surface of lower wall portion100) opposite skirt42of dose setting member30. As for all embodiments, the number and location of the rotation sensor(s) and the sensed element(s) may be varied. For example, the embodiment ofFIGS.6-8may instead include any number of magnetic sensors130evenly or unevenly spaced around skirt42. The sensed component132(FIGS.7and8) comprises a magnetic strip134secured to skirt42, illustratively on the interior of skirt42. In the illustrative embodiment, the strip comprises 5 pairs of north-south magnetic components, e.g.,136and138, each magnetic portion therefore extending for 36°. The magnetic sensors130are positioned at a separation of 18° (FIG.7), and read the digital positions of magnetic strip132, and therefore of skirt42, in a 2-bit grey code fashion. For example, as the sensor detects the passage of an N-S magnetic pair, it is detected that skirt42has rotated 36°, corresponding to 2 units, for example, of dose being added (or subtracted). Other magnetic patterns, including different numbers or locations of magnetic elements, may also be used. Further, in an alternative embodiment, a sensed component133is attached to or integral with flange38of dose setting member30, as illustrated inFIG.9. As previously described, the sensing system84is configured to detect the amount of rotation of the sensed element relative to the magnetic sensors130. This amount of rotation is directly correlated to the amount of dose delivered by the device. The relative rotation is determined by detecting the movements of the skirt42during dose delivery, for example, by identifying the difference between the start and stop positions of skirt42, or by “counting” the number of incremental movements of skirt42during the delivery of medication. Referring toFIGS.10A,10B,11A, and11B, there is shown an exemplary magnetic sensor system150including as the sensed element an annular, ring-shaped, bipolar magnet152having a north pole154and a south pole156. Magnets described herein may also be referred to as diametrically magnetized ring. Magnet152is attached to flange38and therefore rotates with the flange during dose delivery. In one example, the magnet152is attached to the flange38with an attachment carrier as shown inFIGS.31-33. Magnet152may alternately be attached to dose dial32or other members rotationally fixed with the dose setting member. Magnet152may configured from a variety materials, such as, rare-earth magnets, for example, neodymium, and others a described later. Sensor system150further includes a measurement sensor158including one or more sensing elements160operatively connected with sensor electronics (not shown) contained within module82. The sensing elements160of sensor158are shown inFIG.11Aattached to printed circuit board162which is turn attached module82, which is rotationally fixed to dose button56. Consequently, magnet152rotates relative to sensing elements160during dose delivery. Sensing elements160are operable to detect the relative angular position of magnet152. Sensing elements160may include inductive sensors, capacitive sensors, or other contactless sensors when the ring152is a metallic ring. Magnetic sensor system150thereby operates to detect the total rotation of flange38relative to dose button56, and therefore the rotation relative to housing12during dose delivery. In one example, magnetic sensor system150including magnet152and sensor158with sensing elements160may be arranged in the modules shown inFIGS.13,25and35. In one embodiment, magnetic sensor system150includes four sensing elements160equi-radially spaced within module82to define a ring pattern as shown. Alternative numbers and positions of the sensing elements may be used. For example, in another embodiment, shown inFIG.11B, a single sensing element160is used. Further, sensing element160inFIG.11Bis shown centered within module82, although other locations may also be used. In another embodiment, shown inFIG.33andFIG.40, for example, five sensing elements906equi-circumferentially and equi-radially spaced within the module. In the foregoing embodiments, sensing elements160are shown attached within module82. Alternatively, sensing elements160may be attached to any portion of a component rotationally fixed to dose button56such that the component does not rotate relative to housing12during dose delivery. For purposes of illustration, magnet152is shown as a single, annular, bi-polar magnet attached to flange38. However, alternative configurations and locations of magnet152are contemplated. For example, the magnet may comprise multiple poles, such as alternating north and south poles. In one embodiment the magnet comprises a number of pole pairs equaling the number of discrete rotational, dose-setting positions of flange38. Magnet152may also comprise a number of separate magnet members. In addition, the magnet component may be attached to any portion of a member rotationally fixed to flange38during dose delivery, such as skirt42or dose dial member32. Alternatively, the sensor system may be an inductive or capacitive sensor system. This kind of sensor system utilizes a sensed element comprising a metal band attached to the flange similar to the attachment of the magnetic ring described herein. Sensor system further includes one or more sensing elements, such as the four, five, six or more independent antennas or armatures equi-angularly spaced along the distal wall of the module housing or pen housing. These antennas form antenna pairs located 180 degrees or other degrees apart and provide a ratio-metric measurement of the angular position of metal ring proportional to the dose delivered. The metal band ring is shaped such that one or more distinct rotational positions of metal ring relative to the module may be detected. Metal band has a shape which generates a varying signal upon rotation of metal ring relative to antennas. Antennas are operably connected with electronics assembly such that the antennas function to detect positions of metal ring relative to sensors, and therefore relative to housing12of pen10, during dose delivery. Metal band may be a single, cylindrical band attached to the exterior of the flange. However, alternate configurations and locations of the metal band are contemplated. For example, the metal band may comprise multiple discrete metal elements. In one embodiment the metal band comprises a number of elements equal to the number of discrete rotational, dose-setting positions of flange. The metal band in the alternative may be attached to any portion of a component rotationally fixed to flange38during dose delivery, such as dial member32. The metal band may comprise a metal element attached to the rotating member on the inside or the outside of the member, or it may be incorporated into such member, as by metallic particles incorporated in the component, or by over-molding the component with the metal band. MCU is operable to determine the position of the metal ring with the sensors. MCU is operable to determine the start position of magnet152by averaging the number of sensing elements160(for example, four) at a maximum sampling rate according to standard quadrature differential signals calculation. During dose delivery mode, sampling at a targeted frequency is performed by MCU to detect the number of revolutions of magnet152. At end of dose delivery, MCU is operable to determine the final position of magnet152by averaging the number of sensing elements160(for example, four) at a maximum sampling rate according to standard quadrature differential signals calculation. MCU is operable to determine from calculation of the total rotational angle of travel from the determined start position, number of revolutions, and the final position. MCU is operable to determine the number of dose steps or units by dividing the total rotational angle of travel by a predetermined number (such as 10, 15, 18, 20, 24) that is correlated with the design of device and medication. In one aspect, there is disclosed a modular form of the dose detection system. The use of a removably attached module is particularly adapted to use with a medication delivery device in which the actuator and the dose setting member both include portions external to the medication device housing. These external portions allow for direct attachment of the sensing component to the actuator, such as a dose button, and a sensed component to a dose setting member, such as a dose skirt, flange, or dial member, as described herein. In this regard, a “dose button” is used to refer more generally to a component of a medication delivery device which includes a portion located outside of the device housing and includes an exposed surface available for the user to use in order to deliver a set dose. Similarly, a dose “skirt” refers more generally to a component of a medication delivery device which is located outside of the device housing and which thereby has an exposed portion available for the user to grasp and turn the component in order to set a dose. As disclosed herein, the dose skirt rotates relative to the dose button during dose delivery. Also, the dose skirt may be rotationally fixed to the dose button during dose setting, such that either the dose skirt or dose button may be rotated to set a dose. In an alternative embodiment, the delivery device may not include a dose skirt, and a user may grasp and rotate the actuator (e.g., dose button) for dose setting. In some embodiments, with a dose detection module attached to the actuator and/or the dose skirt, the dose detection module may be rotated to thereby rotate the dose setting member of the delivery device to set a dose to be delivered. It is a further feature of the present disclosure that the sensing system of dose detection system80may be originally incorporated into a medication delivery device as an integrated system rather than as an add-on module. The foregoing provides a discussion of various structures and methods for sensing the relative rotation of the dose setting member relative to the actuator during dose delivery. In certain embodiments of medication delivery devices, the actuator moves in a spiral fashion relative to the pen body during dose setting. For illustrative purposes, this disclosure describes the dose detection system in respect to such a spiraling actuator. It will be appreciated by those skilled in the art, however, that the principles and physical operation of the disclosed dose detection system may also be used in combination with an actuator that rotates, but does not translate, during dose delivery. It will also be understood that the dose detection system is operable with other configurations of medical delivery devices provided that the device includes an actuator which rotates relative to a dose setting member during dose injection. Detection systems may also be employed with the module for identifying a characteristic of the medication to be administered by a pen injector. Pen injectors are used with a wide variety of medications, and even with various types of a given medication as already described. For example, insulin is available in different forms depending on the intended purpose. Insulin types include rapid-acting, short-acting, intermediate-acting and long-acting. In another respect, the type of the medication refers to which medication is involved, e.g., insulin versus a non-insulin medication, and/or to a concentration of a medication. It is important not to confuse the type of medication as the consequences may have serious implications. It is possible to correlate certain parameters based on the type of a medication. Using insulin as an example, there are known limitations as to the appropriate amount of a dose based on factors such as which type of insulin is involved, how the type of insulin correlates to the timing of the dose, etc. In another respect, it is necessary to know which type of medication was administered in order to accurately monitor and evaluate a treatment method. In one aspect, there is provided a sensor system which is capable of differentiating the type of medication that is to be administered. For determining the medication type, a module is provided which detects a unique identification of the type of medication, such as, for example, any one of the medications described herein, contained in the medication delivery device. Upon mounting the module to the medication delivery device, e.g., pen injector, the module detects the type of medication and stores it in memory. The module is thereafter able to evaluate a medication setting or delivery in view of the type of medication in the pen, as well as previous dosing history and other information. One example of detecting the type of medication is described later with identification sensor680inFIG.29. Another example is described next. This medication type detection is useful with a variety of sensor systems which are operable to detect a predetermined angular position of sensed elements relative to an alignment feature. These sensor systems include those previously disclosed herein. It is a further aspect that this medication type determination is readily combined with sensor systems for detecting the amount of a dose delivery. The two systems may operate independently or in concert with one another. In a particular aspect, the sensor system used for detecting dose delivery is also used to identify the medication type. For example,FIGS.10A-10BandFIGS.11A-11Band related text describe a magnetic sensor system which includes sensing elements160and a magnet152to determine the amount of a delivered dose. Magnet152has a unique configuration such that the sensor system is able to detect specific angular positions of magnet152relative to the sensing elements. The illustrative sensor system230is also useful as a system which is integrated into a medication delivery device, rather than being provided as a removable module. Referring toFIG.12, there is shown a medication delivery device310substantially the same as device10inFIGS.1-4. Medication delivery device310includes device body11and dose setting member30comprising dose dial member32, flange38, and skirt42. These components are configured to function as previously described. Actuator50comprises clutch52and dose button56attached thereto. Dose button56is rotationally fixed with dose setting member30during dose setting. For dose delivery, this rotational fixing is disengaged, and dose setting member30rotates relative to dose button56in proportion to the amount of dose delivered. Other embodiments of the dose detection systems described herein may be incorporated integrally into the device310. FIGS.13-15depict another example of the module, now referenced as module400, that is attachable to a medication delivery device having the dose button402including a cylindrical sidewall404and a top wall406disposed coaxially about a device axis AA. Top wall406of dose button402includes an upper or proximal axial surface408which is directly pressed by a user to deliver a dose when module400is not mounted on dose button402. Top wall406extends radially-outward of side wall404, thereby forming a lip410. Sidewall404extends between the upper surface408and a distal end as shown inFIG.14. Module400includes a housing411generally comprising a proximal wall412and a distal wall414. Module400further includes perimetric sidewall416extending between and forming a compartment418with proximal wall412and distal wall414. When mounted to a dose button, a distally facing axial surface413of distal wall414is illustratively received against upper surface408of dose button402. The walls of module400are shown in a particular configuration, but the walls may be of any desired configuration suited to forming compartment418. In one example, compartment418may be configured to resist entry of moisture and particulate matter. In another example, compartment418may be configured to resist dust and debris but not resist entry of moisture directly. Industry standards provide guidance for the different standards for moisture and dust protection. Having similar components as module82inFIGS.5-6, compartment418may include a various desired components for use with the medication delivery device, as disclosed herein. Such components may include, for example, measurement or other sensors, one or more batteries, MCU, a clock timer, memory, and a communications assembly. Compartment418may also include various switches for use as described hereafter. Any of the modules described herein can be removably coupled to any of the dose buttons described herein via an attachment element419coupled to module housing411. Attachment element419includes a plurality of distally extending arms420. As shown generally inFIG.13, module400is attached to dose button402by arms420which are attached to and extend distally from housing411. In an exemplary embodiment arms420are equi-radially spaced around dose button402. Arms420are depicted as being attached to distal wall414at attachment location422. Alternatively, arms420may be attached to module400at other locations, such as at sidewall416. Sidewall416may include a distal portion424disposed radially outward from arms420which extends distally from sidewall416a distance farther than the distalmost extension of arms420to at least partially or fully cover arms420to inhibit tampering or access to arms when mounted to device. Distal portion424may include an inwardly-extending portion426which further encloses arms420. Alternatively, distal portion424may be provided as a member which is slidable relative to sidewall416. Arms420are configured to move over lip410of dose button402and to provide frictional engagement with a radially outward facing surface421of sidewall404. Arms420include a first portion428extending axially and configured to extend beyond lip410. Arms420further include a bearing portion430extending radially-inward of first portion428and received against radially outward facing sidewall404of dose button402. Portions428,430may be joined by a rounded base429coupled between them to form a “J” shape with the first portion428forming the staff portion and the base and bearing forming the hook end. Bearing portion430may include an axially-bearing portion432received against the underside of lip410. This provides added resistance to proximal displacement of module400relative to dose button402. However, the engaged surfaces of the underside of lip410and axially-bearing portion432may be provided with angled surfaces to facilitate removal of module400when desired. In one example, each of arms420is radially movable to clear the lip410during attachment to and detachment from dose button. In one example, both portions428,430flex outward, and in some examples, only one of the first portion428or bearing portion430flexes outward to move over lip. Arms420may be biased in a radially inward configuration and may be deflected or pivoted outward about attachment location422. In the biased configuration, arms420are adapted and sized to apply radial normal force against a number of engagement spots along the surface of sidewall404that is suitable for axial retention to dose button402, as well as torque transmission (without or little acceptable slip) during dose setting and/or dose dispensing. An assembly434including arms420attached to distal wall414(shown as molded or manufactured component) is shown inFIG.15. For purposes of fabrication, arms420and other components are combined with distal wall414(shown as a radially outward surface of wall414), which is then attached to other parts of module400.FIGS.16-17shows the distal wall414and some of its component parts. Distal wall414includes an aperture436formed therein to allow an identification sensor, described hereafter, to view the upper surface408of dose button402. Light guide aperture436may have a variety of shapes, including the “D” shape as shown. Another opening438formed therein accommodates a presence switch, also described hereafter, to enable module400to determine when it is mounted upon dose button402. In one example, the opening438is omitted from distal wall414. Sensor receiving recessed locations440are provided in the distal wall for radially spaced placement of four measurement sensors, e.g., magnetic, inductive, or capacitive sensing elements as previously disclosed. The depth of the recesses440is sized to place the sensors in close proximity to the sensed component, while leaving sufficient material thickness to structurally support the sensors during manufacturing and use. Recesses440allow for secure fixing of the sensors so that the sensors maintain their respective locations for more consistent sensing capability. Recesses440are arranged to place the sensors are disposed equi-angularly (four sensors at 90 degrees apart (as shown); five sensors at 72 degrees apart, six sensors at 60 degrees apart, etc.) relative to one another and equi-radially disposed from the module longitudinal axis. Walls defining the recesses440are also structured to disposed the sensors along a common plane. Other ports may be provided for venting of the module. Attachment axial wings441may be provided for coupling distal wall414to a complementary attachment feature of the module housing. The number of arms420may vary, such as, for example, in the range of 3 to 36, due to desired axial retention force and/or torque transmission. Arms420are depicted as being attached to distal wall414at attachment location422defines by posts, which may be a single post or a pair of posts442,444as shown. Assembly434is shown including sixteen arms420. Assembly434is shown including four pairs of mounting posts442,444that are circumferentially spaced around the perimeter of distal wall414. Each pair of mounting posts is configured to support a circumferential segment445having a plurality of arms, such as four arms each. Each segment445includes mounting holes446which receive the mounting posts442,444. Once received in position, the mounting posts442,444are used to heat stake the arm segments to distal wall414in a securely fixed manner. The attachment of the arms420to the housing allows for fabrication of the arms from a variety of materials. These materials may be selected to obtain desired features of strength, elasticity, durability and the like. For example, it has been found that beryllium copper has advantageous properties for use as the arms. The separate attachment also provides flexibility as to the placement of the arms relative to the dose button. For example, the arms may be mounted to various walls of the module, including distal wall414, sidewall416, or distal portion424. Arms420may be suitable for different configurations of surface421of dose button402.FIG.14illustrates the surface421have a smooth (without ribs or grooves or planar variations). The surface421of button may include surface features to enhance torque transmission with arms420. Other embodiments may be used for the interaction between the arms and the perimetric wall of the dose button.FIG.18, for example, shows another example of a dose button470for a device including a sidewall472having spaced, axially-extending ridges474, forming a series of recesses476therebetween. In this embodiment, portions of arms420can be receivable within recesses476. Arms420may be suitable for another configuration of ridges shown inFIG.22. The circumferential width of recesses476may be sized to receive the circumferential width of arms420. The sizing may allow for a snug fit or may allow some circumferential freedom of arm movement. The presence of the adjoining ridges provides further assurance that the module will not rotate relative to the dose button during use.FIG.19shows an alternate design in which dose button480includes a sidewall482provided in a polygonal shape, thereby defining a series of flat surfaces484for reception of the arms of the module. Separating adjacent flat surfaces484is a rounded axial joint485. The use of a flat, smooth cylindrical surface avoids any issues regarding orientation of the module relative to the dose button, while the recessed and polygonal designs provide additional frictional engagement of the arms with the sidewall of the dose button. FIGS.20-24illustrate another example of a module attachment subassembly, now referenced as unit500, configured, when part of a module, to be removably coupled to any of the dose buttons described herein via an attachment element519. Attachment element519is coupled to a tubular attachment housing511(although other parts of the module housing are omitted, aspects of these parts to define a full module housing are shown inFIG.13andFIG.25). Attachment housing511with the attachment element519may form a part of the module600as will be described later. Attachment element519includes a plurality of distally extending arms520. As shown generally inFIG.20, unit500when part of a module is attached to another example of dose button502by arms520which are attached to and extend distally from housing511, and in particular distally from annular housing portion517of housing511at recessed areas defined by the distal wall514. The annular housing defines a cavity to receive for example at least partially electronics. In an exemplary embodiment arms520are equi-radially spaced around dose button502. Arms520are depicted as being coupled to and depending from a distal wall514of attachment housing511. FIG.21depicts arms520being resiliently configured to move over lip510of dose button502and to provide frictional engagement with a radially outward facing surface521of sidewall504of dose button502. With additional reference toFIG.23, arms520include a bearing portion530extending radially-inward of the axial body of arms520and received against radially outward facing sidewall504. Bearing portion530may include a protruding body531extending radially inward from the interior surface of arm520. Protruding body531may include an axially-bearing surface532to be received against or place in close proximity to the underside533of lip510shown inFIG.24. This provides added resistance to proximal displacement of the module relative to dose button502when attached. Protruding body531of bearing portion530may include a distal facing end537. The surface532and/or distal facing end537may be angled at any angle to give the protruding body531a tapered profile. Protruding body531may include a radially facing engagement surface538having an axial length extending between surface532and end537. Engagement surface538may by planar, rounded (as shown), tapered or V-shaped. As shown inFIG.23, protruding body531may have a smaller width than the width of the arm520. In another example, the arms may include more than one protruding body arranged to fit within adjacent ridges or alternating ridges. FIG.22depicts the sidewall504of dose button502includes a plurality of spaced, axially-extending ridges545, forming a series of recesses547therebetween. Button502also includes a proximal wall with a proximal upper surface508. At least a portion of the proximal surface508may have a color to correspond to a unique kind of medication and/or dosage. The button502with color is representative of all the other buttons described herein as those other buttons may have similar color schemes. To this end, any of the modules described herein can be attached to different kinds of pens, and with the use of color detection the module can communicate the identification information to an external device. The module and/or external device may determine a different number of units of medication delivered for the same amount of total rotation due to the pen having a unique rotational profile for a given medication and dosage. In one example, the entire upper surface508of the button502is a single color. In another example, a surface feature or region507A, such as recess or a protrusion or the center of the button surface, may have a first color, and a region507B adjacent to the surface feature or specific region may have a second color different than the first color. The medication identification sensing described herein may be directed to the first color or the second color depending the module's configuration. In this embodiment, at least a portion of the bearing portion530of arms520are receivable within recesses547. In one example, the circumferential width of each of the recesses547may be sized to receive the circumferential width of engagement surface538of bearing portion530, and in other embodiments, recesses547may be sized to receive a tip end portion of the engagement surface of any of the tips of the arms described herein, such, as, for example, as shown inFIG.20. The circumferential width of each bearing portion530may be oversized to fit over the recesses547, engaging adjacent ridges without going into the recesses. In one embodiment, the proximal extent549of the recesses547may extend within the radial lip510. The depth D1of the recesses547, shown inFIG.24, may be constant along the axial extent of the recess. In other examples, the depth of the recesses547may vary along the axial extent, such as, for example being sized to be deeper toward the proximal end than toward the distal end of recess547. Arms520may also suitable for other button surfaces, such as, for example, shown inFIGS.14,18, and19. The overhang axial distance O of axially-bearing surface532of arms520relative to the distally facing axial surface513of distal wall514may be larger than the axial depth D of the radial lip502. With reference toFIG.24the amount of extension length of the arms520, beyond a plane defined by the distally facing axial surface505of distal wall506and orthogonal to the axis AA, may be sized to place the bearing portion530along the radially outward facing surface521of sidewall504of dose button502. In one example, extension length is sized to place the bearing portion530along only a proximal upper portion509of the sidewall504such that a distal lower portion of the sidewall504remains unengaged by any portion of the arms. The dose button shown inFIG.24includes an axial height H measured between the upper surface508of the dose button502and the distal end511of the dose button502. The distal end513of the bearing portion530, that is, the distalmost part of the bearing portion530that is in direct engagement with the sidewall504, of arms520engages the surface521of sidewall504at an axial distance HL, thereby placing the surface engagement portion538of bearing portion530between the radial lip510and the engagement location of distal end513against the sidewall. The bearing portion may axially extend between the underside of the rim510and the engagement location of the distal end513that is located along the upper half of the sidewall504. Axial distance HL is measured between said plane defined by the surface505that is against the upper surface508of dose button502and such engagement location of the distal end513, as shown inFIG.24. In one example, the axial distance HL may be sized up to 50% of the axial height H of the dose button502to place the bearing portion530along the proximal portion509of sidewall504. This position may reduce the spatial impact of the arms within the attached module placed the button. Engagement surface538of the bearing portion530is sized axially larger than the axial thickness of the radial lip510for greater radial force. The bearing portion530of the arms520in a more axially compact configuration as shown may reduce the amount of axial travel and friction causing forces of surface538of the bearing portion along the rim510, and thereby reducing the attachment and/or detachment force for the user. A more axially compact bearing portion of the arms may also reduce the amount of duration for attachment and/or detachment of the module so that user is not left doubting whether attachment was successful. FIG.21illustrates each of arms520is radially movable in a direction of arrow535to clear the lip510during attachment to (or moving module in a proximal direction P relative to the dose button) and detachment from dose button (or moving module in a distal direction DD relative to the dose button). Arms520may be biased in a radially inward configuration and may be deflected or pivoted outward about where the arms depend from the distal wall514. In the biased configuration, arms520are adapted and sized to apply radial normal force against a number of engagement spots along the surface of sidewall504that is suitable for axial retention to dose button502, as well as torque transmission (without or with little acceptable slip) during dose setting and/or dose dispensing. In other words, during dose setting the unit500that is coupled to button502is rotated in a first direction that moves the module/button farther away from the device housing. With any of the attachment elements described herein, such as elements419and519, the attachment force that the user applies in the distal direction DD may be less than the detachment force that the user applies in the proximal direction P. The detachment force may be in the range of 4 N to 30 N. In one example, the arms are configured such that the detachment force is at least 1.5 times the attachment force, and may be at least twice as large as the attachment force to inhibit inadvertent detachment of the module. In one example, the detachment force is over 20 N and the attachment force is under 11 N. In other examples, once the module is attached to the device, a small degree of slippage of the bearing portions along the dose button due to torqueing from dose setting may be permissible in order to avoid over-torqueing and potential damage to the dose setting device components. The arms520and housing511may be formed as an integral unit, such as with molding of a plastic material, such as an acetal thermoplastic (for example, Delrin®), or polycarbonate material (for example, Makrolon®). Such an integral unit561is shown inFIG.23. The plastic materials may be selected to obtain desired features of strength, elasticity, durability and the like. Alternatively, the arms520may be separately made from the housing and later attached via an adhesive or welding. The number of arms520may vary. In the example shown, there are four arms positioned circumferentially spaced equally apart. In some examples, three arms may be provided, in other examples, 5, 6, 7, or 8 arms may be provided. The arms described herein, such as arms420or520, provide a convenient and effective attachment of the module to the dose button. As the module is intended for use on multiple medication delivery devices, the module attachment allows for ready attachment and removal of the module relative to the dose button. This derives from the arms described herein having suitable configurations and physical properties to set the amount of force required to attach/detach the module. The arms described herein are also configured to have sufficient durability for repeated attachments to medication delivery devices, and to retain elasticity to provide proper securement and retention to the button without the use of a separate retainer piece, such as a coiled spring or ring, disposed along the outside to provide radially compressive force. Once mounted to a medication delivery device such as, for example, with the use of any one of the attachment elements419or519, the module is frictionally engaged with the dose button. This allows for use of the module to rotate the dose button as desired, such as during dose setting for some medication delivery devices. The surface engagement of the bearing portions of the arms described herein may be controlled through various parameters. Frictional engagement depends on such factors as the force applied normal to the module surface and the coefficient of friction applicable for the contacting surfaces. The applied radial force is dependent, inter alia, on the sizes and shapes of the arms, the elasticity and resilience of the arms, and other factors. The disclosed attachment elements allow for selection among these and other parameters in order to provide the desired balance to frictionally lock the module with the dose button for rotation, and to allow for ready attachment and detachment of the module relative to the dose button. Any of the modules described herein may include one or more switches to facilitate use of the module, even though the following description is related to the module600. As previously described, the module is releasably attached to a medication delivery device. When desired, the module is removed from one medication delivery device and then is useful in conjunction with another medication delivery device. One skilled in the art would appreciate that various attachment elements described herein may be used for such coupling to the device. Referring toFIGS.25-28, the module600includes a proximal wall assembly602, sidewall604and distal wall606. Walls602,604,606of module600thereby defines an internal compartment608configured to house an electronics assembly610. Wall602may include a transparent or translucent material around the upper edge to provide a light guide when LEDs are employed. Although the attachment element607is illustratively shown as the attachment element419inFIG.15, it should not be limiting as module600can also be provided with any other attachment unit described herein. In such configuration, proximal end opening of the tubular attachment housing511is sized to fit over the circumferential outer surface609of distal wall606with a friction fit or otherwise securely fixed. In this configuration, distal wall606is illustratively shown inFIGS.16-17as the distal wall414(with the feature such as, for example, openings438,436and features440,441), with the exception of the posts442,444and block protrusion disposed between the posts442,444are omitted, thereby providing a smooth outer surface606A of distal wall606that is sized and shaped to receive the unit500. FIGS.25,26,27and29show an example of electronics assembly610that may be used for any of the modules described herein. Assembly610includes a first distal segment612, a second proximal segment614, and a third intermediate segment616therebetween, each having electronically connected by connections and leads, shown generally at618A-B. Segments612,614,616may be coupled coaxially disposed over one another in an “S” pattern. Battery621is shown axially disposed between the first and third segments612,616and captured by resilient arms. The second segment614may include sensor pockets623defined therein for receiving the measurement sensors, such as, for example, sensing elements160. Pockets623are aligned and inserted within recessed locations440of distal wall of module housing. Alternatively, instead of pockets623, the measurement sensors may be coupled directly to the second segment circuit without the pockets. InFIG.27, the first segment612includes a proximal facing surface615and includes an example of a switch622of a wake-up switch system620mounted thereon. Module may include indicator elements624, such as LEDs for indication of operator status of device and/or module. In one example, the indicator elements624are operably mounted to surface615of first segment612. Activation of wake-up switch622may be used to turn on relevant electronics, such as those associated with the delivery of a dose. For example, wake-up switch622may turn on the measurement sensor, such as, for example, the sensing elements160, involved in the measurement of a dose delivery generated by rotation of the sensed element. LEDs or other indicator elements, such as, audible speakers and/or vibration generators, may be used to notify the user of the progression of the system through completion of the dose delivery or notify the user between periods of dose delivery, such as, for example, battery charge indication. In one example, LEDs are mounted on the sides of the switch622. Wake-up switch system may be configured to increase the power to the electronics from a low power state to a full operation state. Any of the module described herein may include a wake-up switch system620. The provision of such wake-up switch with a module may be optional. In one example, the module600shown inFIGS.25-26includes the wake-up switch system620which includes an axially movable segment626disposed within a recess defined in the upper surface of the proximal wall assembly602. Wake-up segment626is able to move distally into module600, and has a biased configuration as shown. Wake-up segment626may for example comprise a flexible disc-shaped member which is normally in a proximal position, or it may be a member that is biased proximally such as by springs (not shown). The material of the wake-up segment may allow for some deflection of the center627of the segment626relative to the circumferential edge629of the segment626. Segment626may be a rigid member slidably disposed along walls defining a recess within the proximal portion602of the module housing. Segment626may include an anchoring segment (not shown) movably coupled to the module housing such that that when segment626is in its biased proximal position, segment remains within module housing without exiting the module. Walls630of proximal wall assembly602may be shaped to define a proximally facing axial surface631configured to define a physical stop or its distalmost position for the distal travel of the segment626from its biased proximal position. Walls630define a smaller sized portion of the throughbore632extending axially along the axis AA through the proximal wall602. When user distally actuates the wake-up segment626, the axial force is sufficient to overcome the biasing force of the spring (not shown) and allow distal movement of the segment626until directly or indirectly causing activation of the switch system620. This axial force to actuate wake-up is less than the axial force to cause actuation of the delivery device for dose delivery. In one example, segment626may be distally moved to engage the axial surface631, while the walls630defining the throughbore632may be sized and shaped to allow continued axial deflection of segment626distally beyond the axial surface630such that there is sufficient to activate the switch system620. The switch shown includes a mechanical switch or rubber dome switch, while other switches are contemplated such as electrical contacts. Switches described herein can be mechanically actuated or triggered by engagement with another component. In one example, switch system620may further include a flexible shroud635configured to limit the travel of distal deflection of segment626when pressed by user to inhibit damage to the wake-up switch620. Shroud635may be axially located between the segment626and the switch622. Axial force from the user may be transmitted via the segment626to shroud635to cause central portion638of shroud635to axially deflect to engage the trigger of the switch622. Shroud635may be configured to have a maximum distal extent of deflection. Such distal extent may be sized to allow engagement of the switch trigger but not farther to a position that may damage the switch. Shroud may have various sizes and shapes for such functionality. FIG.28illustrates one example of shroud635, including a plurality of radial legs640circumferentially disposed relative to one another, extending from a centerpoint of a hub642that surrounds central portion638of shroud. Centerpoint of hub is located coaxially with the axis AA. The hub642and central portion638may have any shape, and may be rectangular, oval, or circular as shown. The central portion642may include a concaved region that extends the hub in the distal direction relative to the surrounding hub region radially outside the concaved region. The end tips643of a first set of legs640A may be coupled to anchor portions644, such as for example the distal surface of anchor portions644having a slotted region sized and shaped to receive the size and shape of the tips643. Anchor portion644extend distally from axially movable segment626, which place the anchor portions644on top of the tips643. Anchor portions644moves axially with segment626within throughbore632when user applies axial force thereto. Anchor portions644may be integrally formed with the segment626such as from molding or portions644may be formed separately and fixedly secured to the distal surface of segment626. The tips646of a second set of legs640B may be free or remain unengaged with the segment626. The first set of legs640A may be contacted by anchor portions644at equi-angularly locations to distribute the axial force and deflection to each of the legs640. In one example, the first set of legs640A are shorter in radial length than the longer second set of legs640B. The first set of legs640A may radially extend directly in between adjacent legs of the second set640B. While all of the legs640may provide flexibility to the shroud635, the free legs640B can inhibit the shroud636to have the maximum distal extent of deflection while force is axially transmitted from segment626to the tips643via the anchor portions644to move the tips643within the throughbore632. In the example shown, there are eight total legs640each disposed radially from the centerpoint by 45 degrees apart. The shorter fixed legs may be disposed 90 degrees apart, and the longer legs may be disposed 90 degrees apart and radially offset relative to the shorter fixed legs. Other numbers of legs and their relative positions may be used. In one example, the electronic assembly610is powered on from a sleep state by axial movement of segment626and shroud635caused by a user to a degree to contact the axial trigger of switch622, such as, for example, without any distal movement of the module and/or dose button. In the alternative, the wake-up switch may include one or more leaf spring electrical contact elements that are biased away from contact with corresponding contact pads mounted on the first segment, and are movable for contacting the contact pads from force transmission via the member626. In some examples, power on of electronic assembly occurs by simultaneous contact of each of the contact elements. Any of the module described herein may include a presence switch system650. The provision of such presence switch with a module may be optional. According toFIGS.25,26and27, module600includes presence switch system650mounted to distal wall606in a manner to detect when module600has been mounted to or removed from a medication delivery device. A presences switch652of system650is operably connected to the proximal face617of the second segment614of electronics assembly610. Switch652includes a pivot switch arm654positioned at least partially overlapping the opening657(see opening438inFIG.16) defined by distal wall606. Distal wall606may include the same layout (or substantially the same layout) of features, such as, for example, openings438,436and features440,441, shown inFIG.16-17. Switch arm654of switch652has a biased position (shown inFIG.27) and a distal position (shown in dashed lines). As represented inFIG.25-26, switch system is movable from its biased distal position (as shown inFIG.26) representing the absence of a medication device, to a proximal position (shown inFIG.25) indicating that module600is mounted to a medication delivery device. Presence switch system650includes a switch actuator660that is mounted to distal wall606. Actuator660includes a first member662in a nesting relationship with a second member664. The second member664has a cup configuration defining a cylindrical cavity to receive the first member662. The second member664is slidably disposed through opening657. The second member664includes an outer radial lip663along its proximal end and housed within module to enhance the inhibition of particulates and/or water ingress. Though the radial lip663is shown inFIG.25disposed away from distal wall, the radial lip663may remain engaged with the distal wall, such as shown inFIG.26, when the module is attached to the device. The second member664may be made of elastomer or soft plastic material for flexibility. Second member664is movable within the module housing to a proximal position by direct engagement with the device when mounting the module to the device. First member662is shaped and sized to fit within the cavity defined by the second member664. First member662includes a cylindrical body666extending axially between its proximal and distal axial ends. An outer radial rim668is shown extending from an intermediate segment of the first member body666such that a distal hat segment670is defined for insertion into a distal end of an actuator spring672. The actuator spring672is fixedly secured at its proximal end to an internal component of the module housing, and the actuator spring's distal end is bearing on the rim668and movable therewith. Rim668may include a distal skirt674depending from the distal surface of the rim668. In one example, the distal skirt674is coupled to the outer radial end of the rim. The rim668may comprise of diametrically disposed radial elements instead of a continuous circumferentially element. Under the biasing force of the actuator spring672, the first member662is in a nested position within the second member664and the rim668of the first member662is configured to contact and distally move the switch arm654to place the system at its biased distal position when the module is removed from the device. Switch system650in its distal position indicates electronically the module is not mounted to a device, and power limitations may be programmed into the processor to perform minimal functions. Skirt674may provide radial pressure along the lip663of the second member against the interior surface of distal wall606to enhance inhibition of particular ingress. Upon coupling the module to the device, the exterior end of the second member664with the first member662is in a nested position contacts the dose button of the device and force is transmitted to the rim via the body of the first member to overcome the force of spring672, thereby causing the first and second members to move proximally within the module housing and thereby allowing the switch system to return to the proximal position. Switch system650in its proximal position indicates electronically the module is mounted to a device, and full power may be programmed into the processor to perform all functions. Actuator660is biased in the distal direction by spring672, and normally extends distally out of opening657when module600is not mounted to a medication delivery device. As shown somewhat diagrammatically inFIG.25, mounting module600to any one of the dose buttons described herein, generally601, causes the upper surface of dose button601to press actuator660proximally, and this movement in turn moves switch arm proximally, triggering presence switch652. MCU of electronic assembly610recognizes the proximal position of switch arm654as a confirmation that unit500is mounted to a medication delivery device. In response, MCU wakes up or provides power to relevant components of electronics assembly610in preparation for use of the medication delivery device. When module600is subsequently removed, spring672moves actuator660back outside of distal wall606and switch arm654returns to its distal position identifying that module600is not mounted to a medication delivery device. MCU then returns the medication delivery device to a non-use state, such as by turning the module systems off or setting them in a sleep mode. One example of electronic assembly610is shown schematically inFIG.46. Illustratively, any of the modules described herein, such as module600, may also include a sensor for identifying the type of medication delivery device, or the type of medication contained by the medication delivery device. Referring toFIG.29, the identification sensor680is operably connected to the distal face617of the third segment616of the electronic assembly610. The second segment614includes a window opening682defined therein. Identification sensor680is located over window opening682and aperture684of distal wall606(see aperture configuration and layout in aperture436inFIGS.16-17) to be able to view the exposed surface of dose button601. A recess686may be formed along the distal face of the distal wall606that overlaps the aperture684. The recess686may receive a coupled lens or shield therein to aid in keeping debris out. Dose button601is provided with indicia visible to type sensor680through aperture684. The indicia correlate to information concerning the medication delivery device, such as the type of device or the medication contained by the device. Identification sensor680reads the indicia and MCU recognizes the indicia as indicating the medication delivery device information. A light guide member685may be disposed within the aperture684to provide an optical path for the identification sensor. Securing light guide member685to distal wall606, such as, by snap fit or adhesive or ultrasonic welding, can prevent light and sensing distortion caused by relative movement or vibration of the light guide member. Light guide member685, which could be made from a transparent or translucent material, such as, for example, a polycarbonate, is shown extending axially between the upper surface of the button601and the opening682. Recess686may be also be configured to receive an enlarged base portion of the light guide member685. By way of example, identification sensor680may comprise an RGB source(s) and sensor to detect color reflected from the dose button and the indicia may comprise different colors, each color being associated with specific information regarding the medication delivery device. Shielding elements may be provided to guide RGB light sources axially to button and to inhibit premature reading of light form sensor. Alternatively, the indicia may comprise grey scale, patterns, or other material that is optically recognizable. In addition, more than one type sensor may be employed to enhance the detection of information regarding the medication delivery device. In one embodiment, identification sensor680, is positioned to detect the near-center or center of the proximal upper surface of dose button601. The indicia may at the same time comprise patterns symmetrically positioned around the center of dose button601, such as concentric color rings. With type sensor680so located, presence switch652is positioned displaced from the center of module600. In use, identification sensor680is activated with module600mounted to a medication delivery device. In one example, presence switch652detects the mounting of unit500on a medication delivery device and identification sensor680is activated at that time. Whenever collected, the sensed information concerning the medication delivery device may be stored and/or transmitted. Module600may then be moved to a lower power mode, such as after a predetermined time period, until reactivated during dose delivery. As shown diagrammatically inFIG.27, light indicator elements624(shown as LEDs), or other signaling devices, may notify the user of the various states of module600, as well as other components including the medication delivery device itself. For example, a light signal may be used to indicate the type of medication delivery device or the medication contained by the medication delivery device. Another signal may be provided to confirm the proper placement of the module on the medication delivery device. Further, a signal may indicate the transition of module600to or from various states, such as waking up or sleeping conditions. Indicator elements may be operable to indicate in one form (such as green) successful attachment or in another form (such as amber) unsuccessful attachment between the module and the dose button of the device. Assembling of the module may be configured in consideration of high volume manufacturing. The following steps may apply to any of the modules described herein, with general reference toFIGS.25and27, and in alternative sequential order than what is described below. The distal wall606as a component is provided in the orientation and arrangement shown inFIG.16. The switch actuator660with the first and second elements is inserted through opening657with the rim668of the first element sized to fit within the axial slots formed by upstanding walls surrounding and extending from the edge of opening (as shown inFIG.16). Actuator spring672is placed on top of the actuator as shown inFIG.25. The second segment614is placed with the interior of the distal wall component in alignment around the various features and openings formed along the distal component. An axial spacer component675(shown inFIG.25) is placed over top of the second segment614and the distal wall. Spacer675includes alignment features to position the segments at a predetermined relative distance. The segments are then folded over along connection618A in order to place the third segment616proximally on top of the spacer675. Battery621is disposed on top of the third segment616and configured to operably provide power to all of the segments. The first segment612is then folded over along connection618B in order to place the first segment612proximally on top of the battery621. Attachment elements are then coupled to distal wall606, either sliding over the distal wall606with the unit500with arms520with the bearing portion as described previously or attachment with the arms of the attachment element419as described previously. Proximal wall portion component602is positioned over the first segment612and includes attachment features for securely attaching to the distal wall606including attachment to the attachment axial wings shown inFIG.16to form a preassembly. Proximal wall portion602may include the axially movable segment626and the shroud635assembled together as descried herein prior to attachment to the sidewall604. Tubular configured sidewall component604is slidably placed radially surrounding the preassembly and its proximal end fixedly secured to the proximal wall portion606. Distal skirt portion677is fixedly secured to the distal end of the sidewall604to thereby form a completely assembled module. Referring toFIG.35, another embodiment of the module, now referred to as module800, includes the proximal wall802, sidewall804and distal wall806. Walls802,804,806of module800thereby defines an internal compartment808configured to house the electronics assembly810. Proximal wall802may have a disk shape and form the finger pad that user presses for device operation. Module may include a ring812of transparent or translucent material around the upper edge to provide a radial light guide when a light source, such as, for example, LEDs, is employed, such as shown inFIG.27. Such light source may be located on the proximal surface of a circuit board809of the assembly810and is positioned to emit light through the opening813defined by the light guide ring812. Confronting surfaces of the ring812and proximal wall802, respectively, may be securely fixed to one another to define the proximal wall assembly of the module housing. In one example, the secure attachment may be by an adhesive, gluing, ultrasonic welding, or the like. In another example, the secure attachment may be a two-sided sticky tape860. The proximal wall assembly may include a white surface or reflective surface disposed covering the opening813for improved radial light transmissivity within the light ring812that is emitted through the opening813. The distal surface of the proximal wall may include the white or reflective surface. In one example, the distal surface862of the tape860includes the white or reflective surface, and in other examples a disk element with a white or reflective surface may be used. The proximal wall assembly described herein may only refer to the proximal wall without the light ring. Ring812may include an attachment element to attach to another module component. For example, ring812may include a plurality of retention snap arms812A depending from a distal surface of ring812. Arms812A are configured to permit axial movement of the proximal wall relative to the housing and including tips configured to prevent removal of the ring812to a certain position. A button gasket811having a ring shape is shown engaging the distal surface of ring812and is disposed radially outward relative to the arms812A.FIG.47depicts an exploded view of one embodiment of the module, such as module800, separated into its individual components along a common axis. Module may include a first spacer element815having a ring shape and defining an inner radial surface817disposed along the circumference defined by the snap arms812A. Surface817configured to allow controlled axial movement of the proximal wall assembly from the proximal position to the distal position for wake-up capability. The distal surface of spacer element815along the inner radial surface817provides an area for the snap arms812A to engage for retention as the proximal wall assembly returns to the proximal positon under the biasing force. In some embodiments, the light ring is omitted and the proximal wall includes the snap arms for engagement with the surface817. Spacer element815may include a proximal flange819A disposed along the radial outward extent of the spacer element. The upper end of flange819A can provide a physical stop to limit distal movement of the proximal wall802. Spacer element815may include a distal flange819B disposed along the radial outward extend of the spacer element and recessed radially inward relative to the proximal flange819A. The recess may be sized to accommodate the thickness of sidewall804when the upper end of the sidewall engages the radial outer surface of the distal flange819B. Button gasket811is disposed axially between the proximal wall802and ring812and a housing portion in the form of the spacer element815. In one example, the button gasket811is engaged between ring812, or the proximal wall if there is no ring, and element815. Gasket811is axially compressible from its natural state. The gasket material, such as for example, a cellular urethane form, may be configured to provide compressibility. The material of gasket811may also provide sealing from liquid egress, but allowing the ventilation. In other embodiments, the gasket material may provide sealing from liquid and air egress. In its natural state, the gasket811may provide a biasing force and support along the outer circumference of the proximal wall assembly to maintain the proximal wall assembly in its extended proximal position. When a user presses down on the proximal wall to use the device, the button gasket811may axially compress as the ring/proximal wall unit moves distally relative to the spacer element815that is in a fixed position. The gasket811may aid in returning the proximal wall assembly to the extended position and provide consistent tactile feedback to the user throughout its movement. Instead of the compressible gasket, a spring with lining or other sealing means may be used. Module may include a second spacer element821disposed distal to the first spacer element815in between the element815and distal wall806. Second spacer element821has a ring shape. The second spacer element821is coupled to the first spacer element815, such as, for example, each having axially extending features that allow for coupling. Battery861is shown disposed between elements815,821. A battery retainer element (not shown) can be coupled to the proximal surface of the second space element. A battery support element864may be included between the proximal side of the battery and one of the circuit boards of the electronics assembly, and in frictional contact with the battery to inhibit movement of the battery within the module. In one example, the battery support element864may include a ring of axially compressible material, such as, closed cell foam. The element864may have a cross-sectional area less than the battery's cross-sectional area. Sidewall804is shown disposed radially outward relative to the contents of the module and axially extended between the first spacer element815and a base ring823that is coupled to the distal end of the sidewall804. Base ring823may be optional. Sidewall804may include a plurality of distally extending retention snap arms804A for engaging with correspondingly shaped recesses formed along the interior surface of the base ring823in a manner to securely fix the components together. Snap arms804A may be disposed radially inward from the general outer circumference of the sidewall804to define a recess sized to receive the general thickness of the upper end of the base ring823. A seat804B may be formed along the interior surface of the sidewall804, extending farther radially inward of the surface. Seat804B is configured to receive a distal gasket825. Distal gasket825has a ring shape and is disposed radially between the interior surface of sidewall804and the outer circumference of the distal wall802, and axially between seat804B and a seat827A defined by a radial flange827extending from the distal wall802. In one example, gasket825is sealably engaged between sidewall804and distal wall802. Gasket825may be made from a gasket material, such as for example, a cellular urethane form, may be configured to provide compressibility. Although the module800is shown with the presence switch omitted, a presence switch system, such as, for example, the system650described earlier may be incorporated into the module as can be appreciated by those skilled in the art. Module800is shown including another embodiment of a wake-up switch system, now referred to as wake-up switch system820. Although wake-up switch system820is illustratively shown, it should not be limiting as module800can also be provided with the wake-up switch system620. Similarly, the other modules described herein may include wake-up switch system820. With additional reference toFIG.36, wake-up switch system820includes one or axially moveable contact arms822and a corresponding contact pad824coupled to the circuit board809, which can be the flexible printed circuit board (FPCB), of the electronics assembly810and in electrical communication with the MCU. Contact arm822is able to move distally from a biased, non-contact natural configuration, as shown in the figures, where the contact arm822is axially spaced from the contact pad824such that there is no electrical communication (thus electronics in a low power state) to a contact configuration by which the contact arm822and contact pad824are in a contacting relationship such that there is electrical communication between the two (thus increasing power to electronics to the full operation state). Contact arm822may have a pre-load to maintain contact with the proximal wall802along different axial positions of the movable proximal wall. The biasing may be provided by a discrete spring or the contact arm822may have a leaf spring configuration, such as shown. In one embodiment, the contact arm822includes a base830fixedly mounted to the circuit board809, a movable arm length portion832coupled to the base830via a joint834. The arm length portion832is capable of pivoting motion relative to the base830about the joint834. The biasing force from the contact arm822may be sufficient to maintain the upper proximal wall802in a proximal first position. When a user distally actuates the proximal wall802, the axial force is sufficient to overcome the biasing force of the contact arm822and allow for the distal movement of the proximal wall802away from its first position to a distal second potion where the contacting arm822and contact pad824are in contact for activation of the switch system and/or wake-up of the control system. Movement of the proximal wall802may occur relative to the module housing that is in a fixed position during this action to power-on the system without an actuation force on the actuator. Movement of the proximal wall802may also occur relative to the module housing that is in the process of moving to a final distal position during the actuation force on the actuator to cause dose delivery. The switch system820may include alternative switch configurations, such as, for example, a mechanical switch or rubber dome switch. Contact length arm portion832may extend from the base830at an acute angle relative to a plan defined by the base830, although the angle of extension of the arm portion may be orthogonal or acute relative to the base. From a radial view perspective, the contact arm may have a V-shaped body. In one example, any part of the arm portion832may include a contacting portion contactable with the contact pad824. In one embodiment shown, the tip end835of the arm portion832defines the contacting portion. In another embodiment, the contacting portion is along the intermediate body of the arm portion832. The contacting portion of the arm portion832may be configured for enhanced contacting the contact pad824, such as, for example, including a polished or smoothed surface and/or a rounded surface or hook shape and/or a domed surface (such as shown inFIGS.35-36). Any application force with the proximal wall802may move the contact arm from its natural state, to its contact configuration. In one embodiment, the arm portion832may be angled along its body at a bearing joint837to define a proximal extending first portion840A and a distally extending second portion840B. The first portion840A extends between the base830and joint834portion and the bearing joint837. The second portion840B extends between the bearing joint837and the tip end835. The length and angle of extension of first portion840A is configured to place the bearing joint837at a location to maintain contact with the interior surface802A of the proximal wall or the light ring, or alternatively corresponding bosses802B extending distally from surface802A, of the proximal upper wall802when moving between its first and second positions. The length and angle of extension of second portion840B in the distal direction is configured to place the tip end835in a spaced relationship with the contact pad824when the proximal wall802is at the first position, and to allow distal movement of the tip end835, together with the proximal wall802, for a sufficient distance to contact the contact pad824when the proximal wall802is at the second position. In an alternative embodiment, the bearing portion837of the contact arm822may be located in closer proximity to the tip end835of the arm portion than the location of the contacting portion. To this end, the contacting portion may be formed along a valley or recess of the arm portion. In some contact arm embodiments, the bearing portion of the contact arm is disposed in a more proximal location than the contacting portion. From an axial view perspective, the configuration of the arm portion832of contact arm822may be linear, angular, or curved.FIG.36illustrates an example of the arm portion832having an arcuate shape. Although one contact arm and contact pad system may be sufficient for wake-up functionality of a module,FIG.36depicts the system including three sets of contact arms822and contact pads (not clearly shown in the figure). As shown, the three contact arms822may be disposed radially from the longitudinal axis about the same distance. The arms822may be disposed circumferentially spaced from one another at equal distance, such as, for example, allowing for 20 to 40 degrees of separation between adjacent ends of the contact arms. Multiple sets, such as, two, three, four, five, or more, may distribute the biasing force from the contact arms822to the upper wall802more evenly. Even with multiple sets, the controls may be configured to require one only set of contact arm822and contact pad824or less than all of the total number sets to make contact for activation. Requiring less than the total amount of contacts for activation can allow the user to press any portion of the proximal wall to cause wake-up, rather than requiring the user accurate finger placement. To aid inadvertent activation, the controls may be configured to require more than one set, such as, for example, all three sets, of contact arms822and contact pads824to make contact for activation. The base830and contact arm portion832may be formed integrally from the same material, such as, an electrically conductive material, such as metal. The contact pad824is made of material conductive with the contact arm. The base and arm portion may be formed separately from same materials or different materials. If formed separately, the base and arm portion may be coupled to one another, such as, for example, welding, metal welding epoxy, brazing, or other means depending on the materials of the components. The base and arm portion may be formed from a plastic material having conductive material impregnating the plastic material in at least the tip end portion or having a conductive material coating along the tip end. In one example, the base and arm portion is formed integrally from an electrically conductive metallic material and are coupled to one another at a living hinge joint such that the contact arm has a leaf spring configuration. FIG.37shows another example of a module attachment subassembly, now referenced as spacer unit839. Unit839is configured, when part of a module, to permit the module800to be removably coupled to any of the dose buttons described herein via the attachment element807. Distal wall806includes the aperture836defined therein for receiving a light guide member849for the identification sensor, such as, for example, identification sensor680inFIG.29. Vent opening841may be defined in the distal wall806. Sensor receiving recessed locations842are defined in the proximal surface of the distal wall806for equi-radially-spaced, and equi-angularly, placement of measurement sensors, e.g., for five magnetic, inductive, or capactive sensing elements or magnetic sensors906as disclosed herein. Recesses842may be located in the distal surface of distal wall806. Attachment stakes843may be provided for coupling distal wall806and/or unit839to a complementary attachment feature of the module housing. With reference toFIG.39, light guide member849is shown with a light guide post853extending from a base855. The light guide member being made of a material, such as an optically clear polycarbonate, that permits at least some light transmission therethrough for the identification sensor to emit and sense light reflected from the colored portion of the proximal surface of the button. The post853is sized to fit within the aperture836. Shown inFIG.38, a recessed region857defined in the distal surface806A of the distal wall806may surround the aperture836. The recessed region857may have a depth and shape to correspond to the thickness and shape of the base855. The aperture836and the recessed region857may be sized and shaped to receive the light guide member849in a secured manner. The axial length of extension can provide a light guide path for the identification sensor from the distal surface of the distal wall806that will abut against the colored surface feature of the device button proximally to directly contact the sensor, or there may be an axially spaced gap, as shown, between the end of the post853and light color sensor. The light guide post853has a cross-sectional shape of any one of a variety of geometric shapes, such as circular, elliptical, or rectangular. In one example, the post853has an elliptical cross-sectional shape. One or more attachment posts859(two shown) may also proximally extend from the base855. Each attachment post859may be spaced radially from the light guide post853. To this end, the base855may include wing portions855A to accommodate the attachment post. A corresponding number of post apertures863may be defined in the distal wall806to receive the attachment posts859during manufacturing. Once received therein, the attachment posts may be heated, such as for example, through ultrasonic welding, to allow material to fill voids the respective post apertures for a secure attachment to enhance consistent sensing capability. Module800includes another embodiment of the attachment element807. Although the attachment element807is illustratively shown, it should not be limiting as module800can also be provided with the attachment unit500or attachment element419. Similarly, the other modules described herein may include the attachment element807. Attachment element807with the distal wall806may form a unit part of the module800. Attachment element807may include a plurality of distally extending arms850. In an exemplary embodiment, arms850are equi-angularly spaced around the dose button. Arms850are depicted as being coupled to and depending distally from the distal wall806. When module is attached to the device, arms850are positioned to contact the radially outward facing surface of the dose button. Arms850include an axial extending body854. Body854may include a protruding bearing portion852extending radially-inward of the body854. Body854of arms850may include a W-shaped body, where outer distally extending legs856A-B of arm body extends from the distal wall806at two attachment locations and the proximal extending inner arm858includes the protruding body852. Surfaces of the protruding body of bearing portion852may be orthogonal, curved and/or angled. Body854may, alternatively, include a J-shape having a portion that defines the proximally extending arm. With additional reference toFIG.35, battery861may provide shielding properties for the magnetic sensors and magnetic ring. In one example, the battery861may be a coin cell battery with a ferromagnetic nickel coating. Placement of the battery861may be axially proximal to the magnetic sensors to provide shielding for the sensors, providing shielding along its proximal side to inhibit magnetic field influences from the proximal direction, and/or providing shielding along its distal side deflecting the magnetic flux from the magnetic ring toward the sensors. In one example, battery861may assist in re-directing the magnetic flux lines, such as, from the ring, such as the rotation sensed element706, toward the position of sensors, such as sensors906, and in re-directing the magnetic flux lines from unwanted external interference away from sensor position. In this example, the size of the battery, such as the radius, may coincide with the radial location of the sensors from the axis. In another example, the make-up of battery861may provide other shielding properties, such as the battery including iron (most series), cobalt or other nickel alloys with appropriate thicknesses. The battery861can have a cross-sectional area size relative to the radial placement of the magnetic sensors and/or can be axially spaced from the magnetic sensors to provide such shielding. Any of the modules described herein, such as, for example, module800, can comprise five (shown) or six sensing elements, such as magnetic sensors. The sensing elements may be disposed within the module compartment808and coupled to the circuit board809of the electronics assembly810and thus to the MCU. In one example, the sensing elements comprises five or six magnetic sensors disposed within corresponding sensor receiving recessed locations842defined within the distal wall806, as shown inFIG.37, although the sensing elements may be disposed on top of the distal wall806(that is, not in recesses), or more proximal to the distal wall806within the compartment of the module. FIGS.40-41depict an example of an arrangement of the sensors relative to the magnetic ring, and is illustrative for all other magnetic dose detection systems described herein.FIG.40illustrates another example of the magnetic sensor system, now referred to as system900, including as the sensed element the diametrically magnetized ring902having the north pole903and the south pole905. Magnetized ring902is attached to the dose setting member, such as, for example the flange, as previously described. The radial placement of the magnetic sensors906, such as, for example, hall-effect sensors, relative to the magnetized ring902, can be in an equi-angularly relative to one another in a ring pattern. In one example, the magnetic sensors906are disposed radially in an overlapping relationship with the outer circumferential edge902A of the magnetized ring902such that a portion of the magnetic sensor906resides over the magnetized ring902and the remaining portion resides outside the magnetized ring902, such as shown inFIG.40. The overlapping arrangement was found to place the sensors in the range for high flux capability and thus for more consistent magnetic flux sensing.FIG.41shows the radial distance907determined from the center of the magnetic sensor906to the axis AA. The radial distance907may be sized to be at least the outer radius908of the magnetized ring902. In one example, the radial distance907is 0.1-20% greater than the outer radius of the magnetized ring902, and in another example, the radial distance907is at least 10% greater than the outer radius of the magnetized ring902. It has been surprising that this position can provide enhanced peak magnetic flux for sensing over other radial positions.FIG.11Adepicts another example of the relevant radial placement with the magnetic sensors disposed entirely over the ring.FIG.11Bdepicts another example of the relevant radial placement with the magnetic sensors disposed entirely inside opening formed by the ring. FIG.41illustrates an example of an axial placement and a radial placement of the magnetic sensors906relative to magnetized ring902. Sensors906may be disposed along the circuit board903of the electronics assembly of the module (module components omitted for clarity) that is disposed along a common plane that is substantially orthogonal to the axis AA. Magnetic ring902of a thickness913may be disposed in a planar positon, parallel to the plane of the sensors906. Ring902may be disposed in the device720arrangement, while the sensor906may be disposed in the module that is removably attachable to the device. In an alternative example, the components of the module, including the sensors906, may be permanently integrated with the device with magnetized ring902like what is shown inFIG.12. Geometry of the ring can be modified within available space constraints to meet the magnetic flux performance requirements for the selected sensors.FIG.41depicts the relative axial position911of the magnetic sensors906over the magnetized ring902when the dose button is uncompressed, such as during dose setting. During dose delivery, the relative axial position of the magnetic sensors906over the magnetized ring902changes after distal displacement of the dose button and sensors906by a distance, shown by arrow909, toward the rotating magnetized ring902that remains axially stationary. The amount of distal movement the magnetic sensors906can be in the range of 1 mm to 3 mm relative to the magnetized ring902. In one example, during use, as the user applies pressure on the top of the module, the button/spring sub-assembly undergoes axial compression, and reduces the relative axial distance between sensor906and magnetized ring902by an axial distance of 1.7 mm. At the dose delivery position, the magnetic flux of magnetized ring902available for reading by the sensors906is at least twice the value than when the sensors906are in the dose setting position. Magnet material for diametrically magnetized ring902should be selected such that flux available at the dialing and dosing distances will be acceptable for reliable sensing. In one example, the magnetic ring use for the sensed component, for example, may be made from sintered Neodymium N35 grade material with nickel coating. A neodymium magnet (also known as NdFeB or NIB or Neo magnet) is a rare-earth permanent magnet made from the alloy of neodymium, iron and boron. Other sintered Neodymium magnet grades such as N42, N45, N50 and alike or bonded Neodymium grade (injection or compression molded with thermoplastic or thermoset) may be considered for the appropriate flux availability at the magnetic sensors. The selected magnet material is expected to meet mechanical strength requirement for firmly fitting against the plastic carrier, such as carrier708, and sized to sustain operational and handing impacts without cracks or failure. The secured magnetized ring is secured fixedly to the dose setting member to not rotate by itself, but does rotate with the dose setting member during dialing or dosing. The axial movement of the sensors relative to the magnetized ring during dose delivery and the change in the magnetic flux due to this axial position change and due to rotation of the ring can make dose detection accuracy challenging. Also, more cost-effective diametrically magnetized rings of sintered N35 Neo magnet can provide non-uniform magnetic field properties, leading to greater inconsistent sensing detection and dial error. The dial error of the module for dose detection is the rotational position difference in degrees between the actual physical rotational position of the device dose components, such as the magnetic ring, (“the dialed position”), and the sensed rotational position detected by the magnetic sensor system (“the detected position”). For example, when a user desires a certain number of units of drug to be delivered from the device, the user rotates the device button with the module attached thereto relative to the device housing by an amount as indicated by the dosing dial, such as 10 units or approximately 180 degrees of rotation based on 18 degrees±X % per 1 unit. When the button is pressed to begin the deliver operation, the dose detection system can track the initial position and the final position at the completion of the dose delivery, in which the difference between initial and final positions corresponds to a number of degrees of rotation and correlated amount of dose units delivered. Dial error may be illustrated with the following example. The dialed initial position may place the dose/dialed member of the device, and thus the magnetic ring, at a nominal zero initial physical position after dose setting has occurred, and a delivered final physical position of the ring after rotation of 90 actual degrees, correlating to five units during dose delivery. With dial errors, the dose detection system in a four-sensor system with regular production diametrically magnetized rings may detect −10 degrees for the nominal zero initial positon of the ring, and 100 degrees for the delivered final position, resulting in a total of 110 degrees of detected rotation of the ring. This would correspond to a sensed dose of over six units delivered, which is greater than the five units actually delivered. Dial errors can be introduced to the system from the magnetic sensors and other factors. The first spatial harmonic waveform (main waveform/signal) can be susceptible to phase, gain or offset errors during rotation of magnetized ring relative to the sensors that measure a sine wave, with the number of sensors equally spaced around a circumference from one another and equally axially spaced from the magnet would represent the number of times the sine wave is sampled. Appropriate calibration of sensors may reduce these errors significantly. However, other error contributions can be from higher harmonics such as third or fourth harmonics to the first harmonic. Some error can be reduced by consistent radial positioning of the magnet sensors from module axis, as well as consistent circumferential spacing between each of the sensors, reducing tilt of plane of co-located sensors to be substantially normal to module axis and in parallel to the magnetic ring, and calibration of the system. Improving the uniformity of the flux in magnetic properties of the diametrically magnetized rings by using higher-grade magnetic material sources, such as, for example, N50 grade Neodymium magnet, or tighter manufacturing controls, may reduce the dial error. Such improved magnetic components would be more expensive and limit the magnet sourcing capability. In addition, there was uncertainty as to whether providing additional magnet sensors (one or two more) that already showed non-uniform properties would improve the sensing capability. It has been discovered that that the use of five or six magnet sensors906for the rotating diametrically magnetized ring902during dose delivery improved the position signals used for dose determination by proper filtering of offset second and third order harmonic signal distortion normally present in regular production magnets, which led to the reduction of dial error. Such filtering was not present with the 4-sensor architecture. To this end, improvement have been discovered to ensure that the amount of units delivered detected by the dose detection system corresponds to the actual amount of units delivered. Regular production N35 Neo sintered diametrically magnetized rings were tested to determine harmonic distortion of sensor signals for second, third, fourth and fifth order harmonics percentage amplitude vs. first order harmonics. Results are shown inFIG.42. A customized magnetic test fixture was built to emulate the magnet-sensor sub-system function arranged in the modules described herein. The fixture is configured to adjust relative radial and circumferential position and axial (tilt out of plane) positions of the sensors and magnetic rings to not only test different configuration, but also reproduce the axial and radial arrangement inFIG.40andFIG.41. Results from individual sensors can be analyzed to understand the effects of magnetic non-uniformity on harmonic distortions and dial/dose errors. Dial errors resulting from 4- vs. 5- and 6-sensor architectures for N35 grade magnets made from regular production (more cost effective) and customized production (less cost effective) methods are shown inFIGS.43-44, respectively.FIG.45illustrates the sensitivity of 4-sensor architecture with regular production N35 Neo sintered diametrically magnetized rings to third harmonics, leading to its susceptibility to the increase of dial errors to over six degrees, and the immunity of 5-sensor architecture with regular production N35 Neo sintered diametrically magnetized rings to third harmonics, leading to a substantial reduction to dial errors to less than two degrees. FIG.42depicts the dial error of a 4-sensor architecture used with regular production N35 magnetic rings. The 4-sensor architecture has been demonstrated to exhibit increased undesirable error contributions from third harmonics affecting the reliability of the position signals. It was thought that the radially equidistant sensor configuration would be immune to small amplitude variations from the magnetic flux of the rotating magnetized ring. Numerical simulation of the 4- vs 5- and 6-sensor architecture considering Neodymium magnet flux properties showed that the addition of sensors equally spaced along the circumference reduced higher order harmonics on angle measurements, thereby reducing the dialing and dosing error variations. Various tests with sintered N35 Neo magnets from regular production (ones originally showing non-uniform properties), sintered N35 magnets with customized production methods (w/tighter controls), and sintered N50 Neo higher grade magnets were performed to compare the sensor architecture effects with each other and to numerical modeling simulations, where it was found that third harmonics had the most influence on angle measurements. To this end, five sensor architecture was able to cancel up to the third harmonic distortion better than the four sensor architecture, while it is possible to cancel up to fourth harmonics with the six sensor architecture. InFIG.42, the effect of the error contributions from higher order harmonics that lead to deviation of the measured rotational magnetic flux waveform during rotational position sensing along 360 degrees (at line1000) for a four-sensor architecture as compared to a calculated mathematic desired model of the magnetic flux waveform during rotational position sensing (at line1010) based on magnet geometry and its properties. Such deviation between the two lines1000,1010may contribute to dial errors in four-sensor systems. From test data, the module with five or six magnetic sensors is configured to have significantly reduce the distortion error in a manner that it is likely to produce a dial error contribution from the magnet distortion from the sensor/ring arrangement that would be two degrees or less. In one example, inFIG.43, for a lot of regular production magnets, the dial error for a 4-sensor architecture was an average of 6.5 degrees (at line1100). The dial error for 5-sensor architecture with similar regular production magnets was an average of 1.2 degrees (at line1110), respectively, and further an average of 0.5 degrees with a 6-sensor architecture (at line1120). Five-sensor or 6-sensor architecture with regular production N35 magnetic rings is shown to have reduced the dial error by over five times compared to the 4-sensor architecture. Five-sensor or 6-sensor architecture with custom production magnets is shown to have reduced the error by over three times compared to the 4-sensor architecture. InFIG.44, for customized production magnets, the dial error reduced from average of 1.4 degrees to an average of 0.4 degrees from 4-sensor (at line1200) to 5-sensor architecture (at line1210), respectively, and to an average of 0.4 degrees with a 6-sensor architecture (at line1220). FIG.45summarizes percentage harmonics variation from three lots (1301,1302,1303) of N35 grade sintered magnetic rings produced by regular production method for 4-sensor and 5-sensor systems. The 4-sensor architecture (at line1310) exhibited up to an average of 3.8 percent third harmonics, while the 5-sensor architecture (at line1320) exhibited an approximately zero percent at the third harmonics. The 5-sensor architecture (at line1320) exhibited up to an average of 0.8 percent fourth harmonics, while the 4-sensor architecture (at line1340) was exhibited an approximately zero percent at the fourth harmonics. The contribution of third harmonics to the main waveform is what resulted in the dial error in the 4-sensor architecture to over six degrees, as shown inFIG.43, while the improvement to the main waveform with the reduction of third harmonics with the addition of sensors to 5-sensor or 6-sensor architecture, resulting in a reduced dial error below two degrees as shown inFIG.43. Further illustrative embodiments of a dose delivery detection system are provided inFIGS.30-34. The embodiments are shown in somewhat diagrammatic fashion, as common details have already been provided with respect toFIGS.1-5. Described herein are several exemplary embodiments of medication delivery devices utilizing magnetic sensing of dose delivery. The ring-shaped element, such as, for example, magnet or metal ring, may be fixedly secured to the dose dial member and/or flange of a device by various attachment means, such as adhesives, welding, or mechanical attachments. For high volume manufacturing, the attachment means may be beneficial. InFIGS.30-34there is shown an illustrative manner of mounting a ring-shaped element to a flange forming a part of a medication delivery device.FIG.30illustrates the components in axial alignment that are coupled to one another as an integral single unit (as shown inFIG.31) which rotates and axial moves as a single unit, including: the dial member700, an exemplary clutch702, a dose setting component, such as, for example, flange704, to receive a rotation sensed element706, a carrier708to fixedly couple the rotation sensed element706to the flange704, a button spring710for biasing a dose button712. Instead of the flange, other dose setting components described herein may be used. Dose button712may have the configuration of any of the buttons described herein. Referring toFIG.31and as previously described with respect toFIGS.1-4, medication delivery device720includes dial member700mounted within device body722. Flange704is received within dose dial member700, and clutch702is positioned within flange704. Dose dial member700, flange704are rotationally fixed together and rotate during dose setting and/or dose delivery in direct relation to the amount of a set or delivered dose. Clutch702includes stem724to which is mounted dose button712. Spring710acts between dose button712and flange704to bias dose button712proximally away from flange704. As previously described, the medication delivery device is further provided with a rotation sensed element attached to the flange such as the sensor is housed entirely within the dose button. Any of the modules described herein includes the electronics assembly and the sensing elements to detect rotation of the rotation sensed element706during dose setting and/or delivery to determine the amount of dose involved. Flange704is generally cylindrical in shape and defines a proximal axial surface732at the end of sidewall734. Flange704further defines a central opening736that is interior of proximal surface732. As shown inFIG.32, the rotational sensor706has an annular shape, such as an annular magnet, metal ring, or magnetized or metalized polymer ring, is positioned on proximal surface732of flange704. Carrier708includes an overlapping proximal lip or support742which is positioned against the proximal surface of the rotational sensor706opposite proximal surface732to sandwich the sensor706therebetweeen. Support742is shown as a generally ring-shaped component, however it may alternatively comprise a segmented ring or a plurality of supports spaced about rotational sensor706. In this configuration, carrier708retains sensor706in position on top of flange704by having support742bear distally against sensor706. This is accomplished by having carrier708fixed axially relative to flange704. In one embodiment, carrier708is attached directly to flange704, for example at a location distal of sensor706. In another illustrative embodiment, carrier704is spring-biased in a distal direction, such as by spring710urging carrier708away from dose button712, or by a spring acting to pull carrier704toward flange704. Referring back toFIG.30, carrier708includes a tubular body750with a plurality of axially extending legs752circumferentially spaced from one another about a generally axial bore754that extends through the carrier. Body750includes support742sized to capture the rotation sensed element706against the flange. Body750is sized to receive the inner diameter or cross-sectional area of the sensor706. As shown inFIG.31, the support742extends radially outward beyond the size of the body750. The portions of the body750with the legs772depending therefrom may include a snap radial lip771positioned distal away from the support742to the size of the axial thickness of the sensor706to engage the distal surface of the sensor706. Each of the legs772includes a radially inward protruding element756sized and shaped for insertion within corresponding suitably sized axial slots760formed in the sidewall734of the flange, as illustrated inFIG.34. Slots may be sized to snugly receive the element756such that through frictional engagement the two component are rotationally locked and torque is transmitted therebetween. The radial ends of the element756may be in engagement with a central hub of the flange704as shown inFIG.31andFIG.33. As shown inFIG.31, in one approach, legs752of carrier708define a circumferential cross-sectional span sized for secure frictional engagement along the cylindrical interior surface759of the flange704when inserted within the opening736of flange704. In one example, legs752extend within central opening736, and in one approach are directly attached to flange704at a location distal of sensor706. The relevant placement of the spring710is shown inFIGS.31and33. Flange704may include a radial slot762formed in its proximal axial surface732. Slots760are formed in the flange in a manner such that the interior surface of the legs752are in close alignment with the interior surface of the outer wall that defines the radial slot762, as shown inFIG.31. In this configuration, the distal end of spring710is positioned to within the radial slot762. The walls defining the radial slot762support the distal end of spring710and allows bearing against the dose button at the mounting collar, thereby urging carrier708in a distal direction away from the dose button. The various components of carrier708may comprise either partial or full circumferential members. For example, the body of the carrier708may extend fully around the flange, or may be formed as spaced segments. Advantageously, use of the carrier means that rotation sensed element is held firmly in place without the use of adhesives. Although adhesives may be used, adhesives can complicate the fabrication process. Electronics assembly610includes a variety of operably connected components for module600as well as any of the other modules described herein, including a battery621for power source and associated contacts, MCU for executing programmed instructions, memory for storing programs and data, a communications assembly for transmitting and/or receiving data, timer for tracking time, and various switches and sensors as described. Any of the modules described herein, such as, for example, modules82,232,400, or600, may be configured to house any of the electronics assemblies described herein, including being configured to house the sensing elements160for use with the sensor system150described previously. FIG.46illustrates an example of the electronics assembly, referred to as1400, which can be included in any of the modules described herein. MCU is programmed to achieve the electronic features of the module. MCU includes control logic operative to perform the operations described herein, including obtaining data used for determining a dose delivered by medication delivery device based on a detected rotation of the dose delivery member relative to the actuator. MCU may be operable to obtain data by determining the amount of rotation of the rotation sensed element fixed to the flange, which is determined by detecting the magnetic field of the rotation sensed element by the sensing elements of the measurement sensor, such as, for example, Hall Effect sensors, of the system. Assembly includes MCU that can be operably coupled to one or more of dose sensors1402A-E, memory1408, identification sensor1404, counter1414, light driver1411and light indicators1412, power-on module1406, communication module1410, display driver/display1416, power source1418, and presence module1420. Assembly1400may include any number of dose sensors, such as, for example, five magnetic sensors1402A-E (shown) or six sensors. MCU is configured to determine the total units of rotation. MCU may be configured via the presence module1420, shown in this embodiment to be optional by dashed lines, to determine via the triggering of the presence switch system whether the module is coupled to the device's button. MCU is configured to determine the color of the dose button via the identification sensor1404, and in some examples, associate the color data determined onboard, or off board with an external device, the color corresponding to a particular medication. MCU is configured to determine triggering of the wake-up switch in order to power on the electronic assembly for use, shown as power-on module1406. In one example, the total rotation may be communicated to an external device that includes a memory having a database, look up table, or other data stored in memory to correlate the total rotational units to an amount of medication delivered for a given medication identified. In another example, MCU's may be configured to determine the amount of medication delivered. MCU may be operative to store the detected dose in local memory1408(e.g., internal flash memory or on-board EEPROM). MCU is further operative to wirelessly transmit a signal representative of device data, such as, for example, (any one or any combination thereof) the rotational units, medication identification (such as color) data, timestamp, time since last dose, battery charge status, module identification number, time of module attachment or detachment, time of inactivity, and/or other errors (such as for example dose detection and/or transmission error, medication identification detection and/or transmission error), to a paired remote electronic device, such as a user's smartphone, over a Bluetooth low energy (BLE) or other suitable short or long-range wireless communication protocol module1410, such as, for example, near-field communication (NFC), WIFI, or cellular network. Illustratively, the BLE control logic and MCU are integrated on a same circuit. In one example, any of the modules described herein, such as module600, may include the display module1420, shown in this embodiment to be optional by dashed lines, for indication of information to a user. Such a display, which may be LEDs, LCD, or other digital or analog displays, may be integrated with proximal portion finger pad. MCU includes a display driver software module and control logic operative to receive and processed sensed data and to display information on said display, such as, for example, dose setting, dosed dispensed, status of injection, completion of injection, date and/or time, or time to next injection. In another example, MCU includes a LED driver1411coupled to one or more LEDS1412, such as, for example, RGB LED, Orange LED and Green LED, used to communicate by sequences of on-off and different colors to the patient of whether data was successfully transmitted, whether the battery charge is high or low, or other clinical communications. Counter1414is shown as a real time clock (RTC) that is electronically coupled to the MCU to track time, such as, for example, dose time. Counter1414may also be a time counter that tracks seconds from zero based on energization. The time or count value may be communicated to the external device. The dose detection systems have been described by way of example with particular designs of a medication delivery device, such as a pen injector. However, the illustrative dose detection systems may also be used with alternative medication delivery devices, and with other sensing configurations, operable in the manner described herein. For example, any one or more of the various sensing and switch systems may be omitted from the module. While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character. For example, device sensing module can sense dose setting amounts if adapted to work with a device portion having suitable parts that experience relative rotation during dose setting. This application is therefore intended to cover any variations, uses or adaptations of the invention using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains. All changes, equivalents, and modifications that come within the spirit of the inventions defined by the claims included herein are desired to be protected. Various aspects are described in this disclosure, which include, but are not limited to, the following aspects: 1. A medication delivery device including a device body; a dose setting component coupled to the device body and rotatable relative to the device body in relation to an amount of a set or delivered dose, the dose setting component having a proximal surface; an annular sensed element positioned on the proximal surface of the dose setting component; and a carrier including a proximal overlapping support contactable against the annular sensed element opposite the proximal surface of the dose setting component, the carrier being axially and rotationally fixed to the dose setting component. 2. The medication delivery device of aspect 1 in which the carrier is secured to the dose setting component at a location distal of the annular sensed element. 3. The medication delivery device of any one of aspects 1-2 in which the carrier includes a plurality of legs extending distally from the support, wherein the dose setting component includes a flange that includes axial slots to receive a portion of the legs to rotationally lock the carrier with the flange. 4. The medication delivery device of any one of aspects 1-3 wherein the annular sensed element is an annular magnet. 5. The medication delivery device of any one of aspects 1-4 wherein the annular sensed element is coupled to the dose setting component with the carrier without an adhesive. 6. The medication delivery device of any one of aspects 1-5 including a dose button coupled to an end of the device body, and a spring disposed between the dose button and the dose setting component to bias the carrier away from the dose button. 7. The medication delivery device of aspect 6 including a dose detection system coupled to the dose button. 8. The medication delivery device of aspect 7 wherein the dose detection system includes a plurality of sensors to detect movement of the annular sensed element. 9. The medication delivery device of aspect 8 wherein the dose detection system is housed in a module that is removably attached to the dose button. 10. The medication delivery device of aspect 9 wherein the module includes a plurality of arms to engage a sidewall of the dose button. 11. The medication delivery device of aspect 8 wherein the dose detection system is housed in the dose button. 12. The medication delivery device of any one of aspects 1-11 wherein the carrier includes a tubular body sized to fit within the annular sensed element. 13. The medication delivery device of aspect 12 wherein the tubular body includes a radial lip positioned distal to the proximal overlapping support. 14. A medication delivery device including: device body; a flange coupled to the device body and rotatable relative to the device body in relation to an amount of a set or delivered dose, the flange having a proximal surface; an annular magnetic element positioned on the proximal surface of the flange; and a carrier including a proximal support overlapping the annular magnetic element opposite the proximal surface of the flange, the carrier being axially and rotationally fixed to the flange. 15. The medication delivery device of aspect 14 in which the carrier is secured to the flange at a location distal of the annular magnetic element. 16. The medication delivery device of any one of aspects 14-15 wherein the carrier includes a tubular body sized to fit within the annular sensed element 17. The medication delivery device of any one of aspects 14-16 in which the carrier includes a plurality of legs extending distally from the proximal support to couple to the flange. 18. The medication delivery device of any one of aspects 14-17 wherein the annular magnetic element is an annular bipolar magnet. 19. The medication delivery device of any one of aspects 1-18 wherein the device body includes a cartridge and a medication contained within the cartridge. 20. A method of coupling a sensed element to a dose setting component of a medication delivery device, the dose setting component having a proximal surface, including: providing a carrier and an annular sensed element, the carrier including a tubular body sized to fit within the annular sensed element, a proximal lip extending radially beyond the tubular body, and a plurality of coupling legs extending distally from the tubular body away from the proximal lip; coupling the annular sensed element over the tubular body of the carrier and in contact underneath the proximal lip; and coupling the carrier with the annular sensed element to the dose setting component for sandwiching the annular sensed element between the radial lip and the proximal surface of the dose setting component, where the coupling legs of the carrier is engaged with the dose setting component to rotationally lock the carrier with the annular sensed element to the dose setting component. | 147,762 |
11857771 | The following reference characters are used in the drawing figures: 10, 210Plunger assembly12, 212Convertible plunger12a-12iConvertible plunger14, 214Plunger rod16, 216Interior shaft16′Tip18, 218Exterior shaft20, 220Distal end22, 222Proximal end24, 224Locking tab25, 225Tapered surface26, 226Actuator28, 228First end30, 230Second end32, 232First recess34, 234Second recess36, 236Inner portion38, 238Thread (of exterior shaft 18, 218)40, 240Thread (of plunger 12, 212)42Insert44Sleeve45Connector body46Outer portion48First cavity48a-gCavity50Second cavity51Storage Sealing Section52Rib of Storage Sealing Section53Liquid Sealing Section54Interior area55Rib of Liquid Sealing Section56Barrel57Valley58Sidewall59Product containing area60Inner surface61Proximal end (of barrel 56)62Insert63Connector body64Sleeve65First section (of connector body 63)66Cavity67Second section (of connector body 63)68Shaft69Third section (of connector body 63)70Outer surface (of insert 62)72Recesses (of insert 62)74Protrusions (of insert 62)76Inner surface (of sleeve 64)77Recesses (of connector body 63)78Protrusions (of sleeve 64)79Protrusions (of connector body 63)80Recesses (of sleeve 64)82Bottom portion (of outer surface 70)84Lower portion (of inner surface 76)86Exterior surface88Film coating90Sidewall (of plunger 12)92Nose cone (of plunger 12)94Film96Forming die98Forming plug100Base wall (of forming plug 98)102Bottom portion (of forming die 96)104Sidewall (of forming die 96)106Coating preform107Mold108Mold cavity110Sidewall (of mold cavity 108)112Bottom wall (of mold cavity 108)113Mold core114Trim tool152Rib194Cap300Spherical mesh insert302Cylindrical insert303Central portion304Protrusion304aCavity304bProtrusion305Opening305a, bOpening306Insert307Wings308Porous material309Stopper310Sealed inner cavity310aCompression material311Tip312Membrane314Juts316Valve318Sliding shaft400Coating set402Tie coating or layer404Barrier coating or layer406pH Protective coating or layer500Sample A502Sample B504Sample C510Set A512Set B514Set C516Bare COP syringe results518Trilayer syringe results520Bare glass syringe results522Glass syringe with PDMS results612Three-position plunger614Plunger rod616Interior shaft618Exterior shaft630Round collar642Insert642aInsert shaft642bInsert flange643Opening644Sleeve647Pre-load cavity648First cavity650Second cavity712, 812, 912Convertible plunger738, 838, 938Thread (of exterior shaft 18, 218)740, 840, 940Thread (of plunger 712, 812, 912)742, 842, 942Insert744, 844, 944Sleeve745, 845, 945Connector body746, 846, 946Outer portion748, 848, 948First cavity750, 850, 950Second cavity751, 851, 951Storage Sealing Section752, 852, 952Rib(s) of Storage Sealing Section753, 853, 953Liquid Sealing Section755, 855, 955Rib of Liquid Sealing Section988Film coating790, 890, 990Sidewall (of plunger 712, 812, 912)792, 892, 992Nose cone1012Convertible plunger or stretchableplunger1038Thread (of exterior shaft 18, 218)1040Thread (of plunger 1012)1044Sleeve1051Storage Sealing Section1052Rib(s) of Storage Sealing Section1053Liquid Sealing Section1094Cap1095Stem1097Stem cover DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will now be described more fully with reference to the accompanying drawings, in which several embodiments are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth here. Rather, these embodiments are examples of the invention, which has the full scope indicated by the language of the claims. Like numbers refer to like elements throughout. Definitions In the context of the present invention, the following definitions and abbreviations are used: For purposes of the present invention, an “organosilicon precursor” is a compound having at least one of the linkages: which is a tetravalent silicon atom connected to an oxygen or nitrogen atom and an organic carbon atom (an organic carbon atom being a carbon atom bonded to at least one hydrogen atom). A volatile organosilicon precursor, defined as such a precursor that can be supplied as a vapor in a PECVD apparatus, is an optional organosilicon precursor. Optionally, the organosilicon precursor is selected from the group consisting of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, an alkyl trimethoxysilane, a linear silazane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, and a combination of any two or more of these precursors. Values of w, x, y, and z are applicable to the empirical composition SiwOxCyHzthroughout this specification. The values of w, x, y, and z used throughout this specification should be understood as ratios or an empirical formula (for example for a coating or layer), rather than as a limit on the number or type of atoms in a molecule. For example, octamethylcyclotetrasiloxane, which has the molecular composition Si4O4C8H24, can be described by the following empirical formula, arrived at by dividing each of w, x, y, and z in the molecular formula by 4, the largest common factor: Si1O1C2H6. The values of w, x, y, and z are also not limited to integers. For example, (acyclic) octamethyltrisiloxane, molecular composition Si3O2C8H24, is reducible to Si1O0.67C2.67H8. Also, although SiOxCyHzis described as equivalent to SiOxCy, it is not necessary to show the presence of hydrogen in any proportion to show the presence of SiOxCy. The term “barrel” refers to a medical barrel, as may be used, e.g., as part of a medical device for containing and dispensing liquid product, such as a syringe. The term “plunger” when used with reference to any embodiment of the present invention (as opposed to with reference to conventional plungers in the art) refers to a convertible plunger according to the present invention. “Frictional resistance” can be static frictional resistance and/or kinetic frictional resistance. The “plunger sliding force” (synonym to “glide force,” “maintenance force”, or Fm, also used in this description) in the context of the present invention is the force required to maintain movement of a plunger tip in a syringe barrel, for example during aspiration or dispense. It can advantageously be determined using the ISO 7886-1:1993 test known in the art. A synonym for “plunger sliding force” often used in the art is “plunger force” or “pushing force”. “Container closure integrity” or “CCI” refers to the ability of a container closure system, e.g., a plunger disposed in a prefilled syringe barrel, to provide protection and maintain efficacy and sterility during the shelf life of a sterile product contained in the container. The “plunger breakout force” (synonym to “breakout force”, “break loose force”, “initiation force”, Fi, also used in this description) in the context of the present invention is the initial force required to move the plunger tip in a syringe, for example in a prefilled syringe. Both “plunger sliding force” and “plunger breakout force” and methods for their measurement are described in more detail in subsequent parts of this description. These two forces can be expressed in N, lbs or kg and all three units are used herein. These units correlate as follows: 1N=0.102 kg=0.2248 lbs (pounds). “Slidably” means that the plunger tip, closure, or other removable part is permitted to slide in a syringe barrel or other vessel. The term “syringe” is broadly defined to include cartridges, injection “pens,” and other types of barrels or reservoirs adapted to be assembled with one or more other components to provide a functional syringe. “Syringe” is also broadly defined to include related articles such as auto-injectors, which provide a mechanism for dispensing the contents. The term “outward radial pressure” refers to pressure applied or exerted in a direction outward from (or away from) the plunger's central axis. The terms “film” and “film coating” may be used interchangeably in this specification. Convertible Plungers and Film-Coated Plungers FIGS.1-2illustrate a two-position plunger assembly10according to an embodiment of the present invention. The plunger assembly10may have a variety of different shapes and sizes. For example, according to an illustrated embodiment, the plunger assembly10may be approximately 79 millimeters long. The plunger assembly10includes a convertible plunger12and a plunger rod14. The plunger rod14may include an interior shaft16and an exterior shaft18. The interior shaft16includes a distal end20, a proximal end22, and a locking tab24. According to certain embodiments, the distal end20of the interior shaft16may be configured to form an actuator26that, during use of the plunger assembly10, is to be pressed upon by a user, such as, for example, by the thumb of the user. The exterior shaft18may include a first end28, a second end30, a first recess32, a second recess34, and an inner portion36. According to certain embodiments, the first end28may be configured for a threaded engagement with the convertible plunger12. For example, as shown, the first end28may include an external thread38that is configured to mate with an internal thread40of the convertible plunger12. At least a portion of the interior shaft16is configured for slideable displacement along the inner portion36of the exterior shaft18. Additionally, the locking tab24may protrude from at least a portion of the interior shaft16. In the illustrated embodiment, the locking tab24has a tapered surface25that may assist in controlling the direction and timing of the displacement of the interior shaft16along the inner portion36of the exterior shaft18. For example, at leastFIG.2illustrates the interior shaft16in a first position relative to the exterior shaft18, with the locking tab24protruding into at least a portion of the first recess32of the exterior shaft18. The orientation of the tapered surface25of the locking tab32allows, when sufficient force is exerted upon the actuator26, for the locking tab32to be at least temporarily compressed or deformed in size so that the locking tab24may at least temporarily enter into the inner portion26as the locking tab25is moved from the first recess32to the second recess34. However, in the absence of sufficient force, the locking tab32may remain in the first recess32, thereby maintaining the interior shaft16in the first position. The distance that the locking tab24is to travel from the first recess32to the second recess34, and thus the distance the interior shaft16is displaced relative to the exterior shaft18when moving from the first position to the second position may vary for different plunger assemblies. For example, according to certain embodiments, the interior shaft16may be displaced approximately 3 to 5 millimeters. Additionally, as shown inFIGS.2and5, according to certain embodiments, the proximal end22of the interior shaft16may or may not be housed in the interior portion36of the exterior shaft18when the interior shaft16is in the first position. Further, the orientation and size of the tapered surface25of the locking tab24may provide the locking tab24with sufficient width to prevent the locking tab24from being pulled into the inner portion36in the general direction of the second end30of the exterior shaft18. Accordingly, when the locking tab24is in the second recess34, and thus the interior shaft16is in the second position, the orientation and size of the tapered surface25of the locking tab24may provide the locking tab24with sufficient width to resist the locking tab24from being pulled back into the first recess32. As shown in at leastFIGS.2-4, the convertible plunger12is configured to be received in an interior area54of a barrel56(e.g., of a syringe). The interior area54may be generally defined by a sidewall58of the barrel56, the sidewall58having an inner surface60. Additionally, the interior area54may include a product containing area59between the convertible plunger12and the proximal end61of the barrel56. According to certain embodiments, as best shown inFIG.3, the convertible plunger12includes an insert42, a sleeve44, and a connector body45. The connector body45may be operably connected to the sleeve44, such as, for example, through the use of over molding, a plastic weld, an adhesive, and/or a mechanical fastener, such as a screw, bolt, pin, or clamp, among other connections. As previously discussed, the connector body45may be configured to be connected to the exterior shaft18, such as, for example, by the threaded engagement of the internal thread40of the connector body45and the external thread38of the exterior shaft18. Additionally, according to certain embodiments, the connector body45may be molded from a relatively stiff and/or rigid material, such as, for example, polyethylene or polypropylene, among other materials. The sleeve44may be configured to provide a first cavity48and a second cavity50. Additionally, the first and second cavities48,50are in communication with each other and are configured to receive the movable insertion of the insert42. The terms “first cavity” and “second cavity” may refer to physically distinct compartments (e.g., having an interruption, transition region, membrane or geometrical change between them, such as shown inFIG.3) or alternatively a single compartment that is adapted to facilitate retaining an insert in a first position within the compartment (i.e., “first cavity”) and then a second position within the same compartment (i.e., “second cavity”), with no interruption, transition region, membrane or geometrical change between the first cavity and second cavity. The outer portion46of the sleeve44comprises a nose cone92(generally facing the syringe contents), and a sidewall90(generally facing the sidewall58of the barrel56). The term “nose cone”92refers to the syringe contents-facing surface of the convertible plunger12, and may be of any suitable geometry (e.g., rounded, cone-shaped, flat, etc.). The sidewall90of the sleeve44includes a storage sealing section51comprising at least one rib52that is preferably generally adjacent to and/or aligned with at least a portion of the first cavity48. For example, as shown by at leastFIG.3, a single rib52of the storage sealing section51is generally adjacent to and/or aligned with the first cavity48. However, the number of ribs52of the storage sealing section51aligned with and/or adjacent to the first cavity48may vary. Further, according to certain embodiments, a rib52of the storage sealing section51may not be positioned adjacent to and/or aligned with the second cavity50. The sleeve44may be constructed from a thermoset rubber (e.g., butyl rubber) having good gas barrier properties, or a thermoplastic elastomer, among other materials. The purpose of the storage sealing section51is to provide CCI and optionally a barrier to one or more gases (e.g., oxygen) when the convertible plunger12is in a “storage mode,” e.g., to seal the contents of a pre-filled syringe when in storage, prior to use. The gas barrier should effectively prevent ingress of gas(es) that may degrade the product contained within the syringe during the product's desired shelf life. The gas barrier should also effectively prevent egress of gas(es) that preferably remain within the product containing area59of the syringe. The particular gas(es) for which the storage sealing section51optionally provides a barrier when the plunger is in storage mode may vary depending on the product contained within the syringe. Optionally (in any embodiment), the gas barrier is an oxygen barrier. When the convertible plunger12is converted from storage mode to dispensing mode, the seal initially provided by the storage sealing section51is either reduced or removed entirely (i.e., such that the storage sealing section51no longer physically contacts the sidewall58of the barrel56). The insert42may also be constructed from a variety of different products, including products that allow the insert to have a lower, similar, or higher rigidity than/to the sleeve44. Preferably, in any embodiment, the insert has a higher rigidity than the sleeve. Additionally, the insert42may have a variety of shapes and be generally configured to occupy at least one of the first and second cavities48,50. According to the embodiment illustrated inFIGS.2-4, the insert42has a generally spherical shape. Alternative insert embodiments and shapes are disclosed below. The sleeve44, and particularly the rib52of the storage sealing section51, and the insert42are configured to provide a force that compresses the rib52against the sidewall58of a barrel56, as shown inFIG.4. Such compression of the rib52of the storage sealing section against the sidewall58provides a seal, such as a compression seal in a “storage mode”, between the convertible plunger12and the sidewall58that protects the sterility and/or integrity of injection product contained in the barrel56. A typical compression may be, e.g., less than 10% of the overall width or diameter of the rib52and/or sleeve44when the convertible plunger12is compressed to form a seal in the barrel56, optionally less than 9%, optionally less than 8%, optionally less than 7%, optionally less than 6%, optionally less than 5%, optionally less than 4%, optionally less than 3%, optionally less than 2%, optionally from 3% to 7%, optionally, from 3% to 6%, optionally from 4% to 6%, optionally from 4.5% to 5.5%, optionally from 4.5% to 5.5%, optionally about 4.8%. The compression is dependent on not only the geometric tolerances of the plunger and syringe barrel but also the material properties of the plunger (e.g., durometer of the rubber). Optionally, additional ribs52of the storage sealing section51may be included, which may increase the integrity of the seal and/or form separate seals between the plunger12and the sidewall58of the barrel56. Embodiments having such additional ribs are illustrated inFIGS.36-38Aand described in detail below. According to certain embodiments, the sleeve44and insert42are sized such that, when the plunger12is in the barrel56and the insert42is in the first cavity48, the insert42prevents or minimizes a reduction in the size of the first cavity48. Such minimizing or prevention of a reduction in size of the first cavity48may minimize the extent the size of the rib52of the storage sealing section51, which is generally adjacent and/or aligned to/with the first cavity48, may be reduced by engagement of the rib52with the sidewall58of the barrel56. According to such embodiment, the rib52may be sized such that, with the support of the insert44in the first cavity48, the rib52is large enough to be compressed between the sleeve44and the sidewall58to form the compression seal for storage mode of the plunger12. Further, according to certain embodiments, the insert42may be configured to limit the compression of the rib52and/or sleeve44such that the rib52and/or sleeve44is compressed less than 20% of the overall width of the sleeve44when the plunger12is being used to form a seal during storage mode in the barrel56. Optionally, the rib52and/or sleeve44are compressed less than 10% of the overall width or diameter of the rib52and/or sleeve44when the plunger12is compressed to form a seal in the barrel56, optionally less than 9%, optionally less than 8%, optionally less than 7%, optionally less than 6%, optionally less than 5%, optionally less than 4%, optionally less than 3%, optionally less than 2%, optionally from 3% to 7%, optionally, from 3% to 6%, optionally from 4% to 6%, optionally from 4.5% to 5.5%, optionally from 4.5% to 5.5%, optionally about 4.8%. Alternatively, according to other embodiments, the insert42may be sized to expand the size of the first cavity48and rib52of the storage sealing section51so as to provide sufficient support to push or force the rib52against the sidewall58to form the compression seal during storage mode of the plunger12. The plunger12may be positioned in the barrel56before or after the plunger12is connected to the exterior shaft18. When injection product in the syringe barrel, such as in the product containing area59of the barrel56, is to be dispensed from the barrel56, a user may depress the actuator26to displace the interior shaft16from the first position to the second position, as previously discussed. In the embodiment shown inFIGS.1-4, as the interior shaft16is displaced to the second position, the proximal end22of the interior shaft16may exit the first end28of the exterior shaft18and enter into the plunger12. As the locking tab24is moved to the second recess34, the interior shaft16may push the insert42from the first cavity48to the second cavity50. With the insert42in the second cavity50, the support and/or force that the insert42had been providing/exerting upon the rib52of the storage sealing section51is reduced and/or removed. Thus, under such circumstances, the force previously exerted by the rib52against the sidewall58of the barrel56is also at least reduced, or preferably removed (i.e., with no contact between the rib52of the sealing section51and the sidewall58of the barrel56when the plunger12is in a “dispensing mode.”). Additionally, according to certain embodiments, a rib52may not be generally adjacent to and/or aligned with the second cavity50of the sleeve44so that the presence of the insert42in the second cavity50is not supporting or pushing a different rib52against the sidewall58. Thus, with the force that had been exerted by the rib52against the sidewall58being removed or reduced by the displacement of the insert42to the second cavity50, the force needed to displace the plunger12along the barrel56is less than the force would have been had the insert42remained in the first cavity48. Thus, the force that had been exerted against the sidewall58by the plunger12is adjusted, and more specifically reduced, when the plunger12is to be displaced for dispensing of the injection product. Moreover, the extent of the force reduction is such that the injection product may be pushed completely forward out of the syringe against the back pressure caused by the viscosity of the injection product and/or the needle gauge. With the insert42in the second cavity50and the interior shaft16in the second position, the plunger assembly10may be displaced to reduce the size of the product containing area, and thereby dispense the injection product from the barrel56. Additionally, according to certain embodiments, the plunger12may optionally be configured such that when the first cavity48is not occupied by the insert42, the rib52nonetheless maintains contact with the sidewall58of the barrel56. Moreover, under such conditions, the rib52may be configured to provide a wiper surface to assist in the removal of injection product from the barrel56as the plunger assembly10is displaced during administration/dispensing of the injection product. Optionally, the outer portion46of the sleeve44may include a liquid sealing section53, preferably on the sidewall90of the sleeve44, optionally adjacent to, distal to or otherwise near to the nose cone92. The liquid sealing section53comprises at least one rib55of the liquid sealing section53. The purpose of the liquid sealing section53is to provide a liquid tight seal both when the plunger12is in a storage mode as explained above, and when the plunger is transitioned into a “dispensing mode,” i.e., when the storage sealing section51reduces or ceases compressive force against the barrel wall58so as to facilitate advancement of the plunger to dispense the contents of the syringe. Optionally, the liquid sealing section53may also provide CCI. Preferably, there is a valley57separating the storage sealing section51from the liquid sealing section53. FIGS.36-38Ashow three alternative optional embodiments of convertible plungers712,812,912, according to aspects of the present invention, wherein each of the plungers712,812,912comprise more than one rib752,852,952of a respective plunger's storage sealing section751,851,951. As shown inFIGS.36-37A, for example, the plungers712,812each include two ribs752,852in their respective storage sealing sections751,851. In an optional alternative of a convertible plunger912shown inFIGS.38and38A, the storage sealing section951of the plunger912includes three ribs952. In certain respects, the plungers712,812,912include some structural components substantially similar to the plunger12ofFIGS.1-4and in certain respects operate in a substantially similar manner to the plunger12. For example, a plunger's connector body745,845,945may be configured to be connected to an exterior shaft of a plunger rod, such as, for example, by the threaded engagement of an internal thread740,840,940of the connector body745,845,945and the external thread738,838,938of a respective exterior shaft. Much of the discussion above concerning the structure and function of the plunger12ofFIGS.1-4is equally applicable to the plungers712,812,912and thus will not be repeated here in full. The following is a non-limiting summary of some structural features of the plungers712,812,912. The plunger712,812,912includes an insert742,842,942, a sleeve744,844,944and a connector body745,845,945. The connector body745,845,945may be operably connected to the sleeve744,844,944in any such manner described herein with respect to the plunger12ofFIGS.1-4. Likewise, the connector body745,845,945may be connected to a plunger rod in any such manner described herein with respect to the plunger12ofFIGS.1-4. The sleeve744,844,944may be configured to provide a first cavity748,848,948and a second cavity750,850,950, which are in communication with each other and are configured to receive the movable insertion of the insert742,842,942. The outer portion746,846,946of the sleeve744,844,944comprises a nose cone792,892,992and a sidewall790,890,990. The sidewall790,890,990of the sleeve744,844,944includes a storage sealing section751,851,951comprising ribs752,852,952that are preferably generally adjacent to and/or aligned with at least a portion of the first cavity748,848,948. As with the plunger12ofFIGS.1-4, the storage sealing section751,851,951of a respective plunger712,812,912is configured (when in storage mode) to provide CCI and optionally a barrier to one or more gases. When the convertible plunger712,812,912is converted from storage mode to dispensing mode, the seal initially provided by the storage sealing section751,851,951is either reduced or removed entirely (i.e., such that the storage sealing section751,851,951no longer physically contacts the sidewall of a syringe barrel in which the plunger712,812,912is disposed). Optionally, the outer portion746,846,946of the sleeve744,844,944may include a liquid sealing section753,853,953preferably on the sidewall790,890,990of the sleeve744,844,944optionally adjacent to, distal to or otherwise near to the nose cone792,892,992. The liquid sealing section753,853,953comprises at least one rib755,855,955of the liquid sealing section753,853,953. The purpose of the liquid sealing section753,853,953is to provide a liquid tight seal both when the plunger712,812,912is in storage mode and when the plunger is transitioned into dispensing mode. Optionally, the liquid sealing section753,853,953may also provide CCI. Preferably, there is a valley separating the storage sealing section751,851,951from the liquid sealing section753,853,953. Optionally, a film coating or cap is applied to a portion of the plunger sleeve744,844,944. While any plunger embodiment of the present invention (e.g.,712,812,912) may include such a film or cap, the plunger912ofFIGS.38and38Aas illustrated includes a film coating988mounted over the nose cone992and a portion of the sidewall990of the film coated plunger912. Preferably, as shown, the film coating988covers the entire nose cone992. The film coating988also optionally covers the rib955of the liquid sealing section953and optionally a small section of the valley adjacent to the rib955. Optionally, as shown inFIG.38A, the valley of the plunger912comprises a descending slope extending distally from the liquid sealing section953, the descending slope leading to a floor, the floor leading to an ascending slope toward the storage sealing section951. As illustrated, the film coating988terminates towards the beginning of the descending slope of the valley. Optionally, the film coating988terminates before the storage sealing section, optionally before the ascending slope, optionally before the floor. In any event, there is preferably no film coating988covering any of the ribs952of the storage sealing section951. The film coating988may be made, e.g., from any materials disclosed elsewhere in this specification with regard to the film coating88or film94(see, e.g.,FIGS.8-10and26). As discussed throughout this specification, an optional feature of convertible plungers according to the present invention is an insert which may be configured to provide outward radial pressure on a rib(s) of the liquid sealing section when the plunger is in storage mode. Such inserts may come in a variety of materials, shapes and configurations. For example, the insert842of plunger812is generally spherical. When the insert842is not in the cavity848, the cavity848optionally has a reduced volume which is expanded (as shown inFIG.37A) by radial pressure the insert842applies on the sleeve844when the insert842is retained therein. The inserts742and942of plungers712and912are generally cylindrical with a slight concavity around the periphery of the sidewall of a respective insert. The central axes of the generally cylindrical inserts742and942are optionally positioned parallel to or preferably in alignment with the central axis of a respective plunger712,912. Optionally, the inner walls of the first cavity include a slightly convex cylindrical outline (seeFIGS.36A and38A) that provides complementary mating geometry to the slightly concave (around its periphery) sidewall of the insert742,942. Such mating geometry may help the insert742,942to find its “home” position within the first cavity during assembly of the plunger742,942and thereafter retain the insert742,942in that position until the plunger712,912is transitioned from storage mode to dispensing mode. It is contemplated that the shape, material and positioning of an insert may be configured to provide a desired level of radial pressure distribution (e.g., even, concentrated in one or more places, in one or more directions, etc.). While a single sealing rib (e.g.,52) on a convertible plunger is within the scope of the present invention, it is contemplated that two sealing ribs (e.g.,752,852) or three sealing ribs (e.g.,952) would better ensure the integrity of the seal. As discussed above, the embodiment of the plunger assembly10shown inFIGS.1-4comprises a sleeve44having two cavities in communication with each other—a first cavity48and a second cavity50. As shown inFIGS.1-4, the initial position of the insert42is in the first cavity48, which compresses the rib52of the storage sealing section51against the sidewall58of the barrel. This positioning of the insert42configures the plunger12in storage sealing mode, as discussed above. During assembly of the syringe, depending on the method used, it may be difficult to insert the plunger12into the barrel56while the plunger12is in storage mode configuration. This is due to the compressive seal the plunger12provides while in storage mode. Accordingly, in another aspect, the invention is directed to convertible plunger assemblies configured to facilitate insertion of a plunger into a barrel, e.g., during assembly of a pre-filled syringe. Referring now toFIGS.31-35, there is shown an alternative convertible plunger, in this case a three-position plunger612. As shown inFIG.31, the three position plunger comprises a sleeve644optionally configured to provide an opening643at a distal end thereof, a pre-load cavity647proximal to the opening, a first cavity648proximal to the pre-load cavity647and a second cavity650proximal to the first cavity648. As shown, the pre-load cavity647is in communication with the first cavity648, which in turn, is in communication with the second cavity650. Aside from the presence of the pre-load cavity647, the plunger sleeve644may be otherwise substantially identical to the sleeve44of the plunger12shown inFIGS.1-4. The cavities647,648,650are configured to receive the movable insertion of an insert. An isolated view of the insert642which may be used with the three-position plunger612, is shown inFIG.32. The insert642resembles the gripping portion of a ball knob. The insert642may be generally partially spherical in shape—“partially” because the insert642is secured to or integral with an insert shaft642a, which interrupts the otherwise spherical geometry of the insert642. The insert shaft642ais secured to or integral with an insert flange642b. Optionally, the insert flange642bdoes not need to be a different diameter than the insert shaft642a. The insert flange642bmay optionally protrude from the sleeve644when the insert642is disposed in the pre-load cavity647and the first cavity648. This feature would enable one to visually observe the position of the insert to confirm its position in the sleeve644. By looking at the syringe or measuring the position of the insert flange642b, one may readily determine whether the insert642is disposed in the pre-load cavity647or the first cavity648, as a way of doing a quality check or confirmation. Referring toFIG.33, there is shown a partial cross-sectional view of a barrel56having a three-position plunger assembly610inserted therein. The plunger assembly610includes a three position plunger612and plunger rod614. The plunger rod614, which comprises an interior shaft616and exterior shaft618, connects to the plunger612and operates substantially as described above with respect to the plunger assembly10ofFIGS.1-4. In brief, the internal shaft616is movable in a proximal direction relative to the external shaft618to press against the insert flange642band thereby drive the insert642from its initial position, i.e., within the pre-load cavity647, to the first cavity648and finally to the second cavity650. The three-position plunger612further comprises a round collar630secured thereto. The round collar630is preferably formed from plastic or another material having a greater rigidity than the plunger material. Optionally, the pre-load cavity is generally aligned with at least a portion of the round collar630. Optionally, the round collar is in the form of a collapsible c-ring. The round collar630protects the plunger, reduces the amount of exposed rubber of the plunger, provides guidance for smooth travel of the plunger612, and provides a rigid surface for the plunger rod614to press against when actuating the plunger612. In use, a syringe may be assembled by providing the plunger612, with the insert642pre-inserted into the pre-load cavity647of the three-position plunger612. The external profile of the plunger and/or compressive force or radial pressure the plunger exerts against the barrel56is unaffected by disposal of the insert642in the pre-load cavity647. Accordingly, the plunger612may be inserted into the barrel56with relative ease. Once the plunger612is sufficiently inserted into the barrel56with the insert disposed in the pre-load cavity647(i.e., in “pre-load mode”), the insert642may be advanced into the first cavity648by applying downward pressure on the insert642. Once the insert642is disposed in the first cavity648, the plunger612is then in storage mode. The plunger will then remain in storage mode until it is time to use the syringe. As described above, transition from the first cavity to the second cavity converts the plunger from a use mode configuration to a dispensing mode configuration. For clarity,FIG.34shows the insert642disposed in the first cavity648andFIG.35shows the insert642disposed in the second cavity650. Optionally, the insert provides a visual indicator showing externally in which cavity the insert642is disposed at a given time, as explained above. This indication can be confirmed by observations or vision inspection to verify that the insert is properly positioned, i.e., either in pre-load mode or storage mode. Optionally, the plunger rod614can be added to the filled syringe at a later time. All of the functions of the plunger612and insert642are self-contained. The plunger rod614or other means may optionally be used to axially displace the insert642. Optionally, a two-position plunger configuration may be employed wherein the second cavity functions both as a pre-load cavity for retaining an insert in preload mode and as a second cavity for retaining the insert in dispensing mode, as disclosed above. For such an embodiment, the insert may be reversibly axially displaceable between second and first cavities more than one time. In this way, the insert may be pre-inserted into the pre-load cavity such that the external profile of the plunger and/or compressive force or radial pressure the plunger exerts against a syringe barrel is unaffected by disposal of the insert in the pre-load cavity. Accordingly, the plunger may be inserted into the barrel with relative ease. Once the plunger is sufficiently inserted into the barrel with the insert disposed in the pre-load cavity in pre-load mode, the insert may be retracted axially into the first cavity by applying upward or pulling pressure on the insert. Once the insert is disposed in the first cavity, the plunger is then in storage mode. The plunger will then remain in storage mode until it is time to use the syringe. To transition the plunger into dispensing mode, downward pressure is applied to the insert to displace it into the second cavity. In this particular embodiment, the presence of the insert in the second cavity places the plunger in both insertion mode and dispensing mode (which mode depends on the action at a given moment that the plunger is intended to facilitate, i.e., insertion or dispensing). FIGS.5-7illustrate an alternative embodiment of the plunger assembly10, and in particular, an alternative plunger12′. The plunger12′ includes an insert62, a connector body63, and a sleeve64. As shown inFIG.5, according to certain embodiments, the sleeve64includes a cavity66configured to receive placement of the proximal end22of the interior shaft16. The insert62may also include a relatively rigid shaft68that assists in the displacement of the insert62and/or deformation of the plunger12′, as discussed below. According to certain embodiments, the connector body63may be molded from a relatively stiff and/or rigid material, such as, for example, polyethylene or polypropylene. Additionally, the connector body63may have a first section65, a second section67, and a third section69. The first section65of the connector body63is configured for a connectable engagement with the exterior shaft18. For example, as shown by at leastFIG.7, the first section65may include an internal thread40that mates with an external thread38of the exterior shaft18. According to certain embodiments, the second section67of the connector body63may provide an internal structure in the plunger12′ that minimizes and/or prevents a reduction in the size, such as the width (as indicated by “W” inFIG.7) of the sleeve64when the plunger12′ is inserted into the barrel56. According to such an embodiment, the sleeve64may be sized such that, when the plunger12′ is positioned in the barrel56, the sleeve64is compressed, with the support of the second section67, between the sidewall58of the barrel56and the second section67of the connector body63. Such compression of the sleeve64may result in the formation of a seal, such as, for example, a compression seal, between the plunger12′ and the barrel56that may be used to maintain the sterility and/or integrity of an injection product stored in the barrel56. In addition to the second section67of the connector body63, according to certain embodiments, the insert62may also be configured to provide support to the sleeve64and/or connector body63when the plunger12′ is inserted into a barrel56. Further, according to certain embodiments, one or more ribs52of a storage sealing section51may extend from the sleeve64and be compressed against the sidewall58of the barrel56to provide CCI during when the plunger is in a “storage mode,” e.g., to seal the contents of a pre-filled syringe when in storage, prior to use. The plunger12′ may further include a liquid sealing section53comprising at least one rib55of the liquid sealing section53. The purpose of the liquid sealing section53is to provide a liquid tight seal both when the plunger12is in a storage mode as explained above, and when the plunger is transitioned into a “dispensing mode,” i.e., when the storage sealing section51reduces or ceases compressive force or radial pressure against the barrel wall58so as to facilitate advancement of the plunger to dispense of the contents of the syringe. Preferably, there is a valley57separating the storage sealing section51from the liquid sealing section53. Alternatively, according to optional embodiments, each rib52,55may form a separate seal when compressed against the sidewall58of the barrel56. For example, in the embodiment illustrated inFIGS.5-7, the sleeve64includes two ribs52,55that may be used to form a seal(s) between the sidewall58of the barrel56and the sleeve64. Further, according to certain embodiments, the second section67and/or insert42may be configured to limit the compression of the rib52and/or sleeve64such that the rib52and/or sleeve64are not compressed more than 20% of the overall width or diameter of the rib52and/or sleeve64when the plunger12′ is compressed to form a seal in the barrel56. Optionally, the rib52and/or sleeve64are compressed less than 10% of the overall width or diameter of the rib52and/or sleeve64when the plunger12′ is compressed to form a seal in the barrel56, optionally less than 9%, optionally less than 8%, optionally less than 7%, optionally less than 6%, optionally less than 5%, optionally less than 4%, optionally less than 3%, optionally less than 2%, optionally from 3% to 7%, optionally, from 3% to 6%, optionally from 4% to 6%, optionally from 4.5% to 5.5%, optionally from 4.5% to 5.5%, optionally about 4.8%. The third section69of the connector body63may provide a surface upon which the insert62may exert a force against to elongate the length (as indicated by the “L” direction inFIG.7), and thereby reduce the width (“W”) of, the plunger12′ when injection product is to be dispensed from the barrel56, as discussed below. According to certain embodiments, the outer surface70of the insert62, the second section of the connector body53, and the inner surface76of the sleeve64may have a plurality of recesses72,77,80and protrusions74,78,79as shown inFIG.7. Moreover, shape provided by the recesses72and protrusions74of the insert62may be generally be followed by the recesses77and protrusions79of the connector body63, which are generally followed by the recesses80and protrusions78of the sleeve64. Such recesses72,77,80and protrusions74,78,79may assist in maintaining the insert62in a sealing position in the barrel56. Moreover, as shown for example inFIG.7, the recesses72,77,80and protrusions74,78,79may provide obstacles that prevent the premature displacement of the insert62. Such an accordion shaped configuration may also assist in the elongation of the plunger12′, and in particular the second section67of the connector body53and the sleeve64when the plunger12′ is to be displaced in the barrel56from a deactivated position, as shown inFIG.7, to an activated position that elongates the length of the sleeve64. More specifically, when the injection product is to be dispensed from the barrel56, the interior shaft16may be displaced from the first position, as shown inFIG.5, to a second position, as previously discussed. As the interior shaft16is displaced toward the second position, the proximal end22of the interior shaft16exerts a pushing force upon an insert62, such as, for example, upon the shaft68of the insert62. As the interior shaft16exerts a force upon the insert62, the insert62is displaced within the sleeve64generally in the direction of the proximal end61of the barrel56, and thus at least a portion of the outer surface70of the insert62pushes against the third section69of the connector body63. As the insert62is displaced and presses upon the third section69, the second section67of the connector body63is elongated, thereby changing the prior accordion shape of the second section67to a generally straighter or flatter configuration. Additionally, the sleeve64is also elongated by this displacement of the insert62in the sleeve64, resulting in the width (as indicated by the “W” direction inFIG.7) of the sleeve64and thus convertible plunger12′ being reduced. The reduction in the width of the sleeve64/convertible plunger12′ results in a reduction in the compressive force that had been used to form the seal between the convertible plunger12′ and the sidewall58of the barrel56. In other words, slight axial stretching of the sleeve64(optionally achieved by displacing the insert62from a deactivated position to an activated position) in turn reduces the width of the sleeve64and convertible plunger12′, thus resulting in reduction in the compressive force that had been used to form the seal between the convertible plunger12′ and the sidewall58of the barrel56. Thus, with the width of the sleeve64/convertible plunger12′ reduced, the force necessary to displace the convertible plunger12′ in the barrel56may also be reduced. Further, as previously discussed, as the interior shaft16may be locked in the second position by the locking tab24, the sleeve64may maintain the elongated shape while the injection product is dispensed from the barrel56. An alternative embodiment of a convertible plunger1012, in this case a stretchable plunger, is illustrated inFIGS.39and39A. The stretchable plunger1012may be connected to an exterior shaft of a plunger rod14, for example, by the threaded engagement of an internal thread1040on a connector body and the external thread1038of the exterior shaft. The plunger1012includes a sleeve1044which may be constructed from any of the same materials of other sleeves (e.g.,44) disclosed in this specification. The outer portion of the sleeve1044comprises a sidewall and nose cone as with other sleeves disclosed in this specification. The sidewall of the sleeve1044includes a storage sealing section1051comprising three ribs1052(although more or fewer ribs may be used). As with the plunger12ofFIGS.1-4, the storage sealing section1051is configured (when in storage mode) to provide CCI and optionally a barrier to one or more gases. When the stretchable plunger1012is converted from storage mode to dispensing mode, the seal initially provided by the storage sealing section1051is either reduced or removed entirely. Optionally, the outer portion of the sleeve1044may include a liquid sealing section1053preferably on the sidewall of the sleeve1044optionally adjacent to, distal to or otherwise near to the nose cone. The purpose of the liquid sealing section1053is to provide a liquid tight seal both when the plunger1012is in a storage mode and when the plunger is transitioned into dispensing mode. Optionally, the liquid sealing section1053may also provide CCI. The plunger1012further comprises a cap1094covering the nose cone and some or all of the liquid sealing section1053. The cap1094is preferably made from an injection moldable thermoplastic material e.g., a cyclic olefin polymer (COP), cyclic olefin copolymer (COC) or polycarbonate. Optionally, the cap1094is an injection moldable part that is assembled onto the sleeve1044. The cap1094may include an elongated stem1095extending into the sleeve1044. Optionally, the sleeve1044includes a stem cover1097which receives and retains (e.g., through interference fit, adhesive, and/or other means) the stem1095, thereby securely retaining the cap1094on the sleeve1044. A user's application of downward pressure onto the interior shaft16of the plunger rod14in turn transfers that pressure onto the stem cover1097, the stem1095and the cap1094. Since the cap1094is secured to the sleeve1044, the initial movement of the interior shaft16does not at first displace the plunger1012down the barrel; rather such initial movement causes the cap1094to pull on and thus slightly stretch the sleeve1044in direction L. In so doing, the width W of the plunger1012is reduced slightly, thus reducing the plunger1012from an expanded state to a constricted state, or from storage mode to dispensing mode. Optionally, the cap is coated with a barrier coating or layer to provide a gas barrier between contents of a syringe and the ambient environment. Optionally, at least one organo-siloxane coating or layer may be applied on top of the barrier coating or layer to protect the barrier layer from being degraded by syringe contents having a pH broadly within the range of 5 to 9. Optionally, a tri-layer coating set may be applied to the cap. These coatings, layers and coating sets are preferably applied via chemical vapor deposition, more preferably plasma enhanced chemical vapor deposition, and are described in detail elsewhere in this specification. Alternatively, two-position plunger assemblies may be desired for some applications wherein the interior shaft is displaced in a direction away from the plunger, rather than towards the plunger, from a first position to a second position relative to the exterior shaft. Such a configuration may be desired where it is preferable not to apply downward pressure on the plunger until it is time to advance the plunger into the barrel to dispense the syringe's contents. For example,FIG.13shows a two-position plunger assembly210that functions in essentially the same way as the assembly10shown inFIG.2, except that the assembly210permits a user to move from a first position to a second position by displacing the interior shaft216away from the plunger212, rather than towards the plunger212. The convertible plunger12of the assembly210ofFIG.13, as shown, includes a first cavity and second cavity with a spherical insert disposed in the first cavity (e.g., as the convertible plunger12ofFIG.3). It should be understood that the plunger embodiment shown is for illustrative purposes only, and that various plunger configurations, including configurations discussed below, may optionally be used as part of the plunger assembly210ofFIG.13. The plunger assembly210includes a plunger212and a plunger rod214. The plunger rod214may include an interior shaft216and an exterior shaft218. The interior shaft216includes a distal end220, a proximal end222, and a locking tab224. According to certain embodiments, the distal end220of the interior shaft216may be configured to form an actuator226that, during use of the plunger assembly210, is to be pressed upon by a user, such as, for example, by the thumb of the user. The exterior shaft218may include a first end228, a second end230, a first recess232, a second recess234, and an inner portion236. According to certain embodiments, the first end228may be configured for a threaded engagement with the plunger212. For example, as shown, the first end228may include an external thread238that is configured to mate with an internal thread240of the plunger212. FIG.13illustrates the interior shaft216in a first position relative to the exterior shaft218, with the locking tab224protruding into at least a portion of the first recess232of the exterior shaft218. The orientation of the tapered surface225of the locking tab232allows, when sufficient force is exerted upon the actuator226, for the locking tab232to be at least temporarily compressed or deformed in size so that the locking tab224may at least temporarily enter into the inner portion226as the locking tab225is moved from the first recess232to the second recess234. However, in the absence of sufficient force, the locking tab232may remain in the first recess232, thereby maintaining the interior shaft216in the first position. The orientation and size of the tapered surface225of the locking tab224may provide the locking tab224with sufficient width to prevent the locking tab224from being pushed into the inner portion236in the general direction of the first end228of the exterior shaft218. Accordingly, when the locking tab224is in the second recess234, and thus the interior shaft216is in the second position, the orientation and size of the tapered surface225of the locking tab224may provide the locking tab224with sufficient width to resist the locking tab224from being pushed back into the first recess232. As such, pressing upon the actuator226would cause the entire plunger assembly210to move together as a single unit, e.g., within a pre-filled syringe barrel to dispense contents held therein. In one aspect, the invention is directed broadly to convertible plungers and assemblies incorporating the same. Convertible plungers according to the present invention are adapted to provide sufficient compressive force against the sidewall of a pre-filled syringe or cartridge barrel to effectively seal and preserve the shelf-life of the contents of the barrel during storage. When a convertible plunger provides container closure integrity (CCI) adequate to effectively seal and preserve the shelf-life of the contents of the barrel during storage, the plunger (or at least a portion of its exterior surface) may alternatively be characterized as being in an expanded state or storage mode. The expanded state or storage mode may be a product of, for example, an expanded outer diameter or profile of at least a portion of the syringe barrel-contacting surface of the plunger and/or the normal force that the plunger exerts on the inner wall of the syringe barrel in which it is disposed. The convertible plunger (or at least a portion of its exterior surface) is reducible to what may be alternatively be characterized as a constricted state or a dispensing mode, wherein the compressive force against the sidewall of the barrel is reduced, allowing a user to more easily advance the plunger in the barrel and thus dispense the contents of the syringe or cartridge. The constricted state or dispensing mode may be a product of, for example, a reduced outer diameter (relative to that of the expanded state) of at least a portion of the syringe barrel-contacting surface of the plunger and/or reduced normal force against the inner wall of the syringe barrel exerted by the plunger. Other examples of what constitutes an expanded state versus constricted state are discussed below. Accordingly, in one aspect, the invention is a convertible plunger comprising an internal portion and a generally cylindrical exterior surface. As used herein, a “generally cylindrical” exterior plunger surface may include minor interruptions or variations in geometry (e.g., due to ribs, valleys, etc.) to the otherwise cylindrical shape of the plunger. For example, a generally cylindrical exterior surface of the plunger may include one or more annular ribs. At least a portion of the exterior surface is maintained in an initial expanded state by a property of the internal portion. The expanded state is reducible to a constricted state by an operation that is applied to the internal portion of the plunger to alter the property. The plunger may be reduced from the expanded state to the constricted state utilizing a variety of methods, which may include two-position configurations, e.g., as described above, or not. As used herein, “expanded state” and “constricted state” may refer to comparative dimensional measurements (e.g., expanded state being wider than constricted state) and/or comparative resistance to inward compression of the plunger (the “expanded state” being more resistant to inward compression and the “constricted state” being less resistant to inward compression) and/or comparative outward radial pressure exerted by at least a portion of the plunger's exterior surface (the plunger's exterior surface in the “expanded state” exerting more outward radial pressure and in the “constricted state” exerting less outward radial pressure). For example, the property that maintains at least a portion of the exterior surface of the plunger in the expanded state may include, e.g., gas pressure, mechanically produced outward radial pressure or outward radial pressure produced by a liquid or gelatinous compression material disposed within one or more cavities within the plunger. Where the property is gas pressure, the property may be altered by releasing at least some of the pressure from the cavity or cavities. Where the property is mechanically produced outward radial pressure, such as that produced by a solid compression material, the property may be altered by, e.g., collapsing, crushing, deforming, breaking, or otherwise altering the structure of the solid compression material in whole or in part, or displacing the solid compression material, so as to reduce the outward radial pressure. Where the property is outward radial pressure produced by a liquid or gelatinous material, the property may be altered by removing at least some of the material from the cavity. Optionally, the convertible plunger may be a component of a plunger assembly, for example, any of the plunger assemblies described above. The assembly comprises a plunger rod having an exterior shaft and an interior shaft. The exterior shaft has an inner portion configured for the slideable insertion of at least a portion of the interior shaft and the interior shaft is configured to be displaced from a first position to a second position relative to the exterior shaft. The assembly further comprises the convertible plunger operably connected to the plunger rod, the convertible plunger configured to receive the insertion of at least a portion of the interior shaft. Depending on the application, the interior shaft may be displaceable from a first position to a second position in a direction towards the plunger (e.g., using the assemblies shown inFIG.2or5), or in a direction away from the plunger (e.g., using the assembly shown inFIG.13). Referring toFIG.14, there is shown a substantially spherical mesh insert300. As shown inFIG.15, the spherical mesh insert300may be disposed within a cavity48aof a convertible plunger12a. The mesh insert is configured to provide mechanically produced outward radial pressure to maintain the exterior surface of the plunger12ain an initial expanded state. When the plunger12ais a component in a plunger assembly such as the assembly10shown inFIG.2, displacement of the interior shaft16relative to the exterior shaft18towards the plunger12acauses the interior shaft16to contact and press into the spherical mesh insert300. When sufficient pressure is applied against the spherical mesh insert300, its structural integrity is compromised, causing it to collapse or deform. This reduces outward radial pressure in the plunger12a, thereby reducing at least a portion of the exterior surface of the plunger12ato a constricted state. Once the exterior surface of the plunger12ais in a constricted state, the plunger rod214, as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. The spherical mesh insert300may be made, e.g., from metal or plastic. A skilled artisan would readily recognize that the invention may be implemented using solid materials other than mesh inserts, for example other collapsible or breakable materials and configurations. For example, referring toFIG.16, there is shown a substantially cylindrical insert302. The cylindrical insert302may be in the form of a collapsible mesh, for example. Alternatively, the cylindrical insert302may be a solid or substantially solid compression material, e.g., a polymer, which is mechanically less resistant to axially applied pressure than to inward radial pressure. While a substantially cylindrical geometry is preferred for this type of insert, it is contemplated that other geometries which are inwardly collapsible or deformable, upon application of axial pressure, may be utilized as well. The cylindrical insert302includes a central portion303. When sufficient pressure is applied to the central portion303, the insert302collapses inward (towards the central axis). Prior to the inward collapse of the insert302, the insert302has a first diameter D1. After the inward collapse of the insert302, the insert302is reduced to a constricted second diameter D2, as shown inFIG.16A. Referring toFIG.17, the cylindrical insert302may be disposed within a cavity48bof a convertible plunger12b. The insert302is configured to provide mechanically produced outward radial pressure to maintain the exterior surface of the plunger12bin an initial expanded state. When the plunger12bis a component in a plunger assembly such as the assembly10shown inFIG.2, displacement of the interior shaft16relative to the exterior shaft18towards the plunger12bcauses a narrow tip16′ on the interior shaft16to contact and press into the central portion303of the insert302. When sufficient pressure is applied against the central portion303, the structural integrity of the insert302is compromised, causing it to collapse or deform inward. This reduces outward radial pressure in the plunger12b, causing at least a portion of the exterior surface of the plunger12bto be reduced to a constricted state. Once the exterior surface of the plunger12bis in a constricted state, the plunger rod14, as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. Referring toFIG.18, there is shown an alternative embodiment of a plunger assembly utilizing the basic configuration of the assembly210shown inFIG.13. This embodiment may include a plunger12csecured to the exterior shaft218and an interior shaft216axially displaceable relative to the exterior shaft218. The plunger12chas a thin, substantially cylindrical cavity48calong the central axis of the plunger12c, with an opening305at the top of the plunger12c. Extending axially from the proximal end222of the interior shaft216is a thin, substantially cylindrical protrusion304having complementary or mating geometry with the cavity48cin the plunger12c. At least a portion of the exterior surface of the plunger12cis maintained in an initial expanded state when the cavity48cis mated with or occupied by the protrusion304. In other words, the protrusion304provides mechanically produced outward radial pressure to maintain the exterior surface of the plunger12cin an expanded state. The protrusion304is removable from the cavity48cby displacing the interior shaft216in a direction away from the plunger12cto retract the protrusion304out of the opening305until the protrusion304no longer occupies the cavity48c, and thus no longer provides the mechanically produced outward radial pressure within the plunger12c. In this position, the empty cavity48cdoes not resist inward compression as well as it did when it was occupied by the protrusion304and thus the exterior surface of the plunger12cis reduced to a constricted state. Optionally, the protrusion304and/or the cavity48care lubricated, e.g., with silicone oil or a lubricious film coating, such as those described below, to facilitate easy removal of the protrusion304from the cavity48c. Once the exterior surface of the plunger12cis in a constricted state, the plunger rod214, as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. Referring toFIG.19, there is shown an anchoring device, or tapered insert306configured much like a plaster anchor. Plaster anchors are hollow, typically tapered tubular members that are adapted to expand upon receipt of a screw or another narrow protrusion. A plaster anchor may revert, at least in part, to its initial unexpanded state upon removal of the screw or other narrow protrusion. Likewise, the insert306, which may comprise one or more axially tapered wings307about its periphery and a narrow axial cavity304a, is in an expanded state when a protrusion304bis inserted in the cavity304a. The insert306is reduced to a less expanded state upon removal of the protrusion304bfrom the cavity304a. Although the embodiment of the insert306as shown is tapered, non-tapered configurations, e.g., with substantially parallel wings or sides, are within the scope of the invention. Referring toFIG.20, there is shown an alternative embodiment of a plunger assembly utilizing the basic configuration of the assembly210shown inFIG.13. This embodiment may include a plunger12dsecured to the exterior shaft218and an interior shaft216axially displaceable relative to the exterior shaft218. The plunger12doptionally has a substantially tapered cavity48dalong the central axis of the plunger12d, with an opening305aat the top of the plunger12d. The insert306is disposed within the cavity48d, and may be integral with the plunger12d(e.g., molded within the plunger) or a separate component inserted within the plunger cavity48d. Extending axially from the proximal end222of the interior shaft216is the thin, substantially cylindrical protrusion304bhaving complementary or mating geometry with the cavity304ain the insert306. At least a portion of the exterior surface of the plunger12dis maintained in an initial expanded state when the cavity304ais mated with or occupied by the protrusion304b. In other words, the protrusion304bexpands the wings307of the insert so as to provide mechanically produced outward radial pressure to maintain the exterior surface of the plunger12din an expanded state. The protrusion304bis removable from the cavity304aby displacing the interior shaft216in a direction away from the plunger12dto retract the protrusion304bout of the opening305auntil the protrusion304bno longer occupies the cavity304a. Once the protrusion304bhas been removed from the cavity304a, the wings307slightly retract inward towards the insert's central axis, thereby reducing outward radial pressure within the plunger12d, thus permitting the exterior surface of the plunger12dto be reduced to a constricted state. Once the exterior surface of the plunger12dis in a constricted state, the plunger rod214, as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. The protrusion304bmay optionally be removed from the cavity304aby pulling the interior shaft216from a first position to a second position, substantially as described above with respect to the assembly210shown inFIG.13. Alternatively, the internal shaft216may be rotatable in relation to the external shaft218, or vice versa. With such a configuration, the protrusion304bmay be threaded and mated with complementary threads within the cavity304a. To remove the insert304bfrom the cavity304a, a user may rotate the internal shaft216relative to the external shaft218(or vice versa), thereby displacing the internal shaft216from a first position (wherein the insert304boccupies the cavity304a) to a second position (wherein the insert304bis removed from the cavity304b). Referring now toFIG.21, there is shown an alternative embodiment of a plunger assembly utilizing the basic configuration of the assembly210shown inFIG.13. This embodiment may include a plunger12esecured to the exterior shaft218and an interior shaft216axially displaceable relative to the exterior shaft218. Part of the internal portion of the plunger12ecomprises a porous material308, such as a foam rubber. Alternatively, part of the internal portion of the plunger12ecomprises empty space. The plunger12efurther includes one or more openings305bin the top thereof, providing a conduit to the porous material308(or empty space, as the case may be). The proximal end of the interior shaft216includes a stopper309, optionally made from a rubber or a polymer. The stopper309provides an air-tight seal between the one or more openings305band the inner portion236of the exterior shaft218. Accordingly, when the interior shaft216is displaced away from the plunger12e, e.g., from a first position to a second position, the stopper effectively sucks air from the porous material308(or empty space) creating therein at least a partial vacuum. This in turn causes the porous material308(or empty space) to collapse, thus reducing at least part of the exterior surface of the plunger12efrom an expanded state to a constricted state. Once the exterior surface of the plunger12eis in a constricted state, the plunger rod214, as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. Referring now toFIG.22, there is shown a convertible plunger12fhaving a sealed inner cavity310and/or a sealed insert comprising a gaseous, gelatinous or liquid compression material310a. The sealed inner cavity310and/or sealed insert comprises an inner surface or membrane312which effectively seals the compression material310awithin the insert. The compression material310ais configured to provide outward radial pressure to maintain at least a portion of the exterior surface of the plunger12fin an initial expanded state. When the plunger12fis a component in a plunger assembly such as the assembly10shown inFIG.2, the proximal end of the interior shaft16includes a substantially sharp tip311extending axially therefrom. Displacement of the interior shaft16relative to the exterior shaft18towards the plunger12fcauses the tip311to contact and press into the top of the plunger12f. When sufficient pressure is applied against the top of the plunger12f, the tip311causes the membrane312to be punctured, thus enabling the egress of at least some of the compression material310afrom the cavity310. This reduces outward radial pressure in the plunger12f, thereby reducing at least a portion of the exterior surface of the plunger12fto a constricted state. Once the exterior surface of the plunger12fis in a constricted state, the plunger rod14, as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. Referring toFIG.23, there is shown an alternative embodiment of a plunger assembly utilizing, e.g., the basic configuration of the assembly210shown inFIG.13. This embodiment may include a convertible plunger12gsecured to the exterior shaft218and an interior shaft216axially displaceable relative to the exterior shaft218. The plunger12ghas a cavity48ewithin the internal portion thereof. Extending from the end of the proximal end of the interior shaft216and into the cavity48eare at least two opposing juts314. Optionally three to eight (or even more) juts314may be used. When the interior shaft216is in a first position, the juts314press into the interior surface of the cavity48e, thereby providing mechanically produced outward radial pressure to maintain the exterior surface of the plunger12gin an expanded state. As shown inFIG.23A, when the interior shaft216is displaced in a direction away from the plunger12gand into a second position relative to the exterior shaft218, the juts314retract inwardly towards the central axis of the interior shaft216. In so doing, the juts314no longer contact the interior surface of the cavity48eand thus no longer provide the mechanically produced outward radial pressure within the plunger12c. In this position, the juts314do not support the cavity408ein resisting inward compression and thus the exterior surface of the plunger12gis reduced to a constricted state. Once the exterior surface of the plunger12gis in a constricted state, the plunger rod214, as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. Referring toFIG.24, there is shown a convertible plunger12hin an expanded or storage state, disposed within a syringe barrel. The plunger12hincludes an internal portion having a cavity48fcharged with gas, e.g., nitrogen, carbon dioxide, air or butane, for example. The gas pressure within the cavity48fshould be above atmospheric pressure, so as to maintain at least a portion of the external surface of the plunger in an initial expanded state. The cavity48fmay include a valve316which maintains the gas pressure within the cavity48f, but is operable to be triggered to release the pressure. The valve may be triggered, for example, by actuating the interior shaft16of the plunger rod, e.g., substantially as discussed above with respect to the assembly shown inFIG.2. When the valve is released, the gas pressure within the cavity48fis reduced, e.g., to atmospheric pressure. In this way, the plunger12heffectively deflates (however insubstantially) thus reducing the profile of the exterior surface from the expanded state to a constricted state. Once the exterior surface of the plunger12his in a constricted state, the plunger rod14, as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. Referring toFIG.25, there is shown a convertible plunger12idisposed within a syringe barrel. The plunger12iincludes an internal portion having an axial cavity48gwith annular grooves322axially spaced apart from one another. The plunger12iis a component of an assembly having a sliding shaft318that is displaceable along its axis. The sliding shaft318includes annular rings320axially spaced apart from one another. The rings320are adapted to mate with the grooves322. In a first position, shown inFIG.25, the rings320do not occupy the grooves322, but instead press against the interior surface of the cavity, providing outward radial pressure that maintains adjacent ribs152of the plunger12iin an expanded state. When the sliding shaft318is displaced further into the plunger12i, the rings320mate with respective grooves322in a second position. In this second position, the outward radial pressure behind the ribs152is reduced, thus reducing the exterior surface of the plunger12gto a constricted state. Once the exterior surface of the plunger12iis in a constricted state, the plunger rod14, as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. Film Coatings and Molded Caps In another aspect, the invention is directed to novel film coatings applied to plungers, e.g., any of the plungers described herein whether convertible or not. It should be understood that films and film coatings, as shown in drawing figures (FIGS.8-12,26and26A), are depicted as having exaggerated thicknesses, for purposes of clarity only. The films and film coatings in reality would optionally be much thinner (e.g., under 100 micrometers) than as depicted in the relevant figures. For example,FIG.8illustrates a cross sectional view of a film coated plunger, and more specifically, a plunger12″ having at least one rib152, and more specifically three ribs152, as well as a film coating88on an exterior surface86of the plunger12″. According to certain embodiments, the sidewall90of the plunger12″ may be coated in a material that minimizes friction between the plunger12″ and the sidewall58of the barrel56as the plunger12″ is displaced in the barrel56during dispensing of the injection product. Additionally, according to certain embodiments, the nose cone92of the plunger12″ may be coated in a material that isolates the plunger12″, and more specifically the material of the plunger12″ and any contaminants thereon, from the injection product contained in product containing area59of the barrel56. Additionally, according to certain embodiments, the film coating88may have different thicknesses at different portions of the exterior surface86of the plunger12″, such as, for example, the nose cone92having a layer of the film coating88that is thicker than the layer of the film coating88along the sidewall90. For example, according to certain embodiments the film coating88about the nose cone92may have a thickness of approximately 50 micrometer (μm), while the thickness of the film coating88along the sidewall may be approximately 25-35 micrometer (μm). Such differences in coating thicknesses may limit interference the film coating88may provide to the ability of the plunger12″ to assert a compressive force against the sidewall58of the barrel56while also providing a sufficiently thick barrier between the material of the plunger12″ and the injection product stored in the product containing area59. Additionally, according to other embodiments, the film coating88may be applied to the nose cone92but not the sidewall90, or vice versa. A variety of different materials may be employed for the film coating88(or cap), such as, for example, an inert fluoropolymer, including, fluorinated ethylene propylene (FEP), ethylene tetrafluoroethylene (ETFE), polytetrafluoroethylene (PTFE), ethylene perfluoroethylenepropylene (EFEP), ethylene chlorotrifluoroethylene (ECTFE), Polychlorotrifluoroethene (PCTFE), perfluoroalkoxy (PFA), among other coatings. Optionally, CPT fluoropolymer may be used. CPT is a modified perfluoroalkoxy (PFA) commercially available from Daikin America, Inc. and generally comprises the addition of PCTFE side chains to a PFA main chain during polymerization, thereby increasing gas and/or liquid barrier properties of standard PFA. Optionally, a perfluoropolyether oil, such as DEMNUM which is commercially available from Daikin America, Inc., may be mixed with resin and extruded into a film, mold or cap. Additionally, according to certain embodiments, the material used for the film coating88may not be an expanded fluoropolymer. Further, according to certain embodiments, additives may be added to the material for the film coating88, such as additives that may improve the adhesion of the film coating88to the plunger12″ and/or decrease the friction between the plunger12″ and the sidewall58of the barrel. Additionally, according to certain embodiments, an adhesion promoting coating or process may be employed, such as, for example, a corona treatment. For some applications, it may be desirable to coextrude different materials to form the film. For example, coextruded film combinations may include a cyclic olefin copolymer (COC) with Aclar, Polyethylene (PE) with Aclar and FEP with PE, among other combinations. For example, according to certain embodiments, a lubricity additive, such as a poly(tetrafluoroethylene) (PTFE) or Teflon® powder may be utilized with a thermoformed film to improve the lubricity of the film coating88. For example, according to certain embodiments, the additive, such as the PTFE, may be applied and/or pressed into the film that is going to be used for the film coating88of the plunger12″. According to certain embodiments, an additive such as PTFE may only be applied to the side of the film for which the additive will have an application, such the side of the film that will be in contact with the sidewall if the additive is to reduce friction between the plunger12″ and the sidewall58of the barrel56, or a side of the film that will assist in adhering the film to the plunger12″. Further, according to certain embodiments, the additive may be added to the film before the film is produce in the film form that is applied to the plunger12″. The film coating88may be applied to the plunger12″, or a portion of the plunger12″, in a variety of different manners. For example, referencingFIG.9, the film coating88may, prior to being applied to the plunger12″, be in the form of a film94(with or without the above discussed additives), such as a film of a thermoformed FEP or other thermoformable fluoropolymer, that is placed over one or more forming dies96. As shown, heat may be applied to at least a portion of the film94to assist in molding the film94into the desired shape of the forming die96. However, in the present example, the sidewall90of the plunger12″ may be coated with a thinner layer of film coating88than the layer covering the nose cone92. This differential thickness is obtainable in part because of the different degree of drawing of the film94between the sidewall90and the nose cone92. Optionally, however, this differential thickness can be increased by providing that at least the portion of the forming plug98that is to contact the film94, such as, for example a base wall100, may be relatively cool. According to certain embodiments, the temperature of the cooled forming plug98and/or base wall100of the forming plug98may depend on the material of the film94. For example, according to certain embodiments, the cooled portion of the forming plug98may have a temperature that is cooled to approximately 25-50 degrees Celsius lower than the melt temperature of the film94. By maintaining the forming plug98at a relatively lower, or cool, temperature, the stretching of the film94that may occur as the forming plug98presses a portion of the film94into the forming die96may occur to a greater extent at the portion of the film94that will eventually be along the sidewall90of the plunger12″. Moreover, with respect to the forming die96, as shown for example inFIG.10, by maintaining the forming plug98at a relatively low or cool temperature, the forming die and plug96,98may be used to form a coating preform106of the film coating88in which the portion of the film94that was pressed into a bottom portion102of the forming die96remains thicker in relation to the portion of the film94that is along the sidewall104of the forming die96. According to certain embodiments, multiple positions of the forming plug98and forming die96are arranged based on mold cavitation. Thus, a plurality of coating preforms106of the coatings88may be maintained on a single piece, or web, of film94. Thus, each coating preform106of the film coating88on the film94may be maintained in position on the film94. The coating preforms106the may be transported together on the film94through the entire process by indexing at each step. However, according to other embodiments, rather than transporting the coating preforms106together via the coating preforms106being connected to the film94, the coating preforms106may be removed from the film prior to other operations, such as, for example, prior to the coating preform106being placed into a mold cavity108, as discussed below. Optionally, a fluoropolymer cap may be formed and inserted into the mold after the film material has been inserted into the mold and before the plunger material is injected into the mold. Thus, in the final product, the plunger may comprise a plunger material, a fluoropolymer cap disposed on the tip of the plunger material and a film covering the cap and the plunger material. The cap may be made from fluoropolymers such as, for example, high density polyethylene (HDPE), low density polyethylene (LDPE), or PTFE, among others. Optionally, PTFE powder may be embedded on the surface of the plunger material. This may be achieved, for example, by coating the mold cavity with PTFE powder and injecting the plunger material into the mold to form the plunger. The PTFE would provide lubricity needed for inserting and operating the plunger in a cartridge or syringe barrel. Alternatively, a high durometer, lubricious TPE material may be used as the plunger material and have no film disposed thereon. FIG.11illustrates a coating preform106formed from the film104after the coating preform106has been loaded into a mold cavity108of a mold107and a vacuum has been applied to pull the coating preform106against the sidewall110and bottom wall112of the mold cavity108. Thus, according to certain embodiments, the shape of the film coating88may have a contour that matches the desired outer shape of the plunger12″. With the mold107closed, a material for the plunger12″, such as, for example, thermoset rubber (e.g., butyl rubber) or a thermoplastic elastomer (TPE) may be injected into the mold cavity108via an injection molding process so that plunger is molded against and/or to the coating preform106and a mold core103. The mold107may then be opened and the mold core103removed. The molded plunger12″ with the film coating88(which may be still attached to the film94) may then be removed from the mold107. FIG.12illustrates the formed plunger12″ and film coating88prior a trim tool114cutting or trimming the film coating88away from the remainder of the film94. While the trim tool114is illustrated as being a mechanical cutting device, a variety of different cutting devices may be employed, such as, for example, a laser, among other cutters. Additionally, the timing that at least the coating preform106and/or film coating88is trimmed from the film94may vary. For example, according to certain embodiments, the coating preform106and/or film coating88may remain connected to the film94so that the coating preform106and/or film coating88may be used to convey a plurality of coating preforms106and/or film coatings88during the manufacturing process (without or without the plunger12″). According to such an embodiment, the coating preform(s)106and/or film coating(s)88may remain attached to the film94up until the time that coating preform(s)106and/or film coating(s)88are trimmed from the film94. The material used for the film coating88may provide the compliance needed for the sealing function of the barrel56, as previously discussed. Further, by being able to use certain materials for the film coating88, such as, for example, a fluoropolymer film, a broader selection of materials for use in forming the plunger12″ may be available, as the film coating88applied to the nose cone92will provide a barrier between the material of the plunger12″ and the injection product contained in the barrel56. Further, according to certain embodiments, the plunger12″ may be configured to limit the degree to which the rib(s)52and/or plunger12″ are compressed when the plunger12″ is inserted into the barrel56. For example, according to certain embodiments, the rib(s)52and/or plunger12″ is configured to not be compressed more than 20% of the overall width of the rib52and/or plunger12″ when the plunger12″ is being used to form a seal in the barrel56. Alternative options for compression percentages are provided above. Referring toFIG.26, there is shown a film coated plunger12according to the present invention. The film coated plunger12comprises a plunger sleeve44(e.g., same as that ofFIG.3) having a film coating88mounted over the nose cone92and a portion of the sidewall90of the film coated plunger12. Preferably, as shown, the film coating88covers the entire nose cone92. The film coating88also optionally covers the rib55of the liquid sealing section53and optionally a small section of the valley57adjacent to the rib55. Optionally, as shown inFIG.26A, the valley57comprises a descending slope57aextending distally from the liquid sealing section53, the descending slope57aleading to a floor57b, the floor57bleading to an ascending slope57ctoward the storage sealing section51. Optionally, the film coating88terminates before the storage sealing section51, optionally before the ascending slope57c, optionally before the floor57b. In any event, there is preferably no film coating88covering the rib52of the storage sealing section51, since thermoset rubber (if that is the material of the rib52) is a better oxygen barrier than contemplated film materials. The film coating88may be made, e.g., from any materials disclosed herein that are suitable for film coatings, e.g., an inert fluoropolymer, optionally polyethylene or polypropylene. Optionally, the film coated plunger ofFIG.26may be part of a plunger assembly10,210described herein and shown inFIG.2or13. Optionally, the film coated plunger ofFIG.26is any one of the plunger embodiments described herein and shown inFIG.3,7,8,15,17,18,20,21,22,23,24or25. Optionally, the film coated plunger ofFIG.26provides a first sealing force against an interior surface of a barrel wall in storage mode and a second sealing force (which is less than the first sealing force) in dispensing mode. Optionally, the first sealing force is provided by a compression material contained within the plunger12and aligned, at least in part, with a rib52of the storage sealing section51. The compression material is configured to provide outward radial force. The second sealing force is attainable by displacing and/or modifying the compression material, for example, in the many ways described herein. The film coating88may be mounted to the plunger sleeve44in various ways. For example, a flat film piece may be placed onto a first surface of a forming block having a round passage leading to a second surface on another side of the forming block. At least an end portion of the round passage leading to the second surface of the forming block has roughly the same diameter as the plunger. A plunger holder grips a substantial portion of the plunger from the rear thereof (e.g., leaving uncovered that portion of the plunger to be covered with film). The plunger holder may be axially driven through the passage of the forming block, e.g., with a (preferably automated) pushing rod. Optionally, the pushing rod protrudes into the plunger cavity (e.g.,48and optionally 50 of the plunger12ofFIG.26), slightly stretching the plunger. Optionally, prior to axially inserting the plunger and plunger holder through the passage, the plunger is heated e.g., to 100° C. to 200° C., optionally 110° C. to 190° C., optionally 120° C. to 180° C., optionally 130° C. to 170° C., optionally 135° C. to 160° C., optionally 145° C. to 155° C., optionally about 150° C. After the optional heating step (if taken), the plunger and plunger holder are axially inserted through the passage thereby mounting the film piece to the plunger. Excess sections of the film piece may be trimmed from the plunger. For high volume production, for example, flat, continuous film strips may be preferred to individual film sheets for each plunger. Alternatively, continuous film strips may be perforated or otherwise weakened in circular patterns so as to provide pre-sized circular films for mounting to plungers. Preferably, such pre-sized circular films would be sized so as to leave no excess film to trim once mounted on the plunger. In this way, the plunger holder and plunger may be aligned with the circular patterns in order to punch through them when the plunger is inserted into the passage so as to mount the pre-sized circular films onto the plunger. Optionally, the film may be applied via cold forming (preferred) or thermoforming, wherein the plunger sleeve is itself used in the thermoforming process (e.g., mold rubber plunger sleeve and then thermoform film to rubber). Referring toFIG.27, there is shown the plunger sleeve44ofFIG.3having a cap194mounted over the nose cone92and a portion of the sidewall90of the plunger12. Preferably, as shown, the cap194covers the entire nose cone92. The cap194also covers the rib55of the liquid sealing section53and a small section of the valley57adjacent to the rib55. Preferably, the cap194does not cover the rib52of the storage sealing section51. Optionally, the cap194terminates in the same places in the valley57as described above vis-à-vis the film coating88as shown inFIG.26A. The cap194may be made from fluoropolymers such as, for example, high density polyethylene (HDPE), low density polyethylene (LDPE), or PTFE, among others. While it is contemplated that the cap194may have a thickness greater than that of the film94discussed above, it should be understood that the thickness of the cap194as shown inFIG.27is not to scale, but is exaggerated for purposes of clarity. The cap194is preferably an injection molded part that is made in a two shot injection mold process with the sleeve44. In other words, optionally, a cap material (e.g. polymer) is injection molded and subsequently the sleeve material (e.g. rubber) is injection molded into the same mold cavity as the cap material in a two shot process. Optionally, in molding, the cap194and sleeve44mate together through a mechanical fit such as an interference fit. Advantageously, the cap can be made from either thermoplastic or thermoset materials. In addition, a molded cap is an easier component to manage in manufacturing than a comparatively thinner film. The use of the fluoropolymer powders may be used in combination with non-fluoropolymer films—like polyethylene or polypropylene films that are more adhesion compatible with the thermoplastic elastomer/rubber plunger materials. The challenge with fluoropolymer films—like FEP is that they may not perfectly adhere to the plunger and can wrinkle when interested into the syringe barrel. A potential solution to the problems of film adhesion and wrinkling contemplated by the inventors is to make the plunger from a liquid silicone rubber, preferably a fluoro liquid silicone rubber. Fluoro liquid silicone rubbers are injection moldable materials that possess good compression set properties, e.g., for long term storage in pre-filled cartridges or syringes, similar to butyl rubber. In addition, they adhere well to fluoropolymers. As such, according to one aspect of the invention, a fluoro liquid silicone rubber plunger (optionally incorporating features of any plunger embodiments disclosed herein) is provided, having a fluoropolymer film disposed thereon. The fluoro liquid silicone rubber plunger provides enhanced bonding with the fluoropolymer film, and thus resists wrinkling of the film. This enhanced bonding and wrinkle resistance would render the plunger more robust for handling and insertion into a syringe or cartridge. An additional potential advantage is that fluoro liquid silicone rubber may be injection molded to achieve better dimensional tolerances than traditional compression molded plungers, such as those made from butyl rubber. In another embodiment, a fluoro liquid silicone rubber plunger is provided which does not include a film disposed thereon. It is contemplated that for some applications, a plunger comprising fluoro liquid silicone rubber will itself (without a film) have adequate compression set properties and would be sufficiently lubricious for insertion and handling in a cartridge or syringe barrel. Examples of potentially suitable fluoro liquid silicone rubber materials for use in plungers according to an aspect of the present invention include, among others, SILASTIC® marketed by Dow Corning Corporation and ELASTOSIL® FLR marketed by Wacker Chemie AG. It is contemplated that fluoro liquid silicone polymer plungers may have comparable or superior properties, in several respects (e.g., in terms of compression setting, film adhesion, plunger force, and plunger extractables), compared to standard, e.g., butyl rubber plungers. It is contemplated that any of the convertible plungers described in this specification and shown in the drawing figures may optionally include film coatings or molded caps as described herein. It is further contemplated that any of the plungers described herein, whether or not they include a film coating, may be made from one or more materials including, but not limited to, a thermoset rubber (e.g., butyl rubber), a thermoplastic elastomer (TPE), liquid silicone rubber and fluoro liquid silicone rubber. It is further contemplated that any plunger embodiments that are described herein without a film may include a film and that any plunger embodiments that are described herein with a film may be used without a film, depending on design requirements and/or functional needs. Plunger Testing Methods and Standards Testing of compression setting properties of the plunger may be conducted using methods known in the art, for example, ASTM D395. Testing of adhesive properties or bonding strength between the film and the plunger may be conducted using methods known in the art, for example, according to ASTM D1995-92(2011) or D1876-08. Plunger sliding force is the force required to maintain movement of a plunger in a syringe or cartridge barrel, for example during aspiration or dispense. It can advantageously be determined using, e.g., the ISO 7886-1:1993 test known in the art, or to the currently pending published test method to be incorporated into ISO 11040-4. Plunger breakout force, which may be tested using the same method as that for testing plunger sliding force, is the force required to start a stationary plunger moving within a syringe or cartridge barrel. Machinery useful in testing plunger sliding and breakout force is, e.g., an Instron machine using a 50 N transducer. Testing for extractables, i.e., amount of material that migrates from the plunger into the liquid within the syringe or cartridge, may be conducted using methods set forth in Ph. Eur. 2.9.17 Test for Extractable Volume of Parenteral Preparations, for example. Testing of container closure integrity (CCI) may be done using a vacuum decay leak detection method, wherein a vacuum his maintained inside of a test volume and pressure rise is measured over time. A large enough pressure rise is an indication that there is flow into the system, which is evidence of a leak. Optionally, the vacuum decay test is implemented over two separate cycles. The first cycle is dedicated to detecting large leaks over a very short duration. A relatively weak vacuum is pulled for the first cycle because if a gross leak is detected, a large pressure differential is not necessary to detect a large pressure rise. Use of a first cycle as described helps to shorten total test time if a gross leak exists. If no leak is detected in the first cycle, a second cycle is run, which complies with ASTM F2338-09 Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method. The second cycle starts out with a system evaluation to lower the signal to noise ratio in the pressure rise measurements. A relatively strong vacuum is pulled for a long period of time in the second cycle to increase the chance of detecting a pressure rise in the system. Syringe Embodiments and PECVD Coatings In another aspect, the present invention includes use of any embodiments (or combination of embodiments) of plungers according to the invention in syringes having a PECVD coating or PECVD coating set. The syringes may be made from, e.g., glass or plastic. Optionally, the syringe barrel according to any embodiment is made from an injection moldable thermoplastic material that appears clear and glass-like in final form, e.g., a cyclic olefin polymer (COP), cyclic olefin copolymer (COC) or polycarbonate. Such materials may be manufactured, e.g., by injection molding, to very tight and precise tolerances (generally much tighter than achievable with glass). This is a benefit when trying to balance the competing considerations of seal tightness and low plunger force in plunger design. This section of the disclosure focuses primarily on pre-filled syringes as a preferred implementation of optional aspects of the invention. Again, however, it should be understood that the present invention may include any parenteral container that utilizes a plunger, such as syringes, cartridges, auto-injectors, pre-filled syringes, pre-filled cartridges or vials. For some applications, it may be desired to provide one or more coatings or layers to the interior wall of a parenteral container to modify the properties of that container. For example, one or more coatings or layers may be added to a parenteral container, e.g., to improve the barrier properties of the container and prevent interaction between the container wall (or an underlying coating) and drug product held within the container. For example, as shown inFIG.4A, which is a first alternative embodiment of an enlarged sectional view of the syringe barrel54ofFIG.4, the sidewall58of the syringe barrel54may include a coating set400comprising one or more coatings or layers. The barrel54may include at least one tie coating or layer402, at least one barrier coating or layer404, and at least one organo-siloxane coating or layer406. The organo-siloxane coating or layer406preferably has pH protective properties. This embodiment of the coating set400is referred to herein as a “trilayer coating set” in which the the barrier coating or layer404of SiOxis protected against contents having a pH otherwise high enough to remove it by being sandwiched between the pH protective organo-siloxane coating or layer406and the tie coating or layer402. The contemplated thicknesses of the respective layers in nm (preferred ranges in parentheses) are given in the following Trilayer Thickness Table: Trilayer Thickness TableAdhesionBarrierProtection5-10020-20050-500(5-20)(20-30)(100-200) Properties and compositions of each of the coatings that make up the trilayer coating set are now described. The tie coating or layer402has at least two functions. One function of the tie coating or layer402is to improve adhesion of a barrier coating or layer404to a substrate (e.g., the sidewall58of the barrel54), in particular a thermoplastic substrate, although a tie layer can be used to improve adhesion to a glass substrate or to another coating or layer. For example, a tie coating or layer, also referred to as an adhesion layer or coating can be applied to the substrate and the barrier layer can be applied to the adhesion layer to improve adhesion of the barrier layer or coating to the substrate. Another function of the tie coating or layer402has been discovered: a tie coating or layer402applied under a barrier coating or layer404can improve the function of a pH protective organo-siloxane coating or layer406applied over the barrier coating or layer404. The tie coating or layer402can be composed of, comprise, or consist essentially of SiOxCy, in which x is between 0.5 and 2.4 and y is between 0.6 and 3. Alternatively, the atomic ratio can be expressed as the formula SiwOxCy. The atomic ratios of Si, O, and C in the tie coating or layer289are, as several options:Si 100:O 50-150:C 90-200 (i.e. w=1, x=0.5 to 1.5, y=0.9 to 2);Si 100:O 70-130:C 90-200 (i.e. w=1, x=0.7 to 1.3, y=0.9 to 2)Si 100:O 80-120:C 90-150 (i.e. w=1, x=0.8 to 1.2, y=0.9 to 1.5)Si 100:O 90-120:C 90-140 (i.e. w=1, x=0.9 to 1.2, y=0.9 to 1.4), orSi 100:O 92-107:C 116-133 (i.e. w=1, x=0.92 to 1.07, y=1.16 to 1.33). The atomic ratio can be determined by XPS. Taking into account the H atoms, which are not measured by XPS, the tie coating or layer402may thus in one aspect have the formula SiwOxCyHz(or its equivalent SiOxCy), for example where w is 1, x is from about 0.5 to about 2.4, y is from about 0.6 to about 3, and z is from about 2 to about 9. Typically, a tie coating or layer402would hence contain 36% to 41% carbon normalized to 100% carbon plus oxygen plus silicon. The barrier coating or layer for any embodiment defined in this specification (unless otherwise specified in a particular instance) is a coating or layer, optionally applied by PECVD as indicated in U.S. Pat. No. 7,985,188. The barrier coating preferably is characterized as a “SiOx” coating, and contains silicon, oxygen, and optionally other elements, in which x, the ratio of oxygen to silicon atoms, is from about 1.5 to about 2.9. The thickness of the SiOxor other barrier coating or layer can be measured, for example, by transmission electron microscopy (TEM), and its composition can be measured by X-ray photoelectron spectroscopy (XPS). The barrier layer is effective to prevent oxygen, carbon dioxide, or other gases from entering the container and/or to prevent leaching of the pharmaceutical material into or through the container wall. Referring again toFIG.4A, the barrier coating or layer404of SiOx, in which x is between 1.5 and 2.9, is applied by plasma enhanced chemical vapor deposition (PECVD) directly or indirectly to the thermoplastic sidewall wall58of the barrel54(in this example, a tie coating or layer402is interposed between them) so that in the filled syringe barrel54, the barrier coating or layer404is located between the inner or interior surface of the sidewall55of the barrel54and the injectable medicine contained within the barrel54. Certain barrier coatings or layers404such as SiOx as defined here have been found to have the characteristic of being subject to being measurably diminished in barrier improvement factor in less than six months as a result of attack by certain relatively high pH contents of the coated vessel as described elsewhere in this specification, particularly where the barrier coating or layer directly contacts the contents. This issue can be addressed using an organo-siloxane coating or layer as discussed in this specification. Preferred methods of applying the barrier layer and tie layer to the inner surface of the barrel54is by plasma enhanced chemical vapor deposition (PECVD), such as described in, e.g., U.S. Pat. App. Pub. No. 20130291632, which is incorporated by reference herein in its entirety. The Applicant has found that barrier layers or coatings of SiOxare eroded or dissolved by some fluids, for example aqueous compositions having a pH above about 5. Since coatings applied by chemical vapor deposition can be very thin—tens to hundreds of nanometers thick—even a relatively slow rate of erosion can remove or reduce the effectiveness of the barrier layer in less time than the desired shelf life of a product package. This is particularly a problem for fluid pharmaceutical compositions, since many of them have a pH of roughly 7, or more broadly in the range of 5 to 9, similar to the pH of blood and other human or animal fluids. The higher the pH of the pharmaceutical preparation, the more quickly it erodes or dissolves the SiOxcoating. Optionally, this problem can be addressed by protecting the barrier coating or layer404, or other pH sensitive material, with a pH protective organo-siloxane coating or layer406. Optionally, the pH protective organo-siloxane coating or layer406can be composed of, comprise, or consist essentially of SiwOxCyHz(or its equivalent SiOxCy) or SiwNxCyHzor its equivalent SiNxCy). The atomic ratio of Si:O:C or Si:N:C can be determined by XPS (X-ray photoelectron spectroscopy). Taking into account the H atoms, the pH protective coating or layer may thus in one aspect have the formula SiwOxCyHz, or its equivalent SiOxCy, for example where w is 1, x is from about 0.5 to about 2.4, y is from about 0.6 to about 3, and z is from about 2 to about 9. Typically, expressed as the formula SiwOxCy, the atomic ratios of Si, O, and C are, as several options:Si 100:O 50-150:C 90-200 (i.e. w=1, x=0.5 to 1.5, y=0.9 to 2);Si 100:O 70-130:C 90-200 (i.e. w=1, x=0.7 to 1.3, y=0.9 to 2)Si 100:O 80-120:C 90-150 (i.e. w=1, x=0.8 to 1.2, y=0.9 to 1.5)Si 100:O 90-120:C 90-140 (i.e. w=1, x=0.9 to 1.2, y=0.9 to 1.4)Si 100:O 92-107:C 116-133 (i.e. w=1, x=0.92 to 1.07, y=1.16 to 1.33), orSi 100:O 80-130:C 90-150. Alternatively, the organo-siloxane coating or layer can have atomic concentrations normalized to 100% carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS) of less than 50% carbon and more than 25% silicon. Alternatively, the atomic concentrations are from 25 to 45% carbon, 25 to 65% silicon, and 10 to 35% oxygen. Alternatively, the atomic concentrations are from 30 to 40% carbon, 32 to 52% silicon, and 20 to 27% oxygen. Alternatively, the atomic concentrations are from 33 to 37% carbon, 37 to 47% silicon, and 22 to 26% oxygen. Optionally, the atomic concentration of carbon in the pH protective coating or layer406, normalized to 100% of carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS), can be greater than the atomic concentration of carbon in the atomic formula for the organosilicon precursor. For example, embodiments are contemplated in which the atomic concentration of carbon increases by from 1 to 80 atomic percent, alternatively from 10 to 70 atomic percent, alternatively from 20 to 60 atomic percent, alternatively from 30 to 50 atomic percent, alternatively from 35 to 45 atomic percent, alternatively from 37 to 41 atomic percent. Optionally, the atomic ratio of carbon to oxygen in the pH protective coating or layer406can be increased in comparison to the organosilicon precursor, and/or the atomic ratio of oxygen to silicon can be decreased in comparison to the organosilicon precursor. An exemplary empirical composition for a pH protective coating according to the present invention is SiO1.3Co0.8H3.6. Optionally in any embodiment, the pH protective coating or layer406comprises, consists essentially of, or consists of PECVD applied silicon carbide. Optionally in any embodiment, the pH protective coating or layer406is applied by employing a precursor comprising, consisting essentially of, or consisting of a silane. Optionally in any embodiment, the silane precursor comprises, consists essentially of, or consists of any one or more of an acyclic or cyclic silane, optionally comprising, consisting essentially of, or consisting of any one or more of silane, trimethylsilane, tetramethylsilane, Si2-Si4 silanes, triethyl silane, tetraethyl silane, tetrapropylsilane, tetrabutylsilane, or octamethylcyclotetrasilane, or tetramethylcyclotetrasilane. Optionally in any embodiment, the pH protective coating or layer406comprises, consists essentially of, or consists of PECVD applied amorphous or diamond-like carbon. Optionally in any embodiment, the amorphous or diamond-like carbon is applied using a hydrocarbon precursor. Optionally in any embodiment, the hydrocarbon precursor comprises, consists essentially of, or consists of a linear, branched, or cyclic alkane, alkene, alkadiene, or alkyne that is saturated or unsaturated, for example acetylene, methane, ethane, ethylene, propane, propylene, n-butane, i-butane, butane, propyne, butyne, cyclopropane, cyclobutane, cyclohexane, cyclohexene, cyclopentadiene, or a combination of two or more of these. Optionally in any embodiment, the amorphous or diamond-like carbon coating has a hydrogen atomic percent of from 0.1% to 40%, alternatively from 0.5% to 10%, alternatively from 1% to 2%, alternatively from 1.1 to 1.8%. Optionally in any embodiment, the pH protective coating or layer406comprises, consists essentially of, or consists of PECVD applied SiNb. Optionally in any embodiment, the PECVD applied SiNb is applied using a silane and a nitrogen-containing compound as precursors. Optionally in any embodiment, the silane is an acyclic or cyclic silane, optionally comprising, consisting essentially of, or consisting of silane, trimethylsilane, tetramethylsilane, Si2-Si4 silanes, triethylsilane, tetraethylsilane, tetrapropylsilane, tetrabutylsilane, octamethylcyclotetrasilane, or a combination of two or more of these. Optionally in any embodiment, the nitrogen-containing compound comprises, consists essentially of, or consists of any one or more of: nitrogen gas, nitrous oxide, ammonia or a silazane. Optionally in any embodiment, the silazane comprises, consists essentially of, or consists of a linear silazane, for example hexamethylene disilazane (HMDZ), a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, or a combination of two or more of these. Optionally in any embodiment, the PECVD for the pH protective coating or layer406is carried out in the substantial absence or complete absence of an oxidizing gas. Optionally in any embodiment, the PECVD for the pH protective coating or layer406is carried out in the substantial absence or complete absence of a carrier gas. Optionally an FTIR absorbance spectrum of the pH protective coating or layer406SiOxCyHz has a ratio greater than 0.75 between the maximum amplitude of the Si—O—Si symmetrical stretch peak normally located between about 1000 and 1040 cm−1, and the maximum amplitude of the Si—O—Si asymmetric stretch peak normally located between about 1060 and about 1100 cm−1. Alternatively in any embodiment, this ratio can be at least 0.8, or at least 0.9, or at least 1.0, or at least 1.1, or at least 1.2. Alternatively in any embodiment, this ratio can be at most 1.7, or at most 1.6, or at most 1.5, or at most 1.4, or at most 1.3. Any minimum ratio stated here can be combined with any maximum ratio stated here, as an alternative embodiment. Optionally, in any embodiment the pH protective coating or layer406, in the absence of the medicament, has a non-oily appearance. This appearance has been observed in some instances to distinguish an effective pH protective coating or layer406from a lubricity layer (e.g., as described in U.S. Pat. No. 7,985,188), which in some instances has been observed to have an oily (i.e. shiny) appearance. The pH protective coating or layer406optionally can be applied by plasma enhanced chemical vapor deposition (PECVD) of a precursor feed comprising an acyclic siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, a silatrane, a silquasilatrane, a silproatrane, an azasilatrane, an azasilquasiatrane, an azasilproatrane, or a combination of any two or more of these precursors. Some particular, non-limiting precursors contemplated for such use include octamethylcyclotetrasiloxane (OMCTS). Optionally, an FTIR absorbance spectrum of the pH protective coating or layer406of composition SiOxCyHz has a ratio greater than 0.75 between the maximum amplitude of the Si—O—Si symmetrical stretch peak between about 1000 and 1040 cm−1, and the maximum amplitude of the Si—O—Si asymmetric stretch peak between about 1060 and about 1100 cm−1. Other precursors and methods can be used to apply the pH protective coating or layer406or passivating treatment. For example, hexamethylene disilazane (HMDZ) can be used as the precursor. HMDZ has the advantage of containing no oxygen in its molecular structure. This passivation treatment is contemplated to be a surface treatment of the SiOx barrier layer with HMDZ. To slow down and/or eliminate the decomposition of the silicon dioxide coatings at silanol bonding sites, the coating must be passivated. It is contemplated that passivation of the surface with HMDZ (and optionally application of a few mono layers of the HMDZ-derived coating) will result in a toughening of the surface against dissolution, resulting in reduced decomposition. It is contemplated that HMDZ will react with the —OH sites that are present in the silicon dioxide coating, resulting in the evolution of NH3 and bonding of S—(CH3)3 to the silicon (it is contemplated that hydrogen atoms will be evolved and bond with nitrogen from the HMDZ to produce NH3). Another way of applying the pH protective coating or layer406is to apply as the pH protective coating or layer406an amorphous carbon or fluorocarbon coating, or a combination of the two. Amorphous carbon coatings can be formed by PECVD using a saturated hydrocarbon, (e.g. methane or propane) or an unsaturated hydrocarbon (e.g. ethylene, acetylene) as a precursor for plasma polymerization. Fluorocarbon coatings can be derived from fluorocarbons (for example, hexafluoroethylene or tetrafluoroethylene). Either type of coating, or a combination of both, can be deposited by vacuum PECVD or atmospheric pressure PECVD. It is contemplated that that an amorphous carbon and/or fluorocarbon coating will provide better passivation of an SiOx barrier layer than a siloxane coating since an amorphous carbon and/or fluorocarbon coating will not contain silanol bonds. It is further contemplated that fluorosilicon precursors can be used to provide a pH protective coating or layer406over a SiOx barrier layer. This can be carried out by using as a precursor a fluorinated silane precursor such as hexafluorosilane and a PECVD process. The resulting coating would also be expected to be a non-wetting coating. Yet another coating modality contemplated for protecting or passivating a SiOx barrier layer is coating the barrier layer using a polyamidoamine epichlorohydrin resin. For example, the barrier coated part can be dip coated in a fluid polyamidoamine epichlorohydrin resin melt, solution or dispersion and cured by autoclaving or other heating at a temperature between 60 and 100° C. It is contemplated that a coating of polyamidoamine epichlorohydrin resin can be preferentially used in aqueous environments between pH 5-8, as such resins are known to provide high wet strength in paper in that pH range. Wet strength is the ability to maintain mechanical strength of paper subjected to complete water soaking for extended periods of time, so it is contemplated that a coating of polyamidoamine epichlorohydrin resin on a SiOx barrier layer will have similar resistance to dissolution in aqueous media. It is also contemplated that, because polyamidoamine epichlorohydrin resin imparts a lubricity improvement to paper, it will also provide lubricity in the form of a coating on a thermoplastic surface made of, for example, COC or COP. Even another approach for protecting a SiOx layer is to apply as a pH protective coating or layer406a liquid-applied coating of a polyfluoroalkyl ether, followed by atmospheric plasma curing the pH protective coating or layer406. For example, it is contemplated that the process practiced under the trademark TriboGlide® can be used to provide a pH protective coating or layer406that is also provides lubricity. Thus, a pH protective coating for a thermoplastic syringe wall according to an aspect of the invention may comprise, consist essentially of, or consist of any one of the following: plasma enhanced chemical vapor deposition (PECVD) applied silicon carbide having the formula SiOxCyHz, in which x is from 0 to 0.5, alternatively from 0 to 0.49, alternatively from 0 to 0.25 as measured by X ray photoelectron spectroscopy (XPS), y is from about 0.5 to about 1.5, alternatively from about 0.8 to about 1.2, alternatively about 1, as measured by XPS, and z is from 0 to 2 as measured by Rutherford Backscattering Spectrometry (RBS), alternatively by Hydrogen Forward Scattering Spectrometry (HFS); or PECVD applied amorphous or diamond-like carbon, CHz, in which z is from 0 to 0.7, alternatively from 0.005 to 0.1, alternatively from 0.01 to 0.02; or PECVD applied SiNb, in which b is from about 0.5 to about 2.1, alternatively from about 0.9 to about 1.6, alternatively from about 1.2 to about 1.4, as measured by XPS. pH Protective Organo-Siloxane Coating—Not as Part of Coating Set Referring now toFIG.4B, there is shown a second alternative embodiment of an enlarged sectional view of the syringe barrel54ofFIG.4. As shown inFIG.4B, the syringe barrel54may include a organo-siloxane coating or layer406disposed directly on the wall58of the syringe barrel54, rather than, e.g., as a top layer of a coating set. Optionally, the organo-siloxane coating or layer406has pH protective properties. Thus an aspect of the invention involves use of a organo-siloxane coating or layer as a plunger-contacting surface, whether the organo-siloxane coating or layer is the top-most layer of a coating set or is by itself disposed directly onto the barrel wall. PECVD Apparatus PECVD apparatus suitable for applying any of the PECVD coatings or layers described in this specification, including the tie coating or layer402, the barrier coating or layer404or the organo-siloxane coating or layer406, is shown and described in U.S. Pat. No. 7,985,188 and U.S. Pat. App. Pub. No. 20130291632. This apparatus optionally includes a vessel holder, an inner electrode, an outer electrode, and a power supply. A vessel seated on the vessel holder defines a plasma reaction chamber, optionally serving as its own vacuum chamber. Optionally, a source of vacuum, a reactant gas source, a gas feed or a combination of two or more of these can be supplied. Optionally, a gas drain, not necessarily including a source of vacuum, is provided to transfer gas to or from the interior of a vessel seated on the port to define a closed chamber. pH Protective Organo-Siloxane Coatings Having Lubricious Properties It is contemplated that syringes having a plunger-contacting inner surface comprising an organo-siloxane coating, without a separate discrete lubricity coating or substantially without the presence of a flowable lubricant, may still provide adequate lubricity for plunger advancement. As used herein, “substantially without the presence of a flowable lubricant,” means that a flowable lubricant (e.g., PDMS) is not provided to a syringe barrel in amounts that would contribute to the lubricity of the plunger-syringe system. Since it is sometimes the practice to use a flowable lubricant when handling plungers prior to assembling them into syringes, “substantially without the presence of a flowable lubricant” in some cases may contemplate the presence of trace amounts of such lubricant as a result of such handling practices. Accordingly, in one aspect, the invention is directed to an organo-siloxane coating on the inner surface of a parenteral container which provides lubricious properties conducive to acceptable plunger operation. The organo-siloxane coating may, for example, be any embodiment of the pH protective coating discussed above. The organo-siloxane coating may be applied directly to the interior wall of the container or as a top layer on a multi-layer coating set, e.g., the trilayer coating set discussed above. Preferably, this embodiment would obviate the need for a discrete lubricity coating, e.g., as described in U.S. Pat. No. 7,985,188 or a flowable lubricant, e.g., silicone oil. The organo-siloxane coating can optionally provide multiple functions: (1) a pH resistant layer that protects an underlying layer or underlying polymer substrate from drug products having a pH from 4-10, optionally from 5-9; (2) a drug contact surface that minimizes aggregation, extractables and leaching; (3) in the case of a protein-based drug, reduced protein binding on the container surface; and (4) a lubricating layer, e.g., to facilitate plunger advancement when dispensing contents of a syringe. Use of an organo-siloxane coating on a polymer-based container as the contact surface for a plunger provides distinct advantages. Plastic syringes and cartridges may be injection molded to tighter tolerances than their glass counterparts. It is contemplated that the dimensional precision achievable through injection molding allows optimization of the inside diameter of a syringe to provide sufficient compression to the plunger for CCI on the one hand, while not over-compressing the plunger so as to provide desired plunger force upon administration of the drug product. Optimally, this would eliminate or dramatically reduce the need for lubricating the syringe or cartridge with a flowable lubricant or a discrete lubricity coating, thus reducing manufacturing complexity and avoiding problems associated with silicone oil. The invention will be illustrated in more detail with reference to the following Examples, but it should be understood that the present invention is not deemed to be limited thereto. EXAMPLES Example 1—Plunger Force Three convertible plunger samples (Samples A (500), B (502) and C (504)), similar to the embodiment of the film coated convertible plunger ofFIG.26, were subjected to plunger force testing. The samples used 3.45 mm diameter spherical inserts. The desired outcome was a glide force of under 15 N, preferably under 10 N, even more preferably at or under 5 N. The samples were tested in a syringe having a plunger contacting surface comprising a pH protective coating made from a TMDSO precursor as part of a trilayer coating set, e.g., as shown inFIG.4Aand as described herein. The sample plunger sleeves were made from butyl rubber and the film was made from 25 micron thick CHEMFILM® DF1100 PTFE. The syringe barrels were 6.35 mm in diameter. As shown in the chart inFIG.28, break loose force for the three samples was between about 3.5N-5.5N. The glide force was relatively constant and consistent for each sample and was between about 2.5N and about 5 N. The test is thus regarded as a success in terms of achieving desired plunger force and consistency in the force profile of each sample (i.e., no drastic changes in glide force for a given sample). Example 2—CCI A CCI test method (vacuum decay test) is described above. Using this test, and referring to the chart inFIG.29, three sets of plungers (Sets A, B and C) were used, all in a 6.35 mm diameter syringe. Set A510included plungers without any inserts, and consequently with no compression between the plunger storage sealing section and the syringe barrel. Set B512included plungers with 3.45 mm diameter spherical inserts, which caused slightly less than 3% compression of the plunger diameters on their respective storage sealing sections. Set C514included plungers with 3.58 mm spherical inserts, which caused about 4.8% compression of the plunger diameters on their respective storage sealing sections. For purposes of maintaining adequate CCI for prefilled syringes, a pressure drop of about 20 Pa or less is acceptable. The chart inFIG.29shows the pressure drop for plunger Sets A, B and C subjected to the vacuum decay test. Set A510showed a pressure drop of well over 20 Pa, while Set B512and Set C512had pressure drops of around 20 Pa or less, which are positive results. This test shows that the spherical inserts (similar to the insert42ofFIGS.3and26) provide compression in the storage sealing section51of the plunger12, resulting in acceptable CCI. By contrast, Set A510, which had no inserts, did not provide adequate CCI. Example 3—Comparative Plunger Forces Using Four Syringe Barrel Embodiments This example describes plunger force testing of several convertible plunger samples, similar to the embodiment of the film coated convertible plunger ofFIG.26. The samples used 3.45 mm diameter spherical inserts. Results of this testing are shown inFIG.30. Four or five plunger samples were tested in each of the following four different syringe barrels: (a) a COP syringe barrel having an inner wall without flowable lubricant disposed between the plunger and the inner wall (the “bare COP syringe,” the force testing results of which are identified by reference numeral516); (b) a COP syringe barrel with a trilayer coating set applied to the inner wall thereof without flowable lubricant disposed between the plunger and the trilayer coating set (the “trilayer syringe,” the force testing results of which are identified by reference numeral518); (c) a glass syringe barrel without any flowable lubricant disposed between the plunger and the inner wall of the barrel (the “bare glass syringe,” the force testing results of which are identified by reference numeral520); and (d) a glass syringe barrel with a flowable lubricant (PDMS) disposed between the plunger and the inner wall of the barrel (the “glass syringe with PDMS,” the force testing results of which are identified by reference numeral522). The break loose forces and maximum glide forces depicted inFIG.30for a given syringe represent averages of results from testing four of five plunger samples with each syringe. The average break loose forces were as follows: (a) between 6 and 7 N for the bare COP syringe516; (b) slightly above 5 N for the trilayer syringe518; (c) between 7 and 8 N for the bare glass syringe520; and (d) between 11 and 12 N for the glass syringe with PDMS522. The average maximum glide forces were as follows: (a) slightly below 4 N for the bare COP syringe516; (b) 4 N for the trilayer syringe518; (c) between 6 and 7 N for the bare glass syringe520; and (d) between 10 and 11 N for the glass syringe with PDMS522. Notably, the trilayer syringe518cumulative force results were optimal in that unlike the other syringes, both the break loose force and maximum glide force averages were about 5 N or under (which is a preferred plunger force). In addition, the differential between break loose force and maximum glide force for the trilayer syringe518was only about 1 N, which is significantly less than the approximately 2.5N differential between break loose force and maximum glide force for the bare COP syringe516. Accordingly, a trilayer syringe with a plunger according to the present invention provides benefits associated with the trilayer syringe itself (e.g., pH protection, tight syringe tolerances, barrier properties) as well as a flowable lubricant free (or substantially flowable lubricant free) plunger system that provides both CCI and desired plunger forces in use. While the invention has been described in detail and with reference to specific examples thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof. | 129,168 |
11857772 | DETAILED DESCRIPTION Certain terminology is used in the following description for convenience only and is not limiting. The word “distal” refers to the front, or patient, end of the device. The word “proximal” refers to the rear, or syringe user, end of the device. The term “longitudinal”, with or without axis, refers to a direction on an axis through the device in the direction of the longest extension of the device. The term “radial” or “transverse/transversal”, with or without axis, refers to a direction generally perpendicular to the longitudinal direction, e.g. “radially outward” would refer to a direction pointing away from the longitudinal axis. The Figures illustrate a reusable needle shield remover (100,200,300,400) provided to remove a needle shield (50) from a syringe (501). FIGS.1a-1dshow an embodiment of a needle shield remover according to the invention. In this embodiment, the remover device (100) has a passageway (117) along a central longitudinal axis (i-ii). The passageway (117) has a cylindrical side wall (123) which extends proximally from a front opening (112) to a rear opening (118). The passageway (117) has an internal diameter great enough so that a needle shield (50) can be received within the passageway (117). The passageway (117) is elongate and of sufficient length to at least partially enclose the needle shield (50). In use, the needle shield (50), is received in the passageway (117) by insertion of the needle shield (50) through the rear opening (118) Located at the rear end of the passageway (117) are means to remove the needle shield (50) from a syringe. In this embodiment, the rear end of the passageway (117) terminates with two rear legs (119). The rear legs are configured to flex radially outwards as the needle shield is inserted into the device. Projections (120) on the internal surface of the rear legs (119) extend radially inwards from the circumference. The proximal face of each projection is angled away from the rear of the device to allow the needle shield (50) to easily pass over the projection (120) as the needle shield (50) is inserted into the needle shield remover (100). The distal face of each projection (120) is flat. The projections (120) are situated part way down the rear legs (110) of the needle shield remover (10). In use, the needle shield (50) is inserted into the passageway (117) past the projections (120). As the syringe (not shown) is then removed from the needle shield (50), the distal face of each projection (120) comes into engagement with the proximal end of the needle shield (50), thereby preventing further rearward movement of the needle shield (50) with the syringe. In a first embodiment, as shown inFIG.1a-1d,located at the front end of the passageway (117) are one or more cut outs (122). In each of the cut outs (122), extending distally from the distal end of the side wall (123) of the passageway (117), is a resilient front leg (121). Each front leg (121) is provided with a projection (124) extending from the leg (121) towards the central axis of the passageway (117). Thus the diameter of the front opening of the passageway (117) including a front leg (121) is less than the diameter between two opposite parts of the wall (123) of the passageway (117). In use, the needle shield (50) is inserted into the passageway (117) until the forward end exits the front opening of the passageway (117) as shown inFIGS.1cand1d. The cut outs (122) allow each front leg (121) to flex radially outwards (122) as the needle shield (50) passes over the projection(s). As the needle shield (50) is removed from the syringe, the projections (124) on the resilient front legs (121) engage the outer surface of the needle shield (50) thereby restricting distal movement of the needle shield (50) further along the passageway. The needle shield (50) is now retained within the needle shield remover. In order for the needle shield (50) to be removed from the passageway (117), the user grasps the protruding needle shield (50) at the front end and pulls the needle shield (50) further in a distal direction against the friction from the flexed resilient front legs (121) gripping the exterior surface of the shield (50). The removed needle shield (50) may disposed of, and the remover device (10) is now able to be reused. The needle shield remover is further provided with a front face (111) and an outer side wall (113). WhileFIG.1dillustrates an open-cup shape to the needle shield remover housing (10), whereby the inner cylindrical wall (123) defining the passageway (117) extends proximally from the front opening, an enclosed hollow or solid form to the housing could be envisioned, whereby the rear edge (115) is joined to the inner cylindrical wall. Optionally, the shape of the front face (111) may by fully or partially circular, elliptical, square, rectangular or any other shape. Preferably, the front face (111) may have a circular or elliptical shape radiating from the central longitudinal axis. Optionally, while a generally symmetrical shape about the longitudinal axis of the housing (10) is illustrated herein, alternative aesthetic shapes to, for example, facilitate an easier hand grip of the housing such as a grip handle, could be envisioned as within the scope of the invention. The cylindrical side wall (113) of the housing (10) may be of uniform diameter along its length, or may be partially flared so as to form, for example, a truncated cone. Optionally, the side wall (113) may comprise indents or protrusions (116) to further facilitate manual gripping of the device by a user. While the embodiments presented herein illustrate the device as centred uniformly about a longitudinal axis i-ii, it is conceivable that an overall aesthetic shape to the device may configure the position of the passageway (117) at any location on the front face (111) of the housing (10). The needle shield remover may be made from any suitable material, or a combination thereof, for example plastic or metal. Preferably, the remover device is made from a rigid or flexible plastic. Optionally the projections (124) may be integral to, and made from, the same material as the front legs (121). Alternatively, the projections (124) may be an elastomeric material such as rubber. The skilled person will understand that the above description is by way of example only. For example, the remover device (10) may not be provided with a front face (111) and outer side wall (113) but rather may only be provided with an inner side wall (123). The inner side wall (123) may be provided in any suitable shape and thickness. Additionally, the inner side wall (123) may be provided with a means for gripping the needle shield remover (10). For example, the inner side wall (123) may be provided with an elastomeric sleeve extending at least part way along the wall (123) or with shaped indents and protrusions such as those shown and described with reference to the outer side wall (113) above. Additionally the needle shield remover (10) may be provided with an outer side wall (113) but not a front face (111) with the inner side wall (123) and outer side wall (113) meeting at a junction. Although the projections (120) on the rear legs (110) of the needle shield remover (10) have been described as being part way down the rear legs (110) the skilled person will understand that the location may be varied. For example, the projections (120) may be located close to, or at the proximal ends of, the rear legs (110). Additionally, the device may not be provided with rear legs but may be provided with alternative means which allows passage of the needle shield (50) past the projections (120) when the needle shield (50) is inserted into the passageway (117). The skilled person will understand that the projections (120) may be of any suitable angle relative to the rear legs (110) Alternative means for removing the needle shield could also be envisioned by the skilled person, such as for example an elastomeric or braided sleeve configured as a friction fit to surround and grasp the needle shield (50) but to allow for movement of the removed needle shield (50) forwards within the passageway (117). Optionally, the front of the passageway (117) may not be provided with cut outs (122) as described previously and shown inFIGS.1a-1dbut instead may be provided with recesses where the diameter of the inner side wall (123) at the recesses is greater than the rest of the inner side wall (123). These recesses provide a cavity into which the front legs can be pushed when the needle shield (50) is inserted into the needle shield remover (10). In a second embodiment, as shown inFIGS.2a-2e,like features are denoted by the same reference number as forFIG.1a-1d,and function in the same way, unless otherwise described. A front end of the housing (20) is set back from the front end (110) of the outer side wall (113), thereby defining an interior wall (201). A front cover (202) comprises a plurality of projections (221). The plurality of projections (221) are received by complementary recesses (207), present in the inner wall (201). The recesses (207) are positioned and configured to receive the projections (221) thereby holding the front cover (202) in engagement with the interior wall (201), thereby forming a cavity. Within the cavity is provided a barrier mechanism (203-206). The mechanism comprises a manual actuator such as a button (203), an arm (204), and a resilient biasing member (206). The manual actuator (203) is situated within a recess (222) in the side wall (113). The manual actuator (203) is connected to the arm (204) which projects from the cavity through a gap in the side wall (113), between the interior wall (201) and the front cover (202). At the opposite end of the arm (204) to the button (203), there is provide a barrier member (205) comprising a circular outer wall (205) with inner passageway (224). The diameter of the outer wall (205) defines the inner passageway (224) to have the same diameter as the passageway (117). Finally, at the opposite end of the barrier member (205) to the arm (204), there is provided a biasing member (206). The biasing member (206) comprises a resilient arcuate wall (226) connected to the barrier member (205) by two arms (225). Each arm (225) is connected at one end to the barrier member (205) and at the other to the arcuate wall (226). When the mechanism is sited within the cavity, as previously stated, the actuator (203) is situated within a recess in the side wall. The arm (204) passes through the gap (222) in the side wall (113). The barrier member (205) is positioned such that the passageway (224) of the barrier member (205) is offset from the passageway (117). The offset means that at least a portion of the barrier member (205) overlaps with the passageway (117), resulting in an effectively reduced diameter of the open passageway. The arcuate wall (226) of the biasing member is in contact with the inner surface of the housing side wall (113). The moulded protrusions (207) on the interior wall (201) provide a path in which the arm (204) of the mechanism sits, allowing only a limited range of transverse radial movement of the arm (204) and therefore the mechanism. At a first position, the barrier member passageway (224) and the passageway (117) are offset, as shown inFIG.2c. The offset is sufficient that when a needle shield (50) is inserted into the passageway (117) a sideways frictional force is applied by the barrier member (205) to the needle shield (50). The external surface of the needle shield (50) is gripped by the wall of the barrier member (204) sufficiently that when the needle shield (50) has the force exerted on it by the projections (120) during syringe removal further distal axial movement is prevented. Applying pressure to the actuator (203) causes the arm (204) and thus the barrier member (205) to move radially inwards to a second position. In this second position the passageway of the barrier member is aligned with that of the passageway (117), as shown inFIG.2d. This movement is against the bias of the arcuate wall (206). In this second position, exit of the retained needle shield (50) is enabled due to the lining up of the passageways (224,117) and thus the removal or reduction of the frictional force exerted by the barrier member (205). When pressure is removed from the actuator (203), the arcuate member (206) returns to its original shape. This causes the barrier member (205) to return to its first position, thereby causing the passageways (223,117)) to once more be offset. Optionally, at least a portion of the wall of the barrier member (204) may be provided with material to increase the friction between the needle shield (50) and the wall of the barrier member (204). This material may be an elastomer, for example, rubber. Alternatively, the barrier member (205) may be provided with teeth which engage with the surface of the needle shield (50) and are disengaged from the surface of the needle shield (50) when the actuator is depressed. The teeth may be made, for example, from a rigid plastic material or from metal. To remove the needle shield from the device in this configuration, the actuator is pressed to release the grip of the barrier member (204) on the needle shield (50). In the instance where the frictional force exerted by the barrier member (205) on the needle shield (50) is sufficient to prevent proximal movement of the needle shield (50) during removal of the syringe the needle shield remover may not be provided with the rearwardly extending legs (119) and/or projections (120) as described previously with reference toFIGS.1a-1d Alternatively, the effective diameter of the offset passageways of the barrier member (205) and the needle shield remover (200) prevents the exit of any portion of the needle shield (50), and as a result the needle shield is completely contained within the passageway. The needle shield (50) may be removed by depressing the button and allowing the needle shield to fall from the needle shield remover as no frictional force is required to prevent axial movement of the needle shield (50) out of the needle shield remover. The recesses (207) may be recesses (204) formed by the inner wall, or recess walls projecting forward from the inner wall. As will be understood by the skilled person, although the recesses are described as being present on the inner wall, the recesses may be present on an inner surface of the front cover with complementary projections present on the inner wall. Additional combinations of projections and recesses may be present on the inner wall and the front cover. Additionally, the cavity may be provided at an intermediate position between the front end of the needle shield remover and the rear end of the needle shield remover. In this instance the cavity will be extended and the front wall adapted accordingly. FIG.5illustrates the device of the second embodiment in use with a syringe (501) inserted into the passageway (117) In a third embodiment, as shown inFIG.3, like features are denoted by the same reference number as forFIG.1, and function in the same way, unless otherwise described. In this embodiment, the passageway of the housing is provided with means to hold the needle shield in frictional engagement with the passageway. This prevents the needle shield from exiting the forward opening of the passageway upon removal of the syringe. The means to hold the needle shield is at least one projection (330) located at, or near to, the front opening (112) of the inner cylindrical wall defining the passageway (117). The at least one projection holds the needle shield with sufficient frictional engagement that any force created through the syringe removal does not result in the needle shield exiting the forward opening of the passageway. Other means may be provided for holding the needle shield in the passageway through frictional engagement, for example the inner wall of the passageway may be provided with one or more sections of an elastomer such as rubber. The sections may be, for example, longitudinal strips, one or more strips formed on the surface of the inner cylindrical wall, or transversely extending strips. In a fourth embodiment, as shown inFIG.4, a needle shield remover (400) is presented in which both the cylindrical sidewall (113) and passageway (117) define cut-out sections that allow insertion of the needle shield (50) into the passageway (117) from the side of the needle shield remover (100). The cut out is such that the width of the cut out is less than the diameter of a needle shield (50). The inner sidewall (123) of the passageway (117) is formed from a material that flexes sufficiently to allow insertion of the needle shield (50) into the passageway (117) but prevents the needle shield (50) from exiting through the cut-out when the syringe is removed from the needle shield (50) out of the rear opening of the passageway (117). Preferably, the cut out in the passageway (117) is provided with a raised area that forms a ramp (130). The raised area facilitated entry of the needle shield (50) into the passageway (117). Additionally, the raised area may help to reinforce the inner sidewall (123) of the passageway (117). The needle shield remover (400) ofFIG.4is illustrated with rear resilient legs and projections as described with reference toFIGS.1a-1d.Additionally, the needle shield remover is provided with cut outs and forward resilient legs as described with reference toFIGS.1a-1d.It will be understood, however, that the needle shield remover may be provided with any suitable means to retain the needle shield (50) within the device when it is removed from a syringe, including but not limited to those means discussed with reference toFIGS.2a-2eandFIG.3. The combined removed needle shield and device are retained until disposal of the needle shield is required, whereupon the needle shield is removed from the device. This is achieved in the first and third embodiments by pulling the partially exposed front portion (51) of the needle shield (50) further in a distal direction through and out of the passageway (117,217). In the second embodiment, a user presses the actuator (203). This causes the arcuate wall of the biasing member to flex thereby releasing the grip of the locking barrier (205) on the needle shield, allowing the shield to be removed from the passageway. It will be understood that whilst in the present description the needle shield (50) is removed by the user extracting it from the distal end of the needle shield remover (100,200,300,400), the needle shield (50) may be removed by exerting an increased pressure on the needle shield (50) from the proximal end of the needle shield remover. The increased pressure causes the needle shield to exit the distal end of the passageway (117). The pressure may be provided, for example, by a rear cap which fits onto the proximal end of the needle shield remover and is provided with an projection that extends down the passageway placing a force on the removeable needle shield (50). With reference to the embodiment ofFIG.4the needle shield remover may be provided with a passageway between the outside to the passageway (117). This passageway allows a tool to be inserted through the passageway and exert a force on the needle shield in order that it exits the device through the cut out. The tool may be, for example, a device configured to fit on the outside of the needle shield remover with a projection on its inside wall. The projection being sized to contact and exert pressure on the needle shield when the device is in contact with the outside wall of the needle shield remover. The embodiments presented herein are illustrative examples presenting combinations of features of the invention. It should be understood that any feature could be combined with any other feature the same as if each and every combination of features were specifically and individually listed. | 20,111 |
11857773 | MODES OF THE INVENTION Hereinafter, a syringe safety cap and a safety syringe including the same according to an embodiment of the present disclosure will be described in detail with reference to the accompanying drawings. The present disclosure will be described below with reference to the accompanying drawings. However, the present disclosure may be implemented in various different forms and thus is not limited to the embodiments described herein. Also, parts unrelated to the description have been omitted from the drawings to clearly describe the present disclosure, and like elements are denoted by like reference numerals throughout the specification. Throughout the specification, when a certain portion is described as being “connected to (linked to, in contact with, coupled to)” another portion, this not only includes a case in which the portion is “directly connected” to the other portion but also includes a case in which the portion is “indirectly connected” to the other portion while another constituent member is disposed therebetween. FIG.1is a perspective view illustrating a safety syringe including a syringe safety cap according to an embodiment of the present disclosure,FIG.2is a perspective view illustrating the syringe safety cap according to an embodiment of the present disclosure, andFIG.3is an exploded perspective view illustrating the syringe safety cap according to an embodiment of the present disclosure. Also,FIG.7is a lateral view of the syringe safety cap according to an embodiment of the present disclosure,FIG.8is a perspective view of a main portion for describing a coupler of a safety cover portion according to another embodiment, andFIG.9is a lateral view for describing an operational state of the syringe safety cap according to an embodiment of the present disclosure. As illustrated inFIGS.1to3, a safety syringe (also abbreviated as “syringe”) may include a cylinder200, an injection needle300, and a syringe safety cap400. The cylinder200may form a main body of the safety syringe and accommodate a medicinal fluid or accommodate different medicines or liquid medicines therein. When two or more types of medicines or liquid medicines are accommodated in the cylinder200, at least two or more rubber stoppers may be arranged inside the cylinder200, and different medicines or liquid medicines may be accommodated in separate accommodation spaces in the cylinder that are isolated by the stoppers. The injection needle300may be provided at one end portion of the cylinder200. Here, a needle holder301may be further provided at the one end portion of the cylinder200, and the injection needle300may be coupled to the needle holder301. That is, the injection needle300may be fixed to the needle holder301, and the needle holder301may be mounted on the cylinder200. Also, a plunger rod may be coupled to the other end portion of the cylinder. A user may press the plunger rod toward the injection needle300to discharge a medicinal fluid, which is in the accommodation space in the cylinder, to the outside through the injection needle300. Also, the syringe safety cap400may be coupled to the cylinder200. For example, the syringe safety cap400may be coupled to the one end portion of the cylinder that is adjacent to the injection needle300. The syringe safety cap400may selectively cover the injection needle300and, in this way, prevent a needlestick injury caused by the injection needle300. For example, the syringe safety cap400may also be fitted and coupled to the cylinder200or heat-bonded to the cylinder200. Also, the syringe safety cap400relating to an embodiment (first embodiment) of the present disclosure may include a base portion410, a link portion430, a first elastic portion440, a safety cover portion450, and a second elastic portion460. Specifically, the syringe safety cap400includes the base portion410having a mounting portion to be mounted on the cylinder200of the syringe, the link portion430rotatably connected to the base portion410, and the first elastic portion440configured to provide a rotational force so that the link portion430rotates with respect to the base portion410. Also, the syringe safety cap400includes the safety cover portion450rotatably connected to the link portion430, detachably fixed to the base portion410, and configured to, when detached from the base portion410and rotating, surround the injection needle300of the syringe, and the second elastic portion460configured to provide a rotational force so that the safety cover portion450rotates with respect to the link portion430. First, the base portion410may be coupled to the one end portion of the cylinder200having a medicinal fluid accommodated therein. Also, the link portion430may be axially coupled (or connected) to the base portion410. In the present document, being “axially coupled (or connected)” refers to being coupled (connected) to be rotatable about a predetermined axis of rotation. For example, the syringe safety cap may have a first axial portion configured to provide a center of rotation of the link portion430with respect to the base portion410. Also, the first axial portion may include the first elastic portion440described above. Here, the first axial portion may include a first rotating shaft434and a first coupling hole417mounted to allow rotation of the first rotating shaft434. Specifically, the link portion430may include any one of the first rotating shaft434and the first coupling hole417constituting the first axial portion, and the base portion410may include the other one of the first rotating shaft434and the first coupling hole417constituting the first axial portion. For example, referring toFIG.3, the link portion430may include the first rotating shaft434and the base portion410may include the first coupling hole417, but the present disclosure is not limited thereto, and the opposite is also possible. Also, the safety cover portion450may be axially coupled (or connected) to the link portion430. The syringe safety cap may have a second axial portion configured to provide a center of rotation of the safety cover portion450with respect to the link portion430. Also, the second axial portion may include the second elastic portion460described above. Here, the second axial portion may include a second rotating shaft452and a second coupling hole433mounted to allow rotation of the second rotating shaft452. Specifically, the link portion430may include any one of the second rotating shaft452and the second coupling hole433constituting the second axial portion, and the safety cover portion450may include the other one of the second rotating shaft452and the second coupling hole433constituting the second axial portion. For example, referring toFIG.3, the safety cover portion450may include the second rotating shaft452and the link portion430may include the second coupling hole433, but the present disclosure is not limited thereto, and the opposite is also possible. Also, the injection needle300of the syringe may be located between the first axial portion, which provides the center of rotation of the link portion430with respect to the base portion410, and the second axial portion, which provides the center of rotation of the safety cover portion with respect to the link portion430. That is, the injection needle300may be located between the first axial portion and the second axial portion. For example, the first axial portion may be located at one end portion of the link portion430, and the second axial portion may be located at the other end portion thereof. Also, in a state in which the safety cover portion450is fixed to the base portion410, the link portion430may be disposed to surround a partial area of the cylinder200. Also, in a process in which the safety cover portion450is detached from the base portion410and surrounds the injection needle300, the safety cover portion450may break away from the cylinder200of the syringe. Meanwhile, in the process in which the safety cover portion450surrounds the injection needle, the second axial portion may be moved to approach the injection needle200of the syringe. Unlike this, the first axial portion may be provided so that a change in the position thereof does not occur in the process in which the safety cover portion450surrounds the injection needle. Also, the first axial portion, which provides the center of rotation of the link portion430with respect to the base portion410, and the second axial portion, which provides the center of rotation of the safety cover portion450with respect to the link portion430, may be arranged to be parallel. Meanwhile, the first axial portion and the second axial portion may each be provided so that the axis of the center of rotation thereof is perpendicular to a direction of a central axis C of the cylinder. In the present document, the reference sign “C” indicates the central axis of the cylinder, and the central axis of the cylinder may be coaxial with the injection needle300. Also, in the process in which the safety cover portion450surrounds the injection needle300, a direction of rotation of the link portion430with respect to the base portion410and a direction of rotation of the safety cover portion450with respect to the link portion430may be provided to be the same. That is, in the process in which the safety cover portion450surrounds the injection needle300, rotation about the first axial portion and rotation about the second axial portion may be performed in the same direction (for example, a first direction of rotation). Also, in the process in which the safety cover portion450is detached (or uncoupled) from the base portion410and surrounds the injection needle300, an angle of rotation of the link portion430with respect to the base portion410may be provided to be smaller than an angle of rotation of the safety cover portion450with respect to the link portion430. That is, the safety cover portion450may rotate about a larger angle as compared to rotation of the link portion430with respect to the base portion410. Also, the first elastic portion440interposed in the first axial portion and the second elastic portion460interposed in the second axial portion may each include a spring (for example, a torsion spring). As described above, referring toFIG.3, the link portion430may have one end portion rotatably coupled to the base portion410through the first rotating shaft434, and when the link portion430rotates in a first direction of rotation R1(seeFIG.5) about the first rotating shaft434, the link portion430may be moved to an outer side of the one end portion of the cylinder200. The first elastic portion440may be mounted on the first rotating shaft434and may provide an elastic force so that the link portion430rotates in the first direction of rotation R1(seeFIG.5). Also, the safety cover portion450may have one end portion rotatably coupled to the link portion430through the second rotating shaft452and may rotate in the first direction of rotation R1(seeFIG.5) about the second rotating shaft452and cover the injection needle300. That is, the first direction of rotation R1may be a direction in which the safety cover portion450is uncoupled from the base portion410and in which the link portion430and the safety cover portion450are unfolded. Also, the second elastic portion460may be mounted on the second rotating shaft452and may provide an elastic force so that the safety cover portion450rotates in the first direction of rotation R1(seeFIG.5). Therefore, in a state in which the safety cover portion450is coupled to the base portion410, when a force is applied from the outside to uncouple the safety cover portion450and the base portion410, the safety cover portion450rotates in the first direction of rotation R1(seeFIG.5) due to the elastic force generated by the second elastic portion460, and simultaneously, the link portion430rotates in the first direction of rotation R1(seeFIG.5) due to the elastic force generated by the first elastic portion440. That is, just by one operation in which a user uncouples the safety cover portion450and the base portion410, the safety cover portion450may be operated to cover the injection needle300, and in this way, the safety cover portion450may protect the injection needle300and prevent a needlestick injury. Referring toFIG.3, the base portion410may have a coupling ring411, a first extension bar412, and a fixing protrusion413. The base portion410may be made of, for example, a resin material. The base portion410may include the coupling ring411configured to provide a mounting portion coupled while surrounding an outer circumferential surface of the cylinder of the syringe in a circumferential direction, the first extension bar412connected to the coupling ring411, formed to extend in a longitudinal direction (or a direction of a central axis) of the cylinder200of the syringe, and having any one of the first rotating shaft and the first coupling hole, which constitute the first axial portion, formed therein, and the fixing protrusion413provided on the coupling ring411and provided to be detachably coupled to the safety cover portion450. Specifically, the coupling ring411may be coupled while surrounding the outer circumferential surface of the one end portion of the cylinder200in the circumferential direction. Also, the first extension bar412may be connected to the coupling ring411and formed to extend toward the one end portion of the cylinder200. Also, the first extension bar412may be provided as a pair of first extension bars412located to be spaced apart at a predetermined interval. Also, a pair of first coupling holes417may be formed to be symmetrical to each other in the first extension bars412. Meanwhile, the fixing protrusion413may have a column414and a stopper415. The column414may be formed to protrude from the coupling ring411in a radial direction of the cylinder200of the syringe. The column414may have a first diameter D1. The stopper415may be formed on an upper end portion of the column414and have a second diameter D2. The second diameter D2may be larger than the first diameter D1. Also, the link portion430may have a link body431and a second extension bar432. The link portion430may be made of, for example, a resin material. Also, the link portion430may include the link body431, which is formed to surround the outer circumferential surface of the cylinder200of the syringe in a state in which the safety cover portion450is fixed to the base portion410and which has one of the second rotating shaft452and the second coupling hole433which constitute the second axial portion, and the second extension bar, which is connected to the link body431and has the other one of the first rotating shaft434and the first coupling hole417which constitute the first axial portion. FIG.3illustrates an embodiment in which the second coupling hole433is provided in the link body431and the first rotating shaft434is provided on the second extension bar. Referring toFIGS.2and3, the link body431may be formed to surround an outer circumferential surface of a stepped portion201formed on the one end portion of the cylinder200. Also, both end portions of the link body431may be formed to be spaced apart from each other and formed to extend to an outer side of the cylinder200. Referring toFIG.3, a pair of second coupling holes433may be formed in both end portions of the link body431. The second extension bar432may be connected to the link body431and extend in a direction perpendicular to the longitudinal direction of the cylinder200. A pair of second extension bars432may be formed to be spaced apart at a predetermined interval, and referring toFIG.3, the first rotating shaft434may be formed on one end portion of the second extension bar432. Also, the first extension bar412of the base portion410may be inserted between the second extension bars432, and the first rotating shaft434may be coupled to the first coupling hole417. As a result, the link portion430may rotate about the first rotating shaft434. The first rotating shaft434may be formed to be perpendicular to the longitudinal direction (or the direction of the central axis) of the cylinder200. The first elastic portion440may be coupled to the first shaft434. For example, the first elastic portion440may be a coil spring or a torsion spring and may provide an elastic force so that the link portion430rotates in the first direction of rotation R1(seeFIG.5) about the first rotating shaft434. Here, when the link portion430rotates in the first direction of rotation R1(seeFIG.5) about the first rotating shaft434, the link body431may be moved to an outer side of one end portion of the base portion410. Also, when the link portion430rotates in a second direction of rotation, which is the opposite direction of the first direction of rotation R1(seeFIG.5) about the first rotating shaft434, the link body431may be located on the stepped portion201formed on the one end portion of the cylinder200, and the stepped portion201may be located at an inner side of the link body431. The second direction of rotation may be a direction in which the link portion430and the safety cover portion450are folded so that the safety cover portion450is fixed to the base portion410. Meanwhile, the safety cover portion450may include a cover body451in which the injection needle300of the syringe is accommodated and the other one of the second rotating shaft452and the second coupling hole433which constitute the second axial portion is provided (in the embodiment illustrated inFIG.3, the second rotating shaft is provided). Also, the cover body451of the safety cover portion450may have a coupling slit454formed to extend through the cover body451in a longitudinal direction thereof to be coupled to the fixing protrusion413. The safety cover portion450may be made of, for example, a resin material. The cover body451may be concavely formed so that the injection needle300is accommodated therein, and the second rotating shaft452may be provided on one end portion of the cover body451. The second rotating shaft452may be provided as a pair of second rotating shafts452symmetrical to each other. Also, the cover body451may have a flat shape instead of being inclined in the longitudinal direction thereof. Referring to the embodiment illustrated inFIG.3, the second rotating shaft452may be coupled to the second coupling hole433of the link portion430. The second rotating shaft452may be formed to be perpendicular to the longitudinal direction (or the direction of the central axis) of the cylinder200. The coupling slit454may be formed to pass through the center of the cover body451and formed to extend in the longitudinal direction of the cover body451. When rotation of the safety cover portion450in the second direction of rotation, which is the opposite direction of the first direction of rotation, is completed and the cover body451is pressed against the coupling ring411, the fixing protrusion413may be inserted into and coupled to the coupling slit454. A width W of at least a partial area of the coupling slit454may be formed to be smaller than the first diameter D1of the column414of the fixing protrusion413. Preferably, the width W of at least a partial area of the coupling slit454may be formed to be slightly smaller than the first diameter D1. Also, the coupling slit454may have a first insertion groove455and a second insertion groove456. The first insertion groove455may be formed in one end portion of the coupling slit454. The first insertion groove455may be formed to have a third diameter D3, which is larger than the second diameter D2of the stopper415of the base portion410, so that the stopper415is insertable into the first insertion groove455. Therefore, the stopper415may be inserted into the first insertion groove455. Also, the second insertion groove456may be formed in a central portion of the coupling slit454. The second insertion groove456may be formed to have a fourth diameter D4which is larger than the first diameter D1of the column414and smaller than the second diameter D2of the stopper415. Accordingly, when the safety cover portion450moves along the cylinder200(for example, moves toward the other end portion thereof) in a state in which the stopper415of the fixing protrusion413is inserted into the first insertion groove455, the column414may be moved along the coupling slit454and inserted into the second insertion groove456. Here, although the width W of at least a partial area of the coupling slit454is smaller than the first diameter D1of the column414, as the coupling slit454widens due to the column414when the safety cover portion450moves toward the other end portion of the cylinder200, the column414may be inserted into the second insertion groove456. The column414inserted into the second insertion groove456may be fixed to the second insertion groove456unless a separate extremal force is applied thereto. Then, when an external force is applied to the safety cover portion450causing the safety cover portion450to move toward the one end portion of the cylinder200, the column414may be moved to the first insertion groove455along the coupling slit454, and when the safety cover portion450rotates in the first direction of rotation R1about the second rotating shaft452, the stopper415may exit the first insertion groove455, and the safety cover portion450and the fixing protrusion413are uncoupled. The second elastic portion460may be coupled to the second shaft452. The second elastic portion460may be a coil spring or a torsion spring and may provide an elastic force so that the safety cover portion450rotates in the first direction of rotation R1(seeFIG.5) about the second rotating shaft452. When the safety cover portion450rotates in the first direction of rotation R1(seeFIG.5) about the second rotating shaft452, as the safety cover portion450rotates toward the injection needle300, the injection needle300may be accommodated in the cover body451. The cover body451may have a wing portion451aformed at both side edges in the longitudinal direction to sufficiently cover the injection needle300when rotation of the cover body451is completed. Referring toFIG.7, the wing portion451amay be provided to, in a state in which the cover body451is fixed to the base portion410, further protrude in the radial direction of the cylinder with respect to a virtual line segment L that is parallel to the central axis C of the cylinder. The safety cover portion450may have a coupler457into which a partial area of the injection needle300is inserted when rotation of the safety cover portion450is completed and the safety cover portion450surrounds the injection needle300. Also, one end portion of the coupler457may be formed to be spaced apart from an inner circumferential surface of the cover body451. Accordingly, a separation portion457amay be formed between the one end portion of the coupler457and the inner circumferential surface of the cover body451. When rotation of the cover body451in the first direction of rotation R1about the second rotating shaft452is completed and the cover body451covers the injection needle300, the injection needle300may be accommodated in the cover body451, and one end portion of the injection needle300may be inserted into the coupler457through the separation portion457aand coupled to the coupler457. Referring toFIG.8, the coupler may include a first protruding portion458and a second protruding portion459that are located to be spaced apart to form an accommodation space S for the injection needle300. Here, the coupler is provided to allow the injection needle300to be inserted into the space between the first protruding portion458and the second protruding portion459, and a catching protrusion458aconfigured to prevent the injection needle300from breaking away is provided on the first protruding portion458. Of course, a predetermined space is provided between the catching protrusion458aand the second protruding portion459, and the space is formed to have a width narrower than that of the accommodation space S. Also, an inclined surface may be provided on an inlet side of the injection needle300on each of the catching protrusion458aand the second protruding portion459. Hereinafter, an operation of the syringe safety cap will be described. FIGS.4to6are exemplary views illustrating operation examples of the syringe safety cap according to an embodiment of the present disclosure. First, as illustrated inFIG.4A, before the syringe is used, the injection needle30may be covered with a needle cap10. The syringe safety cap400may not interfere with the needle cap10being coupled to the one end portion of the cylinder200. In a state in which the needle cap10is coupled, the link portion430of the syringe safety cap400may be in a state of, after rotation thereof in the second direction of rotation is completed, being located to surround the outer circumferential surface of the stepped portion201of the cylinder200, and the safety cover portion450may also be in a state of, after rotation thereof in the second direction of rotation is completed, being coupled and bound to the fixing protrusion413of the base portion410. Accordingly, the safety cover portion450and the link portion430may be fixed so as not to be rotated in the first direction of rotation R1. Also, as illustrated inFIG.4B, the needle cap10may be removed before using the syringe. A user may lightly push up the needle cap10to remove the needle cap10. After removing the needle cap10, the user may give an injection to a patient or the like. Meanwhile, in a state in which use of the syringe is completed, the column414of the fixing protrusion413may be in a state of being inserted into the second insertion groove456. In this state, when the user pushes the safety cover portion450upward as illustrated inFIG.5A, as illustrated inFIG.5B, the column414of the fixing protrusion413is moved along the coupling slit454and moved to the first insertion groove455, and the link portion430rotates in the first direction of rotation R1about the first rotating shaft434. Then, in this state, when the user lifts the safety cover portion450and the stopper415exits the first insertion groove455, the safety cover portion450rotates in the first direction of rotation R1due to the elastic force provided by the second elastic portion460. Also, simultaneously, the link portion430rotates in the first direction of rotation R1due to the elastic force provided by the first elastic portion440. Then, as illustrated inFIG.6, the link body431of the link portion430may be moved to the outer side of the stepped portion201about the first rotating shaft434, and the second rotating shaft452may be moved to an upper side of the cylinder200. Also, the safety cover portion450may rotate about the second rotating shaft452, and an upper end portion of the safety cover portion450may be moved to the upper side of the cylinder200. That is, the safety cover portion450and the link portion430may be unfolded due to moving to the upper side of the cylinder200, and the injection needle300may be accommodated in the cover body451. Also, one end portion of the injection needle300may be inserted and coupled to the coupler457of the safety cover portion450, and in this way, unintentional separation between the safety cover portion450and the injection needle300may be prevented. In this way, according to the present disclosure, just by a simple operation of releasing a coupling force between the fixing protrusion413and the safety cover portion450, the safety cover portion450and the link portion430may simultaneously and automatically rotate due to the elastic force provided by the first elastic portion440and the second elastic portion460, and the safety cover portion450may cover the injection needle300. FIG.10is a perspective view of a main portion illustrating a syringe safety cap according to another embodiment (second embodiment) of the present disclosure, andFIG.11is a lateral view of the syringe safety cap illustrated inFIG.10. Referring toFIGS.10and11, the syringe safety cap according to the second embodiment is different from the syringe safety cap according to the first embodiment only in terms of configurations of a first elastic portion and a first axial portion, and all other elements are the same. Hereinafter, only the configurations different from the first embodiment will be described in detail. Specifically, a first elastic portion500includes one or more bridges510and520which connect the link portion430and the base portion410and in which at least a partial area is bent. In the second embodiment, rotation of the link portion430with respect to the base portion410uses a rotational force using the bent shape of the bridges. Also, a second elastic portion includes a spring as in the first embodiment. Specifically, the bridges may include the first bridge510and the second bridge520which are bent in the opposite directions. The first bridge and the second bridge may be bent in a substantially “V” shape. Also, an angle at which the first bridge510is bent and an angle at which the second bridge520is bent may be different. Also, the number of first bridges510and the number of second bridges520may be different. For example, the first elastic portion500may include a pair of first bridges510, and the second bridge520may be disposed between the pair of first bridges510. Also, in the second embodiment, the first axial portion may consist of one or more bridges connecting the link portion430and the base portion410instead of consisting of a rotating shaft and a coupling hole. The exemplary embodiments of the present disclosure which have been described above are only disclosed for an illustrative purpose, and those of ordinary skill in the art should be able to make various modifications, changes, and additions within the idea and scope of the present disclosure, and such modifications, changes, and additions should be construed as falling within the scope of the claims below. INDUSTRIAL APPLICABILITY According to a syringe safety cap and a safety syringe including the same relating to at least one embodiment of the present disclosure, just by a simple operation of uncoupling a safety cover portion and a fixing protrusion of a base portion, an injection needle can be surrounded and protected by the safety cover portion. | 30,488 |
11857774 | DETAILED DESCRIPTION Some embodiments of the present invention will now be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all, embodiments of the invention are shown. Indeed, various embodiments of the invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. As noted above, fluid delivery to a patient intravenously through IV tubing can be challenging. Fluid delivery while removing air bubbles from the IV tubing is inefficient and sometimes ineffective. Embodiments described herein provide a device to remove air from IV tubing without interrupting fluid flow from a fluid source, such as an IV bag or syringe, to a patient. Embodiments may be employed in any setting where intravenous fluid introduction to a patient is performed using IV tubing. According to an example embodiment provided herein, an air extraction device in-line with intravenous tubing to remove air from fluid flowing through the tubing and to carry the air to a reservoir or vent where the air is safely removed while enabling fluid flow through the IV tubing without air bubbles present after the in-line extraction device. The air extraction device described herein extracts air from IV tubing proximate a patient by establishing a branch from the IV tubing that provides a pathway for air removal from the fluid flow through the tubing. In order to prevent rapidly-infused medications from being forced into the branch tube, a ball valve is used. The fluid as described herein may be any fluid that is supplied to a patient via intravenous infusion. Fluid such as saline and/or liquid medications, for example. Fluid may also include blood infused intravenously from a reservoir or blood infused from a closed-loop dialysis system, for example. Orientation of the air extraction device is imperative to function due to the air having a lower specific gravity than the fluid, where air rises relative to the fluid regardless of the gaseous make up of the air or the type of fluid being used in the IV. The term “air” is used herein to describe any gaseous substance found within the IV system. While atmospheric air is primarily Nitrogen and Oxygen, the air found in an intravenous system may be atmospheric air or may be air from within an IV bag, which may be anaerobic or have other chemical composition. Thus, the term “air” as used herein may be gases of any chemical composition. Due to the air within IV tubing being lighter than the fluid flowing through the IV tubing, the orientation of the air extraction device is important for proper extraction of the air. The branch tube from which air is extracted from the IV tubing is raised relative to the IV tubing to promote air extraction. Embodiments provided herein further include a mechanism by which proper orientation of the air extraction device is maintained while also providing a mechanism to close the branch tube when the orientation of the air extraction device is improper. FIG.1illustrates a conventional IV arrangement for which a patient100receives a fluid intravenously from an IV bag110suspended on a stand120. As shown, the fluid from the IV bag110flows through a first tubing section112to an IV pump130and out of the IV pump along second tubing section114and into an arm of the patient100at IV site116. The IV pump130is optional and not present in all situations in which a patient receives fluid intravenously. Optionally, the fluid may be fed through the IV tubing by gravity with the IV bag110suspended at sufficient height that the fluid flows through the tubing at a metered pace to the patient100. The patient100of the illustrated embodiment is in a hospital bed140with bed rails142. The hospital bed140is one conventional situation for a patient receiving intravenous fluids; however, it is not intended to be limiting. FIG.2illustrates an IV arrangement including an air extraction device150according to example embodiments of the present disclosure. The air extraction device150is positioned along the second tubing section114of the illustrated scenario, located close to the patient100. The air extraction device150includes a branch tube152extending from the air extraction device150, where the branch tube terminates at a reservoir160that may be present to collect the air extracted from the IV fluid. The reservoir160is optional and may be present to capture and monitor a volume of air extracted by the air extraction device150. Further, the reservoir may function to maintain the IV fluid system, from the IV bag110to the patient100, a closed system such that contaminants cannot be introduced to the system. According to the illustrated embodiment ofFIG.2, fluid flows from the IV bag110through the first tubing section112to the IV pump130, and along the second tubing section114. While air has several ways of being introduced to the tubing, air may be introduced when medications are delivered to the IV tubing via a syringe connector. A syringe injecting medicine into the IV tubing may result in some amount of air introduced to the IV tubing. This may be due to air in the syringe, which may occur due to the method of filling the syringe, or the air bubbles may form through cavitation, for instance. Regardless, air bubbles traveling along the second tubing section114encounter the air extraction device150. The air extraction device150separates the air bubbles from the fluid and expels the air along the branch tube152to the reservoir160while the IV fluid continues along the patient-side IV tubing118to the patient IV site116. FIG.3illustrates a diagram of features of the air extraction device150ofFIG.2shown in greater detail. As shown, the air extraction device150includes a fluid inlet214where the second tubing section114enters chamber200. The fluid202in the chamber flows out through fluid outlet218to patient-side IV tubing118. The fluid202fills the chamber200to a fluid level204. A ball206floats at the fluid level204. The ball206density may be chosen based on the type of fluid that is to be intravenously provided to a patient; however, the density is generally such that the ball remains buoyant on the fluid while only partially submerged below the fluid level204. A less dense ball206may be more responsive to fluctuations in fluid; however, a less dense ball may also be subject to premature closing of the ball valve while a more dense ball, while still remaining buoyant in the fluid, may respond more slowly. A more dense ball206may permit fluid flow into the branch tube152in response to a sudden influx of fluid into the chamber200. The chamber200includes at a top portion208that narrows to meet the branch tube152. The narrowing top portion208may be frustoconical or frusto-pyramidal whereby as the fluid level204of the fluid202rises, the ball206floats up. As the fluid level204continues to rise, the ball206is guided by the narrowing top portion208to close off or seal the branch tube152. This ball valve functionality prevents or reduces the likelihood of fluid flow into the branch tube152, and allows the fluid202to continue to flow from the chamber200through fluid outlet218along the patient-side IV tubing118. As will be described further below, this ball valve functionality does not enable air flow through the air extraction device150to the patient despite being able to close off the branch tube152in response to a high fluid level204. FIG.4illustrates the air extraction device during operation, while fluid202is flowing in through the fluid inlet214and out through fluid outlet218of the chamber200. As shown, when fluid is received at the chamber200with air bubbles230, the air bubbles230float up within the chamber200due to the top portion208being elevated relative to the inlet214and the air being lighter than the fluid202. The air bubbles230crest the fluid level204and the air is carried up the branch tube152as illustrated by arrows232. Maintaining fluid level204results in any air introduced into the chamber200further pushing air in the chamber up through the branch tube152. Fluid202, with air bubbles230having escaped, then flows through fluid outlet218to the patient-side IV tubing118as shown by arrows234for delivery to the patient100. The illustration ofFIG.4demonstrates the primary functional purpose of the air extraction device150whereby air is separated from the fluid202and allowed to escape from the IV tubing by way of the branch tube152without disrupting the fluid flow from the IV bag110to the patient100. This extraction of the air from the fluid reduces the chances of an air embolism thereby improving the safety of intravenous fluid infusion. The fluid inlet214is elevated within the chamber200relative to the fluid outlet218to further discourage air from exiting through the fluid outlet218as the air accumulates in the top portion208of the chamber as described above. In some situations, fluid may flow rapidly through the IV fluid system illustrated inFIG.2. Such situations include where rapid rehydration or medication absorption is needed by a patient. In these situations, it remains imperative to extract air from the fluid flow while also precluding fluid from escaping from the system through the branch tube152.FIG.4illustrates an example embodiment in which fluid is flowing rapidly through fluid inlet214into the chamber200. When this begins to happen, the fluid level204will rise quickly. When the fluid level204rises, the ball206is carried by the fluid into the top portion208of the air extraction device150where the ball206plugs the exit of the chamber to the branch tube152. The fluid202is thus precluded from flowing through the branch tube152and away from the patient. The fluid is instead forced to exit the chamber200through the fluid outlet218along the patient-side IV tubing118to the patient100for delivery of the rapidly flowing fluid. While the branch tube152is plugged during rapid fluid flow, the air extraction device150continues to function.FIG.6illustrates that if air bubbles are received while fluid is flowing rapidly through the air extraction device150, the bubbles will rise in the chamber200and accumulate in the top portion108of the chamber around the ball206. When a sufficient amount of air bubbles have been received, the fluid level204descends and opens a pathway for the air to escape through the branch tube152. During rapid fluid flow, the fluid level204may rise to close the branch tube152with ball206, and periodically sufficient air bubbles may be received in the chamber to lower the fluid level204sufficiently to enable air to escape through the branch tube152whereupon the fluid level204may rise again to close the branch tube152with the ball206. Thus, even during rapid fluid flow, the air extraction device150continues to function to extract air from the fluid and expel the air along the branch tube152. FIG.7illustrates a perspective view of the air extraction device with dimensions of an example embodiment. As shown, an air extraction device150of an example embodiment may have a width of 20 millimeters and a height of 60 millimeters. The shape of the chamber200may be cylindrical with a frustoconical top portion208. Optionally, the chamber200may be of a flexible membrane with no structural shape, whereby the chamber200is relatively flat when empty, but inflates with fluid as intravenous fluid enters the chamber through fluid inlet214. Even if the chamber200includes a structural shape, the chamber may be constructed of a flexible material, such as the same material as the intravenous tubing or of a silicone, for example. Embodiments in which the chamber is flexible provide an advantage that the chamber200can be used as a pump to remove airlocks from the intravenous tubing. The flexible nature of the chamber200of some embodiments is counterintuitive to a chamber that includes a ball check valve as disclosed herein. This is due to a conventional ball check valve having a rigid enclosure to enable the ball to move consistently and repeatably. However, applicant has developed a chamber200that can be flexible while including a ball206of a check valve to prevent fluid flow through the branch tube152. According to example embodiments described herein, the ball206only needs to close the branch tube152in response to the chamber filling with fluid. When the chamber200fills with fluid, the chamber volume becomes substantially the maximum volume possible for the chamber, thus establishing the shape defined by the flexible material in an expanded position. As the ball206is only employed for function when the chamber200is filled, the chamber is substantially the same repeatable, and defined shape whenever the ball206is used. Thus, while the chamber may be of a flexible and pliable material that can be used for pumping of fluid as detailed herein, the ball206valve sealing retains full functionality despite the flexible nature of the chamber. Airlocks occur in intravenous tubing where air bubbles exist in the tubing and preclude fluid flow or the flow of the air bubbles through the tubing. Historically these airlocks have been removed by tapping or flicking the IV tubing to drive the air up the tubing to an IV bag. However, embodiments described herein can pump fluid through the chamber200while simultaneously expelling air through the branch tube152by squeezing the chamber. This pumping action may draw the airlock into the chamber200through the fluid inlet214where the air passes through the branch tube while the fluid continues to flow through the fluid outlet218. This pumping action does not preclude functionality of the air extraction device150and instead benefits the air extraction device by providing additional functionality of being a fluid/air pump that pulls fluid and air through the inlet214and expels the fluid and air through different outlets while preventing air from flowing to a patient. In order for the air extraction device150to properly function, the chamber200should be maintained at the height of the patient or lower such that air does not enter the patient-side IV tubing118from the chamber. The arrangement of the air extraction device150below the IV bag110enables flow of fluid to the air extraction device150by gravity feeding or by IV pump130. Further, maintaining the reservoir at the height of the patient's IV site116or lower does not allow air to enter the patient-side IV tubing118. To help maintain this arrangement, embodiments described herein may employ a clip from which the air extraction device150is hung. The clamp may include a normally-closed clip that closes down on the branch tube152to preclude flow of any fluid or air through the branch tube152while the clamp is not attached to an object. FIG.8illustrates an example clamp300that may be used to close the branch tube152while the clamp is not attached to an object, and to open the branch tube152when attached to an object, such as a bed rail320of a hospital bed. The clamp300of the illustrated embodiment includes two primary components of a first part302and a second part304. In the closed position, whereby the branch tube152is closed, a spring biases the second part304toward the first part302, closing a clip308formed by the two parts. This pinches the branch tube152as shown in the top view closed illustration. When the clamp is attached to an object such as a bed rail320of a hospital bed, the first part302is pushed away from the second part304compressing the spring310against element306while opening the clip308. Thus, when the clamp is attached to an object, as to be done by a nurse or attending caregiver, the air extraction device150is ensured to be in the correct orientation with the branch tube152extending upward from the chamber200. If the clamp were not clamped to an object, as shown in the “closed” position ofFIG.8, the orientation of the air extraction device150is not ensured, such that the branch tube152is closed. Embodiments of the air extraction device described herein may be positioned anywhere between the IV fluid source (e.g., the IV bag110) and the patient100provided the air extraction device150is positioned at an appropriate elevation with respect to the fluid source and the patient. However, according to embodiments in which the air extraction device150is located downstream of an IV pump130as shown inFIG.2, the air extraction device may substantially eliminate any air bubbles from the IV tubing. IV pumps130may include air bubble detection means to detect when air exists in the IV tubing. When air is detected in the IV tubing, the IV pump130may cease operation until the issue is rectified by a medical professional, and/or the air detection means may cause an alarm to sound to alert an attending medical professional of the detected air in the IV tubing. When employing the air extraction device150as described herein, the air bubble detection means of an IV pump may be turned off since air bubbles passing through the IV pump will be mitigated downstream by the air extraction device. The turning off of the air bubble detection means and associated alarm reduces the time an attending medical professional has to spend dealing with alarms, both false alarms and legitimate alarms, such that the efficiency and efficacy of the medical professionals can be improved. Any modifications and other embodiments of the inventions set forth herein will come to mind to one skilled in the art to which these inventions pertain having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. Therefore, it is to be understood that the inventions are not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. Moreover, although the foregoing descriptions and the associated drawings describe example embodiments in the context of certain example combinations of elements and/or functions, it should be appreciated that different combinations of elements and/or functions may be provided by alternative embodiments without departing from the scope of the appended claims. In this regard, for example, different combinations of elements and/or functions than those explicitly described above are also contemplated as may be set forth in some of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. | 18,673 |
11857775 | DETAILED DESCRIPTION Some embodiments of the present disclosure will now be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all embodiments are shown. Indeed, the disclosure may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. The terms “or” and “optionally” are used herein in both the alternative and conjunctive sense, unless otherwise indicated. The terms “illustrative” and “exemplary” are used to be examples with no indication of quality level. Like numbers refer to like elements throughout. As used herein, the term “controller” refers to any user device, computing device, object, or system which may be in network communication with the first temperature sensor, the second temperature sensor, and/or the heating element. For example, the controller may refer to a wireless electronic device configured to perform various temperature related operations in response to temperature data generated by the first temperature sensor and/or the second temperature sensor. The controller may be configured to communicate with the first temperature sensor, the second temperature sensor, the heating element, and/or the like via Bluetooth, NFC, Wi-Fi, 3G, 4G, 5G protocols, and the like. In some instances, the controller may comprise the first temperature sensor, the second temperature sensor, and/or the heating element. As used herein, the term “computer-readable medium” refers to non-transitory storage hardware, non-transitory storage device or non-transitory computer system memory that may be accessed by a controller, a microcontroller, a computational system or a module of a computational system to encode thereon computer-executable instructions or software programs. A non-transitory “computer-readable medium” may be accessed by a computational system or a module of a computational system to retrieve and/or execute the computer-executable instructions or software programs encoded on the medium. Exemplary non-transitory computer readable media may include, but are not limited to, one or more types of hardware memory, non-transitory tangible media (for example, one or more magnetic storage disks, one or more optical disks, one or more USB flash drives), computer system memory or random access memory (such as, DRAM, SRAM, EDO RAM), and the like. Having set forth a series of definitions called-upon throughout this application, an example system architecture and example apparatus is described below for implementing example embodiments and features of the present disclosure. Fluid flow systems have fluid sensors to detect air bubbles and debris in Intravenous (IV) tubes by monitoring various parameters, such as pressure, rate of flow of fluids through an IV tube, and amplitude of signal response of a fluid sensor. The fluid sensor detects air bubbles and debris in an IV tube based on radiations emitted by a transmitter of the fluid sensor that propagates through the IV tube and are received by a receiver of the fluid sensor. Existing fluid sensors use high frequency ultrasonic acoustic waves within a range of 1.7 Megahertz (MHz) to 5 MHz using a piezo electric transducer. Such high frequency ultrasonic waves are received and detected by another piezoelectric transducer. The high frequency range is typically used to detect liquid and bubbles in the IV tube. However, not all types of fluid sensors are compatible with such a high frequency range operation. For instance, fluid sensors that use other type of sensors, such as force sensors or pressure sensors with the ultrasonic transducers are not operable with the high frequency range and may have issues regarding operation and accuracy of detection. An optimum frequency range is required for the fluid sensors to operate and achieve a desired efficiency and accuracy of detection of air bubbles and liquid. The IV tube is in surface contact with the fluid sensor with the IV tube pressed against the transmitter and the receiver of the fluid sensor for detection of the radiations. The IV tube may have subtle movements during patient administration, and the surface contact or contact area of the IV tube with the transmitter and the receiver varies causing unwanted variations in amplitude of radiations detected by the receiver and a corresponding output signal. The variations in surface contact or tube contact pressure and area affects the frequency of the ultrasonic signals and response of the force sensor. A poor coupling between the IV tube and the fluid flow sensor results in an insufficient amount of ultrasonic signals propagating through the IV tube and causing improper and inaccurate detection of air bubbles and liquid. Further, in an event of occlusion, the pressure inside the IV tube increases, and the surface of the IV tube becomes stiffer. The change in stiffness of the surface also affects the radiations and the corresponding output signal, as more radiations of higher amplitude are required to propagate through the IV tube to reach the receiver, when the surface is stiffer. This results in erroneous signal detection. For transmitting the ultrasonic signals that propagate through the IV tube, a sufficient level of pressure of the ultrasonic signals is required for uninterrupted detection of air bubbles and liquid. Various example embodiments described in present disclosure relates to a fluid flow system for monitoring delivery of fluids to patients with improved detection of air bubbles and liquid in an IV tube or a flow tube. The fluid flow system has a force sensor that holds the IV tube or the flow tube and monitors the flow tube for various parameters such as flow rate, and pressure, air bubbles and liquid. The force sensor receives ultrasonic signals from the ultrasonic transducer. The fluid flow system has a controller connected to the force sensor. The controller detects an output signal from the force sensor and detects air bubbles or liquid based on the output signal. In an example, the output signal has two components, an Alternating Current (AC) component and a Direct Current (DC) component. An advantage of using such an output signal having both the AC component and the DC component is to receive information about the air bubbles and occlusion from the same signal, thereby preventing use of different or separate signals for each air bubbles and occlusion detection. In an example, the controller detects a change in the output signal from a first output signal to a second output signal, for instance, in response to an uncontrolled sensor position, or movement of the flow tube or change in flow rate or pressure of the liquid in the flow tube. The controller determines a time duration time duration of the second output signal of the force sensor from an instance the first output signal is changed to the second output signal. The controller determines a number of transitions in consecutive signal levels of the DC component from a first signal level to a second signal level. Further, the controller compares the time duration with a predefined time, and the number of transitions with a predefined number of transitions. After comparing, the controller determines a threshold, also referred to as a new threshold herein, for detecting the air bubbles or liquid. The controller then detects the air bubble and the liquid based on the threshold. For instance, when there is a change in the second output signal to a third output signal less than the threshold, an air bubble is detected by the controller. In this manner, the threshold for the fluid flow system is dynamically updated based on the change in the output signal in response to various factors, such as uncontrolled sensor position, or movement of the flow tube or change in flow rate or pressure and other conditions. Thus, the disclosed fluid flow system is robust and accurate in detecting the air bubbles when conditions of the flow tube and the sensor change thereby enhancing reliability of the fluid flow system. In an example, the force sensor is operated at a frequency range of 20 Kilo Hertz (KHz) to 1 Mega Hertz (MHz). The force sensor operated in such a frequency range provides efficient and accurate detection of the air bubbles and the liquid with clear distinction between bubble detection and liquid detection. In an example, the flow tube is disposed within a channel of the force sensor with a tube compression of 10-40% of a diameter of the flow tube to achieve better coupling efficiency. The ultrasonic signals are transmitted with a sufficient Acoustic Power Level (APL) for improved and continuous propagation of the signals through the flow tube. The details regarding components of the fluid flow system and their working is described in detail with reference to subsequent figures. The components illustrated in the figures represent components that may or may not be present in various example embodiments described herein such that embodiments may include fewer or more components than those shown in the figures while not departing from the scope of the disclosure. Turning now to the drawings, the detailed description set forth below in connection with the appended drawings is intended as a description of various example configurations and is not intended to represent the only configurations in which the concepts described herein may be practiced. The detailed description includes specific details for the purpose of providing a thorough understanding of various concepts with like numerals denoting like components throughout the several views. However, it will be apparent to those skilled in the art of the present disclosure that these concepts may be practiced without these specific details. FIGS.1A and1Billustrate perspective and top views of a fluid sensor100of a fluid flow system, in accordance with an example embodiment of the present disclosure. As shown, the fluid sensor100has an outer body or a housing102defining a channel104to hold a flow tube106. The fluid sensor100also comprises multiple indicators, such as indicators108and110on a top face of the housing102. In an example, the housing102defines an exterior of the fluid sensor100and may have a height, length, and a width, wherein the length of the housing102is defined by a distance between a first end and a second end. The housing102defines a shape of the fluid sensor100. For instance, the housing is a cube shown in the figure. The housing102can also have other shapes to fit into the fluid flow system. The channel104is defined on the top face of the housing102and has a predefined width to receive the flow tube106. As shown, the channel104is defined along a center region of the top face of the housing102. The channel104divides the top face of the housing102into two parts, a first portion112and a second portion114. Each of the first portion112and the second portion114houses a sensor as described in more detail with reference to subsequent figures. In various embodiments, the flow tube106has a length, and a diameter, and comprises an outer circumferential wall, an inner circumferential wall, and a wall thickness extending between the outer circumferential wall and the inner circumferential wall. In an example, the flow tube106defines an interior channel within the inner wall configured to direct the flow of fluid from one location to another location. The flow tube106may comprise a resilient material, for e.g., a silicone material, a polyvinyl chloride material, and/or the like. In an example, the indicators108and110glow with different colors to signal when a bubble is detected or a flow occlusion event is detected. For instance, the indicator108glowing with a red color indicates a bubble detected and the indicator110glowing with a red color indicates detection of the flow occlusion event. These signals for air bubble and flow occlusion are electrically communicated to a controller of the fluid flow system for control action as required by the fluid flow system. FIG.2illustrates a fluid flow system200, in accordance with an example embodiment of the present disclosure. The fluid flow system200comprises an ultrasonic transducer202, a force sensor204and a controller206. The controller206is coupled to the ultrasonic transducer202and the force sensor204. Further, the fluid flow system200comprises a power supply208and a server or a computer210. As shown, the housing102comprises the channel104extending from the first end of the housing102to the second end and configured to receive and secure a portion of the flow tube106. The housing102may be configured to enclose both the ultrasonic transducer202and the force sensor204within the interior portion of the housing102. The ultrasonic transducer202and the force sensor204are each coupled to an interior portion of the housing102and are spaced apart within the interior portion of the housing102to define the channel104between the two sensors. The ultrasonic transducer202and the force sensor204of the illustrated embodiment are aligned within the housing102so as to face one another, that is, an emitting face of the ultrasonic transducer202is facing towards a receiving face of the force sensor204such that waves or signals generated by the ultrasonic transducer202and emitted from the emitting face of the ultrasonic transducer202travel towards the receiving face of the force sensor204. In such an exemplary configuration, the ultrasonic transducer202and the force sensor204are arranged to face a direction perpendicular to the length of the channel104, and may define at least a portion of the channel104. The power supply208is configured to receive power and power the fluid sensor100. In an example, the power supply208may comprise one or more batteries, one or more capacitors, one or more constant power supplies, e.g., a wall-outlet, and/or the like. In an example, the power supply208may comprise an external power supply positioned outside the housing102and configured to deliver alternating or direct current power to the fluid sensor100. In another example, the power supply208may comprise an internal power supply integrated within the fluid flow system, for example, one or more batteries, positioned within the housing102, to obtain power from within the fluid flow system. In various embodiments, power may be supplied to the controller206to enable distribution of power to the various components described herein. In some embodiments, each of the components of the fluid sensor100may be connected to controller206(e.g., for electronic communication), which may be configured to facilitate communication and functional control therebetween. As illustrated inFIG.3, the controller206may include an input/output circuitry302, a memory304, a processor306, and communications circuitry308. In an example embodiment, the controller206may include a communication module, an on-board display, and signal analysis circuitry (not shown in the figure). For example, the controller206may comprise a driving circuit and a signal processing circuit. In various embodiments, the controller206may be configured to power the force sensor204and/or receive an output signal from the force sensor204. In various embodiments, the controller206may be configured to power the ultrasonic transducer202and transmit a drive signal to the ultrasonic transducer202. In various embodiments, the controller206may be configured to transmit output signals out to external components via universal serial bus (USB) or any other wired connection. In various embodiments, an on-board display may be configured to display a variety of signals transmitted from or received by the controller206. In various embodiments, the controller206may be embodied as a single chip (e.g., a single integrated-circuit chip) configured to provide power signals to both the ultrasonic transducer202and the force sensor204, to receive and process the output signal from the force sensor204, and/or to compensate for any detected changes in environmental factors such as, for example, temperature, flow, or pressure within the flow tube106. In an example, the controller206is configured so as to enable wireless communication within a network to a variety of wirelessly enabled devices, e.g., a user mobile device, a server or a computer210, and/or the like. The controller206may be configured to execute the operations described below in connection withFIGS.4A and4B. Although components302-308are described in some cases using functional language, it should be understood that the particular implementations necessarily include the use of particular hardware. It should also be understood that certain of these components302-308may include similar or common hardware. For example, two sets of circuitry may both leverage use of the same memory304, the processor306, and the communications circuitry308, or the like to perform their associated functions, such that duplicate hardware is not required for each set of circuitry. The use of the term “circuitry” as used herein includes particular hardware configured to perform the functions associated with respective circuitry described herein. As described in the example above, in some embodiments, various elements or components of the circuitry of the controller206may be housed within the fluid sensor100. It will be understood in this regard that some of the components described in connection with the controller206may be housed within one or more of the device ofFIG.3, while other components are housed within another of these devices, or by yet another device not expressly illustrated inFIG.3. The term “circuitry” should be understood broadly to include hardware, in some embodiments, the term “circuitry” may also include software for configuring the hardware. For example, although “circuitry” may include processing circuitry, storage media, network interfaces, input/output devices, and the like, other elements of the controller206may provide or supplement the functionality of particular circuitry. In some embodiments, the processor306(and/or co-processor or any other processing circuitry assisting or otherwise associated with the processor306) may be in communication with the memory304via a bus for passing information among components of the controller206. The memory304may be non-transitory and may include, for example, one or more volatile and/or non-volatile memories. In other words, for example, the memory may be an electronic storage device (e.g., a non-transitory computer readable storage medium). The memory304may be configured to store information, data, content, applications, instructions, or the like, for enabling the controller206to carry out various functions in accordance with example embodiments of the present invention. The processor306may be embodied in a number of different ways and may, for example, include one or more processing devices configured to perform independently. Additionally or alternatively, the processor306may include one or more processors configured in tandem via a bus to enable independent execution of instructions, pipelining, and/or multithreading. The use of the term “processing circuitry” may be understood to include a single core processor, a multi-core processor, multiple processors internal to the computing device, and/or remote or “cloud” processors. In an example embodiment, the processor306may be configured to execute instructions stored in the memory304or otherwise accessible to the processor306. Alternatively or additionally, the processor306may be configured to execute hard-coded functionality. As such, whether configured by hardware or by a combination of hardware with software, the processor306may represent an entity (e.g., physically embodied in circuitry) capable of performing operations according to an embodiment of the present invention while configured accordingly. Alternatively, as another example, when the processor306is embodied as an executor of software instructions, the instructions may specifically configure the processor306to perform the algorithms and/or operations described herein when the instructions are executed. The controller206further includes input/output circuitry302that may, in turn, be in communication with processor306to provide output to a user and to receive input from a user, user device, or another source. In this regard, the input/output circuitry302may comprise a display that may be manipulated by a mobile application. In some embodiments, the input/output circuitry302may also include additional functionality including a keyboard, a mouse, a joystick, a touch screen, touch areas, soft keys, a microphone, a speaker, or other input/output mechanisms. The processor306and/or user interface circuitry comprising the processor306may be configured to control one or more functions of a display through computer program instructions (e.g., software and/or firmware) stored on a memory accessible to the processor306(e.g., memory304, and/or the like). The communications circuitry308may be any means such as a device or circuitry embodied in either hardware or a combination of hardware and software that is configured to receive and/or transmit data from/to a network and/or any other device, circuitry, or module in communication with the controller206. In this regard, the communications circuitry308may include, for example, a network interface for enabling communications with a wired or wireless communication network. For example, the communications circuitry308may include one or more network interface cards, antennae, buses, switches, routers, modems, and supporting hardware and/or software, or any other device suitable for enabling communications via a network. Additionally or alternatively, the communication interface may include the circuitry for interacting with the antenna(s) to cause transmission of signals via the antenna(s) or to handle receipt of signals received via the antenna(s). In addition, computer program instructions and/or other type of code may be loaded onto a computer, processor or other programmable circuitry to produce a machine, such that the computer, processor other programmable circuitry that execute the code on the machine create the means for implementing the various functions, including those described in connection with the components of controller206. As described above and as will be appreciated based on this disclosure, embodiments of the present invention may be configured as sensors, methods, and the like. Accordingly, embodiments may comprise various means including entirely of hardware or any combination of software with hardware. Furthermore, embodiments may take the form of a computer program product comprising instructions stored on at least one non-transitory computer-readable storage medium (e.g., computer software stored on a hardware device). Any suitable computer-readable storage medium may be utilized including non-transitory hard disks, CD-ROMs, flash memory, optical storage devices, or magnetic storage devices. FIGS.4A,4B and4Care graphical representations of a response of the force sensor204, in accordance with an example embodiment of the present disclosure. The graphical representations400and402ofFIGS.4A and4Bshow a force sensor output and time plotted on y-axis and x-axis respectively. The output signal wave has a Direct Current (DC) component, such as a base line component404and an Alternating Current (AC) component, such as amplitude406. The controller206is configured to enable simultaneous monitoring of both the AC and DC components of the output signal for bubble and occlusion detection. Such a configuration may effectively reduce the error rate of the force sensor204by compensating for unwarranted external forces that may affect the sensor's acoustic baseline and lead in inaccuracies. Such a shift of the sensor's acoustic baseline may be caused by factors such as, for example, tubing/plastic deformation, and temperature change. As shown inFIG.4A, in an initial condition, there is no liquid inside the flow tube106and the flow tube106is filled with air. The ultrasonic transducer202transmits ultrasonic signals, and the ultrasonic signals are received by the force sensor204and detected by the controller206. In an example, the ultrasonic transducer202transmits the ultrasonic signals at 80 Decibel (dB) at 10V drive at 290 KHz frequency. The base line component404and the amplitude406of the output signal detected by the controller206is as shown in the figure. The controller206computes an initial threshold for the initial condition. In an instance, when Intravenous (IV) administration is initiated, the flow tube106is filled with liquid and the output signal from the force sensor204changes from a first output signal to a second output signal. The transition408shows the change of the first output signal from the initial condition to the second output signal when the flow tube106has the liquid. In an example, the controller206determines the change in an amplitude of the AC component of the output signal based on comparing the amplitude of the AC component of the second output signal with the amplitude of the AC component of the first output signal, and computing a difference between the amplitudes of the two AC components. The controller206then compares the difference with a predefined value and determines the change when the difference exceeds the predefined value. In a similar manner, the controller206detects a change in amplitude of the signal as shown in transitions410and412. As shown in410, the amplitude of the AC component of the second output signal decreases to a lower amplitude of a third output signal and in transition412, the amplitude of the AC component of the third output signal increases to a higher amplitude of a fourth output signal. In transitions414and416, the controller206detects a change in the signal levels of the DC component of the output signal. For instance, the controller206detects the signal level of the fourth output signal increases to a higher level in the transition414to a fifth output signal. The controller206measures the signal level of the fourth output signal and compares with the signal level of the fifth output signal to determine the difference between the signal level of the fourth output signal and the fifth output signal. In an example, the controller206determines a number of transitions in consecutive signal levels from the signal level of the fourth output signal to the signal level of the fifth output signal. In an embodiment, the controller206determines the time of the fifth output signal from an instance when the fourth output signal changes to fifth output signal. The controller206detects this change for every such transition in the output signal and compares the change with a predefined time or a predefined number of transition in consecutive signal levels to determine if the threshold is to be determined for a changed signal. For example, in the initial condition, the output signal is at 7 millivolt (mV), and after the transition, the signal is at 10 mV. The controller206determines number of transitions of consecutive signal levels, for instance, from 7 mV to 8 mV, from 8 mV to 9 mV and from 9 mV to 10 mV. In another example, the controller206determines the total time duration for which the signal remains at a new level for instance at the second output signal when the first output signal changes to the second output signal. For example, the second output signal is present for about 1 second. Thereafter, the controller206compares the number of transitions, such as 3, with a predefined number of transitions, for instance, 2 or 3. The controller206compares the total time duration of 1 second with a predefined time, for instance, 0.5-1 second. When the number of transitions exceeds or equals the predefined number of transitions or the predefined time, such as in this example, the controller206recalculates the threshold based on the second output signal. In an example, the controller206calculates the threshold based on a predefined percentage, such as 65% of the output signal after the transition or the change, for instance, the second output signal. For example, if the second output signal is at 10 mV, the controller206calculates the threshold as 65% of 10 mV, i.e. 6.5 mV. The controller206utilizes the threshold for detecting the air bubbles and liquid during operation of the force sensor204. The threshold is calculated to accommodate prevailing tube conditions, such as changed sensor position, change in flow rate or pressure, or change in tube compression. The controller206reliably and accurately detects the state change and direction of state change (from high to low or low to high) of the output signal. In an example, when the flow tube106has a flow occlusion, the DC component of the signal changes and there is no change in the AC component. In such an instance, the controller206may not determine a new threshold. However, when there is a drop in the flow occlusion, the DC component decreases, and the AC component is maintained at a level for the liquid. In such a scenario, if AC component also decreases then such a change is detected as a state change for the signal for detecting presence of air bubbles. In another instance, when the AC component increases, the controller206determines the new threshold. In another example embodiment, in the initial condition, there is liquid inside the flow tube106. Upon powering the fluid flow system200, the initial threshold for bubble detection is calculated by the controller206based on the predefined percentage of the output signal in the initial condition. The flow tube106is continuously monitored by the controller206for possible signal level changes, as shown in transition418ofFIG.4B, for detecting presence of the air bubble based on the predefined percentage of 65% of the output signal. When the signal for bubble detection ends, the amplitude of AC component increases (state changes) and reaches a new level, shown in transition420. At this point, the controller206recalculates the threshold to accommodate prevailing tube conditions. In an example, when the flow tube106has flow occlusion with a low pressure in the flow tube106, the signal level of the DC component decreases from a high signal level to a low signal level (as shown in transition422) without any change in the AC component. In an example, if there is an increase in the AC component, the controller206recalculates the threshold to accommodate new tube conditions. In another example, if there is a decrease in the AC component (shown in transition424), a bubble event is detected by the controller206. If the flow pressure in the flow tube106decreases and air bubble is present, the air bubbles are detected based on the threshold calculated for the previous transition. As shown inFIG.4C, a region426of the output signal shows a condition, when there is no bubble or occlusion in the flow tube106. In an event of presence of air bubble and full occlusion, the DC component of the signal rises to a new level shown in a region428. In this region428, the AC component of the signal decreases. In another condition, when there are no air bubbles and partial occlusion, the signal changes from the region428to a region430. In the region430, the DC component of the signal changes and the amplitude of the signal also varies. In another condition, when there are air bubbles and partial occlusion present in the flow tube106(shown in region432), the DC component of the signal remains constant and there is a slight variation in the amplitude of the signal. Thereafter, in a condition, when there is no bubble and no occlusion, the DC component of the signal falls to a lower level, as shown in a region434. FIG.5illustrates a graphical representation500of a sensitivity of the force sensor204, in accordance with an example embodiment of the present disclosure. The graphical representation500show a force sensor output and frequency plotted on y-axis and x-axis respectively. The force sensor output has two signals, a signal502corresponding to presence of liquid within the flow tube106and a signal504corresponding to presence of air bubbles inside the flow tube106. As shown in the figure, the difference506between the signals502and504is visible on the graphical representation500for the frequency range of 20 Kilo Hertz (KHz) to 1 Mega Hertz (MHz). In an example, at 500 KHz of frequency, the difference506between the signals502and504is maximum. Thus, the frequency range 20 KHz to 1 MHz provides an optimum frequency for the fluid flow system200to operate and distinctively detect bubbles and liquid in the flow tube106. FIGS.6A and6Bare graphical representations of sensitivity of a force sensor, in accordance with an example embodiment of the present disclosure. TheFIGS.6A and6Billustrate force sensor sensitivity for air bubble to liquid in the flow tube106with increased contact area and force by compressing the flow tube106, and at different Acoustic Pressure Levels (APL) and working ultrasonic frequency.FIG.6Ahas the water to bubble difference plotted on the y-axis and a DC offset on the x-axis. The figure illustrates various signal outputs in response to different conditions of a driving voltage. For instance, a signal602is in response to signal parameters of 290 KHz frequency, 78 gain and 10V voltage, a signal604is in response to 290 KHz frequency, 78 gain and 5V voltage. A signal606is corresponding to 64K/32 KHz, 78 gain and 10V voltage and a signal608is corresponding to the signal parameters, 64K/32K, 78 gain and 5V voltage.FIG.6Billustrates a signal610for DC offset and AC peak at frequency of 290 KHz. In an example, the compression of the flow tube106is in a range of 10-40% of a diameter of the flow tube106. In an example, the diameter for the flow tube is in a range of 2.36 millimeters (mm) to 12.7 mm, and an outer diameter is 4.1 mm and inner diameter is 3 mm and with a tube compression of about 20%, the effective gap between the ultrasonic transducer202to the force sensor204is 3.3 mm. Such a compression provides optimum coupling efficiency and facilitates efficient signal propagation through the flow tube106. The operation of the controller206is described later in conjunction withFIGS.7and8. Referring toFIG.7, in conjunction withFIG.1,FIG.2andFIG.3, a flowchart700illustrating detecting air bubbles and liquid in a flow tube, such as the flow tube106is described.FIG.7shows the flowchart700illustrating operation of the controller, in accordance with the example embodiments described herein. Turning first to operation702, a threshold for detecting an air bubble or liquid is determined. In an example, the controller206determines the threshold for detecting air bubble and liquid in the flow tube106based on an initial condition. The initial condition is for instance, when the flow tube106has liquid or air present in the flow tube106and the controller206determines the threshold based on the predefined percentage of the output signal at the initial condition, referred to as the first output signal. At704, a change in an output signal is detected. The change in one example is in response to a change in position of the force sensor204, or change in rate and pressure of the liquid in the flow tube106and causes the output signal to change from the first output signal to the second output signal. The controller206detects the change based on the amplitude of the AC component when the amplitude of the AC component of the first output signal increases or decreases. In another example, the controller206detects the change based on change in the signal level of the DC component of the first output signal when the DC component shifts from the first signal level to the second signal level, also referred to as the new signal. For example, to detect the change in the signal level, the controller measures and records the signal levels of the DC component at multiple time instances and compares the signal level at a time instance ‘t’ with the signal level at an time instance ‘t−2’. For instance, the controller206measures and records the signal level of the first output signal at 30thsecond from the initial condition and compares with the signal level at 28thsecond from the initial condition to detect if the signal levels have changed. Thereafter, at706, the change in the output signal is determined to be present for more than a predefined time or a predefined number of transitions. The controller206determines a time duration of the second output signal from the instance the first output signal is changed to the second output signal, and a number of transitions in consecutive signal levels of the DC component from the first signal level to the second signal level. In an example, when the second output signal is present for more than the predefined time or the predefined number of transitions, then a new threshold is determined based on the output signal, at708. In an example, when the second output signal is present for less than the predefined time or the predefined number of transitions, the controller206monitors the flow tube106for detecting the change in the output signal, at704. At710, the liquid and air bubble are detected based on the new threshold. In an example embodiment, the controller206determines the new threshold and detects the air bubbles and liquid in the flow tube106based on the new threshold. FIG.8illustrates an example method800for detecting air bubble and liquid in a flow tube, such as the flow tube106, in accordance with an example embodiment of the present disclosure. At802, a change is detected in a baseline component of an output signal. For example, the controller206detects the change in the baseline component404or the DC component of the output signal of the force sensor204. At804, the change is determined to be one of a high to low or low to high for the baseline component. In the change of signal levels from low to high, the first signal level of the first output signal changes to the second signal level of the second output signal and the second signal level is higher than the first signal level. In the change of the signal level from high to low, the second signal level is at a lower level than the first signal level. In an example, the rise of the signal level, from low to high, indicates presence of air bubble and occlusion and a fall in the signal level, from high to low, indicates presence of air bubbles and no occlusion, as shown inFIG.4C. At806, a new threshold is determined for the change of the output signal from one of high to low or low to high of the signal level. In an example, the controller206determines the new threshold based on a shift of the base line component when the base line component rises to a higher signal level or falls to a lower signal level. Thereafter, at808, liquid or air bubble are detected based on the new threshold. In an example, the controller206determines the new threshold based on a predefined percentage of the output signal and then detects the liquid or air bubble based on the new threshold. FIG.7illustrates example flowchart andFIG.8illustrates example method describing operations performed in accordance with example embodiments of the present disclosure. It will be understood that each block of the flowcharts, and combinations of blocks in the flowcharts, may be implemented by various means, such as devices comprising hardware, firmware, one or more processors, and/or circuitry associated with execution of software comprising one or more computer program instructions. For example, one or more of the procedures described above may be embodied by computer program instructions residing on a non-transitory computer-readable storage memory. In this regard, the computer program instructions which embody the procedures described above may be stored by a memory of an apparatus employing an embodiment of the present disclosure and executed by a processor of the apparatus. As will be appreciated, any such computer program instructions may be loaded onto a computer or other programmable apparatus (e.g., hardware) to produce a machine, such that the resulting computer or other programmable apparatus provides for implementation of the functions specified in the flowchart blocks. When executed, the instructions stored in the computer-readable storage memory produce an article of manufacture configured to implement the various functions specified in flowchart blocks. Moreover, execution of a computer or other processing circuitry to perform various functions converts the computer or other processing circuitry into a machine configured to perform an example embodiment of the present disclosure. Accordingly, the operations set forth in the flowcharts define one or more algorithms for configuring a computer or processor, to perform an example embodiment. In some cases, a general-purpose computer may be provided with an instance of the processor which performs algorithms described in one or more flowcharts to transform the general-purpose computer into a machine configured to perform an example embodiment. Accordingly, the described flowchart blocks support combinations of means for performing the specified functions and combinations of operations for performing the specified functions. It will also be understood that one or more flowchart blocks, and combinations of flowchart blocks, can be implemented by special purpose hardware-based computer systems which perform the specified functions, or combinations of special purpose hardware that execute computer instructions. In some example embodiments, certain ones of the operations herein may be modified or further amplified as described below. Moreover, in some embodiments additional optional operations may also be included. It should be appreciated that each of the modifications, optional additions or amplifications described herein may be included with the operations herein either alone or in combination with any others among the features described herein. The foregoing method descriptions and the process flow diagrams are provided merely as illustrative examples and are not intended to require or imply that the steps of the various embodiments must be performed in the order presented. As will be appreciated by one of skill in the art the order of steps in the foregoing embodiments may be performed in any order. Words such as “thereafter,” “then,” “next,” and similar words are not intended to limit the order of the steps; these words are simply used to guide the reader through the description of the methods. Further, any reference to claim elements in the singular, for example, using the articles “a,” “an” or “the,” is not to be construed as limiting the element to the singular and may, in some instances, be construed in the plural. In one or more example embodiments, the functions described herein may be implemented by special-purpose hardware or a combination of hardware programmed by firmware or other software. In implementations relying on firmware or other software, the functions may be performed as a result of execution of one or more instructions stored on one or more non-transitory computer-readable media and/or one or more non-transitory processor readable media. These instructions may be embodied by one or more processor-executable software modules that reside on the one or more non-transitory computer-readable or processor-readable storage media. Non-transitory computer-readable or processor-readable storage media may in this regard comprise any storage media that may be accessed by a computer or a processor. By way of example but not limitation, such non-transitory computer readable or processor-readable media may comprise Random Access Memory (RAM), Read Only Memory (ROM), Electrically Erasable Programmable Read-Only Memory (EEPROM), FLASH memory, disk storage, magnetic storage devices, or the like. Disk storage, as used herein, comprises compact disc (CD), laser disc, optical disc, digital versatile disc (DVD), floppy disk, and Blu-ray Disc™, or other storage devices that store data magnetically or optically with lasers. Combinations of the above types of media are also included within the scope of the terms non-transitory computer-readable and processor-readable media. Additionally, any combination of instructions stored on the one or more non-transitory processor-readable or computer-readable media may be referred to herein as a computer program product. References within the specification to “one embodiment,” “an embodiment,” “embodiments”, or “one or more embodiments” are intended to indicate that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. The appearance of such phrases in various places within the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments. Further, various features are described which may be exhibited by some embodiments and not by others. Similarly, various requirements are described which may be requirements for some embodiments, but not other embodiments. It should be noted that, when employed in the present disclosure, the terms “comprises,” “comprising,” and other derivatives from the root term “comprise” are intended to be open-ended terms that specify the presence of any stated features, elements, integers, steps, or components, and are not intended to preclude the presence or addition of one or more other features, elements, integers, steps, components, or groups thereof. As required, detailed embodiments of the present disclosure are disclosed herein; however, it is to be understood that the disclosed embodiments are merely exemplary, which may be embodied in various forms. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure in virtually any appropriately detailed structure. While it is apparent that the illustrative embodiments herein disclosed fulfill the objectives stated above, it will be appreciated that numerous modifications and other embodiments may be devised by one of ordinary skill in the art. Accordingly, it will be understood that the appended claims are intended to cover all such modifications and embodiments, which come within the spirit and scope of the present disclosure. | 46,953 |
11857776 | DETAILED DESCRIPTION The Detailed Description describes exemplary embodiments of the invention and is not intended to limit the scope of the claims in any way. Indeed, the invention is broader than and unlimited by the exemplary embodiments, and the terms used in the claims have their full ordinary meaning, unless otherwise noted in the application. Features and components of one exemplary embodiment may be incorporated into the other exemplary embodiments. Inventions within the scope of this application may include additional features, or may have less features, than those shown in the exemplary embodiments. As described herein, when one or more components are described as being connected, joined, affixed, coupled, attached, or otherwise interconnected, such interconnection may be direct as between the components or may be indirect such as through the use of one or more intermediary components. Also as described herein, reference to a “member,” “component,” or “portion” shall not be limited to a single structural member, component, or element but can include an assembly of components, members, or elements. Also as described herein, the terms “substantially” and “about” are defined as at least close to (and includes) a given value or state (preferably within 10% of, more preferably within 1% of, and most preferably within 0.1% of). In endoscopic surgical procedures, steady distention and clear visibility are important to procedural efficacy and efficiency. Fluid management systems are used to provide fluid to a surgical site such that a surgeon has the desired distention and visualization while performing a surgical procedure. Fluid management systems can also be used to remove fluid from the surgical site. The various embodiments of fluid management systems described herein relate to modular systems that include software-controlled, electro-mechanical devices or modules that may be used in combination with single or multiuse tubing sets. The modular, surgical fluid management systems described herein are fully configurable to meet user needs based on, for example, the types of surgical procedures being performed and the surgical environment. Exemplary functions of the fluid management systems described herein include fluid pressurization, fluid warming, fluid deficit monitoring, suction, suction regulation, fluid collection, and/or fluid evacuation into a facility's waste disposal system. The fluid management systems can be configured based on surgical discipline (e.g., gynecological, urological, and/or orthopedic procedures) and environment (e.g., operating room or physician's office), as well as based on other needs and/or preferences of the user and/or facility. The fluid management systems may be capable of integrated suction and fluid collection and/or may be compatible with third-party suction and fluid collection devices, as well as central suction systems of facilities where the fluid management systems are used. Referring toFIG.1, an exemplary embodiment of a fluid management system100for an operating room environment where gynecological, urological, and orthopedic procedures are performed is shown. The system100includes an elevated structure101, a main unit102, a deficit module104, a fluid collection module106, and a fluid evacuation module108. The system100may also include an aspiration module5201(FIG.52), and/or a fluid flow and evacuation module5101(FIG.51). In some embodiments, the elevated structure101includes wheels103such that the system100can be moved to a desired location within the operating room or to a storage area. The system100may be modular, such that the system100described above can be configured as desired by the user. The main unit102may have a control system that includes one or more processors (not shown) for controlling and/or communicating with the various modules and components of the system100or other facility equipment. The various modules and components may also have one or more processors (not shown) for performing designated functions and/or communicating with the control system of main unit102or other facility equipment. The processor(s) may execute instructions (e.g., software code) stored in memory (not shown) of the system100and/or execute instructions inputted into the system by a user. In some embodiments, the control system may have “Bluetooth” capability for connecting to remotely located components or modules of the system100or other facility equipment and “Wi-Fi” capability for connecting to the internet. The control system may include a touch-screen graphical user interface110for receiving one or more inputs from a user and displaying information of the system100(e.g., information regarding fluid pressure, fluid volume, fluid temperature, fluid deficit, etc.). Referring toFIGS.1through3, the main unit102may also include a pump212(e.g., a peristaltic pump) for fluid pressurization, a heater assembly314for fluid warming, a fluid conditioning assembly315for sensing one or more fluid characteristics (e.g., fluid presence, temperature, etc.), hanging members116(e.g., hooks) for hanging fluid supply and/or return containers (e.g., bags, canisters, vessels, etc.), and a printer218for printing out pertinent procedure information (e.g., information regarding procedure type, procedure start time, procedure end time, total fluid volume, average fluid pressure, total fluid deficit, deficit by fluid type, average fluid temperature, etc.) during or after the surgical procedure. The processor of the control system can be in communication with the pump212, heater assembly314, fluid conditioning assembly315, pressure sensors949(FIG.9), solenoid valve951(FIG.9), hanging members116, printer218, deficit module104, fluid collection module106, fluid evacuation module108, aspiration module5201(FIG.52), fluid flow and evacuation module5101(FIG.51), and/or any other component of the system100. The pump212may be fluidly connected to the fluid container(s) that are hanging on the hanging members116such that the pump can pump fluid through a tubing set to a surgical scope or instrument (e.g., hysteroscope, cystoscope, ureteroscope, nephroscope, etc.) at a surgical site. The tubing set may include a fluid conditioner (e.g., fluid conditioner420shown inFIG.4and described in the present application) that works in combination with one or more non-contact sensors (e.g., non-contact sensors of the fluid conditioning assembly315or any other non-contact sensors in the system100) such that the system100can monitor one or more characteristics of the fluid that is moving to the surgical site. The tubing set may also include a fluid warming cartridge (e.g., fluid warming cartridge422shown inFIG.4and described in the present application) that works in combination with the heater assembly314such that the system100can warm fluid that is moving to the surgical site. A suction source pulls fluid from the surgical site, through a tubing set, and either into a collection container of the collection module106, into a third-party fluid collection system, or into the waste disposal system of the facility in which the system100is being used. In certain embodiments, the suction source is a vacuum pump that is integral to main unit102or the fluid collection module106. In some embodiments, fluid collection module also includes a pump and one or more filters such that the fluid collection module can evacuate and filter surgical smoke to eliminate potentially hazardous byproducts of electrosurgical procedures. Referring toFIG.1, the fluid collection module106may be independently mobile and removably coupled to the elevated structure101such that the module106can be removed from the elevated structure101and transported to a waste disposal area or room for disposal of the collected fluid. In some embodiments, the collection container of the collection module106may include disposable liners that can easily be replaced after the fluid has been evacuated from the suction and collection module106and into the facility's waste disposal system. In some embodiments, the suction source is external to the system100and pulls fluid to either the collection container of the collection module106, a third party-fluid collection system, or the waste disposal system of the facility. In embodiments in which the fluid is pulled directly into the waste disposal system of the facility, the collection module106may be bypassed or removed from the system100during use (e.g., as shown inFIG.50). The fluid collection module106may include a processor that communicates with the main unit102, the deficit module104, the aspiration module5201(FIG.52), other components of the system100, and/or other facility equipment. In some embodiments, the fluid collection module106may include a weight measuring mechanism (e.g., a scale) that allows the fluid management system100to determine a volume of fluid returning from the surgical site for fluid outflow and/or deficit monitoring purposes. Prior to the fluid moving into the collection module106, a third-party fluid collection system, or a waste disposal system of the facility, the fluid may move through a single or multiuse deficit cartridge (e.g., deficit cartridge2010shown inFIG.25and described in the present application) such that the system100can calculate and monitor a fluid deficit between fluid being provided to the surgical site and fluid being returned from the surgical site. The deficit cartridge may work in combination with the deficit module104(or the fluid flow and evacuation module5101shown inFIG.51and described in the present application) and the main unit102to allow the system100to calculate and monitor the fluid deficit. In certain embodiments, system100includes an aspiration module (e.g., aspiration module5201shown inFIG.52and described in the present application), and a single or multiuse pressure regulator (e.g., the pressure regulators5205shown inFIGS.52-73and described in the present application) that is fluidly connected to the tubing set and the suction source. The pressure regulator and aspiration module may work in combination with each other and the main unit102to regulate a vacuum pressure provided to the surgical site by the suction source to pull fluid from the surgical site. FIGS.4through6illustrate an exemplary embodiment of a cartridge assembly419for a single or multiuse disposable tubing set of the system100, where the cartridge assembly419includes a fluid conditioner420and a fluid warming cartridge422. The fluid conditioner420is configured to connect to the warming cartridge422to form the cartridge assembly419(as shown inFIG.4). For example, referring toFIG.5, the fluid conditioner420may have one or more connection members421that are configured to connect to one or more connection members423of the fluid warming cartridge422. The connection members421,423of the fluid conditioner420and the fluid warming cartridge422may be connected by, for example, a snap-fit connection, a friction fit connection, etc. In other embodiments, the fluid conditioner420and the fluid warming cartridge422may be connected by gluing, ultrasonically welding, or any other suitable means of joining the fluid conditioner and the fluid warming cartridge. In certain embodiments, the cartridge assembly419is a single, fully integrated component with combined fluid conditioning and fluid warming functions. In these embodiments, the single, fully integrated component of the cartridge assembly419can be, for example, a single injection molded component. In certain embodiments, the cartridge assembly419is provided as a fully assembled component of a single or multiuse tubing set. In some embodiments, the fluid conditioner420is provided as a fully assembled component of a single or multiuse tubing set (e.g., including the fluid conditioner420and tube841assembly shown inFIG.8), and the warming cartridge422is provided as an accessory component that can be attached to the fluid conditioner420if desired. In such embodiments, the user may configure the tubing set for fluid warming by removing tube841(FIG.8) from the fluid conditioner420and connecting the warming cartridge422to the fluid conditioner420. In certain embodiments, the main unit102can sense whether the fluid conditioner420has been inserted alone (e.g., without the warming cartridge422) into the system100or the cartridge assembly419(that includes the fluid conditioner420and warming cartridge422) has been inserted into the system. For example, the main unit102may include one or more sensors (e.g., proximity sensors, mechanical sensors, optical sensors, laser sensors, etc.) that can detect whether the fluid conditioner420alone or the cartridge assembly419was inserted into the system100. The control system of the system100can then enable the fluid warming function of the system100(e.g., the heater assembly314shown inFIG.3) when a warming cartridge422is inserted into the system100and disable the warming function when a warming cartridge422is not inserted into the system100. Referring toFIG.6, during use of the system100, fluid may be pumped through a first tube624of the tubing set and into an inlet port625of the fluid conditioner420. The fluid then flows along a first flow path626through an inlet chamber1053(FIG.10) of the fluid conditioner, moves through an outlet port527(FIG.5) of the fluid conditioner420, and through an inlet opening528(FIG.5) of the fluid warming cartridge422. The fluid then moves along a first side1671(FIGS.16-18) of the warming cartridge422along a fluid path629, moves through a connector or tube530, and into a second side1670(FIGS.16-18) of the fluid warming cartridge422along a path631. Subsequently, the fluid exits an outlet opening532(FIG.5) and moves through inlet port533(FIG.5) of an outlet chamber1054(FIG.10) of the fluid conditioner420, where the fluid moves along a path636such that the fluid exits outlet634of the fluid conditioner422and moves through a tube635of the disposable tubing set to a surgical instrument at a surgical site. The connector or tube530is shown as having a U-shape, but the connector or tube can take any suitable form that causes the first and second sides of the warming cartridge422to be fluidly connected. While the first and second sides of the fluid warming cartridge are shown being fluidly connected by the connector or tube530, it should be understood that the first and second sides can be fluidly connected without the need for the connector or tube530. For example, the warming cartridge422can have a channel that fluidly connects the first and second sides. In the illustrated embodiment. the fluid enters the fluid path629through the inlet opening528(FIG.5) of the warming cartridge422at a lower position relative to the exit of the fluid path629at the inlet of the connector or tube530, and the fluid enters the fluid path631at the exit of the connector or tube530at a lower position relative to the outlet opening532(FIG.5) of the warming cartridge422. The enter low, exit high configuration for each of the fluid paths629,631promotes a more uniform, controlled warming by reducing Eddy currents and areas of stagnant flow. While the fluid is shown taking the fluid paths629,631through the warming cartridge422, it should be understood that the fluid can take any suitable path through the warming cartridge422. Inserting the cartridge assembly419into the main unit102of the system100aligns the fluid conditioner420with the fluid conditioning assembly315(FIG.3) and the fluid warming cartridge422with the heater assembly314(FIG.3). The fluid conditioner420may have a handle442that allows a user to easily insert the cartridge assembly419into the main unit102. Referring toFIG.7, the heater assembly314(FIG.3) may include an IR lamp assembly737used to warm the fluid moving along the fluid paths629,631(FIG.6) of the warming cartridge422. The IR lamp assembly737may include a support structure738, one or more elongated IR lamps with IR reflective coatings739disposed on each side of the warming cartridge422, and a parabolic reflector740disposed on each side of the warming cartridge422such that the parabolic reflector740focuses the IR energy on the fluid paths. The heater assembly314may, however, utilize other types of IR lamps such as bulbs, rings, panels, circular modules, or any other suitable forms that are capable of warming fluid moving through the warming cartridge422or any other cartridge, tube, or vessel capable of exposing the fluid to IR lamps. Referring toFIG.8, in some embodiments, fluid warming may not be desired or necessary during a procedure. In these embodiments where fluid warming cartridge422is not necessary, a connector or tube841is used to connect the inlet chamber1053(FIG.10) and the outlet chamber1054(FIG.10) of the fluid conditioner420. While the inlet and outlet chambers are shown being fluidly connected by the connector or tube841, it should be understood that the inlet and outlet chambers can be fluidly connected without the need for the connector or tube841. For example, the fluid conditioner420can have a channel that fluidly connects the inlet and outlet chambers. In an alternative embodiment, rather than utilizing the connector or tube841, the fluid conditioner420may be included in a cartridge assembly that has a pulse damping component (not shown) that is similar in construction to the warming cartridge422described below with reference toFIGS.14-18, but the fluid damping component is not used for fluid warming. For example, the pulse damping component may include a rigid body (e.g., similar to rigid body1472shown inFIGS.14-18) and flexible side sheets (e.g., similar to flexible side sheets1473,1474shown inFIGS.14-18), where the rigid body and flexible side sheets at least partially define a fluid path that connects the inlet chamber1053(FIG.10) of the fluid conditioner420to the outlet chamber1054(FIG.10) of the fluid conditioner420. In alternative embodiments, the pulse damping component may comprise a flexible vessel or channel without a rigid body, in which the flexible vessel or channel defines a fluid path that fluidly connects to the inlet chamber1053(FIG.10) and the outlet chamber1054(FIG.10) of the fluid conditioner420. In any of the embodiments described above, the flexible vessel or channel is capable of expanding and contracting to dampen the fluid pulsations. That is, the flexible vessel or flexible side sheets can expand and contract to reduce pulsations of the fluid as pressure of the fluid moving through the conduit fluctuates. This damping of the fluid pulsations facilitates steady distention and good visualization during a surgical procedure. The fluid conditioner420and pulse damping component can be connected by any suitable means, such as, for example, any means discussed in the present application regarding the connection of the fluid conditioner420and the fluid warming cartridge422. In certain embodiments, the fluid conditioner and pulse damping component can be included in an integrated cartridge assembly where the fluid conditioner420and fluid damping component are included in a single cartridge. In certain embodiments, the pulse damping component with a rigid body and flexible side sheets or the flexible vessel or channel used for pulse damping may not be connected to fluid conditioner420, but instead be connected in the tubing set between the outlet port634(FIG.10) and the surgical site. Referring toFIG.9, the fluid conditioner420is configured to connect or align with one or more non-contact sensors (e.g., sensors943-950) of the fluid conditioning assembly315such that the sensors can sense one or more characteristics of the fluid without contacting the fluid. For example, the fluid conditioning assembly315may include one or more fluid presence sensors (943,947,948,950), one or more fluid temperature sensors (944,945,946), and a port1062(FIG.10) that connects to one or more pressure sensors949located in the main unit102. The port1062(FIG.10) that connects to one or more pressure sensors949may also connect to a solenoid valve951for expelling excess air that has accumulated in the fluid conditioner420. The pressure sensors949and the solenoid valve951may be connected to the port1062by one or more tubes or conduits and connection component952. The control system of the fluid management system100may be configured to at least partially control the pressurization of the fluid by pump212, the warming of fluid by the heater assembly314, and the expelling of air from the fluid conditioner420based on the interface between the fluid conditioning assembly315(FIG.3) and the fluid conditioner420. Referring toFIGS.10through13, an exemplary embodiment of the fluid conditioner420may include a rigid body1052that defines a first or inlet chamber1053and a second or outlet chamber1054. In some embodiments, fluid conditioner420may include a fully or partially enclosed middle chamber1075located between the inlet chamber1053and the outlet chamber1054to provide a separation gap between walls of the inlet and outlet chambers. This separation gap created by the middle chamber1075prevents heat transfer between incoming and outgoing fluid that would occur if the inlet chamber1053shared a common wall with the outlet chamber1054. The rigid body1052can be, for example, an injection molded body. Referring toFIGS.12and13, the fluid conditioner420may also include a film1255that is connected to the rigid body1052to further define and enclose the chambers1053,1054to create flow paths. The film1255can be connected to the rigid body1052by gluing, laser welding, ultrasonic welding, or any other suitable means. The film1255is configured to allow one or more sensors of the sensing assembly315(FIG.3) to sense one or more characteristics of the fluid moving through the inlet and outlet chambers1053,1054without contacting the fluid. The film1255can be, for example, a plastic film. In alternative embodiments, the fluid conditioner420does not include the film1255, but rather the fluid conditioner420is a rigid vessel that is configured to allow one or more sensors of the sensing assembly315(FIG.3) to sense one or more characteristics of the fluid without contacting the fluid. In some of these embodiments, a portion of the rigid vessel that aligns with the sensors of the sensing assembly can have a reduced thickness relative to the remainder of the fluid vessel that allows the sensors to sense characteristics of the fluid. In the embodiments mentioned above, the inlet chamber1053may have an inlet port625and an outlet port527, and the outlet chamber1054may have an inlet port533and an outlet port634. Outlet port527and inlet port533can have O-rings (e.g., O-rings1363shown inFIG.13) for making water-tight connections. In certain embodiments, the inlet port625and outlet port634can have barbed and/or glued portions for connecting to fluid tubing. Referring toFIGS.9through11, the fluid inlet chamber1053is aligned with a fluid presence sensor943that targets area1156and a fluid inlet temperature sensor944that targets area1157. Operation of the pump212(FIG.2) causes fluid to flow from a fluid supply bag or container through inlet port625into the inlet chamber1053. The inlet chamber1053may have a protruding wall1058that causes a section of the chamber to become thin or shallow, which mitigates air bubble stagnation by causing laminar flow through this section. The fluid presence sensor943verifies that fluid is present in the inlet chamber1053and, therefore, can be used by the system100to monitor performance and identify any problems. For example, if the pump is operating, but fluid presence sensor943is not detecting fluid, the control system may notify the user to check for a disconnected tubing line or possible occlusions of the fluid path between the fluid containers and the fluid conditioner420, such as, for example, kinked tubing or closed clamps. The fluid temperature sensor944may have several functions. For example, in embodiments in which the heater assembly314is used to warm the fluid to a desired temperature (e.g., a temperature inputted by the user or a default system temperature), fluid temperature sensor944allows the control system to monitor the temperature of the fluid entering the warming cartridge422such that the control system can adjust the amount of IR energy provided by the heater assembly314to cause the fluid entering the outlet chamber1054of the fluid conditioner420to be at the desired temperature. In addition, if the user has hung pre-warmed fluid bags with fluid temperatures at high, potentially unsafe levels, the control system may disable the pump212and/or the heater assembly314, and then notify the user that such operations will remain disabled until the fluid temperature has sufficiently cooled or the fluid supply bags or containers have been changed. Alternatively, the control system may continue operation while increasing air flow through the heater assembly314to sufficiently cool the fluid before it reaches the outlet chamber1054of the fluid conditioner420. If such attempt fails, the fluid outlet temperature sensor945that targets area1159and/or fluid high-limit or thermal cut-off temperature sensor (“TCO Sensor”)946that targets area1160will cause the control system to disable the fluid pumping and warming operations until the temperature of the fluid has sufficiently cooled. Additionally, assuming an operating room environment where the user has enabled the fluid warming function, the temperature sensor944can be used to notify the user if the temperature of the fluid entering the fluid conditioner420may be too cool to achieve the desired fluid temperature. Finally, the control system can also determine if there is a problem with heater assembly314. For example, if the temperature sensor944detects that the temperature entering inlet chamber1053is acceptable, but sensor945detects that the temperature of the fluid did not achieve the desired fluid temperature, the control system will notify the user that there may be a problem with the heater assembly314. Still referring toFIGS.9through11, the outlet chamber1054of the fluid conditioner420may be designed to separate air bubbles from the fluid being delivered to the surgical site that may have been caused by fluid bag changes or the fluid warming process. For example, the fluid outlet chamber1054may have a substantially vertical wall or baffle1061(FIGS.10-11) that causes air bubbles to separate from the fluid when the fluid engages the wall. As shown in the illustrated embodiment, the baffle1061may not be connected to a perimeter of the outlet chamber1054. In certain embodiments, the outlet chamber1054is designed to facilitate fluid pressure monitoring and control via pressure sensors949located in the main unit102. For example, insertion of the fluid conditioner420may cause a connection between the outlet chamber1054of the fluid conditioner420with pressure sensors949located in main unit102via pressure port1062and one or more tubes or conduits (not shown). As the pressure of the pocket of air trapped between the fluid in outlet chamber1054and the pressure sensors949is indicative of the fluid pressure, the control system monitors the fluid pressure being read by the pressure sensors949in relation to the setpoint fluid pressure, and the control system adjusts the speed of the pump212to achieve and maintain the setpoint fluid pressure. To ensure pressure monitoring accuracy and guard against over pressure conditions, the control system constantly compares the readings of the pressure sensors949to ensure they are the same excepting normal tolerances for such sensors. Independent of software, the control system may employ redundant hardware circuits that disable or reverse the pump212if the fluid pressure exceeds the maximum allowable pressure for the procedure. To ensure that the pressure sensors949remain isolated from the fluid, the outlet chamber1054is designed not only to maintain a pocket of air between the pressure sensors949and the fluid, but also to include a hydrophobic filter1065that acts as a fluid barrier. Such hydrophobic filter1065may also act as a bacterial barrier to preserve the sterility of the fluid. To protect the hydrophobic filter1065from coming into contact with fluid entering the outlet chamber1054under turbulent or high flow conditions, outlet chamber1054may include an arcing wall or barrier1066that, in combination with the baffle1061, ensures that any fluid going over the top of the baffle1061is directed away from the hydrophobic filter. The pressure port1062may also include an O-ring1364(FIG.13) for making a fluid tight connection. In addition to the presence sensor943for the inlet chamber1053, there may be at least three additional fluid presence sensors (947,948,950) that are aligned with the outlet chamber1054. The fluid presence sensor947(“fluid outlet sensor”) located at the outlet port634of the outlet chamber1054targets area1167and is used to ensure proper flow of fluid through the fluid conditioner420. For example, if the control system detects that the pump212is pumping fluid, but the fluid outlet sensor947is not detecting fluid, the control system may disable the pump212and/or notify the user of a problem with the system100. In addition, if the fluid warming function is present and enabled, the fluid outlet sensor947ensures that the fluid warming cartridge422is full of fluid before the fluid warming function is commenced or continued. The fluid presence sensor948located at the midpoint of the outlet chamber1054targets area1168and is used to control the amount of air that has accumulated in the outlet chamber1054. During normal operation, the fluid level in the outlet chamber1054should be maintained proximate the midpoint of the outlet chamber. If fluid is not detected by the fluid midpoint sensor948, and the pressure sensors949are reading a positive pressure, the control system opens the solenoid valve951to expel excess air that has accumulated in the outlet chamber1054until the fluid midpoint sensor948detects fluid (i.e., until the fluid level has increased to the midpoint of the outlet chamber1054). To avoid materially impacting the pressure monitoring and control function of the system100, the solenoid valve951may have a small orifice or restriction so that the excess air in the outlet chamber1054bleeds off at a low, controlled rate. Alternatively, the system100can average the fluid pressure readings so that the effects of any minor pressure decreases associated with the air expelling function are mitigated, or the system100can ignore the fluid pressure readings while the solenoid valve951remains open. The fluid presence sensor950located proximate the pressure port1062of the outlet chamber1054targets area1169to ensure proper operation of the pressure sensing function of the system100, which requires that a pocket of air be maintained between the fluid in the outlet chamber1054and the pressure sensors949of the sensing assembly315. The pressure of this pocket of air, which is monitored by the pressure sensors949, increases and decreases as a result of increases and decreases in the fluid pressure. If the fluid level reaches the hydrophobic filter1065that protects the pressure port1062, the control system may lose the ability to accurately monitor the fluid pressure. Accordingly, if the fluid pressure port sensor950senses fluid, the control system may disable pump212. Referring toFIGS.6and14through18, if the system100includes a main unit102with fluid warming capability, for example when configured for an operating room environment, the fluid conditioner420will generally be connected to the fluid warming cartridge component422. Joining the fluid conditioner420and fluid warming cartridge422together form cartridge assembly419and causes fluid connections to be made between the inlet chamber1053(FIG.10) of the fluid conditioner420and the first fluid path629(FIG.6) on a first side1671(FIGS.16-18) of the warming cartridge422. This connection also causes fluid connections between the second fluid path631(FIG.6) on the second side1670(FIGS.16-18) of the warming cartridge422and the outlet chamber1054(FIG.10) of the fluid conditioner420. The fluid warming cartridge422may include a rigid body1472(FIGS.14-18), a first thin flexible sheet1473(FIGS.15-18), and a second thin flexible sheet1474(FIGS.15-18). Referring toFIGS.16-18, the first flexible sheet1474is connected to a first side1671of the rigid body1472to define the first fluid flow path629, and the second flexible sheet1473is connected to a second side1670of the rigid body1472to define the second fluid flow path631. In the illustrated embodiment, the first and second fluid flow paths629,631are connected by a connector or tube530(FIGS.14-15). In other embodiments, the first and second flow paths may be connected by a channel that is integral to the warming cartridge422. The rigid body1472can be, for example, an injection molded body. The flexible side sheets1473,1474can be made of, for example, plastic which is highly transmissive to IR to facilitate the fluid warming function. The rigid body1472and the flexible side sheets may be connected by gluing, laser welding, ultrasonic welding, or any other suitable means. The flexible side sheets1473,1474may be configured to expand and contract to effectively dampen fluid pulsations generated by the pump212, which allows the fluid delivered to the surgical site to be non-pulsatile. That is, although the system100may utilize a peristaltic pump which generates a pulsatile fluid flow, the fluid warming cartridge422, which is downstream of the peristaltic pump, may include thin, flexible side sheets1473,1474to at least partially define the fluid paths and expand and contract as the pressure of the fluid moving through the warming cartridge fluctuates to dampen the fluid pulsations. This damping of the fluid pulsations facilitates steady distention and good visualization during a surgical procedure. Referring toFIG.6, in operation, fluid from the fluid supply bags or containers enters the fluid inlet chamber1053(FIG.10) of the fluid conditioner420via port625, enters the fluid warming cartridge422, flows through the first elongated section of the fluid path629on a first side1671(FIGS.16-18) of fluid warming cartridge422, exits the first elongated section of the fluid path and enters the second elongated section of the fluid path631on a second side1670of the fluid warming cartridge via connector530, exits the fluid warming cartridge422and enters fluid outlet chamber1054of the fluid conditioner420, and then exits the fluid outlet chamber1054for delivery to the surgical site via port634. The system100can control fluid temperature by monitoring the difference between the setpoint fluid temperature and the actual outlet fluid temperature sensed by temperature sensor945(FIG.9) to adjust power to the IR lamp assemblies737(FIG.7) in accordance with proportional integral control and scaling, which is based on the actual fluid flow rate and/or the difference between the actual fluid temperature sensed by the temperature sensor944aligned with the inlet chamber1053of the fluid conditioner420and the actual fluid temperature sensed by the temperature sensor945aligned with the outlet chamber1054of the fluid conditioner420. Alternatively, other suitable open-loop and closed-loop control systems can be employed, such as, for example, proportional control, integral control, proportion-integral-derivative control, mathematical modelling, predictive function control, error squared control, and bang-bang control. In addition to the control scheme, the fluid warming efficiency can be enhanced by utilization of thin, flexible side sheets1473,1474(FIG.15) of the fluid warming cartridge422, which may be highly transmissive to IR energy and an injection molded rigid body1472(e.g., a black injection molded body) that absorbs IR energy from the IR lamp assemblies737(FIG.7) and radiates the IR energy back to the fluid. Additionally, the fluid warming efficiency can be enhanced by the elongated sections of the fluid warming cartridge422that define fluid paths629,631. The elongated sections of the fluid warming cartridge422can facilitate uniform heat distribution by introducing fluid into each section at or below the centerline and exiting fluid from each section at the top of the opposite end such that the fluid moves from a lower position to a higher position as it moves along each of the fluid paths629,631. Referring toFIG.19, in certain embodiments, the fluid warming efficiency of system100can also be enhanced by pre-warming of the fluid containers1901. That is, air intake1903allows air to be drawn by fans316(FIG.3) of heater assembly314(FIG.3) into the main unit102to cool the heater assembly314and the main unit102during the fluid warming process, and this air becomes heated as a result of interacting with the heater assembly314. The heated air is then exhausted by the main unit102through exhaust openings1905and directed towards the fluid containers1901on each side of main unit102such that the fluid within the fluid containers is pre-warmed prior to being pumped through the fluid conditioner420(FIG.6) and fluid warming cartridge422(FIG.6). To guard against overtemperature conditions, the system100has low and high limits that disable the IR lamps739(FIG.7) if the fluid temperature exceeds a low safety limit, and disables the IR lamps739and the pump212if the fluid temperature exceeds a high safety limit. In some embodiments, independent of software, the system100employs a hardware circuit that includes the thermal cutoff sensor (“TCO”)946(FIG.9) to disable the IR lamps and the pump in an overtemperature condition exceeding the high limit. In some embodiments, the system100employs a cooling fan to remove heat to help prevent and/or mitigate overtemperature conditions. The cooling fan may be electronically controlled based on thermistor or other temperature sensor inputs and/or heating algorithm conditions that could lead to overtemperature (e.g. a rapid decrease in flow rate where full heating was required at maximum flow rates). Due in large part to the fluid warming function of the system100, which is intended to rapidly warm fluid up to the setpoint fluid temperature and to maintain the setpoint fluid temperature at high flow rates, the system100, for markets where the nominal supply voltage is 120V, must be connected to a dedicated 20-amp circuit. However, the system100can be configured for connection to a standard 15-amp circuit by utilizing lower wattage lamps and/or current limiting power to the lamps. In certain embodiments, fluid management system100is configured to operate on nominal supply voltage of 120 v or 240 v without requiring a change in lamps. For example, the system100can include a crossover circuit that includes a threshold detector770(FIG.7A) and a relay bank771(FIGS.7B-7C). Referring toFIG.7, in certain embodiments, the lamp assembly737includes four lamps739(e.g., two lamps on each side of the cartridge419).FIG.7Bshows a circuit of a relay bank771for two lamps739of the lamp assembly737(e.g., two lamps739positioned on the same side of the cartridge419) with relay contacts775,777in a first position in which the lamps739are placed into a parallel configuration.FIG.7Ashows a circuit for a threshold detector770that can cause the relay contacts775,777(FIGS.7B-7C) to move to a second position (as shown inFIG.7C) in which the lamps739are placed into a series configuration. WhileFIGS.7B and7Cshow a circuit for a relay bank771of two lamps739that are disposed on one side of the cartridge719shown inFIG.7, it should be understood that the circuit for the other two lamps739on the other side of the cartridge may be identical to the circuit shown inFIGS.7B and7C. Referring toFIG.7A, the threshold detector770has an AC line input772and an AC line input774that each connect to the input side of bi-directional photocoupler776, where the voltage being supplied to the heating assembly314is also applied to the inputs772,774. A first Zener diode778is positioned between the line input772and an input of the photocoupler776, and a second Zener diode780is positioned between the line input774and the input of the photocoupler776. The Zener diodes778,780prevent current flow from the inputs772,774through the photocoupler776until the peak voltage applied to the inputs772,774is greater than or equal to a predetermined amount. The photocoupler776includes a transistor output element782connected to voltage source784, where the transistor output element782is configured to operate between an “On” position and “Off” position with a line786that generates a control signal used to energize relay coils788that operate the relay bank771. The transistor output element782remains off when current is not moving through the input of the photocoupler776, and the transistor output element782turns on when the current flows through Zener diodes778,780and enters the input of the photocoupler776. When the transistor output element782turns on, current from the voltage source784energizes line786to generate the control signal to activate the coils788a-dand move corresponding contacts (e.g., contacts775,777) of the relay bank771from the first position (as shown inFIG.7B) to the second position (as shown inFIG.7C). In some embodiments, the control signal is applied to a Schmitt trigger790and transistor array792prior to energizing the coils788a-d. The Schmitt trigger790ensures that the voltage on line786is stable and exceeds a predetermined limit prior to being connected to the transistor array. The transistor array792energizes coils788a-dand moves the relay contacts775,777from the first position to the second position. Referring toFIG.7B, in the illustrated embodiment, the contacts775,777are in the first position when the lamps739are in a parallel configuration. When in the first position, the contacts775,777are connected at points4and5such that both lamps739are in communication with the inlet773of the circuit. This allows half the current moving through inlet773to move along a first path779into one lamp739and half the current to move through the second path781(through the contact775) and into the second lamp739. In this configuration, the same voltage applied to the inlet773is individually applied across both of the lamps739such that each lamp739receives the voltage entering the circuit. For example, if 120 v is applied to inlet773, the 120 v is connected to both the first path779and the second path781such that each lamp receives 120 v. Referring toFIG.7C, when the threshold detector770(FIG.7A) causes the contacts775,777to move to the second position, an electrical connection is made between points3and5such that the lamps739are connected in a series configuration. In this configuration, all the current applied to the inlet773moves along a single path783(because the disconnection between points4and5prevents the current from moving directly through the contact775after entering the inlet773) such that the current moves through one lamp739, continues to move along the path783such that the current moves through the contact775at points3and5, and the current then moves into the second lamp739. Because both lamps739are disposed along a single path783, the voltage applied to the lamps739is split between the number of lamps disposed on the path783. As the illustrated embodiment includes two lamps739, each lamp739receives half of the voltage entering the inlet773. For example, if 240 v is applied to inlet773, all the current flows along the single path783such that the voltage drop across one lamp739is 120 v and this dropped voltage is applied along the single path783such that the other lamp receives 120 v. The fluid management system100may be configured to provide accurate and reliable flow-based deficit monitoring for surgical procedures performed in an operating room environment. For example,FIGS.20through49illustrate an exemplary embodiment of a deficit module104and a single or multiuse deficit cartridge2010for the fluid management system shown inFIG.1. The use of the deficit cartridge2010negates the need for canisters and avoids exposing the sensors and other durable components of fluid management system100to the fluid returning from the surgical site. The deficit module104works in combination with the control system of the main unit102and a single or multiuse tubing set that includes the deficit cartridge2010to measure and record the fluid volume being returned from the surgical site as it moves through deficit cartridge2010. The fluid is pulled from the surgical site and both into and out of the deficit cartridge2010by a suction source (e.g., a vacuum pump integral or external to the system100). In an alternative embodiment, fluid may be pulled from the surgical site and pushed into the deficit cartridge2010by a more positive pressure than present inside deficit cartridge2010(e.g., a peristaltic pump integral or external to the system100inserted in-line between the surgical site and the deficit cartridge2010and configured to create suction at the surgical site and positive pressure at the inlet to the deficit cartridge2010) and pulled from the deficit cartridge2010by a more negative pressure than present inside deficit cartridge2010(e.g., a vacuum pump integral to or external to the system100or a sufficiently positive pressure inside the deficit cartridge2010due to the positive pressure created by the peristaltic pump to push the fluid out of the deficit cartridge2010to ambient pressure). Referring toFIGS.20through23, the deficit cartridge2010is inserted into the deficit module104. The deficit cartridge2010may include a front section2218that aligns with an opening2220(FIGS.22-23) of the deficit module104and a raised portion2222(FIGS.22-23) that allows for a user to easily grasp the deficit cartridge2010to remove the cartridge from the deficit module104. The deficit cartridge2010includes one or more inlet openings2012,2014that are configured to connect to one or more fluid return tubes of the tubing set such that fluid can move from the surgical site and into the deficit cartridge2010. The deficit cartridge also includes at least one vacuum opening2016that is configured to connect to an evacuation tube such that fluid moves through the evacuation tube after moving through the deficit cartridge2010. The evacuation tube is connected to the suction source such that a vacuum pressure is supplied to the deficit cartridge to pull fluid from the surgical site into and out of the deficit cartridge2010. The fluid return and evacuation tubes may be manually connected to the deficit cartridge2010after insertion of the deficit cartridge into the deficit module104. The control system of the main unit102is configured to determine a deficit of fluid provided to the surgical site and returned from the surgical site by comparing the volume of fluid moving through the deficit cartridge2010to the volume of fluid being supplied to the surgical site. The control system may calculate the volume of fluid being supplied to the surgical site by, for example, monitoring the weight of the fluid supply bags or containers (e.g., by using the hanging members116that are operatively connected to load cells), and/or counting the rotations of a peristaltic pump. Referring toFIGS.24through28, insertion of the deficit cartridge2010into the deficit module104causes a manifold connection assembly2424(FIGS.27-28) to engage the deficit cartridge2010and connect, via a pump manifold assembly (e.g., pump manifold assembly3513shown inFIG.37), positive and negative pressure pumps (3515and3517, respectively, ofFIGS.35-36) and a pressure sensor (not shown) of the deficit module104to pneumatically operated diaphragm regulators/valves (e.g., regulators/valves2628,2630,2632,2634shown inFIG.26) and a pressure sensing area2636(FIG.26) of the deficit cartridge2010. The manifold connection assembly2424has a plurality of connectors (e.g., connectors4510,4511,4512,4513shown inFIGS.45and49) for receiving corresponding ports2540for each of the regulators/valves and the pressure sensing area of the deficit cartridge2010. Referring toFIGS.27-28(andFIGS.42-49), the connectors of the manifold connection assembly2424can be configured to be moved between an engaged or connected state and a disengaged or disconnected state relative to the ports2540by a mechanical or electromechanical mechanism2726(e.g., a manual lever, a Pancake cylinder, or other type of pneumatic, mechanical, or electromechanical actuator). The ports2540of the deficit cartridge2010may include an O-ring that allows for a hermetically sealed connection between the manifold connection assembly2424and the deficit cartridge2010. Insertion of the deficit cartridge2010into the deficit module104also causes one or more non-contact fluid sensors2742(FIGS.30-31) of the deficit module104to align with desired locations of the deficit cartridge2010. The connectors (e.g., connectors4510,4511,4512,4513shown inFIGS.45and49) of the manifold connection assembly2424may be configured to account for any manufacturing or assembly tolerances in the ports2540of the deficit cartridge2010. That is, the connectors may be configured to move to ensure alignment with the corresponding ports2540of the deficit cartridge2010to account for minor differences in the location of the ports2540resulting from manufacturing and assembly of the deficit cartridge2010. For example, referring toFIGS.28A-28C, in certain embodiments, a connector4512(also shown inFIGS.45and49) of the manifold assembly2424may be a separate component that is connected to the manifold assembly2424by an attachment element2815(e.g., an E-clip), and a receiving assembly3511(also shown inFIGS.38-39) of the system100may include an opening3828(also shown inFIGS.38-39) that is larger than the diameter of the connector4512for receiving the connector4512such that the connector4512can move within the opening3828. Referring toFIG.28A, the manifold connection assembly2424is shown in a disengaged position with the port2540of the deficit cartridge2010. Activation of the mechanism2726(FIG.28) causes the manifold connection assembly2424to move in the direction M such that the connector4512engages the port2540of the deficit cartridge2010.FIG.28Bshows the initial engagement between the connector4512and the port2540, andFIG.28Cshows the completed engagement between the connector4512and the port2540. Referring toFIG.28B, the port2540of the deficit cartridge2010is not centered with the connector4512, which causes the port2540to engage an edge of an inlet2813of the connector4512. The large opening3828of the receiving assembly3511allows for the connector4512to move within the opening3828and align with the port2540. That is, referring toFIG.28C, continued movement of the manifold connection assembly2424in the direction M causes the port2540to align with and move into the connector4512. In certain embodiments, the inlet2813of the connector4512is tapered to facilitate movement of the port2540into the connector4512. The connection described above between the connector4512and the port2540allows for an easy and automatic connection between the deficit cartridge2010and the system100(e.g., via the deficit module104). WhileFIGS.28A-28Conly show the connection between connector4512and a port2540of the deficit cartridge2010, it should be understood that the other connectors (e.g., connectors4510,4511,4512,4513shown inFIGS.45and49) may be configured to connect to the ports2540of the deficit cartridge2010in the same manner described inFIGS.28A-28C. Referring toFIGS.29-34, the deficit cartridge2010may include a single chamber2944with three sections2946,2948,2950that are fluidically connected. The three sections include a fill section2946, a measure section2948, and an evacuation section2950that are fluidly connected at all times as the system100alternates between “Fill/Measure” and “Fill/Evacuation” Cycles, which allows the pressure gradient across the three sections to be minimized or substantially equal. The fill section2946is fluidly connected to the inlet openings2012,2014such that fluid returning from a surgical site can move into the fill section2946through the inlet openings2012,2014. The evacuation section2950is fluidly connected to the vacuum port2016such that a suction source can supply a vacuum pressure to the deficit cartridge2010that causes fluid to move from the surgical site, into the deficit cartridge2010through the inlet openings2012,2014, and exit the deficit cartridge2010through the vacuum port2016. In other embodiments, a pump in-line between the surgical site and port2012and/or port2014(e.g., a peristaltic pump) may pull fluid from the surgical site and push the fluid through the inlet openings2012and/or2014and out of the deficit cartridge2010through the vacuum port2016. Alternatively, a pump in-line between the surgical site and port2012and/or port2014(e.g., a peristaltic pump) may pull fluid from the surgical site and push the fluid through the inlet openings2012and/or2014while a separate suction source supplies vacuum pressure to pull fluid out of the deficit cartridge2010through the vacuum port2016. One or more inlet valves2628,2630may be positioned at the inlet openings2012,2014and configured to close to prevent fluid from entering chamber2944to avoid overfill conditions. In certain embodiments, the valves2628,2630are pneumatically-operated diaphragm valves that are connected to a pump assembly (e.g., an assembly including positive pressure pump3515and negative pressure pump3517shown inFIGS.35-36) of the deficit module104such that the pump assembly can move the valves2628,2630between the open and closed positions. In certain embodiments, a negative pressure pump of the pump assembly opens the diaphragm valves and a positive pressure pump of the pump assembly assists closing of the diaphragm valves with positive back pressure. The pneumatically-operated diaphragm valves2628,2630may also work in combination with the pump assembly (e.g., an assembly including positive pressure pump3515and negative pressure pump3517shown inFIGS.35-36) to act as a pressure regulator that regulates the vacuum pressure being supplied to the surgical site. That is, the control system of the fluid management system100may be configured to adjust the amount of pressure applied to the valves2628,2630by the pump assembly, which adjusts the threshold pressure required to displace flexible membrane2956and allow fluid to flow through2628,2630, and thereby allows the control system to control the amount of vacuum pressure supplied to the surgical site via the suction source that is connected to the vacuum port2016. For example, referring toFIG.29, the valves2628,2630may each include a housing component2958that defines a chamber2959, where the chamber2959is connected to the pump assembly of the deficit cartridge. A flexible membrane2956is disposed in the chamber2959and movable within the chamber2959by the pressure pumps. When the valves2628,2630are in the closed position, the membrane2956engages the chamber2944of the deficit cartridge2010to fluidly isolate the fill section2946from the inlet openings2012,2014. The pressure pumps are configured to move the flexible membrane2956within the chamber to open the valves2628,2630, and the pump assembly can adjust the size of the opening by creating a desired pressure differential between the pressure supplied by the pump assembly and the vacuum level within the chamber2944of the deficit cartridge2010. The membrane2956can be made of, for example, neoprene, silicone, natural rubber, nitrile, EPDM, or any other suitable material. The valves2628,2630may also have a hydrophobic filter2960to prevent fluid from traveling to the pump assembly in case of a tear or other failure of the flexible membrane. In other words, the valves2628,2630work similar to the pressure regulator described with respect toFIGS.52-73of the present application to regulate the vacuum pressure supplied to the surgical site. In the illustrated embodiment, the fill section2946is positioned at a top portion of the chamber2944, and the measure section2948is positioned below the fill section2946. A valve2632is positioned in an opening between the fill and measure sections2946,2948and is movable between an open position and a closed position. When the valve2632is in the open position, the fill section2946and the measure section2948are fluidly connected such that fluid in the fill section2946can move into the measure section2948via gravity. One or more sensors of the deficit module104are used to measure the fluid within the measure section2948. In certain embodiments, the measure section includes a main area3276(FIG.32) and a narrow area3277(FIG.32) positioned above the main area3276, where the volume of fluid capable of being disposed in these areas3276,3777are known by the system100such that the system can determine the volume of fluid moving through the measure section2948. The measuring of fluid within the measure section2946will be described in more detail below. The evacuation section2950is positioned below the measure section2948, and a valve2634is positioned in an opening between the measure and evacuation sections and is movable between an open position and a closed position. When the valve2634is in the open position, the measure section2948and the evacuation section2950are fluidly connected such that fluid in the measure section2948can move into the evacuation section2950via gravity. In the illustrated embodiment, the valves2632,2634are pneumatically-operated diaphragm valves that are connected to a pump assembly (e.g., an assembly including pumps3515,3517shown inFIGS.35-36) of the deficit module104such that the pump assembly moves the valves2632,2634between the open and closed positions. Referring toFIG.32, the valves2628,2630,2632,2634may include a flexible membrane (e.g., flexible membrane2956shown inFIG.29) that is movable between an engaged position and a disengaged position with openings3290of the deficit cartridge2010. That is, a portion of the openings3290fluidly connect the inlets2012,2014to the fill section2946, another portion of the openings3290fluidly connect the fill section2946to the measure section2948, and another portion of the openings3290fluidly connect the measure section2948to the evacuation section2950. The flexible membranes of the valves2628,2630,2632,2634engage the openings3290to prevent movement of fluid between the inlets/sections, and disengage at least a portion of the openings3290to allow movement of flow between the inlets/sections. The size and spacing of the openings3290may be configured to prevent extrusion of the flexible membranes through the openings3290when positive pressure is applied to the valves2628,2630,2632,2634. The size and spacing of the openings3290may vary based on the elasticity and/or thickness of the material of the flexible membrane. The number of openings3290associated with each valve2628,2630,2632,2634are configured to ensure adequate flow of fluid through the deficit cartridge2010. In certain embodiments, the combined surface area of the openings on each side of the valves2628,2630,2632,2634is substantially equal to an inner cross-sectional area of tubing that is attached to the inlet ports2012,2014of the deficit cartridge2010. Because gravity is the dominant force acting on the fluid to cause the fluid to move between the sections2946,2948,2950of the chamber2944, in some embodiments, the number of openings3290corresponding to the valves2632,2634is configured to be large enough to allow sufficient flow through the valves2632,2634to achieve high flow rates. For example, the number of openings3290corresponding to each valve2632,2634may be configured to achieve a target flow rate of greater than or equal to 1200 ml/min through the chamber2944without stopping flow from the surgical site. In certain embodiments, because the measure section2948of the chamber2944may be both filled and emptied while fluid continuously flows from the surgical site, the fluid flow rate through the valves2632,2634may be at least twice the target flow rate through the chamber2944. In the illustrated embodiment, the chamber2944includes a channel2952that fluidly connects the fill section2946to the evacuation section2950and a narrow portion3277that fluidly connects the fill section2946to the measure section2948. The channel2952and narrow portion3277allow the fill, measure, and evacuation sections2946,2948, and2950to be fluidly connected at all times, including when one or both of the valves2632,2634are in the closed position. This fluid connection between the fill, measure, and evacuation sections2946,2948, and2950via the channel2952and narrow portion3277allows the pressure gradient across the three sections of the chamber2944to be minimized or substantially equal such that the fluid is not caused to move within the chamber2944by a pressure source, but rather the fluid can move within the chamber2944due to gravity. In certain embodiments, the deficit cartridge includes a wall3252that is positioned to prevent fluid from entering the channel2952and bypassing the measure section2948. In an alternative embodiment, rather than the chamber2944including the channel2952, the deficit cartridge2010can include a connector or tube (e.g., similar to tube841shown inFIG.8for the fluid conditioner420) that fluidly connects the fill section2946to the evacuation section2950such that the fill, measure, and evacuation sections2946,2948, and2950are fluidly connected at all times. While the illustrated embodiment shows the three sections2946,2948,2950being in a stacked configuration, in an alternative embodiment, these three sections can be in a side-by-side configuration, as long as the fluid can travel from the fill section2946to the measure section2948to the evacuation section2950via gravity. In various embodiments, the deficit cartridge2010includes a waste vacuum level sensing and regulation port2636for connecting to a solenoid valve which is open to ambient on one side and a pressure sensor of the deficit module104. The control system of the fluid management system100is capable of sensing the vacuum level of the chamber2944via the pressure sensor of the deficit module104and opening the solenoid valve to atmospheric pressure to down regulate the vacuum pressure being supplied to the deficit cartridge2010via the suction source. Referring toFIG.29, the port2636may include a housing component2973that defines a chamber2975, where the chamber2975is connected to the solenoid valve and pressure sensor of the deficit module104. A flexible membrane2977is disposed in the chamber2975and has an opening2979that enables pressure measurement of the pressure in chamber2944and exposes chamber2944to ambient when the solenoid valve is open. The membrane2977can be made of, for example, neoprene, silicone, natural rubber, nitrile, EPDM, or any other suitable material. The port2971may also have a hydrophobic filter2981. Referring toFIGS.30through32, the deficit cartridge2010is aligned with one or more sensors2742(e.g., sensors3062,3064,3066,3068,3070shown inFIGS.30-31) of the deficit module104such that the control system of the fluid management system100can use the sensors2742to detect a volume of fluid moving through the chamber2944of the deficit cartridge2010and/or detect any potential problems with fluid flow through the deficit cartridge (e.g., potential overflow of fluid within section2946of the chamber2944). In the illustrated embodiment, the one or more sensors2742include a first fluid presence sensor3062, a second fluid presence sensor3064, a third fluid presence sensor3066, a fourth fluid presence sensor3068, and a fifth fluid presence sensor3070. Referring toFIGS.32through34, in the illustrated embodiment, the first and second fluid presence sensors3062,3064are aligned with first and second areas3271,3272, respectively, within the fill section2946. These fluid presence sensors3062,3064are used by the control system to close one or both of the inlet valves2628,2630if the fluid within the fill section2946reaches the first and second areas3271,3272. The third fluid presence sensor3066is aligned with a third area3273in the measure section2948of the chamber2944and is used by the control system to switch from Fill/Measure cycle to the Fill/Evacuation cycle and determine a volume of fluid within the measure section2948prior to switch to the Fill/Evacuation cycle. The fourth fluid presence sensor3068is aligned with a fourth area3274within the measure section2948and is used by the system to switch from the Fill/Evacuation cycle to the Fill/Measure cycle. The fifth fluid presence sensor3070is aligned with a fifth area3275within the measure section2948and is used by the system to provide more accurate real-time fluid volume measurement in measure section2948and to determine a volume of fluid in the measure section2948after the procedure is completed or the type of fluid being monitored for recording a fluid deficit is changed to provide a more accurate fluid deficit calculation for the fluid. While the illustrated embodiment shows the deficit module104having five fluid presence sensors for detecting fluid flow conditions and volume within the chamber2944of the deficit cartridge, it should be understood that any other suitable number of fluid presence sensors can be used by the deficit module to detect fluid flow conditions and volume. The target areas3271-3275may include walls partially surrounding them to mitigate the effects of fluid turbulence on the accuracy of the sensor readings and any flexing of the film2980. Referring toFIG.29, in the illustrated embodiment, the deficit cartridge2010includes a rigid body2978and a film2980. The rigid body2978partially defines the various sections2946,2948,2950and the channel2952and narrow portion3277of the chamber2944, and the film2980is attached to the rigid body2978to enclose the chamber2944. The rigid body2978can be, for example, an injection molded body or any other suitably rigid body. The film2980is configured to allow the one or more sensors of the deficit module104to detect characteristics of the fluid through the film without contacting the fluid. The film2980can be, for example, a plastic film. The film2980can be attached to the rigid body2978with mechanical fasteners or by gluing, laser welding, vibration welding, ultrasonic welding, or any other suitable means. In alternative embodiments, the deficit cartridge2010does not include film2980, but rather is made of an injection molded vessel that is capable of having the one or more sensors of the deficit module104detect characteristics of the fluid through the vessel without contacting the fluid. In other alternative embodiments, vessel may be cast or machined out of a material that is capable of being cleaned and reused. FIGS.33and34illustrate the Fill/Measure cycle and the Fill/Evacuation cycle for the deficit cartridge2010. Referring toFIG.33, during the Fill/Measure cycle, fluid returning from the surgical site is pulled from the surgical site into the fill section2946of the deficit cartridge2010through inlet ports2012,2014via a vacuum pressure from a suction source that is attached to vacuum port2016. The diaphragm operated valve2632is in the open position, which allows fluid to travel from the fill section2946to the measure section2948via gravity. The diaphragm operated valve2634is in the closed position, which prevents fluid from the measure section2948from moving into the evacuation section2950. The Fill/Measure cycle continues until the fluid level in the measure section2948has reached a predetermined level as sensed by the fluid presence sensor3066(FIGS.30-31) of the deficit module104that targets area3273. In the illustrated embodiment, the targeted area3273is disposed in a narrow portion3277(FIG.32) of the measure section2948that extends above from the main portion3276(FIG.32) of the measure section2948. The volume of fluid in the narrow portion3277is small compared to the volume of fluid in the main portion3276of the measure section2948and, therefore, variables including fluid flow rates and turbulence (which can affect the accuracy of the sensed fluid level) do not materially affect the overall accuracy of the measuring function. In certain embodiments, a ratio of the volume of the main portion3276to a volume of the narrow portion can be greater than or equal to 5 to 1, such as greater than or equal to 20 to 1, such as greater than or equal to 50 to 1, such as greater than or equal to 75 to 1, such as greater than or equal to 90 to 1, such as greater than or equal to 100 to 1. In an exemplary embodiment, the ratio of the volume of the main portion3276to the volume of the narrow portion can be about 100 to 1. The volume of fluid within the main portion3276and narrow portion3277of the measure section2948are known by the system100, which allows the system to record the volume of fluid within the measure section for each time the Fill/Measure cycle occurs. The system100records the volume and then transitions to the Fill/Evacuation cycle. Referring toFIG.34, during the Fill/Evacuation cycle, the diaphragm operated valve2632is moved to the closed position, which prevents fluid from the fill section2946from moving into the measure section2948. The diaphragm operated valve2634is moved to the open position, which allows the fluid that was measured in the measure section2948during the Fill/Measure cycle to move into the evacuation section2950via gravity. The fluid entering the evacuation section2950is then evacuated through the vacuum port2016, via the attached suction source, and the fluid is moved to the facility's waste disposal system via indirect-to-drain or direct-to-drain methods. To evacuate fluid from the evacuation section, the evacuation cycle relies upon a vacuum pressure differential between the vacuum pressure provided by the suction source and the down-regulated vacuum pressure inside of the chamber2944(as regulated via the pressure regulation and sensing port2636). When the fluid presence sensor3068(FIGS.30-31) that targets area3274detects no remaining fluid in the measure section2948, the system100transitions back to the Fill/Measure cycle. The alternation between the Fill/Measure cycle and the Fill/Evacuation cycle continues until the procedure is completed, and the control system determines the fluid deficit of the fluid based at least partially on the various volume measurement recordings taken during the various Fill/Measure cycles. The movement of fluid from the fill section2946to the measure section2948and the evacuation section2950is accomplished with gravity, as opposed to external suction or pressure sources. In these embodiments, the valves may be sized to minimize resistance and thereby facilitate high flow rates with relatively low forces. The pneumatically-actuated diaphragm valves2628,2630accomplish the allowance or stoppage of flow into the deficit cartridge2010, and the pneumatically-actuated diaphragm valves2632,2634accomplish the allowance and stoppage of flow between the sections,2946,2948,2950, by setting the pneumatic control pressure by the pressure pumps3515,3517(FIGS.35-36) of the deficit module104to a more positive gauge pressure than the combination of 1) the highest pressure expected on either wetted side of the valve, and 2) any additional pressure required to account for the additional force from the spring coefficient of the valve membrane. To guard against overflow conditions, the deficit module104may have a fluid presence sensor3064(FIGS.30-31) that targets area3272, and the control system may be configured to close the fluid return valve2628(e.g., the valve connected to the underbody drape and/or floor suction at the surgical site) if the fluid presence sensor3064detects fluid at the target area3272. This ensures that the fill section2946does not overfill and flow into the measure section2948through narrow portion3277or the evacuation section2950through the channel2952, and ensures that the remaining capacity of the fill section remains available to receive fluid returning from the surgical instrument at the surgical site so as not to interrupt the surgical procedure. The deficit module may also have a fluid presence sensor3062(FIGS.30-31) that targets area3271, and the control system may be configured to close the fluid return valve2630(e.g., the valve connected to a surgical instrument at the surgical site) if the presence sensor3062detects fluid at the target area3271. In an alternative embodiment, the valve2628can be connected to the surgical instrument at the surgical site, and the valve2630can be connected to the underbody drape and/or floor suction at the surgical site. To provide end of procedure fluid deficit accuracy (assuming the end of the surgical procedure does not coincide with the end of a Fill/Measure or Fill/Evacuation cycle), the deficit module104may include one or more midpoint fluid presence sensors (e.g., sensor3070) that target one or more areas (e.g., area3275) to provide more accurate real-time measurement of the fluid in measure section2948and to measure the fluid in the measure section2948at the end of a surgical procedure or after the type of fluid being used during the surgical procedure has been changed. FIGS.35through48illustrate an exemplary embodiment of a deficit module104that can be used with the fluid management system100shown inFIG.1and the deficit cartridge2010shown inFIGS.20-34. Referring toFIG.35, the deficit module104may include a deficit cartridge receiving assembly3511for receiving the deficit cartridge2010, one or more sensors2742for sensing characteristics of fluid moving through the deficit cartridge without contacting the fluid, a pump assembly3514, a pump manifold assembly3513, a manifold connection assembly2424for connecting the deficit cartridge2010to the pump assembly3514and a solenoid and pressure sensor (via the pump manifold assembly3513), a pneumatic mechanism2726that moves the manifold connection assembly between an engaged position (e.g., as shown inFIGS.47-49) and a disengaged position (e.g., as shown inFIGS.43-45) with the deficit cartridge2010, and a printed circuit board (PCB)3519. Referring toFIGS.38and39, the deficit cartridge receiving assembly3511includes a base3821having a slot or opening3820for receiving the deficit cartridge2010(FIGS.30-34). The receiving assembly3511also includes one or more walls or components3822-3826that substantially separate the deficit cartridge2010from the remainder of the components within the interior of the deficit module104when the deficit cartridge2010is disposed within the receiving assembly3511. The walls or components3822-3826and base3821can be connected by one or more fasteners3827to create the receiving assembly3511. A first wall3822of the receiving assembly3511can be configured to hold the one or more sensors2742for sensing characteristics of fluid moving through the deficit cartridge2010. In the illustrated embodiments, the one or more sensors2742are capacitive sensors that detect fluid presence. However, other fluid level or presence sensing technologies could be utilized including infrared sensors, laser sensors, optical sensors, electro-mechanical sensors (e.g. float with mechanical toggle switch actuation, piezo-electric pressure sensors, etc.), inductive sensors, ultrasonic sensors, or any other suitable sensors. A second wall3823of the receiving assembly3511can include a plurality of openings3828for receiving connectors (e.g., connectors4510-4513shown inFIGS.45and49) of the manifold connection assembly2424such that the pump assembly3514can be operatively connected to the diaphragm valves and pressure port of the deficit cartridge2010, as discussed in more detail below with references toFIGS.42-49. Referring toFIG.39, the manifold connection assembly2424can be connected to or positioned adjacent to the wall3823of the receiving assembly3511, and the pneumatic mechanism2726can be connected to the manifold assembly2424by one or more fasteners and to the deficit module104by a connection element or plate3930. Referring toFIGS.35and36, in the illustrated embodiment, the pump assembly3514includes a positive pressure pump3515and a negative pressure pump3517, where the pump assembly3514is connected to the pneumatic mechanism2726and the connectors of the manifold connection assembly2424via the pump manifold assembly3513. The positive pressure pump3515provides pressure to the pneumatic cylinder2726to move the manifold connection assembly2424between the engaged position (e.g., as shown inFIGS.47-49) and the disengaged position (e.g., as shown inFIGS.43-45) with the deficit cartridge2010. The positive pressure pump3515also expedites closing or augments closing force of the diaphragm valves of the deficit cartridge2010. The negative pressure pump3517provides a vacuum pressure to the diaphragm valves of the deficit cartridge2010to move the diaphragm valves to the open position. Referring toFIG.37, in the illustrated embodiment, the pump manifold assembly3513includes a plurality of accumulators3732and solenoid valves3734for regulating pressure provided by the pumps3515,3517and the opening and closing of the diaphragm valves of the deficit cartridge2010. In certain embodiments, the accumulators3732vary the positive and negative pressures to: (1) allow for the use of smaller pressure pumps that can deliver the necessary flow rates; and (2) aid pressure regulation by reducing the impact of introducing air via a “bang-bang” control scheme (i.e., an open valve, close valve control scheme). In the illustrated embodiment, the pump manifold assembly3513includes five accumulators3732(e.g., holes that extend through the assembly3515) that are capped off at the top and bottom by caps3735). The solenoid valves3734of the pump manifold assembly3513may connect to the connectors of the manifold connection assembly2424via tubing. Referring toFIGS.42-49, the pneumatic mechanism2726is shown moving the manifold connection assembly2424between a disengaged position (FIGS.43-45) with the deficit cartridge2010and an engaged position (FIGS.47-49) with the deficit cartridge2010. Referring toFIGS.43-45, when in the disengaged position, the ports2540for the diaphragm valves and pressure port of the deficit cartridge2010are not engaged by the connectors4510-4513. Referring toFIGS.47-49, the manifold connection assembly2424is moved to the engaged position in the direction D (FIG.49) by the pneumatic mechanism2726such that the connectors4510-4513engage a corresponding port2540of the deficit cartridge2010. When the connectors4510-4513are engaging the ports2540of the deficit cartridge2010, the pump assembly3514is operatively connected to the deficit cartridge2010such that the pump assembly3514can move the diaphragm valves of the deficit cartridge between the open and closed positions and the vacuum pressure supplied to the deficit cartridge2010can be sensed by a pressure sensor in the deficit module and down regulated by opening a solenoid to atmosphere. Referring toFIGS.35-49, in certain embodiments, insertion of the deficit cartridge2010into the receiving assembly3511of the deficit module104causes all of the internal connections between the deficit cartridge2010and the various components of the deficit module104. For example, insertion of the deficit cartridge2010into the receiving assembly3511causes the pneumatic mechanism2726to move the manifold connection assembly to the engaged position with the deficit cartridge (e.g., as shown inFIGS.47-49) and operatively connect the pump assembly3514to the deficit cartridge. Insertion of the deficit cartridge2010into the receiving assembly3511also causes the one or more non-contact sensors2742to be aligned with the chamber2944(FIG.29) of the deficit cartridge2010. These automatic connections between the deficit cartridge2010and the deficit module are advantageous because it limits the amount of connections a user has to make with respect to the deficit cartridge2010. That is, after inserting the deficit cartridge2010into the deficit module104, a user only needs to connect fluid return line(s) to inlet openings2012,2014(FIG.20) of the deficit cartridge2010and an evacuation line to a vacuum opening2016(FIG.20) of the deficit cartridge. Referring toFIG.50, in certain embodiments, the system100may be used for gynecological, urological, and orthopedic procedures that are performed in operating rooms that are equipped with third party suction and fluid collection devices. In these embodiments, the system100can be configured to include a main unit102(e.g., any main unit102described in the present application) and a deficit module104(any deficit module104described in the present application), but not include the fluid suction and collection module106. In this embodiment, a tubing set that includes deficit cartridge2010(FIGS.20-34) can be used in combination with the main unit102and the deficit module104to determine a fluid deficit of a fluid during a surgical procedure. Referring toFIG.51, in some situations, gynecological, urological, and orthopedic procedures are performed in operating rooms in which the facility prefers or requires “direct-to-drain” disposal of fluids returning from the surgical site. In these situations, the facility often prefers or requires the volume of the fluid being returned from the surgical site be recorded. In some embodiments, the system100can be configured to include a fluid flow monitoring and evacuation module5101that includes features of the deficit module104. The fluid flow monitoring and evacuation module5101can work in combination with the central suction system of the facility, main unit102, and a tubing set that includes a deficit cartridge2010(FIGS.20-34) or other similar cartridge to determine a fluid volume returning from the surgical site and entering a waste disposal system of the facility, as well as a fluid deficit for the surgical procedure. The fluid flow monitoring and evacuation module5101may communicate with the main unit102via Bluetooth or other wired or wireless means to measure, record, and display the return fluid volume and/or fluid deficit for the surgical procedure. While the fluid flow monitoring and evacuation module5101is described as working in combination with the main unit102of the fluid management system100, it should be understood that the fluid flow monitoring and evacuation module5101may also function as a stand-alone fluid flow monitoring and evacuation module capable of communicating with other equipment of the facility via Bluetooth or other wired or wireless means. After recording the fluid volume, module5101can then dispose of the fluid directly into a waste disposal system of the facility. In certain embodiments, the fluid flow monitoring and evacuation module5101can be a wall mounted unit or a cart mounted unit. In some embodiments, the fluid flow monitoring and evacuation module5101can include an integrated suction source to work in combination with, or in place of, the central suction system of the facility. As use of the deficit cartridge2010or other similar cartridge isolates the fluid returning from the surgical site from the components (e.g., sensors, pumps, etc.) of the fluid flow monitoring and evacuation module5101, circulation of cleaning solution through the fluid flow monitoring and evacuation module after each procedure is not necessary, which enhances procedure efficiency. The flow-based deficit monitoring feature of the system100(e.g., the combination of the deficit module104and the deficit cartridge2010, or the fluid flow monitoring and evacuation module5101) enables accurate and reliable fluid deficit monitoring that is cost-effective due to the single-use nature of the deficit cartridge2010and the elimination of canisters. This feature also enhances procedure efficiency as interruptions associated with setting up, connecting, changing, and discarding of the canisters will also be eliminated, as well as cleaning the deficit module and/or monitoring and evacuation module after each procedure. In alternative embodiments, the deficit cartridge2010may be configured for multi-procedure use. In certain situations, the fluid management system100may be connected to an external pressure source (e.g., a suction source) that is used to pull fluid from the surgical site. As external suction sources are usually set to high vacuum levels in an operating room environment, down-regulation of the vacuum pressure provided by the external suction source may be necessary for proper operation of certain fluid outflow regulation, deficit monitoring, and/or collection functions. Down-regulation of a vacuum pressure provided by an external suction source can be accomplished via a manually or electronically-controlled regulator (“Regulator”) provided it is isolated from the biohazardous fluid returning from the surgical site because replacing or cleaning the Regulator after every surgical procedure would be prohibitively expensive and/or unduly burdensome. However, isolating the Regulator by placing fluid collection canisters between it and the surgical site is not desirable due to the costs of the canisters, the complexity of setting them up, the need to change them during the procedure when they become full, and the need to dispose of them at the end of the procedure. Referring toFIG.52, to overcome the problems associated with the use of a Regulator, the system100may utilize a single-use or multi-use pressure regulator5205that is cost-effective to manufacture and disposable. The pressure regulator5205does not need to be isolated from the biohazardous fluids returning from the surgical site because of its disposability. The pressure regulator5205can be used in combination with a pressure source (e.g., an air pump) and one or more pressure sensors of the fluid management system100to sense and regulate the vacuum pressure provided by an external suction source to control the rate of fluid outflow from a surgical site and, thereby, assist in efforts to provide good distention and visualization. The pressure pump and pressure sensors may be included in an aspiration module5201that is configured to be operatively connected to the control system of the fluid management system100, or the pressure pump and pressure sensors may be integral to the main unit102of the fluid management system100. In embodiments that include the use of the aspiration module5201, inserting the pressure regulator5205into the aspiration module5201causes fluidic connections between the pressure regulator5205and the pressure sensing and gas bleed mechanisms and integrated pressure pump of the aspiration module5201. After inserting the pressure regulator5205into the aspiration module5201, the user can manually connect an external suction source and the fluid return lines from the surgical site to connection ports5202(e.g., openings5315,5317shown inFIG.53and openings5415,5417shown inFIGS.54-55) of the pressure regulator5205. Referring toFIG.53, a first exemplary embodiment of the pressure regulator5205includes three chambers5307,5309,5311and a flexible membrane5313. The first chamber5307includes an opening or port5315for fluidly connecting to the external suction source. The second chamber5309has an opening or port5317for fluidly connecting to the surgical site (via one or more fluid lines or tubes). The third chamber5311includes one or more ports for connecting to a pressure source (e.g., pressure source7449of aspiration module5201shown inFIG.74) and a pressure sensor (e.g., pressure sensors7451of aspiration module5201shown inFIGS.74-75). In the illustrated embodiment, the third chamber5311has a first opening5319for connecting to the pressure sensor and a second opening5321for connecting to the pressure source. The flexible membrane5313is positioned to fluidly isolate (i.e., seal) the third chamber5311from both of the first chamber5307and the second chamber5309, which allows the pressure source and pressure sensor of the fluid management system100(which are connected to the openings5319,5321of the third chamber5311) to be fluidly isolated from biohazardous fluid returning from the surgical site and moving through the first and second chambers5307,5309. In some embodiments, a hydrophobic filter (not shown) is disposed between the flexible membrane5313and the openings5319,5321to provide further protection in preventing fluid from contacting the pressure source and pressure sensor of the fluid management system100. For example, the hydrophobic filter can prevent fluid from contacting the pressure source and regulator if the flexible membrane5313tears or ruptures. The first chamber5307is adjacent to the second chamber5309and separated from the second chamber5309by a substantially vertical extended member or wall5323and a substantially horizontal extended member or wall5361. The wall5361includes openings5363that fluidly connect the first chamber5307to the second chamber5309. The pressure source of the fluid management system100is configured to move the flexible membrane5313between an engaged position with the wall5361and one or more disengaged positions with the wall5361, where the first and second chambers5307,5309are fluidly isolated from each other when the flexible membrane is in the engaged position, and where the first and second chambers5307,5309are fluidly connected to each other (via openings5363) when the flexible membrane5313is in one of the disengaged positions. The size and spacing between of the openings5363prevent the membrane5313from rupturing due to over-extrusion through the openings when positive pressure is applied to stop flow across the valve. The size and spacing of the openings5363may vary based upon the elasticity and thickness of the material for flexible membrane5313. The number of openings5363can ensure adequate flow, and, in some embodiments, the total combined surface area of the openings on either side of each valve may be roughly equivalent to, or greater than, the inner cross-sectional area of the tubing expected to be attached to the port5315. The fluid management system100is configured to provide pressure to the third chamber5311through opening5319, and the system100is configured to sense and regulate the pressure within the third chamber5311by sensing pressure via the pressure sensor and opening5321and modulating the pressure provided by the pressure source to achieve the desired pressure setpoint (e.g., by modulating the air pump speed of pressure source7449of aspiration module5201shown inFIG.74). The system100controls the pressure source to cause the flexible membrane5313to stretch away from the wall5361when a more positive pressure exists in the chamber5309than the greater of the pressure in the first chamber5307or the pressure in third chamber5311(in addition to the force required to displace the flexible membrane5313). When a more positive pressure exists in the second chamber5309than in the first and third chambers5307,5311(in addition to the force required to displace the flexible membrane5313), fluid is able to displace the flexible membrane5313and create a fluidic connection between chambers5307,5309via the holes5363through the wall5361and the displaced flexible membrane5313such that the desired regulated pressure (e.g., the lesser of the pressure in the first chamber5307or the pressure in the third chamber5311, in addition to the force required to displace the flexible membrane5313) is supplied to the surgical site through the opening5317of the second chamber5309. In nominal conditions, the pressure of the external suction source present in the first chamber5307is the lower than the pressure of the other chambers5309,5311of the pressure regulator5205, the regulated pressure in the third chamber5311is greater than the pressure in the second chamber5309, and the regulated pressure in the third chamber5311is adjustable to allow regulation of the pressure supplied to the surgical site through the opening5317of the second chamber5309. When the first chamber5307and the second chamber5309are fluidly connected, the biohazardous fluid moves from the surgical site, into the second chamber5309through opening5317, through the opening between the flexible membrane5313and the wall5361via holes5363and into the first chamber5307, and through the opening5315to a waste collection of the system100or the facility. When the valve is desired to be closed and flow stopped from the surgical site, the system100applies a pressure more positive in the third chamber5311than the maximum pressure expected in the second chamber5309(e.g., the pressure caused by the weight of the water column in the height difference between the valve inlet5317and the surgical site) and the pressure in the chamber5307, in addition to the pressure required to displace the flexible membrane5313. When the pressure in chamber5311is greater than the pressure in both chambers5307and5309(in addition to the pressure required to displace the flexible membrane), then the flexible membrane5311is held with sufficient force against wall5361to counteract the other system pressures such that flow is substantially halted. The flexible membrane5313seals the third chamber from the first and second chambers5307,5309to prevent the biohazardous fluid from moving into the third chamber5311and contacting the pressure source and/or pressure sensors of the system100. Provided the pressure from the surgical site (as available in chamber5309) is a more positive pressure than the gauge pressure supplied by the external suction source through the first chamber5307, the gauge pressure supplied by the pressure source of the system100into the third chamber5311, and the pressure required to stretch flexible membrane5313, the regulated vacuum pressure supplied to the surgical site can be equal to the more-positive gauge pressure of the gauge pressure supplied by the external suction source (through the first chamber5307) or the gauge pressure supplied by the pressure source of the system100(into the third chamber5311) and the pressure required to stretch the flexible membrane5313. That is, provided the flow rate from the surgical site is negligible with respect to the flow capacity of the external pressure source (supplied through the first chamber5307), the pressure supplied to the surgical site (through chamber5309) will be the pressure closest to absolute vacuum of the pressure supplied by the external pressure source (through the first chamber5307) or the pressure supplied by the pressure source of the system100(into the third chamber5311) and the pressure required to stretch the flexible membrane5313. In certain embodiments, the pressure required to stretch the flexible membrane5313may be modeled by a transfer function to determine a pressure setpoint for the pressure source of the system100(supplied into the third chamber5311) that is required to achieve a desired regulated vacuum pressure in the second chamber5309that is supplied to the surgical site. The system100may be configured to vary the regulated vacuum pressure supplied to the surgical site, via the pressure sensor and pressure pump of the system100, by varying the pressure supplied to the third chamber5311. Also, the pressure supplied by the external suction source (through the first chamber5307) and supplied to the second chamber5309may be regulated to a more positive pressure by regulating the pressure provided to the third chamber5311by the pressure source of the system100to a greater pressure than supplied by the external suction source. Because the regulated pressure setpoint is variable, this also enables the pressure regulator5205to serve as a simple 2-way valve to enable and disable flow on demand by regulating the pressure supplied to the third chamber5311with a pressure greater than the pressure in either the first chamber5307or second chamber5309. In certain embodiments, the flexible membrane5313is configured such that the pressure supplied by the pressure source in the third chamber5311causes the flexible membrane5313to stretch away from the wall5361and cause the regulated vacuum pressure supplied to the surgical site to be between about 10 mmHg and about 30 mmHg greater than the pressure provided by the pressure source of the system100. The flexible membrane5313can be made of, for example, neoprene, silicone, natural rubber, nitrile, EPDM, other rubber compounds, or any other material that allows the flexible membrane to be moved between the engaged and disengaged positions. The pressure regulator5205may have a housing5325that at least partially defines the three chambers5307,5309,5311and includes the openings5315,5317,5319,5321. The housing5325can be made of, for example, polycarbonate, any suitable type of plastic material, or any other suitable material. In certain embodiments, the housing5325has a first component5327that includes the first and second chambers5307,5309, and a second component5329that includes the third chamber5311, where the flexible membrane5313is positioned between the first and second components5327,5329to fluidly isolate the chambers of the first component5327from the chambers of the second component5329. The first component5327, the second component5329, and the flexible membrane5313can be connected by a snap-fit connection, an adhesive connection, one or more fasteners, laser welding, ultrasonic welding, vibration welding, or any other suitable means. Referring to the embodiment shown inFIG.53, if the lowest desired regulated pressure supplied to the surgical site is a positive gauge pressure, the pressure supplied by the external pressure source could be a positive or negative gauge pressure. If the desired regulated pressure is a negative gauge pressure (i.e., a vacuum pressure), then the pressure supplied by the external suction source may be required to be a negative gauge pressure that is more negative than the lowest gauge pressure desired to be regulated because pressure supplied by the external pressure source is not being sensed. In other words, the pressure supplied by the external pressure source (through the first chamber5307) is not required to be consistent (e.g., does not need to be regulated and may have pressure fluctuations) provided the highest gauge pressure supplied by the external pressure source is not a gauge pressure that is higher than the desired regulation pressure setpoint for the regulated source (e.g., the surgical site). Although the embodiment of the pressure regulator5205shown inFIG.53is effective for regulating an external suction source that provides a vacuum level that is known to be more-negative than the desired regulated vacuum pressure provided to the surgical site, a second embodiment of the pressure regulator5205(shown inFIGS.54-73) allows the fluid management system100to regulate an external suction source that is providing an unknown or variable vacuum level and sense when the vacuum level is sufficient to achieve the desired regulation setpoint. Referring toFIGS.54and55, the second embodiment of the pressure regulator5205utilizes two valves of the first embodiment (FIG.53) arranged in series. Referring toFIG.54, the second exemplary embodiment of the pressure regulator5205includes four chambers5407,5409,5411,5412and a flexible membrane5413. The first chamber5407includes an opening or port5415for fluidly connecting to the external suction source. The second chamber5409has an opening or port5417for fluidly connecting to the surgical site (via one or more fluid lines or tubes). The third chamber5411includes one or more ports5419for connecting to a pressure source (e.g., pressure source7449of aspiration module5201shown inFIG.74), and the fourth chamber5412includes one or more openings5421for connecting to one or more pressure sensors (e.g., pressure sensors7451of aspiration module5201shown inFIGS.74-75). Alternative embodiments can incorporate sensors from the same port connections of the pressure regulator5205for redundancy or improved regulation of the pressure source. The flexible membrane5413is positioned to fluidly isolate (i.e., seal) each of the third and fourth chambers5411,5412from both of the first and second chambers5407,5409, which allows the pressure source and pressure sensor of the fluid management system100to be fluidly isolated from biohazardous fluid returning from the surgical site and moving through the first and second chambers5407,5409. The first chamber5407is adjacent to the second chamber5409and separated from the second chamber5409by a vertical extended member or wall5423and a horizontal extended member or wall5465. The wall5465includes openings5467that fluidly connect the first chamber5307to the second chamber5309. The flexible membrane5413is movable from an engaged position and one or more disengaged positions with the wall5465, where the first and second chambers5407,5409are fluidly isolated from each other when the flexible membrane5413is in the engaged position, and where the first and second chambers5407,5409are fluidly connected with each other (via openings5467) when the flexible membrane5413is in the disengaged position. The third chamber5411is adjacent to the fourth chamber5412and separated from the first chamber5412by a vertical extended member or wall5431and a horizontal extended member or wall5461. The wall5461includes openings5463that fluidly connect the third chamber5411to the fourth chamber5413. The flexible membrane5413is also movable from an engaged position and one or more disengaged positions with the wall5461, where the third and fourth chambers5411,5412are fluidly isolated from each other when the flexible membrane5413is in the engaged position, and where the third and fourth chambers5411,5412are fluidly connected with each other (via openings5463) when the flexible membrane5413is in the disengaged position. To better show that the embodiment of the pressure regulator5205shown inFIG.54utilizes two valves of the first embodiment of the pressure regulator shown inFIG.53in series, the first chamber5407is shown as having a first portion5408and a second portion5410, but the pressure across both the first and second portions5408,5410, as supplied by the external suction source, is identical (as there is no barrier capable of sealing the first and second portions5408,5410from each other). Referring toFIG.55, the first valve5501of the pressure regulator5205utilizes the external suction source (via the first portion5408of the first chamber5407) to regulate movement of the pressure supplied by the pressure source of the fluid management system from the third chamber5411to the fourth chamber5412. The second valve5503utilizes the pressure in the fourth chamber5412(via the movement of pressure from the third chamber5411to the fourth chamber5412) to regulate the movement of the pressure supplied by the external suction source from the second portion5410of the first chamber5407to the second chamber5409such that the pressure in the second chamber5409is substantially equal to the desired regulated vacuum pressure at the surgical site. Referring toFIGS.54and55, the pressure at the first portion5408of the first chamber5407causes the flexible membrane5413to be in either the engaged position or the disengaged position with the wall5461. For example, if the vacuum pressure supplied by the external suction source is more negative than the pressure supplied by the pressure source of the system100into the third chamber5411, the flexible membrane5413stretches away from the wall5461such that the third and fourth chambers5411,5412are fluidly connected. When the third and fourth chambers5411,5412are fluidly connected, the pressure in the fourth chamber5412is substantially equal to the pressure in the third chamber5411. Comparatively, if the vacuum pressure supplied by the external suction source is more positive than the pressure supplied by the pressure source into the third chamber5411, the flexible membrane is in the engaged position with the wall5461to fluidly isolate the fourth chamber5412from the third chamber5411. The fluid management system100senses the pressure within the fourth chamber5412via the one or more pressure sensors of the system100, which allows the system100to determine if the pressure supplied by the external suction source is not supplying sufficient vacuum pressure to meet the desired regulated vacuum pressure at the surgical site. That is, if the external suction source is not supplying enough pressure to cause the flexible membrane5413to stretch away from the wall5461, air will slowly bleed out of the fourth chamber5412via a small orifice or valve of the system100that may be constantly or periodically opened to a more positive gauge pressure to gradually bring the pressure in the fourth chamber5412closer to this more positive gauge pressure, and the pressure sensor of the system100will sense that the pressure in the fourth chamber5412is not equal to the pressure supplied by the pressure source to the third chamber5411, which will cause the system to determine that the pressure supplied by the external suction source is not sufficient to meet the desired regulated vacuum pressure at the surgical site. The pressure sensed by the system100in the fourth chamber5412, given enough time to bleed off pressure, can be used to determine the actual pressure present in the first chamber5407if it is less than the positive gauge pressure that is slowly bled into the fourth chamber5412. If the system100determines that the external suction source is not supplying a sufficient vacuum pressure, the system100may be configured to notify the user to adjust the external pressure source (e.g., by increasing the suction setting of external pressure source, unclogging the line leading to the external pressure source, finding a leak in the line leading to the external pressure source, etc.) to ensure it is sufficient to down-regulate the vacuum pressure at the surgical site to the desired regulated vacuum pressure. Referring toFIGS.54and55, the second valve5503of the pressure regulator5205utilizes the pressure supplied by the pressure source of the fluid management system in the fourth chamber5412to regulate the movement of pressure supplied by the external suction source to the second chamber5409and, consequently, the surgical site. That is, the system100controls the pressure source to cause the flexible membrane5413to stretch away from the wall5465to fluidically connect the first and second chambers5407,5409such that the desired regulated vacuum pressure is supplied to the surgical site through the opening5417of the second chamber5409. The biohazardous fluid then moves from the surgical site, into the second chamber5409through opening5417, through the openings5467between the flexible membrane5413the wall5465and into the first chamber5407, and through the opening5415to a waste collection of the system100or the facility. The flexible membrane5413seals each of the third and fourth chambers5411,5412from both of the first and second chambers5407,5409to prevent the biohazardous fluid from contacting the pressure source and/or pressure sensors of the system100. Provided the pressure from the surgical site as available in chamber5409is a more positive pressure than both the gauge pressure supplied by the external suction source (through the first chamber5407) and the gauge pressure supplied by the pressure source of the system100(into the third chamber5411) and the pressure required to stretch flexible membrane5413, the regulated vacuum pressure supplied to the surgical site can be equal to the more-positive gauge pressure of the gauge pressure supplied by the external suction source (through the first chamber5407) or the gauge pressure supplied by the pressure source of the system100(into the third and fourth chambers5411,5412) and the pressure required to stretch the flexible membrane5413. That is, provided the flow rate from the surgical site is negligible with respect to the flow capacity of the external pressure source (supplied through the first chamber5407), the pressure supplied to the surgical site (through chamber5409) will be the pressure closest to absolute vacuum of the pressure supplied by the external pressure source (through the first chamber5407) and the pressure required to stretch the flexible membrane5413or the pressure supplied by the pressure source of the system100(into the third and fourth chambers5411,5412) and the pressure required to stretch the flexible membrane5413. In certain embodiments, the pressure required to stretch the flexible membrane5413may be modeled by a transfer function to determine a pressure setpoint for the pressure source of the system100(supplied into the third and fourth chambers5411,5412) that is required to achieve a desired regulated vacuum pressure in the second chamber5409that is supplied to the surgical site. The system100may be configured to vary the regulated vacuum pressure supplied to the surgical site, via the pressure sensor and pressure pump of the system100, by varying the pressure supplied to the third and fourth chambers5411,5412. Also, the pressure supplied by the external suction source (through the first chamber5407) and supplied to the second chamber5409may be regulated to a more positive pressure by regulating the pressure provided to the third and fourth chambers5411,5412by the pressure source of the system100to a greater pressure than supplied by the external suction source. Because the regulated vacuum pressure setpoint is variable, this also enables the pressure regulator5205to serve as a simple 2-way valve to enable and disable flow on demand by regulating the pressure supplied to the third and fourth chambers5411,5412with a pressure greater than the pressures in either the first chamber5407or second chamber5409. In certain embodiments, the flexible membrane5413is configured such that the pressure supplied by the pressure source in the third and fourth chambers5411,5412causes the flexible membrane5413to stretch away from the wall5423and cause the regulated vacuum pressure supplied to the surgical site to be between about 10 mmHg and about 30 mmHg greater than the pressure provided by the pressure source of the system100, such as about 20 mmHg greater than the pressure provided by the pressure source. The flexible membrane5413can be made of, for example, neoprene, silicone, natural rubber, nitrile, EPDM, other rubber compounds, or any other material that allows the flexible membrane to be moved between the engaged and disengaged positions. In certain embodiments, the fourth chamber5412is pneumatically attached to a small orifice or valve of the fluid management system100that may be constantly or periodically opened to bleed off pressure to a gauge pressure that is greater than or equal to the maximum gauge pressure expected from either the pressure source of the fluid management system100or the external suction source. The opened orifice or valve bleeds off pressure at a negligible flow rate compared to the flow rate capability of the pressure source of the fluid management system to ensure that the pressure inside of the fourth chamber5412is the greater gauge pressure of the external pressure source or the desired regulated pressure in the second chamber5409and any additional force required to stretch or open the flexible membrane5413. The embodiment of the pressure regulator5205shown inFIGS.54and55allows for non-wetted, indirect sensing of the pressure source of the fluid management system100to help ensure that the external suction source is of sufficient pressure to regulate to the desired vacuum pressure of the system's pressure source to down-regulate the vacuum pressure in the second chamber5409and at the surgical site. Being able to indirectly sense the pressure supplied by the external suction source via the cost-effective single use pressure regulator5205is beneficial because it enables the system100to prompt the user to adjust the external suction source (by increasing the suction setting of the external suction source, unclogging the line leading to the external suction source, finding a leak in the line leading to the external suction source, etc.) to ensure it is sufficient to down-regulate the vacuum pressure at the surgical site to the desired regulated vacuum pressure or otherwise prevent operation of the system if the regulated vacuum pressure levels would be detrimental to the safety or efficacy of the intended use of the regulated vacuum pressure from the system. FIGS.56through64show an embodiment of the pressure regulator5205shown inFIGS.54and55. In the illustrated embodiment, the pressure regulator5205includes a housing5625that at least partially defines the four chambers5407,5409,5411,5412and includes the openings5415,5417,5419,5421. The housing5625can be made of, for example, polycarbonate or any other suitable material. Referring toFIG.58, in certain embodiments, the housing5625has a first component5827that includes the first and second chambers5407,5409, and a second component5829that includes the third and fourth chambers5411,5412. The first and second components5827,5829can be, for example, injection molded pieces. The flexible membrane5413is positioned between the two components5827,5829to fluidly isolate the chambers5407,5409of the first component5827from the chambers5411,5412of the second component5829. In some embodiments, the pressure regulator5205may also include covers5833for covering the outer facing portions of the chambers for each component5827,5829. The first component5827, the second component5829, the flexible membrane5413, and the covers5833can be connected by a snap-fit connection, an adhesive connection, one or more fasteners, ultrasonic welding, combinations thereof, or any other suitable means. In some embodiments, the pressure regulator5205may include one or more hydrophobic filters5835for helping maintain a bacterial barrier between the pressure source and pressure sensors of the fluid management system100. Referring toFIG.64, in certain embodiments, the pressure regulator5205shown inFIGS.56-63can be used in combination with an aspiration module (e.g., aspiration module7404shown inFIGS.74-75) that includes a pressure pump (e.g., pressure pump7449shown inFIG.74) and pressure sensors (e.g., pressure sensors7451shown inFIGS.74-75) to sense and regulate the external suction source to control the rate of fluid outflow from a surgical site. When the pressure regulator is inserted into the aspiration module, the pressure regulator5205may be configured to connect to a receiving mechanism6437(FIG.64) that automatically connects the port5419for the third chamber5411to a port6439that is operatively connected to the pressure pump of the aspiration module. The connection between the pressure regulator5205and the receiving mechanism may also automatically connect the port5421for the fourth chamber5412to a port6441that is operatively connected to sensors and or an air bleed mechanism of the aspiration module. The connection mechanism6437may include channels6443for receiving end portions6445of the pressure regulator5205to allow for a secure connection between the pressure regulator5205and the aspiration module. After inserting the pressure regulator into the aspiration module5205, the user can manually connect the external suction source to the port5415for the first chamber5407and manually connect the fluid return lines from the surgical site to the port5417for the second chamber5409. FIGS.65through73show another embodiment of the pressure regulator5205shown inFIGS.54and55. In the illustrated embodiment, the pressure regulator5205includes a housing6525that at least partially defines the four chambers5407,5409,5411,5412and includes the openings5415,5417,5419,5421. The housing5625can be made of, for example, polycarbonate or any other suitable material. In certain embodiments, the housing6525has a first component6829that includes the first and second chambers5407,5409, and a second component6827that includes the third and fourth chambers5411,5412. The first and second components6827,6829can be, for example, injection molded pieces. The flexible membrane5413is positioned between the two components6827,6829to fluidly isolate the chambers5407,5409of the first component6827from the chambers5411,5412of the second component6829. In some embodiments, the pressure regulator5205may also include covers6633for covering the outer facing portions of the chambers for each component6827,6829. The first component6827, the second component6829, the flexible membrane5413, and the covers6533,6633can be connected by a snap-fit connection, an adhesive connection, one or more fasteners, ultrasonic welding, combinations thereof, or any other suitable means. In some embodiments, the pressure regulator5205may include one or more hydrophobic filters6635for helping maintain a bacterial barrier between the pressure source and pressure sensors of the fluid management system100. The pressure regulator5205can also include one or more sealing members6643(e.g., O-rings) for making fluid tight connections. In certain embodiments, the housing6525has a gripping member or handle6547that helps a user insert and remove the pressure regulator from the aspiration module or other component of the fluid management system100. Referring toFIGS.72and73, in certain embodiments, the pressure regulator5205shown inFIGS.65-71can be used in combination with an aspiration module (e.g., aspiration module7404shown inFIGS.74-75) that includes a pressure pump (e.g., pressure pump7449shown inFIG.74) and pressure sensors (e.g., pressure sensors7451shown inFIGS.74-75) to sense and regulate the external suction source to control the rate of fluid outflow from a surgical site. When the pressure regulator5205is inserted into the aspiration module, the pressure regulator5205may be configured to connect to a receiving mechanism7237that automatically connects the port5419for the third chamber5411to a port6439that is operatively connected to the pressure pump of the aspiration module. The connection between the pressure regulator5205and the receiving mechanism may also automatically connect the port5421for the fourth chamber5412to a port7241that is operatively connected to sensors and or an air bleed mechanism of the aspiration module. The connection mechanism6437may include channels (not shown) for receiving end portions of the pressure regulator5205to allow for a secure connection between the pressure regulator5205and the aspiration module (e.g., similar to as shown in the embodiment shown inFIG.64). After inserting the pressure regulator into the aspiration module5205, the user can manually connect the external suction source to the port5415for the first chamber5407and manually connect the fluid return lines from the surgical site to the port5417for the second chamber5409. FIGS.74and75illustrate an exemplary embodiment of the aspiration module5201that can be used with the fluid management system100shown inFIG.1and the various embodiments of the pressure regulators5205shown inFIGS.53-73. The aspiration module5201may include the receiving mechanism7437(e.g., receiving mechanism6437shown inFIG.64or receiving mechanism7237shown inFIG.72) for receiving the pressure regulator5205, an integrated pressure pump7449, one or more valves7452,7453for connecting the pressure pump to the pressure regulator5205, and a printed circuit board (PCB)7448having one or more pressure sensors7451. The integrated pressure pump7449may be configured to supply a positive pressure or a negative pressure to the pressure regulator5205via opening5419(FIG.54) of the pressure regulator. For example, the pump7449may be an air pump that includes two ports (not shown), and the aspiration module5201may include valves7452,7453(e.g., three-way valves) connected to the opening5419of the pressure regulator5205and the ports of the pump7449. A first port of the pump7449may be configured to pull air into the pump7449, and a second port of the pump7449may be configured to push air out of the pump, which allows the pump7449to supply both positive and negative pressures for pressure regulation and stoppage of flow through the valves. For example, if the port which pulls air into the pump7449is left open to ambient and the port which pushes air out of the pump7449is connected to a substantially sealed vessel, then the pump7449will build up positive pressure inside the substantially sealed vessel. Conversely, if the port which pushes air out of the pump7449is left open to ambient and the port which pulls air into the pump7449is connected to a substantially sealed vessel, then the pump7449will build up vacuum pressure inside the substantially sealed vessel. In this embodiment, the valves7452,7453are ported such that the pump ports can each be opened to ambient air pressure and connected to supply pressure to the aspiration module. Software of the control system may modulate the states of the valves7452,7453to configure the pump to supply positive or vacuum pressure to the system based on the desired valve state and regulation setpoint. The pump7449can be fluidly connected to the valves7452,7453by tubing. In other embodiments, the pump7449may be configured to supply either a positive pressure or a negative pressure to the pressure regulator, or the aspiration module5201may include separate positive and negative pressure pumps for supplying pressure to the pressure regulator5205. In certain embodiments, an accumulator7450is fluidly positioned between pressure pump7449and the pressure regulator5205to aid in regulating the pressure provided to the pressure regulator5205by the pressure pump7449. The one or more pressure sensors7451may be used to monitor both the pressure supplied to third chamber5411(FIG.54) of the pressure regulator5205by the pressure pump7449and a pressure within the fourth chamber5412(FIG.54) of the pressure regulator5205. In certain embodiments, the pressure sensors7451can be operatively connected to the accumulator7450by pneumatic tubing to monitor the pressure supplied to the pressure regulator5205, and the pressure sensors7451can be operatively connected to the opening5421(FIG.54) of the pressure regulator5205by pneumatic tubing to monitor the pressure within the fourth chamber5412. The pressure sensors7451allow the fluid management system100to sense the pressure within the fourth chamber5412(FIG.54) of the pressure regulator5205to determine if the pressure supplied by the external suction source that is connected to the first chamber5407(FIG.54) is not supplying sufficient vacuum pressure to meet the desired regulated vacuum pressure at the surgical site. Referring toFIG.75, in certain embodiments, the aspiration module5201includes a valve7554that allows for the fourth chamber5412(FIG.54) of the pressure regulator5205to be constantly or periodically opened to bleed off pressure to a gauge pressure that is greater than or equal to the maximum gauge pressure expected from either the pressure pump7449(FIG.74) or the external suction source. The opened orifice or valve bleeds off pressure at a negligible flow rate compared to the flow rate capability of the pressure pump7449to ensure that the pressure inside of the fourth chamber5412(FIG.54) is the greater gauge pressure of the external pressure source or the desired regulated pressure supplied to the surgical site. Referring to the operation of the fluid management system100discussed in the present application, the control system may be configured to guide the user through the setup process using, for example, instructions, illustrations, animations, video, and/or system feedback via the user interface110. Referring toFIGS.76and77, in certain embodiments, the system100prompts a user (via the user interface110) to select the surgical discipline and procedure that will be performed, which can cause the system100to set default operating parameters for the procedure, as well as safe, permissible adjustment ranges for those parameters (as stored in a memory of the system100). For example, the system100may prompt a user to select a discipline of “Gynecology,” “Urology,” or “Orthopedic”; and, if the user selects “Urology,” the system100may prompt the user to select one of the following procedures: “Cystoscopy,” “PCNL,” “TURBT,” “TURP,” or “Ureteroscopy.” Based on the selection by the user, the system100may then set default operating parameters (e.g., pressure control mode or flow control mode, setpoint fluid pressure or flow rate, fluid warming condition enabled or disabled, fluid deficit monitoring enabled or disabled, etc.) for the procedure. In certain embodiments, the system100may provide instructions to a user for installing the tubing sets to the various components of the system100. For example, the system100may instruct the user to insert the cartridge assembly419(FIG.4) that includes the fluid conditioner420(FIG.4) and fluid warming cartridge422(FIG.4) into the main unit102, and then place or route the tubing that connects the fluid supply containers and the cartridge assembly419into or through the pump212(FIG.2). The system100may then prompt the user to indicate whether fluid deficit monitoring will be performed during the procedure. In certain situations, the system100may require fluid deficit monitoring be performed based on an input from the user as to the type of procedure that is being performed. For example, if the user selects an operative hysteroscopy procedure, fluid deficit monitoring is required. For other gynecological and urological procedures, fluid deficit monitoring may be optional. If the user did not select an operative hysteroscopy procedure and did not elect to enable fluid deficit monitoring for the selected procedure, the system100may instruct the user to spike and hang the fluid bags. If the user selected an operative hysteroscopy, or selected another procedure and elected to enable fluid deficit monitoring feature for the selected procedure, the system100may prompt the user to indicate whether one or more fluid types will be used during the procedure and what the fluid types are, as illustratedFIGS.78through80. In various embodiments, the system100may be configured to monitor and display fluid deficit by fluid type. For example, in operative hysteroscopy, surgeons can utilize multiple fluid types during a procedure based on the type of procedure being performed and the surgical instruments employed. These fluids can differ in osmolality, electrolyte content, and viscosity. The amount of these fluids absorbed by the surgical patient depend on the fluid pressure, the length of the procedure, and the degree of surgical disruption of the venous sinuses in the endometrium and, importantly, the myometrium if the intrauterine fluid pressure is greater than the surgical patient's mean arterial pressure. Thus, the capability of monitoring and displaying fluid deficit by fluid type enhances the safety for the patient. Referring toFIGS.78-80, after the user indicates the number of fluid types that will be used during the procedure, the system100may prompt the user (via the user interface110) to select the specific fluids will be used during the procedure. The system100may then set the maximum allowable deficit limit for each specific fluid type (based on information stored in a memory of the control system or based on information inputted by a user). For example, the maximum allowable deficit limit for hypotonic, electrolyte-free fluids may be 1000 ml, and the maximum allowable deficit limit for isotonic, electrolyte containing fluids may be 2500 ml. The system100may also set a maximum total deficit limit for the procedure based on a sum of the fluid deficits for the selected fluid types. For example, the maximum total deficit limit for the procedure may be 2,500 ml. In various embodiments, the system100will provide a user with instructions (via the user interface110) for hanging the fluid supply containers. For example, with regards to a first fluid type selected by the user, the system100may instruct the user as to which hanging members116(FIGS.1and2) to use, instruct the user to hang the fluid supply container(s) and then monitor the hanging member(s)116(FIGS.1and2) to confirm that the fluid supply container(s) were disposed on the correct hanging members, or prompt the user to indicate which hanging member(s)116(FIGS.1and2) will be used to hold the fluid supply container(s) and then monitor the weight of the hanging member(s)116(e.g., via load cells connected to the hanging members) to determine when the fluid container(s) are disposed on the corresponding hanging members116. The system100can then repeat the above process for the fluid container(s) holding the second fluid type. During the procedure, the system100may be configured to monitor and display the fluid deficit level for the first fluid type (via the user interface110) by subtracting an amount of fluid returned from the surgical site (e.g., as determined using the deficit cartridge2010and deficit module104or by monitoring a weight of fluid collection containers hanging from member(s)116(FIGS.1and2), etc.) from the volume of fluid pumped to the surgical site (e.g., as determined by monitoring the weight of the fluid supply containers, monitoring the amount of pump rotations of the pump212, etc.). In certain embodiments, the user can switch to the second fluid type via the user interface110(e.g., by pressing a “Change Fluid Type” button or other similar button). The system100may then instruct the user to close the tubing line(s) connecting the fluid supply containers for the first fluid type to the pump212(e.g., by closing clamp(s) on the tubing line(s)). The system100may also instruct the user to collect all residual fluid of the first fluid type from the surgical site, underbody drape, and the floor. Subsequently, the system100may instruct the user to fluidly connect the tubing lines of the fluid supply containers for the second fluid type (e.g., by opening clamp(s) on the tubing line(s)). In alternative embodiments, the system100may be configured to detect (via one or more processors of the control system) when a user switches to the second fluid type. In certain embodiments, the tubing lines may be automatically fluidly connected or disconnected by pinch valves. After fluidly connecting the tubing lines for the second fluid type, the user may initiate a purge of the first fluid type from the system100. In certain embodiments, the user will stop the pump, remove the scope and/or surgical instrument from the body cavity constituting the surgical site, and allow the cavity to drain the first fluid type into the underbody drape. When complete, the user will fluidly disconnect the first fluid type from the pump by closing the associated clamp(s), fluidly connect the second fluid type to the pump by opening the associated clamp(s), direct the scope and/or surgical instrument into the underbody drape and press a “Purge” or similar button on the user interface110of system100which will cause the system100to pump the volume of the second fluid type necessary to force the first fluid type from the cartridge assembly419, fluid inflow tube, and scope and/or instrument. In certain embodiments, system100may pump the second fluid type necessary to cause the purge until the user presses a “Stop Purge” or similar button on the user interface110of system100. After the purge has been completed and the underbody drape has emptied, system100will record the fluid deficit for the first fluid type, empty the deficit cartridge2010(FIGS.33-34), and then indicate to the user via user interface110of system100that the procedure can proceed with the second fluid type. This process may be repeated to change back and forth between the first and second fluid types. After the first fluid type is purged from the system100, the system100may commence monitoring and display of the fluid deficit level for the second type of fluid. The system100may be configured to display the total fluid deficit, the deficit of the first fluid type, and/or the deficit of the second fluid type. In certain embodiments, a user may be able to elect, via a toggle switch or similar button on the user interface100, whether the system100displays the total fluid deficit, the deficit of the first fluid type, the deficit of the second fluid type, and/or any combination thereof. In some embodiments, if the user does not notify the system100of a fluid change (i.e., the change from the first fluid to the second fluid), the system100may stop the pump212to pause fluid flow. For example, the system100may prompt the user to indicate whether a change in fluid type was intended, and, if the user indicates that a change in fluid type was not intended, the system can instruct the user to check for any issues that may be affecting the weight on a hanging member associated with the other fluid type (e.g., such as leakage from the bag or an open or partially open clamp). If the user indicates that a change in fluid type was intended, the system100can instruct the user to initiate a purge of the system (as indicated above). The user may switch the fluids multiple times using the procedures described herein. In certain embodiments, a user that initially indicated only one fluid would be used in the procedure, may during the procedure, indicate to system100via user interface110that a second fluid will be used by pressing a “Settings” button or icon or similar button or icon on the user interface110and then pressing an “Add Second Fluid” button or icon or similar button or icon. The system100may then instruct the user via user interface110to hang the second fluid type, purge the first fluid type, record the deficit for the first fluid type, and instruct the user to continue the procedure using the second fluid type as indicated above. The system can then track the deficit for the first fluid type, the second fluid type, and total deficit. In certain embodiments, once the fluid containers have been placed on the hanging members116, the system100may guide the user to complete the tubing installation process. For example, if the fluid suction and collection module106is utilized, but the deficit module104is not utilized, the instructions can include connecting the fluid lines returning from the surgical site, underbody drape, and the floor (if applicable) to the fluid suction and collection module106. If the deficit module104is utilized, the instructions can include inserting the deficit cartridge2010into the deficit module104, connecting the suction source to the deficit cartridge2010(e.g., via vacuum port2016), and connecting the fluid return tubing lines (from the surgical site) to the deficit cartridge2010(e.g., via fluid inlet ports2012,2014). If the aspiration module5201is utilized, the instructions can include inserting the pressure regulator5205into the aspiration module5201, connecting the suction source to the pressure regulator5205(e.g., via port5315shown inFIG.53or port5415shown inFIGS.54-55), and connecting the fluid return tubing lines (from the surgical site) to the pressure regulator5205(e.g., via port5317shown inFIG.53or port5417shown inFIGS.54-55). If the fluid flow and evacuation module5101(FIG.51) is utilized, the instructions can include inserting the deficit cartridge2010(or similar single-use fluid volume monitoring cartridge) into the fluid flow monitoring and evacuation module5101and connecting the fluid return tubing lines (from the surgical site) to the deficit cartridge (e.g., via fluid inlet ports2012,2014). Following the tubing installation process, the system100may instruct the user to complete a priming process. For example, the system100may instruct the user to fluidly disconnect the fluid conditioner420(FIG.10) from the surgical instrument being used at the surgical site (e.g., by closing a clamp on the tubing that connects the fluid conditioner420to the surgical instrument). The system100may also instruct the user to fluidly connect at least one of the fluid supply containers to the pump212(e.g., by opening a clamp on the tubing that connects the fluid supply container to the pump212). Subsequently, the system100may instruct the user to initiate priming of the tubing set (e.g., by pressing a “Prime” button or other similar button), which will cause the system100to pump fluid from the at least one fluid container and into the fluid conditioner420until the pressure sensors of the system100indicate that fluid in the fluid outlet chamber1054(FIG.10) of the fluid conditioner420has reached a certain fluid pressure, and/or until a fluid presence sensor (e.g., fluid presence sensor948shown inFIG.9) of the system100that targets the fluid outlet chamber1054indicates that the fluid has reached a certain level. After the system100determines that the pressure or fluid level in the outlet chamber1054is sufficient, the system100may stop the pump212. The fluid pressure within the outlet chamber1054may then be reduced by reversing the pump212or opening a solenoid valve (e.g., solenoid valve951shown inFIG.9) until the desired fluid pressure or fluid level in the outlet chamber1054of the fluid conditioner420has been achieved. The volume of fluid necessary to prime the tubing set may be known and added as a constant offset for the purposes of monitoring and displaying the volume of fluid pumped and the fluid deficit (if applicable). Referring toFIG.81, the system100may include a procedure run screen8101(via the user interface110). In the illustrated embodiment, the procedure run screen8101is shown for a system that is in pressure control mode. In alternative embodiments, the system100may be in flow control mode or flex control mode. Each of these control modes are discussed in more detail below. The user may start a procedure by pressing the “Play”, “Run”, or similar icon or button8103in the navigation bar at the bottom of the screen8101. The user may also, via adjustment control/buttons on the run screen8101, change default operating settings, such as, for example, the fluid pressure setpoint condition8105(if the system100is in a pressure control mode), the fluid flow rate setpoint condition (not shown—if the system100is in a flow control mode), and the deficit alarm level8107(if the deficit monitoring function is required or has been elected). In certain embodiments, the system100may only allow a user to change the default operating settings to be within the safe, permissible adjustment ranges8111for the procedure. The procedure run screen8101may also allow a user to enable/disable the fluid warming function by using switch8113and display the fluid temperature8112. In addition to displaying an actual condition8115and setpoint condition8105for pressure (or for flow if the system100is in a flow control mode), and an actual condition8117and setpoint condition8107for fluid deficit (if applicable), the procedure run screen8101may also display other information. For example, the procedure run screen8101may display fluid inflow or volume pumped8121to the surgical site, the fluid flow rate8123(if the system100is in pressure control mode), and/or the fluid pressure (not shown—if the system100is in flow control mode). The procedure run screen8101may also have a navigation bar consisting of icons or buttons that can be used before or during the procedure, such as, for examples, a “Settings” button8128, a “Help” or “Troubleshooting” button8127, a “Notifications” button8129, a “Maintenance” button8181, and/or an “End Case” or “End Procedure” button8133. In certain embodiments, pressing the “Settings” button8128brings up a settings screen (not shown) on the user interface110that allows the user to adjust, set, or enable other features of the system100. For example, referring toFIG.82, the system100may include a procedure settings screen8202that allows a user to set or adjust the control mode that the system100will follow for the procedure. In this embodiment, the system100may be set in a pressure control mode8204, a flow control mode8206, or a flex control mode8208. In certain embodiments, the system100may default to one of the control modes (e.g., the pressure control mode8204), but the user can change the type of control mode in the procedure settings screen8202. If the system100is in flow control mode8206, the system varies the speed of the pump212to achieve and maintain a user-selected fluid flow rate setpoint (e.g., as set by the user on the procedure run screen8101) provided, however, that the maximum allowable fluid pressure for the procedure cannot be exceeded. In other words, the fluid pressure is varied to achieve the desired fluid flow rate. If the system100is in pressure control mode8204, the system100varies the speed of the pump212to achieve and maintain a user-selected fluid pressure setpoint (e.g., as set by the user on the procedure run screen8101shown inFIG.81) provided, however, that the maximum allowable fluid flow rate for the procedure cannot be exceeded. In other words, the fluid flow rate is varied to achieve the desired fluid pressure. In some embodiments, the system100can control to the user-selected fluid pressure setpoint as the desired fluid pressure at the system. In some embodiments, the system100can control to the user-selected fluid pressure setpoint as the desired fluid pressure at the surgical scope or instrument. Referring toFIG.81A, for ergonomic reasons corresponding to operating the graphical user interface110, hanging fluid supply containers from hanging members116, and inserting components (e.g., the cartridge assembly419and/or deficit cartridge2010described in the present application) into the main unit102, a height H1of main unit102may be higher than the surgical table8151. In certain embodiments, the system100can compensate for the head pressure resulting from the difference H3between the height H1of the main unit102and the assumed or inputted height H2of a patient8153in calculating the required system pressure. That is, the system100can equate the compensation height H3to a pressure adjustment, and then subtract the pressure adjustment from the user-selected fluid pressure setpoint at the surgical scope or instrument. In some embodiments, the system100can control to the user-selected fluid pressure setpoint as the desired fluid pressure in the body cavity constituting the surgical site. In these embodiments, in addition to calculating the pressure adjustment based on the compensation height H3described with reference toFIG.81A, the system100may also take into account known restrictions of the tubing set and assumed or calibrated restrictions of the surgical scope or instrument to determine the required system pressure. Accordingly, in some embodiments, the user may elect for the system100to monitor and display (via the graphical user interface110) the fluid pressure at the system, fluid pressure at the surgical scope or instrument, or fluid pressure in the body cavity constituting the surgical site. In endoscopic surgical procedures, good, steady distention and clear visibility are important to procedural efficacy and efficiency. Although fluid pressure and flow rate are the primary factors to achieve satisfactory surgical site distention and visibility, some users may lack a clear understanding of how fluid pressure and/or flow rate (as impacted by surgical site conditions and fluid inflow and outflow restrictions of the surgical instrument and the tubing sets delivering fluid to and from the surgical site) affect distention and visibility. Referring toFIG.83, in an exemplary embodiment, the system100may alternatively be set to a flex control mode that allows a user to achieve desired surgical site conditions simply by making distention and visualization adjustments. That is, in this mode, the user is not concerned with whether the system100is operating fluid pressure control mode or the fluid flow rate control mode, nor is the user concerned with the setpoint pressure or flow rate. Instead, the user may provide feedback to the system100regarding the surgical site conditions via the user interface110, and the system100determines whether to operate in pressure or flow control mode, as well as determines the proper setpoint for fluid pressure and/or flow rate for the procedure. Referring toFIG.83, if the user selects the flex control mode, the system100sets a default fluid pressure setpoint for the procedure and presents “Distention” controls or buttons8351,8352and “Visualization” controls or buttons8353,8354on the user interface110. For example, the user may increase distention by pressing the “+” (increase) button8351or may decrease distention by pressing the “−” (decrease) button8352, and the user may increase visualization by pressing the “+” (increase) button8353or may decrease visualization by pressing the “−” (decrease) button8354. The user interface110may also display other information (similar to the procedure run screen8101shown inFIG.81). For example, the user interface110may display fluid inflow or volume pumped8321to the surgical site, the fluid flow rate8323, and/or the fluid pressure8324. The user interface may also display the fluid temperature8312and allow a user to enable/disable the fluid warming function by using switch8313. The user interface110may also have a navigation bar consisting of icons or buttons that can be used before or during the procedure, such as, for examples, a “Settings” button8328, a “Help” or “Troubleshooting” button8327, a “Notifications” button8329, a “Maintenance” button8331, and/or an “End Case” or “End Procedure” button8333. Referring toFIG.84, when the system is set to flex control mode (as shown at8402), the system100may default to pressure control mode (as shown at8404). In the illustrated embodiment, the adjustment of distention puts the system in fluid pressure control mode and adjusts the pressure setpoint for the procedure, and the adjustment of visualization puts the system in fluid flow rate control mode and adjusts the flow rate set point for the procedure. If a user adjusts the distention (as shown at8406), the system100maintains or transitions to the pressure control mode setting (as shown at8408) such that the system100can adjust the setpoint pressure of the procedure to meet the desired distention by the user. In various embodiments, distention adjustment to the fluid pressure setpoint can never exceed the maximum allowable setpoint pressure for the procedure. If the user indicates that additional distention is desirable, but the pressure setpoint is at the maximum allowable level (as shown at8410), the system100determines whether the flow rate for the system100is at the maximum allowable flow rate (as shown at8412). If the flow rate is at the maximum allowable flow rate, the system100can notify the user (via the user interface110) that the system100is operating at its pressure and flow rate limits for the procedure (as shown at8414). If the flow rate is not at the maximum allowable flow rate, the system100can instruct the user to open the scope inflow and outflow valves to increase the fluid flow rate (as shown at8416) and thereby increase the fluid moving through the surgical site. Going back to the step shown at8410, if the setpoint pressure of the fluid is not at the maximum allowable pressure, the system100determines whether the flow rate for the system100is at the maximum allowable flow rate (as shown at8418). If the flow rate is at the maximum allowable flow rate, the system100can instruct the user to restrict fluid outflow from the surgical site (as shown at8420) by partially closing the scope outflow valve, partially closing a clamp on the outflow tubing, and/or using a fixed or variable restrictor component in the outflow tubing of the surgical instrument. If the flow rate is not at the maximum allowable flow rate, the system100can increase the pressure setpoint (as shown at8422) to increase the distention. If a user adjusts the visualization (as shown at8424), the system100maintains or transitions to the flow control mode setting (as shown at8426) such that the system100can adjust the setpoint flow rate of the procedure to meet the desired visualization by the user. In various embodiments, visualization adjustment to the fluid flow rate setpoint can never exceed the maximum allowable setpoint flow rate for the procedure. If the flow rate setpoint is at the maximum allowable level (as shown at8428), the system100determines whether the fluid pressure for the system100is at the maximum allowable pressure (as shown at8430). If the pressure is at the maximum allowable pressure, the system100can notify the user (via the user interface110) that the system100is operating at its pressure and flow rate limits for the procedure (as shown at8414). If the pressure is not at the maximum allowable flow rate, the system100can instruct the user to restrict fluid outflow from the surgical site (as shown at8432), which allows the system100to increase the pressure of the fluid in the surgical site. The user can restrict outflow from the surgical site by, for example, partially closing an outflow valve of the surgical instrument, partially closing a clamp on the outflow tubing, and/or using a fixed or variable restrictor component in the outflow tubing of the surgical instrument. Going back to the step shown at8428, if the setpoint flow rate of the fluid is not at the maximum allowable flow rate, the system100determines whether the fluid pressure for the system100is at the maximum allowable flow rate (as shown at8434). If the pressure is at the maximum allowable pressure, the system100can instruct the user to open scope inflow and outflow valves (as shown at8436) to increase the fluid flow rate through the surgical site. If the pressure is not at the maximum allowable pressure, the system100can increase the flow rate setpoint (as shown at8438) to increase the visualization. In other words, by utilizing the distention controls8351,8352, the user puts the system100in pressure control mode and adjusts the setpoint fluid pressure for the procedure up to the maximum allowable level for the procedure, while maintaining a maximum allowable flow rate which cannot be exceeded. By utilizing the visualization controls8353,8354, the user puts the system100in flow control mode and adjusts the setpoint fluid flow rate for the procedure up to the maximum allowable level for the procedure while maintaining a maximum allowable fluid pressure which cannot be exceeded. Accordingly, the system100provides the user more intuitive control over the surgical site conditions while at all times remaining within the safe pressure and flow rates for the procedure and displaying the actual fluid pressure and flow rate. Referring toFIGS.85through87, the system100may include a bolus feature or device that is used to temporarily increase the fluid pressure and/or flow rate to maintain or increase distention and/or to maintain or increase fluid flow for procedural and/or visualization purposes. The bolus feature or device may include a “Bolus” icon or button on one of the screens comprising the graphical user interface; pneumatic, electric, or wireless foot pedal; and/or other actuating device that allows a surgeon to temporarily increase the fluid pressure and/or flow rate for procedural and visualization purposes. The bolus device may be operatively connected to the pump212(FIG.2) of the system100such that a surgeon can activate the bolus device to temporarily increase the pressure or flow rate by operation of the pump212, and such that the pump returns to the normal setting for providing fluid at the setpoint pressure and flow rate after the surgeon deactivates the bolus device. Because the surgeon operates the bolus device, the bolus device can be provided when needed without requiring manual operation of a bolus device or the interaction of a circulating nurse with the system. The bolus feature also prevents the setpoint pressure and/or flow rate of the fluid management system to be changed for only a temporary increase in the pressure and/or flow rate. The bolus device may interface with the system pneumatically, electrically, or wirelessly (e.g., via Bluetooth). The bolus device can be configured by the user via the user interface110. For example, the user (via the user interface110) may use a toggle switch8510to change the bolus device between an “On” and “Off” state. In certain embodiments, the user may elect to have the bolus device operate in a momentary mode8501where the increase is sustained for as long as the foot pedal is pressed. The user may alternatively elect to have the bolus device operate in a maintained mode8503where the foot pedal is pressed to activate the bolus device and pressed again to deactivate the bolus device. In another embodiment, the user may elect to have the bolus device operated in a timed mode (not shown) where the foot pedal is pressed to activate the bolus device, and the system100maintains the bolus device in the activate state for a desired amount of time. Whether the increase caused by the bolus device is to the fluid pressure or flow rate setpoint may depend, for example, on whether the system100is in pressure mode or flow control mode at the time of bolus activation. The user may elect to have the increase equal a set increment (e.g., a 25 mmHg pressure increase or a 50 ml/min flow rate increase), a percentage increase over setpoint (e.g., 20%), or the maximum allowable fluid pressure or fluid flow rate for the procedure. The increase in fluid pressure and fluid flow rate may be limited to the maximum allowable setpoint for the procedure. The bolus device of the present application is beneficial because the fluid pressure or flow rate increase is known and safe. That is, the user sets the increase, the actual fluid pressure and flow rate are displayed on the user interface110of the system100, and the increase never exceeds the max allowable safe limit for the procedure. In addition, the duration of the increase is appropriate as determined and controlled by the surgeon. Also, because the surgeon controls the bolus device via, for example, a foot pedal, the bolus device does not need to be operated by a circulating nurse, and the bolus device does not involve interacting with the system. In an alternative embodiment, the system100may include a temporary adjustment feature or device that is used to temporarily increase or decrease the fluid pressure and/or flow rate, which allows a user to temporarily increase or decrease distention and/or visualization at the surgical site. This adjustment feature or device may include a “Temporary” icon or button representing a temporary adjustment on one of the screens comprising the graphical user interface in combination with a foot pedal or other type of actuating device. In certain embodiments, the actuating device includes a pneumatic, electric, or wireless foot pedal(s) such as a foot pedal with rocker action or a dual foot pedal arrangement that allows a surgeon to temporarily increase or decrease the fluid pressure and/or flow rate for procedural and visualization purposes. The adjustment device may be operatively connected to the pump212(FIG.2) of the system100such that a surgeon can activate the device to temporarily increase or decrease the pressure or flow rate by operation of the pump212, and such that the pump returns to the normal setting for providing fluid at the setpoint pressure and flow rate after the surgeon deactivates the adjustment device. Because the surgeon operates the adjustment device, the temporary adjustment to pressure and/or flow rate can be provided when needed without requiring manual operation of a device or the interaction of a circulating nurse with the system100. The adjustment device may interface with the system pneumatically, electrically, or wirelessly (e.g., via Bluetooth) and can be configured by the user via the user interface110for mode (momentary or maintained) and adjustment type (fixed, percentage, or max). In certain embodiments, the system100may include a printer (e.g., printer218shown inFIG.2) for printing out pertinent information regarding a surgical procedure during or after the procedure. Referring toFIG.88, in situations in which the system100is tracking a fluid deficit for the procedure, the user may elect (via the user interface110) to have the fluid deficit automatically recorded and printed out at set time intervals during the procedure (e.g., every 10 minutes). As illustrated inFIG.88, the user interface110may include a toggle button to turn on or off the automatic recording and printing of fluid deficit at set time intervals during the procedure. This capability eliminates the need for the user to periodically check and manually record or print out the fluid deficit information. In some embodiments, the user may (via the user interface110) request to have the fluid deficit recorded at set time intervals during the procedure and printed at the end of the procedure. In some embodiments, the user may (via the user interface110) request that the deficit information from previous time intervals be displayed. In some embodiments, the system100may be configured to print the fluid deficit at volume intervals of the deficit monitoring (e.g., every 50 ml of volume for each fluid deficit individually and/or the total fluid deficit). In some embodiments, rather than printing to a printer of the system100itself, the system100may be configured to automatically communicate with a printer of the facility in which the system100is being used (e.g., via wire, Bluetooth, or WiFi) and print pertinent information at during or after the procedure, or at set time intervals during the procedure. The system100can be configured to offer the user the ability to printout pertinent procedure information at the end of the procedure, including, but not limited to, the date, procedure type, start time, end time, fluid volume pumped, fluid deficit (if applicable), fluid deficit at set time intervals (if applicable), average fluid pressure, fluid warming enabled/disabled, and/or average fluid temperature. In some embodiments, the user may be able to elect to have different or additional information printed, including, but not limited to, facility information, physician information, patient information, fluid deficit by fluid type (if applicable), fluid deficit by time increment (if applicable), fluid pressure range, fluid flow range, notifications and alerts list, and alarms list. Additionally, the user may elect to transmit pertinent procedure information via the Bluetooth or Wi-Fi capabilities of the system100to a data collection and/or record retention system of the facility. To avoid procedure interruption caused by depleted fluid supply bags, the system100may record the initial weight of the fluid supply bag hung on each hanging member116(FIG.1), the current weight of the fluid supply bag on each hanging member116, and the current fluid flow rate for the procedure. The system100may also be able to provide audible and/or visual indicators if the system100determines that a fluid bag may become depleted. The system100may also provide an audible and visible indication when the estimated time before a fluid bag will become depleted has fallen below a specified level. Alternatively, referring toFIGS.89through91, the user may elect to receive audible and/or visual indicators (via the user interface110) if the percentage of fluid remaining (based on the initial volume of the fluid bag) falls below a specified level. Referring toFIG.89, the system100can be set to a “Time” setting8902that notifies a user when the amount of time until a bag becomes depleted drops below a predetermined amount of time (as shown at8903) based on the current or average fluid flow rate. The system100may, alternatively, be set to a “Percentage” setting8904that notifies a user when a percentage of the fluid supply remaining drops below a predetermine percentage (as shown at8904). Alternatively, the system100may be set to a “Volume” setting8906that notifies a user when a volume of fluid remaining in the fluid supply container drops below a predetermined volume (as shown at8907). Provided the above-mentioned levels are set appropriately, the user (typically a circulating nurse) has time to replace a fluid bag without an interruption to the procedure. To avoid confusion and ensure elevated levels of attention for alarm conditions, the user may mute or reduce the sound level of certain indicators, alerts, and alarms provided by switch or button8910and selection window8912. In some embodiments, however, adjustment of the alerts/indicators is not possible for certain safety critical alarms. Referring toFIGS.92and93, an exemplary embodiment of a fluid management system9200for a physician's office environment where gynecological and urological procedures are performed is shown. The system9200includes a main unit9202that may include any or all of the features described above for the main unit102of the fluid management system100used in an operating room environment. For example, the main unit9202may include a control system that has one or more processors (not shown) for controlling various components of the system9200(e.g., a user interface, and various fluid pressure sensors, vacuum pressure sensors, fluid temperature sensors, fluid presence sensors, etc.). The processors may execute instructions (e.g., software code) stored in a memory (not shown) of the system100and/or execute instructions inputted into the system by a user. In some embodiments, the control system may have “Bluetooth” capability for connecting to remotely located components or modules of the system9200and “Wi-Fi” capability for connecting to the internet. The control system may include a touch-screen graphical user interface9210for receiving one or more inputs from a user and displaying information of the system9202(e.g., information regarding fluid deficit, fluid temperature, fluid pressure, distention, visualization, etc.). The main unit9202may also include a pump (e.g., pump212shown inFIG.2) for fluid pressurization, a vacuum pump for providing suction, a fluid conditioning assembly (e.g., fluid conditioning assembly315shown inFIG.3) for receiving a fluid conditioner (e.g., fluid conditioner420shown inFIG.10) and sensing one or more characteristics (e.g., fluid presence, fluid temperature, etc.) of fluid moving through the fluid conditioner, hanging members9216(e.g., hooks) for hanging fluid supply or collection containers9217(e.g., bags, canisters, vessels, etc.). In some embodiments, the main unit9202may include a heating assembly (e.g., heating assembly314shown inFIG.3) for receiving a warming cartridge (e.g., warming cartridge422shown inFIGS.14-18) such that system can be configured for fluid warming during the procedure, if applicable. The processor of the control system can be in circuit communication with the pump, sensors, fluid conditioning assembly, heating assembly (if applicable), and hanging members9216; and the processor can be configured to control these components. In certain embodiments, the hanging members9216are operatively connected to load cells such that the control system can monitor a weight of the fluid containers9217. Although the system100for the operating room environment may include a cartridge assembly419(FIG.4) that includes a fluid conditioner420and a fluid warming cartridge422, the system9200for the physician's office may or may not include a fluid warming function. In embodiments that do not include a fluid warming function, the fluid conditioner420described with reference to the system100may also be used with the system9200, but the fluid conditioner420may include a connector or tube841(FIG.8), a pulse damping component, or a channel integral to the fluid conditioner420that connects the inlet chamber1053(FIG.10) to the outlet chamber1054(FIG.10), rather than the warming cartridge422. If the system9200does include a fluid warming component, a warming cartridge (e.g., warming cartridge422shown inFIGS.14-18) can be an accessory that attaches to the fluid conditioner420such that the system9200can perform fluid warming. The system9200may be configured to perform deficit monitoring by a weight-based method, as compared to the flow-based deficit monitoring method described with the fluid management system100. Flow-based deficit monitoring (as used with the system100) is appropriate for the operating room environment due to the generally higher fluid volume usage associated with the longer, more complex surgical procedures performed there. However, the complexity and cost of the flow-based deficit monitoring feature may not be necessary in a physician's office environment, as the surgical procedures performed there are generally shorter and use less fluid. Accordingly, the system9200may be configured to include weight-based deficit monitoring. In certain embodiments, the hanging members9216are configured for the dual purpose of holding and monitoring the weight of the fluid containers9217. That is, the processor of the system9200can be operatively connected to the load cells of the hanging members9216, which allows the system9200to monitor the weight of the fluid containers9217. At least one fluid container9217is for supplying fluid to the surgical site, and at least one fluid container9217is for fluid returning from the surgical site. The system9200monitors the weight of the hanging members9216to determine the fluid inflow volume to the surgical site (by based on the weight of the fluid supply container) and the fluid outflow volume returned from the surgical site (based on the weight of the fluid return container) to calculate the fluid deficit, which is the difference between the fluid inflow volume and the fluid outflow volume. The system9200can be configured to monitor and display the fluid volume and fluid deficit. The system9200can also be configured to provide a notification or alarm if the deficit level exceeds the default limit or the adjusted limit set by the user. Similar to the system100described in the present application, the system9200may be configured to guide the user through the setup process using instructions, illustrations, animations, and/or system feedback via the user interface9210. For example, the system9200may first prompt the user to select the surgical discipline and procedure that will be performed, which can cause the system9200to set the default operating parameters for the procedure as well as the safe, permissible adjustment ranges for those parameters. If deficit monitoring is required or elected by the user, the system9200can prompt the user to indicate the type of fluid that will be utilized and will set the maximum deficit limit for that fluid. The system9200can then instruct the user to hang a fluid supply container and indicate when the container has been placed on the hanging member9216(with the system confirming placement by monitoring the weight of each hanging member). The system9200can also instruct the user to hang the fluid supply container9217on a specific hanging member9216(with the system9200confirming placement by monitoring the weight of the designated hanging member). The system9200may then instruct the user to connect the fluid return lines to a fluid return container9217, connect the fluid return container9217to a suction source (e.g., an integrated suction source of the main unit9200or an external suction source), and then to hang the fluid return container on another hanging member9216. When the system9200senses that the fluid return container9217has been hung, it may set and record the empty fluid container weight to zero such that the system9200can properly calculate the fluid deficit for the procedure. Alternatively, the system9200can instruct the user place fluid supply container9217on the hanging member9216, and when the system9200senses that a fluid supply container is properly placed, the system9200can instruct the user to prepare and hang a fluid return container as discussed above. The system9200can properly assign hanging members for each of the fluid supply containers and fluid return containers by monitoring the weight changes of the respective hanging members during the process, or by comparing the respective weight on the hanging members after the process has been completed. Although the system9200can accommodate standard canisters that can hold up to 5 L of fluid, the packaging of the tubing sets intended for procedures performed in the physician office environment can also be used for the described fluid collection function. If deficit monitoring is not required or elected, the system9200can prompt the user to place the fluid supply containers9217on the hanging members9216, place or route the tubing connecting the fluid containers(s) with the fluid conditioner (e.g., fluid conditioner420), into or through the pump212, and insert the fluid conditioner into the main unit9202. Following the tubing installation process, the system9200can then instruct the user to complete the priming process as described above with reference to the system100. When priming is complete, the user interface can transition to a procedure run screen (e.g., procedure run screen8101) where the user may start and control the procedure. While various inventive aspects, concepts and features of the disclosures may be described and illustrated herein as embodied in combination in the exemplary embodiments, these various aspects, concepts, and features may be used in many alternative embodiments, either individually or in various combinations and sub-combinations thereof. Unless expressly excluded herein all such combinations and sub-combinations are intended to be within the scope of the present application. Still further, while various alternative embodiments as to the various aspects, concepts, and features of the disclosures—such as alternative materials, structures, configurations, methods, devices, and components, alternatives as to form, fit, and function, and so on—may be described herein, such descriptions are not intended to be a complete or exhaustive list of available alternative embodiments, whether presently known or later developed. Those skilled in the art may readily adopt one or more of the inventive aspects, concepts, or features into additional embodiments and uses within the scope of the present application even if such embodiments are not expressly disclosed herein. Additionally, even though some features, concepts, or aspects of the disclosures may be described herein as being a preferred arrangement or method, such description is not intended to suggest that such feature is required or necessary unless expressly so stated. Still further, exemplary or representative values and ranges may be included to assist in understanding the present application, however, such values and ranges are not to be construed in a limiting sense and are intended to be critical values or ranges only if so expressly stated. Moreover, while various aspects, features and concepts may be expressly identified herein as being inventive or forming part of a disclosure, such identification is not intended to be exclusive, but rather there may be inventive aspects, concepts, and features that are fully described herein without being expressly identified as such or as part of a specific disclosure, the disclosures instead being set forth in the appended claims. Descriptions of exemplary methods or processes are not limited to inclusion of all steps as being required in all cases, nor is the order that the steps are presented to be construed as required or necessary unless expressly so stated. The words used in the claims have their full ordinary meanings and are not limited in any way by the description of the embodiments in the specification. | 172,934 |
11857777 | DETAILED DESCRIPTION Refer now to the drawings wherein depicted elements are not necessarily shown to scale and wherein like or similar elements are designated by the same reference numeral through the several views. Referring to the drawings in general, it will be understood that the illustrations are for the purpose of describing particular implementations of the disclosure and are not intended to be limiting thereto. While most of the terms used herein will be recognizable to those of ordinary skill in the art, it should be understood that when not explicitly defined, terms should be interpreted as adopting a meaning presently accepted by those of ordinary skill in the art. I. Overview of Blood Flow Assist Systems Various embodiments disclosed herein relate to a blood flow assist system1configured to provide circulatory support to a patient, as illustrated inFIGS.1A-1D. The system1can be sized for intravascular delivery to a treatment location within the circulatory system of the patient, e.g., to a location within the descending aorta of the patient. As shown inFIG.1A, the system1can have a proximal end21with a connector23configured to connect to an external control system, e.g., a console (not shown). The connector23can provide electrical communication between the control system and a power wire20extending distally along a longitudinal axis L from the connector23and the proximal end21. The power wire20can comprise an elongate body that electrically and mechanically connects to a pump2at or near a distal end22of the blood flow assist system1, with the distal end22spaced apart from the proximal end21along the longitudinal axis L. The pump2can comprise a pump head50including a pump housing35connected to a drive unit9that includes a motor housing29. A retrieval feature48can be provided at a proximal end portion of the pump2. In some embodiments, the retrieval feature can be coupled with the distal end of the power wire20between the power wire20and the motor housing29. After a procedure, the clinician can remove the pump2from the patient by engaging a tool (e.g., a snare, clamp, hook, etc.) with the retrieval feature48to pull the pump2from the patient. For example, the retrieval feature48can comprise a neck49(e.g., a reduced diameter section) at a proximal curved portion51cof the motor housing29and an enlarged diameter section disposed proximal the neck49. The enlarged diameter section can comprise a first curved portion51aand a second curved portion51b, as shown inFIG.1E. The first and second curved portions51a,51bcan comprise convex surfaces, e.g., convex ball portions. The first and second curved portions51a,51bcan have different radii of curvature. For example, as shown inFIG.1E, the first curved portion51acan have a larger radius of curvature than the second curved portion51b. The first curved portion51acan be disposed on opposing sides of the retrieval feature48in some embodiments. The second curved portion51bcan be disposed around the first curved portion51aand can have a radially-outward facing surface and a proximally-facing convex surface coupled to the distal end of the power wire20. The neck49can have a first depth at a first circumferential position of the retrieval feature48and a second depth less than the first depth at a second circumferential position of the retrieval feature48spaced apart from the first circumferential position. Beneficially, as shown inFIG.1E, one or more first planes P1extending parallel to the longitudinal axis L and intersecting the first curved portion51acan have a first angle or taper between the proximal curved portion51cof the motor housing29and the first curved portion51a. One or more second planes P2extending parallel to the longitudinal axis L and intersecting the second curved portion51bcan have a second angle or taper (which is different from the first angle or taper) between the proximal curved portion51cof the motor housing29and the second curved portion51b. The first angle or taper can provide a gradual, continuous (generally monotonically decreasing) geometric transition between the proximal curved portion51cof the motor housing29and the power wire20, which can provide for smooth blood flow and reduce the risk of thrombosis. The second curved portion51bcan serve as a lobe that extends radially outward, e.g., radially farther out than the first curved portion51a. The second curved portion51bcan be used to engage with a retrieval device or snare to remove the pump2from the anatomy. Some cross sections through the longitudinal axis of the retrieval feature48can contain a substantial neck (e.g., a local minimum in the radius of curvature measured along its central axis) while other cross sections through the longitudinal axis of the retrieval feature48can contain an insubstantial local minimum or no local minimum. In the illustrated embodiment, there are two first curved portions51athat can serve as a dual lobe retrieval feature. In other embodiments, more or fewer lobes can be provided to enable pump retrieval while ensuring smooth flow transitions between the motor housing29and power wire20. As shown inFIGS.1B-1C and1E, the neck49can be disposed between the curved portions51a,51band the proximally-facing convex surface51cof the motor housing29. In the illustrated embodiment, the retrieval feature48can be coupled to or integrally formed with the motor housing29. In other arrangements, the retrieval feature48can be disposed at other locations of the pump2. As shown, the retrieval feature48can be symmetrical and continuously disposed about the longitudinal axis L. In other arrangements, the retrieval feature48can comprise a plurality of discrete surfaces spaced apart circumferentially and/or longitudinally. In the illustrated embodiments, the motor housing29(and motor) can be part of the pump2and disposed inside the vasculature of the patient in use. In other embodiments, however, the motor housing29(and motor) can be disposed outside the patient and a drive cable can connect to the impeller6. As shown inFIGS.1A-1C, the drive unit9can be configured to impart rotation to an impeller assembly4disposed in the pump housing35of the pump head50. As explained herein, the drive unit9can include a drive magnet17and a motor30(seeFIGS.6-8A) disposed in the motor housing29capped by a distal drive unit cover11. The drive unit cover11can be formed with or coupled to a drive bearing18. The drive magnet17can magnetically couple with a corresponding driven or rotor magnet12(seeFIG.7) of the impeller assembly4that is disposed within the shroud16proximal the impeller6. The power wire20can extend from the treatment location to outside the body of the patient, and can provide electrical power (e.g., electrical current) and/or control to the motor30. Accordingly, no spinning drive shaft extends outside the body of the patient in some embodiments. As explained herein, the power wire20can energize the motor12, which can cause the drive magnet17to rotate about the longitudinal axis L, which can serve as or be aligned with or correspond to an axis of rotation. Rotation of the drive magnet17can impart rotation of the rotor magnet12and a primary or first impeller6of the impeller assembly4about the longitudinal axis L. For example, as explained herein, the rotor magnet12can cause an impeller shaft5(which can serve as a flow tube) to rotate which, in turn, can cause the first impeller6to rotate to pump blood. In other embodiments, the drive unit9can comprise a stator or other stationary magnetic device. The stator or other magnetic device can be energized, e.g., with alternating current, to impart rotation to the rotor magnet12. In the illustrated embodiments, the impeller6can have one or a plurality of blades40extending radially outward along a radial axis R that is radially transverse to the longitudinal axis L. For example, the first impeller6can have a plurality of (e.g., two) axially-aligned blades40that extend radially outwardly from a common hub and that have a common length along the longitudinal axis L. The curvature and/or overall profile can be selected so as to improve flow rate and reduce shear stresses. Skilled artisans would appreciate that other designs for the first impeller5may be suitable. As shown inFIGS.1A-1C, the impeller assembly4can be disposed in a shroud16. The impeller shaft5can be supported at a distal end by a sleeve bearing15connected to a distal portion of the shroud16. A support structure such as a localization system can comprise a base portion36coupled with the sleeve bearing15and/or the shroud16. In some embodiments, the base portion36, the sleeve bearing15, and/or the shroud16can be welded together. The base portion36of the support structure or localization system, the sleeve bearing15, and the shroud16can cooperate to at least partially define the pump housing35, as shown inFIGS.1A and1C. The localization system can comprise a plurality of self-expanding struts19having convex contact pads24configured to contact a blood vessel wall to maintain spacing of the pump housing35from the blood vessel wall in which the pump housing35is disposed. InFIGS.1A-1C, the struts19of the localization system are illustrated in an expanded, deployed configuration, in which the contact pads24extend radially outward to a position in which the contact pads24would contact a blood vessel wall within which the pump2is disposed to at least partially control position and/or orientation of, e.g., to anchor, the pump2during operation of the system1. A first fluid port27can be provided distal the impeller assembly4at a distal end of the pump housing35. The shroud16can comprise a proximal ring26coupled with the motor housing29and a plurality of second fluid ports25formed in a proximal portion of the shroud16adjacent (e.g., immediately distal) the proximal ring26. As shown inFIG.1C, the second fluid ports25can comprise openings formed between axially-extending members60that extend along the longitudinal axis L between the proximal ring26and a cylindrical section59of the shroud16. In some embodiments, the axially-extending members60(also referred to as pillars) can be shaped to serve as vanes that can shape or direct the flow of blood through the second fluid ports25. For example, in various embodiments, the axially-extending members60can be angled or curved to match the profile of the impeller blades40. In other embodiments, the axially-extending members60may not be angled to match the blades40. In some embodiments, the first fluid port27can comprise an inlet port into which blood flows. In such embodiments, the impeller assembly4can draw blood into the first fluid port27and can expel the blood out of the pump2through the second fluid ports25, which can serve as outlet ports. In other embodiments, however, the direction of blood flow may be reversed, in which case the second fluid ports25may serve as fluid inlets and the first fluid port27may serve as a fluid outlet. Beneficially, the blood flow assist system1can be delivered percutaneously to a treatment location in the patient.FIG.1Dshows the pump2disposed within an elongate sheath28. As shown, the struts19are held in a collapsed configuration by the inner wall of the sheath28. In the collapsed configuration, the struts19can be compressed to a diameter or major lateral dimension at one or more locations that is approximately the same (or slightly smaller than) the diameter of the shroud16. The patient can be prepared for the procedure in a catheterization lab in a standard fashion, and the femoral artery can be exposed. The sheath28(or a dilator structure within the sheath28) can be passed over a guidewire and placed into the treatment location, for example, in the descending aorta. After the sheath28is placed, the pump2can be advanced into the sheath28, with the pump2disposed in the mid-thoracic aorta, approximately 4 cm below the take-off of the left subclavian artery. In other embodiments, the pump2and sheath28can be advanced together to the treatment location. Positioning the pump2at this location can beneficially enable sufficient cardiac support as well as increased perfusion of other organs such as the kidneys. Once at the treatment location, relative motion can be provided between the sheath28and the pump head (e.g., the sheath28can be retracted relative to the pump2, or the pump2can be advanced out of the sheath28). The struts19of the localization system can self-expand radially outwardly along the radial axis R due to stored strain energy into the deployed and expanded configuration shown inFIGS.1A-1C. The convex contact pads24can engage the blood vessel wall to stabilize (e.g., anchor) the pump2in the patient's vascular system. Once anchored at the treatment location, the clinician can engage the control system to activate the motor30to rotate the impeller assembly4to pump blood. Thus, in some embodiments, the pump2can be inserted into the femoral artery and advanced to the desired treatment location in the descending aorta. In such arrangements, the pump2can be positioned such that the distal end22is upstream of the impeller6, e.g., such that the distally-located first fluid port27is upstream of the second fluid port(s)25. In embodiments that access the treatment location via the femoral artery, the first fluid port27can serve as the inlet to the pump2, and the second ports25can serve as the outlet(s) of the pump2. In other embodiments, however, the pump2can be inserted percutaneously through the left subclavian artery and advanced to the desired treatment location in the descending aorta. In such arrangements, the pump2can be positioned such that the distal end22of the system1is downstream of the impeller6, e.g., such that the distally-located first fluid port27is downstream of the second fluid port(s)25. In embodiments that access the treatment location through the left subclavian artery, the second fluid port(s)25can serve as the inlet(s) to the pump2, and the first port27can serve as the outlet of the pump2. When the treatment procedure is complete, the pump2can be removed from the patient. Relative motion opposite to that used for deploying the pump2can be provided between the sheath28and the pump2(e.g., between the sheath28and the impeller assembly4and pump housing35) to collapse the struts19into the sheath28in the collapsed configuration. In some embodiments, the pump2can be withdrawn from the sheath28with the sheath28in the patient's body, and the sheath28can subsequently removed. In other embodiments, the sheath28and the pump2can be removed together from the patient's body. II. Modified Sleeve Bearings As explained above, in some embodiments the sleeve bearing15can support a distal end portion5A of the impeller shaft5, which can support the first impeller6and can also serve as a flow tube. Designs may be generally described from a perspective in which the central axis of rotation of the impeller assembly4is oriented along the longitudinal axis L of the system1, e.g., vertically for purposes of discussion in some instances. As used herein, proximal and distal ends (or end portions) of a component may be axially spaced apart along the longitudinal axis L of the system1. Thus, the sleeve bearing15may be described interchangeably in terms of an associated length or height, which extend along the longitudinal axis L. Generally, a rotating member (a shaft or tube such as the impeller shaft5shown and described herein) rotating inside a tubular sleeve or bearing has a bearing surface that is cylindrically shaped as an open right circular cylinder. This standard bearing design has circular proximal and distal edges (e.g., upper and lower interface edges) that are perpendicular to the longitudinal axis L of the rotating member or axis of rotation, and a cylindrical bearing surface between the edges that remains covered and unexposed by the bearing body. Further, there is a circular set of points where the rotating member (e.g., the shaft5) and bearing interface with one another, which may be referred to herein as a bearing interface or interface edge. In other words, any point on this circle on the rotating member is always perpendicularly aligned with the edge of the sleeve. This condition has been shown to encourage thrombus formation at the sleeve edge(s). This thrombus may grow to form a complete ring around the sleeve edge, thereby impeding proper operation. The designs of the modified sleeve bearing15described herein have a novel design to reduce or prevent thrombus formation during operation. Turning toFIGS.2A-2E, one embodiment of such a sleeve bearing15is illustrated. The sleeve bearing15can comprise an inner support structure including an inner sleeve37that supports the distal portion5A of the impeller shaft5. The inner sleeve37can be mechanically coupled to the first impeller6in some embodiments, e.g., by way of a thrust ring bearing14(seeFIG.6). The thrust bearing14can be laser welded to the inner sleeve37in one embodiment. In other embodiments, there may be no thrust bearing14between the first impeller6and the inner sleeve37. The sleeve bearing15can further include an outer support structure comprising an outer annular or cylindrical member, sometimes referred to herein as an outer sleeve or outer bearing carrier38connected to the shroud16. The outer sleeve or bearing carrier38can comprise a small radially outer portion of the sleeve bearing15. A connecting structure39can extend radially between the inner sleeve37and the outer bearing carrier38to connect the inner sleeve37and the outer bearing carrier38. In variations the connecting structure39can be coupled directly to the shroud16. The outer bearing carrier38can be eliminated in one embodiment. The outer bearing carrier38can be integrated into or be part of the shroud16, such that the structure is a monolithic construction and not the assembly of multiple parts. In other variations the connecting structure39can be indirectly coupled to the shroud16through a structure other than the annular member or bearing carrier38. As explained herein, the pump2can have a primary or first flow pathway3A. Blood can flow along the first flow pathway3A between the outer bearing carrier38and the inner sleeve37and along an exterior surface of the first impeller6. A majority of the blood flow (e.g., a majority of the momentum of the total blood flow) through the pump2can pass along the primary or first flow pathway3A. The first flow pathway3A can extend radially between the rotating first impeller6and the stationary pump housing35. Accordingly, blood can flow over the rotating outermost surface of the first impeller6between the first impeller6and the stationary inner wall of the pump housing35. The pump2can also have a secondary or second flow pathway3B along a lumen of the impeller shaft5, which as explained herein can serve as a flow tube. A minority of the total blood flow can flow along the secondary flow pathway3B. For example, in some embodiments, the volume flow of blood along the secondary flow pathway3B can be in a range of 0.5% to 10% of the volume flow of blood along the primary flow pathway3A, in a range of 1% to 5% of the volume flow of blood along the primary flow pathway3A, or in a range of 2% to 3% of the volume flow of blood along the primary flow pathway3A. As shown inFIGS.2A,2C, and2E, the inner sleeve37can have a bearing interface surface41extending between a proximal edge37B (or “lower edge” if viewed vertically) and a distal edge37A (or “upper edge” if viewed vertically) spaced apart from the proximal edge37B along the longitudinal axis L. The sleeve bearing15can be shaped so that one or more bearing interface surfaces41and/or interface edges (37A,37B) of the inner sleeve37are not perpendicular to the axis of rotation or longitudinal axis L of the sleeve bearing15. In one embodiment, the bearing interface surface41may comprises edges37A,37B that form ellipse(s) tilted or tapered with respect to the longitudinal axis L of the sleeve bearing15(FIGS.2A-2E). In another embodiment, as explained below, the bearing surface(s)41may vary in a sinusoidal way to create crenulated edge(s) (seeFIG.2F). These or other shapes that result in non-circular sleeve edges37A,37B ensure that there are no points on the rotating member or impeller shaft5that remain aligned with the sleeve edges37A,37B throughout the rotation of the rotating member (e.g., shaft5), thereby minimizing the potential for thrombus formation. Whereas conventional designs leave an entire right circular cylinder section covered, the modified sleeve bearings15expose at least one point on the rotating member or shaft5throughout the entire length (or height if the sleeve bearing is viewed as being vertically oriented) of the sleeve bearing15so that the rotating member bearing interface surface41is only covered by the sleeve bearing for a portion of rotation. As such, the interfacing bearing surface(s)41may have better exchange of the lubricating layer of blood than conventional designs. Thus, in some embodiments, the distal edge37A can comprise a distal boundary of the inner sleeve37. The distal boundary (e.g., the distal edge37A) can be angled relative to the axis of rotation (which is aligned with the longitudinal axis L) such that, in a cross-section taken perpendicular to the axis of rotation L, only a portion of the distal boundary (e.g., distal edge37A) is disposed about the impeller shaft5at a selected axial location along the axis of rotation. In some embodiments, only a portion of a proximal boundary can be disposed about the impeller shaft5at a selected axial location along the axis of rotation. For example, as shown inFIG.2E, the bearing interface surface41can have exposed axial regions42A,42B comprising axial location(s) at which an exterior surface5′ (seeFIG.2A) of the impeller shaft5is cyclically exposed to blood that flows along the first flow pathway3A. In the exposed axial regions42A,42B, the bearing interface surface41is disposed about only a portion of a perimeter (e.g., circumference) of the impeller shaft5. Accordingly, when the impeller shaft5is rotated about the axis of rotation (aligned with the longitudinal axis L), an exterior surface of the impeller shaft5at a selected axial location within the exposed axial regions42A,42B is cyclically exposed to blood flow in the first pathway3A during operation of the blood flow assist system1. In some embodiments, such as that shown inFIGS.2A-2E, the inner sleeve37may be partially axially overlapping along the longitudinal axis L. As shown inFIG.2E, for example, at an example overlapping cross-sectional plane43, the bearing surface41of the inner sleeve37may be disposed completely around the exterior surface of the impeller shaft5such that the exterior surface5′ of the shaft5at that overlapping cross-sectional plane43is not exposed to blood flow in the first pathway3A. For example, in some embodiments, the sleeve bearing15can have a length along the longitudinal axis L. The inner sleeve37may be partially overlapping by an amount in a range of 1% to 50% of the length of the sleeve bearing15, in a range of 5% to 50% of the length of the sleeve bearing15, in a range of 10% to 50% of the length of the sleeve bearing15, in a range of 20% to 40% of the length of the sleeve bearing15, or in a range of 25% to 35% of the length of the sleeve bearing15(e.g., about 30% of the length of the sleeve bearing15in some embodiments). In other embodiments, such as that shown inFIG.2F, a sleeve bearing15A can comprise an inner sleeve37which may be non-overlapping such that there are no points on the exterior surface5′ of the impeller shaft5that remain covered by the bearing interface surface41during rotation of the impeller shaft37. InFIG.2F, all axial locations along the length of the inner sleeve37comprise an exposed axial region42, such that the bearing surface41of the inner sleeve37is disposed only partially about the perimeter of the impeller shaft5at all axial locations along the length of the inner sleeve37. For example, the edge(s)37A,37B can comprise non-circular edge(s) that ensures that there are no points on the rotating member or shaft5that remain aligned with the sleeve edge(s)37A,37B throughout an entire rotation of the rotating member or shaft5. The sleeve bearing15A can therefore expose at least one point on the rotating member or shaft5throughout an entire length (or height) of the sleeve bearing15A so that the exterior surface5′ of the shaft5is only covered by the inner sleeve37for a portion of rotation. Accordingly, in some embodiments the bearing edges37A,37B are shaped so that maximum length (or height) of the lower or proximal edge37B is above minimum length (or height) of the upper or distal edge37A in one or more locations around the circumference of the inner sleeve37(FIGS.2E &3F). In these embodiments, there is at least one point on the bearing interface surface41throughout the length (or height) of the bearing interface surface41that is exposed and that is not covered by the inner sleeve37of the sleeve bearing15,15A. In other words, the sleeve bearing15,15A never covers3600of the rotating member or shaft5throughout the entire length or height of the bearing interface region41. This interrupted contact of the disclosed embodiments promotes exchange of a lubricating layer blood over the entire bearing interface41and does not allow blood to stagnate or become trapped. In some embodiments, the tilt or taper of the sleeve edges37A,37B with respect to the longitudinal axis L (and the axis of rotation) may also generate or enhance fluid dynamic forces that contribute to proper bearing operation and reduce contact and wear of the bearing parts. As one non-limiting example, the fluid near the surface of a particular spot on the rotating member (e.g., shaft5) may experience increases and decreases in pressure as it moves under and out from under the inner sleeve37. These pressure changes contribute to lubricating layer formation and dispersal. The interface between the sleeve bearing15,15A and the rotating member (e.g., shaft5) is lubricated by blood. Depending on geometry, materials used, and operating conditions, this lubrication may be hydrodynamic lubrication, elastohydrodynamic lubrication, boundary lubrication, or mixed lubrication. The varying exposure of the rotating member surface and/or varying edge profile of the sleeve bearing edges37A,37B may be designed to help encourage a fluid wedge to improve lubrication. As a non-limiting example, viscous drag from a surface patch of the rotating member or shaft5may increase fluid pressure above that surface patch as it rotates under the sleeve edge(s)37A,37B. In some embodiments, the cross-section of the inner bearing surface41of the sleeve37may optionally be made non-circular to aid in wedge pressure generation, for example by varying the wall thickness of the inner sleeve37. The sleeve edge profile of the edges37A,37B may be beveled or rounded to augment this pressure generation. FIGS.2G and2Hillustrate another example of a sleeve bearing15B that has a non-overlapping design. The sleeve bearing15B comprises a crenulated bearing in which the bearing interface surface41is disposed about the longitudinal axis L in a repeating, undulating or in some cases a sinusoidal pattern44. The sinusoidal pattern44can have alternately exposed gaps about the perimeter of the impeller shaft5during rotation such that all axial locations along the length of the sleeve bearing15B are cyclically exposed to blood flow during operation of the system1.FIG.2Gshows the inner sleeve37′ can have an undulating pattern that has a plurality of (e.g., two) distal peaks61and a plurality of (e.g., two) proximal peaks62. For example, as shown inFIG.2G, the peaks61,62can be generally flat with arcuate sections64extending between the peaks61,62. A gap63between the arcuate sections64can provide for the cyclical exposure of the shaft5to blood flow. Thus, during rotation, the shaft5can transition from covered by the arcuate sections64to being uncovered and exposed through the gaps63. In other variations, there can be more than two peaks in the undulating pattern of the sleeve37′.FIG.2Hshows an inner sleeve37″ with another crenulated structure with a sinusoidal patterns, e.g., with curved peaks61,62. In some arrangements, the use of curved peaks61,61(as opposed to sharp or flat peaks) may beneficially allow for smoother flow profiles. The rotating member5and the sleeve bearings15,15A,15B may each be made of any suitable blood compatible material. As a non-limiting example, the rotating member (e.g., the impeller shaft5) may comprise a flow tube made out a biocompatible polymer, e.g., of PEEK or polyethylene and/or the sleeve bearing15,15A,15B may be made out of a metal, e.g., titanium or stainless steel. Making the rotating member or shaft5as a plastic tube may increase the range over which elastohydrodynamic lubrication is present. For example, the use of materials that enable elastic deformation of the materials during operation can provide an improved pressure profile. III. Modified Cone Bearings As shown inFIGS.1A,1C and6, the drive unit9can comprise a drive magnet17and a drive bearing18between the drive magnet17and the impeller assembly4. The drive bearing18can provide a magnetic coupling and a fluid bearing interface between the drive magnet17and a rotor assembly46that comprises the driven or rotor magnet12and an integrated rotor core8that includes the impeller shaft5and a secondary impeller7, as shown inFIG.6. In various embodiments, the drive bearing18can comprise a segmented cone bearing. Cone bearings can comprise a convex (e.g., generally conical) shaped member45seated inside a generally concave (e.g., conical) opening32or cavity of the rotor assembly46. The concave opening32can serve as a concave bearing surface sized and shaped to mate with the convex member45. The concave opening32can comprise an angled concave cavity sized to receive the convex member45. The drive unit9can comprise a convex member sized to fit within the angled cavity of the concave opening32. The bearing interface region of this bearing design can be formed by the matching surfaces of the conical or convex member45and the conical or concave opening32and the space between them. A cone bearing can provide both axial and radial confinement. The axial confinement from a single cone bearing can be in one direction only. Cone bearings with steep slopes provide relatively more radial confinement, and cone bearings with shallower slopes provide relatively more axial confinement. In some embodiments, the conical shaped member45can be modified to reduce hemolysis and/or clotting. In some embodiments, the conical member45can be truncated by a cylinder coaxial to the axis of the cone (or axis of rotation) to remove base portions of the cone. In some embodiments, the conical member45can be truncated by a plane perpendicular to the axis of the cone (creating a frustrum or a frustoconical surface). In other embodiments, the conical member45can be truncated by both a cylinder and a cone. In some embodiments, the surface of the conical opening32may be modified in a similar manner in conjunction with the conical member45or instead of the conical member45. One or the other or both of the surfaces of the conical member45and conical opening32may also be modified by holes, gaps, channels, grooves, bumps, ridges, and/or projections. Each of the surfaces of the conical member45and conical opening32may also be formed as part of other components of the pump with any overall shape. Given the general possibility of holes, grooves, channels, or gaps in either the conical member45and/or conical opening32, either of their surfaces comprise of a plurality of separate bearing surfaces in the plane of the generally conical shape defining the member45or opening32. In such a manner the opening32and/or the conical member45of the bearing pair may be formed by a plurality of separate surfaces or a segmented surface. The plurality of separate surfaces or the segmented surface that make up either the conical member45or conical opening32of the bearing pair may extend from the same component or part, or may extend from distinct components or parts. Grooves and gaps in either the conical member45and/or conical opening32may be created by removing material from a single generally conical surface or by using a plurality of separate surfaces. In some embodiments of a modified cone bearing, the conical member45of the bearing pair can comprise a convex bearing surface having a segmented frustoconical shape formed from a plurality of distally-extending segments33(FIGS.3A-3D). The distally-extending segments33can extend distally from the drive unit cover11. The segments33can be spaced apart circumferentially to define at least one channel34between adjacent segments33. Three segments33are shown inFIGS.3A-3D, but any suitable number of segments33may be utilized. As shown, the segments33can be separate components arising from a common part with gaps or channels34between them, but the segments33may also be separated by shallow or deep grooves. The gaps, grooves or channels34may follow any path. In the illustrated embodiment, the channel(s)34extend radially outward from a central recess or hollow31(also referred to herein as a void) at a location proximal a proximal end portion5B of the impeller shaft5. In some embodiments, the width and depth of any groove or channel34may vary along its path. In some embodiments, two or more channels34may join or separate. In certain embodiments, two or more channels34may join to form the central hollow area31coaxial with the axis of the conical surfaces and/or with the longitudinal axis of rotation L. In some embodiments, the conical opening32of the bearing pair can be a continuous (e.g., no gaps, channels, or grooves), generally conical surface. The relative angles of the cone bearings (e.g., the segments33) and spacing between segments33can be selected to provide a desired flow profile through the channel(s)34described herein. For example, increased spacing between the segments33can provide increased flow through the channels34. Together, the segmented conical member45of the drive bearing18with channels34between the segments33and the continuous conical opening32can serve as a “segmented cone bearing”. The channels34between the segments33allow interrupted contact between bearing surfaces similar to the interrupted contact described above for the modified sleeve bearing15,15A,15B discussed previously. This interrupted contact provides, without limitation, benefits for the segmented cone bearing analogous to those it provides to the modified sleeve bearing15,15A,15B. For example, in embodiments in which the conical opening32is part of the rotating member (e.g., the impeller shaft5), the channels34between the segments33can ensure that at least one point throughout the length or height of the conical opening32on the rotating member5is intermittently exposed by the conical opening32and not continuously covered by the bearing pair. This design promotes exchange of a lubricating layer blood over the entire bearing interface. The channels34also generate pressure changes that contribute to lubricating layer formation and dispersal as described above for the sleeve bearing15,15A,15B. In some embodiments, additional features may promote blood flow through the central hollow31and channels34of the segmented cone bearing. In some embodiments blood may flow in through the channels34and exit via the central hollow31. In other embodiments blood may flow into the central hollow31(e.g., from the secondary flow pathway3B of the impeller shaft5) and exit via the channels34. This net flow of blood through the central hollow31and channels34may serve to ensure the volume of blood in the channels34and central hollow31is constantly flowing to provide a source of fresh blood for lubricating layer exchange, to carry away heat, and/or to reduce the time that blood is exposed to conditions within the bearing region that may increase the potential for hemolysis or thrombus formation. Accordingly, in various embodiments, a concave bearing surface (which can comprise or be defined by the concave opening32) can include a fluid port to deliver blood proximally along the second flow pathway3B. The convex bearing surface (which can comprise the convex member45) can including a void (e.g., the central hollow31), which can be disposed on the longitudinal axis L. The one or more channels34can extend radially outward from the void or central hollow31. The void can be in fluid communication with the fluid port (e.g., an interface between the flow tube5and the conical opening32) so as to direct blood radially outward along at least one channel34. As shown inFIG.5A, the segments33of the convex member45can be shaped to fit within the concave bearing surface comprising the concave opening32. In some embodiments, as shown inFIGS.4A-5B, a direct secondary flow pathway3B (for example through the flow tube of the impeller shaft5shown inFIGS.4B-4D and5B) may provide proximally-flowing blood into the central hollow31. In some embodiments a secondary or second impeller7may be used to drive the secondary flow of blood through the bearing region, e.g., through the second flow pathway3B, the central hollow32, and radially outwardly through the channel(s)34. The primary impeller6of the pump and/or the additional secondary impeller7may assist in drawing the blood proximally and directing the blood radially outwardly along the channel(s)34.FIGS.4A-4Dshow the secondary impeller7that draws blood out through the channels34of the segmented cone bearing. As explained herein, the secondary impeller7and impeller shaft5can form an integrated rotor core8. The secondary impeller7can have a plurality of vanes10as explained herein to assist in directing blood radially outward through the channel(s)34of the drive bearing18. Keeping the segmented cone bearing elements or segments33near the central longitudinal axis L of the pump can have several advantages. For example, in the illustrated embodiment, the bearing elements33can be more directly exposed to the blood flow from the flow tube of the impeller shaft5along the second flow pathway3B. Further, the bearing elements33can have a smaller radius where the linear speed of the rotating member is lower. Placing the bearing elements or segments33near the axis L of the pump allows the vanes10of the secondary impeller7to be placed at a greater radius where the linear speed of the rotating member or shaft5is higher. FIG.3Dshows an embodiment in which the channels34between the segments33follow a curved path from the central hollow31. The channels34can be configured to increase flow and reduce shear forces on the blood. In some embodiments, the depth of the channels34may be varied to form a central flow diverter31aas shown in, e.g.,FIG.3E. The flow diverter31amay comprise a distally-extending projection (e.g., a cylindrical projection, a conical projection, a pyramidal projection, etc.) disposed in a central region of the bearing between the segments33. In the illustrated embodiment, the flow diverter31acan comprise a symmetrical flow diverter. The flow diverter31amay aid blood coming from the flow tube or lumen of the shaft5to transition from axial flow to radial flow to exit through the channels34. The flow diverter may optionally be manufactured as one or more separate pieces that are then attached in the central hollow31and/or channels34. In some embodiments, the flow diverter31amay comprise a generally right cylindrical shape extending distally from the bearing18. In other embodiments, the flow diverter31acan have a tapered, for example, conical, profile. The interface between the segments33of the conical member45and concave, e.g., conical, opening32of the segmented cone bearing can be lubricated by blood. Depending on geometry, materials used, and operating conditions, this lubrication may be hydrodynamic lubrication, elastohydrodynamic lubrication, boundary lubrication, or mixed lubrication. The channels34between the segments33of the conical member45of the bearing pair may promote fluid exchange so that a portion of the blood that makes up the lubricating layer between a region of the conical opening32of the bearing pair over one segment33of the conical member of the bearing pair is replaced by fresh blood in the lubricating layer that forms between that same region of the conical opening32of the bearing pair and the next segment33of the conical member of the bearing pair during rotation. The width and depth of the channels34can be altered to encourage this exchange. In various embodiments, the height and lateral spacing of the segments33can be selected to provide a desired channel depth and width. For example, a width of the channels34can be in a range of 0.02″ to 0.06″, in a range of 0.03″ to 0.05″, or in a range of 0.035″ to 0.045″ (for example, about 0.04″ in some embodiments). The surfaces of the segments33of conical member of the bearing pair along the channels34form the leading and trailing edges (as seen by a region of the conical opening32of the bearing pair) of the segments33of the conical member of the bearing pair. The distance of the leading and trailing edges from the conical opening32may also be modified to encourage fluid exchange. For example, the edges may be beveled or rounded or the distance of the leading and trailing edges may taper away or towards the surface of the conical opening32. The surfaces of the segments33of the conical member45of the bearing pair may also be modified to diverge from a perfect conical surface to promote formation of a lubricating layer. For example, one or more surfaces of the segments33of the conical member45of the bearing pair may be shaped so the normal distance to the surface of the conical opening32of the bearing pair decreases from the leading edge to the trailing edge. Such a surface contour may encourage creation of fluid wedges between the segments33of the conical member45and the conical opening32of the bearing pair for improved lubrication. In another embodiment, the surfaces of the segments33of the conical member45and conical opening32of the bearing pair may be smooth and well matched to allow a relatively thin lubricating layer of relatively uniform thickness to form. It should be appreciated that although conical member45and conical opening32are described as having a generally conical shape in some embodiments, the member45and opening32may generally be considered convex member45and concave opening32. The shapes of the convex member and the concave opening32may be any suitable mating shapes. The flow of blood driven by the secondary impeller7from the central hollow31through the channels34provides fresh blood for exchange of the lubricating layers and carries away heat in the bearing region. Both functions are important to reducing the potential for thrombus formation in the segmented cone bearing. The segments33of the conical member45of the bearing pair and the conical opening32of the bearing pair may each be made of any suitable blood compatible bearing material. As a non-limiting example, the segments33of the conical member of the bearing pair may be made out of titanium or stainless steel and/or the conical opening32of the bearing pair may be made out of PEEK or polyethylene. By making one side of the bearing pair relatively hard and the other side of the bearing pair relatively soft, the bearing pair may initially undergo boundary or mixed lubrication where surface asperities are worn to the point where the surfaces of the conical member and conical opening are smooth and well-matched enough for hydrodynamic or elastohydrodynamic lubrication to dominate. Having one side of the bearing pair be relatively softer may increase the range over which elastohydrodynamic lubrication is present. In some embodiments, the continuous, conical opening32of the bearing pair will be softer and the segmented, conical member of the bearing pair will be harder. This arrangement may help preserve special geometric features of the segments33on the conical member of the bearing pair. In some embodiments, the continuous, conical opening32of the bearing pair will be harder and the segmented, conical member45of the bearing pair will be softer. This arrangement may help preserve the surface of the opening32as a surface of rotation about the longitudinal axis L. In other variations the conical opening32and the conical member45can be of similar or even the same hardness which can provide the advantage of dimensional and shape stability throughout the operation of the pump2. In cases where hydrodynamic lubrication dominates, the normal distance between the segments33on the conical member of the bearing pair and the conical opening32of the bearing pair may be small enough to exclude red blood cells. In these cases, exchange of the lubricating layer may be less important as long as heat is still transferred away. Given sufficient exclusion of red blood cells, a continuous (e.g., without channels or grooves) conical member45of the bearing pair may still demonstrate low potential for thrombus formation as long as heat can be transferred away quickly enough. In some embodiments, this may be accomplished by eliminating or covering the channels34to form a continuous conical surface. Blood flow through the covered channels34may transfer sufficient heat from the bearing pair. The segmented bearing embodiments described above provide an additional advantage of enhancing the flexibility of the portion of the pump2in the vicinity of the pump head50. The impeller assembly4can be coupled with the drive unit9in a manner that permits some motion between the impeller assembly4and the cover11. For example, the pump2may be delivered through tortuous or curving vasculature or may be inserted from outside the patient to inside a blood vessel in tight bends. The impeller assembly4can tip toward one or more of the segments33and away from one or more segments at the conical opening32such that proximal end face of the impeller assembly is at a non-parallel angle to the distal face of the cover11. The motion may be significant compared to a mounting of the impeller assembly4on a shaft rotatably supported in a drive unit. The tipping of the impeller assembly4can occur with a flexing of the shroud16, which may be flexed in high bending stress maneuvers. In some embodiments, the shroud16is made of an elastic material, such as nitinol, such that the pump head50can flex and elastically return to an undeflected state without elongation. IV. Impeller Shaft with Flow Tube Through Primary Impeller FIGS.4A-5B and7illustrate how the flow tube of the impeller shaft5may be routed through the primary impeller6. This allows for a compact pump rotor assembly46in which the primary and secondary flow pathways3A,3B are separate and flow in the same direction through the system1as shown inFIGS.9A-9B. Having the two flow paths flow pathways3A,3B in the same direction minimizes or reduces the probability of blood recirculating through the pump. In some embodiments, the primary impeller6may also have a thrust ring14or thrust surface designed to limit axial motion in the upstream or distal direction by contacting a corresponding thrust ring or thrust surface of the sleeve bearing15. The primary impeller6may have the features described in U.S. Pat. Pub. No. 2017/0087288, incorporated by reference herein. V. Secondary Impeller As explained herein, the secondary impeller7can be disposed proximal the primary impeller6. In some embodiments, as shown inFIGS.4A-7, the secondary impeller7can comprise a flange47extending non-parallel (e.g., radially outward along the radial axis R) from the proximal end portion5B of the impeller shaft5and a plurality of vanes10on a proximally-facing surface of the flange47. The flange47can extend non-parallel and radially outward from the impeller shaft5. In some embodiments, the flange47may not extend radially beyond the shroud16. In some embodiments, the flange47may not extend radially beyond an adjacent portion of the impeller assembly4, e.g., may not extend radially beyond an integrated streamlined fairing13, discussed below. In some of these embodiments, the flange47can comprise a section of the combined rotor surface that lies in a plane perpendicular to the longitudinal axis L. As shown inFIGS.4A-4C and5A, the vanes10can extend proximally from the flange47and can have a curved profile circumferentially about the longitudinal axis L. The vanes10can be disposed in the space between the proximal face of the flange47and the distal end of the drive unit9. The concave opening32can comprise an angled cavity extending inwardly and distally relative to the generally proximally-facing surface of the flange47. The rotor magnet12can be disposed adjacent a distally-facing surface of the flange47. Each of the vanes10can have an inner end10adisposed at or near the concave opening32and an outer end10bextending radially and circumferentially outward from the inner end10aalong the flange47. The flange47can be coupled to or formed with the proximal end of the impeller shaft5. In some embodiments, for example, the flange47can be monolithically formed with (e.g., seamlessly formed with) the impeller shaft5. In other embodiments, the flange47and impeller shaft5can be separate components that are mechanically connected to one another (e.g., welded or otherwise coupled). In some embodiments, the vanes10can be monolithically formed with the proximally-facing surface of the flange47. In other embodiments, the vanes10can be mechanically connected to the proximally-facing surface of the flange47. As shown inFIG.4D, the vanes10can extend circumferentially about the longitudinal axis L in a manner such that adjacent vanes10circumferentially overlap. For example, the radially outer end10bof one vane can circumferentially overlap with, and be disposed radially outward from, the radially inner end10aof an adjacent vane. The vanes10can be prevented from contacting the drive unit9by the thrust bearing aspect of the segmented cone bearing. As the impeller assembly4rotates, the vanes10can pump blood radially out of the channels34in the segmented cone bearing and thereby increase net flow through the flow tube of the impeller shaft5and segmented cone bearing. As shown, blood can exit the flow tube of the impeller shaft5at a location proximal the primary impeller6and be driven radially out of the channels34by the vanes10. In the illustrated embodiment, five (5) vanes10are used, but it should be appreciated that fewer than five or more than five vanes10can be used. As shown inFIGS.4A,4C, and5A, the secondary impeller7can have a proximal end52at a proximal edge of the vanes10. Further as shown inFIGS.3A and3C, the drive unit9can have a distal end53at a distal end of the distally-projecting segments33. As explained above, the distally projecting convex segments33can be received within the concave opening32of the rotor assembly46. When the convex segments33are mated within the concave opening32, the distal end53of the drive unit9is distal the proximal end52of the second impeller7(e.g., distal the proximal-most end of the rotor assembly46) as shown, for example, inFIG.7. VI. Integrated Rotor Core As explained herein, in some embodiments the flow tube of the impeller shaft5, the concave opening32of the segmented cone bearing, and the secondary impeller7can be integrated into one part as an integrated rotor core8. Advantages of this approach include, without limitation, simpler assembly (as described below) and minimization or reduction of joints between parts (particularly on the inner surface of the flow tube of the shaft5). Beneficially, the primary impeller6can be disposed on (e.g., mounted on and secured to (e.g., welded to or adhered to)) the impeller shaft5, which can provide a compact design. In various embodiments, therefore, the primary impeller6and the impeller shaft5may be separate components, with the impeller6mechanically connected to the impeller shaft5. In other embodiments, the primary impeller6and impeller shaft5can comprise a unitary or monolithic structure (e.g., a molded or cast structure). Such unitary or monolithic structures can be formed without seams or joints between the components of the unitary or monolithic structure. Similarly, the secondary impeller7can be disposed on (e.g., mechanically secured to) the proximal end of the impeller shaft5. In some embodiments, the secondary impeller7can be monolithically formed with the impeller shaft5so as to form a unitary component (e.g., molded, cast, etc.). In other embodiments, the secondary impeller7and the impeller shaft5can comprise separate components. In some embodiments, the primary impeller6, the secondary impeller7(including the flange47), and the impeller shaft5can form a unitary or monolithic component or body. In some embodiments, for example, the primary impeller6, the secondary impeller7, and the impeller shaft5can be injection molded over the rotor magnet12. Where the secondary impeller5is molded over the magnet12, the surface on which the secondary impeller6is disposed can be considered a flange where the surface extends radially outward from a lumen formed in a central portion of the molded part. Beneficially, as explained above, the integrated rotor core8can form a compact structure. Rotation of the drive magnet17can impart rotation to the rotor magnet12, which is also disposed on (e.g., mechanically connected or mounted on) the impeller shaft5. Rotation of the rotor magnet12can impart common rotation to the impeller shaft5, the primary impeller6, and the secondary impeller7. VII. Example Assembled Blood Flow Assist System FIGS.7and8A-8Dshow an example schematic view various features of the blood flow assist system1described herein. The features described above may also be combined in other ways. As shown inFIGS.7and8A, the system1comprises the drive unit9with the motor30that can be sealed in the motor housing29. The drive magnet17can be rotatable by the motor30by way of a motor shaft51. The motor30can electrically connect to the power wire20. As shown inFIGS.8A and8C, the power wire20can comprise an insulating body having a central lumen55and a plurality of (e.g., three) outer lumens56A-56C extending along a length of the power wire20. The outer lumens56A-56C can be sized and shaped to receive corresponding electrodes or electrical wire (not shown) to provide electrical power to the motor30. For example, the lumens56A-56C can receive, respectively, a hot electrode or wire, a neutral electrode or wire, and a ground electrode or wire. The electrodes can extend through corresponding openings57A-57C of a motor mounting support54configured to support the motor30. The central lumen55can be sized and shaped to receive an elongate stiffening member or guidewire (not shown). The stiffening member or guidewire can be inserted into the central lumen55to help guide the pump2to the treatment location. As shown inFIG.8D, the connector23near the proximal end21of the system1can have electrical contacts58A-58C electrically connected to the electrodes in the corresponding outer lumens56A-56C. The contacts58A-58C can comprise rings spaced apart by an insulating material and can be configured to electrically connect to corresponding electrical components in the control system or console (not shown). The drive magnet17can be sealed within the drive unit9by the drive unit cover11that may also have features that act as the bearing components (e.g., the distally-projecting segments33). In some embodiments, the top distal portion of the cover11may provide the segments33forming the conical member45of the segmented cone bearing as described in this disclosure. The corresponding conical opening32of this bearing pair can be built into a rotatable piece that comprises the secondary impeller7and flow tube or impeller shaft5(together, the integrated rotor core8). The convex member45matches the contour and fits inside of the concave opening32of the rotatable piece. The channels34in the segmented cone bearing provide fluid passages for blood entering the bearing region through the flow tube5and forced out of the bearing region by the secondary impeller7. A lubricating layer of blood between the bearing surfaces of the integrated rotor core8and the matching surfaces of the cone segments33provides lubrication, reduces wear, and eases relative motion of the two components. Depending on the geometry, rotational speed, and materials making up the interface, this may be hydrodynamic, elastohydrodynamic, boundary, or mixed lubrication. The rotor magnet12of the rotor assembly46can be positioned on the integrated rotor core8to be in close proximity to the drive unit9, thereby allowing the integrated rotor core8to be magnetically coupled to the drive unit9and rotated as desired. The first or primary impeller6with an integrated streamlined fairing13can be is placed over the rotor magnet12and joined to the integrated rotor core8to at least partially form the pump rotor assembly46. The three-piece construction (integrated rotor core8, magnet, and primary impeller6with integrated fairing) can have advantages as discussed previously related to ease of construction and compact design. In some embodiments, the portion of the primary impeller6that interfaces with the flow tube5may be shaped to function as a thrust pad or to be fit with a separate thrust ring14to interface with a matching thrust pad on the sleeve bearing15that fits around the flow tube5. The rotor magnet12and primary impeller6with the fairing13may be secured to the integrated rotor core8so that the components rotate together. Alternatively, the pump rotor could be assembled from more than three pieces. In one alternative embodiment, the primary impeller6and the fairing13are separate pieces. This can allow the primary impeller6and the fairing13to be made of different materials. Alternatively, the rotor magnet12may be coated to be suitable for blood contact and may not be covered by the fairing13, but rather directly joined to the primary impeller6. Such a configuration may allow use of a larger diameter magnet (with corresponding higher torque coupling) in the same pump rotor diameter than would be possible with a magnet inside a fairing. In another alternative embodiment, a separate ring14may be added around the flow tube5above the primary impeller6. This separate ring would then serve as the thrust interface that mates with the thrust surface of the sleeve bearing. The separate ring could be made of a different material than the flow tube5or primary impeller6. The flow tube of the impeller shaft5of the pump rotor can fit inside a fixed (non-rotating) sleeve bearing15(FIG.7). As explained above, the sleeve bearing15can provide radial confinement of the impeller assembly4and the rotor assembly46. The bearing interface comprises the outer surface of the impeller shaft5and the inner surface of the sleeve bearing15. The sleeve bearing15can have a modified geometry as explained above that reduces or minimizes continuous coverage of the outer surface of the impeller shaft5and thereby reduces the potential for thrombosis. The sleeve bearing15may also optionally provide a thrust bearing surface that interfaces with the optional thrust bearing surface of the primary impeller6or optional thrust ring14. The outer bearing carrier38of the sleeve bearing15can attach to the shroud16that fits around the impeller assembly4and is attached to the drive unit cover11of the drive unit9. The connecting structure39can include an arm or arms may attach directly to the shroud16or may attach to a ring that is then attached to the shroud16to provide improved rigidity and circularity of the shroud16. The shroud16can comprise a tube with an inlet end and an outlet end. The shroud16can be placed over the various internal components that make up the pump rotor (e.g., the impeller assembly4and the rotor assembly46). The outlet end of the shroud16can be secured to the drive unit cover11of the drive unit9. The inlet side of the shroud16can be open to create an inlet port27. The front bearing is placed within the inlet port of the shroud16as described above. The outlet side of the shroud16has openings25in the surface of the shroud (outlet ports) that provide outlets for fluid driven by the primary impeller6and secondary impeller7. While some drawings of the system are shown without struts for clarity, the pump may include struts or any other securing means for securing the pump in the circulatory system, such as illustrated in U.S. Pat. Nos. 8,012,079 and 9,572,915 and U.S. Pat. Pub. No. 2017/0087288. VIII. Operation As shown inFIGS.9A and9B, various embodiments of the pump2provide two flow paths3A,3B as explained herein. The first flow pathway3A (red inFIGS.9A-9B) is driven by the primary impeller6, which draws fluid in through the inlet port27of the shroud16and directs the fluid out of the outlet ports25of the shroud16. The second flow path3B (yellow inFIG.9Aand blue inFIG.9B) is driven by the secondary impeller7, which draws fluid through the internal secondary flow path3B, e.g., a lumen or flow tube of the impeller shaft5. The internal flow path passes through the flow tube of the shaft5of the integrated rotor core8. As the fluid reaches the proximal end5B of the shaft5, some of the fluid passes through the channels34between the cone segments33and a smaller fraction passes between the matching conical surfaces of the bearing interfaces (e.g., between the convex member45and the concave opening or cavity32). The fluid can be driven radially outward by the vanes10of the secondary impeller7. Notably, flow from both flow paths can be directed from the inlet27to the outlet25in the illustrated embodiment. In other embodiments, as described herein, the flow of blood can be reversed. It shall be apparent to one of ordinary skill in the art that fluid flowing through the secondary flow path, particularly the fluid layer between the matching cone bearing interface surfaces, acts as a lubricating layer between the rotor assembly46and the fixed segments33of the segmented cone bearing. Further, the matching conical surfaces of the segmented cone bearing can provide both axial and radial confinement of the pump assembly46. IX. Advantages Various embodiments disclosed herein can have a number of unique advantages. Many of these advantages are described herein, but they are not an exhaustive list. The following are only additional non-limiting examples of advantages, one or more of which can apply to particular embodiments. a. Bearing elements (e.g., the sleeve bearing15,15A,15B and/or the segmented cone bearing) can have surface area contact rather than point contact or line contact. b. Secondary flow along the second pathway3B may be in the same direction as the primary flow pathway3A to reduce or to minimize potential recirculation of blood. c. The flow tube or shaft5, conical opening32of segmented cone bearing, and the secondary impeller7can be beneficially integrated in an integrated rotor core8. d. Attractive force of the magnetic coupling utilizes a thrust bearing in only one direction to support the external rotor; no thrust bearing may be used to prevent movement of the pump rotor8away from the drive unit9. Embodiments described herein are included to demonstrate particular aspects of the present disclosure. It should be appreciated by those of ordinary skill in the art that the embodiments described herein merely represent non-limiting embodiments of the disclosure. Those of ordinary skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments described, including various combinations of the different elements, components, steps, features, or the like of the embodiments described, and still obtain a like or similar result without departing from the spirit and scope of the present disclosure. From the foregoing description, one of ordinary skill in the art can easily ascertain the essential characteristics of this disclosure, and without departing from the spirit and scope thereof, can make various changes and modifications to adapt the disclosure to various usages and conditions. The embodiments described hereinabove are meant to be illustrative only and should not be taken as limiting of the scope of the disclosure. Conditional language, such as “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain embodiments include, while other embodiments do not include, certain features, elements, and/or steps. Thus, such conditional language is not generally intended to imply that features, elements, and/or steps are in any way required for one or more embodiments. The terms “comprising,” “including,” “having,” and the like are synonymous and are used inclusively, in an open-ended fashion, and do not exclude additional elements, features, acts, operations, and so forth. Also, the term “or” is used in its inclusive sense (and not in its exclusive sense) so that when used, for example, to connect a list of elements, the term “or” means one, some, or all of the elements in the list. In addition, the articles “a,” “an,” and “the” as used in this application and the appended claims are to be construed to mean “one or more” or “at least one” unless specified otherwise. The ranges disclosed herein also encompass any and all overlap, sub-ranges, and combinations thereof. Language such as “up to,” “at least,” “greater than,” “less than,” “between,” and the like includes the number recited. Numbers preceded by a term such as “about” or “approximately” include the recited numbers and should be interpreted based on the circumstances (e.g., as accurate as reasonably possible under the circumstances, for example ±5%, ±10%, ±15%, etc.). For example, “about 1” includes “1.” Phrases preceded by a term such as “substantially,” “generally,” and the like include the recited phrase and should be interpreted based on the circumstances (e.g., as much as reasonably possible under the circumstances). For example, “substantially spherical” includes “spherical.” Unless stated otherwise, all measurements are at standard conditions including temperature and pressure. As used herein, a phrase referring to “at least one of” a list of items refers to any combination of those items, including single members. As an example, “at least one of: A, B, or C” is intended to cover: A, B, C, A and B, A and C, B and C, and A, B, and C. Conjunctive language such as the phrase “at least one of X, Y and Z,” unless specifically stated otherwise, is otherwise understood with the context as used in general to convey that an item, term, etc. may be at least one of X, Y or Z. Thus, such conjunctive language is not generally intended to imply that certain embodiments require at least one of X, at least one of Y and at least one of Z to each be present. Although certain embodiments and examples have been described herein, it should be emphasized that many variations and modifications may be made to the humeral head assembly shown and described in the present disclosure, the elements of which are to be understood as being differently combined and/or modified to form still further embodiments or acceptable examples. All such modifications and variations are intended to be included herein within the scope of this disclosure. A wide variety of designs and approaches are possible. No feature, structure, or step disclosed herein is essential or indispensable. Some embodiments have been described in connection with the accompanying drawings. However, it should be understood that the figures are not drawn to scale. Distances, angles, etc. are merely illustrative and do not necessarily bear an exact relationship to actual dimensions and layout of the devices illustrated. Components can be added, removed, and/or rearranged. Further, the disclosure herein of any particular feature, aspect, method, property, characteristic, quality, attribute, element, or the like in connection with various embodiments can be used in all other embodiments set forth herein. Additionally, it will be recognized that any methods described herein may be practiced using any device suitable for performing the recited steps. For purposes of this disclosure, certain aspects, advantages, and novel features are described herein. It is to be understood that not necessarily all such advantages may be achieved in accordance with any particular embodiment. Thus, for example, those skilled in the art will recognize that the disclosure may be embodied or carried out in a manner that achieves one advantage or a group of advantages as taught herein without necessarily achieving other advantages as may be taught or suggested herein. Moreover, while illustrative embodiments have been described herein, it will be understood by those skilled in the art that the scope of the inventions extends beyond the specifically disclosed embodiments to any and all embodiments having equivalent elements, modifications, omissions, combinations or sub-combinations of the specific features and aspects of the embodiments (e.g., of aspects across various embodiments), adaptations and/or alterations, and uses of the inventions as would be appreciated by those in the art based on the present disclosure. The limitations in the claims are to be interpreted fairly based on the language employed in the claims and not limited to the examples described in the present specification or during the prosecution of the application, which examples are to be construed as non-exclusive. Further, the actions of the disclosed processes and methods may be modified in any manner, including by reordering actions and/or inserting additional actions and/or deleting actions. It is intended, therefore, that the specification and examples be considered as illustrative only, with a true scope and spirit being indicated by the claims and their full scope of equivalents. | 70,598 |
11857778 | DETAILED DESCRIPTION Several embodiments of the invention relate generally to the treatment of inflammatory bowel diseases and chronic inflammation of the digestive tract which may be due to an autoimmune response, including ulcerative colitis, Crohn's disease, microscopic colitis, and irritable bowel syndrome, and more specifically to systems and methods of treating inflammatory bowel diseases, including ulcerative colitis, Crohn's disease, and microscopic colitis through noninvasive peripheral nerve stimulation. Other non-limiting examples of indications for systems and methods as disclosed herein are also disclosed. Not to be limited by theory, some mechanism of actions including pathways that can be utilized by systems and methods as disclosed herein will now be described. Stimulation of peripheral nerves, such as, for example, vagus, median, radial, ulnar, tibial, sacral, or saphenous nerve can modulate autonomic tone. In some embodiments, there can be a synergistic effect of modulating both the parasympathetic and sympathetic nervous systems in activating the anti-inflammatory pathway. Activation of parasympathetic outflow can inhibit cytokine synthesis by release of acetylcholine, which bind to microphages in the blood stream to inhibit the release of TNF. Activation of the sympathetic outflow can increase local concentrations of adrenaline and noradrenaline, which can suppress inflammation further by inhibiting the release of TNF. In some embodiments and not to be limited by theory, stimulation of specific peripheral nerves such as, for example, the vagus and/or tibial nerves can modulate parasympathetic tone; the saphenous nerve, among others can modulate sympathetic tone. Some nerves, such as, for example, the median, radial, or ulnar nerves can modulate sympathetic and parasympathetic tone, depending on the parameters of the electrical waveform used to stimulate the nerve. Not to be limited by theory, stimulation of peripheral nerves can enhance maintenance of homeostasis of the autonomic nervous system. For example, a change of sympathetic outflow can trigger a subsequent change of the parasympathetic outflow to maintain homeostasis of the autonomic nervous system. Thus, acute, repeated increases in sympathetic outflow by stimulation of peripheral nerves may also increase parasympathetic outflow, which then increases release of acetylcholine and inhibition of cytokine synthesis to reduce symptoms associated with chronic inflammation. In another example, a change in parasympathetic outflow can trigger a subsequent change of sympathetic outflow. Thus, acute, repeated, increases in parasympathetic outflow by stimulation of peripheral nerves may also increase sympathetic outflow. In some embodiments, stimulation of peripheral nerves may increase or decrease sympathetic and parasympathetic activity, which increases or decreases overall autonomic tone but maintains homeostasis. In some embodiments, sympathetic and parasympathetic activity can be measured with body-worn sensors, including but not limited to pulse or heart rate, heart rate variability, electrocardiogram (ECG or EKG), electrodermal activity or galvanic skin response, blood pressure, skin temperature, pupil dilation. Pulse, heart rate, or electrocardiogram sensors can measure changes in electrical activity when worn on the hand, wrist or chest, typically with multiple leads, or can use optical sensors as part of a photoplethysmogram system that measure changes in blood flow to calculate heart rate. Electrodermal activity or galvanic skin response, signal that reflects the action of sympathetic nerve traffic on eccrine sweat glands, measures changes in electrical properties of the skin, such as resistance, in the presence of a small electrical current or differences in the electrical potential between different parts of the skin. Blood pressure measurement devices measure changes in blood pressure during cardiac activity using an inflatable cuff, typically placed on the arm, wrist or fingers. Blood pressure can also be measured with other sensors placed on the skin, such as accelerometers or strain sensors that measure displacement of blood vessels. Skin temperature can be measured with a thermistor, thermocouple, or temperature sensor placed on the skin. Pupil dilation can be measured optically with image processing of video data, where for example, the video camera is disposed in a wearable set of eye glasses. The vagus nerve is the longest nerve in the body and innervates numerous organs, including the organs within the gastrointestinal tract. The vagus nerve is the major neural pathway for the parasympathetic branch of the autonomic nervous system and is a mixed nerve that includes approximately 80% afferent fibers and 20% efferent fibers. The efferent fibers of the vagus nerve contribute to control of GI motility and secretion. Afferent vagus nerve fibers synapse bilaterally on the Nucleus Tractus Solitarius (NTS) in the dorsal medulla. The NTS sends information to efferent (e.g., 30 premotor) parasympathetic nuclei located in the medulla. These efferent regions include the dorsal motor nucleus of the vagus (DMNX) and the nucleus ambiguus (NAmb), and outflow from these regions course through efferent fibers of the vagus nerve. The NTS also transfers information to the parabrachial nucleus (PBN) in the pons, which then relays signals to the visceral primary sensorimotor cortex. Moreover, the DMNX, NAmb, and NTS further communicate with a set of brain regions including the Locus coeruleus (LC, noradrenergic), rostral Ventromedial Medulla (rVMM, serotoninergic), midbrain periaqueductal gray (PAG), hypothalamus, amygdala, and dorsomedial prefrontal and anterior cingulate cortices. Thus, the NTS connects with a diffuse system of brain regions. Thus, stimulation of vagal afferents induces vagal outflow, such as though NTS/NAmb connectivity. The auricular vagus nerve is a branch of the vagus nerve that innervates the ear in the area of the cymba concha, cavum, and/or tragus. The auricular vagus is accessible for electrical stimulation by transcutaneous or percutaneous electrodes. Generally, the GI tract is innervated by the sacral parasympathetic fibers through the pelvic nerves originating in the S2 to S4 spinal segments, and lumbothoracic sympathetic fibers originating in the T11 to L2 segments of the spinal cord. The sympathetic fibers travel through the hypogastric nerve and inferior mesenteric ganglia, while the parasympathetic fibers travel in the pelvic nerves and plexus. Any number of the foregoing nerves, among others, can be modulated with systems and methods as disclosed herein. In some cases, effective frequency band for parasympathetic modulation can be, for example, around the frequency band of 10 to 20 Hz, while the frequency band for sympathetic modulation can be, in some cases, as high as 30 Hz or as low as 5 Hz. In a further embodiment, current level can be held constant as frequency is adjusted to maximize activation, or vice versa (frequency held constant, current level adjusted). In an additional embodiment, pulse width can be held constant as frequency is adjusted to maximize activation. In an additional further embodiment, current level and frequency can be held constant as pulse width is modified to maximize efficacy. In an additional further embodiment, current level and pulse width can be held constant as frequency is modified to maximize activation. In a further embodiment targeting afferent fibers, current or voltage level may be determined by finding a minimum sensory threshold for each individual or before each stimulation session. In a further embodiment targeting efferent fibers, current or voltage level may be determined by finding a muscle contraction threshold for each nerve on each individual or before each stimulation session. In some embodiments, systems and methods can involve stimulation parameters including frequency and spatial selectivity on the surface of the distal limb to selectively modulate and balance the sympathetic and parasympathetic system. Not to be limited by theory, stimulation of a first target nerve, such as the saphenous nerve can provide sympathetic modulation of the anti-inflammatory pathway. Specifically, electrical stimulation tuned to excite large myelinated fibers in a target nerve, e.g., the saphenous nerve can provide somatic afferent input to the lumbar plexus, mediating the sympathetic input to the GI tract via the hypogastric nerve. Sympathetic nerves increase local concentrations of adrenaline and noradrenaline, which can suppress inflammation in the GI tract by inhibiting the release of TNF. Stimulation of a second target nerve, e.g., the tibial nerve can provide parasympathetic modulation of the anti-inflammatory pathway. Specifically, electrical stimulation tuned to excite large myelinated fibers in the tibial nerve provides somatic afferent input to sacral plexus, mediating parasympathetic input to the GI tract via the pelvic nerves via release of cholinergic transmitters that bind to microphages in the blood stream to inhibit the release of TNF. In general, stimulation of superficial and/or cutaneous afferent and/or efferent nerves can prevent an inflammatory response by inhibiting the nucleus of the solitary tract and vagal nuclei. Stimulation of deep afferent and/or efferent nerves can prevent an inflammatory response by exciting the arcuate nucleus-ventral periaqueductal gray-nuclei raphe pathway, inhibiting the rostral ventrolateral medulla (rVLM) and thereby the sympathetic outflow. Superficial fibers are finer (e.g., smaller diameter) afferents that relay sensory information to the superficial dorsal horn, which is a distinct region of the dorsal horn and spinal gray matter; deep fibers are thicker (e.g., larger diameter) afferents that relay sensory information to the deep dorsal horn. Transcutaneous stimulation of one, two, or more target nerves of interest, e.g., the saphenous, tibial, median and/or vagus nerve stimulation can be effective. However, in some embodiments, transcutaneous stimulation can be preferred. The feasibility of home-based stimulation has been limited by device form factor and limited programming flexibility of current devices. In some embodiments, more continuous stimulation at can potentially improve the efficacy of peripheral nerve stimulation for conditions such as, for example, inflammatory bowel disease. An implanted, transcutaneous, and/or percutaneous nerve stimulator can be efficacious and safe. Some embodiments can use frequencies of, for example, between about 1 kHz and about 100 kHz, 1 Hz and about 100 Hz, between about 1 Hz and about 50 Hz, between about 5 Hz and about 30 Hz, or between about 10 Hz and about 20 Hz stimulation for a specified period of time, such as about, at least about, or no more than about 20, 30, 40, 50 or 60, 90, 120, or 240 minutes at a sensory or sub-sensory threshold or below motor contraction threshold that is tolerable to the patient. Varying the regularity of stimulation and the frequency of the stimulation waveform may improve tolerance or efficacy in some cases. An increased frequency of stimulation may be more effective but could require a more chronic at-home portable system to provide continuous transcutaneous stimulation throughout the day. In some embodiments, stimulation of a target nerve can utilize a frequency of between about 5 Hz and about 200 Hz, between about 2 Hz and about 150 Hz, or about 2 Hz, 5 Hz, 10 Hz, 20 Hz, 30 Hz, 40 Hz, 50 Hz, 60 Hz, 70 Hz, 80 Hz, 90 Hz, 100 Hz, 110 Hz, 120 Hz, 130 Hz, 140 Hz, 150 Hz, 160 Hz, 170 Hz, 180 Hz, 190 Hz, 200 Hz, or ranges including any two of the foregoing values. In some embodiments, the target nerve is the tibial nerve or the saphenous nerve. In some embodiments, the target nerve is the median nerve or the ABVN. Stimulating at intensities below the sensory threshold or with high frequencies (e.g., between about 1 kHz to about 100 kHz) can avoid the discomfort (tingling, numbness, pain) that can be associated with peripheral nerve stimulation. Because the exact electrode position, size and surface contact can have a large effect on the stimulation level and the anatomical structures that receive the stimulation, the sensory threshold may need to be calibrated for each patient and even for each session. This calibration may be done by the user manually setting the stimulation parameters or otherwise indicating their sensory threshold. Another possible embodiment is for the device to automatically sweep through a range of stimulation parameters and the patient chooses the most comfortable set of parameter values. Another possible embodiment is for the patient to choose from among a set of previously chosen parameter values that provided effective and comfortable stimulation. The stimulation waveforms described herein can be applied continuously to target nerves, or can be provided in a manner that is adaptive in applying stimulation of various durations or by adjusting properties of the stimulation waveform to maximize efficacy, including but not limited to current or voltage amplitude, frequency, and pulse width, in response to different inputs in the system. In some embodiments, the system could include closed loop control, using one or more signals measured by the device or feedback input into the device by the patient or physician to modulate the stimulation to improve efficacy. The signals or input could include, for example, any number of the following: sensors on-board the device or sensor in other devices with data stored in a remote server via wireless communicates (e.g., data stored in a cloud server via cellular connection) or sensors in other devices in direct communication with the stimulator, either wired or wirelessly; evaluation of autonomic function, reflex loop integrity, or excitability using heart rate variability, galvanic skin response, or pupil dilation, measuring muscle sympathetic nerve activity (MSNA), and/or measuring h-reflex by sending a stimulation signal and measure response with EMG. In some embodiments, the signals or input can also include sleep sensor sets, including but not limited to accelerometers, gyroscopes, infrared based motion sensors, and/or pressure sensors under a mattress, to measure night time motion as a measure of night time bowel events. For example, patients may wear a stimulator while sleeping and therapy can be triggered by night time restlessness, which is an indicator of an upcoming event. An EEG headband could be used to measure different sleep states. Patient and/or physician input can provide feedback on the effectiveness of and/or satisfaction with the therapy into the device or into another connected device. Also, usage of the stimulation device can be tracked; and specific stimulation programs (e.g., a specified set of stimulation parameters) can be changed based on symptoms presented by the patient or outcomes of the therapy. In a further embodiment, current level can be held constant as frequency is adjusted to maximize efficacy. In an additional embodiment, pulse width can be held constant as frequency is adjusted to maximize efficacy, or vice versa (pulse width adjusted, frequency held constant). In an additional further embodiment, current level and pulse width can be held constant as frequency is modified to maximize efficacy. In an additional further embodiment, current level and frequency can be held constant as pulse width is modified to maximize efficacy. In some embodiments, a stimulator can be part of a system with sensors to assess the state of sleep and modulate stimulation based on the wearer's sleep state. Sensors could include motion sensors (e.g., body worn accelerometers and gyroscopes, or wireless motion tracking via video or infrared), temperature sensors to measure body temperature, pressure sensor under the mattress to measure movement, heart rate sensors to measure HRV, other sensors to measure sympathetic and parasympathetic activity, and/or EEG sensors to measure brain activity to assess the wearer's sleep state. For example, if night time events occur during slow wave sleep when parasympathetic activity can be elevated, stimulation parameters are modulated to affect parasympathetic activity, and vice-versa for sympathetic activity. In some embodiments, a first stimulation frequency can be provided for short term benefit, and a second stimulation frequency different (e.g., higher or lower) from the first stimulation frequency can be provided for long-term benefit. For example, 10 Hz stimulation can provide a short term benefit and 20 Hz stimulation can provide a long term benefit in some cases. As one example, 10 Hz stimulation can be provided in an initial period with the therapy (e.g., 3 weeks) for acute therapy, then 20 Hz stimulation can be provided for long term maintenance or condition therapy, or vice versa depending on the desired clinical result. In some embodiments, particular sympathetic and/or parasympathetic nervous system targets and circuits can be specifically targeted to modulate upward or downward sympathetic and/or parasympathetic nervous system activity depending on the patient's underlying autonomic nervous system activity. Utilization of data and/or sensors directly or indirectly measuring sympathetic and/or parasympathetic nervous system activity as disclosed, for example, elsewhere herein can be utilized as closed loop feedback inputs into a hardware and/or software controller to modify stimulation parameters, including on a near real-time basis. In some embodiments, the therapy (e.g., stimulation) can be applied for about, at least about, or no more than about 5 minutes, 10 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, or more a day. In some embodiments, the patient is treated nocturnally, such as during sleep, and/or during waking hours. The treatment can be repeated 1, 2, 3, 4, 5, or more times daily or weekly, every other day, every third day, weekly, or other interval depending on the desired clinical result. In some embodiments, the responsiveness could be dependent on different times of day. In some embodiments, stimulation schemes are applied to restore autonomic dysregulation based on natural diurnal patterns of sympathetic or parasympathetic activity. Treatment could also occur at irregular intervals that are human-entered or predicted by machine learning from previous days' voiding incidents. In some embodiments, a first frequency (e.g., 10 Hz or 20 Hz) therapy can be applied in the morning for acute day time relief, and a second different higher or lower frequency (e.g., 20 Hz or 10 Hz) therapy can be provided before bed for longer night time relief. In some embodiments, specific fiber types within a nerve or nerves can be selectively activated (e.g., create action potentials in such specific fiber types) to restore autonomic balance by specifically modulating sympathetic and parasympathetic limbs of the autonomic nervous system (e.g., selectively only one, or more than one of A-alpha, A-beta, A-delta, B, and/or C fibers; afferent fibers or efferent fibers, sympathetic or parasympathetic). In some embodiments, systems and methods do not stimulate or substantially stimulate A-alpha, A-beta, A-delta, B fibers, or C fibers. Some embodiments can include preferential stimulation of cutaneous fibers (e.g., A-alpha, A-beta, A-delta, and/or C; afferent or efferent, sympathetic or parasympathetic) fibers to inhibit sympathetic activity of via the stellate ganglion. Stimulation of select cutaneous fibers at the wrist can carry sensory information by way of the medial cutaneous nerve and the medial cord of the brachial plexus, which innervates the spinal cord at the level of C8-T1; stimulation in turn modulates sympathetic activity by way of the stellate or cervicothoracic ganglion, which are a collection of sympathetic nerves at the level of C7-T1. Some embodiments can include preferential stimulation of efferent or afferent fibers of vagus nerve or other peripheral nerves to modulate systemic inflammation via the cholinergic parasympathetic system. For example, efferent stimulation of the vagus nerve may facilitate lymphocyte release from thymus through a nicotinic acetylcholine receptor response, and nicotine administration can be effective for treating some cases of inflammatory bowel disease. In some embodiments, afferent or efferent nerves may be preferentially stimulated by delivering stimulation at a level above or below the motor threshold (e.g., threshold of electrical potential required to active a nerve). Not to be limited by theory, peripheral nerve fibers are classified based on the diameter, nerve conduction velocity, and the amount of myelination on the axons. These classifications apply to afferent and efferent fibers. Fibers of the A group have a large diameter, high conduction velocity, and are myelinated. The A group is further subdivided into four types: A-alpha (primary receptors of the muscle spindle and golgi tendon organ), A-beta (secondary receptors of the muscle spindle and cutaneous mechanoreceptors), A-delta (free nerve endings that conduct sensory stimuli related to pressure and temperature), and A-gamma (typically efferent neurons that control the activation of the muscle spindle) fibers. Fibers of the B group are myelinated with a small diameter and have a low conduction velocity. The primary role of B fibers is to transmit autonomic information. Fibers of the C group are unmyelinated, have a small diameter, and low conduction velocity. The lack of myelination in the C group is the primary cause of their slow conduction velocity. Additionally, for example, the vagus nerve consists of between 80-90% afferent fibers. Some embodiments can include preferential stimulation of sympathetic or parasympathetic fibers of vagus nerve or parasympathetic nerves or fibers, sympathetic nerves or fibers, and/or other peripheral nerves to modulate systemic inflammation via the cholinergic parasympathetic system or sympathetically-driven release of adrenaline and noradrenaline, respectively. Preferential stimulation can be enabled by stimulating nerves within specific ranges of one or more electrical waveform parameters, including but not limited to current or voltage level, pulse width, stimulation frequency, inter-pulse spacing, waveform shape, and/or bursting frequency. In some embodiments, afferent fibers of a mixed peripheral nerve can be preferentially stimulated by adjusting the stimulation current or voltage to a level that does not induce muscle contraction, and thus is activating little to no efferent fibers. In another embodiment, larger diameter fibers at the same level of depth as other nerve fibers may be preferentially stimulated by adjusting voltage or current levels that are high enough to activate A-fibers, but not B- or C-fibers; or activate A- and B-fibers, but not C-fibers; or activate A-alpha and A-beta fibers, and A-delta fibers but not A-gamma, B-, or C-fibers. Not to be limited by theory, chronaxie (chronaxy) is the minimum time required for an electric current, double the strength of the rheobase, to stimulate a nerve. Rheobase is the lowest current or voltage level, assuming an indefinite pulse width, required to stimulate a nerve or neuron. Chronaxie is dependent on the density of voltage-gated sodium channels in the cell, which affect that cell's excitability. Chronaxie varies across different nerves, neurons, and nerve fiber types. Stimulation pulse width (or pulse duration, depending on the shape of the waveform) can be modified to maximize activation of targeted neurons, nerves or nerve fibers based on the average chronaxie of the targeted nerve, neuron, or nerve fiber. In some embodiments, electrical pulses with the pulse width or pulse duration equal or nearly equal to the chronaxie are most effective (at relatively low amplitudes) to elicit action potentials. For example, Act fibers can be activated at short pulse durations, such as about 0.1 ms, at relatively low current amplitudes while avoiding the stimulation of C-type pain fibers (FIG.17). Typical chronaxie durations vary by fiber type, for example about 50-100 μs (Act fibers), about 170 μs (A6 fibers), and about 400 μs or greater (C fibers). In some embodiments, afferent fibers of various diameters or types can be preferentially stimulated by adjusting pulse width and/or frequency to deliver energy at a rate that maximized activation based on the average chronaxie dynamics of the specific neuron, nerve, or nerve fiber type targeted to be stimulated. In a further embodiment, current level can be held constant as pulse width and frequency are modified to maximize activation. In an additional embodiment, current level and frequency can be held constant as pulse width is modified to maximize activation. In an additional embodiment, current level and pulse width can be held constant as frequency is modified to maximize activation. In some embodiments, current level may be determined by finding a minimum sensory threshold for each individual or before each stimulation session. In a further embodiment of the system, one or more additional sensing electrodes can be placed along the pathway of the target nerve being stimulated that measure conduction velocity of the stimulated nerve to assess engagement of specific fiber types; pulse width can be modified to maximize activation of a specific fiber type corresponding to the measured conduction velocity. In some embodiments, stimulation can occur within about 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less of the chronaxie, or ranges including any two of the foregoing values. In another embodiment, afferent or efferent fibers can be preferentially stimulated by adjusting pulse width. For example, not to be limited by theory, shorter pulse widths (e.g., less than 200 μs) can preferentially activate efferent fibers, and longer pulse widths (e.g., greater than 500 μs) can preferentially activate afferent fibers. In some embodiments, the pulse width could be between about 50 μs and about 400 μs, such as about 50 μs, 100 μs, 150 μs, 200 μs, 250 μs, 300 μs, 350 μs, 400 μs, 450 μs, 500 μs, or ranges including any two of the foregoing values. In a further embodiment, current level can be held constant as pulse width is modified to maximize activation. In an additional embodiment, frequency can be held constant as pulse width is modified to maximize activation. In an additional further embodiment, current level and frequency can be held constant as pulse width is modified to maximize activation. In a further embodiment targeting afferent fibers, current or voltage level may be determined by finding a minimum sensory threshold for each individual or before each stimulation session. In a further embodiment targeting efferent fibers, current or voltage level may be determined by finding a muscle contraction threshold. In a further embodiment of the system, one or more additional sensing electrodes can be placed along the pathway of the target nerve being stimulated that measure conduction velocity of the stimulated nerve to assess engagement of specific fiber types; pulse width can be modified to maximize activation of a specific fiber type corresponding to the measured conduction velocity. In some embodiments, an electrical stimulation and sensing device can comprise a stimulation pulse generator configured to deliver an electrical stimulation to a patient, the electrical stimulation comprising a stimulation pulse delivered to a peripheral nerve of the patient via a first peripheral nerve effector placed on the patient's skin adjacent to the peripheral nerve. The first electrical stimulation pulse can be delivered to activate the peripheral nerve and evoke an action potential. The device can further comprise a sensor configured to measure the action potential evoked in the peripheral nerve by the first electrical stimulation pulse via a second peripheral nerve effector placed on the patient's skin, and a processor configured to adjust one or more parameters of the electrical stimulation, including but not limited to current or voltage intensity, pulse width (or pulse duration), and frequency, based on a predetermined feature of the sensed action potential, including but not limited to nerve conduction velocity. In some embodiments, the sensing peripheral nerve effector can be placed orthodromically or antidromically with respect to the stimulation adjacent to the stimulated peripheral nerve. In an additional embodiment, the system can have a single sensing effector placed in a location that can measure nerve activity of the first stimulated peripheral nerve and the second stimulated peripheral nerves, only when the two nerves are not stimulated simultaneously. For example, a single sensing effector could be place adjacent to the brachial plexus to measure stimulated nerve activity of both the radian and medial nerves, only when they are not stimulated simultaneously. In a further embodiment, an electrical stimulation and sensing device can comprise a stimulation pulse generator configured to deliver an electrical stimulation to a patient. The electrical stimulation can comprise a first stimulation pulse delivered to a first peripheral nerve of the patient via a first peripheral nerve effector placed on the patient's skin adjacent to the first peripheral nerve and a second stimulation pulse delivered to a second peripheral nerve of the patient via a second peripheral nerve effector placed on the patient's skin adjacent to the second peripheral nerve. The first electrical stimulation pulse can be delivered to activate the first peripheral nerve and evoke a first action potential and the second electrical stimulation pulse can be delivered to activate the second peripheral nerve and evoke a second action potential. The device can further comprise a first sensor configured to measure the first action potential evoked in the first peripheral nerve by the first electrical stimulation pulse via a third peripheral nerve effector placed on the patient's skin, and a second sensor configured to measure the second action potential evoked in the second peripheral nerve by the second electrical stimulation pulse via a fourth peripheral nerve effector placed on the patient's skin, and a processor configured to adjust one or more parameters of the electrical stimulation, including but not limited to current or voltage intensity, pulse width (or pulse duration), and frequency, based on a predetermined feature of the sensed action potential. In some embodiments, the sensing peripheral nerve effectors can be placed adjacent to the stimulated peripheral nerve either orthodromically or antidromically with respect to the stimulating peripheral nerve effector. In some embodiments, the device further comprises an additional set of sensors configured to measure action potentials of the stimulated nerve both orthodromically and antidromically with respect to the stimulating peripheral nerve effector(s). In a further embodiment, the device includes a processor configured to adjust one or more parameters of the electrical stimulation based on one or more predominant features of nerve conduction velocity derived from the sensed action potential. The derived features can be associated with a preferential activation of specific fiber type(s). In another embodiment, afferent or efferent fibers can be preferentially stimulated by adjusting pulse width. For example, not to be limited by theory, shorter pulse widths (e.g., less than 200 μs) can preferentially activate efferent fibers, and longer pulse widths (e.g., greater than 500 μs) can preferentially activate afferent fibers. In a further embodiment, current level can be held constant as pulse width is modified to maximize activation. In an additional embodiment, frequency can be held constant as pulse width is modified to maximize activation. In an additional further embodiment, current level and frequency can be held constant as pulse width is modified to maximize activation. In a further embodiment targeting afferent fibers, current or voltage level may be determined by finding a minimum sensory threshold for each individual or before each stimulation session. In a further embodiment targeting efferent fibers, current or voltage level may be determined by finding a muscle contraction threshold. In a further embodiment of the system, one or more additional sensing electrodes can be placed along the pathway of the target nerve being stimulated that measure conduction velocity of the stimulated nerve to assess engagement of specific fiber types; pulse width can be modified to maximize activation of a specific fiber type corresponding to the measured conduction velocity. In some embodiments, peripheral nerve effectors can be positioned on the patient's skin such as on the medial side of the forearm as to stimulate the median cutaneous nerve but not stimulate or not substantially stimulate the median, radial, or ulnar nerves, or at least stimulate the medial cutaneous nerve preferentially. In some embodiments, the lateral cutaneous nerve and/or musculocutaneous nerve, or specific fibers thereof can be preferentially or specifically stimulated. In some embodiments, only a single type of nerve fiber is activated, while other types are not activated. Selective activation of various nerve fiber types can be accomplished in various ways. In some embodiments, stimulation parameters such as pulse width of a biphasic square wave (shown schematically inFIG.1) can be controlled to selectively activate specific fiber types (e.g., without activating other fiber types). For example, pulse widths of about 50-100 μs can selectively stimulate larger A-alpha fibers; pulse widths of about 150-200 μs can selectively stimulate smaller A-delta fibers; and pulse widths of about 300-400 μs can selectively stimulate even smaller C fibers. In some embodiments, a device can include electrodes configured to selectively stimulate superficial nerve fibers (e.g., fibers closer to the surface of the skin) by aligning the electrodes along the length of the nerve axon.FIG.2Apreviously described schematically illustrates an example on the wrist. In some embodiments, electrodes of a device can be selectively configured to selectively stimulate deep nerve fibers (e.g., fibers further away from the surface of the skin) by transversely aligning the electrodes across the limb.FIG.2Bpreviously described schematically shows an example on the wrist. In some embodiments, stimulation systems and methods can be configured to increase blood flow at a target region (e.g., in the gut) to improve clearance of inflammatory biomarkers (e.g., cytokines). In some embodiments, noninvasive neuromodulation for autonomic regulation for IBD and other diseases can be performed. Autonomic nervous system imbalance with a dominant activation of the sympathetic nervous system and inadequate parasympathetic tone may have a key role in the pathogenesis of various immune related disorders including IBD. In some embodiments, increased local blood flow can improve cytokine (or other inflammatory marker) clearance from the GI tract. Anatomical studies have shown large amounts of sympathetic adrenergic/noradrenergic fibers innervate both into the dome region of the follicles where fibers are in direct contact with lymphoid cells and in the lamina propria where fibers are mainly associated with blood vessels. Non-invasive nerve stimulation can regulate blood flow changes and inflammatory marker clearance. In some embodiments, tibial stimulation can tap into the enteric nervous system via the pelvic nerve, modulating transmucosal fluid fluxes, local blood flow and other functions. In some embodiments, systems and methods as disclosed herein can increase blood flow to a target region of the anatomy by at least about, about, or no more than about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or more, or ranges including any of the aforementioned values. The enteric nervous system (ENS) is a major division of the autonomic nervous system with a mesh-like system of nerves that regulates the gastrointestinal (GI) tract, which includes the splanchnic organs like stomach, small intestines, and large intestines. Splanchnic circulation, or circulation of the GI tract, is composed of gastric, small intestinal, colonic, pancreatic, hepatic, and splenic circulations, arranged in parallel with one another. The three major arteries that supply the splanchnic organs, celiac and superior and inferior mesenteric, give rise to smaller arteries that anastomose extensively. The circulation of some splanchnic organs is complicated by the existence of an intramural circulation, and redistribution of total blood flow between intramural vascular circuits may be as important as total blood flow. Numerous factors influence the splanchnic circulation, including external factors such as activity of the autonomic nervous system, the state of the cardiovascular system, and concentrations of neurohormones circulating in the blood. Blood flow rate in vessels is governed primarily by the arterial-to-venous pressure gradient and the mechanical resistance to the flow of blood along the vessel. Small changes in the vascular smooth muscle tone can alter the diameter of the vessel. The vascular resistance is inversely related to the fourth power of the radius of the vessel, thus a small change in internal diameter will produce a large change in resistance and blood flow. For example, a small decrease in diameter of a blood vessel would produce a large increase in resistance and thus a large decrease in blood flow, and vice-versa. Blood vessels that provide the greatest changes in resistance to blood flow, like small arteries and arterioles, are densely innervated by the sympathetic nervous system. The splanchnic organs are innervated by the autonomic nervous system, including the sympathetic and parasympathetic limbs. Activation of parasympathetic fibers modulate secretion and motility that lead to metabolic and mechanical changes that affect blood flow. Postganglionic sympathetic fibers innervate and act directly on the vascular smooth muscle, and activation leads to changes in vessel diameter, tone, and thus blood flow. Generally, stimulation of the sympathetic fibers increases vascular tone and decreases blood flow to the splanchnic organs. Acute sympathetic stimulation contract venous smooth muscle and expels a large volume of pooled blood from the splanchnic venous system and into systemic circulation. Sustained sympathetic stimulation or activity leads to a decrease in blood flow mainly in the superior mesenteric and hepatic arteries. Additionally, sympathetic stimulation causes the release of neurohormones like epinephrine and norepinephrine that also alter vascular resistance and decrease blood flow. Insufficient blood flow within the enteric system can also lead to the further release of inflammatory cytokines, including interleukin 1, tumor necrosis factor, interleukin 6, and interleukin 8, and others. Thus, mechanisms that increase splanchnic circulation can improve symptoms associated with immune related disorders, including inflammatory bowel diseases, by reducing the release of inflammatory cytokines or other markers and/or by increasing the clearance of inflammatory cytokines or other markers in circulation via the liver, spleen, and/or kidneys. Not to be limited by theory, stimulation of a first target nerve, such as the saphenous nerve can provide sympathetic modulation to reduce sympathetic tone and increase blood flow. Specifically, electrical stimulation tuned to excite large myelinated fibers in a target nerve, e.g., the saphenous nerve can provide somatic afferent input to the lumbar plexus, mediating the sympathetic input to the GI tract via the hypogastric nerve. Stimulation of a second target nerve, e.g., the tibial nerve can provide parasympathetic modulation of the enteric nervous system. Specifically, electrical stimulation tuned to excite large myelinated fibers in the tibial nerve provides somatic afferent input to sacral plexus, mediating parasympathetic input to the GI tract via the pelvic nerves to modulate secretion and motility that lead to metabolic and mechanical changes that increase blood flow. In another embodiment, stimulation of a first target nerve, such as the auricular vagus nerve, can provide modulation of vagal tone and reduction of sympathetic activity to increase blood vessel dilation, modulate secretion and motility, and thus increase blood flow. In another embodiment, stimulation of a first target nerve, such as the sacral parasympathetic fibers of the pelvic nerves, originating in the S2 to S4 spinal segments, can be stimulated directly by electrodes placed over the sacral region. Electrodes can be transcutaneous, percutaneous, and/or implanted. Stimulation of a second target nerve, such as the lumbothoracic sympathetic fibers originating in the T11 to L2 segments of the spinal cord, can be stimulated directly by electrodes placed over the lumbar region.FIG.3schematically illustrates layers of the gastrointestinal tract, as well as certain autonomic innervation. In some embodiments, systems and methods can include monitoring skin turgor and/or electrodermal activity as a marker of inflammation and hydration status using, for example, a galvanic coupling method. The etiology and pathogenesis of inflammatory bowel disease (IBD) has not yet been elucidated, yet many environmental factors are suspected to contribute to the development of IBD, including diet and hydration levels. Studies have shown negative correlations between total fluid consumption in a person's diet and the risk for developing IBD. Thus, preventing dehydration in people with or at risk of developing IBD can be important for preventing or alleviating symptoms by reducing the expression of inflammatory markers, such as cytokines. Some embodiments can involve a closed-loop approach to treating IBD and other diseases that involves using a galvanic coupling method to identify changes in hydration status with immediate or near real-time feedback to the subject to encourage hydration while also administering therapy via electrical stimulation. The system may target other nerves or dermatomes that modulate the parasympathetic and/or sympathetic nervous system, including but not limited to, the median nerve, ulnar, or radial nerve in the wrist, the lumbothoracic region, the sacral region, the stomach, and/or the foot including the bottom of the foot. Dehydration can be assessed by various methods, including but not limited to a skin turgor assessment, which evaluates the level of skin elasticity, and galvanic skin response, which measures skin impedance by passing small amount of current between two electrodes. Some embodiments describe a system that incorporates a wearable sensor to measure body hydration levels, store this data over time, provide feedback to the wearer and/or adjust stimulation parameters to improve therapeutic benefit of the stimulation. In one embodiment, the wearable system includes a sensor for detecting galvanic skin response, memory for storing data from the sensor, a computational unit for assessing sensor data, a feedback device, such as a display or haptic motor to display sensor output or trigger the wearer, and/or controller unit to control output of stimulation. The galvanic skin response sensor can be embedded in a device that is placed transcutaneously on the surface of the skin in locations including, but not limited to, the wrist, arm, leg, chest, or abdomen. The sensor may be disposed in an adhesive patch placed anywhere on the body, or disposed in an enclosure that houses all parts of the system. In some embodiments, the sensor may be a separate device from the stimulation and is in wireless or wired communication with the stimulator. In some embodiments, the sensor data is transmitted to an external computational device or transmitted wirelessly to a database (e.g., the cloud) for further processing. In one embodiment, the wearable system includes a sensor for detecting skin elasticity. Skin elasticity can be measured mechanically by stretching the skin and measuring the resistive force during stretching. A device may house effector end points connected to electric motors that stretch the skin in a linear or rotational motion and measure the resistive force due to the stretching. The ratio of the amount of skin stretch to resistive force can be calculated to assess skin elasticity. FIG.4schematically illustrates a skin stretch sensor4000that moves effectors4002in a linear motion on the skin S to measure displacement and force (e.g., elasticity) which can be utilized to correlate to the subject's hydration status. FIG.5schematically illustrates a skin stretch sensor that moves effectors in a rotational motion on the skin S to measure displacement and force which can be utilized to correlate to the subject's hydration status. In another embodiment, the sensor for detecting skin elasticity can be an adhesive patch with strain sensors that measure strain due to skin stretch during normal or directed motions. Strain sensors measure strain of an object by measuring the change in electrical resistivity of the sensor as it is deformed, and strain is a measure of deformation representing the displacement between particles in the body relative to a reference length. Strain measurements can be stored over time to assess the state of skin elasticity and correlate the measure to the wearer's level of dehydration.FIG.6schematically illustrates a strain gauge circuit6000that can include an etched metal foil6002, backing material6004, solder terminals6006, and connecting wires (leads)6008. Arrows illustrate schematically a direction of strain. A quarter bridge circuit6010can be used to measure a resistance change in the strain gauge6000. In some embodiments, not to be limited by theory, alternating bursting stimulation on two or more different nerves, e.g., the medial, radial, and/or ulnar nerves can prevent or reduce an inflammatory response by having a synergistic effect that increases input to stellate ganglion via the brachial plexus to inhibit sympathetic activity or modulate vagal tone via the carotid sinus nerve. In some embodiments, a system can include a plurality of stimulators that communicate with each other wirelessly and provided a synchronized continuous or patterned stimulation, and/or synchronize the timing of different stimulations. In some embodiments, multiple stimulators may be in electrical connection with multiple electrode pairs to stimulate multiple nerves simultaneously. Each stimulator in the system can communicate with each other via a wired or wireless connection. Multiple stimulators can provide synchronized stimulation to the multiple nerves. Stimulation may be, for example, burst, offset, or alternating between the multiple nerves. In some embodiments, a stimulation system with a plurality of stimulator housings that can include or be operably connected to a patch having electrodes and a skin-contacting surface. Each individual stimulator can be placed, for example, transcutaneously just below the knee and/or just above the ankle as illustrated. The stimulators can be placed sufficient to stimulate the saphenous and/or tibial nerves. The stimulators can be placed in some cases between the knee and the ankle, such as in the proximal calf (such as within the most 25% proximal section of the calf, or between the 25% and 50% most proximal section of the calf), distal calf (such as the most 25% distal section of the calf or between the 25% and 50% most distal section of the calf), or combinations thereof. The stimulators can be physically discrete for each other, or combined into a single housing such as a calf band or other form factor as described elsewhere herein. In some embodiments, the electrodes, constructed from an adhesive hydrogel, are disposed in the housing of the device allowing the device to adhere to the wearer's skin. In other embodiment, the electrodes are dry or non-adhesive and are disposed in the device with a strap to securely connect to electrodes to a limb, such as on the wrist or ankle. In some embodiments, a system can include a plurality of stimulators that communicate with each other wirelessly and provided a synchronized continuous or patterned stimulation. In some embodiments, multiple stimulators may be in electrical connection with multiple electrode pairs to stimulate multiple nerves simultaneously. Each stimulator in the system can communicate with each other via a wired or wireless connection. Multiple stimulators can provide synchronized stimulation to the multiple nerves. Stimulation may be, for example, burst, offset, or alternating between the multiple nerves.FIG.6Aschematically illustrates a stimulation system6001with a plurality of stimulator housings6000that can include or be operably connected to a patch6002having electrodes6004and a skin contacting surface. Each individual stimulator6006(shown positioned to stimulate the tibial nerve TN) or stimulator6008(shown positioned to stimulate the saphenous nerve SN) can be placed, for example, transcutaneously just below the knee and/or just above the ankle as illustrated. The stimulators can be placed sufficient to stimulate the saphenous and/or tibial nerves. The stimulators can be placed in some cases between the knee and the ankle, such as in the proximal calf (such as within the most 25% proximal section of the calf, or between the 25% and 50% most proximal section of the calf), distal calf (such as the most 25% distal section of the calf or between the 25% and 50% most distal section of the calf), or combinations thereof. The stimulators can be physically discrete for each other, or combined into a single housing such as a calf band, wrist band, in-ear electrode or other form factor as described elsewhere herein. In some embodiments, dry electrodes can be utilized, such as dry electrodes that include a conductive backing layer (e.g., a metal foil material, such as disposed on a flexible polymer substrate) and a skin contact layer disposed on the conductive backing layer, that can include for example a polymer, plastic, or rubber material, and a conductive filler material (e.g., powder, fine particulate material, metal, carbon, mixtures thereof, or porous material treated with a conductive coating) dispersed substantially evenly throughout the silicone, plastic, or rubber material. In some embodiments, the skin contact layer has a skin facing surface that is not coated with a hydrogel or liquid. In some embodiments, the dry electrodes can be as disclosed in PCT App. No. PCT/US2017/040920, filed on Jul. 6, 2017, hereby incorporated by reference in its entirety. In some embodiments if the electrodes are sticky, as shown in the embodiment ofFIGS.6B and6C, a device in the form of a bandage can be made, which circumferentially or non-circumferentially envelop a portion of a body part, such as an extremity. The strip can be any shape, including an annular, square, rectangular, triangular, or other shape. In some cases, the electronics can be located inside a removable housing that can be removably attached at site from the entire device when the disposable is thrown away.FIG.6Bis a bottom view, whileFIG.6Cis a top view of the device. In some embodiments, median, radial, and/or ulnar stimulation can be combined for a synergistic effect at the brachial plexus. The median, radial, and ulnar nerves innervate different levels of the spinal cord at the brachial plexus, with pathways that proceed to different target locations and organs. Some embodiments can provide timed stimulation, either simultaneously or with a delay, to the median, radial, and/or ulnar nerves to control targeting within the brachial plexus to provide a synergistic effect of neural activation at the brachial plexus, which leads to the stellate ganglia and the sympathetic chain. This synergistic effect can provide an advantage of greater therapeutic benefit with less discomfort and less current (e.g., less power for longer battery life). Timing of the stimulation may be simultaneous, or with a delay to account for differences in conduction velocities for the different nerves such that the signals reach the brachial plexus at the same time. Not to be limited by theory, but simultaneous or near simultaneous activation of the brachial plexus can enhance stimulation through the pathway to the stellate ganglia, and increase the effect (e.g., inhibition) of the sympathetic nervous system. For example, the average conduction velocities of sensory nerves of radial, median, and ulnar nerves are about 51 m/s, 60 m/s, and 63 m/s respectively. Based on variation in nerve length from the wrist to the brachial plexus from 1st percentile female to 99th percentile male, this would require a delay in stimulation between the median and radial nerves of about 1.3 to about 1.7 milliseconds, between median and ulnar of about 0.3 and about 0.4 ms, and between radial and ulnar of about 1.6 ms and about 2.1 ms. In some embodiments the delay in stimulation between a first nerve and a second nerve can be between about 0.3 ms and about 1.7 ms, or between about 0.2 ms and about 2.0 ms, between about 1.2 ms and about 2.1 ms, or between about 1 ms and about 2 ms. Lower threshold stimulation on the median, radial, and/or ulnar nerves in combination can advantageously require lower threshold stimulation on the individual nerves with a resultant synergistic effect at the brachial plexus. In some embodiments, a system could include a nerve conduction velocity measurement by applying a stimulation source on a distal portion of the nerve(s) and a measurement electrode on a proximal portion of the nerve(s) to measure an individual's nerve conduction velocities and modify the timed delay based on the individualized measurements. In some embodiments, a system could include an electrode configuration to stimulate nerves (e.g., radial, median, and/or ulnar) in an alternating pattern that could be rhythmic or pseudorandom. For rhythmic alternating patterns, the alternating frequency can be in a range from 1-100 Hz, which has been shown improve efficiency of therapy by promoting plasticity of corticospinal circuits. In some embodiments, a device embodiment could include an electrode configuration to alternate stimulation of nerves (e.g., radial, median, and/or ulnar) and adjust stimulation parameters (e.g., stimulation frequency, alternating frequency, duration of stimulation, stimulation time of day) based on an assessment of autonomic balance, for example, by measuring heart rate variability (HRV) and analyzing sympathovagal balance as a the ratio of absolute low frequency (LF) to absolute high frequency (HF) power, or LF/HF of measured HRV as noted elsewhere herein. Sympathetic and parasympathetic activity can be measured through several methods, including microneurography (MSNA), catecholamine tests, heart rate, HRV, or galvanic skin response. HRV can provide a quick and effective approximation of autonomic activity in the body. HRV can be determined by analyzing the time intervals between heartbeats, also known as RR intervals. Heart rate can be accurately captured, for example, through recording devices such as chest straps or finger sensors. The differences between successive RR intervals can provide a picture of one's heart health and autonomic activity. Generally speaking, healthier hearts have more variability between successive RR intervals. This interbeat data can also be used to denote an individual's sympathetic and parasympathetic activity levels. Through frequency-domain analysis, heartbeat frequencies can be separated into distinct bands. High-frequency signals (˜0.15-0.4 Hz) can almost exclusively reflect parasympathetic activity, and low-frequency signals (˜0.04-0.15 Hz) can represent a mixture of sympathetic and parasympathetic activity. Therefore, taking the ratio of high frequency (HF) to low frequency (LF) signals can yield an approximation of one's sympathetic tone. In some embodiments, HRV can be analyzed, for example, under time domain, geometric domain methods in addition to frequency domain methods. In some embodiments, increased heart rate variability can signify increased parasympathetic response and/or decreased sympathetic response. Decreased heart rate variability can signify decreased parasympathetic response and/or increased sympathetic response. In some embodiments, a system can sense an increase or decrease in HRV of about or more than about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 75%, 100%, or more over a baseline value (or target desired HRV value) and institute a change in one, two, or more stimulation modality parameters accordingly. In some embodiments, the one, two, or more stimulation modalities can be configured to modulate, such as increase or decrease stimulation to one or more nerves (e.g., peripheral nerves) associated with the sympathetic and/or parasympathetic nervous system, and a response to therapy can be confirmed by sensing an increase or decrease in parasympathetic or sympathetic tone, including but not limited to increase or decrease in HRV, changes in high frequency content of HRV, and changes in the ratio of high frequency and low frequency content of HRV. In some embodiments, balance of parasympathetic and sympathetic activity of the inflammatory response reflex loop can be assessed with frequency analysis of heart rate variability measured with pulsed plethysmography with an LED light source and optical sensor disposed in the device that measures fluctuations in light level due to blood flow that target one of the major blood vessels around the knee, which could include one or more of the following, femoral, popliteal, tibial, posterior tibial, anterior tibial, and/or descending genicular arteries or veins, or vessels around the wrist, or in the arm or neck or ear in other embodiments. In some embodiments, heart rate could be measured using accelerometer-based sensors or with electrical-based sensors, similar to single or multiple-lead ECG monitors. A large source of error in optical measurements of heart rate is motion artifacts due to relative motion between the optical sensor and the blood vessel being measured. In some embodiments, the optical heart rate sensor has an adhesive on the side of housing that contacts the wearer's skin to reduce relative motion between the sensor and the target blood vessel. In some embodiments, one, two, or more additional sensors are disposed in the device, including electrical sensors in contact with the wearer's skin to measure cardiac activity or pressure sensors to measure changes in blood vessels, to be used in combination with an optical sensor to improve the fidelity of heart rate measurement. In some embodiments, the system and device have memory and a processor to extract RR intervals from sensor data, calculate variability of RR intervals, transform data into frequency domain, and calculate high frequency signals, low frequency signals, and the ration of the high frequency and low frequency signals. In some embodiments, the heart rate sensor can store collected data for specified time periods to gather adequate data for heart rate variability calculation. Specified time period can range in some cases from 1-60 seconds, and may extend to 10 minutes or more. In some embodiments, electrodermal activity, also known as galvanic skin response or skin conductance response, for example, can be measured using sensors, such as electrodes. Galvanic skin response is the change of the electrical resistance of the skin caused by emotional stress, and measurable with, e.g., a sensitive galvanometer. Not to be limited by theory, skin resistance varies with the state of sweat glands in the skin. Sweating is controlled by the sympathetic nervous system, and skin conductance can be an indication of psychological or physiological arousal. If the sympathetic nervous system is highly aroused, then sweat gland activity also increases, which in turn increases skin conductance. In this way, skin conductance can be a measure of emotional and sympathetic responses, which can be measured, and the feedback data can be sent to the controller, which will in turn modulate stimulation to, for example, decrease sympathetic nervous system activity. Other nonlimiting parameters associated with sympathetic and/or parasympathetic nervous system activity that can be sensed include, for example, sweating during particular times of the day and/or night, sleep states as detected, for example, by an EEG headband (to determine when sympathetic and/or parasympathetic activity is particularly high or low, and potentially correlating a sleep state such as stage 1, 2, 3, 4, or REM with nocturia), and/or motion. In some embodiments, a diagnostic and/or combination diagnostic/stimulation device can be configured to measure a person's heart rate and galvanic skin response for improved estimation of the person's autonomic activity. In some embodiments, a wearable device, such as a wrist-worn device can include both electrodermal activity (EDA) sensors and optical heart rate sensors. This combination of data can in some embodiments advantageously and synergistically provide improved estimation of sympathetic and parasympathetic activity than a single measure alone. In some embodiments, the system can include multiple sensors to measure electrodermal activity in conjunction with heart rate and HRV. Data from the multiple sensors can be analyzed by a hardware or software processor and combined to provide a more accurate estimation of sympathetic and/or parasympathetic activity. In some embodiments, the EDA and HR sensors can be disposed in a wrist-worn device that communicates via a wired or wireless connection to the stimulator or to send data to a centralized remote server (e.g., the cloud). Stimulation parameters, nerve target locations (e.g., tibial and/or saphenous nerves for example) or dosing regimen (e.g., duration or frequency of stimulation sessions) could be adjusted based on estimations of sympathetic and/or parasympathetic activity. Adjustments could be made in real-time, or in subsequent stimulation sessions. In some embodiments, stimulation frequency can be adjusted to either increase or decrease autonomic activity modulated by a single specific nerve, or multiple nerves. For example, in some embodiments, relatively low frequency stimulation of a target nerve (e.g., below a threshold value, e.g., about 5 Hz) can potentially inhibit the nerve and thus decreases sympathetic activity, while higher frequency stimulation (e.g., above a threshold value, e.g., about 5 Hz) can potentially excite the nerve and thus increases sympathetic activity. The same effect can occur with the same or other target nerves to regulate parasympathetic activity. In other words, in some embodiments, relatively low frequency stimulation of the target nerve (e.g., below a threshold value, e.g., about 5 Hz) can potentially inhibit the nerve and thus decreases parasympathetic activity, while higher frequency stimulation (e.g., above a threshold value, e.g., about 5 Hz) can potentially excite the nerve and thus increases parasympathetic activity. Not to be limited by theory, depending on the stimulation parameters for example, in some cases stimulating the target nerve can increase or decrease either sympathetic activity, parasympathetic activity, or both. In some embodiments, stimulation of the saphenous nerve can affect sympathetic activity, and stimulation of the tibial nerve can affect parasympathetic activity. In some embodiments, any form of stimulation as disclosed herein can be utilized to apply stimulation to one, two, or more acupuncture points. In some embodiments, the acupuncture points to be stimulated could include any one, two, three, four, five, six, seven, eight, nine, ten, or any other number of the following: BL18 (Ganshu), BL23 (Shenshu), BL27 (Xiaochangshu); BL28 (Pangguangshu); BL32 (Ciliao); BL33 (Zhongliao); BL53 (Baohuang); CV2 (Qugu); CV3 (Zhongji); CV4 (Guanyuan); CV5 (Shinen); CV6 (Qihai); GB34 (Yanglingquan); KI7 (Fuliu); KI10 (Yingu); LR1 (Dadun); LR2 (Xingjian); LR8 (Quan); N-BW-38 (Xiajiaoshu); SP6 (Sanyinjiao); SP9 (Yinlingquan); and/or ST28 (Shuidao). In some embodiments, the points to be stimulated include BL18, BL23, BL28, and CV2. In some embodiments, the points to be stimulated include ST28, SP6, BL23, BL28, BL32, BL33, BL53, CV3, and N-BW-38. In some embodiments, the points to be stimulated include SP6, BL23, BL27, BL28, BL33, and CV4. In some embodiments, the points to be stimulated include SP9, LR1, LR2, CV4, and CV6. In some embodiments, the points to be stimulated include SP6, SP9, BL23, CV3, and CV6. In some embodiments, the points to be stimulated include SP9 and GB34. In some embodiments, the points to be stimulated include SP9, KI7, KI10, and LR8. In some embodiments, the point to be stimulated is either CV5 alone or BL39 alone, or a combination thereof. Other permutations of stimulation points are also possible, depending on the desired clinical result.FIGS.6D-6Hillustrate non-limiting examples of potential acupuncture points that can be stimulated, in accordance with some embodiments of the invention. The system may run on a selection of pre-specified programs that vary stimulation parameters and target one or more nerves individually or in combination to improve symptoms of inflammatory bowel disease or another disease in a specific patient. Alternatively, the system may use closed loop feedback or statistical analyses or machine learning techniques that utilize a number of parameters including: the subject's symptomatic history, including voiding events, or manually entered bowel event indicated on board the device or a secondary device; direct detection of sympathetic and parasympathetic tone in the GI tract or general circuitry, including HRV and galvanic skin response; previous usage of device, e.g., purely sympathetic excitation may be enhanced by brief periods of parasympathetic balance; medical history; medication usage; activity or steps. Some embodiments of a system could centrally store data from a plurality of sensors worn by multiple wearers on a remote server system (e.g., the cloud), along with other relevant demographic data about each wearer, including age, weight, height, gender, ethnicity, etc. Data collected from multiple wearers can be analyzed using standard statistical analysis, machine learning, deep learning, or big data techniques, such as a logistic regression or Naive Bayes classifier (or other classifiers), to improve prediction of inflammation by determining correlations between biological measures and other recorded symptom events and inflammation events. These correlations can be used to set parameters of the stimulation waveform applied by the stimulation device, determine best time to apply stimulation therapy, and/or adapt the stimulation waveform applied by the therapy unit in real time. In some embodiments, one, two, or more sensors can be housed in the device to collect, store, and analyze biological measures about the wearer including, but not limited to, motion (e.g., accelerometers, gyroscopes, magnetometer, bend sensors), ground reaction force or foot pressure (e.g., force sensors or pressure insoles), muscle activity (e.g., EMG), cardiovascular measures (e.g., heart rate, heart rate variability (HRV), photoplethysmography (PPG), or ventricular and/or atrial dyssynchrony using electrodes to measure ECG and/or heart rhythm abnormalities), skin conductance (e.g., skin conductance response, galvanic skin response), respiratory rate, skin temperature, pupil diameter, and sleep state (e.g., awake, light sleep, deep sleep, REM). Using standard statistical analysis, machine learning, deep learning, or big data techniques, such as a logistical regression or a Naïve Bayesian classifier, these biological measures can be analyzed to assess the wearer's activity state, such as sedentary versus active, level of stress and the like, which in turn, can serve as a predictor of inflammation and/or GI symptoms. FIG.6illustrates an embodiment of a system for treating inflammatory bowel diseases using a wearable therapy device. As described above, the therapy device may include two parts, a band500and a therapy unit502. A base station600, which may replace the charger in the kit described above, can be used to both charge the therapy device and to receive and transmit data to the therapy device and to the cloud602. Communication between the base station600and the therapy device can be wireless, such as through Bluetooth and/or Wi-Fi, and communication between the base station600and the cloud602can be through a cellular network, using a 3G or 4G connection, or through a wired connection to the internet, using DSL or cable or Ethernet, for example. A physician or other user can view and/or retrieve data stored on the cloud602using an online portal or a physician web portal604. In addition, the physician can prescribe and/or modify a treatment regimen on the therapy unit502through the cloud602and base station600using the web portal604. In some embodiments, the base station600is used to receive and transmit relatively large amounts of data that may require a high bandwidth, such as the transmission of raw data from the therapy device, which may be about or at least about 10 to 100 Mb/day, or about or at least about 10, 20, 30, 40, or 50 Mb/day. In some embodiments, the data may be stored in memory in the base station600and transmitted at another interval, such as weekly or twice weekly, with a scaling up of the bandwidth of transmission. The high bandwidth transmission of the raw data can occur daily while the therapy device is being charged, such as at night during a regular charging period. In some embodiments, the raw data can be processed by the cloud and/or the physician into processed data and sent back to the therapy device. In some embodiments, the system may optionally include a portable computing device606, such as a smart phone or tablet, to provide a secondary display and user interface for the patient and to run applications to more easily control the therapy device and view the raw and processed data. The portable computing device can be used to make patient or physician adjustments to the therapy device, such as adjusting the stimulation parameters and dosing, and can receive device state data from the therapy device, which includes data relating to the device, such as when the device was used, errors, therapy parameters such as amplitude and when they were set and delivered. In some embodiments, the portable computing device606can receive processed data from the cloud602through a cellular network and/or through an internet connection using Wi-Fi, for example. FIG.7illustrates the various components that can be included in a therapy unit700, band702, and base station704. These components are described in detail above and also below as non-limiting embodiments. For example, the therapy unit700includes one or more indicators706, which can be LEDs, and a user interface708, which can be push buttons, for example. The therapy unit700can also have a stimulator710with stimulation electronics and may include the capability to measure current and voltage. The therapy unit700can also have a battery712, which may be rechargeable and can be recharged using charging circuitry714, which may be inductive. The therapy unit710may further include a processor716and memory718to store and execute programs and instructions to accomplish the functions described herein. The therapy unit710may also include sensors720, such as blood pressure sensors, and a communications module722, which may be wireless and can communicate with the base station704and/or a secondary display/computing device. The band702can have electrodes724and may also include memory to store identification information or may include some other form of identifier726as described herein. The base station704can include charging circuitry728, which may also be inductive and can transmit power to the complementary charging circuitry714on the therapy unit700. The base station704can also have a processor and memory for storing and executing instructions and programs. The base station704can further include a communication module732, which may be cellular, to communicate with the cloud, and another communication module734, which may be wireless and used to communicate with the therapy unit. In some embodiments, the device can be a biological sensor, such as a heart rate or respiratory monitor worn on the body, which could include an integrated nerve stimulator. In some embodiments, the nerve stimulator and sensor device can be separate devices that communicate wirelessly. In some embodiments, the device can measure a biological measurement over the course of minutes, hours, days, weeks and/or months to determine whether the patient's condition is increasing, decreasing, or staying the same. In some embodiments, the measurements are time averaged over a window, which can be days, weeks, or months. In some embodiments, a sensor, such as a motion sensor, IMU, or GPS, can be used to detect patient activity, which can affect other measurements. In some embodiments, the sensor can be an electrode that measures galvanic skin response, which can be correlated to stress, a known trigger for inflammatory bowel disease, inflammation, or symptoms caused by other inflammatory conditions. In some embodiments, measurements are collected at the same time each day with the same conditions to improve measurement consistency and to reduce variability. In some embodiments, the stimulator is applied to one wrist or arm or ear to stimulate one peripheral nerve in the arm, such as the median nerve or ABVN, or specific nerve location, such as an acu-pressure point or meridians. The number of episodes of symptoms such as inflammatory bowel disease could be detected in various ways to control the stimulation applied by system and devices. In some embodiments, the patient can enter events related to symptoms of inflammatory bowel disease, including but not limited to fecal voiding events, urgency events, incontinence events, or abdominal pain on a mobile device. In some embodiments, location services on the device, such as GPS, can detect when the person has entered a building or bathroom. Information regarding bowel voiding can be combined in some embodiments with an understanding of the amount of food and fluids a person has consumed in order to better apply a desired amount of treatment. For example, in days where more food and drink were consumed by an individual, more bowel voiding would be expected.FIGS.6I-6Kschematically illustrates flow charts incorporating a stimulation protocol, according to some embodiments of the invention, including a sample diagnosis, prescription, and usage workflow. A physician can diagnose a patient with a disorder, such as IBD or another disease (box1734,1742) as disclosed elsewhere herein for example. The physician can utilize an assessment kit (box1736,1744); and the patient can track symptoms on a software app or other log (box1738,1746), as well as via sensors, e.g., HRV or others as disclosed herein. The physician can then review the data and prescribe an appropriate therapy (box1740,1748). A customized IBD kit can then be provided to the patient (box1750,1758), who can apply the neuromodulation device (box1752,1760), which can be in the form on a disposable electrode patch (box1754,1762) in some cases. The times, amounts, and types of food ingested by a patient over the day, and/or symptom tracking (box1756,1764) can be recorded manually or electronically, such as in a software application. Knowing when and what was consumed can be used to predict when and how much a person's bowels should be emptied and the amount of treatment can be applied accordingly. The information regarding the processing time of a certain amount of food in the human body could be used to anticipate through literature studies with additional information from the patient (such as gender, weight, and height). This processing and consolidation of data to anticipate the amount and timing of treatment necessary can be done within a single device or utilizing another separate device, for instance a mobile phone. In this manner, stimulation can be applied accordingly based on the number of episodes a person experiences. One method of recording the times and types of food and drink consumed is through a journal or diary, for example on a smartphone, tablet, or other device. In some embodiments, the systems and methods use one or more sensor devices to measure or detect breathing activity, heart rate, or blood flow pulsatility over time, then based on a predetermined relation of the measured activity, a stimulator is instructed to provide neurostimulation to at least one, two, or more of the nerve targets described. In some embodiments, the stimulated nerve targets may selectively activate the parasympathetic nervous system, the sympathetic nervous system, or both. FIGS.6L-6Nillustrate non-limiting embodiments of potential electrode placement locations for nerve stimulation. The sensor systems, including those disclosed herein can communicate via wires or wirelessly to the stimulator5002. Placement of the electrodes of the tibial stimulator could vary with electrodes5000placed along the tibial nerve (FIG.6L), at the bottom of the foot (FIG.6M), or on either side of the ankle or attached to a stimulator (FIG.6N). In some embodiments, disclosed herein are systems and methods for stimulating a plurality of nerves for the treatment of conditions including but not limited to IBD. Stimulation of 2, 3, or more nerves, such as the saphenous and tibial nerve could be used for the treatment of conditions such as IBD. Dual nerve stimulation can in some cases synergistically increase the effectiveness of therapy by combining synergistically the effects of, for example, saphenous and tibial nerve stimulation. In some embodiments, including those disclosed in connection withFIGS.6O and6Pbelow, the system can be configured to independently control stimulation of a first target nerve (including stimulation parameters such as frequency and others listed herein) and a second target nerve respectively. In other words, the first target nerve and the second target nerve can be stimulated with either the same or different parameters, and can be stimulated simultaneously or in alternating or other fashion. In some embodiments, the stimulation systems can include a plurality of independent stimulation circuits, or a common circuit with a controller configured to switch stimulation parameters for one, two, or more nerves. In some embodiments, as illustrated schematically inFIG.6O, a system1400can utilize three electrodes: a first electrode1404positioned over a first nerve, e.g., the tibial nerve1402, a second electrode1406positioned over a second nerve, e.g., the saphenous nerve1408, and a third electrode1410positioned, for example, on the outer side of the leg, opposite to the first two electrodes1404,1406. This third electrode1410would serve as a common cathode for the other two electrodes1404,1406. The three electrodes1404,1406,1410can be oriented in such a way that the electric fields between each of the first two electrodes1404,1406and the common cathode1410pass through the tibial nerve1402and saphenous nerve1408, respectively. Another possible configuration shown inFIG.6Putilizes four electrodes. Similar to the embodiment illustrated inFIG.6O, three channels are used: a first targeting the tibial nerve1402, a second targeting the saphenous nerve1408, and one acting as a common cathode1410. However, the cathode in the electronics is split between two common electrodes1411,1413, each serving as a cathode electrode for the other two electrodes1404,1406. Thus, a first electrode1404is positioned over the tibial nerve1402with a first cathode electrode1411positioned directly below it and a second electrode1406is positioned over the saphenous nerve1408with a second common electrode1413positioned directly below it. Each electrode pair1404,1411and1406,1413can be oriented in such a way that the electric field between the two electrodes (the electrode over the nerve and its respective common electrode) passes through the intended nerve (e.g., tibial or saphenous). In some embodiments, stimulation can be timed to changes in heart rate and/or rhythm, as a transient tachycardia arises with every breath. A heart rate sensor could detect this rhythmic tachycardia and generate a control signal to trigger stimulation. Heart rate or rhythm sensor could be multiple or single-lead ECG sensors, wrist worn optical heart rate sensor, also known as photoplethysmograms (PPG). In some embodiments, disclosed herein is a wearable device to deliver patterned transcutaneous electrical stimulation to peripheral nerves. In some embodiments, patterned stimulation can include one or more techniques, including but not limited to synchronizing stimulation to a phase or feature of the cardiac cycle, synchronizing stimulation to specific features of neural oscillations such as power or frequency, and alternating stimulation bilaterally across two or more nerve targets. Synchronizing stimulation to neural oscillations can promote biofeedback for the patient by promoting and reinforcing alpha wave activity in the brain, which has been shown to improve symptoms associated with inflammation. The device can include any number of a controller; a first peripheral nerve effector, comprising at least one stimulation electrode configured to be positioned to transcutaneously modulate a first afferent peripheral nerve; and at least one biomedical sensor or data input source configured to provide feedback information. The feedback information could include physiologic parameters including vital signs, measures of sympathetic or parasympathetic activity, and other information disclosed herein. The controller can include a processor and a memory for receiving the feedback information from the sensor, that when executed by the processor, cause the device to adjust one or more parameters of a first electrical stimulus based at least in part on the feedback information; and/or deliver the first electrical stimulus to the first afferent peripheral nerve to the first peripheral nerve effector. The first electrical stimulus can include patterned, such as burst (e.g., theta burst) electrical stimulation configured to induce neural plasticity and reduce symptoms due to inflammatory diseases. The stimulation can be continuous, intermittent, or intermediate theta burst stimulation in some embodiments. The device can also be configured to deliver a priming electrical nerve stimulation signal prior to the first electrical stimulation signal, which can be a non-theta burst stimulation signal. The device can further include a second peripheral nerve effector, including at least one stimulation electrode configured to be positioned to transcutaneously modulate a second afferent peripheral nerve, and is configured to deliver a second electrical nerve stimulation signal transcutaneously to the afferent peripheral nerve of the user. The signal can include, for example, electrical theta burst stimulation. In some embodiments, inhibition of the inflammatory response by stimulation may also reduce the symptoms of other diseases, including but not limited to, rheumatoid arthritis or other non-limiting examples disclosed herein, or acute or chronic injury/trauma. Direct stimulation could be applied to the joint in some cases. Stimulation could be gated based on swelling measured in the joint, pain or activities of daily living scores, and the like. In some embodiments, inflammation can be assessed in a patient by a sensor or plurality of sensors to quantify the level of inflammation. Inflammation is a central component of innate (non-specific) immunity. In generic terms, inflammation is a local response to cellular injury that is marked by increased blood flow, capillary dilatation, leucocyte infiltration, and the localized production of a host of chemical mediators, which serves to initiate the elimination of toxic agents and the repair of damaged tissue. Termination of inflammation is an active process involving cytokines and other anti-inflammatory mediators, particularly lipids, rather than simply being the switching off of pro-inflammatory pathways. Inflammation can be assessed non-invasively in some cases by ultrasound molecular imaging with a dual P- and E-selectin-targeted contrast agent. Inflammation can also be assessed by a range of blood cellular markers (e.g. total leukocytes, granulocytes and activated monocytes) and soluble mediators (cytokines and chemokines (TNF, IL-1, IL-6, IL-8, CC chemokine ligand 2 (CCL2), CCL3, CCL5), adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin), adipokines (adiponectin) and acute-phase proteins (ESR, CRP, serum amyloid A, fibrinogen)). The markers can be assessed via periodic blood draws, or indwelling biosensors in some cases. In some embodiments, disclosed herein are wearable systems and methods that can utilize transcutaneous sensory stimulation in the form of a burst pattern, e.g., a theta burst pattern to improve inflammatory bowel disease, and/or a variety of other inflammatory conditions, including but not limited to those disclosed herein. Noninvasive peripheral nerve theta burst stimulation may be effective in some cases in driving cortical or spinal plasticity more efficiently than continuous stimulation to reduce symptoms and improve an individual's quality of life. In some embodiments, the stimulation involves patterns of electromagnetic stimulation of peripheral nerves. The patterned stimulation could be a bursting stimulation, such as an on/off pattern that repeats at regular intervals (e.g., on for 10 ms, off for 20 ms, etc.), or non-burst patterned stimulation that can be more complex in some embodiments, such as a stochastic pattern or a sinusoidal envelope for example. The electromagnetic stimulation could include, for example, electrical energy, mechanical energy (e.g., vibration), magnetic energy, ultrasound energy, radiofrequency energy, thermal energy, light energy (such as infrared or ultraviolet energy for example), and/or microwave energy, or combinations thereof. In some embodiments, the stimulation is limited to only electrical energy (e.g., no magnetic or other types of energy are applied). The peripheral stimulation could include transcutaneous, percutaneous, and/or implanted stimulation. Some embodiments can involve rhythmic bursting on the median, radial, and/or ulnar nerves to balance sympathetic and parasympathetic tone. Not to be limited by theory, alternating bursting stimulation on the medial, radial, and/or ulnar nerves can prevent inflammation by having a synergistic effect that increases input to the nucleus of the solitary tract (NTS) in the medulla and influences the activity of NTS neurons projecting to the inhibitory vagal efferent neurons of the dorsal vagal nucleus (DVN) and nucleus ambiguous (NA). Alternating bursting stimulation of the medial, radial, and/or ulnar nerves may also excite NTS neurons sending excitatory projections to the caudal ventrolateral medulla (CVLM). The CVLM inhibits the rostroventrolateral medulla (RVLM) which is the primary source of excitatory drive to sympathetic preganglionic neurons in the intermediolateral cell column (IML) of the spinal cord. This inhibition could decrease sympathetic activity. This stimulation pattern could improve sympathovagal balance to reduce inflammation. Interferential Stimulation can be utilized in some cases. In some embodiments, a device can include a plurality of electrodes, e.g., four electrodes to where a first electrode pair stimulates at a specified first frequency, f Hz, and a second electrode pair stimulates at a second frequency slightly higher or lower than the first pair, f±x Hz. In some embodiments, the second frequency can be different from that of, but within about ±20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the first frequency. In some embodiments, stimulation does not involve interferential stimulation. In some embodiments, the electrode pairs can be spaced on the limb, as shown inFIG.7A, such that the stimulation waveforms combine at a specific crossing point to target deep fibers in the limb by creating an interferential pattern of stimulation with a frequency that is the difference between the frequencies of the two waveforms, e.g., x Hz. The stimulation frequency can be varied depending on the desired clinical result. In some embodiments, a relatively higher frequency, such as between about 10 Hz and about 33 Hz, between about 10 Hz and about 30 Hz, between about 10 Hz and about 20 Hz, or between about 20 Hz and about 33 Hz, or about or at least about 10 Hz, 15 Hz, 20 Hz, 25 Hz, 30 Hz, 33 Hz, 35 Hz, or more can be used. The stimulation frequency can also be tailored to the specific nerve targeted. In some embodiments, lower stimulation rates such as 2 Hz can have an excitatory effect. However, in some embodiments, a frequency of about or no more than about 10 Hz, 9 Hz, 8 Hz, 7 Hz, 6 Hz, 5 Hz, 4 Hz, 3 Hz, 2 Hz, or 1 Hz can be utilized. In some embodiments, the stimulation frequency could be in the kHz range, such as, for example, between about 1 kHz and about 100 kHz, such as between about 10 kHz and about 50 kHz. The stimulation could be regular, irregular, or random in some embodiments. In some embodiments, a frequency or a plurality of frequencies for one, two, or more nerves could be selected from, for example, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50 Hz. In some embodiments, two or more of the same or different frequencies or frequency ranges can be applied to the same or different target nerves. In some embodiments, waveforms including those described herein can be modified over time in order to minimize certain effects, such as habituation. One way of decreasing habituation is to modify the frequency, pulse width, or amplitude of the stimulation. For instance, randomizing or pseudo-randomizing parameters such as, for example, the frequency or pulse width can reduce habituation. Using a Gaussian distribution for randomization can be effective in some cases, and used in such waveforms as stochastic waveforms. Another way of reducing habituation is to the lower the frequency below a certain threshold, such as, for example, no more than about 60 Hz, 55 Hz, 50 Hz, 45 Hz, or 40 Hz, in which humans tend not to habituate. Bursting to improve efficiency or efficacy of stimulation can also be used. Not to be limited by theory, bursting at a rhythmic pattern can improve efficiency of therapeutic benefit by promoting plasticity of corticospinal circuits. Rhythmic or pseudorandom bursting patterns can prevent habituation of nerves, which occurs with constant stimulation. Some embodiments can involve stimulation patterns (e.g., bursting, pulse patterns, random, pseudo-random, or noise) selected to improve the efficiency and efficacy of stimulation. In some embodiments, as illustrated schematically inFIG.7B, an array of electrodes can be aligned along the axon of the nerve that stimulate adjacent pairs of electrodes at regular intervals such that specific points along the nerve are stimulated at a velocity of, for example, between about 1 cm/s and about 10 cm/s. In some embodiments, stimulation can be provided in a bursting pattern where the bursting can either be rhythmic (e.g., at regular intervals) or pseudorandom. In some embodiments, a stimulation waveform can be provided that combines infraslow stimulation frequency (0.01-0.1 Hz) with a higher frequency stimulation (1-200 Hz), or lower frequency (1-200 Hz) with very high frequencies (1000-10 kHz). In some embodiments, the stimulation involves non-invasive transcutaneous electrical patterned or burst stimulation of peripheral nerves, including afferent and/or efferent nerves. Not to be limited by theory, but burst stimulation of peripheral nerves can unexpectedly result in one or more of the following compared with conventional or continuous stimulation: greater efficacy; greater plasticity; increased tolerance or tolerability; reduced effects of habituation; increased comfort; and/or reduced treatment time required to achieve the same beneficial effects. Burst stimulation of peripheral nerves, including afferent nerves, can in some cases deliver a more efficacious therapy by remotely accelerating plasticity of one or more central nervous system (e.g., brain and/or spinal cord) circuits, in other words creating plasticity in neural circuits for a period of time that is far longer than the duration of the stimulation session, such as, for example, about or at least about 6 hours, 12 hours, 24 hours, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 9 months, 12 months, 18 months, 24 months, 36 months, or even longer. Peripheral stimulation in some cases can be more convenient and comfortable for the user than central stimulation (e.g., transcranial stimulation and/or spinal stimulation) and can be more suitable for home and ambulatory use. In some embodiments, the burst stimulation includes theta burst stimulation. Theta burst stimulation (TBS) is a patterned form of repetitive stimulation that uses high frequency pulses separated by varying inter-burst intervals. Originally used for the induction of long term potentiation in hippocampal learning and memory research, theta burst stimulation in the form of repetitive magnetic stimulation (rTMS) has been demonstrated to noninvasively induce plasticity in humans in the motor, sensory and visual cortex. Depending on various parameters including the duration and continuity of stimulation, a long term potentiation or depression (LTP/LTD) like effect can be observed, which are surrogate measures of synaptic efficacy. The number of sessions and the spacing interval between individual sessions of stimulation can also have an effect on the duration of the induced response. The level of muscle relaxation before or during stimulation can also affect the resulting direction or amplitude of plasticity induction suggesting that homeostatic mechanisms are in place that adjust the threshold for plasticity depending on prior synaptic activity. The effective modulation of nervous system plasticity demonstrated with theta burst stimulation can have great potential for the treatment of various neurologic disorders, and can have an effect on other central neural circuits. In some embodiments, theta burst stimulation can take the form of intermittent theta burst stimulation (iTBS), continuous theta burst stimulation (cTBS), and intermediate theta burst stimulation (imTBS). Non-limiting examples of iTBS, cTBS, and imTBS are illustrated inFIG.8. Each illustrate examples of TBS including a burst of 3 stimuli at 50 Hz (20 ms between each stimulus) which was repeated at inter-burst intervals of 200 ms (5 Hz). In the iTBS example pattern, an about 2 second train of TBS is repeated about every 10 seconds for a total of 190 seconds (600 pulses). In the imTBS example pattern, an about 10 second train of TBS is repeated every 15 seconds for a total of 11 seconds (600 pulses). In the cTBS pattern, a 40 second train of uninterrupted TBS is given (600 pulses). The burst pattern (or a combination of two or more burst patterns) can be selected depending on the desired clinical result. In some cases, cTBS can be inhibitory, iTBS can be excitatory, and imTBS can be neither excitatory nor inhibitory, but this may be varied depending on the parameters. In some embodiments, inhibitory stimulation of a first nerve (e.g., the median, ulnar, or radial nerve) can be used alone or in combination with excitatory stimulation of a second nerve (e.g., the median, ulnar, or radial nerve), such as to restore or improve sympathetic and parasympathetic balance. In some embodiments, inhibitory or excitatory stimulation of a nerve can be controlled by adjusting frequency or pulse width of the stimulation waveform. FIG.9Aillustrates a flow chart of an example of a therapeutic protocol for treating IBD or another disorder, according to some embodiments of the invention. In some embodiments, sympathetic and parasympathetic activity can be assessed during a baseline period (e.g., from about 24 hours to about 30 days in some embodiments) using sensors that measure heart rate and heart rate variability, and/or electrodermal activity1600. Heart rate and HRV can be measured in various ways and sympathetic and/or parasympathetic overactivation or underactivation assessed1702, including an optical sensor in a wrist worn device, a chest strap or patch that measures changes in electrical activity, a pulse oximeter worn on the finger, and the like. Sympathetic and parasympathetic activity can also be measured using electrodermal activity sensors as described elsewhere herein. In some embodiments, a single device can include both an optical heart rate sensor and electrodermal activity sensors to improve the estimation of sympathetic and parasympathetic activity. If sympathetic overactivation is identified1704(e.g., from HRV and/or other autonomic measurements), saphenous nerve stimulation can be initiated (e.g., saphenous nerve stimulation alone without tibial nerve stimulation). If parasympathetic overactivation is identified1706, tibial nerve stimulation can be initiated (e.g., tibial nerve stimulation alone without saphenous nerve stimulation). After a period (e.g., about 1-4 weeks) of stimulation, a controlled measure of autonomic function, e.g., HRV, can be reassessed1708. In some embodiments, sympathetic and parasympathetic activity are assessed prior to initial stimulation to select specific nerve targets, stimulation waveforms, stimulator parameters, or dosing of stimulation (e.g., time of day, duration of stimulation, number of times per day or week). In other embodiments, a default stimulation is applied in a trial fashion, and only if a person does not respond to treatment is sympathetic and parasympathetic activity assessed. In some embodiments, sympathetic and parasympathetic activity are assessed over a single day or over multiple days during an initial period of treatment to measure any changes in autonomic activity. In some embodiments, IBD or other symptoms may be tracked by the patient, either manually or on paper, onboard the stimulation device, or on an external computing device such as a smartphone, tablet, laptop, etc. to be correlated with parameters, such as HRV and changes in autonomic activity, for example. As illustrated inFIG.9B, a default therapy is prescribed (e.g., 10 Hz saphenous nerve stimulation)1710, and parameters such as HRV are measured (e.g., during the first 1-4 weeks of therapy), and symptoms tracked1712. If there is an acceptable response to therapy, it can be continued as prescribed1714. If no response to therapy and parasympathetic overactivation is determined1716, a second therapy can be added (e.g., 10 Hz tibial nerve stimulation). If there is no response and sympathetic overactivation is determined, therapy can be switched to an alternative therapy1718(e.g., 20 Hz saphenous nerve stimulation). Parameters such as HRV are measured, and symptoms tracked during a subsequent therapy period1720. As illustrated inFIG.9C, a default therapy is prescribed (e.g., 10 Hz saphenous nerve stimulation)1722, although parameters such as HRV need not necessarily be measured. If there is an acceptable response to therapy, it can be continued as prescribed1724. If no acceptable response to therapy, parameters such as HRV can be measured1726. If no response to therapy and parasympathetic overactivation is determined1728, a second therapy can be added (e.g., 10 Hz tibial nerve stimulation). If there is no response and sympathetic overactivation is determined, therapy can be switched to an alternative therapy1730(e.g., 20 Hz saphenous nerve stimulation). If no response, parameters such as HRV are measured, and symptoms tracked during a subsequent therapy period1732. In some embodiments, if a person does not respond to therapy, a number of parameters can be altered to modify therapy, including but not limited to increasing or decreasing, or otherwise changing any number of the following: duration of session (e.g., 20-120 minutes); number of sessions per day or week (e.g., 2 times per day to 3 times per week); time of day or night of stimulation; stimulation frequency; bursting or other stimulation pattern (including bursting frequency); nerve target (e.g., saphenous or tibial); and/or stimulation amplitude. In some embodiments, therapy can have an unexpectedly synergistic effect when combined with one, two, or more pharmacologic agents. Anti-inflammatory drugs are often the first step in the treatment of inflammatory bowel disease. Anti-inflammatories include corticosteroids and aminosalicylates, such as mesalamine (Asacol HD, Delzicol, others), balsalazide (Colazal) and olsalazine (Dipentum). Immunosuppressant drugs can also be utilized in therapy. Some examples of immunosuppressant drugs include azathioprine (Azasan, Imuran), mercaptopurine (Purinethol, Purixan), cyclosporine (Gengraf, Neoral, Sandimmune), tacrolimus, and methotrexate (Trexall). One class of drugs called tumor necrosis factor (TNF)-alpha inhibitors, or biologics, works by neutralizing a protein produced by the immune system, such as with a monoclonal antibody. Examples include infliximab (Remicade), adalimumab (Humira) and golimumab (Simponi). Other biologic therapies that may be used are natalizumab (Tysabri), vedolizumab (Entyvio) and ustekinumab (Stelara). Antibiotics may be used in addition to other medications or when infection is a concern—in cases of perianal Crohn's disease, small intestinal bacterial overgrowth (SIBO), and others for example. Frequently prescribed antibiotics include a quinolone such as ciprofloxacin (Cipro), metronidazole (Flagyl), vancomycin (Vancocin), and rifaximin (Xifaxan), among others. In some embodiments, the effector can be excitatory to the nerve. In other embodiments, the effector can be inhibitory to the nerve. In some embodiments, the system can be used to excite the nerve during some portions of the treatment and inhibit the nerve during other portions of the treatment. In several embodiments, over-the-counter agents such as loperamide and bismuth compounds (e.g., loperamide hydrochloride and bismuth subsalicylate) work in a synergistically beneficial manner with the neuromodulation (e.g., neurostimulation) embodiments described herein. In some embodiments, the use of neuromodulation (e.g., neurostimulation) as described herein results in a greater half-life of pharmacological agents and/or a reduced dosage. This can be particularly helpful to manage the side effects of these agents, which can be exacerbated in patients with sensitive digestive tracts. Dosages when combined with neurostimulation are reduced, in some embodiments, by at least 5%, 10-20%, 20-40%, 40-60% or more (including overlapping ranges therein) as compared to dosages needed to achieve a similar effect in the absence of neurostimulation. In one embodiment, the combination of neurostimulation and a pharmacological agent allows the pharmacological agent to work more quickly (e.g., 20-60% more rapidly, or higher). Some embodiments, as shown inFIGS.11,12A-12Dfor example, are related to a device and system that provides peripheral nerve stimulation, targeting individual nerves. Some embodiments involve a device and system10that allows customization and optimization of electrical treatment to an individual. In particular, the device10described can be configured for electrical stimulation of the median, radial, ulnar, auricular vagus, peroneal, saphenous, tibial and/or other nerves or meridians accessible on the limbs, head, neck, or ears, for treating inflammatory bowel diseases. Targeting those specific nerves and utilizing appropriately customized stimulation surprisingly results in more effective therapy. In some embodiments, therapy can reduce or eliminate the number, dose, and/or frequency of medications that a patient may need to take for their inflammatory bowel disease or other medical condition, advantageously reducing side effects/potential toxicities. In some embodiments, therapy can have an unexpectedly synergistic effect when combined with one, two, or more pharmacologic agents. Afferent nerves in the periphery or distal limbs, including but not limited to the median nerve, are connected via neural pathways to sensitized peripheral and central neurons connected to the nucleus tractus solitarus; vagus nerve; or other regions of the brain and brain stem associated with regulation of inflammation, as illustrated inFIGS.10A-10B. FIGS.11,12A-12Dillustrate an embodiment of a device and system10that provides transcutaneous peripheral nerve stimulation, targeting individual nerves, to treat inflammatory bowel disease or other inflammatory conditions. In some embodiments, the device10is designed to be worn on the wrist or arm; leg; or in or around the ear. In some embodiments, electronics located in a watch-like housing12measure heart rate, motion, and/or electrodermal activity, and also generate an electrical stimulation waveform. Electrical contacts in a band14and/or housing12transmit the stimulation waveform to the disposable electrodes16. The location of the contacts in the band12is arranged such that one or more specific nerves are targeted at the wrist, such as the median, radial, and/or ulnar nerves on the arm; tibial, saphenous and/or peroneal on the leg; auricular branch of the vagus nerve or trigeminal nerve in or around the ear. The electronics housing12also can have a digital display screen to provide feedback about the stimulation and sensor measurements, derived characteristics and history to the wearer of the device. In some embodiments, the treatment device10is a wrist-worn device that can include, for example, 1) an array of electrodes16encircling the wrist, 2) a skin interface to ensure good electrical contact to the person, 3) an electronics box or housing12containing the stimulator or pulse generator18, sensors20, and other associated electronics such as a controller or processor22for executing instructions, memory24for storing instructions, a user interface26which can include a display and buttons, a communications module28, a battery30that can be rechargeable, and optionally an inductive coil32for charging the battery30, and the like, and 4) a band to hold all the components together and securely fasten the device around the wrist of an individual. InFIG.12D, electrodes16are placed circumferentially around the wrist and excited on opposite sides of the wrist, the electric field extends through the wrist and this enables excitation of nerves deeper in the tissue. Therefore, the circumferential array is compact, allowing a band width that is approximately the same size as the electrode width, and thus advantageous for wearable devices. In some embodiments, the advantage of having the configurability of the array is that the same nerves can be reached, but in a more compact form factor than conventional median nerve excitation. The devices described herein may be described and illustrated with electrodes placed circumferentially or longitudinally, but it should be understood that either electrode configuration can be used by the devices. In addition, the devices may be described and shown with 2, 3 or more electrodes, but it should be understood that the device can have only 2 electrodes, or can have more than 2 electrodes. Some devices may be designed to stimulate just a single nerve, such as the median nerve, and some devices may be designed to stimulate more than one nerve. One embodiment, as shown inFIG.13A, is a two-part system310including a monitor unit312that can be wearable in some embodiments and a therapy unit314. In some embodiments, the therapy unit314can be can be detachable and can be reversibly attached to the wearable monitor unit312. The therapy unit314may contain an electrical stimulation signal generator316, power source318, and a microprocessor and/or microcontroller320to control the stimulation. The therapy unit314can reversibly connect and communicate directly and/or wirelessly to the wearable monitor312. In some embodiments, the therapy unit314may remain separate from the wearable monitor unit312and can communicate wirelessly with the wearable monitor unit312. In some embodiments, the therapy unit314can have a data/power port315, such as a USB port that allows a user to charge the power source318, update the software and/or parameters on the microcontroller320, and/or retrieve data from memory on the wearable monitor unit312and/or therapy unit314. In some embodiments, the data/power port can be located on the wearable monitor unit312or both the wearable monitor unit12and therapy unit314. In some embodiments, the wearable monitor unit312and/or therapy unit314can communicate wirelessly with an external computing device to update the software and/or parameters and/or retrieve data. In some embodiments, the wearable monitor unit312can have a housing with a user interface322that encloses one or more sensors324. In some embodiments, the wearable monitor312can be used to measure heart rate, rhythm, heart rate variability (HRV), or other measures correlated or related to inflammatory bowel disease or other inflammatory conditions, or response of the autonomic nervous system. In some embodiments, the wearable monitor312can have one or more electrodes326located on the base of the housing that makes contact with the patient's skin. In addition, or alternatively, the wearable monitor312can have a band328or other securement feature with one or more electrodes on the skin facing side of the band328. In some embodiments, the wearable monitor unit312has exactly or no more than 2 or 3 electrodes, or at least 2 or 3 electrodes. In some embodiments, the wearable monitor unit312lacks a power source and relies on the power source318in the therapy unit314for power. In other embodiments, both the wearable monitor unit312and the therapy unit314have power sources. In some embodiments, only the wearable monitor unit312has a power source and the therapy unit relies on power from the monitoring unit. In some embodiments, as shown inFIG.13B, the therapy unit314′ may directly make contact with the wearer's skin and have the capability to provide electrical stimulation of targeted nerves, such as the median, radial, ulnar, and/or ABVN, using electrodes326. In some embodiments, the therapy unit14′ has 2 or 3 electrodes, or at least 2 or 3 electrodes. These electrodes326may be located on the housing of the therapy unit314′ and/or the therapy unit314′ may also have a band328or securement feature with electrodes326. In some embodiments, when the therapy unit314′ has electrodes326, the wearable monitor unit312′ does not have electrodes. In some embodiments, both the monitor unit and the therapy unit can have electrodes. As above, the therapy unit314′ can have a stimulator316, power source318, and microcontroller320. The wearable monitor unit312′ can have a user interface322and one or more sensors324and, optionally, a power source330and microcontroller321. In some embodiments, when the monitor unit has a power source330and/or a microcontroller321, the therapy unit does not have a power source and/or a microcontroller. In some embodiments, the wearable monitor unit312′ is a smart watch or other wearable device, such as the Apple Watch or an Android based smart watch, with an application that allows the wearable device to communicate with the therapy unit and perform as a monitor unit. In some embodiments, the wearable monitor unit312′ can communicate with the therapy unit314′ wirelessly, and one or both of these devices can also communicate with an external computing device wirelessly. In some embodiments, one or both of the wearable monitor unit312′ and the therapy unit314′ can have a data/power port315. In some embodiments, the wearable monitor unit312and the therapy unit314′ can be connected to each other through the data/power ports315. In some embodiments, the sensors can be located in or on the therapy unit instead of the monitoring unit. In some embodiments, the sensors can be located on both the therapy unit and the monitoring unit. In some embodiments, one or more sensors can be located on a separate wearable device, such as a sensor on a band that can be worn around the arm, leg, neck, or chest, or a sensor implanted inside the body, which may communicate via a wired or wireless connection with the therapy unit and/or the monitoring unit. In some embodiments, the monitor unit can instead be carried by the user in, for example, the user's hand or pocket, rather than be worn. For example, a monitor unit carried by the user can be a smart phone, such as an Android smartphone or iPhone. In some embodiments, the two-part system or the monitor unit may instruct the user to perform an action, such as to sit and relax the arm, or to remain still or to attempt to remain still while the wearable monitor unit takes a measurement with one of the sensors. In some embodiments, the user interface can include a display. In some embodiments, the display can be a touch screen display or capacitive sensor. In some embodiments, the display can be an array of LED lights. In some embodiments, the user interface can include one or more buttons, a dial, and/or a keyboard. In some embodiments, the electrodes can be dry-contact (e.g., fabric, metal, silicone or any other plastic impregnated with conductive fillers, or a combination), use a conductive gel (e.g., hydrogels), or have a wet electrode surface (e.g., a sponge with water or conductive liquids or gels), or have fine micro needles, for example. In some embodiments, the electrodes can have a foam backing. In some embodiments, the monitor unit can be a wearable monitor having a housing with a user interface. The housing can use a plurality of sensors to collect, store, and analyze biological measures about the wearer including, but not limited to, blood pressure, motion (e.g., accelerometers, gyroscopes, magnetometer, bend sensors), muscle activity (e.g., EMG using electrodes), cardiovascular rhythm measures (e.g., heart rate, heart rate variability, or ventricular and/or atrial dyssynchrony using electrodes to measure ECG, heart rhythm abnormalities), skin conductance (e.g., skin conductance response, galvanic skin response, using electrodes), skin temperature, pupil diameter, and sleep state (e.g., awake, light sleep, deep sleep, REM). Heart rhythm measures can be recorded with optical, electrical, and/or accelerometry-based sensors. In particular, studies have shown that increased stress levels can increase blood pressure. Activities such as exercise, can also affect onset of inflammatory bowel diseases or other inflammatory conditions—measuring accelerometry (motion), heart rate, etc. could help identify these activities and normalize the measurements by similar activities. Thus, using standard statistical analysis, machine learning, deep learning, or big data techniques, such as a logistical regression or Naïve Bayes classifier, these biological measures can be analyzed to assess a person's state, such as level of stress, which in turn, can serve as a predictor for inflammatory bowel disease or other inflammatory conditions. In some embodiments, the device can provide stimulation based on measurements of one or more biological measures, a determination of a person's state, and/or a prediction of inflammatory bowel disease or other inflammatory conditions. In some embodiments, the responsiveness of stimulation could be dependent on one, two, or more sensors housed in the device to collect, store, and analyze biological measures about the wearer including, but not limited to, motion (e.g., accelerometers, gyroscopes, magnetometer, bend sensors), ground reaction force or foot pressure (e.g., force sensors or pressure insoles), muscle activity (e.g., EMG), cardiovascular measures (e.g., heart rate, heart rate variability (HRV), photoplethysmography (PPG), or ventricular and/or atrial dyssynchrony using electrodes to measure ECG and/or heart rhythm abnormalities), skin conductance (e.g., skin conductance response, galvanic skin response), respiratory rate, skin temperature, pupil diameter, and sleep state (e.g., awake, light sleep, deep sleep, REM). Using standard statistical analysis, machine learning, deep learning, or big data techniques, such as a logistical regression or a Naïve Bayesian classifier, these biological measures can be analyzed to assess the wearer's activity state, such as sedentary versus active, level of stress and the like, which in turn, can serve as a predictor inflammatory bowel disease or other inflammatory conditions. In some embodiments, stimulation of one, two, or more nerves in the upper and/or lower extremity can be combined with stimulation of the ABVN, such as by way of the cymba concha or tragus, to modulate vagal activity and restore balance of the autonomic nervous system. In some embodiments, the system can stimulate solely the ABVN.FIG.13Cillustrates select anatomy of the ear390, including a relatively medial area of the ear390generally innervated by the auriculotemporal nerve399, the tragus398, the helix397, the concha396, an area innervated by the great auricular nerve395generally at the inferior and lateral edge of the ear, and an area innervated by the ABVN394more centrally and generally in the vicinity of the cymba concha or tragus398. In some embodiments, systems and methods do not directly stimulate the cervical vagus nerve, and/or any nerve within the neck. In some embodiments, systems and methods do not involve trans-spinal stimulation, such as trans-spinal direct current stimulation. In some embodiments, systems and methods do not involve transcranial and/or peripheral magnetic stimulation. In some embodiments, systems and methods do not stimulate a nerve within the abdomen, such as any number of the splenic nerve, celiac plexus, celiac ganglion, aorticrenal ganglion, greater thoracic splanchnic nerve, and/or lesser thoracic splanchnic nerve. Stimulation of the cymba concha or tragus can occur, for example, noninvasively via a plug, earpiece, or other device that can include electrodes for transcutaneous electrical stimulation in some cases.FIG.13Dillustrates an embodiment of a tragus stimulator392with an earbud configuration positioned in the tragus398of the ear390. The stimulator392can be wired as shown, or wireless in other embodiments. The stimulator392can include a distal ear receptacle portion389that can include a cathode387and an anode388, a hub386proximate the receptacle portion389, and a conduit388to a source of electromagnetic energy, such as electrical energy. In some embodiments, the auricular stimulator392includes one or more sensors for measuring parameters relating to stimulation and/or physiologic function as discussed elsewhere herein. The auricular stimulator392can be unilateral or bilateral (e.g., placed in both ears). In some embodiments, a system can include a plurality of stimulators that communicate with each other wirelessly and provided a synchronized, patterned stimulation. In some embodiments, multiple stimulators may be in electrical connection with multiple electrode pairs to stimulate multiple nerves simultaneously. In one embodiment, a system can include a stimulator on the wrist to target median nerve and a stimulator in the ear to target the ABVN. Each stimulator in the system can communicate with each other via a wired or wireless connection. Multiple stimulators can provide synchronized stimulation to the multiple nerves. Stimulation may be, for example, burst, offset, or alternating between the multiple nerves. The device could also be responsive to number of episodes of symptoms, including but not limited voiding, incontinence, sense of urgency, nocturia, abdominal or intestinal pain. If more episodes occur in one day, treatment can be increased by increasing the amplitude of the stimulation, duration of the stimulation, or number of treatment sessions, for example. The number of episodes of symptoms could be detected in various ways to control the stimulation applied by system and devices. In some embodiments, the patient can enter events related to symptoms, including but not limited voiding, incontinence, sense of urgency, nocturia, abdominal or intestinal pain. One embodiment of the system could centrally store biological measures from multiple wearers on a server system (e.g., the cloud), along with other relevant demographic data about each user, including age, weight, height, gender, ethnicity, etc. Data collected from multiple wearers can be analyzed using standard statistical analysis, machine learning, deep learning, or big data techniques, such as a logistic regression or Naive Bayes classifier (or other classifiers), to improve prediction of episodes of inflammatory bowel disease or other inflammatory conditions by determining correlations between biological measures and other recorded symptom events associated with the treated disease. These correlations can be used to set parameters of the stimulation waveform applied by the therapy unit, determine best time to apply stimulation therapy, and/or adapt the stimulation waveform applied by the therapy unit in real time. In one embodiment of the system, the wearable monitor automatically detects and records the dosage and consumption of medications to (1) track compliance of the patient; (2) combine with the logging of symptom events to assess therapeutic effectiveness, and (3) determine or predict unpleasant symptoms associated with inflammatory bowel disease or other inflammatory diseases. The dosage and consumption of medications can be detected and recorded in multiple ways, including (1) using a visual scanner to record a marking on the pill pack or bottle each time medication is consumed, (2) a smart pill cap with force sensors and a wireless transmitter to detect each time the medication is consumed from a pill bottle, (3) an RFID chip that is of similar size and shape as a pill that is consumed with each dosage of medication that is activated by digestion and communicates with the monitor device, (4) an RFID chip embedded in a sugar pill that is consumed with each dosage of medication that is activated by digestion and communicates with the monitor device, (5) a pill with a visual encoding that is scanned and recorded by a camera on the monitor unit each time medication is consumed, or (6) by having the patient logging drug consumption into the device. The system can also log the patient satisfaction after each stimulation session or the end of a specified period, like a day or week or month, via an input on the device, which provides another piece of information to help feedback application of therapy. In some cases, if a person is satisfied, the therapy is maintained at the current stimulation waveforms and levels. In other cases, this may mean that the stimulation treatment may need to be optimized, for example, by changing stimulation parameters such as waveform frequency or amplitude. In some embodiments, the wearable monitor can have a visual, auditory, tactile (e.g., squeezing band), or vibrotactile cues to notify the wearer of key events based on analysis of biological measures, including, but not limited to, prediction of symptoms caused by inflammatory bowel diseases or other inflammatory conditions, and/or increase in stress level, heart rate, heart rate variability, or other parameters. The cuing system could also notify the wearer of other predetermined events or reminders set by the wearer. In some embodiments, the form of the wearable monitor and/or therapy unit could be a wrist band or watch, a ring, a glove, an arm sleeve or arm band or cuff, knee band, sock, leg sleeve or cuff, an ear piece/headphone, head band, a necklace or neck band, or a compliant patch that conforms to multiple locations on the body. In one embodiment, the wearable monitor can have a processing unit and memory that collects, stores, processes, and analyzes the biological measures, along with other data input by the wearer. In some embodiments, the wearable monitor can take user input about events, including diet history, medication history, caffeine intake, alcohol intake, sodium intake, etc. The monitor can use accelerometers to measure specific movements, gestures, or tapping patterns to record user inputs at specific prompts. Other touch sensors, such as resistive strips or pressure sensitive screens, could be used to measure specific gestures to record user inputs. These gesture-based measures to record user input minimize the complexity of steps required to input user data into the device. The data can be stored in memory and processed by the processing unit. In some embodiments, the data can be transmitted from the wearable monitor to an external computing device. In one embodiment, the wearable monitor and/or the therapy unit can connect with other applications, such as calendars and activity logs, to sync and track events or a saved calendar can be saved and stored on the device. In some embodiments, the wearable monitor and/or the therapy unit can communicate with a variety of computing devices, such as a smart phone, a smart watch, a tablet, a laptop computer, or a desktop computer, for example, that have these applications. In some embodiments, the wearable monitor can include an ambulatory blood pressure monitor. In one embodiment, the monitor unit and/or therapy unit can have a GPS or similar device to track the location and assess activity of the wearer. GPS measures can be combined with mapping or location systems to determine context of the wearer's activity (e.g., gym, office, home) or determine changes in elevation during specific activities, such as running or cycling. FIGS.14A-14Eillustrates another embodiment of a two-part therapy system that includes a disposable band500and a therapy unit502that can be reversibly attached to the disposable band500. The disposable band500can have two or more electrodes504disposed on a skin facing or inside surface of the band and a receptacle506or receiving portion for reversibly receiving the therapy unit502. Within the band500are wires and/or conductive traces that form a flexible circuit505that runs from the electrodes504to the receptacle506for electrically connecting the electrodes504to the therapy unit502when the therapy unit502is disposed in the receptacle506. In some embodiments, the wires and/or conductive traces of the flexible circuit505are arranged in a wave or undulating pattern in order to improve its ability to flex. In some embodiments, the receptacle506can have one or more electrical contact points, such as one or more pin holes507, for receiving one or more complementary electrical contacts, such as pins509, from the therapy unit502. The flexible circuit505can extend to the pin holes507such that an electrical connection is formed when the pins are inserted into the pin holes. The electrodes504can be dry electrodes or can be coated with a conductive gel. In some embodiments, the therapy unit502can include a battery, which may be rechargeable, and electronics to deliver electrical stimulation through the electrodes to the patient's nerves. The electronics can include a stimulator and a microcontroller, and may also include memory and one or more sensors, such as a blood pressure sensor and/or a sensor to measure heart rate and/or heart rate variability and/or galvanic skin response, or one, two, or more ECG electrodes to measure dyssynchrony. In some embodiments, the device is able to sense the impedance of the electrodes in order to assess the integrity of the electrode to skin interface. In some embodiments, there can be an electrical indication (e.g. reading of a chip, pushing in of a sensor on the connector, etc.) to detect integrity of the connection between the band and the therapy unit. In some embodiments, the therapy unit502can have one or more LEDs, mini OLED screens, LCS, or indicators501that can indicate the status of the therapy unit502, such as whether the therapy unit502is connected to the band500, the power remaining in the battery of the therapy unit502, whether a stimulation is being delivered, the stimulation level, whether data is being transmitted, whether a sensor measurement is being taken, whether a calibration routine is being performed, whether the therapy unit502is initializing, whether the therapy unit502is paired with another device such as a smart watch and/or smart phone, whether the battery is being charged, and the like. In some embodiments, the therapy unit502may also include a user interface503, such as one or more buttons. FIG.14Billustrates a kit including a wrist worn device that can be sent to a user. The kit can contain a plurality of bands500of different sizes, shapes, colors, etc. to accommodate patients having different wrist sizes or other body part sizes, such as ankles, arms, fingers, and legs and to accommodate different types of connected accessories like secondary displays (e.g. smart watch). In some embodiments, the kit has three bands to accommodate a majority of wrist sizes. In some embodiments, the kit has two bands to cover most sizes. Additionally, the kit can contain one or more electronic units502. If multiple electronic units502are provided in the kit, the battery capacity of the different electronic units502can be different to accommodate different usage types. For example, a relatively low capacity battery can be used for on-demand stimulation, while a relatively high capacity battery can be used for automated and/or responsive stimulation driven by the microcontroller. In some embodiments, only a single electronic unit is provided. In other embodiments, a plurality of electronic units are provided while a single band is provided. The kit may also include a charger508to charge the therapy unit502. In some embodiments, the charger508can inductively charge the therapy unit502. In other embodiments, the charger508can charge the therapy unit with a charge cable that can be inserted into a power port in the therapy unit. In some embodiments, the therapy unit502can be docked with the charger508for charging. FIG.14Cillustrates an embodiment where a smart watch510, such as the Apple Watch, is reversibly or permanently fastened to a band500, which may also have a therapy unit502. In some embodiments, the smart watch510may provide a display and a user interface for the therapy unit502. The smart watch510may communicate with the therapy unit502wirelessly, such as through Bluetooth or Wi-Fi, or through a direct connection through a data port in the smart watch and a data port in the therapy unit502. In some embodiments, the electronic unit502and/or smart watch510may communicate with a smart phone512, as described herein, to transmit data or to update the software and/or stimulation parameters on the therapy unit502and/or smart watch510. In some embodiments, the band500and therapy unit502are permanently affixed or integrated together while the smart watch510is reversibly attachable to the band500. The smart phone512and/or the smart watch510can include an application, which may be downloaded through the cloud or a computer, configured to interface with the therapy unit502. FIGS.14D and14Eillustrate that the wearable two-part system can be worn and used throughout the day. When the power remaining in the battery of the therapy unit is low, the therapy unit502can be recharged with the charger508. Charging can be performed at night or whenever the battery is low or when desired. In some embodiments, the therapy unit can be removed from the band before charging. In some embodiments, the user can swap a low charge therapy unit with a high charged therapy unit so that the user can always be wearing a therapy unit. In some embodiments, the kit illustrated inFIG.14Bcan be used as a diagnostic trial kit. The patient can initially wear the therapy system for about, at least about, or no more than about 1 day to about 90 days, or about or at least about 1, 2, 3, 4, 5, 6, 9, 12, or more months, or for a predetermined length of time. This initial period is used to collect data with the sensors in the therapy unit and/or band in order to characterize the patient's symptomology, or other related measures, or other disease variables, and assess the patient's response to the therapy during the trial period in order to identify how well the patient is responding to the various treatments. The sensor data can be stored in memory in the therapy unit, and/or can be transmitted through a network to the cloud or a server or to another computing device, which can be accessed by the patient's physician, the company, or another third party. FIG.15illustrates an embodiment of a system for treating inflammatory bowel disease or other conditions including those disclosed herein using a wearable therapy device. As described above, the therapy device may have two parts, a band500and therapy unit502. A base station600, which may replace the charger in the kit described above, can be used to both charge the therapy device and to receive and transmit data to the therapy device and to the cloud602. Communication between the base station600and the therapy device can be wireless, such as through Bluetooth and/or Wi-Fi, and communication between the base station600and the cloud602can be through a cellular network, using a 3G or 4G connection, or through a wired connection to the internet, using DSL or cable or Ethernet, for example. A physician or other user can view and/or retrieve data stored on the cloud602using an online portal or a physician web portal604. In addition, the physician can prescribe and/or modify a treatment regimen on the therapy unit502through the cloud602and base station600using the web portal604. In some embodiments, the base station600is used to receive and transmit relatively large amounts of data that may require a high bandwidth, such as the transmission of raw data from the therapy device, which may be about 10 to 100 Mb/day, or about 10, 20, 30, 40, or 50 Mb/day. In some embodiments, the data may be stored in memory in the base station600and transmitted at another interval, such as weekly or twice weekly, with a scaling up of the bandwidth of transmission. The high bandwidth transmission of the raw data can occur daily while the therapy device is being charged, such as at night during a regular charging period. In some embodiments, the raw data can be processed by the cloud and/or the physician into processed data and sent back to the therapy device. In some embodiments, the system may optionally include a portable computing device606, such as a smart phone or tablet, to provide a secondary display and user interface for the patient and to run applications to more easily control the therapy device and view the raw and processed data. The portable computing device can be used to make patient or physician adjustments to the therapy device, such as adjusting the stimulation parameters and dosing, and can receive device state data from the therapy device, which includes data relating to the device, such as when the device was used, errors, therapy parameters such as amplitude and when they were set and delivered. In some embodiments, the portable computing device606can receive processed data from the cloud602through a cellular network and/or through an internet connection using Wi-Fi, for example. FIG.16illustrates the various components that can be included in a therapy unit700, band702, and base station704. These components are described in detail above and also below as one particular embodiment. For example, the therapy unit700includes one or more indicators706, which can be LEDs, and a user interface708, which can be push buttons, for example. The therapy unit700can also have a stimulator710with stimulation electronics and may include the capability to measure current and voltage. The therapy unit700can also have a battery712, which may be rechargeable and can be recharged using charging circuitry714, which may be inductive. The therapy unit710may further include a processor716and memory718to store and execute programs and instructions to accomplish the functions described herein. The therapy unit710may also include sensors720, such as blood pressure sensors, and a communications module722, which may be wireless and can communicate with the base station704and/or a secondary display/computing device. The band702can have electrodes724and may also include memory to store identification information or may include some other form of identifier726as described herein. The base station704can include charging circuitry728, which may also be inductive and can transmit power to the complementary charging circuitry714on the therapy unit700. The base station704can also have a processor and memory for storing and executing instructions and programs. The base station704can further include a communication module732, which may be cellular, to communicate with the cloud, and another communication module734, which may be wireless and used to communicate with the therapy unit. In some embodiments, the device can be a biological sensor, such as a heart rate monitor worn on the body, which could include an integrated nerve stimulator. In some embodiments, the nerve stimulator and sensor device can be separate devices that communicate wirelessly. In some embodiments, the device can measure a biological measurement over the course of minutes, hours, days, weeks and/or months to determine whether the patient's condition is increasing, decreasing, or staying the same. In some embodiments, the measurements are time averaged over a window, which can be days, weeks, or months. In some embodiments, a sensor, such as a motion sensor, IMU, or GPS, can be used to detect patient activity, which can affect other measurements. In some embodiments, the sensor can be an electrode that measures galvanic skin response, which can be correlated to stress, a known trigger for inflammatory exacerbations. In some embodiments, measurements are collected at the same time each day with the same conditions to improve measurement consistency and to reduce variability. In some embodiments, the stimulator is applied to one wrist or arm or ear to stimulate one peripheral nerve in the arm, such as the median nerve or ABVN, or specific nerve location, such as an acu-pressure point or meridians. When a feature or element is herein referred to as being “on” another feature or element, it can be directly on the other feature or element or intervening features and/or elements may also be present. In contrast, when a feature or element is referred to as being “directly on” another feature or element, there are no intervening features or elements present. It will also be understood that, when a feature or element is referred to as being “connected”, “attached” or “coupled” to another feature or element, it can be directly connected, attached or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being “directly connected”, “directly attached” or “directly coupled” to another feature or element, there are no intervening features or elements present. Although described or shown with respect to one embodiment, the features and elements so described or shown can apply to other embodiments. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature. Terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. For example, as used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or groups thereof. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as “/”. Spatially relative terms, such as “under”, “below”, “lower”, “over”, “upper” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the exemplary term “under” can encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms “upwardly”, “downwardly”, “vertical”, “horizontal” and the like are used herein for the purpose of explanation only unless specifically indicated otherwise. Although the terms “first” and “second” may be used herein to describe various features/elements (including steps), these features/elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one feature/element from another feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and similarly, a second feature/element discussed below could be termed a first feature/element without departing from the teachings of the present invention. Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising” means various components can be co-jointly employed in the methods and articles (e.g., compositions and apparatuses including device and methods). For example, the term “comprising” will be understood to imply the inclusion of any stated elements or steps but not the exclusion of any other elements or steps. As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word “about” or “approximately,” even if the term does not expressly appear. The phrase “about” or “approximately” may be used when describing magnitude and/or position to indicate that the value and/or position described is within a reasonable expected range of values and/or positions. For example, a numeric value may have a value that is +/−0.1% of the stated value (or range of values), +/−1% of the stated value (or range of values), +/−2% of the stated value (or range of values), +/−5% of the stated value (or range of values), +/−10% of the stated value (or range of values), etc. Any numerical values given herein should also be understood to include about or approximately that value, unless the context indicates otherwise. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein. It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value “X” is disclosed the “less than or equal to X” as well as “greater than or equal to X” (e.g., where X is a numerical value) is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point “15” are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed. Although various illustrative embodiments are described above, any of a number of changes may be made to various embodiments without departing from the scope of the invention as described by the claims. For example, the order in which various described method steps are performed may often be changed in alternative embodiments, and in other alternative embodiments one or more method steps may be skipped altogether. Optional features of various device and system embodiments may be included in some embodiments and not in others. Therefore, the foregoing description is provided primarily for exemplary purposes and should not be interpreted to limit the scope of the invention as it is set forth in the claims. The examples and illustrations included herein show, by way of illustration and not of limitation, specific embodiments in which the subject matter may be practiced. As mentioned, other embodiments may be utilized and derived there from, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to herein individually or collectively by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any single invention or inventive concept, if more than one is, in fact, disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description. The methods disclosed herein include certain actions taken by a practitioner; however, they can also include any third-party instruction of those actions, either expressly or by implication. For example, actions such as “percutaneously stimulating an afferent peripheral nerve” includes “instructing the stimulation of an afferent peripheral nerve.” | 148,574 |
11857779 | DETAILED DESCRIPTION FIGS.1A-Care conceptual diagrams of an implantable cardiac system10implanted within a patient12.FIG.1Ais a front view of patient12implanted with implantable cardiac system10.FIG.1Bis a side view of patient12with implantable cardiac system10.FIG.1Cis a transverse view of patient12with implantable cardiac system10. Implantable cardiac system10includes an implantable medical device, in this example an ICD14, connected to a defibrillation lead16and a pacing lead18. In the example illustrated inFIGS.1A-C, ICD14is implanted subcutaneously on the left side of patient12above the ribcage. ICD14may, in some instances, be implanted between the left posterior axillary line and the left anterior axillary line of patient12. ICD14may, however, be implanted at other subcutaneous locations on patient12as described later. Defibrillation lead16includes a proximal end that includes a connector (not shown) configured to be connected to ICD14and a distal portion that includes electrodes24,28, and30. Defibrillation lead16extends subcutaneously above the ribcage from ICD14toward a center of the torso of patient12, e.g., toward xiphoid process20of patient12. At a location near xiphoid process20, defibrillation lead16bends or turns and extends superior subcutaneously above the ribcage and/or sternum, substantially parallel to sternum22. Although illustrated inFIGS.1A-Cas being offset laterally from and extending substantially parallel to sternum22, defibrillation lead16may be implanted at other locations, such as over sternum22, offset to the right of sternum22, angled lateral from sternum22at either the proximal or distal end, or the like. Defibrillation lead16includes a defibrillation electrode24toward the distal portion of defibrillation lead16, e.g., toward the portion of defibrillation lead16extending superior near sternum22. Defibrillation lead16is placed along sternum22such that a therapy vector between defibrillation electrode24and a housing electrode of ICD14(or other second electrode of the therapy vector) is substantially across the ventricle(s) of heart26. The therapy vector may, in one example, be viewed as a line that extends from a point on defibrillation electrode24, e.g., center of defibrillation electrode24, to a point on the housing electrode of ICD14, e.g., center of the housing electrode. In one example, the therapy vector between defibrillation electrode24and the housing electrode of ICD14(or other second electrode of the therapy vector) is substantially across the right ventricle of heart26. Defibrillation electrode24is illustrated inFIG.1as being an elongated coil electrode. Defibrillation electrode24may vary in length depending on a number of variables. Defibrillation electrode24may, in one example, have a length of between approximately 5-10 centimeters (cm). However, defibrillation electrode24may have a length less than 5 cm and greater than 10 cm in other embodiments. Another example, defibrillation electrode24may have a length of approximately 2-16 cm. In other embodiments, however, defibrillation electrode24may be a flat ribbon electrode, paddle electrode, braided or woven electrode, mesh electrode, segmented electrode, directional electrode, patch electrode or other type of electrode besides an elongated coil electrode. In one example, defibrillation electrode24may be formed of a first segment and a second segment separated by a distance and having at least one sensing electrode located between the first and second defibrillation electrode segments. In other embodiments, defibrillation lead16may include more than one defibrillation electrode. For example, defibrillation lead16may include a second defibrillation electrode (e.g., second elongated coil electrode) near a proximal end of lead16or near a middle of lead16. Defibrillation lead16also includes electrodes28and30located along the distal portion of defibrillation lead16. In the example illustrated inFIGS.1A-C, electrode28and30are separated from one another by defibrillation electrode24. In other examples, however, electrodes28and30may be both distal of defibrillation electrode24or both proximal of defibrillation electrode24. In instances in which defibrillation electrode24is a segmented electrode with two defibrillation segments, one or both electrodes28and30may be located between the two segments and, in some cases, lead16may include additional electrodes proximal or distal to the defibrillation segments. Electrodes28and30may comprise ring electrodes, short coil electrodes, paddle electrodes, hemispherical electrodes, segmented electrodes, directional electrodes, or the like. Electrodes28and30of lead16may have substantially the same outer diameter as the lead body. In one example, electrodes28and30may have surface areas between 1.6-55 mm2. Electrodes28and30may, in some instances, have relatively the same surface area or different surface areas. Depending on the configuration of lead16, electrodes28and30may be spaced apart by the length of defibrillation electrode24plus some insulated length on each side of defibrillation electrode, e.g., approximately 2-16 cm. In other instances, such as when defibrillation28and30are between a segmented defibrillation electrode, the electrode spacing may be smaller, e.g., less than 2 cm or less than 1 cm. The example dimensions provided above are exemplary in nature and should not be considered limiting of the embodiments described herein. In other embodiments, defibrillation lead16may not include electrodes28and/or30. In this case, defibrillation lead16would only include defibrillation electrode24and sensing may be achieved using sensing electrodes of pacing lead18, as described further below. Alternatively, defibrillation lead16may include more than two pace/sense electrodes. ICD14may obtain sensed electrical signals corresponding with electrical activity of heart26via a combination of sensing vectors that include combinations of electrodes28and/or30and the housing electrode of ICD14. For example, ICD14may obtain electrical signals sensed using a sensing vector between electrodes28and30, obtain electrical signals sensed using a sensing vector between electrode28and the conductive housing electrode of ICD14, obtain electrical signals sensed using a sensing vector between electrode30and the conductive housing electrode of ICD14, or a combination thereof. In some instances, ICD14may even obtain sensed electrical signals using a sensing vector that includes defibrillation electrode24. Pacing lead18includes a proximal end that includes a connector configured to be connected to ICD14and a distal portion that includes electrodes32and34. Pacing lead18extends subcutaneously above the ribcage from ICD14toward the center of the torso of patient12, e.g., toward xiphoid process20. At a location near xiphoid process20, pacing lead18bends or turns and extends superior underneath/below sternum22in anterior mediastinum36. Anterior mediastinum36may be viewed as being bounded laterally by pleurae40, posteriorly by pericardium38, and anteriorly by sternum22. In some instances, the anterior wall of anterior mediastinum36may also be formed by the transversus thoracis and one or more costal cartilages. Anterior mediastinum36includes a quantity of loose connective tissue (such as areolar tissue), some lymph vessels, lymph glands, substernal musculature (e.g., transverse thoracic muscle), branches of the internal thoracic artery, and the internal thoracic vein. In one example, the distal portion of lead18extends along the posterior side of sternum22substantially within the loose connective tissue and/or substernal musculature of anterior mediastinum36. A lead implanted with the distal portion substantially within anterior mediastinum36will be referred to herein as a substernal lead. Also, electrical stimulation, such as pacing, provided by a lead implanted with the distal portion substantially within anterior mediastinum36will be referred to herein as substernal electrical stimulation or substernal pacing. Pacing lead18is implanted within anterior mediastinum36such that electrodes32and34are located near the ventricle of heart26. For instance, the distal portion of pacing lead18may be implanted substantially within anterior mediastinum36such that electrodes32and34are located over a cardiac silhouette of the ventricle as observed via an anterior-posterior (AP) fluoroscopic view of heart26. In one example, pacing lead18may be implanted such that one or both of a unipolar pacing vector from electrode32to a housing electrode of ICD14and/or a unipolar pacing vector from electrode34to the housing electrode of ICD14are substantially across the ventricles of heart26. The therapy vector may again be viewed as a line that extends from a point on electrode32or34, e.g., center of electrode32or34, to a point on the housing electrode of ICD14, e.g., center of the housing electrode. In another example, the spacing between electrodes32and34as well as the placement of pacing lead18may be such that a bipolar pacing vector between electrode32and electrode34is centered or otherwise located over the ventricle. However, pacing lead18may be positioned at other locations as long as unipolar and/or bipolar pacing vectors using electrodes32and34result in capture of the ventricle of the heart. In the example illustrated inFIGS.1A-C, pacing lead18is located substantially centered under sternum22. In other instances, however, pacing lead18may be implanted such that it is offset laterally from the center of sternum22. In some instances, pacing lead18may extend laterally enough such that all or a portion of the distal portion of pacing lead18is underneath/below the ribcage in addition to or instead of sternum22while still within the anterior mediastinum22. The distal portion of lead18is described herein as being implanted substantially within anterior mediastinum36. Thus, points along the distal portion of lead18may extend out of anterior mediastinum36, but the majority of the distal portion is within anterior mediastinum36. In other embodiments, the distal portion of lead18may be implanted in other non-vascular, extra-pericardial locations, including the gap, tissue, or other anatomical features around the perimeter of and adjacent to, but not attached to, the pericardium or other portion of heart26and not above sternum22or ribcage. As such, lead16may be implanted anywhere within the “substernal space” defined by the undersurface between the sternum and/or ribcage and the body cavity but not including the pericardium or other portion of heart26. The substernal space may alternatively be referred to by the terms “retrosternal space” or “mediastinum” or “infrasternal” as is known to those skilled in the art and includes the anterior mediastinum36. The sub sternal space may also include the anatomical region described in Baudoin, Y. P., et al., entitled “The superior epigastric artery does not pass through Larrey's space (trigonum sternocostale).” Surg. Radiol. Anat. 25.3-4 (2003): 259-62 as Larrey's space. In other words, the distal portion of lead18may be implanted in the region around the outer surface of heart26, but not attached to heart26. Pacing lead18includes an elongated lead body that contains one or more elongated electrical conductors (not illustrated) that extend within the lead body from the connector at the proximal lead end to electrodes32and34located along the distal portion of lead18. The elongated lead body may have a generally uniform shape along the length of the lead body. In one example, the elongated lead body may have a generally tubular or cylindrical shape along the length of the lead body. The elongated lead body may have a diameter of between 3 and 9 French (Fr) in some instances. However, lead bodies of less than 3 Fr and more than 9 Fr may also be utilized. In another example, the distal portion (or all of) the elongated lead body may have a flat, ribbon or paddle shape. In this instance, the width across the flat portion of the flat, ribbon or paddle shape may be between 1 and 3.5 mm. The lead body of lead18may be formed from a non-conductive material, including silicone, polyurethane, fluoropolymers, mixtures thereof, and other appropriate materials, and shaped to form one or more lumens within which the one or more conductors extend. However, the techniques are not limited to such constructions. The one or more elongated electrical conductors contained within the lead body of lead18may engage with respective ones of electrodes32and34. In one example, each of electrodes32and34is electrically coupled to a respective conductor within the lead body. The respective conductors may electrically couple to circuitry, such as a therapy module or a sensing module, of ICD14via connections in connector assembly, including associated feedthroughs. The electrical conductors transmit therapy from a therapy module within ICD14to one or more of electrodes32and34and transmit sensed electrical signals from one or more of electrodes32and34to the sensing module within ICD14. Electrodes32and34may comprise ring electrodes, hemispherical electrodes, coil electrodes, helix electrodes, segmented electrodes, directional electrodes, or other types of electrodes, or combination thereof. Electrodes32and34may be the same type of electrodes or different types of electrodes. In the example illustrated inFIGS.1A-Celectrode32is a hemispherical electrode and electrode34is a ring or coil electrode. Electrodes32and34of lead18may have substantially the same outer diameter as the lead body. In one example, electrodes32and34may have surface areas between 1.6-55 mm2. In another example, one or both of electrodes32and34may be coil electrodes and may have surface areas of up to 200 mm2. Electrodes32and34may, in some instances, have relatively the same surface area or different surface areas. For example, electrode32may have a surface area of approximately 2-5 mm2and electrode34may have a surface area between 15-44 mm2. In some instances, electrodes32and34may be spaced apart by approximately 5-15 mm. In other instances, electrodes32and34may be spaced apart by distances greater than 15 mm. For example, electrodes32and34may be spaced apart between 2-8 cm and still both be substantially over the ventricles. In another example, electrodes32and34may be spaced apart by greater than 8 cm, e.g., up to 16 cm apart, as may be the case to obtain atrial and ventricular pacing or sensing. The example dimensions provided above are exemplary in nature and should not be considered limiting of the embodiments described herein. In other examples, lead18may include a single electrode or more than two electrodes. In further examples, lead18may include one or more additional electrodes outside of the substernal space, e.g., near the apex of the heart or near a proximal end of lead18. ICD14may generate and deliver pacing pulses to provide anti-tachycardia pacing (ATP), bradycardia pacing, post-shock pacing, or other pacing therapies or combination of pacing therapies via pacing vectors formed using electrodes32and/or34. The pacing therapy, whether it be ATP, post-shock pacing, bradycardia pacing, or other pacing therapy may be painlessly provided in an ICD system without entering the vasculature or the pericardial space, and without being attached to the heart. To the contrary, pacing therapy provided by a subcutaneous ICD system, if provided at all, is provided using pulse energies that may be uncomfortable for patient12. ICD14may deliver pacing pulses to heart26via a pacing vector that includes any combination of one or both of electrodes32and34and a housing electrode of ICD14. For example, ICD14may deliver pacing pulses using a bipolar pacing vector between electrodes32and34. In another example, ICD14may deliver pacing pulses using a unipolar pacing vector (e.g., between electrode32and the conductive housing electrode of ICD14or between electrode34and the conductive housing electrode of ICD14). In a further example, ICD14may deliver pacing pulses via pacing vector in which electrodes32and34together form the cathode (or anode) of the pacing vector and the housing electrode of ICD14functions as the anode (or cathode) of the pacing vector. In still further instances, ICD14may deliver pacing therapy via a pacing vector between electrode32(or electrode34) and an electrode of defibrillation lead16, e.g., defibrillation electrode24or one of electrodes28or30. ICD14may also obtain sensed electrical signals corresponding with electrical activity of heart26via one or more sensing vectors that include combinations of electrodes32and34and/or the housing electrode of ICD14. For example, ICD14may obtain electrical signals sensed using a bipolar sensing vector (e.g., between electrodes32and34) or via a unipolar sensing vector (e.g., between electrode32and the conductive housing electrode of ICD14or between electrode34and the conductive housing electrode of ICD14), or a combination thereof. In some instances, ICD14may obtain sensed electrical activity of heart26via a sensing vector between one of electrode32(or electrode34) and electrodes24,28and30of defibrillation lead16. ICD14may deliver the pacing therapy based on the electrical signals sensed via the one or more of the sensing vectors of pacing lead18. Alternatively or additionally, ICD14may deliver the pacing therapy based on the electrical signals sensed via the one or more of the sensing vectors of defibrillation lead16or based on both the electrical signals sensed via the sensing vector(s) of pacing lead18and defibrillation lead16. Pacing lead18may, in alternative embodiments, include more than two electrodes or only a single electrode. In instances in which pacing lead18includes more than two electrodes, ICD14may deliver pacing pulses and/or obtain sensed electrical signals of heart26via any of a number of combinations of the electrodes. For example, lead18may be a quadripolar lead having four ring electrodes toward a distal end of lead18and ICD14may deliver pacing pulses and/or sense electrical signals via any of the combinations of electrodes or between any one of the electrodes and the housing electrode of ICD14. ICD14analyzes the sensed electrical signals obtained from one or more of the sensing vectors of pacing lead18and/or one or more of the sensing vectors of defibrillation lead16to detect tachycardia, such as ventricular tachycardia or ventricular fibrillation. ICD14may analyze the heart rate and/or morphology of the sensed electrical signals to monitor for tachyarrhythmia in accordance with any of a number of techniques known in the art. One example technique for detecting tachyarrhythmia is described in U.S. Pat. No. 7,761,150 to Ghanem et al., entitled “METHOD AND APPARATUS FOR DETECTING ARRHYTHMIAS IN A MEDICAL DEVICE.” The entire content of the tachyarrhythmia detection algorithm described in Ghanem et al. are incorporated by reference herein in their entirety. Sensing may be completely performed via electrodes32and34of pacing lead18such that defibrillation lead16only includes a defibrillation electrode24and no sensing electrodes28or30. In another example, ICD14may detect ventricular tachycardia or ventricular fibrillation using the signals sensed via electrodes28or30of defibrillation lead16and using the signals sensed via electrodes32or34of pacing lead18as a verification of the tachycardia or fibrillation. In some instances, ICD14delivers one or more ATP therapies via the one or more pacing or therapy vectors of pacing lead18in response to detecting the tachycardia in an attempt to terminate the tachycardia without delivering a high voltage therapy, e.g., defibrillation shock or cardioversion shock. If the one or more ATP therapies are not successful or it is determined that ATP therapy is not desired, ICD14may deliver one or more cardioversion or defibrillation shocks via defibrillation electrode24of defibrillation lead16. In other examples, ICD14may be configured to provide pacing therapy via a combination of therapy vectors that include combinations of electrodes28and/or30and the housing electrode of ICD14or via a therapy vector that includes one of electrodes28or30(or defibrillation electrode24) and one of electrodes32or34of pacing lead18. For example, ICD14may provide ATP and post-shock pacing using at least one electrode of defibrillation lead16. In this case, lead18may be only utilized for sensing. In another example, ICD14may provide ATP using a therapy vector using an electrode of pacing lead18and deliver post-shock therapy using a therapy vector including an electrode of lead16. The configuration described above inFIGS.1A-1Cis directed to providing ventricular therapies via defibrillation lead16and pacing lead18. In some instances, it may be desirable to provide atrial therapy in addition to or instead of ventricular therapy. In situations in which atrial pacing or sensing is desired in addition to or instead of ventricular pacing, pacing lead18may be positioned further superior. A pacing lead configured to deliver pacing pulses to both the atrium and ventricle may have more electrodes. For example, the pacing lead may have one or more electrodes located over a cardiac silhouette of the atrium as observed via the AP fluoroscopic view of heart26and one or more electrodes located over a cardiac silhouette of the ventricle as observed via the AP fluoroscopic view of heart26. A pacing lead configured to deliver pacing pulses to only the atrium may, for example, have one or more electrodes located over a cardiac silhouette of the atrium as observed via the AP fluoroscopic view of heart26. In some instances, two substernal pacing leads may be utilized with one being an atrial pacing lead implanted such that the electrodes are located over a cardiac silhouette of the atrium as observed via the AP fluoroscopic view of heart26and the other being a ventricle pacing lead being implanted such that the electrodes are located over a cardiac silhouette of the ventricle as observed via the AP fluoroscopic view of heart26. Likewise, it may be desirable to provide atrial therapies using defibrillation lead16. In such a case, defibrillation lead16may include more than one defibrillation electrode and be placed further superior along sternum22such that a first therapy vector exists for the ventricle (e.g., via defibrillation electrode24) and a second therapy vector exists for the atrium (e.g., via a second defibrillation electrode). In another example, defibrillation lead16may be placed further superior along sternum22such that a therapy vector between defibrillation electrode24and a housing electrode of ICD14is substantially across an atrium of heart26, such that extravascular ICD system10may be used to provide atrial therapies to treat atrial fibrillation. ICD14may include a housing that forms a hermetic seal that protects components of ICD14. The housing of ICD14may be formed of a conductive material, such as titanium. ICD14may also include a connector assembly (also referred to as a connector block or header) that includes electrical feedthroughs through which electrical connections are made between conductors within leads16and18and electronic components included within the housing. As will be described in further detail herein, housing may house one or more processors, memories, transmitters, receivers, sensors, sensing circuitry, therapy circuitry, power sources and other appropriate components. The housing is configured to be implanted in a patient, such as patient12. Like lead18, lead16includes a lead body that contain one or more elongated electrical conductors (not illustrated) that extend through the lead body from the connector at a proximal lead end to the electrodes24,28, and30. The lead bodies of leads16and18may be formed from a non-conductive material, including silicone, polyurethane, fluoropolymers, mixtures thereof, and other appropriate materials, and shaped to form one or more lumens within which the one or more conductors extend. The respective conductors may electrically couple to circuitry, such as a therapy module or a sensing module, of ICD14via connections in connector assembly, including associated feedthroughs. The electrical conductors transmit therapy from a therapy module within ICD14to one or more of electrodes24,28, and30and transmit sensed electrical signals from one or more of electrodes24,28, and30to the sensing module within ICD14. However, the techniques are not limited to such constructions. The leads16and18may further include one or more anchoring mechanisms that are positioned along the length of the lead body. The anchoring mechanisms affix the lead18that is implanted in a substernal space in a fixed location to prevent dislodging of the lead18once it is implanted. For example, the lead18may be anchored at one or more locations situated between the distal lead end positioned within the substernal space of patient12and a point along the length of the portion of the lead body at or near the insertion point of the lead body into the substernal space. The one or more anchoring mechanism(s) may either engage bone, fascia, muscle or other tissue of patient12or may simply be wedged therein to affix the lead under the sternum to prevent excessive motion or dislogment. Furthermore, it should be understood that various anchoring mechanisms described in this disclosure may additionally be utilized for delivery of a stimulation therapy as is known in the art. In accordance with various embodiments of the invention, this disclosure describes anchoring mechanisms that are integrated into the lead body. In such embodiments, a portion or segment of the lead body may be formed with materials that function to encase conductors and other elements internal to the lead while also anchoring the lead within the implant environment. In alternative embodiments, anchoring mechanisms of the disclosure are described as discrete elements that may be formed in line with the lead body. In some embodiments, the discrete components may be provided in a fixedly-secured relationship to the lead body. In other embodiments, the anchoring mechanism may be detachedly coupled in a sliding relationship over the lead body. The anchoring mechanisms may include a passive anchoring mechanism, an active anchoring mechanism or a combination of both. In one embodiment, the anchoring mechanism is coupled at a distal end of the lead body and may also function as an electrically active element. Examples of passive anchoring mechanisms include flanges, disks, pliant tines, flaps, porous structures such as a mesh-like element that facilitate tissue growth for engagement, bio-adhesive surfaces, and/or any other non-piercing elements. Examples of active anchoring mechanisms may include rigid tines, prongs, barbs, clips, screws, and/or other projecting elements that pierce and penetrate into tissue to anchor the lead. As another example of an active anchoring mechanism, the lead may be provided with a side helix for engaging tissue. The various examples of the anchoring mechanisms may be deployable. As such, the anchoring mechanism assumes a first state during maneuvering of the lead (during which time the lead is disposed within a lumen of a delivery system or overtop a guidewire or stylet) to the desired implant location. Subsequently, the anchoring mechanism assumes a second state following the release of the lead from the delivery system into the substernal space to thereby anchor the distal end portion of the lead body relative to the adjacent tissue. In addition or alternatively, the lead may be anchored through a suture that fixedly-secures the lead to the patient's musculature, tissue or bone at the xiphoid entry site. In some embodiments, the suture may be sewn through pre-formed suture holes to the patient. The examples illustrated inFIGS.1A-Care exemplary in nature and should not be considered limiting of the techniques described in this disclosure. In other examples, ICD14, defibrillation lead16, and pacing lead18may be implanted at other locations. For example, ICD14may be implanted in a subcutaneous pocket in the right pectoral region. In this example, defibrillation lead16may extend subcutaneously from the device toward the manubrium of the sternum and bend or turn and extend subcutaneously inferiorly from the manubrium of the sternum, substantially parallel with the sternum and pacing lead18may extend subcutaneously from the device toward the manubrium of the sternum to the desired location and bend or turn and extend inferior from the manubrium underneath/below sternum22to the desired location. In yet another example, implantable pulse generator14may be placed abdominally. In the example illustrated inFIG.1, system10is an ICD system that provides cardioversion/defibrillation and pacing therapy. However, these techniques may be applicable to other cardiac systems, including cardiac resynchronization therapy defibrillator (CRT-D) systems or other cardiac stimulation therapies, or combinations thereof. For example, ICD14may be configured to provide electrical stimulation pulses to stimulate nerves, skeletal muscles, diaphragmatic muscles, e.g., for various neuro-cardiac applications and/or for apnea or respiration therapy. In addition, it should be noted that system10may not be limited to treatment of a human patient. In alternative examples, system10may be implemented in non-human patients, e.g., primates, canines, equines, pigs, ovines, bovines, and felines. These other animals may undergo clinical or research therapies that may benefit from the subject matter of this disclosure. FIG.2is a functional block diagram of an example configuration of electronic components of an example ICD14. ICD14includes a control module60, sensing module62, therapy module64, communication module68, and memory70. The electronic components may receive power from a power source66, which may, for example, be a rechargeable or non-rechargeable battery. In other embodiments, ICD14may include more or fewer electronic components. The described modules may be implemented together on a common hardware component or separately as discrete but interoperable hardware, firmware or software components. Depiction of different features as modules is intended to highlight different functional aspects and does not necessarily imply that such modules must be realized by separate hardware, firmware or software components. Rather, functionality associated with one or more modules may be performed by separate hardware, firmware or software components, or integrated within common or separate hardware, firmware or software components. Sensing module62is electrically coupled to some or all of electrodes24,28,30,32, and34via the conductors of leads16and18and one or more electrical feedthroughs, and is also electrically coupled to the housing electrode via conductors internal to the housing of ICD14. Sensing module62is configured to obtain signals sensed via one or more combinations of electrodes24,28,30,32,34, and the housing electrode of ICD14and process the obtained signals. The components of sensing module62may be analog components, digital components or a combination thereof. Sensing module62may, for example, include one or more sense amplifiers, filters, rectifiers, threshold detectors, analog-to-digital converters (ADCs) or the like. Sensing module62may convert the sensed signals to digital form and provide the digital signals to control module60for processing or analysis. For example, sensing module62may amplify signals from the sensing electrodes and convert the amplified signals to multi-bit digital signals by an ADC. Sensing module62may also compare processed signals to a threshold to detect the existence of atrial or ventricular depolarizations (e.g., P- or R-waves) and indicate the existence of the atrial depolarization (e.g., P-waves) or ventricular depolarizations (e.g., R-waves) to control module60. Control module60may process the signals from sensing module62to monitor electrical activity of heart26of patient12. Control module60may store signals obtained by sensing module62as well as any generated EGM waveforms, marker channel data or other data derived based on the sensed signals in memory70. Control module60also analyzes the EGM waveforms and/or marker channel data to detect cardiac events (e.g., tachycardia). In response to detecting the cardiac event, control module60may control therapy module64to generate and deliver the desired therapy according to one or more therapy programs, which may be stored in memory70, to treat the cardiac event. The therapy may include, but is not limited to, defibrillation or cardioversion shock(s), ATP, post-shock pacing, bradycardia pacing, or the like. Therapy module64is configured to generate and deliver electrical stimulation therapy to heart26. Therapy module64may include one or more pulse generators, capacitors, and/or other components capable of generating and/or storing energy to deliver as pacing therapy, defibrillation therapy, cardioversion therapy, cardiac resynchronization therapy, other therapy or a combination of therapies. In some instances, therapy module64may include a first set of components configured to provide pacing therapy and a second set of components configured to provide defibrillation therapy. In other instances, the same set of components may be configurable to provide both pacing and defibrillation therapy. In still other instances, some of the defibrillation and pacing therapy components may be shared components while others are used solely for defibrillation or pacing. Therapy module64delivers the generated therapy to heart26via one or more combinations of electrodes24,28,30,32,34, and the housing electrode of ICD14. Control module60controls therapy module64to generate electrical stimulation therapy with the amplitudes, pulse widths, timing, frequencies, or electrode combinations specified by the selected therapy program. In the case of pacing therapy, e.g., ATP, post-shock pacing, and/or bradycardia pacing provided via electrodes32and/or34of pacing lead18, control module60controls therapy module64to generate and deliver pacing pulses with any of a number of amplitudes and pulse widths to capture heart26. The pacing thresholds of heart26when delivering pacing pulses from the anterior mediastinum using pacing lead18may depend upon a number of factors, including location, type, size, orientation, and/or spacing of electrodes32and34, location of ICD14relative to electrodes32and34, physical abnormalities of heart26(e.g., pericardial adhesions or myocardial infarctions), or other factor(s). The increased distance from electrodes32and34of pacing lead18to the heart tissue may result in heart26having increased pacing thresholds compared to transvenous pacing thresholds. To this end, therapy module64may be configured to generate and deliver pacing pulses having larger amplitudes and/or pulse widths than conventionally required to obtain capture via transvenously implanted lead or a lead attached to heart26. In one example, therapy module64may generate and deliver pacing pulses having amplitudes of less than or equal to 8 volts and pulse widths between 0.5-3.0 milliseconds. In another example, therapy module64may generate and deliver pacing pluses having amplitudes of between 5 and 10 volts and pulse widths between approximately 3.0 milliseconds and 10.0 milliseconds. In another example, therapy module64may generate and deliver pacing pluses having pulse widths between approximately 2.0 milliseconds and 8.0 milliseconds. In a further example, therapy module64may generate and deliver pacing pluses having pulse widths between approximately 0.5 milliseconds and 20.0 milliseconds. In another example, therapy module64may generate and deliver pacing pluses having pulse widths between approximately 1.5 milliseconds and 20.0 milliseconds. In some cases, therapy module64may generate pacing pulses having longer pulse durations than conventional transvenous pacing pulses to achieve lower energy consumption. For example, therapy module64may be configured to generate and deliver pacing pulses having pulse widths or durations of greater than two (2) milliseconds. In another example, therapy module64may be configured to generate and deliver pacing pulses having pulse widths or durations of between greater than two (2) milliseconds and less than or equal to three (3) milliseconds. In another example, therapy module64may be configured to generate and deliver pacing pulses having pulse widths or durations of greater than or equal to three (3) milliseconds. In another example, therapy module64may be configured to generate and deliver pacing pulses having pulse widths or durations of greater than or equal to five (5) milliseconds. In another example, therapy module64may be configured to generate and deliver pacing pulses having pulse widths or durations of greater than or equal to ten (10) milliseconds. In a further example, therapy module64may be configured to generate and deliver pacing pulses having pulse widths between approximately 3-10 milliseconds. In a further example, therapy module64may be configured to generate and deliver pacing pulses having pulse widths or durations of greater than or equal to fifteen (15) milliseconds. In yet another example, therapy module64may be configured to generate and deliver pacing pulses having pulse widths or durations of greater than or equal to twenty (20) milliseconds. Depending on the pulse widths, ICD14may be configured to deliver pacing pulses having pulse amplitudes less than or equal to twenty (20) volts, deliver pacing pulses having pulse amplitudes less than or equal to ten (10) volts, deliver pacing pulses having pulse amplitudes less than or equal to five (5) volts, deliver pacing pulses having pulse amplitudes less than or equal to two and one-half (2.5) volts, deliver pacing pulses having pulse amplitudes less than or equal to one (1) volt. In other examples, the pacing pulse amplitudes may be greater than 20 volts. Typically the lower amplitudes require longer pacing widths as illustrated in the experimental results. Reducing the amplitude of pacing pulses delivered by ICD14reduces the likelihood of extra-cardiac stimulation. Some experimental results are provided later illustrating some example combinations of pacing amplitudes and widths. In the case of defibrillation therapy, e.g., defibrillation or cardioversion shocks provided by defibrillation electrode24of defibrillation lead16, control module60controls therapy module64to generate defibrillation or cardioversion shocks having any of a number of waveform properties, including leading-edge voltage, tilt, delivered energy, pulse phases, and the like. Therapy module64may, for instance, generate monophasic, biphasic or multiphasic waveforms. Additionally, therapy module64may generate defibrillation waveforms having different amounts of energy. For example, therapy module64may generate defibrillation waveforms that deliver a total of between approximately 60-80 Joules (J) of energy. Therapy module64may also generate defibrillation waveforms having different tilts. In the case of a biphasic defibrillation waveform, therapy module64may use a 65/65 tilt, a 50/50 tilt, or other combinations of tilt. The tilts on each phase of the biphasic or multiphasic waveforms may be the same in some instances, e.g., 65/65 tilt. However, in other instances, the tilts on each phase of the biphasic or multiphasic waveforms may be different, e.g., 65 tilt on the first phase and 55 tilt on the second phase. The example delivered energies, leading-edge voltages, phases, tilts, and the like are provided for example purposes only and should not be considered as limiting of the types of waveform properties that may be utilized to provide subcutaneous defibrillation via defibrillation electrode24. Communication module68includes any suitable hardware, firmware, software or any combination thereof for communicating with another device, such as a clinician programmer, a patient monitoring device, or the like. For example, communication module68may include appropriate modulation, demodulation, frequency conversion, filtering, and amplifier components for transmission and reception of data with the aid of antenna72. Antenna72may be located within the connector block of ICD14or within housing ICD14. The various modules of ICD14may include any one or more processors, controllers, digital signal processors (DSPs), application specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), or equivalent discrete or integrated circuitry, including analog circuitry, digital circuitry, or logic circuitry. Memory70may include computer-readable instructions that, when executed by control module60or other component of ICD14, cause one or more components of ICD14to perform various functions attributed to those components in this disclosure. Memory70may include any volatile, non-volatile, magnetic, optical, or electrical media, such as a random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), static non-volatile RAM (SRAM), electrically-erasable programmable ROM (EEPROM), flash memory, or any other non-transitory computer-readable storage media. FIG.3is a flow diagram illustrating example operation of an implantable cardiac system, such as implantable cardiac system10ofFIGS.1A-1C. Initially, ICD14analyzes sensed electrical signals from one or more sensing vectors of pacing lead18and/or one or more sensing vectors of defibrillation lead16to detect tachycardia, such as ventricular tachycardia or ventricular fibrillation (90). ICD14deliver a sequence of ATP pacing pulses via a therapy vector that includes at least one electrode of pacing lead18, which is implanted in the substernal space (92). ICD14may deliver the sequence of ATP pacing pulses to heart26via a pacing vector that includes any combination of one or both of electrodes32and34and a housing electrode of ICD14, e.g., via a bipolar or unipolar pacing vector. Alternatively, ICD14may deliver the sequence of ATP pacing pulses via a therapy vector between one of the electrodes of pacing lead18and an electrode of defibrillation lead16. As described above, the pacing pulses provided by ICD14may have longer pulse widths than conventional pacing pulses. For example, ICD14may be configured to deliver pacing pulses having pulse widths of greater than two milliseconds. In other instances, ICD14may be configured to deliver pacing pulses having pulse widths of between three and ten milliseconds. Other ranges of pulse widths, as well as pacing amplitudes, rates, number of pulses, and the like and various combinations of characteristics are described in further detail herein. In some instances, ICD14may be configured to only deliver ATP to particular types of tachyarrhythmias. ICD14may, for example, distinguish between VT and VF and only provide ATP in instances in which the tachycardia is VT. If the tachycardia is VF, the ICD14may be configured to not provide ATP and instead only deliver defibrillation therapy. After delivery of the sequence of ATP pacing pulses, ICD14determines whether the tachycardia is terminated (94). ICD14may, for example, analyze the most recent sensed activity of the heart to determine if the sequence of ATP pacing pulses terminated the tachycardia. When ICD14determines that the tachycardia has terminated (“YES” branch of block94), ICD14ends the tachycardia therapy and returns to analyzing sensed electrical signals (96). When ICD14determines that the tachycardia has not terminated (“NO” branch of block94), ICD14determines whether additional sequences of ATP pacing pulses will be provided (98). ICD14may, for example, be configured to deliver ATP therapy that consists of two or more sequences of ATP pacing pulses. When ICD14determines that additional sequences of ATP pacing pulses will be provided (“YES” branch of block98), ICD14delivers a second sequence of ATP pacing pulses via a therapy vector that includes at least one electrode of pacing lead18, which is implanted in the substernal space (92). The second sequence of pacing pulses may be the same as the first sequence. Alternatively, the second sequence of pacing pulses may be different than the first sequence. For example, the ATP pulses of the first and second sequences of pulses may have one or more different characteristics including, but not limited to, different pacing amplitudes, pulse widths, rates, therapy vectors, and/or variation among pacing pulses. When ICD14determines that no additional sequences of ATP pacing pulses will be provided (“NO” branch of block98), ICD14delivers a defibrillation pulse via a therapy vector that includes defibrillation electrode24of defibrillation lead16(99). As described with respect toFIGS.1A-1C, defibrillation lead16may, in some instances, be implanted subcutaneously between the skin and the sternum and/or ribcage. Alternatively, defibrillation lead16may be implanted at least partially in the substernal space or other extravascular location, as described with respect toFIGS.10A and10B. The amount of energy of the defibrillation pulse will depend on the location of the defibrillation electrode24as described in further detail herein. EXPERIMENTS Three acute procedures were performed using pigs, with the animals in a dorsal recumbency. An incision was made near the xiphoid process and a Model 4194 lead was delivered to the substernal/retrosternal space using a 6996T tunneling tool and sheath. An active can emulator (ACE) was placed in a subcutaneous pocket on either the right chest (first acute experiment) or the left midaxillary (second and third acute experiments). Various pacing configurations were tried and different pieces of equipment were used as the source of stimulation. Multiple pulse widths were used in delivering the pacing pulse. Across experiments, several different substernal/retrosternal lead electrode locations were utilized. In the second and third experiments the impact of lead location on electrical performance was investigated by moving the lead to several locations under the sternum and collecting data to generate strength-duration curves at each location. In all three acute experiments, the substernal/retrosternal lead was placed and electrical data collected. The lead was moved intentionally many times across experiments to better understand the location best suited to capturing the heart at low pacing thresholds, with different locations and parameters tried until pacing capability was gained and lost. A range of thresholds based on location and pacing configuration was recorded. For this reason, the lowest threshold result for each acute experiment is reported, as are strength-duration curves showing the range of pacing values obtained from suitable pacing locations. In all cases, it was determined that positioning the substernal/retrosternal pacing electrode approximately over the ventricle of the cardiac silhouette provided best results. Experiment 1 In the first acute study, a Medtronic Attain bipolar OTW 4194 lead was implanted substernally/retrosternally, and two active can emulators were positioned, one in the right dorsal lateral region (ACE1) and one on the right midaxillary (ACE2). The 4194 lead was placed directly below the sternum, in the mediastinum, with the lead tip and body running parallel to the length of the sternum. Various pacing configurations were tried and electrical data collected. The smallest threshold observed was 0.8 volts, obtained when pacing from the tip of the substernal/retrosternal 4194 lead to ACE1 (10 ms pulse width and Frederick Heir instrument as the source of stimulation). It was possible to capture using a smaller pulse width, though threshold increased as the pulse width shortened (1.5V at 2 ms in this same configuration with a bp isolater, made by FHC product #74-65-7, referred to herein as “Frederick Heir Stimulator.” Many additional low thresholds (1-2 volts) were obtained with different pacing configurations and pulse durations. FIG.4illustrates a strength-duration curve showing the capture thresholds obtained at various pulse widths during the first acute study. Note that all configurations paced from either the tip or the ring of the substernally/retrosternally implanted 4194 lead (−) to one of the two active can emulators (+). In one instance, a large spade electrode (instead of a Model 4194 lead) was used as the substernal/retrosternal electrode, as noted in the legend ofFIG.4. As shown, several pacing configurations and parameters were tried. Across the configurations reported in the graph above, threshold values ranged from 0.8 volts to 5.0 volts, with threshold generally increasing as pulse width was shortened. In a few instances, the threshold at 1.5 ms pulse width was smaller than the threshold at 2.0 ms. It should be noted that the threshold value obtained at 1.5 ms was always recorded using the Medtronic 2290 analyzer as the stimulation source, whereas all other threshold measurements for the first acute experiment (at pulse widths of 2, 10, 15 and 20 ms) were obtained using a Frederick Heir instrument as the source of stimulation. Differences in these two instruments may account for the difference in threshold values at similar pulse widths (1.5 ms and 2 ms). In general, the first acute experiment demonstrated the feasibility of substernal/retrosternal pacing by producing small capture thresholds (average=2.5±1.2 volts), using several different pacing configurations and parameters. Experiment 2 A second acute experiment was conducted. In the second acute, however, the animal presented with pericardial adhesions to the sternum. Because of the pericardial adhesion, the ventricular surface of the cardiac silhouette was rotated away from the sternum—an anatomical difference that may have resulted in higher thresholds throughout this experiment. As in the previous acute experiment, a Model 4194 lead was placed under the sternum. An active can emulator was placed on the left midaxillary. The tip to ring section of the 4194 was positioned over the cardiac silhouette of the ventricle, as observed by fluoroscopy, and this position is notated “Position A” on the strength-duration graph illustrated inFIG.5. The lead eventually migrated a very short distance closer to the xiphoid process during stimulation (still under the sternum) to reach “Position B,” and additional electrical measurements were obtained successfully from this position as well. The smallest threshold observed in the second acute experiment was 7V, obtained when pacing from the substernal/retrosternal 4194 ring electrode (−) to an ACE (+) on the left midaxillary in the first lead position (5 ms, 15 ms and 20 ms pulse widths, Frederick Heir stimulator). Additionally, thresholds of 8 and 9 volts were obtained with the lead in the second anatomical position, both from 4194 tip to ACE (unipolar) and 4194 tip to ring (bipolar) configurations at multiple pulse widths. The two lines that appear to run off the chart were instances of no capture. All of the electrical values reported inFIG.5were collected with the Frederick Heir instrument as the stimulation source. Extra-cardiac stimulation was observed with many of the electrical measurements obtained in a unipolar pacing configuration. No obvious extra-cardiac stimulation was observed when pacing in a bipolar configuration (4194 tip to ring), though a low level of stimulation could be felt with a hand on the animal's chest. Experiment 3 A third and final acute experiment was conducted demonstrating the feasibility of substernal/retrosternal pacing. As in the previous two acute experiments, a 4194 lead was placed under the sternum. An active can emulator was placed on the left midaxillary. In this experiment, the substernal/retrosternal 4194 lead was intentionally positioned so that the lead tip was initially near the second rib, far above the cardiac silhouette of the ventricle. The lead tip was then pulled back (toward the xiphoid process) one rib space at a time, collecting electrical data at each position. As in previous experiments, low capture thresholds were obtained when the pacing electrodes were approximately positioned over the ventricular surface of the cardiac silhouette, as observed via fluoroscopy. When the lead tip was not over the ventricular surface of the cardiac silhouette, “no capture” was often the result. As in previous experiments, pacing was performed from either the tip or the ring of the substernal/retrosternal 4194 lead (−) to the ACE (+) on the left midaxillary. However, in this acute experiment, a subcutaneous ICD lead was also positioned in its subcutaneous arrangement (as illustrated and described inFIGS.1A-C). In some instances, the pacing configuration was from either the tip or the ring of the substernal/retrosternal 4194 lead (−) to either the ring or the coil of the subcutaneous ICD lead (+), so that the ICD lead and not the ACE was the indifferent electrode. The smallest threshold observed across the experiment was 0.8V, obtained when pacing from the substernal/retrosternal 4194 tip electrode (−) to an ACE (+) on the left midaxillary when the lead was positioned such that the lead tip electrode was approximately under the sixth rib (20 ms pulse width and Frederick Heir stimulator). Many additional low thresholds were obtained with different pacing configurations, shorter pulse durations and different lead positions, again demonstrating the feasibility of substernal/retrosternal pacing. Obvious extra-cardiac stimulation generally was not observed with lower threshold measurements (at longer pulse durations) but was observed at higher thresholds. The strength duration curves for lead positions 3-5 are presented inFIGS.7-9, with individual graphs for each location due to the breadth of electrical data collected. Measurements made with the 2290 analyzer as the source of stimulation are noted. Other electrical measurements were made with the Frederick Heir instrument as the stimulation source. FIG.6illustrates the strength-duration curve of electrical data from the third acute experiment when the 4194 lead tip was positioned under the sternum near the location of the 4thrib. Several therapy vectors resulted in low pacing thresholds, generally when pulse widths were quite long. At shorter pulse widths, threshold increased. FIG.7illustrates the strength-duration curve of electrical data from the third acute experiment when the 4194 lead tip was positioned under the sternum near the location of the 5thrib. The two lines that appear to run off the chart at 0.2 ms were instances of no capture.FIG.7demonstrates the position dependence of the substernal/retrosternal lead. Thresholds were higher overall in this anatomical location (the lead tip near the 5thrib), though capture was still possible and in the 4194 ring (−) to ACE (+) configuration, moderately low (2 volts at 20 ms). There generally was no significant extra-cardiac stimulation observed except with pulse widths of 0.2 ms and 0.5 ms in the 4194 tip (−) to ACE (+) configuration and in the unipolar configuration going from the 4194 tip (−) to the coil of the subcutaneous ICD lead at pulse widths of 1.5 ms and shorter, all of which resulted in the highest recorded threshold readings in this lead position. FIG.8illustrates the strength-duration curve of electrical data from the third acute experiment when the 4194 lead tip was positioned under the sternum near the location of the 6thrib.FIG.8shows the position dependence of the substernal/retrosternal electrode. When the pacing electrode is optimally located over the ventricular surface of the cardiac silhouette (as observed via fluoroscopy), pacing threshold is low. Low thresholds were very repeatable in this anatomical location, even at shorter pulse durations and in many different pacing configurations. Extra-cardiac stimulation generally was not apparent at low thresholds and longer pulse durations throughout this experiment. All three acute experiments demonstrated the feasibility of pacing from a sub sternal/retrosternal electrode location. The lowest threshold results across the three acute procedures were 0.8 volts, 7 volts and 0.8 volts, respectively, with the second acute procedure involving an anatomical difference (pericardial adhesions) that tipped the ventricular surface of the heart away from its normal orientation with the sternum, resulting in higher pacing thresholds. However, for the purposes of anti-tachycardia pacing, conventional devices typically default to maximum output (8V at 1.5 ms) for ATP therapy delivery. Given this, even the 7V threshold obtained in the second acute experiment could be satisfactory for ATP therapy. The ability to capture the heart at low pacing thresholds was dependent upon electrode position. As observed through these experiments, the substernal/retrosternal pacing electrode provide the best outcomes when positioned approximately over the ventricular surface of the cardiac silhouette, which is easily observed via fluoroscopy and encompasses a reasonably large target area for lead placement. In the third acute experiment, for example, capture was achieved at three separate positions, with the lead tip at approximately ribs 4, 5 and 6, all of which were near the ventricular surface of the cardiac silhouette. Pacing thresholds increased with shorter pulse durations. In many instances, however, low pacing thresholds were obtained even at short pulse widths, especially when the substernal/retrosternal pacing electrode was positioned over the ventricular surface of the cardiac silhouette. In other instances, longer pulse durations (10-20 ms) were necessary to obtain capture or to achieve lower capture thresholds. Across experiments, it was possible to pace from the substernal/retrosternal lead to an active can emulator positioned near the animal's side (unipolar) and also from the substernal/retrosternal lead to a subcutaneous ICD lead (unipolar). If a subcutaneous ICD system incorporated a pacing lead, placed substernally/retrosternally, for the purpose of anti-tachycardia pacing, both of the aforementioned unipolar pacing configurations would be available for a physician to choose from. These experiments also demonstrated the ability to pace in a bipolar configuration entirely under the sternum (4194 tip (−) to 4194 ring (+), substernally/retrosternally), indicating that either a bipolar lead positioned under the sternum might be used for anti-tachycardia pacing purposes. Overall, the results of these acute experiments demonstrate the ability to pace the heart from a substernal/retrosternal location, with the lead not entering the vasculature or the pericardial space, nor making intimate contact with the heart. The low threshold values obtained when pacing from a substernal/retrosternal lead location in these acute experiments suggest that pain-free pacing for the purpose of anti-tachycardia pacing in a subcutaneous ICD system is within reach. In some instances, electrodes of pacing lead18may be shaped, oriented, designed or otherwise configured to reduce extra-cardiac stimulation.FIG.9is a schematic diagram illustrating an example electrode configuration for pacing lead18. In the example ofFIG.9, electrode100is attached to the underside of a pad102. Pad102may be constructed of a non-conductive material such as a polymer. Pacing lead18may be anchored to under the sternum in such a manner to direct or point electrode100toward heart26. In this manner, pacing pulses delivered by ICD14via the pacing lead are directed toward heart26and not outward toward skeletal muscle. The electrode illustrated inFIG.9may be incorporated within a lead, such as pacing lead18. In some instances, pad102may also provide an anchoring mechanism such as an adhesive.FIG.9illustrates one example design of an electrode configured to reduce extra-cardiac stimulation by focusing or directing or pointing the stimulation energy toward heart26. However, other configurations of electrodes may be utilized to perform such a function. As another example, one or both of electrodes32and34may be partially coated or masked with a polymer (e.g., polyurethane) or another coating material (e.g., tantalum pentoxide) on one side or in different regions so as to direct the pacing signal toward heart26and not outward toward skeletal muscle. FIGS.10A and10Bare conceptual diagrams of patient12implanted with another example implantable cardiac system110.FIG.10Ais a front view of patient12implanted with implantable cardiac system110.FIG.10Bis a transverse view of patient12with implantable cardiac system110. Implantable cardiac system110conforms substantially to implantable cardiac system10ofFIGS.1A-1C, but defibrillation lead16of system110is implanted at least partially in the substernal/retrosternal space. In this manner, both defibrillation lead16and pacing lead18are implanted within the substernal space. Like pacing lead18ofFIGS.1A-1C, defibrillation lead16extends subcutaneously from ICD14toward xiphoid process20, and at a location near xiphoid process20bends or turns and extends superior in the substernal space. In one example, the distal portion of defibrillation lead16may be placed in anterior mediastinum36similar to lead18. In this manner, ICD14may be configured to deliver both defibrillation therapy and pacing therapy to patient12substernally. In other instances, defibrillation lead16and/or pacing lead18may be implanted elsewhere in the substernal space. The benefits of placing pacing lead18in this location are described in detail above. Placing defibrillation lead16in the substernal space also provides a number of advantages. As described above, ICD14generates and delivers defibrillation energy of approximately 80 Joules (J) when defibrillation lead16is implanted subcutaneously. Placing defibrillation lead16in the substernal space significantly may reduce the amount of energy that needs to be delivered to defibrillate heart26. As one example, ICD14may generate and deliver cardioversion or defibrillation shocks having energies of less than 80 J. As another example, ICD14may generate and deliver cardioversion or defibrillation shocks having energies of less than 65 J. As one example, ICD14may generate and deliver cardioversion or defibrillation shocks having energies of less than 60 Joules (J). In some instances, ICD14may generate and deliver cardioversion or defibrillation shocks having energies between 40-50 J. In other instances ICD14may generate and deliver cardioversion or defibrillation shocks having energies between 35-60 J. In still other instances, ICD14may generate and deliver cardioversion or defibrillation shocks having energies less than 35 J. As such, placing defibrillation lead16within the substernal space, e.g., with the distal portion substantially within anterior mediastinum36, may result in reduced energy consumption and, in turn, smaller devices and/or devices having increased longevity. Various examples have been described. These and other examples are within the scope of the following claims. | 63,488 |
11857780 | DETAILED DESCRIPTION Some implementations of the present disclosure will now be described more fully hereinafter with reference to the accompanying figures, in which some, but not all implementations of the disclosure are shown. Indeed, various implementations of the disclosure may be expressed in many different forms and should not be construed as limited to the implementations set forth herein; rather, these example implementations are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art. As used herein, the term “and/or” and the “/” symbol includes any and all combinations of one or more of the associated listed items. Also, for example, reference may be made herein to quantitative measures, values, relationships or the like. Unless otherwise stated, any one or more if not all of these may be absolute or approximate to account for acceptable variations that may occur, such as those due to engineering tolerances or the like. Further, unless otherwise indicated, something being described as being a first, second or the like should not be construed to imply a particular order. It should be understood that the terms first, second, etc. may be used herein to describe various steps, calculations, positions and/or the like, these steps, calculations or positions should not be limited to these terms. These terms are only used to distinguish one operation, calculation, or position from another. For example, a first position may be termed a second position, and, similarly, a second step may be termed a first step, without departing from the scope of this disclosure. Additionally, something may be described as being above something else (unless otherwise indicated) may instead be below, and vice versa; and similarly, something described as being to the left of something else may instead be to the right, and vice versa. As used in the specification, and in the appended claims, the singular forms “a,” “an,” “the,” include plural referents unless the context clearly dictates otherwise. Like reference numerals refer to like elements throughout. Example implementations of the present disclosure provide an electrical probe assembly for electrically stimulating an object or recording stimulated object activity. Generally, the electrical probe assembly may include at least an electrical probe. Where the As used herein, an “electrical probe,” “nerve probe,” and the like may refer to either a stimulus (stim) probe that uses electrical energy to stimulate (innervate) an object, or a recording probe that records activity (e.g., electrical signals, such as a reflex arc or a reflex pathway), which may result from electrically stimulating the object. Notably, where tissue is the object to be stimulated or recorded, the electrical probe assembly disclosed herein is referred to as a “nerve probe assembly,” although “nerve probe assembly” and “electrical probe assembly” may be used interchangeably. As used herein, an “object” may refer to tissue such as human, non-human animal or plant tissue. This includes human or non-human animal tissue, such as, for example, connective tissue, muscle tissue, nervous tissue, and epithelial tissue. Plant tissue includes, such as, for example, meristematic tissue and permanent tissue. In other examples, an “object” may refer to an electrically-conductive inorganic material, such as, for example, a glass, a ceramic, and a metal. Any other type of material that may be electrically-conductive or can produce an electrical signal can also be considered an “object” as used in this disclosure. In some example implementations, an electrical probe assembly advantageously is adaptable for electrically-stimulating objects or recording stimulated object activity in various different environments. As such, the electrical probe may include an electrode disposed about an end thereof. The electrical probe may define an axial length that comprises a conductive material, while the electrode may likewise comprise a conductive material. The axial length of the electrical probe may include a shapeable part. As used herein, “shapeable” or “shapeability” refers to an ability of the shapeable part of the axial length of the electrical probe to be manually manipulated into different configurations (e.g., shapes). The shapeable part of the axial length of the electrical probe (or more simply, the shapeable part of the electrical probe) may be pliant, such that the shapeable part is easily manipulated by a user (e.g., a human user, a robotic user, or the like) into one or more different shapes. After manipulation into a first shape, the shapeable part may remain in the first shape until the user manipulates the shapeable part into subsequent different shapes, such as a second shape, a third shape, a fourth shape, etc. The shapeable part may then be manipulated back to the first shape or any previous shapes. The shapeable part of the electrical probe may also be adaptable for different flexibilities, ranging from “stiff” to “flexible.” “Flexible,” “flexibility,” etc., refers to how the shapeable part of the electrical probe reacts to a non-axial force. A “stiff” shapeable part of the electrical probe may be a shapeable part that may experience zero deflection under zero force (i.e., is rigid or stiff); although, some degree of non-axial force may introduce some resultant deflection of the shapeable part. By contrast, a “flexible” shapeable part of the electrical probe may be a shapeable part that may exhibit a degree of deflection through minimal non-axial force. The flexibility of the shapeable part of the electrical probe may be modified by an adjustment structure that adjusts exposure of the axial length of the electrical probe relative to a rigid sheathing that may cover at least a portion of the shapeable part of the electrical probe. Increased exposure of the axial length of the electrical probe relative to the rigid sheathing may increase a degree of deflection of the shapeable part from non-axial force, while decreased exposure of the axial length of the electrical probe relative to the rigid sheathing may decrease a degree of deflection of the shapeable part from non-axial force. Accordingly, for purposes of the present disclosure, shapeability of the shapeable part of the electrical probe refers to variations of the shape of the shapeable part, while flexibility of the shapeable part of the electrical probe refers to variations of the degree of deflection of the shapeable part in response to non-axial force. In some example implementations, the nerve probe assembly may include more than one electrical probe, such as two, three, four, five, etc., electrical probes. The multiple electrical probes may each include an electrode disposed about respective ends thereof. A handle may include a corresponding number of arms adapted to carry the electrical probes. As such, the multiple electrical probes may be carried in respective arms in a single plane or may be carried in different planes. A spatial distance between the electrodes of each of the electrical probes may be adjusted by a spatial positioning mechanism, which may be coupled to the handle or one or more of the number of arms. An adjustment structure may also be coupled to the handle or one or more of the numbers such that adjustment of the adjustment structure may correspondingly adjust the spatial positioning mechanism. Accordingly, the nerve probe assembly disclosed herein may perform the role of multiple, different nerve probe assemblies since the nerve probe assembly disclosed herein is shapeable, flexible, and/or multipolar to meet a variety of electrical-stimulation and/or recordation needs. As such, the nerve probe assembly may be utilized in applications such as surgeries, electrotherapies, electromyogram (EMG) biofeedback procedures, and the like, so as to advantageously, for example, electrically-stimulate tissue and/or record electrically-stimulated tissue activity, which otherwise may not be reachable by a straight-shafted electrical probe, electrically stimulate multiple areas of tissue at one time and/or record activity of the stimulated multiple areas of tissue at one time, limit electrical-conductivity to where tissue is disposed, thereby decreasing the need for excessive movement (e.g., lifting) of anatomical obstacles such as nerves and potentially decreasing risk for stretching the anatomical obstacle, and the like. Referring now toFIG.1, a schematic of an example electrical probe assembly100for electrically stimulating an object or recording stimulated activity of an object, such as tissue102, is illustrated according to example implementations of the present disclosure. The electrical probe assembly may comprise an electrical probe104including an electrode106disposed on or about an end thereof. The nerve probe assembly may comprise more than one electrical probe, such as, for example, two electrical probes including first and second electrodes disposed on or about respective ends thereof, three electrical probes including first, second, and third electrodes disposed on or about respective ends thereof, etc. In some example implementations, an axial length of the electrical probe may include a shapeable part108. The shapeable part may be shapeable into different shapes, such as, for example, a straight shape, an angled shape, and the like. As such, the shapeable part may comprise a material that allows a user to manually manipulate the shapeable part into a first shape, a second shape, a third shape, etc., where the shapeable part remains in that shape until further manipulation into subsequent different shapes. For example, after manipulation of the shapeable part into a first shape, the shapeable part may remain in the first shape until the user manipulates the shapeable part into a second shape, a third shape, a fourth shape, etc. The shapeable part may then be manipulated back to the first shape or any previous shapes. In some example implementations, the electrical probe104may comprise wire extending along the axial length thereof. The wire of the electrical probe may include one or more strands of wire (e.g., lead wire). There may be one wire, two strands of wire, three strands of wire, four strands of wire, etc., which may be wound together. The strands of wire may comprise an electrically-conductive material, such as, but not limited to platinum iridium, stainless steel, gold-plated silver, and the like. The strands of wire may be covered in a similar, electrically-conductive material, which may vary in composition along the axial length of the electrical probe. For example, a rigid part of the electrical probe may comprise the strands of wire covered in a non-pliant, electrically-conductive material such that the rigid part cannot be easily shaped, while the shapeable part108may comprise electrically-conductive wire covered in a pliant, electrically-conductive material such that the shapeable part may be easily shaped into different shapes. FIGS.2A-2Cillustrate different example wire configurations for axial lengths of electrical probes,200A-200C, for a nerve probe assembly, such as the nerve probe assembly100. InFIG.2A, for example, an axial length of a shapeable portion202A is illustrated, with three (3) strands of wire204A wound together and with a single electrode206A defining a ball tip electrode at the end thereof. InFIG.2B, for example, an axial length of a shapeable portion202B is illustrated, with seven (7) strands of wire204B wound together and with a single electrode206B defining a ball tip electrode at the end thereof. InFIG.2C, for example, an axial length of a shapeable portion202C is illustrated, with nineteen (19) strands of wire204C wound together and with a single electrode206C defining a ball tip electrode at the end thereof. In some example implementations, the strands of wire extending through the shapeable part108of the electrical probe102may be split into groups of one or more strands of wire each, where each group may be individually shapeable. The groups of wire may be bonded together (e.g., with a heat shrink) along an axial length of the electrical probe. For example, the groups of wire may be bonded along the shapeable part, and may be separable beginning from the end of the electrical probe where the electrode is disposed, so that the electrodes of each group of the one or more wires may be separated at a distance from one another. In this manner, a user may be able to make small adjustments to a shape of the shapeable part by adjusting a shape of each group of the one or more wires. FIGS.3A-3Cillustrate different example configurations of shapeable parts300A-300C of an electrical probe assembly, such as the nerve probe assembly100, where the shapeable parts are each split into groups of one or more strands of wire each. InFIG.3A, the shapeable part300A is split into two groups of one or more strands of wire302A,304A, which are bonded along an axial length of an electrical probe306A and are separated beginning from an end of the electrical probe where electrodes308A are disposed to about midway along an axial length of the shapeable part. InFIG.3B, the shapeable part300B is split into two groups of one or more strands of wire302B,304B, which are bonded along an axial length of an electrical probe306B and are separated beginning from an end of the electrical probe where electrodes308B are disposed to about three quarters of the way along an axial length of the shapeable part. The axial length of the shapeable part inFIG.3Bis shorter than the axial length of the shapeable part inFIG.3A. InFIG.3C, the shapeable part300C is split into two groups of one or more strands of wire302C,304C, which are bonded along an axial length of an electrical probe306C and are separated beginning from an end of the electrical probe where electrodes308C are disposed about midway along an axial length of the shapeable part. The axial length of the shapeable part inFIG.3Cis shorter than the axial length of the shapeable part300A inFIG.3A, and about a same or substantially a same length of the shapeable part300B inFIG.3B. A spacer310is provided along the axial length of the shapeable part300C inFIG.3Cand may be coupled to each of the two groups of one or more strands of wire302C,304C. The spacer may assist in retaining the separation between the groups so that the corresponding distance between the electrodes308C is maintained. However, translating the spacer along the axial length of the electrical probe306C may increase or decrease the separation between the electrodes of each group. For example, where the spacer is moved along an axial length of the electrical probe away from the end thereof, the separation between the electrodes of each group of one or more wires may be increased. In another example, where the spacer is moved along an axial length of the electrical probe toward the end thereof, the separation between the electrodes of each group of one or more wires may be decreased. Referring back toFIG.1, the electrode106may be disposed on or about an end of the electrical probe104so that the electrode is disposed on or about an end of the shapeable part108. The strands of wire extending through the axial length of the electrical probe may connect the electrode to at least one cathode (e.g., three cathodes) and at least one anode (e.g., two anodes) of an electrical power source (e.g., a battery) so as to conduct electrical current through the strands of wire extending along the axial length of the electrical probe to the electrode. The electrode106may define a single electrode (monopolar) or may define two or more electrodes (multipolar) in various arrangements. For example, the electrode may define two electrodes, three electrodes, four electrodes, etc. Where there are multiple electrodes, at least one of the electrodes may comprise a stimulation electrode to stimulate an object, such as tissue, while at least another one of the electrodes may comprise a recording electrode to record activity of a stimulated object, such as tissue. A stimulating tip may be configured to electrically innervate or communicate electrical energy to an object, such as tissue. A recording tip may be configured to record a reflex arc or a reflex pathway that results from electrically stimulating the object. In some example implementations, the electrode may include one or more stimulating tips. For example, an electrode defining a first stimulating tip (monopolar) may be utilized for stimulating an object, such as tissue, such that the first stimulating tip is a first pole, which references another electrode separate from the stimulation probe assembly (i.e., is a second pole). In another example, an electrode defining first and second stimulating tips (bipolar) may utilize the first stimulating tip as an anode and the second stimulating tip as a cathode, or vice versa. In a still further example, an electrode defining first, second, and third stimulating tips (pseudo bipolar) may utilize the first and third stimulating tips as a combined anode and the second stimulating tip as a cathode. Other combinations are also contemplated herein, such as electrodes defining both recording and stimulating tips, only recording tips, etc. The electrode106may comprise an electrically-conductive material, which may be the same material or a different material from the electrically-conductive material covering the axial length of the electrical probe. The electrically-conductive material of the electrode may thus comprise, but is not limited to, platinum iridium, stainless steel, gold-plated silver, and the like. FIGS.4A-4Fillustrate different example electrodes400A-400F disposed on or about an end of electrical probes for a nerve probe assembly, such as the nerve probe assembly100. InFIG.4A, a single electrode400A is shaped as a sphere (i.e., a ball tip electrode). InFIG.4B, a single electrode400B is shaped to be flush with an end of an electrical probe (i.e., a flush tip electrode). InFIG.4C, a single electrode400C is shaped as a cylinder with a domed top (i.e., a rounded tip electrode). InFIG.4D, two electrodes400D are shaped to be flush with an end of an electrical probe and are arranged in concentric circles (i.e., a concentric bipolar tip electrode). InFIG.4E, two electrodes400E are shaped as cylinders with domed tops and are linearly arranged adjacent to one another (i.e., a side-by-side bipolar tip electrode). InFIG.4F, three electrodes400F are shaped as cylinders with domed tops and are linearly arranged adjacent to one another (i.e., a side-by-side tripolar tip electrode). Other electrode configurations not illustrated inFIGS.4A-4Fare also contemplated by this disclosure. One example implementation by may include two stimulating electrodes arranged in concentric circles on or about an end of an electrical probe and two or more recording electrodes extending on or about an end of the electrical probe or on or about an axial length of the electrical probe. Referring back toFIG.1, the electrical probe104may comprise an electrically-insulating sheathing110that extends along or at least partially along the electrical probe. The electrically-insulating sheathing may comprise a material whose internal electrical charges do not flow freely so that very little electrical current flows through it under the influence of an electric field. The electrically-insulating sheathing may, thus, comprise a material such, as for example, glass, paper, polymers, plastics, and the like. In some example implementations, the electrically-insulating sheathing110may extend along the axial length of the electrical probe104up to but not including the end of the electrical probe so that only the electrode106is exposed. As used herein, “expose” refers to electrical current being allowed to flow freely or not be inhibited by any insulating material, so that the electrical current can be transferred. In another example, the electrically-insulating sheathing may extend along the axial length of the electrical probe up to and including the end of the electrical probe, and around the electrode so that only the electrode is exposed. The electrically-insulating sheathing may define an opening or a window so that the exposed portion of the axial length of the electrical probe defines the electrode for electrically stimulating the tissue or recording activity of the stimulated tissue. FIGS.5A-5Fillustrate different example configurations of electrically-insulating sheathings500A-500F on axial lengths of electrical probes and electrodes of electrical probes for a nerve probe assembly, such as nerve probe assembly100.FIG.5Aillustrates an electrically-insulating sheathing500A that extends along an axial length of an electrical probe502A up to the electrode504A shaped as a crook so that only the electrode is exposed. FIGS.5B-5Fillustrate an electrically-insulating sheathing that defines an opening or window defining an exposed part of an electrical probe, with an end shaped as a crook or hook, to thereby define an electrode of the electrical probe. This may be advantageous when a user elevates an object (e.g., nerves) from surrounding objects (e.g., tissues). One of the primary reasons users may utilize a crooked electrical probe to elevate nerves is to electrically isolate the nerve from the surrounding tissue in order to stimulate that nerve without electrically activating the surrounding tissue. However, elevating nerves by lifting them with a conventional crooked electrode may stretch the nerve. The electrically-insulating sheathing that defines an opening or window about an electrical probe with an end shaped as a crook or hook, as disclosed herein, advantageously enables a user to mechanically hold and elevate tissue a minimal amount without stimulating said tissue, while electrically stimulating only what is underneath the tissue being held. As such, the disclosed configuration may decrease the amount of elevation required to electrically isolate the nerve beneath the tissue, thereby potentially decreasing the risk for nerve injury due to nerve stretching. FIG.5Billustrates an electrically-insulating sheathing500B that extends along an axial length of an electrical probe502B shaped as a crook. In this manner, the electrically-conductive sheathing inFIG.5Bdefines an electrode504B via an opening or a window506B in the electrically-insulating sheathing. The opening exposes the electrode defined thereby about an interior portion of the crook. FIGS.5C and5Dillustrate two different configurations of electrically-insulating sheathing500C and500D (respectively) that extend along axial lengths of electrical probes502C and502D shaped as crooks. In this manner, the electrically-conductive sheathing defines electrodes504C,504D via openings506C,506D in the electrically-insulating sheathings. The openings expose the electrode defined thereby. The electrodes inFIGS.5C and5Dare smaller than the electrode504B illustrated inFIG.5B. InFIG.5C, the opening is located on an interior portion of the crook, closer to an end of the electrical probe, while inFIG.5D, the opening is located on an interior portion of the crook, farther away from the end of the electrical probe. FIG.5Eillustrates an electrically-insulating sheathing500E that extends along an axial length of an electrical probe502E shaped as a crook. In this manner, the electrically-conductive sheathing inFIG.5Edefines an electrode504E via an opening or window506E in the electrically-insulating sheathing. The opening or window is located on an exterior portion of the crook. FIG.5Fillustrates an electrically-insulating sheathing500F that extends along an axial length of an electrical probe502F shaped as a crook. In this manner, the electrically-conductive sheathing inFIG.5Fdefines an electrode504F via an opening or window506F in the electrically-insulating sheathing. The opening or window is located on an interior portion of the crook. The electrode ofFIG.5Fis larger than that illustrated inFIGS.5B-5E. FIG.5Gillustrates an electrically-insulating sheathing500G that extends along an axial length of an electrical probe502G shaped as a straight shape. In this manner, the electrically-conductive sheathing inFIG.5Gdefines an electrode504G via an opening506G in the electrically-insulating sheathing. The window or opening is located on an interior portion of the straight shape. The electrode inFIG.5Gis smaller than that illustrated inFIGS.5B-5F. Returning back toFIG.1, the nerve probe assembly100may comprise a rigid sheathing112adapted to cover and thereby inhibit a portion of the shapeable part108of the axial length of the electrical probe from being shaped, such that the portion of the shapeable part covered by the rigid sheathing is adjustable. More particularly, the axial length of the electrical probe may extend through the rigid sheathing so that at least the electrode106is exposed. The rigid sheathing may be considered non-shapeable, non-flexible or stiff, such that it cannot be shaped at all or cannot be easily shaped in comparison with the shapeable part of the electrical probe. In some example implementations, an adjustment structure114and a handle116may be affixed to respective ones of the electrical probe104and the rigid sheathing112. The handle may define an internal cavity sized to fit the adjustment structure. In this manner, the adjustment structure may be adapted to cooperate with the handle to enable adjustment of an amount of the adjustment structure that extends out of the handle, and thereby adjustment of the portion of the shapeable part108of the axial length of the electrical probe covered by the rigid sheathing. Specific examples of the cooperation of the adjustment structure and the handle to adjust an amount of the adjustment structure that extends out of the handle are illustrated inFIGS.6A-6C(back-drive nerve probe assembly) andFIGS.7A-7D(front-drive nerve probe assembly). In some other example implementations, the adjustment structure114may be coupled to one or more portions of the handle116(e.g., a first arm or a second arm). In this manner, the adjustment structure may be adapted to enable adjustment of a distance between multiple electrodes104(e.g., first and second electrodes). Specific examples of the cooperation of the adjustment structure and the handle to enable adjustment of a distance between multiple electrodes are illustrated inFIGS.10A and10B. The nerve probe assembly100may also further comprise an indexing mechanism118coupled to or integrated with the adjustment structure114and arranged to index the adjustment structure in a plurality of pre-determined positions (i.e., pre-determined increments) relative to the handle116. The plurality of positions may include an extended position, a retracted position, and at least one intermediate position therebetween. The extended position and the retracted position may be respectively opposing ends of a range of positions that the adjustment structure can be positioned in, with the extended position being the most extended position and the minimum position being the most retracted position that the adjustment structure may be positionable in. Example implementations of an indexing mechanism are illustrated inFIGS.9A and9B and10A-10C. FIGS.6A-6Cillustrate an example implementation of a nerve probe assembly as generally described inFIG.1. InFIGS.6A-6C, the nerve probe assembly600is configured as a “back-drive” assembly, where an adjustment structure extends between a plurality of positions between an extended position and a retracted position relative to a back end of a handle. InFIG.6A, the nerve probe assembly600comprises an electrical probe602including an electrode604disposed on or about an end thereof for electrically stimulating tissue or recording stimulated tissue activity. The electrode may define a single electrode or two or more electrodes. Where the electrode defines two or more electrodes, the two or more electrodes may include a stimulation electrode for electrically-stimulating tissue, and a recording electrode for recording stimulated tissue activity. Where the electrode defines the two or more electrodes, the two or more electrodes may be arranged as concentric electrodes or side-by-side electrodes. An axial length of the electrical probe602includes a shapeable part606. The axial length of the electrical probe may also define a stiff portion608that is not shapeable or is not easily shapeable as compared to the shapeable part. In some example implementations, and as illustrated inFIG.6A, the electrical probe602may further include an electrically-insulating sheathing610that extends along the axial length of the electrical probe either up to but not including the end of the electrical probe or up to and including the end of the electrical probe and around the electrode604. As such, the electrically-insulating sheathing may expose only a portion of or a substantial entirety or entirety of the electrical probe so as to define an electrode. The nerve probe assembly600further comprises a rigid sheathing612adapted to cover and thereby inhibit a portion of the shapeable part606of the axial length of the electrical probe602from being shaped. The portion of the shapeable part covered by the rigid sheathing is adjustable so that an amount of the shapeable part not covered by the rigid sheathing is adjusted. In some example implementations, and as illustrated inFIGS.6B and6C, at least the electrode604of the electrical probe602extends out of the rigid sheathing so that at least the electrode is exposed. The nerve probe assembly still further comprises an adjustment structure614and a handle616. The adjustment structure and the handle are affixed to respective ones of the electrical probe602and the rigid sheathing612. The handle defines an internal cavity sized to fit the adjustment structure such that the handle and the adjustment structure are adapted to cooperate to enable adjustment of an amount of the adjustment structure that extends out of the handle, and thereby adjustment of the portion of the shapeable part606of the axial length of the electrical probe covered by the rigid sheathing. In some example implementations, the electrical probe602and the rigid sheathing612may be affixed to respectively the adjustment structure614and the handle616. In this manner, the inner cavity of the handle may be arranged to operatively receive the adjustment structure through an end (back end) of the handle, as illustrated for example inFIGS.6B and6C. The handle may include a gripping region including, for example, a plurality of protrusions for gripping. As such, the rigid sheathing may be coupled to and in coaxial alignment with an opposing end (front end) of the handle, through which the electrical probe602is received. As illustrated inFIGS.6B and6C, for example, the electrode604of the electrical probe extends out of the rigid sheathing so that at least the electrode is exposed relative to the rigid sheathing. In some example implementations, the adjustment structure614may comprise a threaded insert including or defining a plurality threads. The handle616may comprise a corresponding interior thread adapted to threadably engage the threaded insert. For example, the corresponding interior thread of the handle may extend from the end (back end) of the handle so that the threaded insert received through the back end of the handle is threadably engaged with the corresponding thread of the handle. Specifically, and as illustrated inFIGS.6B and6C, the threaded insert extends from a back end of the handle, so that the nerve probe assembly is considered to be “back-driven.” The threaded insert of the adjustment structure614may be rotatable within the internal cavity with the corresponding interior thread to adjust the amount of the threaded insert that extends out of the handle616, and thereby adjust the portion of the shapeable part606of the axial length of the electrical probe602covered by the rigid sheathing612. The threaded insert may be rotatable to a plurality of positions.FIG.6BandFIG.6Cillustrate the threaded insert in a retracted position (FIG.6B) and an extended position (FIG.6C) relative to the end (back end) of the handle. InFIG.6B, the threaded insert is rotated to the retracted position in which a minimum amount of the threaded insert extends out of the handle616, and thereby a minimum portion of the shapeable part606is covered by the rigid sheathing612. The minimum amount of the threaded insert that extends out of the handle may be the smallest amount that the threaded insert can extend out of the handle, such that the minimum amount is none or only a de minimis amount of an axial length of the threaded insert. Where the minimum portion of the shapeable part is covered by the rigid sheathing, then a maximum uncovered portion of the shapeable part of the electrical probe602and the electrode604are exposed relative to the rigid sheathing. InFIG.6C, the threaded insert is rotated to the extended position in which a maximum amount of the threaded insert extends out of the handle616, and thereby a maximum portion of the shapeable part606is covered by the rigid sheathing612. The maximum amount of the threaded insert that extends out of the handle may be the greatest amount that the threaded insert can extend out of the handle, such that the maximum amount is all or substantially all of the of an axial length of the threaded insert. Where the maximum portion of the shapeable part is covered by the rigid sheathing, then only the electrode604is exposed relative to the rigid sheathing. In further example implementations, the plurality of positions further includes at least one intermediate position between the extended position and the retracted position. Rotating the threaded insert to at least one of the intermediate positions may result in the amount that the threaded insert extends out of the handle being between the maximum amount and the minimum amount, and thereby the portion of the shapeable part606covered by the rigid sheathing612is between the maximum portion and the minimum portion. Where the portion of the shapeable part covered by the rigid sheathing is between the maximum portion and the minimum portion, then a corresponding uncovered portion of the shapeable part and the electrode604are exposed relative to the rigid sheathing. As such, the shapeable part may be shapeable to different shapes and more flexible when the threaded insert is rotated to the retracted position or an intermediate position. In some example implementations, “back-drive” nerve probe assemblies, other than the back-drive nerve probe assembly600illustrated inFIGS.6A-6Care also contemplated by the present disclosure. For example, a back-drive nerve probe assembly may comprise a smooth (unthreaded) insert, which may be slidably received in a back end of a handle. FIGS.7A-7Dillustrate an example implementation of a nerve probe assembly as generally described inFIG.1. InFIGS.7A-7D, the nerve probe assembly700is configured as a “front-drive” assembly, where an adjustment structure extends between a plurality of positions between an extended position and a retracted position relative to a front end of a handle. InFIGS.7A-7D, the nerve probe assembly700comprises an electrical probe702including an electrode704disposed on or about an end thereof for electrically stimulating tissue or recording stimulated tissue activity. The electrode may define a single electrode or two or more electrodes. Where the electrode defines two or more electrodes, the two or more electrodes may include a stimulation electrode for electrically-stimulating tissue, and a recording electrode for recording stimulated tissue activity. Where the electrode defines the two or more electrodes, the two or more electrodes may be arranged as concentric electrodes or side-by-side electrodes. An axial length of the electrical probe702includes a shapeable part706. The axial length of the electrical probe may also define a stiff portion708that is not shapeable or is not easily shapeable as compared to the shapeable part. In some example implementations, and as illustrated inFIGS.7B and7C, the electrical probe702may include an electrically-insulating sheathing710that extends along the axial length of the electrical probe either up to but not including the end of the electrical probe or up to and including the end of the electrical probe and around the electrode704. As such, the electrically-insulating sheathing may expose only a portion of or a substantial entirety or entirety of the electrical probe so as to define an electrode. The nerve probe assembly700further comprises a rigid sheathing712adapted to cover and thereby inhibit a portion of the shapeable part of the axial length of the electrical probe702from being shaped. The portion of the shapeable part covered by the rigid sheathing is adjustable. In some example implementations, and as illustrated inFIGS.7B-7D, at least the electrode704of the electrical probe702extends out of the rigid sheathing so that at least the electrode is exposed. The nerve probe assembly still further comprises an adjustment structure714and a handle716. The adjustment structure and the handle are affixed to respective ones of the electrical probe702and the rigid sheathing712. The handle defines an internal cavity sized to fit the adjustment structure such that the handle and the adjustment structure are adapted to cooperate to enable adjustment of an amount of the adjustment structure that extends out of the handle, and thereby adjustment of the portion of the shapeable part706of the axial length of the electrical probe covered by the rigid sheathing. In some example implementations, the electrical probe702and the rigid sheathing712may be affixed to respectively the handle716and the adjustment structure714. In this manner, the internal cavity of the handle may be arranged to operatively receive the adjustment structure714through an end (front end) of the handle. The handle may include a gripping region including, for example, a plurality of protrusions for gripping. As such, the rigid sheathing712may be coupled to the adjustment structure and may be arranged in coaxial alignment with the handle and the adjustment structure, so that the electrical probe702may be fixedly received through an opposing end (back end) of the handle and may extend through the rigid sheathing at the end (front end). As illustrated inFIGS.7B-7D, for example, the electrode704of the electrical probe extends out of the rigid sheathing so that at least the electrode is exposed relative to the rigid sheathing. In some example implementations, the adjustment structure714may comprise a threaded insert including or defining a plurality of threads. The handle716may comprise a corresponding interior thread adapted to threadably engage the threaded insert. For example, the corresponding interior thread of the handle may extend from the end (front end) of the handle so that the threaded insert received through the front end of the handle is threadably engaged with the corresponding thread of the handle Specifically, as illustrated inFIGS.7B-7D, the threaded insert extends from a front end of the handle, so that the nerve probe assembly is considered to be “front-driven.” The threaded insert of the adjustment structure714may be rotatable within the internal cavity with the corresponding interior thread to adjust the amount of the threaded insert that extends out of the handle716, and thereby adjust the portion of the shapeable part706of the axial length of the electrical probe702covered by the rigid sheathing712. The threaded insert may be rotatable to a plurality of positions.FIGS.7B-7Dillustrate the threaded insert in a retracted position (FIGS.7B and7C) and an extended position (FIG.7D) relative to the end (front end) of the handle. Notably, in the retracted position, the shapeable part706is shapeable to different shapes and is more flexible because a maximum portion of the shapeable part is uncovered by the rigid sheathing712. However, in some example implementations, the rigid sheathing itself may be pre-shaped, such that the shapeable part conforms to the pre-shaped rigid sheathing.FIGS.8A-8Cillustrate different shapes of rigid sheathings of a front-drive nerve probe assembly800A-800C, similar to the front-drive nerve probe assembly700. However, the shapes illustrated inFIGS.8A-8Cmay be applicable to any nerve probe assembly disclosed herein, where a rigid sheathing is utilized to inhibit a portion of a shapeable part of an axial length of an electrical probe from being shaped. For example inFIG.8A, a rigid sheathing802A of an electrical probe is in a first shape (straight shape), such that a shapeable part is also in a straight shape. A straight shape may be a rigid sheathing/shapeable part that is in coaxial alignment with a handle of an electrical probe. In another example inFIG.8B, a rigid sheathing802B of an electrical probe is in a second shape (angled shape), such that a shapeable part is also in an angled shape. An angled shape may be a rigid sheathing/shapeable part that is in non-coaxial alignment with an axial length of a handle, i.e., the rigid sheathing/shapeable part is angled relative to an axial length of the handle In a still further example inFIG.8C, the rigid sheathing802C of an electrical probe is in a third shape (bayonet shape), such that a shapeable part is also in a bayonet shape. A bayonet shape may be a rigid sheathing/shapeable part that is bent twice relative to an axial length of a handle, so that both bends of the rigid sheathing/shapeable part result in the rigid sheathing/shapeable part being in non-coaxial alignment with an axial length of the handle in two places. However, any other shape of a rigid sheathing/shapeable part of an electrical probe is also contemplated herein, such as, for example, a hooked shape, a curved shape, etc. Returning toFIGS.7A-7D, inFIGS.7B and7C, the threaded insert714is rotated to the retracted position in which a minimum amount of the threaded insert extends out of the handle716, and thereby a minimum portion of the shapeable part706is covered by the rigid sheathing712. The minimum amount of the threaded insert that extends out of the handle may be none or only a de minimis amount of the threaded insert. Where the minimum portion of the shapeable part is covered by the rigid sheathing, then a maximum uncovered portion of the shapeable part of the electrical probe702and the electrode604are exposed relative to the rigid sheathing. InFIG.7B, the shapeable part is in a first shape (straight shape) and inFIG.7C, the shapeable part is in a second shape (angled shape). InFIG.7D, the threaded insert714is rotated to the extended position in which a maximum amount of the threaded insert extends out of the handle716, and thereby a maximum portion of the shapeable part706is covered by the rigid sheathing712. The maximum amount of the threaded insert that extends out of the handle may be all or substantially all of the of the threaded insert. Where the maximum portion of the shapeable part is covered by the rigid sheathing, then only the electrode704is exposed relative to the rigid sheathing. In further example implementations, the plurality of positions further includes at least one intermediate position between the extended position and the retracted position. Rotating the threaded insert to the at least one intermediate position may result in the amount that the threaded insert extends out of the handle being between the maximum amount and the minimum amount, and thereby the portion of the shapeable part706covered by the rigid sheathing712is between the maximum portion and the minimum portion. Where the portion of the shapeable part covered by the rigid sheathing is between the maximum portion and the minimum portion, then a corresponding uncovered portion of the shapeable part and the electrode704are exposed relative to the rigid sheathing. As such, the shapeable part may be shapeable to different shapes and more flexible when the threaded insert is rotated to the extended position or an intermediate position. In some example implementations, “front-drive” nerve probe assemblies, other than the front-drive nerve probe assembly700illustrated inFIGS.7A-7Dare also contemplated by the present disclosure. For example, a front-drive nerve probe assembly may include a snappable rigid sheathing, where an uncovered portion of a shapeable part of an electrical probe is snapped into or otherwise removeably fixed into a front end of a rigid sheathing. In another example, an adjustment structure may include a smooth (unthreaded) insert, which may be slidably received in a front end of a handle. Indexing mechanisms may be included, in some example implementations, in nerve probe assemblies, such as the nerve probe assembly600inFIGS.6A-6C(i.e., back-drive nerve probe assemblies) and the nerve probe assembly700inFIGS.7A-7D(i.e., front-drive nerve probe assemblies). Indexing mechanisms may also be included in any other nerve probe assembly contemplated herein. Typical indexing mechanisms may be coupled to or integrated with an adjustment structure and arranged to index the adjustment structure into a plurality of predetermined positions relative to a handle The plurality of predetermined positions may include an extended position, a retracted position, and at least one intermediate position therebetween. FIGS.9A and9Billustrate different views of an indexing mechanism coupled to or integrated with an adjustment structure of a nerve probe assembly900according to example implementations of the present disclosure. The nerve probe assembly illustrated inFIGS.9A and9Bmay comprise an adjustment structure902that comprises a threaded insert including threads904. The threads may define respective notches906along a length of the threaded insert. The threaded insert illustrated inFIGS.9A and9Bmay be a threaded insert such as that illustrated inFIGS.6A-6C and7A-7D. The nerve probe assembly900may also comprise a handle908defining a corresponding interior thread adapted to threadably engage the threaded insert. The corresponding interior thread of the handle may define a protrusion910, such that a notch of the respective notches906and the protrusion may be alignable. In some example implementations, the threaded insert902of the adjustment structure received through the end of the handle908is rotatable within the corresponding interior thread of the handle between adjacent ones of the respective notches906, which may translate into adjustment of the threaded insert into positions of the plurality of positions, including an extended position, a retracted position, and at least one intermediate position therebetween. For example, and as illustrated inFIGS.9A and9B, the threaded insert902extends to an intermediate position out of the handle908. As can be seen inFIG.9B, a notch of the notches906defined on a thread included between a first end and an opposing second end of the threaded insert is aligned with the protrusion910of the handle, such that the threaded insert extends an intermediate amount (i.e., between a maximum and a minimum amount) out of the handle. FIGS.10A-10Cillustrate different views of an indexing mechanism coupled to or integrated with an adjustment structure of a nerve probe assembly1000according to other example implementations of the present disclosure. The nerve probe assembly illustrated inFIGS.10A-10Cmay comprise an adjustment structure1002that comprises an insert with at least a partially smooth outer surface1004. A protrusion1006may be disposed on the smooth outer surface of the insert. A handle1008may define a slot1010arranged to receive the protrusion. In this manner, the insert may be receivable through the end (front end or back end) of the handle so that the protrusion is received in the slot. As illustrated inFIGS.10A-10C, the insert is received through the front end of the handle. In some example implementations, the insert1002received through the end of the handle1008is translatable along an axial length of the handle to adjust exposure of the axial length of a shapeable part1012of an electrical probe1014relative to a rigid sheathing1016. The insert may, thus, be translatable to a plurality of positions including an extended position and a retracted position, as well as any intermediate positions therebetween. The insert1002may be extendable to an extended position. For example, inFIG.10A, a maximum amount of the insert extends out of the handle1008, and the protrusion1006contacts a first end of the slot1010, such that only an electrode1018of the electrical probe1014is exposed. The insert may also be retractable to a retracted position. In another example, inFIG.10B, a minimum amount of the insert extends out of the handle, and the protrusion contacts an opposing second end of the slot, such that the electrode and a maximum portion of the shapeable part1012is uncovered by the rigid sheathing. The insert may also be positionable into at least one intermediate position between the extended position and the retracted position. In a still further example, inFIG.10C, an intermediate amount (i.e., between the maximum and minimum amount) of the insert extends out of the handle, and the protrusion is between the first end and the opposing second end of the slot, such that the electrode and a portion of the shapeable part between the maximum portion and the minimum portion is uncovered by the rigid sheathing. Turning now toFIGS.11A and11B, different views of an example implementation of a multipole nerve probe assembly, as generally described inFIG.1, are illustrated according to example implementations of the present disclosure. InFIGS.11A and11B, the nerve probe assembly1100is configured as a “multipole” assembly, where three electrical probes are provided, and a distance between respective electrodes of the electrical probes is adjusted. A multipole electrical probe assembly as illustrated inFIGS.11A and11Bmay be useful when it is desirable to stimulate at least two different regions or record stimulated activity of an object, such as tissue. More particularly, for example, the nerve probe assembly1100comprises first and second electrical probes1102A,1102B including first and second electrodes1104A,1104B disposed on or about respective ends thereof for electrically stimulating tissue or recording stimulated tissue activity. In some example implementations, the nerve probe assembly1100may comprise a third electrical probe1102C including a third electrode1104C disposed on or about an end thereof. Still further, the nerve probe assembly may comprise at least a fourth, a fifth, a sixth, a seventh, etc., electrical probe. As illustrated inFIGS.11A and11B, for example, the nerve probe assembly comprises three electrical probes including the first, second, and third electrodes disposed on or about respective ends. The first, second, and third electrodes1104A-1104C may each define a single electrode or two or more electrodes. Where the first, second, and third electrodes each define two or more electrodes, the two or more electrodes may include a stimulation electrode for electrically-stimulating tissue, and a recording electrode for recording stimulated tissue activity. Where the first, second, and third electrodes each define the two or more electrodes, the two or more electrodes may be arranged as concentric electrodes or side-by-side electrodes. The nerve probe assembly1100illustrated inFIGS.11A and11Bfurther comprises a handle1106including first and second arms1108A,1108B adapted to carry respectively the first and second electrical probes1102A,1102B. In some example implementations, the first and second arms are separate and distinct arms that are joined at one end and are separate at another end. In this example, the first and second arms include respective ends from which the first and second electrical probes extend, so that at least the first and second electrodes1104A,1104B are exposed relative to the respective first and second arms. In some example implementations, the handle1106includes a third arm1108C adapted to carry the third electrical probe1102C. Like the first and second arms1108A,1108B, the third arm may include an end from which the third electrical probe extends. As illustrated inFIGS.11A and11B, the first, second, and third arms may be joined at one end and are separate at another end, so at the respective ends of the first, second, and third arms the electrodes extend and are exposed relative thereto. In some example implementations, an axial length of at least one of the first, second, and third electrical probes1102A-1102C may include a shapeable part (not shown) shapeable to different shapes. A rigid sheathing (not shown) may be adapted to cover and thereby inhibit a portion of the shapeable part of the axial length of the first, second, and third electrical probes from being shaped. However, the portion of the shapeable part covered by the rigid sheathing may be adjustable, such that different amounts of corresponding other portions of the shapeable part of the axial length of the first, second, and third electrical probes may be exposed. FIGS.11A and11Billustrate the first, second, and third electrical probes1102A-1102C in fully retracted positions, so that only the first, second, and third electrodes1104A-1104C are exposed relative to the respective arms1108A-1108C. However, adjustment of the first, second, and third electrical probes may expose at least a portion of a shapeable part of the axial length of the first, second, and third electrical probes so that the portion of the shapeable part may be shaped into different shapes, while stiffness of the first, second, and third electrical probes may also be adjusted. In some example implementations, the first, second, and third electrical probes1102A-1102C may further include an electrically-insulating sheathing (not shown) that extends along the axial length of one or more of the first, second, and third electrical probes either up to but not including the respective ends of the first, second, and third electrical probes or up to and including the respective ends of the first, second, and third electrical probes and around the first, second, and third electrodes1104A-1104C. As such, the electrically-insulating sheathing may expose only a portion of or a substantial entirety or entirety of the first, second, and third electrical probes so as to define the first, second, and third electrodes. In some example implementations, as illustrated inFIGS.11A and11B, the first, second, and third arms1108A-1108C of the handle1106are arranged in a single plane, such that the corresponding electrical probes1102A-1102C are also arranged in a single plane. However, a multipole nerve probe assembly may also be arranged so that the multiple arms of the handle are arranged in one or more different planes, such that the corresponding electrical probes are also arranged in the one or more different planes. The nerve probe assembly1100also comprises an adjustment structure1110coupled to the first arm1108A or the second arm1108B. The adjustment structure may also be coupled to the third arm1108C. The adjustment structure is adapted to enable adjustment of a distance between the respective ends of the first and second arms, and thereby adjust a corresponding distance between the first and second electrodes1104A,1104B. However, the adjustment structure may also be arranged to adjust at least one of exposure of the axial length of the first and second electrical probes relative to any of the first and second arms. As illustrated inFIGS.11A and11B, the adjustment structure1110is arranged between the first arm1108A and the third arm1108C, and is coupled to the second arm1108B to adjust the distance between the respective ends of the first and third arms relative to the second arm, and thereby adjust the corresponding distance between the first and third electrodes1104A,1104C relative to the second electrode1104B. In order to adjust the distance between the respective ends of the first and third arms relative to the second arm, and thereby adjust the corresponding distance between the first and third electrodes1104A,1104C relative to the second electrode1104B, the adjustment structure1110may be adjusted between a retracted position and an extended position. InFIG.11A, for example, the adjustment structure is provided in a retracted position, so that the adjustment structure is positioned at a minimum distance from the second arm1108B. InFIG.11B, the adjustment structure is provided in an extended position, so that the adjustment structure is positioned at a maximum distance from the second arm. The adjustment structure may also be positionable into at least one intermediate position (i.e., between the retracted position and the extended position), which may result in the adjustment structure being positioned at an intermediate distance (i.e., between the minimum distance and the maximum distance) from the second arm. In some example implementations, and as illustrated inFIGS.11A and11B, the adjustment structure1110is an axial screw1112coupled with the second arm1108B and arranged in two halves with a sleeve1114arranged to receive each of the halves at opposing ends thereof. The sleeve may be a threaded sleeve that threads onto threads defined by the axial screw. Each half of the axial screw may be in coaxial alignment with the second arm. However, the adjustment structure may also comprise other example implementations, such as, for example and not limited to, a center screw mechanism, a side screw mechanism, a slide mechanism, a sleeved screw mechanism, a slotted slide mechanism, a spring mechanism, an alternate spring mechanism, and the like. The nerve probe assembly1100also comprises, in some example implementations, a spatial positioning mechanism1116A and1116B, which may be part of or separate from the adjustment structure1110. As illustrated inFIGS.11A and11B, the spatial positioning mechanism is separate from, but adjustable in response to adjustment of the adjustment structure. The spatial positioning mechanism may be coupled between the second arm1108B and each of the first arm1108A and the third arm1108C to adjust a distance between the respective ends of the first and third arms relative to the second arm, and thereby adjust the corresponding distance between the first and third electrodes1104A,1104C relative to the second electrode1104B. As such, and as illustrated inFIGS.11A and11B, adjustment of the adjustment structure (e.g., rotation of the sleeve1114about the axial screw1112) correspondingly adjusts the spatial positioning mechanism1116A and1116B. The spatial positioning mechanism1116A and1116B inFIGS.11A and11Bcomprises pivotable arms, with the first pivoting arm1116A being coupled between the first arm1108A and the second arm1108B and the second pivoting arm1116B being coupled between the third arm1108C and the second arm. However, the spatial positioning mechanism inFIGS.11A and11B, is just one example implementation of a spatial positioning mechanism Other spatial positioning mechanisms are contemplated herein, such as, for example and not limited to, flexible arms, pivotable pin arms, flexible spring arms, ramp tips, flexible pivot arms, slotted pin arms, and the like. In some example implementations, adjustment or translation of the adjustment structure1110, such as the halves of the axial screw1112and the sleeve1114, into one of a plurality of positions including and in between the retracted position and the extended position relative to the second arm1108B, results in correspondingly adjusting the spatial positioning mechanism1116A and1116B into the same positions. The retracted position is a position in which a retracted position in the distance between the respective ends of the first and third arms1108A and1108C relative to the end of the second arm1108B is at a minimum distance and the corresponding distance between the first and third electrodes1104A and1104C relative to the second electrode1104B is at a minimum distance. For example, and as illustrated inFIG.11A, in the retracted position, the sleeve1114has been rotated in a first direction about the axial screw1112(e.g., clockwise) so as to retract the halves of the axial screw relative to the sleeve. Doing so decreases the distance between the sleeve and the second arm, such that the spatial positioning mechanisms1116A and1116B being coupled to the second arm are, thus, pulled into axial alignment with the first arm1108A and the third arm1108C. The distance between the first and third arms and relative to the end of the second arm is therefore at a minimum distance and the corresponding distance between the first and third electrodes and relative to the second electrode is at a minimum distance. The extended position is a position in which the distance between the respective ends of the first and third arms1108A and1108C relative to the end of the second arm1108B is at a maximum distance and the corresponding distance between the first and third electrodes1104A and1104C relative to the second electrode1104B is at a maximum distance. For example, and as illustrated inFIG.11B, in the extended position, the sleeve1114has been rotated in a second direction about the axial screw1112(e.g., counter-clockwise) so as to extend the halves of the axial screw relative to the sleeve. Doing so increases the distance between the sleeve and the second arm, such that the spatial positioning mechanisms1116A and1116B being coupled to the second arm are, thus, pushed out of axial alignment with the first arm1108A and the third arm1108C. The distance between the first and third arms relative to the end of the third arm is therefore at a maximum distance and the corresponding distance between the first and third electrodes and relative to the second electrode is at a maximum distance. The at least one intermediate position is a position between the extended position and the retracted position in which the adjustment structure1110is at an intermediate distance from the second arm1108B such that the distance between the respective ends of the first and third arms1108A and1108C relative to the end of the second arm is at an intermediate distance and the corresponding distance between the first and third electrodes1104A and1104C relative to the second electrode1104B is at an intermediate distance. The distances are between the maximum and minimum distances. More particularly, in this example, rotation of the sleeve1114in either the first or the second direction about the axial screw1112(i.e., clockwise or counter-clockwise) may extend or retract the halves of the axial screw relative to the sleeve. Doing so may increase or decrease the distance between the sleeve and the second arm to an intermediate distance between the minimum distance and the maximum distance, such that the spatial positioning mechanisms1116A and1116B being coupled to the second arm are, thus, pushed out of axial alignment with the first arm1108A and the third arm1108C. The spatial positioning mechanisms may be at an intermediate angle (non-coaxial) that is less than the maximum angle relative to the axes of the first and third arms. The distance between the first and third arms and relative to the end of the second arm is therefore at an intermediate distance and the corresponding distance between the first and third electrodes and relative to the second electrode is at an intermediate distance. Many modifications and other implementations of the disclosure set forth herein will come to mind to one skilled in the art to which this disclosure pertain having the benefit of the teachings presented in the foregoing descriptions and the associated figures. Therefore, it is to be understood that the disclosure are not to be limited to the specific implementations disclosed and that modifications and other implementations are intended to be included within the scope of the appended claims Moreover, although the foregoing descriptions and the associated figures describe example implementations in the context of certain example combinations of elements and/or functions, it should be appreciated that different combinations of elements and/or functions may be provided by alternative implementations without departing from the scope of the appended claims. In this regard, for example, different combinations of elements and/or functions than those explicitly described above are also contemplated as may be set forth in some of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. | 65,280 |
11857781 | DETAILED DESCRIPTION The above and other aspects, features, and advantages of the inventive concept will become apparent from the following description of embodiments given in conjunction with the accompanying drawings. However, the inventive concept is not limited to the embodiments disclosed herein and may be implemented in various different forms. Herein, the embodiments are provided to provide complete disclosure of the inventive concept and to provide thorough understanding of the inventive concept to those skilled in the art to which the inventive concept pertains, and the scope of the inventive concept should be limited only by the accompanying claims and equivalents thereof. Terms used herein are only for description of embodiments and are not intended to limit the inventive concept. As used herein, the singular forms are intended to include the plural forms as well, unless context clearly indicates otherwise. It will be further understood that the terms “comprise” and/or “comprising” specify the presence of stated features, components, and/or operations, but do not preclude the presence or addition of one or more other features, components, and/or operations. In addition, identical numerals will denote identical components throughout the specification, and the meaning of “and/or” includes each mentioned item and every combination of mentioned items. It will be understood that, although the terms first, second, etc. may be used herein to describe various components, these components should not be limited by these terms. These terms are only used to distinguish one component from another component. Thus, a first component discussed below could be termed a second component without departing from the teachings of the inventive concept. Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by those skilled in the art to which the inventive concept pertains. It will be further understood that terms, such as those defined in commonly used dictionaries, should not be interpreted in an idealized or overly formal sense unless expressly so defined herein. Spatially relative terms, such as “beneath”, “below”, “lower”, “above”, “upper” and the like, may be used herein for ease of description to describe one component or feature's relationship to another component(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, components described as “below” or “beneath” other components or features would then be oriented “above” the other components or features. Thus, the exemplary term “below” can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Hereinafter, embodiments of the inventive concept will be described in detail with reference to the accompanying drawings. FIG.3is an exploded perspective view illustrating a skin treatment apparatus according to an embodiment of the inventive concept, andFIG.4is a sectional view illustrating the skin treatment apparatus according to an embodiment of the inventive concept. As illustrated inFIGS.3and4, the skin treatment apparatus according to an embodiment of the inventive concept may include a casing110, a needle tip for application of current, an actuator140, an electricity supply device150, a connector160, a cartridge170, a connecting member180, and a controller (not illustrated). The casing110accommodates the actuator140and the electricity supply device150. The cartridge170is coupled to one side of the casing110so as to be replaceable, and the connector160is coupled to an opposite side of the casing110through the connecting member180. The casing110may be divided into a left casing and a right casing. The left casing and the right casing may be detachably coupled together through bolts113, inserts114, a first coupling member111, and a second coupling member112. The bolts113may fasten the left casing and the right casing. The inserts114may surround heads of the bolts113. One end and an opposite end of the first coupling member111may be fit into the left casing110and the right casing110, respectively. One end and an opposite end of the second coupling member112may be fit into the left casing110and the right casing110, respectively. The opposite side of the casing110may be coupled with the connecting member180through a third coupling member115and a fourth coupling member116. The insides of the third coupling member115, the fourth coupling member116, and the connecting member180may be connected to allow electrical cables of the connector160to pass therethrough. The needle tip for application of current may transfer electrical energy generated by current applied by the electricity supply device150to a target region of skin to remove damaged collagen or elastic fibers in the target region of the skin and facilitate forming new collagen or elastic fibers. The needle tip may include a needle fixing part120and a plurality of needles130. The needle fixing part120may be disposed inside the cartridge170and may be reciprocally moved into or out of the cartridge170by the actuator140. The needle fixing part120may fix the plurality of needles130. Accordingly, when the needle fixing part120is reciprocally moved into or out of the cartridge170by the actuator140, the plurality of needles130may also be reciprocally moved into or out of the cartridge170by the actuator140. For example, on one surface of the needle fixing part120, the plurality of needles130may be fixedly arranged to have at least one of one or more rows and one or more columns. Furthermore, the needle fixing part120may have, in the one surface thereof, a plurality of through-holes through which the plurality of needles130are inserted. The plurality of needles130are inserted into the skin to transfer the electrical energy generated by the current applied by the electricity supply device150to the target region of the skin. Specifically, while the surface of the skin is brought into close contact with a contact surface of the cartridge170, the plurality of needles130are moved out of the cartridge170together with the needle fixing part120and inserted into the skin by the actuator140and transfer the electrical energy, which is generated by the current applied by the electricity supply device150, to the target region of the skin. Meanwhile, the plurality of needles130inserted into the skin have to be rapidly pulled out to prevent a risk of accident and reduce a pain in the skin. Accordingly, the controller, which will be described below, may operate the actuator40to rapidly pull out the plurality of needles130inserted into the skin. The plurality of needles130may be implemented in a bipolar type including both needles130having a positive (+) polarity and needles130having a negative (−) polarity. In the bipolar type, the current applied to the needles130having the positive (+) polarity reflux the needles130having the negative (−) polarity. As a result, an energy transfer region, to which electrical energy is transferred, may be formed between active regions132aor132bof the plurality of needles130. Meanwhile, the positive (+) polarity may be a positive electrode, and the negative (−) polarity may be a negative electrode. The needles130may have an empty space inside and may be formed of a conductive material, such as metal or silicone, or a non-conductive material. In a case where the needles130are formed of a non-conductive material, the needles130may be formed in a structure in which the non-conductive material is plated with a conductive material. A partial region of each of the needles130that includes a tip end may be coated with an insulating material, and the tip end may be formed in a sharp structure. The insulating material coating may be implemented with a parylene coating, a Teflon coating, or a ceramic coating. The insulating material-coated partial region (e.g., a first insulated region or a second insulated region) of the needle130that includes the tip end will be described below. In addition, the non-insulating material-coated active regions of the needles130are electromagnetically energized. Accordingly, the current applied to the active regions of the needles130having the positive (+) polarity reflux the active regions of the needles130having the negative (−) polarity. As a result, electrical energy may be transferred to between the active regions of the plurality of needles130. The active regions will be described below. The actuator140is installed inside the casing110and reciprocally moves the needle fixing part120and the plurality of needles130into or out of the cartridge170. The actuator140may be driven by any one of an electromagnetic force caused by an electrical signal, hydraulic pressure, pneumatic pressure, and a solenoid valve. The electricity supply device150is installed inside the casing110and applies current to the plurality of needles130. The current applied to the plurality of needles130by the electricity supply device150may RF current, and the strength of the current applied to the plurality of needles130by the electricity supply device150may be controlled by the controller. The connector160may be electrically connected to an external power supply and may have the electrical cables that electrically connect the actuator140, the controller, and the electricity supply device150with the external power supply. The connecting member180connects the connector160and the opposite side of the casing110, and the electrical cables of the connector160pass through the connecting member180. The cartridge170may be a housing in which the needle tip for application of current is received. Hereinafter, the cartridge170is defined as the housing in which the needle tip for application of current is received. The cartridge170may have a contact surface brought into close contact with the surface of the skin into which the plurality of needles130are inserted, and may be detachably coupled to the one side of the casing110. As described above, the cartridge170may contain the plurality of needles130fixed to the needle fixing part120that is reciprocally moved into or out of the cartridge170by the actuator140. The contact surface of the cartridge170may be formed to be a flat surface. Accordingly, the surface of the skin brought into close contact with the contact surface of the cartridge170may be in a flat state. Due to this, the plurality of needles130may be inserted into the surface of the skin in the flat state, and the depths by which the plurality of needles130are inserted into the skin may be the same. As a result, only a region up to a specific depth of the skin may be uniformly disposed between the plurality of needles130, and thus electrical energy transferred to between the plurality of needles130may be transferred only to the specific depth of the skin. The cartridge170may have, in the contact surface thereof, a plurality of through-holes through which the needles130pass. Accordingly, the needles130may protrude outward from the cartridge170through the plurality of through-holes. The contact surface of the cartridge170may be formed of rubber or silicone so as to be easily brought into close contact with the surface of the skin. Furthermore, the contact surface of the cartridge170may be formed in a circular or polygonal shape. Meanwhile, the cartridge170may have a first space formed between the contact surface of the cartridge170, which is brought into close contact with the surface of the skin, and the needle fixing part120, and negative pressure may be formed in the first space before the plurality of needles130are inserted into the skin. The negative pressure may be formed by the controller when the surface of the skin is brought into close contact with the contact surface of the cartridge170, or when the needle fixing part120and the plurality of needles130are moved out of the cartridge170by the actuator140. Furthermore, the negative pressure may be formed by a pump (not illustrated) that suctions air in the first space, and the pump may be installed inside the casing110. Accordingly, when the surface of the skin is brought into close contact with the contact surface of the cartridge170, the negative pressure is formed in the first space, and the surface of the skin sticks to the contact surface of the cartridge170. As a result, the surface of the skin brought into close contact with the contact surface of the cartridge170may be in a flat state. The controller serves to control the actuator140and the electricity supply device150. For example, the controller may control the distance by which the actuator140reciprocates the needle fixing part120and the plurality of needles130such that the plurality of needles130are inserted into the target region of the skin in the state in which the surface of the skin is brought into close contact with the contact surface of the cartridge170. In addition, the controller may operate the electricity supply device150such that electrical energy is transferred to the skin through the plurality of needles130in the state in which the plurality of needles130are inserted into the skin. Meanwhile, when the plurality of needles130are inserted into the skin in the state in which the surface of the skin is brought into close contact with the contact surface of the cartridge170, the surface of the skin brought into close contact with the contact surface of the cartridge170may be deflected by pressure applied to the surface of the skin by the plurality of needles130. To compensate for the deflection, the needles130fixed to the needle fixing part120may preferably have different lengths. For example, when the plurality of needles130are inserted into the skin, needles130disposed on the center of the needle fixing part120among the plurality of needles130may be inserted in a more sagged state than needles130disposed on the periphery of the needle fixing part120. To compensate for the deflection, the needles130disposed on the center of the needle fixing part120may have a greater length than the needles130disposed on the periphery of the needle fixing part120. That is, the needles130disposed on the center of the needle fixing part120further protrude from the needle fixing part120beyond the needles130disposed on the periphery of the needle fixing part120. FIG.5is a plan view illustrating a state in which needles are disposed on the needle fixing part of the needle tip for application of current according to an embodiment of the inventive concept (bipolar type).FIG.6is a schematic view illustrating needles according to an embodiment of the inventive concept.FIG.7is a schematic view illustrating energy transfer regions of the needle tip for application of current according to an embodiment of the inventive concept (bipolar type).FIGS.8A and8Bare views illustrating electrical energy transfer effects of needles according to an embodiment of the inventive concept (bipolar type). Referring toFIG.5, the needle tip for application of current according to an embodiment of the inventive concept serves to transfer, to the target region of the skin, electrical energy generated by current (that is, RF current) applied by the external power supply. The needle tip may include the needle fixing part120and the plurality of needles130. The needle fixing part120is the same as the needle fixing part120of the skin treatment apparatus described above. Therefore, detailed description thereof will be omitted. The plurality of needles130, after inserted into the skin, transfer the electrical energy generated by the current applied by the external power supply to the target region of the skin. Here, the insertion of the plurality of needles130into the skin may be performed by the actuator and the controller of the skin treatment apparatus described above. The plurality of needles130may be fixedly disposed on one surface of the needle fixing part120. For example, on the one surface of the needle fixing part120, the plurality of needles130may be fixedly arranged to have at least one of one or more rows and one or more columns. In each row and column, needles130adjacent to each other among the plurality of needles130may output different polarities, and the plurality of needles130may be implemented in a bipolar type including both needles130having a positive (+) polarity and needles130having a negative (−) polarity. Referring toFIG.5, the plurality of needles130may alternately output a positive (+) polarity and a negative (−) polarity for each row of the needles130and may alternately output a positive (+) polarity and a negative (−) polarity for each column of the needles130. Accordingly, two needles130adjacent to each other along a row or column include a needle130having a positive (+) polarity and a needle130having a negative (−) polarity. When current is applied to the plurality of needles130of a bipolar type, the current applied to the needles130having the positive (+) polarity reflux the needles130having the negative (−) polarity, or the current applied to the needles130having the negative (−) polarity reflux the needles130having the positive (+) polarity. As a result, damaged regions may be formed at specific depths of the skin through energy transfer regions A and C where electrical energy is transferred to between the active regions132aand132bof the plurality of needles130. The inventive concept may form the damaged regions at the specific depths of the skin through the energy transfer regions A and C where the electrical energy is transferred to between the active regions132aand132bof the plurality of needles130. Meanwhile, at least one of two or more needles130adjacent to one needle130may have the same polarity as the one needle130. Referring toFIGS.6and7, each of the plurality of needles130may have a first insulated region131aor131bformed at a tip end thereof, and at least one active region132aor132band at least one second insulated region133aor133bformed in the remaining portion thereof. The first insulated region131aor131bmay be formed by coating the tip end of the needle130with an insulating material. The active region132aor132bis a predetermined exposed region other than the tip end of the needle130. Specifically, the active region132aor132bis exposed by not coating a predetermined region other than the tip end of the needle130with an insulating material. The active region132aor132bis electromagnetically energized by current applied to the needle130. Meanwhile, when the plurality of needles130of a bipolar type are inserted into the skin and current is applied to the plurality of needles130, the current applied to the active regions132aand132bof the needles130having the positive (+) polarity reflux the active regions132aand132bof the needles130having the negative (−) polarity, and the energy transfer regions A and C where electrical energy is transferred to between the active regions132aand132bof the plurality of needles130are formed. Damaged regions D having a uniform thickness are formed in the skin through the energy transfer regions A and C. Because the tip ends of the plurality of needles130are insulated by the first insulated regions131aand131b, electrical energy is not transferred to the skin from the tip ends of the plurality of needles130on which the RF current is concentrated. Accordingly, unlike existing needles (that is, needles, tip ends of which are not coated with an insulating material), the plurality of needles130may prevent a damaged region having a bell shape from being generated in the skin adjacent to the tip ends of the plurality of needles130. Referring toFIG.8A, it can be seen that laceration and a damaged region having a bell shape, which are caused by the existing needles (that is, needles, tip ends of which are not coated with an insulating material), are not generated in the skin adjacent to the tip ends of the plurality of needles130. Furthermore, as the energy transfer regions A and C of the plurality of needles130are generated in the skin adjacent to the active regions132aand132bof sidewalls of the plurality of needles130, the damaged regions D are preferentially generated in the skin adjacent to the sidewalls of the plurality of needles130. In contrast, referring toFIG.8B, when RF current is concentrated on tip ends of the plurality of existing needles of a bipolar type (that is, needles, tip ends of which are not coated with an insulating material) due to the nature of the RF current, excessive electrical energy is transferred from the tip ends to the skin, and therefore first damaged regions22ahaving a bell shape and laceration are generated in the skin adjacent to the tip ends. Furthermore, as energy transfer regions of the plurality of existing needles to which electrical energy is transferred are preferentially generated in the skin adjacent to the tip ends of the plurality of existing needles and are generated later in the skin adjacent to sidewalls of the plurality of existing needles, the first damaged regions22aare preferentially generated in the skin adjacent to the tip ends of the plurality of existing needles, and thereafter second damaged regions22bare generated in the skin adjacent to the sidewalls of the plurality of existing needles. Therefore, even in a case where the second damaged regions22bare desired to be preferentially generated in the skin adjacent to the sidewalls of the plurality of existing needles, the first damaged regions22aare generated in the skin adjacent to the tip ends, and thereafter the second damaged regions22bare generated in the skin adjacent to the sidewalls. Accordingly, unnecessary electrical energy is supplied, and treatment time is delayed. Referring toFIGS.6and7, the plurality of needles130may include a first needle130aand a second needle130b. Hereinafter, for convenience of description, the first needle130aand the second needle130bwill be described as examples of the plurality of needles130. The first needle130amay have the first insulated region131aformed at the tip end thereof, and a plurality of active regions132aand a plurality of second insulated regions133aalternately formed in the remaining portion thereof. For example, the first needle130amay have the single first insulated region131, and two or more active regions132aand two or more second insulated regions133aalternately formed (refer to the left side ofFIG.6). In a case where the plurality of needles130include only the first needles130a, when the plurality of first needles130aare inserted into the skin, the plurality of energy transfer regions A spaced apart from each other are formed between the plurality of first needles130a, and electrical energy is supplied to a plurality of skin regions through the plurality of energy transfer regions A spaced apart from each other. The second needle130bmay have the single first insulated region131b, the single active region132b, and the single second insulated region133b. That is, the second needle130bmay have the first insulated region131bformed at the tip end thereof, and the single active region132band the single second insulated region133bformed along the lengthwise direction in the remaining portion thereof (refer to the right side ofFIG.6). Referring toFIG.7, as the plurality of needles130have one or more active regions132aand132bdisposed at the same height, the energy transfer regions A and C formed between the active regions132aand132bof the needles130are disposed only at a specific depth of the skin when the plurality of needles130are inserted into the skin. Accordingly, electrical energy may be supplied to the specific depth of the skin through the energy transfer regions A and C disposed at the specific depth of the skin. The active regions132aand132bof the needles130may be formed to have the same size. Specifically, the active regions132aof the needles130may have the same length and thickness. Meanwhile, the sizes (e.g., depths and widths) by which the energy transfer regions A and C are formed in the skin may be adjusted by adjusting the strength of current applied to the plurality of needles130. The electricity supply device or the controller of the skin treatment apparatus described above may be used to adjust the strength of the current, and detailed description thereabout will be given in an experimental example that will be described below. Referring to the left side ofFIG.7, in a case where the plurality of needles130are constituted by the plurality of first needles130ahaving the plurality of active regions132aspaced apart from each other and the plurality of energy transfer regions A are formed between the plurality of first needles130a, electrical energy may be supplied to a plurality of skin regions through the plurality of energy transfer regions A when the plurality of first needles130aare inserted into the skin. However, according to the need of a user, it may be necessary to transfer electrical energy to between the energy transfer regions A. To achieve this, the plurality of energy transfer regions A formed between the plurality of first needles130amay be spread in the lengthwise direction by adjusting the strength of current applied to the plurality of first needles130awithin a specific numerical range. As a result, electrical energy may be transferred to between the plurality of energy transfer regions A. In this case, the diameter of the first needle130amay range from 0.23 mm to 0.27 mm, the length t1of the first insulated region131aof the first needle130amay range from 0.28 mm to 0.32 mm, the length t1of the active region132aof the first needle130amay range from 0.23 mm to 0.27 mm, the separation distance t2between the active regions132aof the first needles130a(that is, the length of the second insulated region133alocated between the active regions132aof the first needles130a) may range from 0.28 mm to 0.32 mm, and the length of the second insulated region133alocated at the top of the first needle130ais not specially limited. In addition, the gap between the plurality of first needles130amay range from 1 mm to 2.4 mm. However, the inventive concept is not limited thereto. The reason for the above-described numerical values will be described below in the experimental example. Experimental Example FIGS.9A to9Dillustrate a graph depicting the depth from the outermost layer of skin to a coagulation zone formed in the skin through energy transfer regions formed between a plurality of first needles, a graph depicting the length of the coagulation zone, and a graph depicting the width of the coagulation zone according to an embodiment of the inventive concept. The depth from the outermost layer of the skin to the coagulation zone formed in the skin through the two energy transfer regions A formed between the two active regions132aof the plurality of first needles130aand the length and width of the coagulation zone formed in the skin were measured after the plurality of first needles130aconstituted by the first insulated region131ahaving the above-described numerical value and the second insulated region133ainterposed between the two active regions132ahaving the above-described numerical value were inserted into the skin and current was applied to the plurality of first needles130a. Here, the strength of the current applied to the plurality of first needles130awas adjusted to 20 W to 60 W. The electricity supply device or the controller of the skin treatment apparatus described above was used to adjust the strength of the current. As a result, in the case where the current ranging from 20 W to 60 W was applied to the plurality of first needles130a, the depth from the outermost layer of the skin to the coagulation zone (that is, the depth by which the energy transfer regions were formed in the skin) was adjusted to 0.71 mm to 1.00 mm. That is, it can be seen that the depth by which the energy transfer regions A were formed in the skin was adjusted by adjusting the strength of the current applied to the plurality of first needles130a(refer to the graphs ofFIGS.9A and9Cthat depict the depth from the outermost layer of the skin to the coagulation zone). Furthermore, in the case where the current ranging from 20 W to 60 W was applied to the plurality of first needles130a, the width of the coagulation zone (that is, the width by which the energy transfer regions were formed in the skin) was adjusted to 0.18 mm to 0.48 mm. That is, it can be seen that the width by which the energy transfer regions A were formed in the skin was adjusted by adjusting the strength of the current applied to the plurality of first needles130a(refer to the graphs ofFIGS.9A and9Dthat depict the width of the coagulation zone). Moreover, in the case where the current ranging from 20 W to 50 W was applied to the plurality of first needles130a, the maximum length obtained by adding the lengths of the two active regions132awas 0.54 mm (that is, 0.27 mm×2), and the length of the coagulation zone formed in the skin through the two energy transfer regions A ranged from 0.542 mm to 0.790 mm. That is, it can be seen that the length of the coagulation zone formed in the skin through the two energy transfer regions A was greater than the maximum length obtained by adding the lengths of the two active regions132a. Accordingly, it can be seen that the two energy transfer regions A were spread in the lengthwise direction. However, in the case where the current smaller than 20 W or greater than 50 W was applied to the plurality of first needles130a, the two energy transfer regions were not spread in the lengthwise direction. Accordingly, the strength of current applied to the first needles130apreferably ranges from 20 W to 50 W (refer to the graphs ofFIGS.9A and9Bthat depict the length of the coagulation zone). In addition, in the case where the strength of current applied to the plurality of first needles130awas 42 W, the maximum length obtained by adding the lengths of the two active regions132aand the second insulated region133awas 0.74 mm (that is, 0.23 mm×2+0.28 mm), and the length of the coagulation zone formed in the skin through the two energy transfer regions A was 0.790 mm. That is, it can be seen that the length of the coagulation zone formed in the skin through the two energy transfer regions A was greater than the maximum length obtained by adding the lengths of the two active regions132aand the second insulated region133a. Accordingly, it can be seen that the two energy transfer regions A had the overlapping region B having the length of 0.05 mm (0.790 mm-0.74 mm) (refer toFIG.7and the graphs ofFIGS.9A and9Bthat depict the length of the coagulation zone). The concept of the overlapping region B is illustrated on the left side ofFIG.7. As described above, the plurality of energy transfer regions A spaced apart from each other in the lengthwise direction may be formed between the plurality of first needles130a. In the case where the strength of current applied to the plurality of first needles130ais 42 W, the plurality of energy transfer regions A formed between the plurality of first needles130aare spread along the lengthwise direction by more than half of the length of the second insulated region133a. Accordingly, the overlapping region B is formed in the plurality of energy transfer regions A. The length t5by which the plurality of energy transfer regions A are spread in the lengthwise direction may range from 0.23 mm to 0.25 mm, and the total length t6of two energy transfer regions A adjacent to each other among the plurality of energy transfer regions A spread as described above may range from 1.25 mm to 1.32 mm. Referring to the right side ofFIG.7, for example, in the case where the plurality of needles130are constituted by the plurality of second needles130b, an energy transfer region C may be formed between the active regions132bof the plurality of second needles130b. When the plurality of second needles130bare inserted into the skin, electrical energy may be supplied to a single skin region through the energy transfer region C. Referring to the left side ofFIG.6and the right side ofFIG.7, for example, the diameter of the second needle130bmay range from 0.23 mm to 0.27 mm, the length t3of the first insulated region131bof the second needle130bmay range from 0.18 mm to 0.22 mm, the length t4of the active region132bof the second needle130bmay range from 0.48 mm to 0.52 mm, and the length of the second insulated region133blocated at the top of the second needle130bis not specially limited. In addition, the gap between the second needles130bmay range from 1 mm to 2.4 mm. However, the inventive concept is not limited thereto. Meanwhile, in the case where the strength of current applied to the plurality of second needles130branges from 20 W to 50 W, the energy transfer region C formed between the active regions132bof the plurality of second needles130bwas spread in the lengthwise direction. The length by which the energy transfer region C is spread may range from 0.23 mm to 0.25 mm, and the total length of the energy transfer region C may range from 0.98 mm to 1.02 mm. Accordingly, as the first insulated regions are formed at the tip ends of the needles, the needle tip for application of current according the embodiment of the inventive concept may prevent electrical energy concentrated on the tip ends of the needles from being transferred to the skin to generate damaged regions having a bell shape. Furthermore, as the active regions of the plurality of needles are disposed at the same height, the needle tip for application of current according to the embodiment of the inventive concept may supply electrical energy only to a specific depth of the skin through the energy transfer regions formed between the active regions of the needles. For example, the plurality of needles130may be implemented in a mono-polar type in which the plurality of needles130are connected to one or more RF sources (e.g., the electricity supply device of the skin treatment apparatus), the plurality of needles130arranged in at least one of the longitudinal direction and the lateral direction alternately output the same polarity separately or in combination thereof, and a ground electrode having an opposite polarity is provided. For example, the plurality of needles130may all output a positive (+) polarity, and the ground electrode may be implemented to have a negative (−) polarity. Alternatively, the plurality of needles130may all output a negative (−) polarity, and the ground electrode may be implemented to have a positive (+) polarity. FIGS.10A and10Bare views illustrating electrical energy transfer effects of needles according to an embodiment of the inventive concept (mono-polar type). Hereinafter, for convenience of description, needles130of a mono-polar type will be described based on first needles130aof a mono-polar type. Second needles130bof a mono-polar type have the same function and effect as the first needles130aof a mono-polar type. Referring toFIG.10A, when the first needles130aof a mono-polar type are inserted into skin and RF current is applied to the first needles130a, the RF current is concentrated on tip ends of the first needles130adue to the nature of the RF current. As the tip ends of the first needles130aare insulated and active regions132aof sidewalls of the first needles130aare exposed, the RF current applied to the first needles130acirculates from the active regions132aof the sidewalls of the first needles130ato a ground electrode disposed at a non-target point (e.g., outside the skin). As a result, energy transfer regions E to which electrical energy is transferred from the active regions132aof the sidewalls of the first needles130aare formed over a wide range, and a wide skin region may be treated through the energy transfer regions E. That is, the skin treatment range of the first needles130ais improved. Because electrical energy is not transferred from the tip ends of the first needles130a, on which the RF current is concentrated, to the skin even though the first needles130aremain inserted into the skin and the RF current is continually applied, a damaged region having a bell shape and laceration may be prevented from being generated in the skin adjacent to the tip ends of the first needles. Furthermore, as the energy transfer regions E of the first needles130aare generated from skin regions adjacent to the active regions132aof the sidewalls of the first needles130a, damaged regions are preferentially generated from the skin regions adjacent to the sidewalls of the first needles130a. In contrast, referring toFIG.10B, when existing needles30of a mono-polar type (that is, needles, the tip ends of which are not coated with an insulating material) are inserted into skin and RF current is applied to the existing needles30, the RF current is concentrated on tip ends of the existing needles30due to the nature of the RF current. As the tip ends of the existing needles30are exposed, the current applied to the existing needles30circulates to a ground electrode disposed at a non-target point (e.g., outside the skin) with respect to the tip ends of the existing needles30. As a result, energy transfer regions30ato which electrical energy is transferred with respect to the tip ends of the existing needles30are formed over a narrow range, and a narrow skin region may be treated through the energy transfer regions30a. That is, the skin treatment range of the existing needles30is limited. Because excessive electrical energy is transferred from the tip ends of the existing needles30, on which the RF current is concentrated, to the skin when the existing needles30remain inserted into the skin and the RF current is continually applied, a damaged region having a bell shape and laceration are generated in skin regions adjacent to the tip ends of the existing needles30. Furthermore, as the energy transfer regions30aof the existing needles30are preferentially generated in the skin regions adjacent to the tip ends of the existing needles30and thereafter generated in skin regions adjacent to sidewalls of the existing needles30, first damaged regions are preferentially generated in the skin regions adjacent to the tip ends, and thereafter second damaged regions are generated in the skin regions adjacent to the sidewalls. Accordingly, even in a case where the second damaged regions are desired to be preferentially generated in the skin regions adjacent to the sidewalls of the existing needles30, the second damaged regions are generated in the skin regions adjacent to the sidewalls after the first damaged regions are generated in the skin regions adjacent to the tip ends. As a result, unnecessary electrical energy is supplied, and treatment time is delayed. Meanwhile, the plurality of needles130of a mono-polar type may include the first needles130aand the second needles130balternately arranged along a row and a column. The first needles130amay be grouped into a group of first needles130a, and the second needles130bmay be grouped into a group of second needles130b. For example, based onFIG.5, the needles130represented by (+) may be grouped into the group of first needles130a, and the needles130represented by (−) may be grouped into the group of second needles130b. RF current may be alternately applied to the group of first needles130aand the group of second needles130b. For example, the group of first needles130aand the group of second needles130bmay be connected in parallel to the same RF source, and RF current may be alternately applied to the group of first needles130aand the group of second needles130bby switching the same RF source. In another example, the group of first needles130aand the group of second needles130bmay be separately connected to different RF sources, and as the different RF sources apply RF current at different time, the RF current may be alternately applied to the group of first needles130aand the group of second needles130b. When the RF current is applied to the group of first needles130aand the group of second needles130bat different time, a proximity effect occurring in the plurality of needles130of a mono-polar type that have the group of first needles130aand the group of second needles130bmay be prevented. Here, the proximity effect means that the RF current applied to the plurality of needles130of a mono-polar type flows through only a part of the plurality of needles130of a mono-polar type. For example, the proximity effect may mean that the RF current flows through only needles located at the periphery among the plurality of needles130of a mono-polar type, or may mean that the RF current flows through only needles located in the center among the plurality of needles130of a mono-polar type. FIG.11is a schematic view illustrating energy transfer regions of a first needle and a second needle according to an embodiment of the inventive concept. As illustrated inFIG.11, the depth C1of skin by which electrical energy needs to be transferred to treat freckles may be 0.5 mm or less, the depth C2of skin by which electrical energy needs to be transferred for skin tone, skin texture, and skin tightening may be 1 mm or less, and the depth C3of skin by which electrical energy needs to be transferred to treat hair follicles and rosacea may be 1.25 mm or less. That is, because the depth of skin by which electrical energy needs to be transferred varies depending on treatment targets, the first needle130aand the second needle130bof the inventive concept may form energy transfer regions at different skin depths. Furthermore, the first needle130amay form an energy transfer region at a skin depth for treatment of freckles, skin ton, skin texture, skin tightening, hair follicles, and rosacea, and the second needle130bmay form an energy transfer region at a skin depth for treatment of freckles, skin tone, skin texture, and skin tightening. FIG.12is a perspective view illustrating a hand piece according to an embodiment of the inventive concept.FIG.13is a sectional view illustrating a needle tip for application of current mounted on the hand piece according to an embodiment of the inventive concept.FIG.14is a sectional view illustrating a state in which a pumping effect occurs in the needle tip for application of current mounted on the hand piece according to an embodiment of the inventive concept. As illustrated inFIGS.12to14, the hand piece500may be included. The hand piece500is a part that a doctor grasps. The doctor may change a target point (e.g., a portion of a face) by moving the hand piece500in a state of bringing the hand piece500into contact with the skin of a target person. The hand piece500may be connected to the skin treatment apparatus through a cable. An actuator module700and a power supply module may be embedded in the hand piece500. The cable may electrically connect the actuator module700and the power supply module, which are embedded in the hand piece500, with an electronic control module embedded in the skin treatment apparatus. The needle tip600for application of current may be mounted on an end portion of the hand piece500. In this case, the needle tip600for application of current may be mounted on the end portion of the hand piece500by being received in a cartridge that is mounted on the end portion of the hand piece500so as to be replaceable. The hand piece500may include, on the exterior thereof, a first conductive member501that electrically connects a needle unit620of the needle tip600for application of current and the power supply module and a second conductive member502that is docked with a cable connector503and that electrically connects the power supply module and the cable. In this case, the first conductive member501and the second conductive member502may be manufactured in the form of a film. For example, the first conductive member501and the second conductive member502may be flexible printed circuit boards (FPCBs). Because the needle unit620of the needle tip600for application of current reciprocally moves (operates) as will be described below, the conductive line that electrically connects the needle unit620of the needle tip600for application of current and the power module and the conductive line that electrically connects the power module and the cable are provided on the exterior of the hand piece500such that the conductive lines are not brought into contact with the needle unit620during the reciprocation of the needle unit620of the needle tip600for application of current. The needle tip600for application of current may be member that applies radio frequency (RF) to a deep skin portion at the target point. The needle tip600for application of current may be mounted on the end portion of the hand piece500so as to be removable. The needle tip600for application of current may include a cylinder610and the needle unit620. The cylinder610, which is a stator, may be mounted on the end portion of the hand piece500so as to be removable. The needle unit620, which is a movable component (moving in the vertical direction), may include one or more needles621and may be inserted into the deep skin portion at the target point according to a predetermined period (an operating period of the actuator module). The needle unit620may apply radio frequency (RF) to the dermal layer of the skin as needed. The cylinder610may have an empty space formed therein in the vertical direction. The needle unit620may be disposed in the interior space of the cylinder610. The cylinder610may be open at the bottom, and a lower end portion of the cylinder610may be disposed on the surface of the skin at the target point. Accordingly, the open portion of the cylinder610may be closed by the surface of the skin at the target point. The cylinder610may include a first cylinder611and a second cylinder612. In this case, the first cylinder611may be located on an upper side, and the second cylinder612may be located on a lower side. A lower end of the first cylinder611and an upper end of the second cylinder612may be connected. The second cylinder612may be open at the bottom. The needle unit620may be disposed in the first cylinder611and the second cylinder612, and a connecting portion between the first cylinder611and the second cylinder612may be closed by the needle unit620. A connecting rod625of the needle unit620may pass through an upper surface of the first cylinder611. In the first cylinder611, a first space1and an available space1-1may be formed by a first plunger623-1of the needle unit620. That is, the interior space of the first cylinder611may be closed in the vertical direction by the first plunger623-1of the needle unit620and may be divided into the first space1located on an upper side and the available space1-1located on a lower side. To maintain the air-tightness of the first space1of the first cylinder611, a gasket626may be disposed between the upper surface of the first cylinder611and the connecting rod625of the needle unit620. Furthermore, a gasket626may be disposed between the inner circumferential surface of the first cylinder611and the outer circumferential surface of the first plunger623-1of the needle unit620. A lower end of the second cylinder612may be disposed on the surface of the skin at the target point. Accordingly, the open lower portion of the second cylinder612may be closed by the surface of the skin at the target point. In the second cylinder612, an open-bottomed second space2may be formed by a second plunger623-2of the needle unit620. The interior space of the second cylinder612may be closed in the vertical direction by the second plunger623-2of the needle unit620. A holder622of the needle unit620and the second plunger623-2of the needle unit620may be disposed on an upper side of the interior space of the second cylinder612, and the open-bottomed second space2may be located on a lower side of the interior space of the second cylinder612. One or more recesses612-1may be formed on a lower surface of the second cylinder612(refer toFIG.3). The one or more recesses612-1of the second cylinder612may be formed from the outer circumferential surface of the second cylinder612to the inner circumferential surface of the second cylinder612. That is, the one or more recesses612-1of the second cylinder612may be formed through the second cylinder612. Furthermore, the one or more recesses612-1of the second cylinder612may be arranged to be spaced apart from each other along the periphery of the lower surface of the second cylinder612. That is, the one or more recesses612-1of the second cylinder612may be formed to be spaced apart from each other in the circumferential direction. Meanwhile, as described above, the open lower portion of the second space2may be closed by the surface of the skin at the target point. In this case, a gasket626may be disposed between the inner circumferential surface of the second cylinder612and the outer circumferential surface of the second plunger623-2of the needle unit620to maintain the air-tightness of the second space2. Meanwhile, in the state of maintaining the air-tightness, only a lower end portion of the second space2is selectively connected with the outside by the one or more recesses612-1of the second cylinder612to raise a pumping effect. The one or more needles621of the needle unit620may be disposed in the second space2. Because the lower surface of the second space2is open as described above, the one or more needles621may pass through the open portion of the second space2and may penetrate the surface of the skin at the target point. The cross-sectional area of the first cylinder611that is perpendicular to the vertical direction may be larger than the cross-sectional area of the second cylinder612that is perpendicular to the vertical direction. Accordingly, by reciprocation of a plunger623of the needle unit620in the vertical direction, a change in the volume of the first space1in the first cylinder611may be greater than a change in the volume of the second space2in the second cylinder612. The cylinder610may further include a seat613(refer toFIG.11). The seat613may be located in the second space2. The seat613may be disposed to be downwardly inclined toward the inside from the inner circumferential surface of the second cylinder612. The seat613may have a ring shape and may be disposed along the inner circumferential surface of the second cylinder612. In this case, likewise to the form of a valve seat, the seat613of the inventive concept may be disposed around the one or more needles621of the needle unit620. That is, the seat613may cover the periphery of the one or more needles621of the needle unit620. An outer end portion of the seat613may be a fixed end, and an inner end portion of the seat613may be a free end. Accordingly, the angle by which the seat613is downwardly inclined may be varied by a flow of air around the seat613. To improve the variation of the inclined angle, the seat613may be formed of an elastic material. The outer end portion of the seat613may be disposed in a higher position than the one or more recesses612-1of the second cylinder612. As a result, the inclination angle of the seat613may be varied depending on a flow of air flowing through the one or more recesses612-1of the second cylinder612. The seat613may interact with the one or more recesses612-1of the second cylinder612to raise the pumping effect that will be described below. The needle unit620may be disposed in the cylinder610. The needle unit620may be reciprocated in the vertical direction by the actuator module700. That is, the needle unit620may be disposed in the first cylinder611and the second cylinder612and may perform reciprocating motion, like a piston. In addition, the plunger623may partition the interior spaces of the first cylinder611and the second cylinder612and may change the volumes of the interior spaces of the first cylinder611and the second cylinder612. The needle unit620may be repeatedly (periodically) inserted into the skin at the target point by performing reciprocating motion in the vertical direction. In addition, the needle unit620may generate radio frequency in the deep skin portion at the target point, and collagen and elastic fibers damaged by thermal energy caused by the radio frequency may be regenerated over time to increase skin elasticity. The needle unit620may include the one or more needles621, the holder622, the plunger623, and the connecting rod625. The needles621may be the needles130described above, and the holder622may be the needle fixing part120described above. The one or more needles621may be alternately inserted into and pulled out of the skin while reciprocating together with the plunger623. Radio frequency may be applied to the one or more needles621to generate thermal energy in the deep skin portion at the target point. Without being limited thereto, however, electrical energy and ultrasonic waves in various wavelength bands, in addition to the radio frequency, may be applied to the one or more needles621. In addition, as described above, electrical energy or ultrasonic waves may not be applied to the one or more needles621. In the case where electrical energy such as radio frequency is applied to the one or more needles621, the one or more needles621may be electrically connected with the power supply module and may be supplied with power. To achieve this, the one or more needles621may be electrically connected with the power supply module through the first conductive member501described above. Meanwhile, the one or more needles621may be an electrode unit of a bipolar type in which a plurality of electrodes have two polarities and radio frequency is generated between adjacent electrodes, or the one or more needles621may be an electrode unit of a mono-polar type in which a plurality of electrodes all have the same polarity. In the case where the one or more needles621are of a mono-polar type, a ground electrode module (not illustrated) that circulates radio frequency generated from the one or more needles621may be additionally provided. The one or more needles621may be supported by the holder622. The one or more needles621may extend downward from the holder622. The one or more needles621may be disposed in the second space2of the second cylinder612. The one or more needles621may be reciprocated in the vertical direction by a driving force of the actuator module700. At the bottom dead point of the needle unit620, lower end portions of the one or more needles621may be disposed in the deep skin portion at the target point, and at the top dead point of the needle unit620, the lower end portions of the one or more needles621may be disposed above the surface of the skin. Accordingly, the one or more needles621may be repeatedly inserted into the deep skin portion at the target point. In this case, the one or more needles621may protrude downward through the open lower portion of the second space2in the second cylinder612and thereafter may retract upward. Meanwhile, the depth by which the one or more needles621are inserted into the skin may be about 2.1 mm. The holder622may be a member that supports the one or more needles621. Likewise to the one or more needles621, the holder622may be disposed in the second space2of the second cylinder612. Furthermore, the holder622may be disposed on a lower surface of the second plunger623-2and may be coupled with the second plunger623-2. In addition, the holder622may be omitted in some cases. In this case, the one or more needles621may be directly disposed on the plunger623. The plunger623may form the first space1and the second space2in the cylinder610while reciprocating in the vertical direction. Furthermore, a first channel3that connects the first space1and the second space2may be formed in the plunger623. A change in the volume of the first space1by the reciprocation of the plunger623is greater than a change in the volume of the second space2by the reciprocation of the plunger623. Therefore, when the plunger moves downward, gas in the second space2may move into the first space1through the first channel3, and when the plunger moves upward, the gas in the first space1may move into the second space2through the first channel3. Accordingly, when the plunger623moves downward, the one or more needles621may be inserted into the skin, and a negative pressure state may be formed in the second space2(the pressure may be decreased), and when the plunger623moves upward, the one or more needles621may be pulled out of the skin, and a positive pressure state may be formed in the second space2(the pressure may be increased). The plunger623may include the first plunger623-1and the second plunger623-2. The first plunger623-1may be disposed in the interior space of the first cylinder611. The first plunger623-1may close the interior space of the first cylinder611in the vertical direction to form the first space1located on the upper side of the first cylinder611and the available space1-1located on the lower side of the first cylinder611. The first plunger623-1may be reciprocated in the vertical direction by a driving force of the actuator module700. When the first plunger623-1moves downward, the volume of the first space1may be increased, and the volume of the available space1-1may be decreased (refer to (1) ofFIG.14). When the first plunger623-1moves upward, the volume of the first space1may be decreased, and the volume of the available space1-1may be increased (refer to (2) ofFIG.14). The second plunger623-2may be located in the interior space of the second cylinder612. The second plunger623-2may close the interior space of the second cylinder612in the vertical direction to form the second space2in the second cylinder612. The second plunger623-2may be reciprocated in the vertical direction by a driving force of the actuator module700. When the second plunger623-2moves downward, the volume of the second space2may be decreased (refer to (1) ofFIG.5). When the second plunger623-2moves upward, the volume of the second space2may be increased. The first channel3that connects the first space1and the second space2may be formed in the first plunger623-1and the second plunger623-2. In this case, the first channel3formed in the first plunger623-1and the second plunger623-2may be at least one flow passages3-1formed through the first plunger623-1and the second plunger623-2(or, formed in the first plunger and the second plunger) in the vertical direction. The connecting rod625may be disposed above the first plunger623-1. The connecting rod625may be moved in the vertical direction by a driving force of the actuator module700. The connecting rod625may be connected with the actuator module700and the first plunger623-1and may perform a function of transferring the driving force of the actuator module700to the first plunger623-1. Hereinafter, an operation (a pumping effect) of the needle tip600for application of current will be described with reference toFIG.14. When the skin treatment apparatus of the inventive concept is operated, the needle unit620may be repeatedly inserted into the skin at the target point while performing reciprocating motion in the vertical direction (the up/down direction) (in a case where radio frequency is applied, thermal energy is generated in the deep skin portion). Meanwhile, a medicine may be applied to the surface of the skin at the target point to alleviate a pain caused by the insertion of the needle unit620and facilitate regeneration of a wound. When the needle unit620moves downward, the volume of the first space1may be increased, and the volume of the second space2may be decreased. In this case, due to the difference between the cross-sectional areas of the first and second spaces1and2perpendicular to the vertical direction, a change in the volume of the first space1may be greater than a change in the volume of the second space2. That is, the increase in the volume of the first space1may be greater than the decrease in the volume of the second space2. Meanwhile, because the first space1and the second space2are connected by the first channel3, gas in the second space2may move into the first space1through the first channel3(refer to (1) ofFIG.11, a movement by a pressure difference caused by the volume change). Accordingly, the second space2may be in a negative pressure state (pressure decrease; in contrast, the first space is in a positive pressure state) and may suction the surface of the skin at the target point to make the height of the surface of the skin at the target point uniform. As a result, the one or more needles621may be inserted to a uniform depth (an effect of inserting the needles621to an equal depth, because the plurality of needles all irradiate radio frequency at a depth (a preset depth) that meets a medical design condition). When the needle unit620moves upward, the volume of the first space1may be decreased, and the volume of the second space2may be increased. In this case, due to the difference between the cross-sectional areas of the first and second spaces1and2perpendicular to the vertical direction, a change in the volume of the first space1may be greater than a change in the volume of the second space2. That is, the decrease in the volume of the first space1may be greater than the increase in the volume of the second space2. Meanwhile, because the first space1and the second space2are connected by the first channel3, the gas in the first space1may move into the second space2through the first channel3(refer to (2) ofFIG.5, a movement by a pressure difference caused by the volume change). As a result, the second space2may be in a positive pressure state (pressure increase; in contrast, the first space is in a negative pressure state) and may inject the medicine, which is applied to the surface of the skin at the target point, deep into the skin (a hole formed by inserting and pulling out the needle electrode) (an effect of injecting the medicine deep into the skin). Meanwhile, a second channel4that connects the available space1-1and the outside may be formed in the first cylinder611. The second channel4may prevent the pressure of gas in the available space1-1from hampering reciprocation of the first plunger623-1in the vertical direction. That is, when the needle unit620moves downward, the second channel4may release air in the available space101to the outside to remove a resistive force. In an embodiment, a needle of the inventive concept may be manufactured as follows. Silicone having a thickness by which an active region corresponding to a non-insulated region is to be formed may be prepared. A needle may be coupled to a cartridge. The needle may be inserted into the silicone to a location where the active region of the needle is desired to be formed. A first insulated region and a second insulated region may be formed by spraying an insulating material in a state in which the needle is inserted into the silicone. Meanwhile, the needle may be finally assembled after manufactured such that a partial region is not insulated, or the needle may be insulated by being inserted into a silicone layer after manufactured. Specifically, in a case of manufacturing a needle tip for application of current that includes the same number of active regions in the same specific positions, non-insulated needles are fixed to a cartridge, and the needles are inserted into silicone having a thickness corresponding to active region ranges. At this time, to simultaneously dispose the needles at the same depth, a silicone pad having a specific thickness may be pulled in opposite directions so as not to sag when the needles are inserted. Furthermore, in a case of forming the active regions in the same positions of the needles, the needles are inserted in a state in which the silicone pad having a thickness corresponding to the active region ranges is maintained by the distance between the active regions. Thereafter, the needles are insulated in a state in which the silicone is disposed in a position where the active regions are desired to be formed. Accordingly, the needles may have the active regions formed in the same positions. Here, the silicone may be replaced by various materials through which needles are disposed in desired positions and that enable active regions to be formed within a desired thickness range. For example, a flexible material such as silicone or rubber may be used. A method for manufacturing a needle tip for application of current according to an embodiment of the inventive concept includes preparing silicone having a thickness by which an active region corresponding to a non-insulated region is to be formed, coupling a plurality of needles to a needle fixing part, inserting the plurality of needles into the silicone up to locations of the plurality of needles where the active region is desired to be formed, and forming a tip end and an insulated region by spraying an insulating material in a state in which the plurality of needles are inserted into the silicone. As described above, the active regions of the plurality of needles of the needle tip for application of current are disposed at the same height. Accordingly, the needle tip for application of current may supply electrical energy only to a specific depth of skin through the energy transfer regions formed between the active regions of the needles. In addition, the tip ends of the needles are insulated. Accordingly, the needle tip for application of current may prevent excessive electrical energy concentrated on the tip ends of the needles from being transferred to skin. Effects of the inventive concept are not limited to the aforementioned effects, and any other effects not mentioned herein will be clearly understood from the following description by those skilled in the art to which the inventive concept pertains. While the inventive concept has been described with reference to exemplary embodiments, it will be apparent to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the inventive concept. Therefore, it should be understood that the above embodiments are not limiting, but illustrative. | 66,887 |
11857782 | Various embodiments are described in detail below with reference to the accompanying drawings, wherein like reference numerals represent like elements, and wherein dotted lines represent implanted components. DESCRIPTION OF THE PREFERRED EMBODIMENTS Instead of using transducer arrays positioned on the patient's skin to deliver TTFields (as in theFIG.1embodiment described above), the embodiments described herein use transducer arrays that are implanted within a patient's body to deliver TTFields. Implanting the transducer arrays can provide a number of potential advantages. These potential advantages include (1) hiding of the arrays from people with whom the patient interacts; (2) improving patient comfort (by avoiding the skin irritation, sensations of heating, and/or limitations on motion that can result from arrays that are positioned on the patient's skin); (3) improving electrical contact between the transducer arrays and the patient's body; (4) eliminating the need for shaving regions on which the arrays are placed (as hair growth can interfere with the delivery of TTFields); (5) avoiding the risk that detachment of the transducer arrays will interrupt the delivery of TTFields; (6) significantly reducing the power required to deliver TTFields (e.g., by reducing the physical distance between the transducer arrays and the tumor and bypassing anatomical structures that have high resistivity, e.g., the skull); (7) significantly reducing the weight of the device that must be carried by the patient (e.g., by using smaller batteries to take advantage of the reduced power requirements); (8) avoiding the skin irritation that can occur when transducer arrays are positioned on the patient's skin; and (9) making it possible to deliver TTFields to anatomic structures that cannot be treated using transducer arrays positioned on the patient's skin (e.g., the spinal cord, which is surrounded by highly conductive cerebrospinal fluid that is in turn surrounded by the bony structure of the spine, both of which interfere with the penetration of TTFields into the spinal cord itself). Note that in all of the embodiments described herein, it is important to include sensors for measuring temperature (such as thermistors) on or near the transducer arrays so that tissue temperature can be controlled and thermal damage to tissue avoided. In situations where a given transducer array is made up of a plurality of individual elements (e.g., ceramic discs) it is preferable to distribute a plurality of temperature sensors (e.g., thermistors) among the plurality of individual elements. One approach (not shown) for using implantable electrodes has a block diagram that is similar to the prior artFIG.1embodiment described above, except that the transducer arrays A, A, B, B are all implanted in the patient's body (e.g., between the scalp and the skull, or adjacent to the dura). While this approach enjoys advantages 1-8 listed above, it also suffers from a number of disadvantages. More specifically, each of the transducer arrays is connected to the cable box/AC voltage generator via a relatively long and bulky 10-conductor cable that extends outside of the body through a surgical incision or port (1 conductor for applying the AC voltage to the respective transducer array, plus 9 conductors that are used to obtain temperature readings from 8 different locations on the respective transducer array). The use of 10 conductor cables could make the system cumbersome. In addition, including a component that passes through the person's skin into the person's head raises the risk of acquiring an infection, which can be particularly problematic in the context of the brain. FIG.2depicts an improvement with respect to the approach described in the previous paragraph. In this approach, the number of conductors in each cable that must pass through the patient's skin is reduced from 10 to 4, which will significantly reduce the bulk and size of those cables. This may be accomplished, for example, by implanting additional electronics E adjacent to each of the implanted transducer arrays A, B and using a hub-based architecture. When the hub-based architecture is used, each of the electronic blocks E includes a multiplexor that reduces the number of conductors required for obtaining temperature measurements from 9 to 3, and a hub30his used to collect the temperature readings from each of the transducer arrays and forward those readings to the AC voltage generator30g. The AC voltage generator30gcan then control the current that is applied to each of the transducer array pairs A/A, BB in order to ensure that the transducer arrays do not overheat. Examples of circuitry that may be used to implement these electronic blocks E and the hub can be found in US 2018/0050200, entitled Temperature Measurement in Arrays for Delivering TTFields, which is incorporated herein by reference in its entirety. Note that while this embodiment does reduce the size and bulk of the wires that must pass through the person's skin, and provides advantages 1-8 listed above, it does not alleviate the risk of infection that is associated with a component that passes through the person's skin into the person's head. FIG.3depicts a variation on theFIG.2approach. In theFIG.3embodiment, instead of positioning the hub outside the patient's body and running four cables through the patient's skin (as inFIG.2), the electronics E, the transducer arrays A, B, and the hub30hare implanted in the patient's body. In thisFIG.3embodiment, only a single cable (i.e., the cable that runs between the hub30hand the AC voltage generator30g) must pass through the patient's skin. Optionally, this cable is connectorized using the depicted port12. In the example depicted inFIG.3, the hub30his positioned somewhere in the patient's thorax, and four 4-conductor cables run between the electronics E and the transducer arrays A, B in the patient's head and the hub30hin the patient's thorax. This positioning is advantageous because there are no wires that pass directly from the outside world directly into the patient's head, thereby reducing the risk of a serious infection. But in variations of theFIG.3embodiment, the hub30hmay be positioned in the patient's head, in which case the port12that provides access would also be positioned in the patient's head. In theseFIG.3embodiments, the hub30hcollects temperature measurements from each of the transducer arrays A, B via the electronics E and forwards those temperature measurements to the AC voltage generator30gvia the port12. The AC voltage generator30gcan then control the current that is applied to each of the transducer array pairs A/A, BB in order to ensure that the transducer arrays do not overheat. This embodiment also provides advantages 1-8 listed above. FIG.4depicts another approach that uses implantable electrodes and also provides advantages 1-8 listed above. In this embodiment, the electrodes A, B, the hub30h, and the AC voltage generator30gare all implanted within the patient's body. Power for the hub30hand the AC voltage generator30gis provided via a port14that is positioned somewhere on the patient's skin (e.g. in the thorax). The power source (e.g. the battery) in this embodiment is external, and the battery provides power to the hub30hand AC voltage generator30gvia the port. The port14is connected to the hub30hand AC voltage generator via appropriate wiring (e.g. a two conductor cable). Since effective delivery of TTFields requires delivery of power on the order of 10-100 W, care must be taken to minimize heat dissipation in all embodiments where the AC voltage generator30gis implanted within a patient's body (including thisFIG.4embodiment). This is because any inefficiencies will lead to heating of tissue surrounding the field generator, which could lead to thermal damage of tissue in the patient's body. To accomplish this, the AC voltage generator30gmust operate with very high efficiency. One example of a circuit that is suitable for implementing a high efficiency AC voltage generator is described in U.S. Pat. No. 9,910,453, entitled High Voltage, High Efficiency Sine Wave Generator with Pre-Set Frequency and Adjustable Amplitude, which is incorporated herein by reference in its entirety. The AC voltage generator30gin these embodiments may optionally operate by starting with a low-voltage AC signal and amplifying and filtering that signal using circuitry integrating a transformer and LC filter. In some embodiments, an independent circuit combining the transformer and LC filter could be connected to each transducer array (or even to each element of each transducer array). In these embodiments, the low-voltage signal generator could be connected to each array (or element) via a wire placed remotely from the arrays. In this configuration, heat generated through losses within the system would be spread over a larger volume thereby reducing the risk of thermal damage to tissue, while enabling delivery of higher field intensities. To further reduce losses, the circuit on each array (or element) could be designed with a switch that switches the low voltage signal coming from the signal generator, thereby potentially reducing the losses within the system associated with switching at the arrays. Optionally, the power source in theFIG.4embodiment may comprise multiple small batteries that are woven into a piece of clothing. This type of design would enable delivery of high power for extended periods of time while minimizing patient discomfort. FIG.5depicts a variation on theFIG.4embodiments that also provides advantages 1-8 listed above. In theFIG.5embodiments, instead of providing power to the hub30hand AC voltage generator30gdirectly via a wired connection that passes from the outside world into the patient's body via a port14that is installed on the person's skin (as inFIG.4), power in theFIG.5embodiment is provided to the hub30hand the AC voltage generator30gusing a wireless connection. This may be accomplished, for example, by implanting a first circuit21inside the patient's body close to the patient's skin. The first circuit is configured to receive energy via inductive coupling. A second circuit22(which may optionally be powered by a battery and/or the AC main) is configured to transmit energy to the first circuit21via inductive coupling. The second circuit22is positioned outside the patient's body adjacent to the first circuit21during operation, so that energy can be inductively coupled from the second circuit22into the first circuit21. The construction of these circuits21,22for transmitting and receiving energy via inductive coupling are well known in the art and are commonly used, for example, for charging cell phones etc. Optionally, the bulk and weight of the hardware that must be carried around by the patient can be advantageously reduced by providing multiple copies of the second circuit22at various locations that are frequented by the patient. For example, one copy of the second circuit22may be provided at the patient's office, a second copy of the second circuit22may be provided in the patient's car, a third copy of the second circuit22may be provided in the patient's living room, and a fourth copy of the second circuit22may be provided in or near the patient's bed. When multiple copies of the second circuit22are provided, the patient places the inductive coupling region of whichever second circuit22is nearby adjacent to the first circuit21implanted in their body so that the nearby second circuit22can power the implanted AC voltage generator30gvia inductive coupling. This arrangement can be particularly advantageous for people that move between various locations in a repeatable pattern (e.g., people who drive to work in the same car every day, work at the same desk every day, relax in the same living room every evening, and sleep in the same bed every night. Optionally, multiple copies of the second circuit22may be incorporated into a mattress so that the patient will not have to be hooked up to wires when they sleep, and can move around on the mattress. FIG.6depicts yet another embodiment that uses implanted electrodes and also provides advantages 1-8 listed above. Notably, the battery25in theFIG.6embodiment is implanted in the patient's body, and the implanted battery25is charged via induction. One challenge with this design is that the implanted battery25has to store relatively large amounts of energy. Thus, charging the battery25via induction may require the creation of large magnetic fluxes over extended periods of times. One method for overcoming this problem is a system in which a mattress incorporating a coil is used. The patient sleeps on this mattress, and the battery25powering the TTFields device is charged as the patient sleeps. In other embodiments, the coil could surround the bed. Alternatively, a transcutaneous energy transfer system (see, e.g., Dissanayake et. al., IFMBE proceeding vol. 23) could be used to charge the implanted battery25. In this case, a coil connected to a circuit designed to charge the implanted battery would be implanted transcutaneously. Charging would be performed with a separate device24, which the patient would place close to the implanted coil23. The external device could be fixed to the patient's body using a garment designed to fit tightly to the body, or using a medical adhesive. The patient would only be required to use the external charger when charging the implanted battery. This could occur for instance at night, while the patient is sleeping, thereby minimizing the need for the patient to carry an external device. Optionally, the implanted transducer array elements may be configured to permit dynamic alteration of the field distribution in order to optimize delivery of TTFields. Unlike the situation with external transducer arrays, once the transducer arrays have been implanted it will be impractical to adjust the position of the transducer arrays in order to optimize the field distribution within the patient's body. A different approach for controlling the field distribution within the patient's body is therefore desirable when implantable arrays are used. One suitable approach for this purpose would be to implant transducer arrays with a relatively large number of switchable elements. The field can then be shaped by choosing subsets of array elements that are switched on when the field is delivered. As the tumor changes over time (response or progression), the field distribution could be changed by changing the array elements through which the field is generated. Optionally, in any of the embodiments described above, the transducer arrays may be positioned on the dura. The advantage of this configuration is that power required to deliver TTFields to the brain would be reduced, because the field would not have to pass through the highly resistive layer of the skull. At the same time, this placement would reduce the need for invasive placement of the arrays in the brain-reducing the risk of damage to brain tissue and possibly the risk of infections. This configuration would also enable delivery of TTFields to large portions of the brain, as opposed to only delivering the TTFields to the tumor. In some cases, treating large portions of the brain may be advantageous. For instance, when treating the brain for metastases. In some embodiments, when treating regions of the body other than the head, the arrays could be placed subcutaneously to enable treatment of large regions. In other embodiments, the arrays could be placed in close proximity to the tumor. Placement in close proximity to the tumor would enable localized delivery of TTFields and reduce the power needed to deliver the fields. In all of the embodiments described above, any component that is described as being implanted must be configured for implantation before it is actually implanted in a person's body. This means that it must be dimensioned to fit within the location where it will be implanted, and that all surfaces that might come into contact with tissue in the person's body must be biocompatible. Optionally, in any of the embodiments described above, when the transducer arrays are implanted in the immediate vicinity of a tumor, the arrays could be made from or coated with a cytotoxic agent (e.g., platinum). Electrolysis caused by electric fields is expected to lead to release of platinum into the region around the tumor. Platinum is known to exert a cytotoxic effect on cancer cells, and therefore, release of platinum into the tumor may advantageously increase the anti-cancer effect of the TTFields treatment. Optionally, in any of the embodiments described above, the transducer arrays A, B and the electronics E that are implanted into the patient's head may be designed as described below in connection withFIG.7. The advantage of this configuration is that average field intensity can be maximized while minimizing the risk of heating by monitoring and adjusting the current to each electrode element in each transducer array independently, thereby improving the efficiency of TTFields delivery. These embodiments operate by alternately switching the current on and off for each individual electrode element that begins to overheat in order to reduce the average current for those electrode elements, without affecting the current that passes through the remaining electrode elements (which are not overheating). Assume, for example, a situation in which 500 mA of current is passing through a transducer array that includes 10 electrode elements, and only a single one of those electrode elements begins to overheat. Assume further that a 10% reduction of current through the single electrode element would be necessary to prevent that single electrode element from overheating. The embodiments described herein can cut the average current through the single electrode element by 10% by switching the current through that single electrode element on and off with a 90% duty cycle, while leaving the current on full-time for all the remaining electrode elements. Note that the switching rate must be sufficiently fast so that the instantaneous temperature at the single electrode element is never too hot, in view of the thermal inertia of the electrode elements. For example, a 90% duty cycle could be achieved by switching the current on for 90 ms and switching the current off for 10 ms. In some preferred embodiments, the period of switching the current on and off is less than 1 s. When this approach is used, the current through the remaining 9 electrode elements can remain unchanged (i.e., 50 mA per electrode element), and only the current through the single electrode element is reduced to an average of 45 mA. The average net total current through the transducer array will then be 495 mA (i.e., 9×50+45), which means that significantly more current can be coupled into the person's body without overheating at any of the electrode elements. The system may even be configured to increase the current through the remaining nine electrode elements in order to compensate for the reduction in current through the single electrode element. For example, the current through the remaining nine electrode elements could be increased to 50.5 mA per electrode element (e.g., by sending a request to the AC voltage generator to increase the voltage by 1%). If this solution is implemented, the average net total current through the entire transducer array would be (9 electrodes×50.5 mA+1 electrode×50.5 mA×0.9 duty cycle)=499.95 mA, which is extremely close to the original 500 mA of current. If, at some subsequent time (or even at the same time), the temperature at a second electrode element begins to overheat, a similar technique (i.e. a reduction in the duty cycle from 100% to something less than 100%) may be used to prevent the second electrode element from overheating. In some embodiments, this technique may be used to individually customize the duty cycle at each of the electrode elements in order to maximize the current that flows through each of those electrode elements without overheating. Optionally, instead of taking remedial action to reduce the duty cycle only when a given electrode element begins to overheat, the system may be configured to proactively set the duty cycle at each of the electrode elements in a given transducer array individually so as to equalize the temperature across all of the electrode elements in the array. For example, the system could be configured to individually set the duty cycle at each electrode element so as to maintain a temperature that hovers around a set temperature at each of the electrode elements. Optionally, the system may be configured to send a request to the AC voltage generator to increase or decrease the voltage as required in order to achieve this result. This approach can be used to ensure that each and every electrode element will carry the maximum average current possible (without overheating), which will provide an increased field strength in the tumor and a corresponding improvement in the treatment. FIG.7depicts an embodiment that periodically switches the current on and off for each individual electrode element that begins to overheat. The hub/AC voltage generator30has two outputs (OUT1 and OUT2), each of which has two terminals. The hub/AC voltage generator30generates an AC signal (e.g. a 200 kHz sine wave) between the two terminals of each of those outputs in an alternating sequence (e.g., activating OUT1 for 1 sec., then activating OUT2 for 1 sec., in an alternating sequence). A pair of conductors51are connected to the two terminals of OUT1, and each of those conductors51goes to a respective one of the left and right transducer assemblies31,32. Each of these transducer assemblies includes a plurality of electrode elements52(which collectively correspond to the transducer arrays A, B inFIGS.2-6) and electronic components56,85(which correspond to the electronics E inFIGS.2-6). A second pair of conductors51are connected to the two terminals of OUT2 and each of those conductors51goes to a respective one of the front and back transducer assemblies (not shown). The construction and operation of the front and back transducer assemblies is similar to the construction of the left and right transducer assemblies31,32depicted inFIG.7. Each of the transducer assemblies31,32includes a plurality of electrode elements52. In some preferred embodiments, each of these electrode elements52is a capacitively coupled electrode element. However, in thisFIG.7embodiment, instead of wiring all of the electrode elements52in parallel, an electrically controlled switch (S)56is wired in series with each electrode element (E)52, and all of these S+E combinations 56+52 are wired in parallel. Each of the switches56is configured to switch on or off independently of other switches based on a state of a respective control input that arrives from the digital output of the respective controller85. When a given one of the switches56is on (in response to a first state of the respective control input), current can flow between the electrical conductor51and the respective electrode element52. Conversely, when a given one of the switches56is off (in response to a second state of the respective control input), current cannot flow between the electrical conductor51and the respective electrode element52. In some preferred embodiments, each of the capacitively coupled electrode elements52is disc-shaped and has a dielectric layer on one side. In some preferred embodiments, each of the capacitively coupled electrode elements52comprises a conductive plate with a flat face, and the dielectric layer is disposed on the flat face of the conductive plate. In some preferred embodiments, all of the capacitively coupled electrode elements are held in place by a support structure. In some preferred embodiments, the electrical connection to each of the electrode elements52comprises a trace on a flex circuit. Each of the transducer assemblies31,32also includes a temperature sensor54(e.g., a thermistor) positioned at each of the electrode elements52so that each temperature sensor54can sense the temperature of a respective electrode element52. Each of the temperature sensors54generates a signal indicative of the temperature at (e.g., beneath) the respective electrode element52. The signals from the temperature sensors54are provided to the analog front and of the respective controller85. In embodiments where thermistors are used as the temperature sensors54, temperature readings may be obtained by routing a known current through each thermistor and measuring the voltage that appears across each thermistor. In some embodiments, thermistor-based temperature measurements may be implemented using a bidirectional analog multiplexer to select each of the thermistors in turn, with a current source that generates a known current (e.g., 150 μA) positioned behind the multiplexer, so that the known current will be routed into whichever thermistor is selected by the analog multiplexer at any given instant. The known current will cause a voltage to appear across the selected thermistor, and the temperature of the selected thermistor can be determined by measuring this voltage. The controller85runs a program that selects each of the thermistors in turn and measures the voltage that appears across each of the thermistors (which is indicative of the temperature at the selected thermistor) in turn. An example of suitable hardware and procedures that may be used to obtain temperature readings from each of the thermistors is described in US 2018/0050200, which is incorporated herein by reference in its entirety. In some preferred embodiments, the controller85may be implemented using a single-chip microcontroller or Programmable System on Chip (PSoC) with a built in analog front end and multiplexer. Suitable part numbers for this purpose include the CY8C4124LQI-443. In alternative embodiments, other microcontrollers may be used with either built-in or discrete analog front ends and multiplexers, as will be apparent to persons skilled in the relevant arts. In alternative embodiments, not shown, an alternative approach (e.g., the conventional voltage divider approach) for interfacing with the thermistors may be used in place of the constant current approach described above. In other alternative embodiments, a different type of temperature sensor may be used in place of the thermistors described above. Examples include thermocouples, RTDs, and integrated circuit temperature sensors such as the Analog Devices AD590 and the Texas Instruments LM135. Of course, when any of these alternative temperature sensors is used, appropriate modifications to the circuit (which will be apparent to persons skilled in the relevant arts) will be required. In some embodiments, the controller85is programmed to keep the temperature at all of the electrode elements below a safety threshold using intelligence that is built into each transducer assembly31. This may be accomplished, for example, by programming the controller85to start out by setting its digital output so that each of the switches56is continuously on (i.e., with a 100% duty cycle). Then, based on signals arriving via the controller85analog front end, the controller85determines whether the temperature at each of the electrode elements exceeds an upper threshold that is below the safety threshold. When the controller85detects this condition, the controller85reduces the duty cycle for the corresponding switch56by toggling the corresponding digital output at the desired duty cycle. This will interrupt the current to the corresponding electrode element52at the same duty cycle, thereby reducing the average current at the specific electrode elements52whose temperature exceeds that upper threshold. The level of reduction in current is determined by the duty cycle. For example, using a 50% duty cycle will cut the current by half; and using a 75% duty cycle will cut the current by 25%. Notably, this procedure only interrupts the current to specific ones of the electrode elements52on the transducer assembly31, and does not interrupt the current to the remaining electrode elements52on that transducer assembly31. This eliminates or reduces the need to cut the current that is being routed through the electrode elements when only a small number of those electrode elements are getting hot. A numeric example will be useful to illustrate this point. Assume, in theFIG.7embodiment, that the left and right transducer assemblies31,32are implanted on the left and right sides of a subject's head, respectively; that all of the switches56in the transducer assemblies31,32are in the ON state with a 100% duty cycle; and that the hub/AC voltage generator30is initially outputting 500 mA of current into the conductors51. An AC voltage will appear between the electrode elements52of the left transducer assembly31and the electrode elements52of the right transducer assembly32, and the 500 mA AC current will be capacitively coupled through the electrode elements52through the subject's head. The controller85in each of the transducer assemblies31,32monitors the temperature at each of the electrode elements52in that transducer assembly by inputting signals from each of the temperature sensors54via the analog front end of the controller85. Now assume that a given one of the electrode elements52in the transducer assembly31begins to overheat. This condition will be reported to the controller85in the transducer assembly31via a signal from the corresponding temperature sensor54. When the controller85recognizes that the given electrode element52is overheating, the controller85will toggle the control signal that goes to the corresponding switch56at the desired duty cycle in order to periodically interrupt the current to the given electrode element52and maintain a lower average current. Note that if the duty cycle at only one of the remaining electrode elements52is being reduced, it may be possible to maintain the original 500 mA current (and enjoy the advantages that arise from using the full current). However, if the duty cycle at a large enough number of the electrode elements52is being reduced, the original 500 mA current may have to be dropped. To accomplish this, the controller85can send a request to the hub/AC voltage generator30via the UART in the controller85. When the hub/AC voltage generator30receives this request, the hub/AC voltage generator30will reduce the output current at its corresponding output OUT1. Optionally, the duty cycle that is selected by the controller85may be controlled based on the speed at which the given electrode element52heats up after current is applied to the given electrode element52(as measured via the temperature sensors54and the analog front end of the controller85). More specifically, if the controller85recognizes that a given electrode element52is heating up twice as fast as expected, the controller85can select a duty cycle of 50% for that electrode element. Similarly, if the controller85recognizes that a given electrode element52is heating up 10% faster than expected, the controller85can select a duty cycle of 90% for that electrode element. In other embodiments, instead of deterministically cutting the average current by reducing the duty cycle, the controller85can reduce the average current at a given electrode element52based on real-time temperature measurements by turning off the current to the given electrode element52and waiting until temperature measured using the temperature sensors54drops below a second temperature threshold. Once the temperature drops below this second temperature threshold, the controller85can restore the current to the given electrode element52. This may be accomplished, for example, by controlling the state of the control input to the switch56that was previously turned off so that the switch56reverts to the ON state, which will allow current to flow between the electrical conductor and the respective electrode element52. In these embodiments, the current to a given electrode element52may be repeatedly switched off and on based on real-time temperature measurements in order to keep the temperature at the given electrode element52below the safety threshold. In theFIG.7embodiment, each of the transducer assemblies31,32is connected to the hub/AC voltage generator30via a respective cable. Notably only 4 conductors are required in each of the cables that run between the transducer assembly and the hub/AC voltage generator30(i.e., Vcc, data, and ground for implementing serial data communication, plus one additional conductor51for the AC current TTFields signal). Note that inFIG.7, each transducer assembly31,32includes nine electrode elements52, nine switches56, and nine temperature sensors54. But in alternative embodiments, each transducer assembly31,32can include a different number (e.g., between 8 and 25) of electrode elements52and a corresponding number of switches and temperature sensors. In these embodiments, the decision to adjust the duty cycle or turn off one or more of the switches56in a given transducer assembly31,32in order to reduce the average current to one or more of the electrode elements52is made locally in each transducer assembly31,32by the controller85within that transducer assembly31,32. But in alternative embodiments, the decision to adjust the duty cycle or turn off one or more of the switches56may be made by the hub/AC voltage generator30(or another remote device). In these embodiments, the controller85in each of the transducer assemblies31,32obtains the temperature readings from each of the temperature sensors54in the respective transducer assembly and transmits those temperature readings to the hub/AC voltage generator30via the UART of the controller85. The hub/AC voltage generator30decides which, if any, of the switches require a duty cycle adjustment or should be turned off based on the temperature readings that it received, and transmits a corresponding command to the corresponding controller85in the corresponding transducer assembly31,32. When the controller85receives this command from the hub/AC voltage generator30, the controller85responds by setting its digital output to a state that will switch off the corresponding switch56at the appropriate times, in order to carry out the command that was issued by the hub/AC voltage generator30. In these embodiments, the hub/AC voltage generator30can also be programmed to reduce its output current if a reduction in current is necessary to keep the temperature at each of the electrode elements52below the safety threshold. In these embodiments, the controller85may be programmed to operate as a slave to a master controller located in the hub/AC voltage generator30. In these embodiments, the controller85starts out in a quiescent state, where all it does is monitor incoming commands from the master controller that arrive via the UART. Examples of commands that can arrive from the master controller include a “collect temperature data” command, a “send temperature data” command, and a “set switches” command. When the controller85recognizes that a “collect temperature data” command has arrived, the controller85will obtain temperature readings from each of the temperature sensors54and store the result in a buffer. When the controller85recognizes that a “send temperature data” command has arrived, the controller85will execute a procedure that transmits the previously collected temperature readings from the buffer to the hub/AC voltage generator30via the UART86. And when the controller85recognizes that a “set switches” command has arrived, the controller85will execute a procedure to output appropriate voltages on its digital output in order to set each of the switches56to a desired state (i.e., either ON, OFF, or switching between on and off at a commanded duty cycle) based on data that arrives from the hub/AC voltage generator30. In the embodiments described above, a single controller85is used in each of the transducer assemblies31,32to control the switches56in that assembly and also to obtain temperature measurements from each of the temperature sensors54in that assembly. In alternative embodiments, instead of using a single controller85to control the switches56and to obtain the temperature measurements, those two tasks may be divided between two controllers, one of which is only used to control the switches56, and the other of which is used to obtain the temperature measurements from each of the temperature sensors54(e.g., using any of the approaches described above). In these embodiments, these two controllers may communicate directly with each other, and/or the hub/AC voltage generator30. In other alternative embodiments (not shown), temperature measurement does not rely on a local controller that is positioned in the vicinity of the electrode elements52. Instead, wires run from each of the temperature sensors54back to the hub/AC voltage generator30, and the hub/AC voltage generator uses signals that arrive via these wires to determine the temperature at each of the temperature sensors54. FIG.8is a schematic diagram of a circuit that is suitable for implementing the switches56,56′ in theFIG.7embodiment described above. The circuit includes two field effect transistors66,67wired in series, which is a configuration that can pass current in either direction. One example of a suitable FET for this circuit is the BSC320N20NSE. (Note that the diodes depicted inFIG.8are inherently included within the FETs66,67themselves.) The series combination of the two FETs66,67will either conduct or block the flow of electricity, depending on the state of the control input that arrives from one of the digital outputs of the controller85described above. When the series combination is conducting, current can flow between the shared conductor51and the respective electrode element52,52′. On the other hand, when the series combination of FETs66,67is not conducting, current will not flow between the shared conductor51and the respective electrode element52,52′. Optionally, a current sensing circuit60may be positioned in series with the switch56,56′. The current sensing circuit60may be implemented using any of a variety of conventional approaches that will be apparent to persons skilled in the relevant arts. When the current sensing circuit60is included, it generates an output that is representative of the current, and this output is reported back to the controller85(shown inFIG.7). The controller can then use this information to determine whether the measured current is as expected and take appropriate action if necessary. For example, if an overcurrent condition is detected, the controller85can turn off the corresponding switch. Of course, in those embodiments where the current sensing circuit60is omitted, it should be replaced with the wire (or other conductor) so that the current can flow between the shared conductor51and the top leg of the upper FET60. In the illustrated embodiment, the current sensing circuit60is positioned between the shared conductor51and the top leg of the upper FET60. But in alternative embodiments, the current sensing circuit may be positioned between the bottom leg of the lower FET67and the respective electrode element52,52′. And in other alternative embodiments (not shown), the current sensing circuit may be integrated within the circuitry of the switch itself. While the present invention has been disclosed with reference to certain embodiments, numerous modifications, alterations, and changes to the described embodiments are possible without departing from the sphere and scope of the present invention, as defined in the appended claims. Accordingly, it is intended that the present invention not be limited to the described embodiments, but that it has the full scope defined by the language of the following claims, and equivalents thereof. | 40,189 |
11857783 | DETAILED DESCRIPTION A first aspect of the technology described herein is based on systems and methods for implementation of a disposable miniaturized implant for treatment of treating gastrointestinal dysmotility, including dysphagia, gastroesophageal reflux disease (GERD), nausea, functional dyspepsia, blockage of transit, and obstruction of the GI tract (e.g., gastroparesis, post-operative ileus, inflammatory bowel diseases). One function of the implant is to provide electrical stimulation to the GI tract through direct stimulation on enteric nervous system/ICCs or the cercial and celiac branches of the vagus nerve. A second function of the implant is to provide electrical stimulation to the part of bowel going through surgery to expedite the healing process while recording the smooth muscle activities simultaneously; the third function of the implant is to reduce regulating GI motility through intestinal electrical stimulation for treating obesity. A fourth function of the implant is to record the pH value, pressure, transits time. Disposability of the implant is a key feature, as patients with POI would be less willing to undergo anther surgery to remove the device. For other chronic disease, the device would be a permanent implant. A second aspect of the technology described herein is based on systems and methods for non-invasive, transcutaneous stimulation of anatomy within the abdomen of the patient. A. Disposable Gastrointestinal Stimulator FIG.1throughFIG.3show schematic side view of three different gastrointestinal (GI) stimulation implants (10athrough10c, respectively) in accordance with the present description. GI stimulation implants10athrough10cpreferably comprise disposable GI implants that are battery powered (preferably with a rechargeable battery) to perform current mode stimulation. The GI stimulation implants10athrough10care implemented by heterogeneously integrating the microelectronics (i.e., the system-on-a-chip SoC), the battery, the antenna, other passive/active surface mounted components, and the electrode array into a single biocompatible package. In a preferred embodiment, the GI stimulation implants10athrough10celectrically modulate the gastrointestinal tract smooth muscles and the neurons residing in the muscularis externa to restore GI motility and inflammatory responses, as well as wirelessly record the GI motility by measuring the electrode-tissue impedance, pH value, transit time, and pressure. In another embodiment, the implants10athrough10care configured to electrically modulate the vagus nerve to regulate autonomic functions. FIG.1illustrates a first configuration of a GI implant10ahaving a battery24placed on the bottom side of the printed circuit board (PCB) interposer18a. In this embodiment, the PCB interposer18ais also used as an antenna for wireless signal transmission and recording. A substrate36acomprising an electrode array16ais provided for delivering GI stimulation. Electrode array16amay also be configured as a cuff electrode (not shown) for nerve stimulation. In a preferred embodiment, the substrate36acomprises a flexible material, such as polyimide, parylene, silicone, or PDMS, or the like, with a thickness generally ranging from 5 um to 50 um. The flexible substrate36aalso serves as a soft interposer board in which electrical connections are made by deposition of metal bumps28(e.g., Pt, Pt black, Titanium, gold, etc.) at pads34. An SoC12is positioned underneath the flexible substrate36asuch that specified openings (e.g., round shape or square shape openings) disposed through the flexible substrate36aexpose the metal pads32of the SoC12to the metallic bumps28other passive/active components14a. The openings on the substrate36aare aligned to the metal pads32of the SoC enable its operation. In one embodiment, Gold/alumina bumps28with a diameter from about 20 μm to about 50 μm are positioned on top of the opening to link the SoC12and the flexible substrate36a. The SoC12sits on top of a PCB interposer18a, which has patterned metal to serve as an antenna and an interposer for the connection with the battery24. The connection of the PCB interposer18ato the wireless transmitter/receiver in the SoC12is made by wire bonding22to pads38. The use of PCB is important because the flexible substrate36ahas a higher signal loss and its thin metal trace usually results in high resistivity, not suitable for relaying high frequency and weak electrical signal. In a preferred embodiment, the all or a portion of the stimulation implant10ais encapsulated in a capsule26comprising a biocompatible material (i.e. silicone, PDMS, glass, titanium, ceramic, and epoxy), which may be similar to the shape to a medicine capsule. FIG.2illustrates an alternative configuration of a GI implant10bhaving the battery, passive and active components (collectively14b) integrated with or adjacent to the SoC12on the same side or bottom side of the flexible substrate36b. In this configuration, the resistance of the metal traces on the flexible substrate36bare taken into consideration. A PCB antenna18bis disposed for wireless signal transmission and recording. Substrate36bcomprising an electrode array16bis provided for delivering GI stimulation. In a preferred embodiment, the substrate36bcomprises a flexible material, such as polyimide, parylene, silicone, or PDMS, or the like, with a thickness generally ranging from 5 um to 50 um. The flexible substrate36balso serves as a soft interposer board in which electrical connections are made by deposition of metal bumps28(e.g., Pt, Pt black, Titanium, gold, etc.) at pads34. An SoC12is positioned on a bottom surface of the flexible substrate36bsuch that specified openings (e.g., round shape or square shape openings) disposed through the flexible substrate36bexpose the metal pads32of the SoC12to the metallic bumps28or other passive/active components14b. The openings on the substrate36bare aligned to the metal pads32of the SoC enable its operation. In one embodiment, Gold/alumina bumps28with a diameter from 20-50 μm are positioned on top of the opening to link the SoC12and the flexible substrate36b. The SoC12sits on top of a PCB antenna18b, which has patterned metal to serve as an antenna and for the connection with the battery in components package14b. The connection of the PCB antenna18bto the SoC12is made by wire bonding22to pad38. In a preferred embodiment, the all or a portion of the stimulation implant10bis encapsulated in a capsule26comprising a biocompatible material (e.g., silicone, PDMS, glass, ceramic, titanium, epoxy, or like material), which may be similar to the shape to a medicine capsule. The GI/nerve implant10balso comprises one or more implant coils/wire antenna40. The implantable coils40are preferably configured to couple an external device or controller (not shown) via a wireless inductive coupling such that one or more of power and commands may be transmitted to/from the external device to apply a stimulus voltage at a treatment location in a body tissue. In one embodiment (not shown), the inductive coupling is achieved through a power and stimulator module and reverse telemetry module connected to the implant coil. Wherein the implant coil is inductively coupled to an external power coil that is configured to send a power signal to said implant coil, as well as send control stimulation parameters and process reverse telemetry. As shown inFIG.2, the flexible substrate36bis folded over (in a U-shape to wrap around below the SoC12and components14b, and has an embedded array of electrodes16bdirected downward from the device. Referring now toFIG.3, an alternative configuration of a GI implant10cis illustrated that is similar to the embodiment ofFIG.2except that the flexible substrate36cupon which the electrode array16cis disposed is laid straight depending on the needs of different clinical applications. For critical connections, such as power, ground connection and high frequency signal input/output, bonding wires22are used to form the electrical connection, in addition to using the metal trace on the flexible substrate36c, for the purpose of minimizing the parasitic resistance/capacitance contributed by the flexible substrate36c. In a preferred embodiment, the substrate36ccomprises a flexible material, such as polyimide, parylene, silicone, or PDMS, or the like, with a thickness generally ranging from 5 um to 50 um. The flexible substrate36calso serves as a soft interposer board in which electrical connections are made by deposition of metal bumps28(e.g., Pt, Pt black, Titanium, gold, etc.) at pads34. An SoC12is positioned on a bottom surface of the flexible substrate36csuch that specified openings (e.g., round shape or square shape openings) disposed through the flexible substrate36cexpose the metal pads32of the SoC12and/or other passive/active components14c(which may also comprise a battery and/or antenna) to the metallic bumps28. The openings on the substrate36care aligned to the metal pads32of the SoC12and components14cto enable their operation. In one embodiment, Gold/alumina bumps28with a diameter from 20-50 μm are positioned on top of the openings to link the SoC12and components14cand the flexible substrate36c. One or more of the SoC and active/passive components comprise application programming and a processor for activating the electrode array16according to a stimulation waveform as shown inFIG.5or6, discussed in more detail below. FIG.4AthroughFIG.4Cshow the bottom views of the intraluminal electrode arrays (50athrough50c, respectively). So that the gastrointestinal tract is not obstructed, electrode arrays50athrough50cpreferably have footprints such that length (L1) and width (W1) and height (into page) are configured to be less than about 1 cm. Sutures holes52may be provided through the substrate, and in one configuration the suture holes52are distributed on four sides of the electrode array50a,50b, and50cto allow clinicians purchase for anchoring the device inside the GI tract or the nerve through a buckle (not shown). For the application of transient GI implant for POI, the size of the suture holes52is generally in the range of 0.05 to 0.7 mm, allowing the use of synthetic absorbable/biodegradable suture wires (not shown) with different gauges. The absorbable/biodegradable suture wires are configured to dissolve after a period of time, thus allowing the implant to pass out of the GI tract without surgery for removal. The number of electrodes16may vary from the simplest configuration of two electrodes in the array50aofFIG.4Ato the four-electrode array50bofFIG.4B, six-electrode array50cofFIG.4C, as well as any number of electrodes, or even a cuff electrode for nerve stimulation and recording. In the two-electrode configuration50aofFIG.4A, one electrode serves as the stimulation/recording electrode and the other one is the return/ground electrode or vice versa. In a preferred embodiment, each of the electrodes in the array50athrough50care individually addressable for stimulation at distinct timing, frequency, or power. The size of the electrodes16preferably ranges to be below 9 mm2(e.g., 3 mm×3 mm) with a spacing of <2 mm. In the electrode array configuration, the size of each electrode is set to <2 mm2with a spacing of <2 mm. Each electrode16can be configured as ground/return, stimulation, recording, or concurrent stimulation and recording electrode. Multiple electrodes16can be used to deliver stimulus simultaneously with different parameters. The material of the electrode16can be silver, gold, platinum, titanium, or alloys. The electrode shape can also be strip, instead of round shape as shown, to ensure the device can interface with the biological tissue, regardless of its displacement. In one embodiment, pH sensing material may be coated on the electrode16for pH measurement. FIG.5shows one configuration of the current stimulation waveforms that may be delivered from any of the electrodes16or electrode arrays in the intraluminal implants detailed above. It is appreciated that while a single polarity stimulus is shown inFIG.5for the purpose of illustration, the stimulus may also be a biphasic stimulus (i.e. either cathodic first and anodic first), or other form know to one of skill in the art. Stimulus A is a high intensity pulse used to trigger the muscle/neurons. Its pulse width, PW1, is configured to be in the range of 0.5 ms-100 ms, with intensity from 0.5 mA to 10 mA. The stimulation frequency, 1/T1, is preferably set from 0.01 Hz to 300 Hz. A low intensity short stimulus, B1, is inserted between each strong stimulus. Stimulus B1should be issued after the electrode overpotential is back to its baseline value after the perturbation of stimulus A. The separation between stimuli A and B1(i.e., T2) can be more precisely determined based on the electrode-tissue impedance. In one embodiment, the purpose of stimulus B1is to monitor the tissue impedance during the contraction and/or relaxation of the GI smooth muscle. Tissue impedance is derived by measuring the electrode overpotential evoked by stimulus B1. The pulse width of stimulus B1can be set in the range of 10 μs to 1000 μs, based on the size of the electrode16(i.e., impedance of the electrode used) such that the delivered current (i.e., electric charge) flows to the tissue through the non-faradic reaction via the double layer capacitance of the electrode-tissue interface. Under such, the varying tissue impedance can be simply acquired by measuring the peak evoked electrode overpotential resulting from stimulus B and the known stimulation intensity. The intensity should be set to a range in order to ensure that the evoked electrode overpotential does not saturate the signal-recording circuit of the implant. Stimulation intensity used in our proof-of-concept experiment is from <1 μA to 1 mA. In order to measure the GI propagation wave during smooth muscle contraction and/or relaxation, multiple electrodes can be used for GI impedance/motility recording. This is done by employing other electrodes to deliver low-intensity stimuli (e.g., B2and B3) and carefully assigned a firing timing offset (i.e., T2-T4#0). If B1-3have different polarity than the stimulus A, firing timing of B1-3needs to be offset from that of stimulus A to ensure that the current contributed by B1-3does not flow directly to the electrode that delivers stimulus A, affecting the accuracy of the impedance/motility measurement. Because stimuli B1-B3are not designed to fire simultaneously, special consideration must be taken to determine the minimum delays between each stimulus. This is important, as many stimulators adopt passive charge to remove its residual charge by shorting the electrodes to the ground/reference electrode after each stimulation. It is therefore possible that during the firing of B1the injected current would simply flow to the adjacent electrode configured to fire B2, if it happens to perform passive discharge. The firing delay of stimuli for impedance/motility measurement (e.g., T2, and T3) can be determined based on the discharging time estimated by deriving the impedance of electrode-tissue interface. At least, T1-T3should be set at least 2 times the value of PW2. In another embodiment, the delivered stimuli are configured to mimic the nature electrophysiological signals, including one or more of: EMG, EGG, ECG, action potentials, and local-field potentials. FIG.6shows another configuration of stimulation parameters. Several pulses are grouped to trigger the activation of muscle/neurons during the duration of T4. T4is generally set to the range between 0.5 ms to 60 s, depending on the number of stimulus to be sent. The stimulation frequency, 1/T5, generally ranges from 0.01 Hz to 300 Hz. Between each group of stimuli, again, low intensity stimulus is inserted for impedance/motility measurement, in which the firing frequency, 1/T6, will ideally be the same as 1/T5to avoid the overlapping of both types of stimuli. The stimulus for impedance measurement can be either a single pulse, a pulse train, a sinusoidal wave, or the like. B. Non-Invasive Gastrointestinal Stimulator In addition to performing intraluminal stimulation and motility recording via the implant10athrough10cshown inFIG.1throughFIG.3, non-invasive transcutaneous electrical stimulation may also be employed for gastrointestinal therapeutics. FIG.7Ashows a front view of ventral body anatomy with acupuncture points and the transcutaneous electrical stimulation array60of the present description.FIG.7Bshows a side view of the patient with a transcutaneous GI stimulation system100and transcutaneous electrical stimulation array60disposed on the abdomen/abdominal wall of a patient in accordance with the present description. Unlike other conventional transcutaneous electrical nerve stimulation (TENS) devices that uses pairs of electrodes to perform bipolar stimulation for pain suppression and simple stimulation strategy/waveform, a multiple electrode array60is implemented to allow: 1) the spatial steering of the injected electrical charge to the target locations/tissues of interest within the anatomy; 2) a unique retarded stimulation waveform to minimize the unwanted edge effect during stimulation; and 3) electrode structures that not only lower the electrode-tissue interface impedance, but also avoid the influence of sweat that might create direct short circuit between two adjacent electrodes. Referring toFIG.7A, the diameter (D1) of the electrodes16generally ranges from 5 mm to 50 mm. The spacing (D2) between electrodes generally ranges from 3 mm to 100 mm. The number of electrodes (M by N) may be varied based on the area of the stimulation target region. The electrode array60may be directly placed on top of the acupuncture points62that govern/facilitate the functionalities of the internal organs (i.e., stomach, intestine, colon, bowel, liver and so on). Each electrode16in electrode array60is independently addressable for stimulation, and multiple electrodes16may be used to deliver stimuli simultaneously with different parameters to shape the resulting electrical field (FIG.7B) for focused stimulation. Each electrode can also be used to record the electrophysiological signals produced by the GI tract non-invasively. Thus, stimulation system100is not only capable of stimulating the acupuncture points62, but the stimulation current can be steered and applied to the target inside the body. In one example, if the patient received a surgery and has a surgical cut64made on his colon, stimulation current can be delivered from the electrodes on the abdominal wall which is close to the colonic segment undergoing surgery. By deliberately setting the stimulation parameters, the current that would otherwise spread to unwanted (i.e. non-treatment) regions within the body is minimized. In the example shown inFIG.7A, a cathodic first biphasic stimulus is applied to a center electrode67, and four adjacent electrodes65are given anodic first stimuli concurrent to focalize the stimulation current. More complex current weighting can be applied based on the depth, size, and location of the stimulation site. The duration for continuous stimulation should generally be less than 30 minutes in order to avoid unwanted tissue/neural damage. In another example, the electrode array can be placed on the back of the patient to stimulate the spinal ganglion for the modulating of GI motility and autonomic nervous system. Referring toFIG.7B, a return/ground electrode66is positioned on the back of the subject opposite the stimulation array60, or vice versa. In one application, the location of return/ground electrode66may be close to the midline or midline of the thoracic, lumbar, and sacral spines, allowing the stimulation current to pass through spinal ganglions where neuron/sympathetic/parasympathetic nerves reside, and then to be collected by the return/ground electrode66. With respect to a patient's skin, the stratum corneum (SC) is the outmost part of the skin, with a thickness in the range of 10-40 μm, and is thought to be the main contributor of the skin impedance. Conventional planar electrodes used for stimulation inject current from the high impedance SC layer, and thus inevitably set a requirement of high compliance voltage for the stimulator. For an electrode-tissue impedance of 2 kΩ using a planar electrode, delivering a 100 mA stimulus necessitates a high compliance voltage of 200 V for the stimulator, drastically increasing the its power consumption and possibly resulting in skin burning. Equally important, sweating is a non-negligible concern that needs to be taken into consideration during stimulation. The average density of sweat gland is 200 per square centimeter. The sweat gland resides in the dermis layer, and its duct conveys sweat to the surface of the skin. Excessive sweating may create direct shorting between electrodes or cause the stimulation current to spread to undesired targets. FIG.8is an enlarged side view of the electrode array60structure in accordance with the present description. In a preferred embodiment, the electrode array60comprises a plurality of conical penetrating spike electrodes16array, with only the tips54of the spikes exposed. The substrate56supporting the electrodes16, and a lower portion of the spike are preferably electrically insulated, e.g., by coating a lower portion of the spike and substrate56with a layer of non-conductive biocompatible material (i.e., epoxy, PDMS, polyimide, parylene, and silicone). The insulation layer ensures excessive sweat will not create shorting between electrodes, especially in the scenario that a high intensity current is used for neuromodulation. The height of the electrode16is configured to be larger than the thickness of the SC layer (e.g., 15-140 μm), and pierce the skin to bypass the high-impedance SC layer and the sweat gland. With such configuration, the compliance voltage of the stimulator may be much less stringent. In one example, the height h1of the exposed tip54of each spike on one electrode ranges from 5 μm-100 μm with an angle of α, where α ranges from 5° to 45°. The height of the insulated section (h2) of each spike may be set according to desired protection from electrode16shorting. Since the electrode tips54are exposed to low-impedance skin layers, under the same intensity of stimulus as conventional planar electrode or spike electrode with no insulation layer, less power is consumed (i.e., Power=Current×Impedance2), and hence less heat is generated for minimizing the possibility of skin burning. The shape of the electrode substrate56is also configured for mitigating the stimulation edge effect, in which the edge of the electrode16has the strongest electric field during the onset of electrical stimulation. Edge effect results in uncontrolled strong E-field that possibly damages the tissue/neuron/skin. Thus, unlike widely used circular/square/rectangular electrodes, the electrode substrate56presented herein is configured in such a way that its shape is symmetric, but has different path lengths from the center to the edge of the electrode for reducing the edge effect, such as a heptagram and octagram. The array60may further comprise an insulated electron holder58and conductor68that provides transfer of electrical current to the electrons. As shown in the embodiment ofFIG.8, the shown series of six spikes make up one electrode16. FIG.9AandFIG.9Bshow images of exemplary stimulation waveforms that may be used for stimulating a target region of interest.FIG.9Ashows a retarded stimulation waveform that has been commonly used to reduce the edge effect. In contrast to the square stimulation pulse, a predetermined rising time of the stimulus (Δt) is inserted for injecting a stimulus with the intensity Ipeak. Though this is a method for mitigating edge effect, it imposes stringent hardware specification for the stimulator when high frequency stimulus is required. For example, there are applications that fire 5-10 kHz stimulus (0.1 ms pulse width) in the form of pulse train into the tissue. The purpose of the 5-10 kHz stimulus is reported to block the pain fiber so that the subject does not feel pain during the stimulation. If the retarded waveform has a rising time of 1/10thof its pulse width and there are 10 steps increment for the current to go from 0 to Ipeak, the circuits of the stimulator, such as DAC, need to be able to produce its output rate at a minimum of 1 Mbps, possibly increasing the design complexity and performance requirement of the circuit components. FIG.9Billustrates a stepwise stimulation waveform using a stepwise pulse train to mitigate the stimulation edge effect in accordance with the present description. Each pulse is either mono-phasic or biphasic stimulus. Ipeakis the targeted stimulation intensity, which may vary from sub-1 mA to 300 mA. PW3and PW4are the pulse widths of each stimulus, which do not need to be equal, (as well as all other pulses in pulse train). In one embodiment, the pulse width varies from 10 μs to 10 ms. Tgapis the separation between two consecutive pulses and may vary from 0 to 100 times the pulse width. Again, Tgapcan vary between each consecutive two pulses. Lastly, Tperiodis the separation between two pulse trains and 1/Tperiod, is configured to be from sub-1 Hz to 300 Hz. The stimulation waveform is generated by first determining the number of steps N and the peak stimulation current Ipeak. For example, if N=10 and Ipeakis 100 mA, 9 (i.e. N−1) step-up current pulses would first be generated before reaching 100 mA. Subsequently, based on the user's specification and clinical performance of the subject, a specific number of stimuli with 100 mA intensity are fired. In the end of the pulse train stimulation, corresponding 9 step-down pulses are fired in the reciprocal order of the initial 9 step-up current pulses. When multiple channels are turned on simultaneously, the onset time of each group of pulse train is interleaved to avoid the concurrent firing, meaning Tdelayshould be larger than the length of the pulse train and smaller than Tperiod. This arrangement alleviates the design burden of the power management circuits in the stimulator, and avoids the risk of injecting a large current into the subject. In the scenario of DC current stimulation, concurrent firing of multi-channel would limit the overall injected current to <10 mA to avoid tissue/neuron damage. FIG.10AthroughFIG.10Dshow various stimulation current injection schemes in accordance with the present description. In addition to stimulating through a specific electrode or a group of electrodes concurrently with different current ratios, the stimuli may be delivered into the electrodes of interests based on an order defined by the clinician/researcher/scientist/patient. The purpose of the ordered stimulation onset is to mimic to physical massage in which muscles are kneaded in a certain order. A subset of examples of the stimulation order is demonstrated inFIG.10AthroughFIG.10D, which show an 8×8 electrode array60(for exemplary purposes only). The arrow sign indicates the direction of onset sequence of the stimulation. FIG.10Ashows stimulated electrodes70ain an onset sequence of stimulation horizontally from left to the right. Electrodes72aare not engaged in this sequence. FIG.10Bshows stimulated electrodes70bin a diagonal onset sequence of stimulation. Electrodes72bare not engaged in this sequence. FIG.10Cshows stimulated electrodes70cin a clockwise rectangular onset sequence of stimulation. Electrodes72care not engaged in this sequence.FIG.10Dshows stimulated electrodes70din a clockwise spiral onset sequence of stimulation. Electrodes72dare not engaged in this sequence. Multiple electrodes can also be activated to deliver electrical stimuli to through the skin. It is appreciated the sequences shown inFIG.10AthroughFIG.10Dare for illustrative purposes only, and any arrangement or number of sequences may be implemented according to the desired therapy and/or target tissue region. FIG.11shows a schematic block diagram of the non-invasive transcutaneous stimulator system100of the present description. The system100is configured for use with a mobile device104(i.e., cell phone, smart watch, tablet, laptop or like device) to transmit commands122to the stimulator through a wireless signal such as Bluetooth or WiFi. The command122is received by a wireless circuitry110and subsequently processed by a microprocessor102(e.g., MCU/FPGA/DSP or a customized application specific integrated chip (ASIC)), and then stored in the memory106. Based on the received commands, the application programming108stored in memory106executes instructions related to command122via MCU/FPGA/DSP/ASIC102, which delivers the control signals to the digital-to-analog converters (DACs)114to configure the stimulation current. Mobile device104may also comprise application programming (in addition to or in place of instructions in programming108) that contains instructions for providing the command122stimulus/stimuli, and associated memory for storing the programming and processor for executing and transmitting command122. It is important to point out that conventional stimulator designs adopt current mirrors to amplify the output current of the DAC and to convey the amplified current to the stimulator output stage. If this configuration is implemented using integrated microelectronics, the DAC usually outputs a small current while the current mirror is designated to support high current gain to optimize the power consumption of the electronics at the cost of larger chip area. In contrast, if the stimulator is to be developed using off-the-shelf components, there are generally no off-the-shelf high-gain current mirrors available, and thus inevitably increases the footprint of the stimulator when a high gain ration is desired. Moreover, as a high-compliance voltage is required for the stimulator to accommodate various electrode-tissue impedances and large stimulation current, the adoption of current mirrors further increases the power consumption of the stimulator. Hence, a viable solution is setting the stimulation current by directly configuring the base/gate voltage of the transistor (e.g., BJT or MOSFET). In the stimulator ofFIG.11, BJT1, and BJT2form the output stage of the stimulator. R3and R4, along with the current generated by the PGA outputs, form the base current of the BJTs or the overdrive voltage when MOSFETs are used. V+ and V− are the supply voltage of the stimulator and their value ranges from ±10V to ±100V to support a wide range of stimulation current and various types of electrodes. The base node of the BJT1-2is tied to its emitter through the pull-up resistor, R3-4, to ensure there is no output current when the stimulator is set to be off and no command signal is issued. Subsequently, when stimulation is on, the DAC's114deliver current or voltage output to the programmable gain amplifiers (PGAs)116. The (PGAs)116can be a voltage- or current-mode amplifier that generate voltage or current outputs. Note that the function of resistor R1is to convert the output current of the DACs114into voltage if a current-mode DAC is adopted. The DACs114can also be integrated in the ASIC so that multiple DACs can be incorporated to build a multi-channel stimulator without taking too much space of the stimulator. The gain of the PGA116is set based on the desired output current. The PGA116then drives the BJT through a high pass filter (HPF) made of R3-4and C1-2. The use of the HPF provides the advantage that the DAC/PGA can be powered using low supply voltages (e.g., 1.8V/3.3V/5V) to significantly reduce the overall system power consumption. During the stimulation, the stimulation command is sent preferably using the pulse waveform, e.g., similar to the waveform ofFIG.9B, to the base of the BJT (or the gate of a MOSFET). The amplitude and width of each pulse then results in the intended stimulation current waveform set by the user. A discharge switch, S1118, is connected to the stimulator output. Switch118is shorted to ground/return electrode66at the end of each stimulus to remove the residual charge. The control voltage to the discharge may be set to avoid the undesired turn-on of the discharge switch118during stimulation. For example, the control voltage can be either V+ to enable the charge cancellation or V− to disable charge cancellation. A one-to-N output de-multiplexer120is also connected to the stimulator output for the purpose of expanding the number of electrodes in array60driven by the stimulator. An impedance measurement circuit112is also connected to the stimulator output to measure the electrode-tissue impedance. This measurement can be performed, for example, by injecting a sinusoidal/square current and measuring the evoked electrode bio-potential, or by using the techniques described in PCT International Publication No. WO 2015/168162 published on Nov. 5, 2015 and incorporated herein by reference in its entirety. Measuring impedance can ensure the reliability of the electrode and be used as indicator to dynamically adjust the compliance voltage of the stimulator for power saving. For instance, if the electrode-tissue impedance is 0.5 kohm and a 100 mA stimulus is delivered to the electrode, then the compliance voltage should be set as ±50V. If the stimulation intensity is dropped to 50 mA, the required compliance voltage is only ±25V. Adaptively adjusting the compliance voltage based on the known stimulation intensity and the electrode-tissue impedance can optimize the power efficiency of the stimulator. The impedance measuring circuit may also measure conductivity between any two electrodes to determine if a short circuit has formed between electrodes and monitor a reparation rate of the patient. FIG.12shows a schematic diagram of a power management circuit150to be used with stimulation system100. Its main function is to generate both high negative and positive supply voltages for the stimulator from a battery154. The first DC-DC power converter156produces 1.8/3.3/5V from the battery154, and the 2ndDC-DC power converter158produces-1.8/−3.3/−5V by taking the 1.8/3.3/5V input. The 3rdDC-DC power converter160subsequently generates both positive and negative high compliance voltages. Capacitors, C3and C4, are connected to the power converter outputs and share the same common node connected to the ground/return electrode60/66. The use of C3-4helps define the positive and negative compliance voltages162a/162brelative to the body potential sensed by the ground/return electrode60/66. Once the electrode-tissue impedance164is known and the stimulation intensity is determined, the MCU/FPGA/DSP/ASIC102sends a command to the voltage tuning circuits152, which may comprise a resistor ladder, to adjust the output of the 3rdDC-DC power converter160. Embodiments of the present technology may be described herein with reference to flowchart illustrations of methods and systems according to embodiments of the technology, and/or procedures, algorithms, steps, operations, formulae, or other computational depictions, which may also be implemented as computer program products. In this regard, each block or step of a flowchart, and combinations of blocks (and/or steps) in a flowchart, as well as any procedure, algorithm, step, operation, formula, or computational depiction can be implemented by various means, such as hardware, firmware, and/or software including one or more computer program instructions embodied in computer-readable program code. As will be appreciated, any such computer program instructions may be executed by one or more computer processors, including without limitation a general-purpose computer or special purpose computer, or other programmable processing apparatus to produce a machine, such that the computer program instructions which execute on the computer processor(s) or other programmable processing apparatus create means for implementing the function(s) specified. Accordingly, blocks of the flowcharts, and procedures, algorithms, steps, operations, formulae, or computational depictions described herein support combinations of means for performing the specified function(s), combinations of steps for performing the specified function(s), and computer program instructions, such as embodied in computer-readable program code logic means, for performing the specified function(s). It will also be understood that each block of the flowchart illustrations, as well as any procedures, algorithms, steps, operations, formulae, or computational depictions and combinations thereof described herein, can be implemented by special purpose hardware-based computer systems which perform the specified function(s) or step(s), or combinations of special purpose hardware and computer-readable program code. Furthermore, these computer program instructions, such as embodied in computer-readable program code, may also be stored in one or more computer-readable memory or memory devices that can direct a computer processor or other programmable processing apparatus to function in a particular manner, such that the instructions stored in the computer-readable memory or memory devices produce an article of manufacture including instruction means which implement the function specified in the block(s) of the flowchart(s). The computer program instructions may also be executed by a computer processor or other programmable processing apparatus to cause a series of operational steps to be performed on the computer processor or other programmable processing apparatus to produce a computer-implemented process such that the instructions which execute on the computer processor or other programmable processing apparatus provide steps for implementing the functions specified in the block(s) of the flowchart(s), procedure (s) algorithm(s), step(s), operation(s), formula(e), or computational depiction(s). It will further be appreciated that the terms “programming” or “program executable” as used herein refer to one or more instructions that can be executed by one or more computer processors to perform one or more functions as described herein. The instructions can be embodied in software, in firmware, or in a combination of software and firmware. The instructions can be stored local to the device in non-transitory media, or can be stored remotely such as on a server, or all or a portion of the instructions can be stored locally and remotely. Instructions stored remotely can be downloaded (pushed) to the device by user initiation, or automatically based on one or more factors. It will further be appreciated that as used herein, that the terms processor, hardware processor, computer processor, central processing unit (CPU), and computer are used synonymously to denote a device capable of executing the instructions and communicating with input/output interfaces and/or peripheral devices, and that the terms processor, hardware processor, computer processor, CPU, and computer are intended to encompass single or multiple devices, single core and multicore devices, and variations thereof. From the description herein, it will be appreciated that the present disclosure encompasses multiple embodiments which include, but are not limited to, the following: 1. An implantable apparatus for stimulating a target anatomy, comprising: a flexible substrate configured to house a plurality of electrodes disposed in an electrode array; a system-on-chip (SoC) coupled to the flexible substrate; wherein the SoC is positioned on one side of the flexible substrate such that specified openings disposed through the flexible substrate align with conductive pads of the SoC; and passive/active components coupled to the SoC; wherein the implantable apparatus is configured to be installed at a treatment location of a gastrointestinal (GI) tract of a patient or the vagus nerve and its associated branches; and wherein the electrode array is configured to be activated to electrically modulate and record one or more of GI tract smooth muscles, associated neurons, and nerve fibers to restore GI motility and inflammatory responses within the GI tract. 2. The system, apparatus or method of any preceding or following embodiment, further comprising: a printed circuit board (PCB) antenna coupled to the SoC, the PCB antenna configured to receive signals from an external device for wireless activation of the electrode array and recording of signals from the electrode array; wherein the SoC is disposed between the PCB antenna and the flexible substrate. 3. The system, apparatus or method of any preceding or following embodiment, wherein the PCB antenna acts as an interposer between the SoC and a battery configured to power the apparatus. 4. The system, apparatus or method of any preceding or following embodiment, wherein the flexible substrate wraps around the SoC and PCB antenna. 5. The system, apparatus or method of any preceding or following embodiment, wherein all or a portion of the apparatus is encapsulated in a biocompatible material. 6. The system, apparatus or method of any preceding or following embodiment, wherein the flexible substrate comprises a plurality of suture holes for anchoring the apparatus within the GI tract via an absorbable suture. 7. The system, apparatus or method of any preceding or following embodiment, wherein one or more of the SoC and active/passive components comprise: a processor; a non-transitory memory storing instructions executable by the processor; wherein said instructions, when executed by the processor, perform steps comprising: activating the electrode array according to a user-determined stimulation waveform that is configurable based on the patient's physiological status. 8. The system, apparatus or method of any preceding or following embodiment, wherein the stimulation pattern comprises: a periodic stimulus comprising high-intensity pulses used to trigger muscle or neurons in the GI tract; a low-intensity stimulus comprising a short pulse inserted between each high-intensity stimulus; and wherein the low-intensity stimulus is used to monitor the tissue impedance during a contraction or relaxation of the GI smooth muscle. 9. The system, apparatus or method of any preceding or following embodiment, wherein the tissue impedance is derived by measuring the electrode overpotential evoked by the low-intensity stimulus. 10. The system, apparatus or method of any preceding or following embodiment, wherein said instructions, when executed by the processor, further perform steps comprising: delivering a second low-intensity stimulus via a second electrode in the electrode array separate from a first electrode in the electrode array, the first electrode generating the first low-intensity stimulus; and measuring a GI propagation wave during the smooth muscle contraction/relaxation. 11. The system, apparatus or method of any preceding or following embodiment, wherein the low-intensity stimulus pulse is inserted between a group of at least two high-intensity stimulus pulses. 12. A method for treating post-operative ileus, comprising: installing the disposable implant at a treatment location of a gastrointestinal (GI) tract of a patient; and electrically modulating one or more gastrointestinal tract smooth muscles and associated neurons to restore GI motility and reduce inflammatory responses. 13. The system, apparatus or method of any preceding or following embodiment, further comprising: wirelessly recording the GI motility by measuring one or more of the electrode-tissue impedance, GI pH value, and transit time. 14. The system, apparatus or method of any preceding or following embodiment, further comprising: applying an electrical stimulation at the treatment location at or near a vagus nerve ending to reduce a level of tumor necrosis factor (TNF) associate with the GI tract. 15. The system, apparatus or method of any preceding or following embodiment, wherein modulating is performed by activating the electrode array according to a user defined stimulation pulse waveform that is further adjustable based on the patient's physiological feedback to optimize treatment efficacy. 16. The system, apparatus or method of any preceding or following embodiment, wherein the stimulation pulse waveform is generated via one of more commands sent wirelessly to the implant from a device external to the patient. 17. The system, apparatus or method of any preceding or following embodiment, wherein the stimulation waveform is configured for simultaneous GI stimulation and motility recording, and comprises: a periodic stimulus comprising high-intensity pulses used to trigger muscle or neurons in the GI tract; a low-intensity stimulus comprising a short pulse inserted between each high-intensity stimulus; and wherein the low-intensity stimulus is used to monitor the tissue impedance during a contraction or relaxation of the GI smooth muscle. 18. The system, apparatus or method of any preceding or following embodiment, wherein the tissue impedance is derived by measuring the electrode overpotential evoked by the low-intensity stimulus. 19. The system, apparatus or method of any preceding or following embodiment, the method further comprising; delivering a second low-intensity stimulus via a second electrode in the electrode array separate from a first electrode in the electrode array, the first electrode generating the first low-intensity stimulus; and measuring a GI propagation wave during the smooth muscle contraction/relaxation. 20. The system, apparatus or method of any preceding or following embodiment, wherein the low-intensity stimulus pulse is inserted between a group of high intensity stimulus pulses. 21. A system for stimulating a target tissue of a patient, comprising: (a) a stimulator comprising an array of electrodes configured to transcutaneously deliver an electric field into the target tissue from a first surface on the patient, each electrode the array being independently addressable for stimulation at distinct timing or frequency; (b) a return electrode configured to be positioned on a second surface of the patient opposite the target tissue from the first surface; (c) a processor; (d) a non-transitory memory storing instructions executable by the processor; (e) wherein said instructions, when executed by the processor, perform steps comprising: (i) delivering stimuli to the array of electrodes such that the array simultaneously with different stimulation parameters; and (ii) emitting a shaped and focused electrical field from the array into the target tissue for stimulation of the target tissue; (iii) wherein at least two of the electrodes in the array are sequentially activated with a specified timing so as to generate the shaped and focused electrical field. 22. The system, apparatus or method of any preceding or following embodiment, wherein said delivering stimuli to the array comprises: applying a cathodic biphasic stimulus to a center electrode; and applying an anodic biphasic stimulus to four electrodes adjacent to the center electrode. 23. The system, apparatus or method of any preceding or following embodiment, further comprising: a mobile device wirelessly coupled to the stimulator; wherein the command is delivered to the stimulator from the mobile device; and wherein a recorded physiological signal is delivered to the mobile device from the stimulator. 24. The system, apparatus or method of any preceding or following embodiment: wherein the stimulator is configured to be positioned on an abdominal wall or back surface of the patient; and wherein the return electrode is configured to be positioned on a surface opposite the abdomen of the patient from the stimulator such that the shaped and focused electrical field is directed through the abdomen to be collected by the return electrode. 25. The system, apparatus or method of any preceding or following embodiment, wherein the shaped and focused electrical field is directed through spinal ganglions where neurons, sympathetic, or parasympathetic nerves. 26. The system, apparatus or method of any preceding or following embodiment, wherein the stimuli are delivered as a stepwise stimulation waveform comprising a plurality of spaced apart stepwise pulse trains configured to mitigate the stimulation edge effect. 27. The system, apparatus or method of any preceding or following embodiment, wherein each stepwise pulse train comprises: a series of step-up stimulation pulses each having a current that incrementally increases until a specified peak stimulation current is achieved; one or more subsequent peak intensity pulses at the peak stimulation current; and a series of step-down stimulation pulses each having a current that incrementally decreases. 28. The system, apparatus or method of any preceding or following embodiment, wherein the number of step-up stimulation pulses matches the number of step-down stimulation pulses. 29. The system, apparatus or method of any preceding or following embodiment: wherein two or more electrodes are activated simultaneously; and wherein the onset time of the stepwise pulse train delivered to each electrode is interleaved to avoid the concurrent firing of stepwise pulse trains in separate electrodes to ensure the overall stimulation current does not exceed a safe stimulation limit. 30. The system, apparatus or method of any preceding or following embodiment, wherein the electrode array comprises: a plurality of conical spikes each having an electrically insulated portion and a non-insulated tip; wherein the non-insulated tip has a shape and height configured to penetrate the patient's skin to bypass one or more of or sweat gland of the patient's skin. 31. The system, apparatus or method of any preceding or following embodiment, wherein stimulator comprises: a processor; one or more digital-to-analog converters (DACs) coupled to the processor; and an output stage comprising one or more transistors; wherein the stimulation current of the stimuli delivered to the electrodes is directly configured as a function of base/gate voltage of the one or more transistors. 32. The system, apparatus or method of any preceding or following embodiment, further comprising: one or more programmable gain amplifiers (PGAs) coupled to the one or more DACs; and a high pass filter coupled to the output stage; wherein the current or voltage output are delivered between the one or more DACs and the one or more PGAs to drive the one or more transistors of the output stage through the high pass filter (HPF). 33. The system, apparatus or method of any preceding or following embodiment, further comprising: a discharge switch coupled to an output of the stimulator and the return electrode; wherein discharge switch is shorted to return electrode at an end of each stimulus or group of stimuli to remove any residual charge when necessary. 34. The system, apparatus or method of any preceding or following embodiment, further comprising: an impedance measurement circuit coupled to an output of the stimulator; wherein said instructions, when executed by the processor, further perform steps comprising: (iv) measuring an electrode-tissue impedance; and (v) adaptively adjusting a compliance voltage of the stimulator as a function of a known stimulation intensity and the measured electrode-tissue. 35. The system, apparatus or method of any preceding or following embodiment, wherein said instructions, when executed by the processor, further perform steps comprising: (vi) measuring conductivity between any two electrodes to determine if a short circuit has formed between electrodes. 36. The system, apparatus or method of any preceding or following embodiment, wherein said instructions, when executed by the processor, further perform steps comprising: (vi) monitoring a reparation rate of the patient from the measured electrode-tissue impedance. 37. The system, apparatus or method of any preceding or following embodiment, wherein measuring an electrode-tissue impedance comprises injecting a sinusoidal or square current into the target tissue and measuring an evoked electrode bio-potential. 38. The system, apparatus or method of any preceding or following embodiment, further comprising: a battery coupled to the stimulator; and wherein the stimulator comprises a power management circuit configured to generate both high negative and positive supply voltages from the battery. 39. The system, apparatus or method of any preceding or following embodiment, wherein the power management circuit comprises: a first DC-DC power converter that is configured to produce a first voltage from the battery; a second DC-DC power converter that is configured to produce a second voltage; and a third DC-DC power converter that generates positive and negative high compliance voltages from the first and second voltages. 40. The system, apparatus or method of any preceding or following embodiment, wherein the delivered stimuli are configured to mimic the nature electrophysiological signals, including one or more of: EMG, EGG, ECG, action potentials, and local-field potentials. 41. An implantable apparatus for stimulating tissue, comprising: an implantable coil; a power and stimulator module connected to the implantable coil; a voltage stimulus electrode connected to the power and stimulator module; a reverse telemetry module connected to the implantable coil; a sensor connected to the reverse telemetry module; and a recording electrode connected to the sensor; wherein the implantable coil is configured to couple an external device via a wireless inductive coupling such that the power and stimulator module receives power and commands from the external device to apply a stimulus voltage at a treatment location in a body tissue through the voltage stimulus electrode; wherein the sensor is configured to receive one or more of a stimulus intensity applied by the stimulator module and a physiological signal received from the body tissue; and wherein the physiological signal is transmitted to the external device through wireless inductive coupling. 42. A system for stimulating tissue, comprising: (a) an implantable apparatus; (b) an external device; (c) the implantable apparatus comprising: (i) an implantable coil/antenna; (ii) a power and stimulator module connected to the implantable coil/antenna; (iii) a voltage stimulus electrode connected to the power and stimulator module; (iv) a reverse telemetry module connected to the implantable coil/antenna; (v) a sensor connected to the reverse telemetry module; and (vi) a recording electrode connected to the sensor; (vii) a battery powering the device); (d) the external device comprising: (i) an external power coil; (ii) a power transmitter connected to the external power coil and configured to send a power signal to said implantable coil; and (iii) a controller connected to the external power coil and configured to control stimulation parameters and process reverse telemetry of the implantable apparatus. 43. The system of any preceding embodiment: wherein the implantable apparatus is configured to couple to the external device via a wireless inductive coupling such that the power and stimulator module receives power and commands from the external device to apply a stimulus voltage at a treatment location in a body tissue through the voltage stimulus electrode; and wherein the sensor is configured to receive one or more of a stimulus intensity applied by the stimulator module and a physiological signal received from the body tissue. 44. The system, apparatus or method of any preceding or following embodiment: wherein the wireless inductive coupling comprises a modulated power signal; and wherein transmitted data is inserted at the end of the power signal. 45. The system, apparatus or method of any preceding or following embodiment, wherein the stimulus voltage is configured by modifying a base/gate voltage of a transistor of an output stage of the power and stimulator module 46. The system, apparatus or method of any preceding or following embodiment, wherein the commands from the external device comprises a stimulation command sent using the pulse waveform. 47. A method for treating post-operative ileus, comprising: installing the disposable implant of any of the preceding embodiments at a treatment location of a gastrointestinal (GI) tract of a patient; and applying an electrical stimulation at the treatment location at or near a vagus nerve ending to reduce a level of tumor necrosis factor (TN F) associate with the GI tract. 48. A method treating GI dysmotility and inflammation, comprising installing the implant of any of the preceding embodiments at a treatment location of a gastrointestinal (GI) tract or vagus nerve and its branches of a patient; and applying an electrical stimulation at the treatment location at or near a vagus nerve ending to reduce a level of tumor necrosis factor (TNF) associate with the GI tract or activating smooth muscle activities. As used herein, the singular terms “a,” “an,” and “the” may include plural referents unless the context clearly dictates otherwise. Reference to an object in the singular is not intended to mean “one and only one” unless explicitly so stated, but rather “one or more.” As used herein, the term “set” refers to a collection of one or more objects. Thus, for example, a set of objects can include a single object or multiple objects. As used herein, the terms “substantially” and “about” are used to describe and account for small variations. When used in conjunction with an event or circumstance, the terms can refer to instances in which the event or circumstance occurs precisely as well as instances in which the event or circumstance occurs to a close approximation. When used in conjunction with a numerical value, the terms can refer to a range of variation of less than or equal to ±10% of that numerical value, such as less than or equal to ±5%, less than or equal to ±4%, less than or equal to ±3%, less than or equal to ±2%, less than or equal to ±1%, less than or equal to ±0.5%, less than or equal to ±0.1%, or less than or equal to ±0.05%. For example, “substantially” aligned can refer to a range of angular variation of less than or equal to ±10°, such as less than or equal to ±5°, less than or equal to ±4°, less than or equal to ±3°, less than or equal to ±2°, less than or equal to ±1°, less than or equal to ±0.5°, less than or equal to ±0.1°, or less than or equal to ±0.05°. Additionally, amounts, ratios, and other numerical values may sometimes be presented herein in a range format. It is to be understood that such range format is used for convenience and brevity and should be understood flexibly to include numerical values explicitly specified as limits of a range, but also to include all individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly specified. For example, a ratio in the range of about 1 to about 200 should be understood to include the explicitly recited limits of about 1 and about 200, but also to include individual ratios such as about 2, about 3, and about 4, and sub-ranges such as about 10 to about 50, about 20 to about 100, and so forth. Although the description herein contains many details, these should not be construed as limiting the scope of the disclosure but as merely providing illustrations of some of the presently preferred embodiments. Therefore, it will be appreciated that the scope of the disclosure fully encompasses other embodiments which may become obvious to those skilled in the art. All structural and functional equivalents to the elements of the disclosed embodiments that are known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be encompassed by the present claims. Furthermore, no element, component, or method step in the present disclosure is intended to be dedicated to the public regardless of whether the element, component, or method step is explicitly recited in the claims. No claim element herein is to be construed as a “means plus function” element unless the element is expressly recited using the phrase “means for”. No claim element herein is to be construed as a “step plus function” element unless the element is expressly recited using the phrase “step for”. | 60,765 |
11857784 | DESCRIPTION OF EMBODIMENTS The present invention relates to a thermal stimulus transmission evaluation method and a method for evaluating drug benefits by thermal stimulus transmission for evaluating thermal stimulus applied to a specific site on a skin surface by controlling an electrical thermal stimulus apparatus so as to treat medical conditions such as psychological stress. A thermal stimulus evaluation method to evaluate the thermal stimulus applied to a specific site on a skin surface is carried by controlling an electrical thermal stimulus controller so as to treat medical conditions such as psychological stress. The thermal stimulus evaluation method comprises as follows; A blood flow with a laser Doppler tissue blood flowmeter mounted at the center of an inside wrist joint, before and after the application of thermal stimulus to a specific site that is selected for the application of thermal stimulus is measured. The increase rate of the blood flow before and after the application of thermal stimulus is obtained. The increase rate of blood flow before and after the application of thermal stimulus step is compared with the increase rate in the database storing the increase rate of blood flow which is previously effective on a medical condition, And when the increase rate of blood flow by application of the thermal stimulus at a selected specific site reaches is nearly the same as or higher than the increase rate blood flow which is previously effective on a medical condition, the effect of thermal stimulus is recognized, and the increase rate of blood flow is effective on a medical condition is 30% or more, preferably 100% or more. And, after the increase rate of blood flow by application of the thermal stimulus at a selected specific site reaches is nearly the same as or higher than the increase rate of blood flow which is previously effective on a medical condition, the drug is supplied into a body. The thermal stimulus transmission evaluation method includes the following steps. (1) Step of Examining Medical Conditions such as Psychological Stress Examination categories of examining medical conditions such as psychological stress include blood pressure, a deep body temperature, salivary amylase and a heart rate (arterial age) immediately before stimulus application after a subject is kept quiet in a face-up position for twenty minutes in consideration of the effect on psychological stress through an autonomic nerve. (2) Step of Selecting at a Specific Site for Application of the Thermal Stimulus. The specific site comprises at least one part of os metatarsale primam 1 and 2 interosseous, part os metatarsale primam 2 and 3 interosseous, and part that intersects the perpendicular line of the medial malleolus on an extension line of the medial margin on os metatarsale primam 1 and 2 in foot sole of right and left. (3) A blood flow is measured with a laser Doppler tissue blood flowmeter mounted at the center of an inside wrist joint, before and after the application of thermal stimulus to a specific site. And the rate of increase of blood flow applying stimulus to a specific site is obtained before and after the application of thermal stimulus. And the increase rate before and after the application of stimulus is compared with the increase rate in the database storing the rate of increase which is previously effective on a medical condition. FIG.2-4shows the database the rate of increase of the blood flow which is previously effective on a medical condition.FIG.2shows the rate increase of the blood flow in the thermal stimulus sites inFIG.1. In the table, (A) is os metatarsale primam 1 and 2 interosseous, (B) is part os metatarsale primam 2 and 3 interosseous, and (F) is part that intersects the perpendicular line of the medial malleolus on an extension line of the medial margin on os metatarsale primam 1 and 2. The favorable combination is (A) and (F). The rate increase in A is +1.30 or more, the rate increase in B is +1.30 or more, the rate increase in F is +1.30 or more and the rate increase in B+F is +1.40 or more. FIG.3is a database indicating the increase rate of blood flow in medical conditions. As for the examples of medical conditions, the increase rate of blood flow in excess stress, cardiac failure and weak constitutions are shown. It is found that the increase rate of blood flow for excess stress is +1.4 or more, the increase rate of blood flow for cardiac failure is +1.6 or more, and the increase rate of blood flow for weak constitutions is +1.7 or more. FIG.4is a database indicating the increase rate of blood flow of eleven patients. The effects were recognized with the increase rate of blood flow of +1.6 or more. The increase rate of blood flow at the measurement before and after the application of thermal stimulus to a specific site are compared with the increase rate of blood flow in a database, which is provided with the increase rate of blood flow recognized as effective on medical conditions. And the thermal stimulus is evaluated based on the increase rate of blood flow. It is desirable to measure the volume of blood flow by the laser Doppler tissue rheometer which is attached to an inner and central part of a wrist joint. In a laser tissue blood flowmeter ALF21D (manufactured by ADOVANS), when a living tissue is irradiated with semiconductor laser light (whose wavelength is 780 nm), light reflected from the tissue is converted into an electric signal and the electric signal is processed, thereby obtaining the blood flow information. A C type laser probe (10 mm in diameter, 3 mm in thickness, 2 mm 2 in a laser irradiation area, and 1 mm in measurement depth) of the laser tissue blood flowmeter ALF21D was attached to a central part of a wrist joint horizontal line of a healthy adult, and change of the blood flow was measured, taking a 15-minute rest after a stimulus. (4) An electrical thermal stimulus controller controls the increase rate of blood flow before and after the application of stimulus. It is preferable that an electrical thermal stimulus controller that is built into an electrical thermal stimulator is driven so as to vary at least one of a thermal stimulus temperature, thermal stimulus time period, a thermal stimulus application method, a pattern of thermal stimulus and a condition of thermal stimulus. (5) The increase rate of blood flow before and after thermal stimulus application is compared with the increase rate in a database storing the increase rate which is previously effective on medical conditions. The thermal stimulus is evaluated based on the increase rate of blood flow. Based on the difference of the increase rate between the increase rate of blood flow before and after thermal stimulus application and the increase rate which is previously effective on a medical condition, the effect of thermal stimulus by the application of thermal stimulus is determined. When the increase rate of blood flow by the application of stimulus reaches the increase rate which is previously effective on a medical condition, the effect of the application of thermal stimulus is recognized. When the increase rate by application of thermal stimulus not reaches the increase rate which are previously effective on medical conditions, it is preferable that the electrical thermal stimulus controller is driven so as to vary at least one of a thermal stimulus temperature, thermal stimulus time period, a thermal stimulus application method, a pattern of thermal stimulus and a condition of thermal stimulus. Again, the increase rate of blood flow by the application of thermal stimulus to the site is compared the increase rate which is previously effective on a medical condition in the database When the increase rate of blood flow by the application of stimulus reaches the increase rate which is previously effective on a medical condition, the effect of the application of thermal stimulus is recognized. The method for evaluating drug benefits by thermal stimulus transmission comprises as follows; A laser Doppler tissue blood flowmeter mounted at the center of an inside wrist joint is provided to measure blood flow. A blood flow before and after the application of thermal stimulus to a specific site that is selected for the application of thermal stimulus is measured with a laser Doppler tissue blood flowmeter mounted at the center of an inside wrist joint. The increase rate of blood flow measured before and after the application of thermal stimulus to a specific site is compared with the increase rate of blood flow in the database storing blood flow which is previously effective on medical conditions. The drug is supplied in the body. And at the time of supplying of the drug, the increase rate of blood flow by application of the thermal stimulus at a selected specific site is preferred to reach the increase rate of blood flow which is previously effective on a medical condition. On the other hand, when the increase rate of blood flow before and after application of the thermal stimulus at a selected specific site not reaches the increase rate of blood flow which is previously effective on a medical condition, the effect by the supplying the drug is not recognized. In this case, the thermal stimulus at a selected specific site is applied by changing the thermal stimulus conditions. And when the increase rate of blood flow before and after application of the thermal stimulus at a selected specific site reaches the increase rate of blood flow which is previously effective on a medical condition, the effect of thermal stimulus is recognized, and the effect by the supplying the drug is recognized. Wherein the drug may be supplied by changing the dose amount and/or an alternate drug. The sites of the thermal stimulus applied a body surface comprises at least two of part of os metatarsale primam 1 and 2 interosseous, part os metatarsale primam 2 and 3 interosseous, and part that intersects the perpendicular line of the medial malleolus on an extension line of the medial margin on os metatarsale primam 1 and 2 in foot sole of right and left. (6) “Tanden” breathing method may be further performed in the thermal stimulus evaluation. The “Tanden” is located at about one fist length down from the navel. In the Tanden breathing method, breathing is performed slowly while bulging out our abdomen. As the diaphragm lowers and the thorax expands further, large breaths can be taken. With this large breathing, attention is paid on inhaling and exhaling breaths with a long interval in-between to empty mind (mindlessness). Accordingly, autonomic nerve which is disturbed by stress can be adjusted. FIG.5a schematic view of an electrical thermal stimulus apparatus according to the present invention. FIG.6is a schematic view of a circuit diagram of the electrical thermal stimulus apparatus. An electrical thermal stimulus apparatus comprises the apparatus body10comprising a control function, and thermal guide element14which is connected to the apparatus body10by a lead12. As shown inFIG.5, the apparatus body10comprises a memory unit16, in which the thermal stimulus patterns are stored, a control unit (CPU)18, which reads out a thermal stimulus pattern from the memory unit16, and an output unit20, which supplies the thermal stimulus pattern to the thermal stimulus guide element14for a thermal stimulus. A thermal stimulus is applied to a thermal stimulus applied site, according to the thermal stimulus pattern. A control unit (CPU)18is connected to the memory unit16. A thermal stimulus pattern for obtaining a stimulus condition equivalent to that obtained from combustion of moxa is stored in the memory unit16. The control unit (CPU)18reads out the thermal stimulus pattern from the memory unit16, and controls an output to a thermal stimulus guide element(s) based on detection of an temperature sensor22, and outputs the thermal stimulus pattern to the thermal stimulus guide element(s). The apparatus body10is connected to two or more thermal stimulus guide elements for a thermal stimulus in order to supply the thermal stimulus pattern to at least two different a thermal stimulus applied site. In this manner, the selected thermal stimulus pattern is applied to the thermal stimulus applied site through the thermal guide elements for thermal stimulus. A temperature sensor22is provided in a position(s) which is correlated with a temperature of an affected area near the heating elements. The thermal stimulus guide elements for a thermal stimulus have a structure set forth below. The thermal stimulus guide element14for a thermal stimulus comprises a casing of apparatus body, a heater which is provided in the casing, and is used as a source of heating for applying thermal stimulus, a heat conduction board, which is provided on a lower face of the casing and which conducts heat of the heater to a skin of a patient, and a seal board provided on an upper face of the casing. The thermal stimulus guide elements are provides a heat conduction board made of at least two kinds of materials. In the example, the heat conduction board use aluminum and platinum. A temperature sensor is provided in a predetermined position of the housing which is in contact with a thermal stimulus applied site of a human body, and detects the temperature of the position, so as to send a detection signal to a sensor amplifier. The control unit (CPU) controls an output of an electric power generating circuit so that the temperature of the portion, which is in contact with a skin surface of a human body contact, may not exceed a predetermined temperature. When the heating temperature of the thermal stimulus guide elements detected by the temperature sensor is equal to or lower than a reference temperature, a positive side period of a pulse signal is controlled so as to be long and a negative side period of the pulse signal is controlled so as to be short, according to the output of the temperature sensor. On the contrary, when it is in a state at the reference temperature, a positive side period is controlled so as to be short and a negative side period thereof is controlled so as to be long. The method of operation in the thermal stimulus apparatus is as follows. The case where the guide elements are fixed to two thermal stimulus applied sites, which are different from one another, will describe below. The guide elements are fixed to the selected thermal stimulus applied sites, and electric power is supplied from the electric thermal stimulus apparatus. Here, in temperature setting and stimulus application method of the thermal stimulus guide elements, when the number of thermal stimulus applied site is two, the thermal stimulus guide elements 1 and 2 are used (FIG.7). The temperature is adjusted by a temperature setting switch. Every time the switch is pushed, the temperature of the elements is controlled in a range of from 46.5 to 52.5 in order of 1-2-3-4-5. A mode selection button for selecting a warming mode, that is, an alternate mode or a sequential mode, is provided therein. In the alternate mode, heating and pausing of the two guide elements 1 and 2 are alternatively repeated. In the sequential mode, thermal stimulus of the two guide elements which are different from one another is carried out one by one in order. In this way, thermal stimulus is non-simultaneously applied to the two different sites independently of one another. The four guide elements is uses for heating (worming) the four sites. In addition, a mode of a heating interval (time) can be chosen. The alternate mode can be chosen. After, an interval mode (short, long) can be chosen. For example, in the alternate mode and short time, the guide elements 1 and 2 is heated alternately, and after five second (at time, after 10 second, also at long time, after 15 second), the heating may be stopped. In the sequential mode, the guide elements 1 and 2 is heated for 7.5 second sequentially. FIG.8shows the pattern of the thermal stimulus. The pattern of the thermal stimulus is read out from the controller. The pattern read out of the thermal stimulus provides a thermal waveform8and an interval7. The thermal stimulus waveform includes a heating waveform32obtained by heating it to a determined peak temperature, for example, 50±5 degrees Celsius, and a thermal release waveform34which is formed by stopping heating after it reaches the peak temperature. The intensity of the thermal stimulus may be varying the thermal stimulus zone. The intensity of the thermal stimulus is obtained by increasing an area of the warming zone, by increasing a peak temperature, by increasing the gradient of the rising in the heating waveform, by decreasing an area of thermal release zone, by decreasing the gradient of the falling in the release waveform, by decreasing the time of interval, by increasing an time of the thermal stimulus pattern. The thermal stimulus pattern desirably includes non-simultaneously and independent thermal stimulus waveforms whose phases are shifted so that the patterns of thermal stimulus do not substantially overlap each other at a least different two thermal stimulus applied site. The thermal stimulus is desirably a thermal stimulus. The first thermal stimulus pattern comprises the thermal stimulus waveform configured by the heating waveform and a thermal release waveform, and an interval to the following thermal stimulus waveform in one cycle of the thermal stimulus patterns, The second thermal stimulus pattern comprises the thermal stimulus waveform for a time in the interval of first thermal stimulus pattern. The one cycle of the thermal stimulus pattern is preferably repeated at 10 to 15 minutes. And, after the cycle of the thermal stimulus pattern is repeated at 10 to 15 minutes, and the cycle of the thermal stimulus pattern is repeated at 10 to 15 minutes. The thermal stimulus pattern and the thermal stimulus waveform are stored in memory. EXAMPLE Example 1 The thermal stimulus apparatus is manufactured by BESTEC., Co. Ltd, and the thermal stimulus is carry out by using the thermal stimulus apparatus. And, the protocol of the thermal stimulus is shown inFIG.9. The thermal stimulus is carry out applying on thermal guide element at the specific site. The thermal guide element has a diameter; 10 mm and is set at a peak temperature; 50±5 degrees Celsius. The subjects are men and women of adult. The thermal stimulus applied sites of a body surface preferably comprises at least one of part of os metatarsale primam 1 and 2 interosseous, part os metatarsale primam 2 and 3 interosseous, and part that intersects the perpendicular line of the medial malleolus on an extension line of the medial margin on os metatarsale primam 1 and 2 in foot sole of right and left. The above-noted rates of increase which are previously effective on medical conditions stored in a database inFIG.2toFIG.4, are recognized as effective on the following medical conditions. 1. Thermal Stimulus to Site so as to Improve Stress (Parasympathetic Nerve is Predominant) Based on Deep Body Temperature, Stress Indicator and Systolic Blood Pressure A deep body temperature increased at all the sites tested in this experiment. Among them, particularly at a site between the second and the third metatarsal heads, an increase in a temperature by 2.0625° C. is recognized after stimulus. Salivary amylase is one indicator for evaluating stress, and it was shown that salivary amylase was likely to increase after stimulating a sole junction along a perpendicular line between the extended line between the first and second toes, and an inner ankle. Also, it was suggested that cortisol decreased at the same site. It was recognized that systolic blood pressure decreased significantly by 13 mmHg at a site between the first and second metatarsal heads. 2. Thermal Stimulus to Site so as to Improve Liver Function It was shown that liver functions were likely to improve by stimulating a sole junction along a perpendicular line between the extended line between the first and second toes, and an inner ankle. 3. Thermal Stimulus on Site so as to Prevent Arteriosclerosis It was suggested that the blood pressure was decreased further (prevention of arteriosclerosis) by continuously applying thermal stimulus between the first and second metatarsal heads. 4. Thermal Stimulus to Site so as to be Effective on Diabetes It was confirmed that glucose levels decreased by 5.00 to 5.33 between the first and second metatarsal heads and between the second and third metatarsal heads. 5. Thermal Stimulus to Site so as to Accelerate Peristaltic Motion and Absorption of Intestines It was found that the secretional capacity of gastrin as a gastrointestinal hormone accelerated significantly when stimulating a sole junction along a perpendicular line between the extended line between the first and second toes, and an inner ankle, which suggested that digestion absorption and the peristaltic motion of intestines would accelerate. 6. Thermal Stimulus to Site so as to Turn “ON” Genes of Longevity It was shown that Adiponectin was likely to increase after stimulating a site between the first and second metatarsal heads. Adiponectin is considered as one of the substances that activate Sirtuin genes, and is one of the genes related to longevity. Thus, it is suggested that the genes related to longevity are turned ON by stimulating two locations on a sole. 7. Thermal Stimulus to Site for Dieting Effect and Obesity Prevention Secretional capacities decreased in order of a site between the first and second metatarsal heads and a sole junction along a perpendicular line between the extended line between the first and second toes, and an inner ankle. Example 2 A system and method for conducting a thermal stimulation treatment according to the present invention will be explained below. Any device and method disclosed above may be used to conduct the following treatments. In accordance with a system or method for conducting a stimulus treatment of a subject or patient according to the present invention, the treatment may be conducted by using the combination of a stimulation application treatment, a dietary treatment, and a body exercise treatment so as to increase a blood flow in the subject staying in a thermal stimulation treatment institution (treatment provider or site), based on a treatment schedule prepared by the thermal stimulation treatment institution. The subject may continue to stay overnight in the institution. The system for the stimulus treatment includes the following steps: (1) conducting a health examination of the subject by a medical institution (any health care provider) before the subject makes her/his reservation for the stimulus treatment at the stimulation treatment institution and sending a result of the health examination to the stimulation treatment institution in which the subject is supposed to have the treatment; (2) sending to the subject a schedule of the stimulus treatment considered to be suitable for the subject in view of the result of the health examination; (3) making a reservation for the stimulus treatment to be performed in the stimulation treatment institution; (4) examining the health conditions of the subject to obtain her/his examination data information after the subject starts to stay at the stimulation treatment institution and registering (storing) the examination data information in an information accumulation device; (5) planning the schedule of the stimulus treatment, which is suitable for the subject in consideration of the examination data information obtained in the stimulation treatment institution; (6) based on the schedule of the stimulus treatment, conducting the stimulation application treatment on the subject, i.e., applying a stimulation to a predetermined stimulation receiving site of the subject utilizing a stimulation application device (as disclosed in the present application), in which the stimulation application device is controlled so as to increase the blood flow of the subject by 60% or more after the application of stimulation, as compared to the blood flow before the application of the stimulation; and (7) in addition to the stimulation application treatment, conducting the dietary treatment and the body exercise treatment in combination with the stimulation application treatment, utilizing the blood flow as index for the treatments. Here, the stimulation receiving site comprises at least one area selected from: (F) site that intersects the perpendicular line of the medial malleolus on an extension line of the medial margin on os metatarsale primam 1 and 2 in foot sole; (L) incisurasive foramen supraorbitalis site; (K) site where the lintersection of the line connecting an augulus oculi medialis of eye and L site, and perpendicular of an augulus oculi lateralis of eye is located; and/or (M) site of augulus oculi lateralis located above 1 horizontal finger from center of the line where connect the inner end of left and right eyebrow. More particularly, the stimulation receiving sites (L), (K), (M) and (F) are defined as follows: (L) incisurasive foramen supraorbitalis site:site of augulus oculi lateralis located above 1 cm from orbital height.Site where supraorbitalis artery, vein, and supraorbitalis nerve branche at face.Site to stimulate the blood vessel (artery) and nerve of eye; (K) site;Site where the lintersection of the line connecting an augulus oculi medialis of eye and (L) site, and perpendicular of an augulus oculi lateralis of eye is located.Site where the blood flow of artery in eye amplifySite to stimulate the peripheral nerves of eye; (M) site;site of augulus oculi lateralis located above 1 horizontal finger from center of the line where connect the inner end of left and right eyebrow,Site to stimulate the trochlear of eye; (F) site (above mentioned);Site that intersects the perpendicular line of the medial malleolus on an extension line of the medial margin on os metatarsale primam 1 and 2 in foot sole. The blood flow is preferably measured by a laser Doppler tissue blood flowmeter mounted at the center of the inside wrist joint of the subject. The stimulation treatment institution may obtain normal (standard or threshold) examination data information including heartbeat, irregular heartbeat, and the like (threshold values), which is associated with the decrease in the blood flow of the subject, during the stay of the subject. The normal examination data information may be accumulated (stored) in the information accumulation device and compared with additional examination data information newly obtained from the subject. When the newly-obtained examination data information has any value outside the normal examination data information, the information accumulation device will inform the subject of the abnormality of examination data information. When the newly-obtained examination data information is found to have any value outside the normal examination data information, the information accumulation device may send a notification to the stimulation treatment institution as well as informing the subject of the abnormality, which then allows the stimulation treatment institution to send appropriate health care advice to the subject. The information accumulation device may be provided with an information telecommunication device which has a button with a function to send and receive the examination data information. The information accumulation device may be configured such that, when the button is one-clicked by the user, the newly-obtained examination data information is sent out to the stimulation treatment institution via the information telecommunication device. The stimulation treatment institution may provide reward point system. Reward points may be given to the subject in accordance with the obtained increase of the blood flow such that one point may be awarded if the subject achieves 1% increase of the blood flow, for example. The subject may be rewarded with free or discount tickets or coupons for playing golf, utilizing a swimming pool, any recreation spots, restaurants, an extended stay, or a discount on treatment fees at the stimulation treatment institution based on the reward points. The stimulation treatment institution may be constructed with such affiliated facilities. The stimulation type applied to the subject is not limited, but may be selected from thermal stimulation, electric stimulation, light stimulation, or the like. Given any type of the stimulation, the stimulation application device may preferably be adjusted and controlled, by the method discussed above in this application, so as to increase the blood flow of the stimulated site of the subject by 60% or more after the stimulation, in comparison with the blood flow before the stimulation. In addition to the stimulation application treatment, an acupuncture treatment may preferably be performed to the subject. In addition to the stimulation application treatment, so-called “Tanden” point which is a point in a center low part of the abdomen of the subject may preferably be stimulated. | 29,330 |
11857785 | DETAILED DESCRIPTION Systems, devices and methods are provided for delivering electrical impulses to bodily tissue. The systems, devices and methods are particularly useful for promoting bone healing and controlling pain in for example, spinal fusion patients. In some embodiments, a therapeutic stimulator system enables improved tracking and sharing of treatment and status information. In some embodiments, the therapeutic stimulator system includes a wearable, non-invasive stimulator device and a hub device, such as a smartphone or tablet, that captures stimulator usage data, user motion data and user-provided status data. The captured data can be aggregated to provide feedback to the user and their healthcare provider to improve the user's recovery. The systems and devices also help ensure and demonstrate both compliance with the therapy and higher patient satisfaction through richer and more frequent data sharing between the physician and patient. The present therapeutic stimulator systems increase efficiency and improve ease of use over conventional systems by reducing power consumption and decreasing quantities of data stored and transferred. For example, in some embodiments, the therapeutic stimulator systems can reduce power drain and provide long battery life (e.g., greater than 24 hours) by manually or periodically pulling data from the stimulator devices, instead of maintaining communication with, for example, a base station that constantly pulls data from the stimulator devices. Additionally, for example, in some embodiments the therapeutic stimulator systems can decrease quantities of information (e.g., accelerometer data) stored and transferred by the stimulation devices by combining it into a histogram using an algorithm, which parse the information and converts it into a form that is more meaningful to users (e.g., “active hours”). While the following disclosure is presented with respect to electrical stimulation devices for enhancing bone healing in spinal fusion patients, it should be understood that the features of the presently described devices may be readily adapted for use in any type of electrical stimulation device, such as electrotherapy devices, muscle stimulation devices (e.g., transcutaneous electrical nerve stimulation or TENS), nerve stimulation devices, such as sacral nerve stimulators, vagus nerve stimulators, peripheral nerve stimulation (PNS), spinal cord stimulation, tibial nerve stimulators and the like. In addition, while the present disclosure primarily describes non-invasive, transcutaneous nerve stimulation, the features described herein may be readily adapted for other approaches, such as implantable nerve and muscle stimulators and/or percutaneous nerve stimulators. Referring now toFIG.1, a portable stimulation device10will now be described. As shown, stimulation device10comprises a housing12with upper and lower surfaces14,16and first and second opposing side surfaces18,20connecting upper surface14to lower surface16. In certain embodiments, housing12is generally rectangular with side surfaces18,20each having a curved end portion22,24that forms a continuous surface around housing12(see alsoFIG.2). Side surfaces18,20may be substantially linear, or they may be curved depending on a location housing12is worn on a patient's body. For example, inner side surface12may have a slightly concave surface while outer side surface14may be slightly convex to provide enhanced conformity with a patient's waist. Housing12is preferably lightweight and compact to augment comfort and wearability. Housing12may be constructed of any suitable material that provides such functionality, such as metal (e.g., stainless steel or aluminum), plastic (e.g., polycarbonate, polypropylene or polyethylene) or the like. Housing12is also relatively thin and ergonomic, preferably having a wall thickness of about 0.05 to 2.0 mm, preferably about 1.0 mm and an enclosure depth of about 15 mm to about 20 mm, preferably about 17.5 mm. Housing12includes an energy source, such as a rechargeable battery (not shown). The rechargeable battery is housed within a battery pack30that is removably coupled to lower surface16of housing12. The system may further include a recharging outlet or station (also not shown) configured to receive the rechargeable battery. Alternatively, battery pack30may comprise an outlet or other coupling element for directly charging the battery with a suitable electrical connector (i.e., without removing battery pack30from housing12). Providing a rechargeable battery that may be easily switched out allows 24 hour use of the device, which may increase the effectiveness of the device. In other embodiments, the energy source may be located exterior to housing12and either directly connected thereto with wires or other electrical connections, or wirelessly coupled to housing12via a suitable wireless energy transmitter/receiver device. In certain embodiments, battery pack30includes a data storage component (not shown) coupled to a processor240(seeFIG.6) within stimulation device10. Processor240is configured to transfer data, such as motion data, usage levels, or any other data collected by processor240, to the data storage component. The data storage component may be accessed by a separate processor external to the stimulation device (e.g., in the mobile device60or a separate processing device) when the battery is removed for recharging. This allows large amounts of data to be transferred from the stimulation device to the mobile device, i.e., larger amounts of data that may be possible through wireless transmission alone. Stimulation device10further includes first and second electrodes40,42coupled to housing via flexible lead wires44,46. Lead wires44,46are preferably at least long enough to extend from housing12to the target location on the patient's back (seeFIG.3) when housing12is attached to the patient's waist (seeFIG.2). In certain embodiments, lead wires44,46are long enough to allow the patient to attach electrodes40,42to the target location without wearing housing12(e.g., by placing it on the bedside table during sleep, carrying housing12in a backpack or the like). Lead wires44,46are attached to a connection terminal48on upper surface14of housing12, which is coupled to a signal generator232within housing12(discussed below in reference toFIG.6). Alternatively, connection terminal48may be located on lower surface16or opposing side surfaces18,20. In yet another embodiment, electrodes40,42may be wirelessly coupled to housing12such that lead wires44,46are not required. Electrodes40,42may comprise any suitable skin pad electrodes configured to contact, and adhere to, an outer skin surface of the patient and to deliver electrical impulses through the outer skin surface to a target location within the patient's body. In one embodiment, electrodes40,42comprise conductive gel pads and have a suitable adhesive layer for bonding electrodes40,42to the patient's skin (seeFIG.3). Referring now toFIG.2, housing12further includes an attachment element, such as a clip50, that allows the patient to attach housing12to a wearable garment57, such as a belt, pants, skirt, shorts, or the like. Of course, the attachment element may comprise any suitable releasable coupling element, such as fasteners, snaps, interference fit structures, Velcro and the like. As shown, housing12is designed to be worn on the side of the patient's waist to minimize interference with movement, such as walking, kneeling, sitting, bending over or laying down. This ensures that housing is comfortable and non-intrusive to wear, which increases patience compliance with the therapy regimen prescribed by the caregiver. Of course, it should be recognized that the present disclosure is not limited to an attachment element that couples the housing12of device10to the patient's waist. For example, device10may be configured for attachment to a variety of different wearable garments, such as hats, socks, robes, jackets, pants, shirts, vests, shorts, bibs, coveralls, boots, scarves, ear-muffs, beanies, underwear, wetsuits and the like, and/or to other non-wearable items, such as blankets, sheets, towels, bandages, seats, mattresses, sleeping-bags, and the like. In one embodiment, significant portions of the control of stimulation device10may reside in controller components that are physically separate from the housing12. For example, the power supply and other electronic components of stimulation device10may be located in a separate controller device. In this embodiment, separate components of the controller and stimulator housing generally communicate with one another wirelessly. Thus, the use of wireless technology avoids the inconvenience and distance limitations of interconnecting cables. In addition, the stimulator device10may be constructed with the minimum number of components needed to generate the stimulation pulses, with the remaining components placed in parts of a controller that reside outside the stimulator housing, resulting in a lighter and smaller stimulator housing. In fact, the stimulator housing12may be made so small that it could be difficult to place user inputs or indicators on the stimulator housing's exterior. Instead, the user interface may be located on a separate control device, such as smartphone touchscreen (discussed below). In these embodiments, device10may be incorporated into a wearable garment. For example, a wearable garment, such as a shirt or pants, may include one or more internal recesses for housing electrodes40,42such that the electrodes can be placed against a target location on the patient's outer skin surface when the patient wears the garment. The wearable garment may include additional features, such as multiple hardpoints, straps or the like, for ensuring that electrodes contact the patient's skin surface and engage this surface sufficiently to transmit the electrical impulses therethrough. The wearable garment may also include a waterproof outer shell around the recesses to insulate the electrodes and associated electronic circuits from moisture, water or other fluids that may contact the garment. In this embodiment, the electrodes40,42may be coupled to housing12through wires, or wirelessly. In either embodiment, the housing may be attached to a different location on the patient (e.g., the waist) or it may be entirely separate from the patient. Alternatively, stimulation device10may be configured for attachment to an accessory device, such as a necklace, watch, earrings, headband or the like. In this latter configuration, device10would be much smaller and may, for example, incorporate fewer elements (i.e., electrodes40,42, a wireless receiver and associated electronics). Housing12further includes a user interface52disposed on upper surface16of housing12. User interface52comprises one or more user input controls54that allow the user to control device10, and one or more indicators or icons56that provide information to the user about the status of device10. As shown inFIG.2, user interface52faces towards the patient's head when housing12is clipped to the patient's waist. This allows the patient to simply look down and view and/or manipulate user interface52without having to remove device10from his/her waist or bend into an awkward position to access user interface52. Input controls54are preferably designed such that a single user input results in only one single output. Similarly, icons56are designed such that each indicator corresponds to only one data point, or action required by the user. For example, input controls54may include a power control that turns the device On/Off and a signal control that causes the signal generator to transmit electrical impulses to the electrodes. Icons56may include a treating indicator, a battery level indicator, a wireless connection indicator, a circuit complete indicator and/or an error/malfunction indicator. Icons56may further include a single indicator that alerts the patient that the electrodes are not properly positioned against an outer skin surface such that current may pass therethrough. In addition to visual indications, device10may include an accompanying vibration and/or audible signal or buzzer in case the icons are not visible or when the patient is asleep or otherwise not able to view user interface52. In this embodiment, input controls54may further comprise controls that turn ON/OFF the vibration or the audible signals (e.g., a mute button). Referring now toFIG.4, the therapy system may include a mobile device60that is wirelessly coupled to stimulation device10, such as a Smartphone, PDA, tablet PC, palm device, IWatch, laptop computer or the like, Mobile device60includes at least a user interface, a user display, a processor and a wireless receiver/transmitter for transmitting data to and from stimulation device10and/or to and from other processors (discussed in more detail below). Alternatively, mobile device60may also include a direct connector, such as a USB plug, for directly connecting to stimulation device10. Mobile device60may further include a device identifier configured to identify an individual stimulation device10. The device identifier allows the mobile device60to ensure that data transmitted thereto is data from device10. In certain embodiments, mobile device60includes a suitable user interface and a computer-readable storage device and/or one or more software applications that allow a patient to input current user status information into mobile device60. The mobile device60may include an alert or other alarm that reminds the patient to input user status information on a regular time schedule. The user status information may include, for example, a current level of pain, a satisfaction level, a current mood, an amount of recent medication use (e.g., pain medication), a perceived activity level, the amount of sleep that the patient has recently received or any other data related to the patient's general health or recovery. This user status information is stored within device60and may be displayed in a variety of different forms for the user: list form, graphical form, activity reports and the like. The user status information allows the user (and the prescribing physician) to document the user status information, and it may provide historical trends of this information (e.g., have pain levels or medication use gone down over time) to provide a more holistic picture of his/her progress with the therapy regimen. In certain embodiments, mobile device60includes a processor that correlates the user status information with other data received from stimulation device10, such as motion data and/or usage levels of the device (discussed below). The processor may be configured to allow the display of this correlated information on the mobile device so that the user and/or physician can compare and track the user status information with the motion and usage levels. This provides valuable data to both the user and the physician to help them visualize the effectiveness of the stimulation therapy. In addition, this provides a historical record of this effectiveness so that the patient does not have to remember the user status information at, for example, follow-up visits with the physician. For example, if the patient sees that higher usage levels of the device (and/or usage levels that substantially track the prescribing physician's recommendations) correlate with lower pain levels, higher satisfaction, better moods, etc., the patient will understand that compliance with the therapy regimen (e.g., routine, timing and duration) provides better outcomes. This understanding may provide better patient compliance with the therapy regimen. Stimulation device10may transmit other information to mobile device60or directly to a separate processing device (e.g., one operated by a caregiver). This information may include, for example, error data and/or incomplete circuit data produced by stimulation device10. For example, if the stimulation device10produces an incomplete circuit data, this could mean that the patient requires assistance in placement of the electrodes. If the stimulation device10produces error data, this could mean that the patient requires assistance troubleshooting device10. Mobile device60preferably includes one or more software applications that display information that enhances the user experience with stimulation device10and enables the patient to track the progress he/she has made with the therapy regimen. In addition, it may provide information on the particular surgical procedure that the patient has undergone, and relevant stage-based content on what the patient may expect during recovery. For example, upon opening the application and creating a profile, the patient may be prompted to provide baseline information on user status, such as mood, pain-level, prescribed medications and the like. The software application may also be configured to prompt the patient to set goals or milestones for his/her recovery, such as pain-free activities. The software application may provide a dashboard or similar display that provides a summary of the data that has been collected during the therapy regimen. This summary data may include, for example, progress towards milestones or goals achieved, progress on recovery, such as pain levels, emotional state and/or activity levels and the like. This information may help the patient avoid recovery setbacks and improve compliance with the therapy. In certain embodiments, mobile device60may include software applications that monitor activity levels of the patient, compare these activity levels to prescribed levels for the individual patient's procedure and/or other data collected from the patient or device10(e.g., pain data) and then provide messages to the patient regarding such activity levels (e.g., a warning if the patient is pushing the limits of the prescribed activity levels). The application may also include a list of “approved activities” that are generated by the caregiver that will suit the patient's lifestyle without compromising his/her recovery. In certain embodiments, the mobile device60may be configured to transmit the usage status data, the motion data and/or the usage level data to a separate processor, such as one operated by the caregiver. In these embodiments, the caregiver may also track and record the same correlated information. In certain applications, mobile device60may include a patient or user software application and a separate caregiver (e.g., physician) software application. In an exemplary embodiment, the physician software application may be configured to allow the data from individual patients to be aggregated together to form data across a plurality of different patients. This aggregated data may allow the physician to determine the overall effectiveness of the therapy across multiple patients. In addition, it may allow the physician to better understand the impact of usage of the device with the effectiveness of the therapy. For example, the data may show that increased usage of the device and/or improved compliance with the therapy regimen increases overall effectiveness, speed of recovery or reduction in pain. In certain embodiments, the physician software application may be configured to automatically produce reports of complied data from mobile device60and/or stimulation device10that may include, for example, patient compliance with the therapy regimen, patient status data (e.g., pain), patient activity information from motion data and/or usage level data. The software application may be designed to aggregate these data into single reports that allow the physician to easily compare, for example, usage level data with pain, patient satisfaction, medication user, activity levels and the like. Although the device shown inFIG.4is an adapted commercially available smartphone, it is understood that in some embodiments, the housing of the stimulator may also be joined to and/or powered by a wireless device that is not a phone (e.g., Wi-Fi enabled device). Alternatively, the stimulator may be coupled to a phone or other Wi-Fi enabled device through a wireless connection for exchanging data at short distances, such as Bluetooth or the like. In this embodiment, the stimulator housing is not attached to the smartphone and, therefore, may comprise a variety of other shapes and sizes that are convenient for the patient to carry in his or her purse, wallet or pocket. Referring now toFIG.5, a therapy system200comprises a stimulation device10, one or more electrodes202, a mobile device60, such as a Smartphone or similar device as discussed above, and an external processing device206, such as computer, server or other database. Mobile device60preferably includes a user interface (not shown) for allowing the patient to input user status data and a wireless receiver/transmitter for receiving data from stimulation device10and for transmitting data to external processing device206. Electrodes202may be coupled to stimulation device10via leads (as discussed above in reference toFIGS.1-4) or they may be coupled wirelessly to stimulation device10. In the latter embodiment, electrodes202may also include a wireless receiver for receiving the stimulation signal and suitable electronics for converting the received signal to electrical impulses, as discussed above. The system200may include one or more sensors (not shown) coupled to housing12, mobile device60or an external processor. The sensors may be configured to detect a physiological parameter of the patient, such as body temperature, blood flow, blood oxygen, heart rate, heart rate variability, heart rhythm, blood pressure, gaze and gait. The system may further include a computer-readable storage device that stores program instructions to compare the physiological parameters with usage levels of the device or with patient status data. Suitable sensors for use in the present systems, methods and devices may include PCT and microarray based sensors, optical sensors (e.g., bioluminescence and fluorescence), piezoelectric, potentiometric, amperometric, conductometric, nanosensors or the like. Referring now toFIG.6, a block diagram of certain internal components of stimulation device10will now be described. As shown, stimulator device10comprises housing12and a power module230, such as the rechargeable battery described above. Housing10further includes a signal generator232, an impedance sensor234, a timing module236and a motion sensor238coupled to a processor240. Housing10may also include a wireless transmitter/receiver242and a user interface244, as discussed above. In certain embodiments, device10can comprise a one-way buffer or Firewall between the treatment and communication components of housing60to prevent interference/interaction between these two functions of device10. Signal generator232can generate a therapeutic signal (i.e., electrical impulses) that can be transmitted to electrodes40,42. Signal generator232may be implemented using power module236and a control unit or processor240having, for instance, a clock, a memory, etc., to produce a pulse train to the electrodes40,42that deliver a stimulating, blocking and/or modulating impulse to the patient's body. The parameters of the electrical impulses, such as the frequency, amplitude, duty cycle, pulse width, pulse shape, etc., may be programmable by the caregiver. An external communication device may modify the pulse generator programming to improve treatment. The electrical impulses preferably have a frequency, an amplitude, a duty cycle, a pulse width, a pulse shape, etc. selected to influence the therapeutic result. In an exemplary embodiment, the therapeutic signal comprises a waveform suitable for transcutaneous delivery through an outer skin surface of a patient to a target location (e.g., joint, muscle, nerve, bone, ligament, vasculature, and/or other hard or soft tissue, etc.) within the patient's spine. In this embodiment, the electrical impulses are preferably sufficient to enhance bone healing within the spine, and are particularly suitable for patients recovering from spinal fusion. In an exemplary embodiment, the signal comprises an output waveform of sinusoidal pulses having a frequency of about 50 KHz to about 70 KHz, preferably about 60 KHz. The amplitude of the waveform is preferably in the range of about 5 to about 10 mA (r.m.s.) at impedances between about 100 and 450 Ohms. The amplitude may be greater than about 3 mA (r.m.s.) at impedances between about 450 Ohms and about 750 Ohms. Impedance sensor232is also coupled to electrodes40,42and functions to measure the impedance from current flow between the electrodes40,42and to transmit this impedance to processor240. Impedance sensor232may be located within housing12as shown inFIG.6, or it may be located within connection terminal48(FIG.1), or any other location between electrodes40,42and signal generator232. Processor240includes software program instructions to adjust the amplitude of the current transmitted to electrodes40,42based on this impedance. As discussed further below, this ensures that the amplitude of the electrical impulses transmitted to the target location within the patient will remain substantially within the therapeutic range. Impedance sensor232may also be coupled to timing module236for measuring usage levels of device10, as discussed below. Motion sensor238may comprise one or more accelerometers that detect three-axis motion. In certain embodiments, motion sensor238can sample outputs of the accelerometers between about five (5) to about one hundred (100) times per second, preferably about twenty-five (25) times per second. Processor240may then convert these individual samples into vectors, and the magnitude of the individual vectors are calculated over a time frame (e.g., one second). Processor240may then determine the maximum value of the vectors' magnitudes within their respective time frames and may transfer this data to a remote source, such as mobile device60, via wireless transmitter/receiver242. Processor240may also be configured to group the motion data into a plurality of bins to create a histogram of the motion data. The details of this functionality are discussed in more detail below. One of the challenges with providing motion data for a therapeutic device that operates over a long period of time is that the motion sensor generates a significant amount of data that would require substantial storage space on the device. Since the device is designed to be wearable, this storage requirement could make the device bulky and more cumbersome for the patient. In addition, the wireless transfer of this large amount of data to a mobile device or other remote processor would take an extensive amount of time. The motion data would either be transferred automatically by the device or manually by the patient through one or more user input controls. In the former case, the automatic transfer of this data would require the device to constantly search for something to wirelessly connect, or pair, with, thereby prematurely draining the battery. In the latter case, the patient would be required to monitor the device during this data transfer, thereby curtailing ease of use and potentially reducing compliance with the therapy regimen. The present systems and devices provide a solution to these challenges by extracting enough data to provide useful information from the vast amount of data generated by motion sensor238. This is achieved by parsing the data from the motion sensor238into a histogram and then converting this parsed data or histogram into meaningful patient information on a suitable display device. In one embodiment, processor240determines a specific parameter set detected by motion sensor238. This specific parameter set may be, for example, a peak vector magnitude or an average vector magnitude over a specific period of time, e.g., about 0.1 to 10 seconds, preferably about 0.5 to 2 seconds. Processor240then stores only the specific parameter set (rather than every data point detected by motion sensor238) which reduces the overall storage requirements of device10, and reduces the quantity of data that is transferred from device10to, for example, a mobile device or other remote processor. In certain embodiments, mobile device60may include software applications that include goals or milestones for patient activity levels throughout the therapy. The software applications are configured to compare the motion data collected from stimulation device10with these goals and to display this comparison on mobile device60and/or the caregiver's display. This facilitates compliance with “physician instructed activity” during the patient's recovery. Timing module236may comprise a real-time clock coupled to processor240and functions to measure usage levels of device10, e.g., treatment time, errors (type and when). In some embodiments, timing module236tracks the amount of time that signal generator232applies electrical impulses to electrodes40,42and transfers this data to processor240. In other embodiments, timing module236can also determine usage information based on impedance measured between electrodes40,42. In either of these embodiments, processor240is configured to transfer this data to a remote source, such as mobile device60, via wireless transmitter/receiver242. Wireless transmitter/receiver242may comprise any suitable device which converts alternating currents to radio waves (or vice versa) for transmitting data to and from stimulation device10and mobile device60. Transmitter/receiver242may comprise a radio frequency current generator, one or more antennas and associated firmware. In certain embodiments, device10is designed to only transmit information or data from the device10to mobile device60or another remote source. In these embodiments, element242is only a transmitter and device60cannot be controlled or otherwise manipulated from an external source. In certain embodiments, the signal waveform that is to be applied to electrodes40,42of the stimulator device10is initially generated exterior to device10. In these embodiments, stimulator device10preferably includes a software application that can be downloaded into the device to receive, from the external control component, a wirelessly transmitted waveform, or to receive a waveform that is transmitted by cable. If the waveforms are transmitted in compressed form, they are preferably compressed in a lossless manner, e.g., making use of FLAC (Free Lossless Audio Codec). Alternatively, the downloaded software application may itself be coded to generate a particular waveform that is to be applied to the electrodes40,42. In yet another embodiment, the software application is not downloaded from outside the device, but is instead available internally, for example, within read-only-memory that is present within device10. A power amplifier within the housing of the stimulator may then drive the signal onto the electrodes, in a fashion that is analogous to the use of an audio power amplifier to drive loudspeakers. Alternatively, the signal processing and amplification may be implemented in a separate device that can be plugged into sockets on the phone and/or housing of the stimulator to couple the software application and the electrodes. In addition to passing the stimulation waveform from an external controller to the stimulator housing as described above, the external controller may also pass control signals to the stimulator housing. Thus, the stimulation waveform may generally be regarded as a type of analog, pseudo-audio signal, but if the signal contains a signature series of pulses signifying that a digital control signal is about to be sent, logic circuitry in the stimulator housing may then be set to decode the series of digital pulses that follows the signature series of pulses, analogous to the operation of a modem. Many of the steps that direct the waveform to the electrodes, including steps that may be controlled by the user via the touchscreen of mobile device60are implemented in the above-mentioned software application. By way of example, the software application may be written for a phone that uses the Android operating system. Such applications are typically developed in the Java programming language using the Android Software Development Kit (SDK), in an integrated development environment (IDE), such as Eclipse. In another embodiment, a base station is provided that that may send/receive data to/from the stimulator, and may send/receive data to/from databases and other components of the system, including those that are accessible via the internet. Typically, the base station will be a laptop computer attached to additional components needed for it to accomplish its function. Thus, prior to any particular stimulation session, the base station may load into the stimulator device10parameters of the session, including waveform parameters, or the actual waveform. In one embodiment, the base station is also used to limit the amount of stimulation energy that may be consumed by the patient during the session, by charging the stimulator's rechargable battery with only a specified amount of releasable electrical energy, which is different than setting a parameter to restrict the duration of a stimulation session. This may help to ensure that the temperature of the device remains within acceptable limits for continuous use and wearing of the device. Thus, the base station may comprise a power supply that may be connected to the stimulator's rechargeable battery, and the base station meters the recharge. As a practical matter, the stimulator may therefore use two batteries, one for applying stimulation energy to the electrodes (the charge of which may be limited by the base station) and the other for performing other functions. Alternatively, control components within the stimulator housing may monitor the amount of electrode stimulation energy that has been consumed during a stimulation session and stop the stimulation session when a limit has been reached, irrespective of the time when the limit has been reached. FIG.7shows a block diagram illustrating an example of an environment500for implementing the present systems, methods, and computer program products. The environment500can include a user501, a stimulation device503, a signal transmitter505, a biometric sensor device506, a battery charger507, a user device509, a provider device511, and a reference database512. The stimulation device503, the signal transmitter505, and the user device509can be the same or similar to those previously described above (e.g., stimulation device10, electrodes40,42, and mobile device60, respectively). The user501can be any individual. In the non-limiting examples described herein, the user501can be a post-surgical patient or an individual with chronic pain. For example, the user501can be a patient receiving therapeutic treatment using the stimulation device503and the signal transmitter505while recovering from spinal fusion surgery. In some embodiments, the user501of the stimulation device503can periodically provide user status information523to the user device509throughout the course of the therapeutic treatment. The user status information523can include, for example, information indicating the user's level of pain, satisfaction level, mood, medication use, activity level, and amount of sleep, and the like. In some embodiments, the user501provides the user status information523directly to the user device509via a user interface provided by the user device509. The stimulation device503can generate a stimulation signal515and apply it to the user501via the signal transmitter505, as previously described herein. For example, the stimulation device503can be a level 1 clinical device and the stimulation signal515can be a therapeutic electric signal. In some embodiments, the stimulation signal515comprises a waveform for transcutaneous delivery through an outer skin surface of a patient to a target location within the user's spine. The stimulation signal515can have a frequency, an amplitude, a duty cycle, a pulse width, a pulse shape, etc. selected to provide a therapeutic benefit. For example, the stimulation signal515can be a waveform of substantially sinusoidal pulses having a frequency of about 50 kHz to about 70 kHz, about 60 kHz. The amplitude of the waveform can be in the range of about 5 to about 10 mA (r.m.s.) at impedances between about 100 and about 450 Ohms. The amplitude may be greater than about 3 mA (r.m.s.) at impedances between about 450 Ohms and about 750 Ohms. In some embodiments, the stimulation device503provides a user-interface (e.g., user interface52) that controls operation of the stimulation device503, including controlling and modifying the stimulation signal515. In some embodiments, the user interface allows the user501to select one or more parameters or combinations of parameters for the stimulation signal515. For example, the user501can select one of a number of preprogramed profiles for the stimulation signal515having different amplitudes and pulse widths. The stimulation device503can generate a data digest519. In some embodiments, the data digest519can be a data structure that logs activity of the user501and the user's use of the stimulation device503in a time-ordered sequence. For example, the data digest519can be a time-indexed data structure that stores data samples from various sources in time-wise association with one another. In some embodiments the data digest519includes information indicating usage periods of the stimulation device503, motion levels of user501, and errors detected by the stimulation device503. For example, the stimulation device503can generate the data digest519based on an impedance signal517received from the signal transmitter505and motion data generated by motion sensors in the stimulation device503. The biometric sensor device506can be a wearable device including one or more sensors that generate biometric data525indicating physiological parameters of the user501and provide the biometric data525to the user device509. The biometric sensor device506can be, for example, a smartwatch, waistband, instrumented shoes, instrumented headgear, or the like. The biometric sensor device506can include one or more of “PCT” sensors, microarray sensors, optical sensors (e.g., bioluminescence and fluorescence), microelectromechanical sensors, piezoelectric sensors, potentiometric sensors, amperometric sensors, conductometric sensors, nanosensors, or other suitable sensors. The physiological parameters detected by the sensors can include or more of body temperature, blood flow, heart rate, heart rate variation, heart rhythm, blood pressure, blood oxygen, gaze, and gait. The signal transmitter505can be one or more devices that receives the therapeutic stimulation signal515from the stimulation device503and applies the stimulation signal515to the user501. As previously described, the signal transmitter505can include a receiver for receiving the stimulation signal515and for converting it to electrical impulses. In some embodiments, the signal transmitter505comprises two or more electrodes (e.g., electrodes40,42) that adhere to skin of the user501and provide the stimulation signal515to a surgical site through direct contact with skin of the user501. In some other embodiments, the signal transmitter505is incorporated into a wearable unit (e.g., wearable garment57) that retains the electrodes in contact with the skin of the user501. The battery charger507can be a device configured to connect with one or more batteries533A,533B of the stimulation device503and provide power to the batteries533A,533B. For example, a housing of the battery charger507can have an interior volume corresponding to the shape of the outer housing of the batteries533A,533B. The battery charger507can include a power supply and control electronics that manage recharging of the batteries533A,533B. Additionally, in some embodiments, the battery charger507includes communication electronics that receive the data digest519stored in the batteries533A,533B by the stimulation device503, and can share the data digest519with other devices, such as the user device509and the provider device511while one of the batteries533A,533B is not in use. For example, in response to detecting insertion of the battery533B, the battery charger507can provide the data digest519to the provider device511via a wireless connection to the Internet. In some embodiments, the battery charger507can store the data digest519, and periodically provide it to the user device509and the provider device511(e.g., once per day). In some other embodiments, the battery charger507provides the data digest519once per charging session, such as in response to the battery533B being connected to the battery charger507. As a practical matter, the stimulation device503can use two batteries533A and533B, wherein the battery533A powers the signal transmitter505and store the data digest519. Meanwhile, the battery charger507recharges the second battery533B while communicating information previously recorded in the data digest519. The user device509can be a computing device that communicates with the user501, the stimulation device503, the biometric device506, the battery charger507, and the reference database512via one or more wired or wireless data communication channels. In some embodiments, the user device509is a portable computing device, which can be the same or similar to that previously described herein (e.g., user device60). In some other embodiments, the user device509is a desktop computer or a laptop computer. In some other embodiments, the user device509is a communication node that relays information from the user501, the stimulation device503, the biometric sensor device506, and the reference database512through a network (e.g., the Internet) to a remote computing system, such as the provider device511. The user device509can receive information, including the data digest519from the stimulation device503, user status information523from the user501, biometric data525from the biometric sensor device506, and reference data527from the reference database512. In some other embodiments, the user device509receives the data digest519from the batteries533A,533B during recharging in the battery charger507. The user device509can log information in association with timestamps indicating a time the information was generated or received. For example, the information received from the user501, the stimulation device503, the biometric sensor device506, and the reference database512can be stored in time-wise association with one another based on their respective timestamps. Additionally, the user device509can store and process the data digest519, the user status information523, and the biometric data525to determine correlations and trends. Further, the user device509can use this information to generate reports529providing feedback to the user501and the provider device511. In some embodiments, the reports529indicate the user's activity, daily treatment schedule compliance, and historical performance. For example, the reports529can aggregate time-indexed data indicating the user's usage, activity, and user status (e.g., pain, discomfort, and mood) over a period of time (e.g., daily, monthly, quarterly, and annually). Further, in some embodiments, the user device509provides user interfaces for configuring and controlling the stimulation device503, for receiving information from the user501(e.g., user status information523and biometric data525), and providing information to the user (e.g., reports529). Configuring and controlling the stimulation device503can include receiving selections of stimulation parameters521, such as waveform parameters, or an actual waveform. In some embodiments, the stimulation parameters521can limit energy consumed during a therapeutic session to a predetermined maximum amount of total power, which is different than setting a parameter to restrict the duration of a stimulation session to prevent a temperature of the stimulation device503from exceeding a predetermined limit for continuous use and wearing of the device. The user interface can also interact with the user501periodically elicit and receive the user status information523form the user501. The user interface can also interact with the user501to configure and display various reports529, such as usage reports, activity reports, user status reports, and the like. In some embodiments, the user interface combines information included in the reports529with other information, such as user-specific goal and target information stored on the user device509or at the reference database512. The provider device511can be one or more computing devices that receive the reports529from one or more user devices509of one or more users501. In some embodiments, the provider device511can be a server or a personal computer. Additionally, in some embodiments, the provider device511can also receive anonymized user data aggregated from a number of different user devices other than the user device509used by users other than the user501. In some embodiments, the provider device511is a computing device of a healthcare provider that is authorized to view the user's data. The reference database512can be one or more storage systems storing reference data527and communicatively linked to the user device509and the provider device511. In some embodiments, the reference database512is a network storage system remote from the user device509and the provider device511. In some other embodiments, the reference database512is stored locally by the user device509or provider device511. The reference data527can include, for example, user data, provider data, and device data. The user data can include, for example, registration data, profile data, prescription information, medical history data, and scheduling information. The user data can also include therapeutic plans, goals, targets, timelines, and milestones. The provider data can include, for example, provider profile data, scheduling information, and medication prescription information. The device data can include, for example, device profile and setting information for the stimulation device503. FIG.8shows a system block diagram illustrating an example of a stimulation device503. The stimulation device503includes hardware and software that perform processes and functions described herein. In some embodiments, the stimulation device503includes a computing device605, a signal generator606, an impedance sensor607, a motion sensor608, I/O devices609, and a storage system610. In some embodiments, the computing device605can include one or more processors612(e.g., microprocessor, microchip, or application-specific integrated circuit), one or more memory devices613(e.g., random-access memory and/or read-only memory), and I/O interface615, and a communication interface617. In some embodiments, the processor612includes a real-time clock that produces one or more clock signals that can be used to timestamp data. The memory devices613can include a local memory (e.g., a random-access memory and a cache memory) employed during execution of program instructions. Additionally, the computing device605can include at least one communication channel619(e.g., a data bus) by which it communicates with the storage system610, the memory device613, the I/O interface615, and the communication interface617. It is understood that the computing device605can comprise any general-purpose computing article of manufacture capable of executing computer program instructions installed thereon. However, the computing device605is only representative of various possible computing devices that can perform the processes described herein. To this extent, in embodiments, the functionality provided by the computing device605can be any combination of general and/or specific purpose hardware and/or computer program instructions. In each embodiment, the program instructions and hardware can be created using standard programming and engineering techniques. The signal generator606can be a device that generates the stimulation signal515. The signal generator606can, for example, produce one or more selectable signal pulse trains. In some embodiments, a user (e.g., user501) can select one or more parameters (e.g., stimulation parameters521) of the stimulation signal515, such as frequency, amplitude, duty cycle, pulse width, pulse shape, via the I/O devices609. Additionally or alternatively, in some embodiments, an external device (e.g., provider device511or reference database512) can provide the stimulation parameters521or other control information to the stimulation device503. The impedance sensor607can be one or more devices that measure impedance from current flow of a signal transmitter (e.g., signal transmitter505), such as between electrodes (e.g., electrodes40,42) and generates an impedance signal517indicating the magnitude of the impedance. In some embodiments, the impedance signal517is a logical signal (e.g., having either a low or a high state) indicating whether or not the signal transmitter is conducting current through the user's skin. The motion sensor608can be one or more devices that generate motion data by detecting movement of the stimulation device503. In some embodiments, the motion sensor608can include one or more accelerometers. For example, the motion sensor608can be a three-axis accelerometer. The motion data can be a representing magnitude of the accelerations along one or more of the axes, or a combination thereof. For example, values included in the signal or data stream output by the motion sensor608can indicate a total magnitude of the accelerations along the three axes. The magnitude of the signal or a data stream can correspond to different levels of user activity, for example, sleeping, sitting, walking, jogging, sprinting, or any other activity. The I/O devices609can include one or more devices that enable the user to interact with the stimulation device503(e.g., a user interface) and/or any device that enables the stimulation device503to communicate with one or more other computing devices using any type of communication link. The I/O devices609can include, for example, a touchscreen display, a keypad, one or more selectors, one or more indicators. The I/O device609can provide a user interface, as previously described herein and additionally described below. The storage device610can store data received and generated by the stimulation device503, including a data digest519and stimulation parameters521. The data digest519can store a time-indexed log of data obtained from the motion sensors608and impedance data obtained from the impedance signal517. The I/O interface615can control data flow between the processor612and the signal generator606, the impedance sensor607, the motion sensor608, and the I/O devices609. For example, the I/O interface615can communicate selected stimulation parameters521from the processor612to the signal generator606. The I/O interface615can also communicate impendence information from the impedance sensor607to the processor612. Further, the I/O interface615can communicate motion information from the motion sensor608to the processor612. Moreover, the I/O interface615can communicate user inputs and indications transmitted between the I/O devices609and the processor612. The communication interface617can include any device interconnecting the computing device605with an information network (e.g., a local area network, a wide area network, and the Internet) enabling the stimulation device503to communicate with other computing systems and information storage systems (e.g., user device509). In some embodiments, the communication interface617uses communication protocols that establish secure communication links satisfying HIPPA requirements. The processor612executes computer program instructions (e.g., an operating system and/or application programs), which can be stored in the memory device613and/or the storage device610. In some embodiments, the processor612can also execute computer program instructions for a sensor module635and a stimulation module637. The sensor module635can be software, hardware, or a combination thereof that processes the information provided by the impedance sensor607and the motion sensor608(e.g., via the I/O interface615). In some embodiments, the sensor module635samples the impedance information and the motion information at a predetermined rate. Additionally, the sensor module635can timestamp the samples of the impedance information and the motion information using a real-time clock. Further, the sensor module635can condition the samples of the impedance information and the motion information to, for example, amplify, normalize, de-jitter, and de-noise the information. For example, the sensor module635can sample the impedance information and the motion information respectively output by the impedance sensor607and the motion sensor608at a rate of about 30 Hertz, determine values of the output within one of 15 predefined ranges, and record the values along with timestamps in the data digest519. The stimulation module637can be software, hardware, or a combination thereof that that controls the signal generator606to generate the stimulation signal515based on stimulation parameters521. As noted above the stimulation parameters521of the stimulation signal515can include frequency, an amplitude, a duty cycle, a pulse width, and a pulse shape. In some embodiments, the stimulation parameters521can be predetermined values stored in the storage device610. In some other embodiments, the stimulation parameters521can be dynamically updated and provided from an external device (e.g., user device509, provider device511, or reference data527). In some embodiments, the stimulation module637adjusts the amplitude of the stimulation parameters521based on the impedance data output by the sensor module635based on the impedance signal517. By doing so, the amplitude of the stimulation parameters521transmitted to the user can remain substantially within a desired therapeutic range. It is understood that, in some embodiments, the signal waveform can be generated externally from the stimulation device503. In such embodiments, the stimulation device10can include a software application that can be downloaded into the device to receive, from the external control component, a wirelessly transmitted waveform, or to receive a waveform that is transmitted by cable. If the waveforms are transmitted in compressed form, they can be compressed in a lossless manner, e.g., making use of FLAC (Free Lossless Audio Codec). Alternatively, the downloaded software application may itself be coded to generate a particular waveform that is to be output by the signal generator606. FIG.9shows a system block diagram illustrating an example of a user device509, which can be the same or similar to that described above. The user device509includes hardware and software that perform processes and functions described herein. In some embodiments, the user device509includes one or more input/output (I/O) devices707, storage system709, one or more processors711, one or more memory devices713, an I/O interface715, a communication interface717, and a data bus719, all of which can be the same or similar to those previously described above. The processor711executes computer program instructions (e.g., an operating system and/or application programs), which can be stored in the memory device713and/or the storage system709. The processor711can also execute computer program instructions for a data conversion module733, a user status module735, and a reporting module737. The data conversion module733can be software, hardware, or a combination thereof that processes motion and usage information in the data digest519to determine the activity data545and store it in the storage device709. Determining the activity data can include sampling the motion and usage information in consecutive time frames (e.g., one second), determining a peak value of the information in the individual time frames, and classifying the samples as one of a predetermined number (e.g., 15) of activity levels based on their respective peak values. Determining the activity data can also include grouping the samples from a predetermined time period (e.g., an hour) together based on their respective activity levels. The user status module735can be software, hardware, or a combination thereof that elicits and receive the user status information523from a user and records it in the storage device709. In some embodiments, the user status module735elicits the user status information523by periodically and automatically displaying prompts to the user via the I/O device707. For example, the I/O device707can be a touchscreen graphic user interface of a smartphone. The user status module735can periodically (e.g., hourly) display interactive pop-up messages prompting the user to enter the user status information523, such as illustrated inFIG.15B. Further, the user status module735can display an interactive data entry form using the I/O device707prompting the user to enter information regarding, for example, their level of pain, their satisfaction level, their mood, their recent medication use, their activity level, their amount and quality of sleep, and other such related their current condition, The user status module735can periodically (e.g., hourly) display interactive pop-up messages prompting the user to enter the user status information523, such as illustrated inFIG.15C. In some embodiments, the prompts may include questions and information tailored to the user based on, for example, user-specific and provider-specific information, such as prescription regimens, treatment plans, goals, milestones, and the like, which can be stored in the reference data527. The reporting module737can be software, hardware, or a combination thereof that generates reports529, stores the reports529in the data storage device709, provides interactive user interfaces for selecting and displaying the reports529using the I/O interface707, and communicate the reports529using the communications interface717. The reporting module737can use predefined schema to collect, organize, and format the user status data523, the activity data545, the reference data527in portion, in full, and in combination to generate the reports529. For example,FIGS.15A to15Dillustrate examples of graphic user interfaces1310,1320,1330, and1331provided on the I/O device707of the user device509providing selections for accessing and displaying reports of stimulation device usage1332, user activity1334, user status1336, and combined information1338.FIG.15Eillustrates an example graphic user interface1340displaying and example stimulation device usage report.FIG.15Fillustrates an example graphic user interface1360displaying and example user activity report based on data included in data digest519and the activity data545.FIG.15Gillustrates an example graphic user interface1370displaying an example histogram of user activity based on data included in data digest519and the activity data545. It is understood that the data can be displayed in other manners (e.g., line charts, pie charts, etc.). Further, it can combine and overlay the user status data523, the activity data545, the reference data527in various fashions. FIG.10shows a system block diagram illustrating an example of a battery533and a battery charger507, which can be the same or similar to those previously described above. The battery533can include a non-volatile data storage device805, an input/output device809, which can be the same or similar to those previously described herein. Additionally, the battery533can include a housing811and an input/output connector815. The battery charger507can include a processor825, non-volatile data storage device827, an input/output device829, and communications interface833, which can be the same or similar to those previously described herein. Additionally, the battery charger510can include a power supply841, a housing845and an input/output connector849. In some embodiments, the battery533connects to the battery charger507via input/output connectors815and849. The battery533can receive power from the power supply841via the input/output connectors815and849and recharges the battery533. Additionally, the battery533can provide data, such as data digest519, stored in the data storage device805to the data storage device527of the battery charger510via input/output connectors815and849and I/O devices809and829under control of the processor825. In some embodiments, the battery charger507can receive and mate with the battery533. For example, the housing811of the battery533can be inserted in the battery charger507such that the connector815of the battery533mates with the connector849of the battery charger507. It is understood that other methods and structures for connecting the battery charger507and the battery533can be used. As illustrated above inFIG.7, the battery533can also connect to a stimulation device (e.g., stimulation device503) to receive and store the data digest519. It is understood that the battery533can connect to the stimulation device in a similar manner as is described above regarding the battery charger507. More specifically, the battery533can receive power from the power supply841via the input/output connectors849to a corresponding connector of the user device and power the user device. The battery533can store the data digest519in the data storage device505via input/output connectors815and the I/O device809under control of a processor (e.g., processor612) of the stimulation device. FIG.11shows a functional flow block diagram illustrating an example of a process900performed by a system. The process900includes user501, stimulation device503, signal transmitter505, biometric sensor device506, user device509, and provider device511, all of which can be the same or similar to those previously described herein. The stimulation device503can be communicatively connected to the user501via the signal transmitter505. The stimulation module637can control the signal generator606to generate the stimulation signal515based on the stimulation parameters521. The signal parameters521can be stored in the user device509(e.g., in storage device610). In some embodiments, the stimulation parameters521can be provided to the stimulation device503by the user device509. The signal transmitter505can apply the stimulation signal515transcutaneously through the skin of the user501to the target treatment site (e.g., joint, muscle, nerve, bone, ligament, vasculature, and/or other hard or soft tissue, etc.) Additionally, the signal transmitter505can provide an impedance signal517representing a measurement of impedance to a flow of electrical current across the skin of the user501to the sensor module635. The sensor module635can generate impedance information by conditioning the impedance signal517, periodically sampling it, and storing timestamped values of the samples in the data digest519. In some embodiments, the stimulation module637controls the signal generator606to modify the stimulation signal515based on the impendence data stored in the data digest519to account for changes in impedance in the user's skin over time. Further, the biometric sensor device506and the motion sensor608can detect physical parameters of the user501and provide motion data and biometric data525to the user device509. In some embodiments, the sensor module635can condition the motion data and the biometric data525received from the biometric sensor device506and the motion sensor608, periodically sample them, and store timestamped values of the samples in the data digest519. It is understood that, in some embodiments, the motion data and the biometric data525can be provided as time stamped samples and the user device509can store the information directly in the data digest519without being sampled or modified by the sensor module635. The user device509can receive and store the data digest519generated by the stimulation device503. In some embodiments, stimulation device503transmits the data digest519to the user device509. For example, the communication interface617of the stimulation device503periodically transmits the data digest519to the communication interface717of the user device509(e.g., about every 12 hours). In some other embodiments, the stimulation device503asynchronously transmits the data digest519to the user device509. In some other embodiments, as detailed above, a removable battery (e.g., battery533) of the stimulation device503stores the data digest519and provides it to the user device509while recharging in a battery charger (e.g., battery charger507). Additionally, the user device509can receive the user status information523from the user via one or more of the input/output devices609. In some embodiments, the input/output devices609can include a touchscreen user interface, and the user status module735can periodically prompt the user501to input information describing the user's current conditions, such as mood, pain level, and medications taken. For example, based on a predetermined medication schedule (e.g., included in reference data527), the user status module735can initiate alerts and prompts for the user501to take medication and receive confirmation from the user501that the medication was taken. The user status module735can timestamp the user status information523and store it in activity data545. Using the information in the data digest519, as well as user status information523from the user501and biometric data535from the biometric sensor device506, the user device509can determine the activity data545. The reporting module737can use the activity data545to generate the reports529, which can indicate user activity levels over periods of time. The activity level reported529can include, for example, one or more histograms illustrating activity levels during individual hours of individual days throughout the user's treatment. The user device509can display the reports529to the user501using an input/output device (e.g., I/O device707) and provide the reports to the provider device511. Further, the reporting module737can process the activity data545to determine correlations, identify trends, and generate reports529. The reporting module737can output the reports to the input/output device609for display to the user501via user interface. In some embodiments, using the impedance data in the data digest519, the reporting module737can determine the time and the duration of use of the signal transmitter505by the user101. Further, in some embodiments, using the data from the motion sensor608and biometric sensor device506, the reporting module737can determine timing, duration, and intensity of the user's501activity. Additionally, in some embodiment, the user device509can suggest diagnoses of other maladies based on the data from the motion sensor608and the biometric sensor device506. FIG.12shows a functional flow block diagram illustrating an example of a process1000for generating activity data545. The process1000can use information contained in data digest519, data conversion module733, memory device713, and storage device709, all of which can be the same or similar to those previously described herein. The data conversion module733can include an activity level classifier1005and an activity class parser1009. While the activity level classifier1005and the activity class parser1009are described as separate processing modules, it is understood that some or all of their functionality can be performed by a single module, such as the data conversion module733, or their functionality can be divided among more modules. As illustrated inFIG.12, the activity level classifier1005can receive the data digest519. As described previously, the data digest519can include time-indexed information recorded by a stimulation device (e.g., stimulation device503). In some embodiments, the data digest519can include motion information generated by motion sensors (e.g., motion sensor608of the stimulation device503) and impedance information indicating user application of a stimulation signal (e.g., stimulation signal515) to a user (e.g., user701). The information in the data digest519can be correlated with one another based on their respective timestamps. In some embodiments, the activity level classifier1005determines levels of activity by sampling the data digest519during individual time frames, determining values of the samples for the individual time frames, and determining a corresponding activity level group (e.g., a corresponding bin) for the individual samples from a plurality of predetermined activity level groups including different respective ranges of motion values. For example, the data digest519can include information recorded once every second (e.g., 1 Hertz), as indicated by timestamps. For data in the digest519sampled over a first minute (e.g., 60 records) of the information in the data digest519, the activity level classifier1005can determine the peak values of the data in the first minute and classify the first minute into one of a predetermined number of activity levels, and store the determined activity level in the memory device713at, for example, record 0000. For example, the activity level classifier1005can use 15 levels, including level 0, level 1, level 2 . . . level 14. Samples in level 0 can have values from zero to 1/15th of the maximum possible value. Samples in level 1 can have values from 1/15th to 2/15th of the maximum, and so on up to level 14, which can include samples having values between 13/14th to the maximum. Hence, if the sample for the first minute of the data digest519indicates zero activity, the activity level classifier1005can classify the first minute in the lowest activity level (e.g., level 0) and store the activity level in the memory device713in a respective r, such as record 0000. Whereas, if the sample for the first minute of the data digest519indicate extremely high activity, the activity level classifier1005can classify the first minute in the highest activity level (e.g., level 14) and store that activity level in the respective record. The activity level classifier1005can sample succussive minutes of data in the data digest519, determine the peak value of the data, and classify the individual samples into respective activity levels. Hence, at the end of a day, for example, all of a user's activity for individual minutes can be classified into one of the activity levels 0-14. In a non-limiting example, the user may have performed activities over 50 seconds that are detected by a motion sensor and recorded in the data digest519. The activity level classifier1005can sample the data including that activity in the data digest519, determine a value of the data by converting the data to a vector, and determine a peak magnitude of the vector of the sample. The activity level classifier1005can determine that the peak magnitude of the vector was between 1/15th and 2/15th of the maximum vector possible, which can correspond to activity level 1 and store the determined level as a record (e.g., record 0000) in the memory device713. Additionally, the activity class parser1009can parse samples into activity level groups for predetermined time periods (e.g., one hour time periods) based on their respective activity levels. For instance, the activity levels included in individual hours of the day (e.g., hours 0, 1, 2 . . . 23), the activity class parser1009can determine how many samples in the memory device713are classified in the individual the activity levels. For example, a first hour of a day (e.g., hour 0), which can include records 0000 to 003B in memory device713, the activity class parser1009can determine a first quantity of the samples included in activity level group 0, a second quantity of samples included in activity level group 1, a third quantity of samples included in activity level group 2, and so on up to a fifteenth quantity of samples included in activity level group 14. For example,FIG.13shows a data structure1100containing activity data determined by the activity class parser1009using information contain in the memory device713. The data structure1100can includes records associating individual hours 1105 (hours 0-23) of an individual day (e.g., day 52 of 270) with 15 activity levels 1110 (levels 0-14). For a fourth hour of the day (e.g., hour 3), the activity class parser1009can determine that the records 00F0 to 012B are stored in the memory device713include 295 samples in activity level group 0, a 95 samples included in activity level group 1, 118 samples included in activity level group 2, 35 samples included in activity level group 3, 44 samples included in activity level group 4, 53 samples included in activity level group 5, 65 samples included in activity level group 6, 8 samples included in activity level group 7, 3 samples included in activity level group 8, 1 sample included in activity level group 9, 0 samples included in activity level group 10, 0 samples included in activity level group 11, 0 samples included in activity level group 12, 0 samples included in activity level group 13, and 0 samples included in activity level group 14. Based on the samples determined to be in the individual activity level groups, the system can determine a quantity of time included in the activity levels within the time period. The flow diagram inFIG.14illustrates an example of the functionality and operation of possible embodiments of systems, methods, and computer program products according to various embodiments described herein. The flow diagram can represent a module, segment, or portion of program instructions, which includes one or more computer executable instructions for implementing the illustrated functions and operations. In some alternative embodiments, the functions and/or operations illustrated in a particular block of the flow diagram can occur out of the order shown inFIG.14. For example, two blocks shown in succession can be executed substantially concurrently, or the blocks can sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the flow diagram and combinations of blocks in the block can be implemented by special purpose hardware-based systems that perform the specified functions or acts, or combinations of special purpose hardware and computer instructions. At block1203, the system (e.g., stimulation device503executing stimulation module637) can output a therapeutic stimulation signal (e.g., stimulation signal515) for a user (e.g., user501). As detailed above, the system can generate the stimulation signal based on predetermined or dynamically determined parameters (e.g., stimulation parameters521) using a signal generator (e.g., signal generator606) via a signal transmitter (e.g., electrodes40,42in signal transmitter505). At block1205, the system (e.g., stimulation device503executing sensor module635) can log impedance information from the signal transmitter. In some embodiments, the system can periodically determine magnitudes of samples of an impedance signal (e.g., impedance signal517) output from the signal transmitter, timestamp the values of the samples, and store the timestamped impedance values in a data digest (e.g., data digest519). At block1209, the system can log motion information from motion sensors (e.g., motion sensor608) of the stimulation device. In some embodiments, the system can periodically determine values of samples of motion signals (e.g., magnitudes of acceleration vectors) output from the motion sensors, timestamp the values of the samples and store the timestamped motion values in the data digest in association with the impedance values logged at block1205based on their respective timestamps. At block1213, the system (e.g., user device509executing data conversion module733) can determine the user's activity levels (e.g., activity data545) based on the samples in the data digest. As previously described, determining the activity levels can include determining the values of the samples over individual time frames (e.g., one minute increments), determining the maximum value of the samples included in their respective time frames, and classifying the individual samples into one of a number of predetermined activity levels (e.g., one of levels 0-14) based on their respective maximum values. Determining the values of the samples can include converting values of the samples into vectors and determining the maximum magnitudes of the individual vectors. Based on the activity levels of the time frames, the system can create activity data by parsing the records into a plurality of groups based on their respective activity levels determined at block1213and determine the quantity activity levels records included in the individual groups, such as illustrated inFIG.13. At block1217, the system (e.g., user device509executing user status module735) can obtain user status information (e.g., user status data523) from the user. As previously described above and illustrated inFIGS.15B and15C, the system can generate and display interactive user interfaces prompting the user to enter the user status information. Additionally, at block1221, the system (e.g., user device509executing user status module735) can obtain biometric information (e.g., biometric data525) from the biometric sensor device (e.g., biometric sensor device506). At block1225, the system (e.g., user device509executing user reporting module737) can generate or determine one or more usage reports (e.g., reports529) based on the activity levels determined at block1213, the user status information logged at block1217, and the biometric information logged at block1221. In some embodiments, the report illustrates the activity levels and the usage levels as histograms, bar charts, line charts, pie charts, or the like. Further, in some embodiments, the reports may combine user status information, such as pain data, with the motion levels and the usage levels. For example, the active usage report can indicate a time-correlation between user pain and activity levels by superimposing user pain data over levels over activity illustrate in particular time frames (e.g., daily, weekly, or monthly). It is understood that other types of graphical representations of the information can be used. At block1229, the system can provide the usage report determined at block1225to the user and to a monitor device (e.g., monitor device111). This description and the accompanying drawings illustrate exemplary embodiments and should not be taken as limiting, with the claims defining the scope of the present disclosure, including equivalents. Various mechanical, compositional, structural, and operational changes may be made without departing from the scope of this description and the claims, including equivalents. Like numbers in two or more figures represent the same or similar elements. Furthermore, elements and their associated aspects that are described in detail with reference to one embodiment may, whenever practical, be included in other embodiments in which they are not specifically shown or described. For example, if an element is described in detail with reference to one embodiment and is not described with reference to a second embodiment, the element may nevertheless be claimed as included in the second embodiment. Moreover, the depictions herein are for illustrative purposes only and do not necessarily reflect the actual shape, size, or dimensions of the system or illustrated components. With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity. It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.” In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group. | 83,962 |
11857786 | DETAILED DESCRIPTION Systems and methods are described herein that apply electrical stimulation to the head region, for stimulation of peripheral and/or cranial nerves, transcranial stimulation of brain regions, and sensing of body parameters, while monitoring the tissue and adapting the electrical stimulation signal to the user's characteristics and to changes over time. The systems and methods ensure effective electrical stimulation while avoiding damage to scalp tissue as well as discomfort to the user, and operate in a safe and robust fashion. The inventive methods may be applied using a head mounted construction serving as a platform for applying electrical stimulation in accordance with the inventive methods to treat various conditions such as migraine and tension headaches, cluster headaches, fibromyalgia, depression, post-traumatic stress disorder (PTSD), anxiety, obsessive compulsive disorder (OCD), insomnia, epilepsy, attention deficit hyperactivity disorder (ADHD), Parkinson's disease, Alzheimer's disease, obesity, multiple sclerosis, traumatic brain injury (TBI) and stroke. The quality of contact between the stimulation electrodes and the scalp is a fundamental aspect in the provision of neurostimulation. Given the fact that such contact, and the resulting conductivity are not always optimal, the inventors have developed a method for compensating for reduced conductivity or increased impedance, for example due to presence of hair, lack of humidity, and the like, while maintaining the user's skin integrity, comfort, and ensuring proper neurostimulation. Electrical stimulation of a pure sensory nerve elicits radiation of a paresthesia sensation along the distribution of the nerve. The existence of paresthesia at the relevant anatomical area is an indication that effective nerve excitation is taking place. Conversely, absence of paresthesia along the distribution of the nerve during stimulation may reflect an inability to reach effective nerve excitation due to inappropriate stimulation parameters such as excessively low intensity, insufficient current density or charge, or due to other reasons such as inappropriate electrode location or high impedance. Eliciting paresthesia is an important factor also in the treatment of pain. According to the “Gate-control theory”, activation of large sensory Aβ nerve fibers, which is indicated by the paresthesia sensation, leads to inhibition of small diameter nociceptive Aδ and C fibers and thereby impedes the sensation of pain. As such, it is desirable to maintain the user's sensation of paresthesia during neurostimulation treatment. Several aspects of the present invention relate to methods and techniques that are aimed at ensuring that the electrical current is properly and effectively delivered from the electrodes to the target tissues while keeping the voltage applied to the tissue sufficiently low. Reference is now made toFIG.1A, which is a schematic block diagram of an embodiment of an inventive system for neurostimulation according to an embodiment of the teachings herein. As seen, a system100for neurostimulation may include at least two stimulating electrodes102, and in some embodiments may further include at least two sensing electrodes104, both the electrodes102and104functionally associated with an electronic circuit106. The stimulating electrodes102are adapted to engage the skin of the user's scalp so as to deliver current thereto as described hereinbelow. In some embodiments, one or more of sensing electrodes104may be adapted to engage the skin of the user, and may be configured to sense at least one electrical parameter of a body portion of the user, such as, for example, electroencephalogram (EEG), skin conductance response (SCR), impedance plethysmograph (IPG), electromyograph (EMG), and the like. According to features of the teachings herein, system100, and specifically the electronic circuit106, may be suited for applying transcranial electrical stimulation using suitable methods such as Transcranial Direct Current Stimulation (tDCS), Transcranial Alternating Current Stimulation (tACS), and Transcranial Random Noise Stimulation (tRNS). As seen, the electronic circuit106may include any one or more of a microcontroller108, a high voltage circuit110, a stimulation circuit112, an internal power supply114, a radio-frequency (RF) transceiver116, an analog signal processing circuit118, a rechargeable battery120electrically associated with a charging circuit122, a sensor array124including one or more of an accelerometer126, a temperature sensor128, a pressure sensor130, and a humidity sensor132, and a user interface134. In some embodiments, the electronic circuit106may be electrically associated with and powered by rechargeable battery120that is electrically connected to internal power supply114. In some embodiments, the internal power supply114provides power to high voltage circuit110, which in turn is electrically connected to stimulation circuit112. The charging circuit122is electrically associated with rechargeable battery120, and may interface with an external power supply, such as a charger140. The high voltage circuit110provides to stimulation circuit112current with voltage in the range of 1 to 150 V. In some embodiments, the stimulation circuit112receives information and/or commands from the microcontroller108. The stimulation circuit112is configured to provide electrical stimulation pulses to the user's nerve tissues via the stimulation electrodes102. The stimulation circuit112may be configured to produce biphasic, charged balanced electrical pulses, mono-phasic electrical pulses, and/or direct current stimulation. According to still further features of the described preferred embodiments, the stimulation circuit112may be configured to produce electrical stimulation within an intensity range of 0-60 mA, 0-40 mA, 0-20 m, or 0-15 mA. According to still further features of the described preferred embodiments, the stimulation circuit112may be configured to produce stimulation pulses with a duration of 10-1000 μsec, 50-600 μsec, 100-500 μsec. According to still further features of the described preferred embodiments, the stimulation circuit112may be configured to produce stimulation pulses at a frequency of 1-20,000 Hz, 1-10,000 Hz, 1-500 Hz, 10-300 Hz, 10-250 Hz, 20-180 Hz, 30-180 Hz or 40-100 Hz. In some embodiments, electronic circuit106may include two or more high voltage circuits (not shown) similar to circuit112, each high voltage circuit providing current at a voltage of 1-150V, 1-120V, 1-100V, to at least two of stimulation electrodes102. In some embodiments, electronic circuit106may include at least two isolated output channels (not shown), each output channel providing output to at least two of stimulation electrodes102. In some embodiments, the electronic circuit106also includes a feedback & measurements circuit142, which collects voltage or current level information from the stimulation electrodes102, and provides the collected information to the microcontroller108. The microcontroller108uses the provided feedback to monitor and control the voltage and current levels in stimulation electrodes102via stimulation circuit112in accordance with the method disclosed herein with respect toFIGS.2and3. In some embodiments, the microcontroller108may alert the user, for example by providing an audible or tactile indication, or may halt the provision of current for stimulation in the case of an emergency or of incorrect function of the system, as described hereinbelow with reference toFIG.2. In some embodiments, the microcontroller108may instruct the stimulation circuit112to output electrical current in various patterns and/or for various periods of time, and/or may instruct the stimulation circuit112with regards to various stimulation parameters, such as the current amplitude, pulse frequency, phase duration, and amplitude of the current output by the stimulation circuit, as described hereinbelow with reference toFIG.2. In some embodiments, the microcontroller108may instruct the stimulation circuit112to provide an output signal having a different pattern for each of a plurality of activated pairs of electrodes. For example, the stimulation circuit112may stimulate one pair of electrodes at a pulse frequency of 50 Hz and a phase duration of 300 μsec and another pair of electrodes at a pulse frequency of 100 Hz and a phase duration of 200 μsec. In some embodiments, at any given time the microcontroller108may activate only one pair of electrodes, may activate a combination of electrodes, and/or may activate several electrodes simultaneously, sequentially, or alternately. In some embodiments, some electrodes102may provide as output an alternating current signal, whereas other electrodes102may provide as output a direct current. In some embodiments, at least two electrodes102may alternate the type of current provided as output between alternating current and direct current. In some embodiments, during direct current stimulation in which excitation of a certain region of the brain is determined based on the polarity of an electrode which is positioned above that region of the brain, at least one electrode102may be assigned by the microcontroller108to be the anode, or positively charged electrode, and at least one other electrode102may be assigned to be the cathode, or negatively charged electrode. In some embodiments, stimulation patterns determined by or assigned by the microcontroller108as described hereinbelow with reference toFIG.2, as well as feedback data received from electrodes102and/or from sensing electrodes104may be stored in the microcontroller108or in a volatile or non-volatile memory (not shown) associated therewith. In some embodiments, the stored stimulation patterns may be used to create a personalized neurostimulation protocol for the user, as described hereinbelow with reference toFIG.3. In some embodiments, electronic circuit106may be configured to receive analog signal input, such as electroencephalogram (EEG) signals, skin conductance response (SCR) signals, impedance plethysmograph (IPG) signals, electromyograph (EMG) signals, or other bio-signals, from one or more sensors, such as sensing electrodes104, which bio-signals may be indicative of the impedance of the tissue receiving the neurostimulation signal, the charge provided to the tissue, or the like. The analog signal input received from sensing electrodes104may be processed by analog signal processing circuit118, and may be transferred therefrom to microcontroller108. In some embodiments, electronic circuit106may be configured to receive digital, analog, or other input from additional sensors adapted to sense the vicinity of the user or characteristics thereof. In some embodiments, one or more stimulation parameters may be altered by the microcontroller108due to inputs received from one or more of the additional sensors, as described hereinbelow. In some embodiments, accelerometer126, or any other suitable orientation sensor, may be configured to sense the angular position of the user's head or of the system100(and particularly portions thereof engaging the user's head), and thereby may enable microcontroller108to identify a change in the user's and/or system's conditions and to adjust or adapt the pulse provided by stimulating electrodes102. For example, a change in the position of the user may result in a change in the pressure applied to the electrodes, thus changing how close the electrodes are to the user's skin and consequently changing the impedance in the system and requiring adaptation of the pulse applied to the tissue via the electrodes, as described hereinbelow. In some embodiments, temperature sensor128may be configured to sense a temperature in the vicinity of the system100or of the stimulating electrodes102, and thereby may enable microcontroller108to identify a change in the user's and/or system's conditions and to adjust or adapt the pulse provided by stimulating electrodes102. For example, an increase in the temperature in the vicinity of the user or of the electrodes102may result in more rapid dehydration of the electrodes or of conducting material applied thereto, thus increasing the impedance in the system and requiring adaptation of the pulse applied to the tissue via the electrodes, as described hereinbelow. In some embodiments, pressure sensor130may be configured to sense pressure applied to the user's head in the vicinity of electrodes102or pressure applied directly to electrodes102, and thereby may enable microcontroller108to identify a change in the user's and/or system's conditions and to adjust or adapt the pulse provided by stimulating electrodes102. For example, an increase in the amount of pressure applied to electrodes102pushing them towards the user's scalp is expected to reduce the distance between the electrodes and the scalp, and in some cases the distance between the electrode and the target nerve, thereby reducing the impedance in the system and requiring, or allowing, adaptation of the pulse applied to the tissue via the electrodes, as described hereinbelow. In some embodiments, humidity sensor132may be configured to sense a humidity or moisture level in the vicinity of the system100or of the stimulating electrodes102, and thereby may enable microcontroller108to identify a change in the user's and/or system's conditions and to adjust or adapt the pulse provided by stimulating electrodes102. For example, a decrease in the sensed humidity in the vicinity of the electrodes102may be indicative of dehydration of the electrodes or of conducting material applied thereto, thus increasing the impedance in the system and requiring adaptation of the pulse applied to the tissue via the electrodes, as described hereinbelow. In some embodiments, user interface134may be configured to receive from the user an indication of the sensation the user is feeling, such as an indication of pain, an indication of discomfort, or an indication of decreased, or no, paresthesia. Such an indication from the user of a change in the sensation the user feels may enable microcontroller108to adjust or adapt the pulse provided by stimulating electrodes102. In some embodiments, RF transceiver116may enable the microcontroller108to communicate with an interface of an external device150, such as a mobile phone, a tablet, a computer, or a cloud based database, by way of radio frequency. The RF transceiver116may transmit digital information to and may receive digital information from the microcontroller108, for example for personalization of the neurostimulation provided by system100, as described hereinbelow with reference toFIG.3. The interface of device150may comprise a software application that may be downloadable from a readily accessible resource, such as from the Internet. The interface may provide to a user thereof an indication, for example by way of a display, of the status of the system100, including, for example, information relating to active stimulation channels, stimulation intensity, active program, treatment time, battery status, and RF communication status, as well as various alerts such as alerts relating to electrode contact quality and to proper or improper system alignment on the head. Additionally, the interface may provide to the user, for example by way of a display, usage logs and/or reports, such as information relating to daily stimulation time, stimulation parameters which were used during stimulation, and treatment programs which were used. The interface may also display, or otherwise provide, to the user raw or processed information received from sensors included in or associated with the headset. In some embodiments, the system may be controlled remotely via the interface of external device150. For example, the external interface may enable a user thereof to activate or turn off the system, start or pause stimulation, adjust the stimulation intensity for one or more channels, and select a treatment program. In some embodiments, information collected by the microprocessor108may be transmitted, via the external interface, to a remote location, such as a cloud based portal, where the information may be stored or may be analyzed and/or monitored, for example as described hereinbelow with reference toFIG.3. Reference is now made toFIG.1B, which is a perspective view schematic illustration of an embodiment of the inventive system100ofFIG.1Ain the form of a headset communicating with external data sources according to the teachings herein. As seen, a headset160may implement the system100ofFIG.1A, and may be configured to include an anterior member162connected to a pair of flexible arm members164, which may also be called interim members, each terminating in a posterior member166. Anterior member162, flexible arm members164, and posterior members166together form the headset body. In some embodiments, each posterior member166comprises a terminal portion having a tapered end terminating in a closure mechanism168. Anterior member162may be configured to contain, on an interior surface thereof, one or more anterior electrode systems172, and each of posterior members166may be configured to contain, on an interior surface thereof, one or more posterior electrode systems174, electrode systems172and174implementing or being similar to stimulating electrodes102ofFIG.1A. Each of electrode systems172and174may comprise an electrode base and a disposable electrode unit, which may, in some embodiments, be structured and functional as described in patent application publications US2015/0374971, AU2015227382, EP2981326, CN105188835, WO2014/141213 and IL241026, all entitled HEADSET FOR TREATMENT AND ASSESSMENT OF MEDICAL CONDITIONS, and WO2016/042499 entitled HEADSET FOR NEUROSTIMULATION AND SENSING OF BODY PARAMETERS filed by the present inventors, which are incorporated by reference as if fully set forth herein. In some embodiments, electrode systems172may comprise anterior electrodes adapted to be located at the supraorbital region of the head over the trigeminal nerve branches for stimulation thereof, or may be electrodes suitable for transcranial stimulation of the frontal and prefrontal region of the brain. In some embodiments, electrode systems174may comprise posterior electrodes adapted to be located at the occipital region of the head over the occipital nerve branches for stimulation thereof, or may be electrodes suitable for transcranial stimulation of the occipital region of the brain. In some embodiments, one or more of electrode systems172and174may comprise sensing electrodes similar to sensing electrodes104ofFIG.1A, configured to sense at least one electrical parameter of a body portion of said user, such as, for example, electroencephalogram (EEG), skin conductance response (SCR), impedance plethysmograph (IPG), electromyograph (EMG), and the like. It will be appreciated that headset160may include additional electrodes having similar structure and/or functionality to those of electrode systems172and174. It is further appreciated that electrode systems172and/or174may be obviated, or moved to other locations on headset160, as suitable for stimulating specific nerves or nerve sets, specific brain regions, or for sensing specific parameters. For example, electrode systems174may be moved to be along the flexible arm members164. As another example, the headset160may include only a single pair of electrode systems located on arm members164, which electrodes may be configured to be positioned, when the headset is donned, under the hair, while electrode systems172and174may be obviated. Anterior member162may be configured to contain an electronic circuit176, similar to electronic circuit106ofFIG.1A, which may be configured to be electrically coupled by conductive wires (not shown) to a power source177, such as a battery similar to battery120ofFIG.1A, and to electrodes systems172and174. In some embodiments, at least a portion of the conductive wires extends to posterior electrode systems174via arm members164. In some embodiments, the electronic circuit176and/or the battery177may be external to headset160, and/or may communicate remotely with headset160. As discussed hereinabove with reference toFIG.1A, the electronic circuit176may include a stimulation circuit, a microprocessor, a charging circuit and a user interface. In some embodiments, headset160may be configured to connect to an external electronic circuit and/or stimulation circuit, and thereby to transfer electrical current from an external stimulator to the electrode systems172and/or174. In some embodiments, headset160may be configured to connect to at least one external electrode that may be located at various areas of the body. In some embodiments, headset160may be configured to connect to an external electronic circuit and processor in order to transfer signals from sensors disposed on the headset160to the external processor. In some embodiments, battery177may be disposed within anterior member162, and may be recharged by plugging a charger into charging port178located, according to certain embodiments, on anterior member162. Anterior member162may also be configured to include, on an external surface thereof, user controls and interface180, which may be similar to user interface134ofFIG.1A. That said, in some embodiments, other portions of headset160, such as posterior members166or arms164, may be configured to include user interface180. In some embodiments, user interface180, or an additional user interface (not shown) may be external to headset160and may communicate with headset160remotely, using wired or wireless communication, as explained hereinabove with reference toFIG.1A. Electronic circuit176and user interface180may be configured to control and/or activate electrodes included in headset160. In some embodiments, user interface180is configured to control and/or activate at least two, and in some embodiments more than two, pairs of electrodes. As such, in some embodiments, the stimulation circuit and/or user interface180are configured to enable activation of a specific electrode or of a specific pair, or channel, of electrodes, as well as adjustment of the intensity of current supplied by the activated electrodes or of other stimulation parameters of the activated electrodes and provision of user indications such as a user indication of pain, a user indication of discomfort, or a user indication of reduced or increased paresthesia. In some embodiments, any subset of the electrodes may be activated simultaneously, and in some embodiments specific subsets are predefined, for example during manufacture of the electronic circuit176. In some such embodiments, user interface180enables control not only of a specific electrode or of a specific channel, but also of activated subsets of the electrodes. In some embodiments, user controls and interface180includes a pair of anterior intensity buttons181aand181bfor respectively increasing and decreasing the intensity of stimulation provided by anterior electrode systems172, and a pair of posterior intensity buttons182aand182bfor respectively increasing and decreasing the intensity of stimulation provided by posterior electrode systems174. It will be appreciated that user control and interface180may include similar intensity buttons for each electrode included in the headset160. The user controls and interface180may further include a mode changing button184for activating and disabling the electronic circuit176, as well as for changing between modes of operation of headset160. For example, headset160may have multiple preset modes of operation, such as a sleep mode, a maintenance mode, and a treatment mode, and repeated operation of button184may switch between these modes, in addition to turning the headset on and off. A user indication button, for example allowing the user to provide a user indication of pain, discomfort, or reduced paresthesia, may form part of user controls and interface180and may be disposed on an exterior surface of anterior member162. In some embodiments, the user controls and interface180may further include an audio element (not shown), such as a speaker or buzzer, for providing to the user an audible indication of use of the headset180, such as an indication of activation of the headset, shutting down of the headset, pressing a button on interface180, changing the stimulation mode, and the like. As explained hereinabove, the electronic circuit and the user interface are configured to control and/or activate electrodes included in headset160. In some embodiments, the user interface is configured to control and/or activate at least two, and in some embodiments more than two, pairs of electrodes. As such, in some embodiments, the stimulation circuit and/or the user interface are configured to enable activation of a specific electrode or of a specific pair, or channel, of electrodes, as well as adjustment of the intensity of current supplied by the activated electrodes or of other stimulation parameters of the activated electrodes. In some embodiments, any subset of the electrodes may be activated simultaneously, and in some embodiments specific subsets are predefined, for example during manufacture of the electronic circuit. In some such embodiments, the user interface enables control not only of a specific electrode or of a specific channel, but also of activated subsets of the electrodes. In some embodiments, electronic circuit176includes a transceiver196, similar to transceiver116ofFIG.1A, which transceiver is configured to remotely communicate with a communication device197external to headset160and similar to external device150ofFIG.1A, such as a mobile telephone, a tablet computer, and the like. Communication device197may further communicate with a remote storage location, such as a cloud based storage location indicated by reference numeral198, for storage of data therein or retrieval of data thereof. For example, in some embodiments, data relating to the specific stimulation protocol used for a specific user may be transmitted from transmitter196to cloud based storage location198for storage therein via communication device197, and may be retrieved from the cloud based storage location in the future in order to facilitate personalization of the stimulation protocol for the specific user, substantially as described hereinbelow with reference toFIG.3. As another example, reference data may be transmitted from cloud computing storage location198to transceiver196, for example via communication device197, in order to facilitate personalization of the stimulation protocol as described herein with reference toFIG.3. Reference is now made toFIG.2, which is a flow chart of an embodiment of a method for neurostimulation of a head region having high impedance according to the teachings herein, using the system ofFIG.1A. Initially, at step200, the microcontroller108instructs the stimulation circuit112to provide, via the stimulation electrodes102that engage the user's scalp surface, one or more electrically balanced singular pulses, each having a single positive phase and a single negative phase. An example of such a pulse, provided under standard impedance conditions, is illustrated inFIG.4Aas pulse400. In some embodiments, the pulse may have an intensity range of 0-60 mA, 0-40 mA, 0-20 m, or 0-15 mA. In some embodiments, the pulse may have a duration of 10-2000 μsec, 100-1600 μsec, 200-1400 μsec, or 300-1000 μsec. In some embodiments, the pulse may have a frequency in the range of 1-20,000 Hz, 1-10,000 Hz, 1-500 Hz, 10-300 Hz, 10-250 Hz, 20-180 Hz, 30-180 Hz or 40-100 Hz. The microcontroller108continuously, periodically or intermittently evaluates whether the voltage required by the electrodes to provide the pulse has reached a predetermined threshold value, or upper voltage threshold, at step202. The threshold value may be equal to the compliance voltage of the circuit106, or may be a fraction or percentage thereof. In some embodiments, the threshold value is 60%-70% of the compliance voltage. In some embodiments, following evaluation of the voltage required by the electrodes to provide the pulse, or concurrently therewith, the microcontroller108evaluates whether the impedance in the system has reached a predetermined impedance threshold value, at step204. This would be suitable when predetermined impedance is reached even if voltage threshold is not reached, for example if the pulse is provided at a relatively low current. In some embodiments, the impedance threshold may be greater than 8KΩ, greater than 10KΩ or greater than 12KΩ. If the voltage has not reached the voltage threshold, and the impedance has not reached the impedance threshold, the microcontroller108instructs the stimulation circuit112to continue providing, via the stimulation electrodes102, a balanced singular pulses at step200. It will be appreciated that when the voltage in the system is insufficient for providing the pulse, or if the impedance in the system is too high, then according to Ohm's law the current provided by the electrodes will be insufficient to allow for the full charge to be provided to the tissue.FIG.4Billustrates an example of the current provided by singular pulse400under high impedance conditions, and as can be seen, the positive phase of the pulse is cut beginning at a time point indicated by reference numeral410, such that the pulse does not provide the charge intended to be provided.FIG.4Cillustrates the voltage on the electrodes102under high impedance conditions, and as seen the voltage required by the electrodes rises until an upper voltage threshold is reached. In the illustrated embodiment, the upper voltage threshold is the compliance voltage of the system. Comparison ofFIGS.4B and4Cdemonstrates that the time point410, where the pulse becomes cut (FIG.4B), corresponds to the time at which the compliance voltage was reached (FIG.4C). As such, if the evaluation at step202determines that the voltage has reached the voltage threshold, and/or if the evaluation at step204determines that the impedance has reached the impedance threshold, the pulse provided by the electrodes102will be cut. Consequently, at step206the microcontroller108instructs the stimulation circuit112to change the pulse provided via electrodes102to be a phase train pulse, similar to the pulse shown inFIG.5A. Referring also toFIG.5A, it is seen that the pulse now provided by the electrodes102is a balanced pulse500including a positive phase train502immediately followed by a negative phase train508. The positive phase train502includes a streak of constant current positive phases504separated by rest times506, and the negative phase train508includes a streak of constant current negative phases510separated by rest times512. Each of the positive phases504and the negative phases510is intended to provide a predetermined amount of charge. It will be appreciated that the term “predetermined amount of charge” relates to an amount of charge equal to the intended amount of charge, as well as to an amount of charge differing from the intended amount of charge by at most 15%, at most 10%, at most 5%, at most 3%, or at most 1%. The inventors have found that the transition from the singular pulse ofFIG.4Ato the phase-train pulse ofFIG.5Aresults in the reduction of the impedance of the layers underlying the electrodes, such as the hair and tissue layers, and consequently in reduction of the voltage required to provide the required charge. As such, as seen inFIG.5A, in each of the phases504and510the pulse is complete, and the intended amount of charge, or an amount of charge deviating from the intended amount of charge by at most 15%, at most 10%, at most 5%, at most 3%, or at most 1% is provided to the scalp of the user. It is a particular feature of the teachings herein that a time ratio trpbetween a cumulative duration drtpof the rest times506between the positive phases504and a cumulative duration dspof the positive phases504is smaller than a predetermined ratio. Similarly, a time ratio trnbetween a cumulative duration drtnof the rest times512between the negative phases510and a cumulative duration dsnof the negative phases510is smaller than a predetermined threshold ratio. In some embodiments, the predetermined threshold ratio is in the range of 0.4-1.2, 0.5-1 or 0.55-0.75. In some embodiments, the predetermined threshold ratio is 0.6, as explained hereinbelow in Example 1. In some embodiments, such as the embodiment ofFIG.5A, the positive phases504and the negative phases510have a common phase width wl. However, in other embodiments, the positive phases504may have a common phase width wp, which may be different from a common phase width wnof the negative phases510. In yet further embodiments, the positive phases need not have a common phase width, and the negative phases need not have a common phase width. It will be appreciated that for the purposes of this specification and the claims that follow the term “common phase width” relates to an equal phase width, but also includes phase widths with at most 20%, at most 15%, at most 10%, at most 5%, or at most 1% deviation from one another. In some embodiments, the rest times506between immediate successor positive phases504and the rest times512between immediate successor negative phases510have a common rest-time value rtl. In other embodiments, the rest times506between immediate successor positive phases504have a common rest time value rtp, which may be different from a common rest time value rtnof the rest times512between immediate successor negative phases510. In yet further embodiments, the rest times506need not have a common rest time value, and the rest times512need not have a common rest time value. It will be appreciated that for the purposes of this specification and the claims that follow the term “common rest time value” relates to an equal rest time values, but also includes rest time values with at most 20%, at most 15%, at most 10%, at most 5%, or at most 1% deviation from one another. In some embodiments, a duration of the positive phase train502is equal to a duration of the negative phase train508, though it need not necessarily be equal. In some embodiments, the cumulative duration dspof the positive phases504is equal to the cumulative duration dsnof the negative phases510, though it need not necessarily be equal. In some embodiments, the cumulative duration drtpof the rest times506between the positive phases504is equal to the cumulative duration drtnof the rest times512between negative phases510, though it need not necessarily be equal. The number of positive phases504in positive phase train502, and the number of negative phases510in negative phase train508, is in the range of 2-30. In some embodiments, the number of positive phases504in positive phase train502is equal to the number of negative phases510in negative phase train508, though it need not necessarily be equal. In some embodiments, the duration of each rest time506or512is at least 5 μsec. In some embodiments, the phase width of each positive phase504and of each negative phase510is at most 600 μsec, at most 400 μsec, at most 300 μsec, at most 200 μsec, at most 100 μsec, or at most 50 μsec. Returning toFIG.2, following transition to a phase-train pulse at step206, the results of the transition are evaluated in an attempt to reach a pulse which requires the lowest voltage, while providing sufficient charge to the user's scalp. As such, at step208the microcontroller108evaluates, or monitors, whether sufficient charge is being provided by each of the positive phases504and the negative phases510. It will be appreciated that the charge is considered sufficient if it is equal to the intended charge, or if it deviates from the intended charge by at most 15%, at most 10%, at most 5%, at most 3%, or at most 1%. In some embodiments, the charge provided by the phases is monitored by sensing electrodes104, which, in some embodiments, may be the same electrodes as stimulating electrodes102. In some embodiments, the charge is monitored by an additional sensor, external to the stimulating electrodes102and sensing electrodes104, which is functionally associated with circuit106, such as for example a sensor in sensor array124. In some embodiments, the charge is monitored by monitoring a waveform of each provided phase, to identify whether the provided waveform for the phase is identical to an intended waveform, or deviates from the intended waveform by at most 15%, at most 10%, at most 5%, at most 3%, or at most 1%. In some embodiments, a reduction in the charge provided to the scalp, or insufficient charge, is indicated by the provided waveform differing from the intended waveform more than the permissible deviation, and specifically by the provided waveform dropping, or being “cut”, toward the end of a phase. Referring additionally toFIG.5B, which shows the phase train pulse500ofFIG.5Ain a situation where insufficient charge is provided, it is seen that the waveform of positive phase504adoes not form a right angle at the end, or is incomplete, which is indicative of the charge being provided by the phase504ato the scalp being less than the intended charge. If at step208it is determined that insufficient charge is being provided, for example by determining that the waveform of the pulse is similar to that shown in FIG.5B, at step210the microcontroller108evaluates whether the time ratio trp, between the cumulative duration drtpof the rest times between the positive phases and the cumulative duration dspof the positive phases, and the time ratio trn, between the cumulative duration drtnof the rest times between the negative phases and the cumulative duration dsnof the negative phases, are smaller than a predetermined threshold ratio. Stated differently, at step210the microcontroller108evaluates whether the cumulative rest time in the pulse is less than the maximal allowed rest time, or is equal to the maximal allowed rest time. If at step210the microcontroller108determines that the maximal allowed rest time has not been reached, at step212the microcontroller108instructs the stimulation circuit112to update at least one rest time in the provided pulse. Due to the fact that the maximal allowed rest time has not been reached, the microcontroller updates the pulse by increasing at least one rest time in the positive phase train and/or in the negative phase train. In some embodiments, the microcontroller108instructs the stimulation circuit112to update the pulse by increasing all the rest times in the positive phase train, and/or all the rest times in the negative phase train. In some embodiments, the microcontroller108instructs the stimulation circuit112to increase the common rest time value rtpin the positive phase train, the common rest time value rtnin the negative phase train, or the common rest time value rtlin the pulse. FIG.5Cillustrates the phase train pulse500ofFIGS.5A and5B, following an increase in the common rest time between the phases. As seen inFIG.5C, in some cases, following the increase in the rest times, the pulse waveform is once again “complete” and the expected amount of charge is being provided by the pulse to the scalp of the user. If the maximal allowed rest time has been reached at step210, at step214the microcontroller108evaluates whether the voltage provided by the electrodes has reached a predetermined voltage threshold, such as the compliance voltage of the system or a predetermined fraction or percentage thereof. If at step214the microcontroller108determines that the voltage threshold has been reached, that means that the rest times cannot be increased (due to the determination at step210), and the voltage cannot be increased (due to the determination at step214). As such, it is likely that there is a bad electrical contact between the electrodes102and the user's scalp, or another malfunction in the system, and at step216the microcontroller108may provide to the user an indication of such a malfunction or bad electrical contact, for example via user interface134. Subsequently, treatment is aborted. Alternately, if at step214the microcontroller108determines that the voltage threshold has not been reached, at step218the microcontroller108instructs the stimulation circuit112to increase the voltage to be applied by electrodes102, and subsequently updates at least one rest time in the provided pulse at step212. In some embodiments, due to the fact that the maximal allowed rest time has been reached, the microcontroller108instructs the stimulation circuit112to update the pulse by reducing at least one of the rest times in the positive phase train and/or in the negative phase train. In some embodiments, the microcontroller108instructs the stimulation circuit112to update the pulse by reducing all the rest times in the positive phase train, and/or all the rest times in the negative phase train. In some embodiments, the microcontroller108instructs the stimulation circuit112to reduce the common rest time value rtpin the positive phase train, the common rest time value rtnin the negative phase train, or the common rest time value rtlin the pulse. In some embodiments, following the increase in voltage at step218, and the reduction in the rest time at step212, the phase train pulse has the waveform shown inFIG.5A. In some embodiments, any rest time reduced by the microcontroller108or by stimulation circuit112is reduced to a minimal rest time, which, in some embodiments, is not less than 5 μsec. It will be appreciated that in some embodiments, the change to the rest times is carried out by microcontroller108instructing the stimulation circuit112to change one or both of the time ratio trp, between a cumulative duration drtpof the rest times506between the positive phases504and a cumulative duration dspof the positive phases504, and the time ratio trn, between a cumulative duration drtnof the rest times512between the negative phases510and a cumulative duration dsnof the negative phases510. In some embodiments, at step212the microcontroller108may instruct the stimulation circuit112to adapt additional characteristics of the pulse. In some embodiments, at step212the microcontroller108may also instruct the stimulation circuit112to adapt the number of positive phases in the positive phase train and/or the number of negative phases in the negative phase train. In some embodiments, at step212the microcontroller108may also instruct the stimulation circuit112to adapt the phase width of one or more of the positive phases, or a common phase width wPof the positive phases. In some embodiments, at step212the microcontroller108may also instruct the stimulation circuit112to adapt the phase width of one or more of the negative phases, or a common phase width wnof the negative phases. In some embodiments, the microcontroller108may also instruct the stimulation circuit112to adapt the amplitude of one or more of the positive phases and/or of one or more of the negative phases. Following the change to the rest times applied by the microcontroller108at step212, the microcontroller108continues to evaluate whether or not sufficient charge is provided by each phase of the pulse at step208, and additional updates to the rest-time and/or voltage may be applied. At any occurrence of step208, if the microcontroller108determines that sufficient charge is being provided by each phase of the pulse to the scalp of the user, at step220the microcontroller108instructs the stimulation circuit112to continue to provide the pulse as established. The microcontroller108then waits for an indication that additional monitoring is required, at step222. When such an indication is provided, the microcontroller returns to step208and assesses whether the pulse is providing sufficient charge, and flow continues from there as described hereinabove. Otherwise, the microcontroller continues to provide the established pulse. In some embodiments, the indication is a microcontroller-internal indication, for example a time indication for periodic monitoring, for example provided every 10 minutes, every 5 minutes, or every 3 minutes. In some such embodiments, additional monitoring may be carried out more frequently at the initial part of the treatment, and then carried out less frequently at later stages of the treatment once the system has reached an equilibrium. In other embodiments, the indication may be received from a component external to the microcontroller. For example, the indication may be an indication of discomfort, pain, or reduced paresthesia, provided by the user, via user interface134. In some embodiments, the indication may be provided by a sensor sensing a change in the system. For example, microcontroller108may receive from a humidity sensor forming part of sensor array124a signal indicating a change in the humidity in the vicinity of electrodes102, which requires additional monitoring. As another example, microcontroller108may receive from a temperature sensor forming part of sensor array124a signal indicating a change in the temperature in the vicinity of electrodes102, which requires additional monitoring. As a further example, microcontroller108may receive from a pressure sensor forming part of sensor array124a signal indicating a change in the pressure applied to electrodes102, which requires additional monitoring. As yet another example, the microcontroller108may receive from an accelerometer forming part of sensor array124a signal indicating a change in the position of the user or in the position of the electrodes, which may indicate that additional monitoring is required (for example, if the user was supine and is now standing, less pressure is applied to the electrodes, which may increase the impedance). It will be appreciated that in order to evaluate the quality of signal transduction in the system (at step208), one may replace the evaluation of the charge provided by the phases of the pulse with an evaluation of the impedance in the system, which, due to Ohm's law, is equivalent to the evaluation of the charge. In such embodiments, the rest times in the provided pulse and/or voltage of the provided pulse would be updated if the impedance measured between the electrodes102is above a predetermined impedance threshold. In some embodiments, the impedance threshold may be greater than 8KΩ, greater than 10KΩ or greater than 12KΩ. Reference is now made toFIG.3, which a flow chart of an embodiment of a method for personalization of the method ofFIG.2according to the teachings herein. As seen at step300, initially, data for generating a treatment model for a specific user is obtained. In some embodiments, the data may be obtained from a remote database, either based in a server or Cloud based. In some embodiments, the data may be based on specific information relating to the user, such as characteristics of the patient such as age, weight, and hair type, and values collected during previous treatments such as stimulation intensity, impedance levels reached, voltage levels reached, changes in voltage/impedance during treatment, and/or treatment duration. Subsequently, at step302, a treatment model is generated based on default values modified in accordance with the obtained data. In some embodiments, the treatment model takes into consideration currently collected treatment data, such as information relating to the current state of the system as identified by sensors in the system (e.g. sensors in sensor array124), which information may include humidity information as identified by a humidity sensor, temperature information as identified by a temperature sensor, position information as identified by an accelerometer, and the like. Additionally, the system may allow the user to provide input, for example via user interface134, relating to the current state of the system, and to use the input to generate the treatment model. For example, the user may indicate that skin irritation or excess skin erythema occurred, which can be used to update the treatment model for this specific user. At step304, the microcontroller of the system generates a prediction of the voltage and/or pulse form that will be required in order to provide sufficient charge to the specific user's scalp, while using a reasonable voltage and short rest times between phases. At step306, the prediction is used to initiate treatment in accordance with the method ofFIG.2, where the predicted voltage is used as the initial voltage in the treatment. At step308, during and/or after treatment, the actual voltage required in order to provide sufficient charge to the user's scalp and/or parameters of the actual waveform used to provide such charge (for example the number of positive and negative phases, the length of each positive and negative phase, the lengths of the rest times between phases, and the like) are recorded by the microcontroller, and stored in a memory associated therewith. In some embodiments, the recorded data may be transmitted to a remote database, either located at a remote server or Cloud based, as seen at step310. The data may be stored in the remote database, in some embodiments associated with at least one identifier of the specific user, such as an identification number or name of the user, or with at least one identifier of the device used by the user, so that it may be readily used in the next treatment session, for example as the data obtained at step300. Reference is now made to the following example, which together with the above description, illustrates the invention in a non-limiting fashion. Example Ten users were treated using the system ofFIG.1Band the method ofFIG.2. The treatment included stimulation of the greater occipital nerve. A headset, similar to that shown inFIG.1B, was placed on each user's head so that the posterior electrodes were placed under the hair over the left and right greater occipital nerve branches at the level of the external occipital protuberance. Stimulation in the form of electrically balanced pulses was applied at a constant current of 5 mA and at a frequency of 80 Hz. In a baseline round, the provided positive and negative phases were singular phases each having a phase duration of 400 μsec, as described hereinabove with reference toFIG.4A. The voltage level was recorded. The users were asked to note the intensity of paresthesia felt at the nerve distribution region, and this intensity was considered baseline intensity and assigned a score of 10. In each subsequent round of treatment, the pulse included a positive phase train and a negative phase train as described hereinabove with reference toFIG.5A. The cumulative duration of the stimulation phases, or the “on-time” in each of the positive and negative phase trains, remained 400 μsec. In each round, the cumulative rest time in each phase train was increased, and the resulting change in voltage required to provide the pulse was recorded. Additionally, the users were asked to assign a score of 1-10 to the paresthesia felt in the nerve distribution region, where 10 is the baseline paresthesia and 1 is negligible paresthesia. The results are summarized inFIG.6A, which illustrates a table including the change in voltage and in paresthesia following the change to the cumulative rest time of the provided pulse. The table600includes a title row602, a first baseline row604, and a plurality of treatment rows606, each relating to a single round of treatment. Each of the rows is divided into a plurality of columns608, including: column608ashowing the cumulative rest time, in μsec, in each of the positive and negative phase trains in that round of treatment; column608bshowing the percentage of the cumulative length of the rest time from the cumulative phase durations, or, stated differently, the percentage of the “off time” from the “on time” for each of the positive and negative phase trains—for example, if the cumulative rest time is 100 μsec, and as mentioned above the cumulative phase duration in each phase train in all the rounds is 400 μsec, then the percentage shown in column608bwould be 25%; column608cshowing the average voltage required in order to provide sufficient charge, given the rest time specified in column608a; column608dshowing the percent of decrease in average voltage, relative to the baseline voltage; and column608eshowing the average paresthesia score provided by users for the treatment round. FIGS.6B and6Cprovide schematic graphic representations of the results shown inFIG.6A. Specifically,FIG.6Billustrates the change in voltage as a result of the change in the pulse waveform in the different treatment rounds, andFIG.6Cillustrates the change in experienced paresthesia as a result of a change in the pulse waveform in each pulse round. A closer look at table600shows that as the cumulative rest time increases, the voltage required in order to provide sufficient charge to the scalp of the user decreases, as well as the paresthesia experienced by the user. Looking specifically at the lowest row606hof the table600, it is seen that the voltage required to provide the pulse, when the cumulative rest time is double the length of the cumulative phase duration, has decreased by as much as 67%, and the paresthesia experienced by the user has decreased entirely, to the point that the users only felt negligible paresthesia, if any. As seen inFIG.6C, the paresthesia experienced by the users (y-axis) is plotted against the percentage of the total rest time from the total phase duration, or stated differently, the percentage of the total “off time” from the total “on time” (x-axis). As seen, the graph initially decreases at section620a, then plateaus at section620b, and subsequently decreases at section620c, substantially linearly, until reaching the score of 1. As seen, at the point of the plateau having the greatest rest time percentage, indicated inFIG.6Cby reference numeral622a, the user still experiences significant paresthesia (with an average score of 8). In the present example, this point is at a rest time percentage of 60%, or a ratio of 0.6 between the cumulative rest time and the cumulative phase duration. Turning toFIG.6B, it is seen that the percentage of decrease of the voltage required to provide sufficient charge from voltage baseline (y-axis) is plotted against the percentage of the total rest time from the total phase duration, or stated differently, the percentage of the total “off time” from the total “on time” (x-axis). At point622b, which corresponds in the rest time percentage to point622aofFIG.6C, the voltage required to provide sufficient charge to the user's scalp is approximately 25% lower than the baseline voltage. It will be appreciated that in accordance with the illustrated results, the identified rest time percentage of 60% is particularly suitable as the rest time threshold as it significantly reduces the voltage required in order to provide sufficient charge to the user's scalp, while the user continues to feel significant levels of paresthesia in the nerve distribution region, which is desirable. As used herein in the specification and in the claims section that follows, the term “or” is considered as inclusive, and therefore the phrase “A or B” means any of the groups “A”, “B”, and “A and B”. As used herein in the specification and in the claims section that follows, the term “pulse” relates to an electrical signal, for example applied via an electrode or sensed by an electrode. As used herein in the specification and in the claims section that follows, the term “phase” relates to a pulse or a portion thereof, having current starting from a zero amplitude, changing to a higher amplitude, and returning to zero amplitude. As used herein in the specification and in the claims section that follows, the term “positive phase” relates to a phase providing current which flows in the positive direction. As used herein in the specification and in the claims section that follows, the term “negative phase” relates to a phase providing current which flows in the negative direction. As used herein in the specification and in the claims section that follows, the term “balanced pulse” relates to a pulse including a positive portion including at least one positive phase and a negative portion including at least one negative phase, such that the magnitude, or charge, of the positive and negative portions is equal, or is within 15%, within 10%, within 5%, within 3%, or within 1% of one another. As used herein, in the specification and in the claims section that follows, the term “phase train” relates to a pulse including two or more consecutive phases of the same type or magnitude, or in the same direction. For example, a positive phase train includes two or more consecutive positive phases and a negative phase train includes two or more consecutive negative phases. Any phases in the opposite direction, having a charge of up to 30% of the charge of the lowest-charge phase in the phase train, are considered as noise and are disregarded when defining a phase train and identifying consecutive phases. For example, a pulse including two positive phases, then a very small short negative phase, and then additional phases, would be considered a positive phase train, because the small short negative phase is disregarded. As used herein, in the specification and in the claims section that follows, the term “phase train pulse” relates to a pulse including at least one positive phase train and at least one negative phase train. As used herein, in the specification and in the claims section that follows, the term “balanced phase train pulse” relates to a balanced pulse including at least one positive phase train and at least one negative phase train. As used herein, in the specification and in the claims section that follows, the term “singular pulse” relates to a pulse including a single positive phase and/or a single negative phase, and not including a phase train. It will be appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination. Similarly, the content of a claim depending from one or more particular claims may generally depend from the other, unspecified claims, or be combined with the content thereof, absent any specific, manifest incompatibility therebetween. Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. | 59,354 |
11857787 | DETAILED DESCRIPTION Aspects of the present invention are generally directed to a connector for a prosthesis configured to be worn behind the ear of an individual or recipient, commonly referred to as behind-the-ear (BTE) devices. BTE devices may be a component of a conventional hearing aid and/or cochlear implant, or a component of any other medical systems or prosthesis. BTE devices, whether implemented as a component of a hearing aid, cochlear implant, middle ear implant or other medical systems/prosthesis, are collectively and generally referred to herein as a BTE prosthetic devices. In certain aspects of the present invention, a BTE prosthetic device for use in a medical system or prosthesis, (collectively and generally referred to as medical systems herein) comprises a connector configured to mechanically attach an auxiliary device of the system to the BTE prosthetic device. The connector is electrically connected to a transceiver of the BTE prosthetic device. The transceiver may comprise any combination of a transmitter and/or a receiver. Furthermore, the transceiver may comprise only a transmitter or a receiver. The connector is configured to operate as an electromagnetic antenna for transmitting and/or receiving signals between the BTE prosthetic and other components of the medical system. The electromagnetic antenna may be, for example, operable in the far-field. As noted, embodiments of the present invention may be implemented with a number of BTE prosthetic devices in a variety of medical systems. Embodiments of the present invention will be described herein with reference to one specific type of BTE prosthetic device and medical system, namely a BTE prosthetic device which is a component of a partially implantable hearing aid system.FIG.1illustrates such a partially implantable hearing aid system, comprising BTE prosthetic device100in communication with one or more cochlear stimulating implants, shown generally as implants600and one or more remote units700. Implants600may each comprise a variety of implantable cochlear stimulating devices, such as an implantable electrode arrays, middle ear implants, or the like. As described in more detail below, BTE prosthetic device100may communicate with other components of the partially implantable hearing aid system via one or more wireless communication links, shown as communication links610,620,710,720,810and820. In the illustrated embodiment ofFIG.1, BTE prosthetic device100comprises a microphone101to receive acoustic sounds, and a signal processor110. BTE prosthetic device100converts and processes the received acoustic sounds received by microphone101, or various other received auditory signals, to a format which may be used by the implants600. In accordance with the illustrated embodiments, BTE prosthetic device100further comprises one or more transceivers108which may transmit processed signals to implants600. BTE prosthetic device100has sufficient persistent and non-persistent memory. Furthermore, BTE prosthetic device100is powered by a battery104. Additional controls102and interfaces103facilitate human interaction with the hearing aid system. In certain embodiments, the main housing of BTE prosthetic device100may accept removable plug-in modules, such as batteries, an ear hook, a headpiece, etc. BTE prosthetic device100may also be provided with input and output jacks105and106. As noted, a variety of cochlear stimulating implants may be used in accordance with embodiments of the present invention.FIG.1illustrates specific implants600which comprise an implantable electrode array640that stimulate the recipient's cochlea with electrical signals. The implant converts the signals received from the BTE prosthetic device100into stimuli signals and then applies them to the cochlea via electrode array640. Depending on cause of the recipient's deafness, implant600may optionally comprise a mechanical implantable actuator650configured to stimulate middle or inner ear parts, in addition to, or in place of, electrode array640. In embodiments of the present invention, BTE prosthetic device100comprises a lower radio frequency (RF) band transceiver108for wireless communication over a magnetic induction link, such as links810and820. Transceiver108may be configured to transmit and/or receive wireless communications. Low RF band transceiver108may be connected, in certain embodiments, to a connector socket109, which accepts a plug114of a headpiece116. Headpiece116comprises an extension cable115between plug114and an antenna coil or closed-wire loop116. Antenna coil116is configured to transmit signals to coil antenna630of an implant600, and/or receive signals from coil antenna630. Antennas116and630may be placed in close proximity of each other. The above-described communication link810and820between BTE prosthetic device100and implant600operates in the reactive near-field, by magnetic induction in a non-propagating quasi-static magnetic field. Both bidirectional data transfer and power transfer towards the implant are possible. In accordance with certain embodiments of the present invention, communication between components of a medical system may occur in a near-field or far EM-field, via, for example, electromagnetic field propagation. This type of communication has the advantage that it takes place over larger distances, which would permit components of the communication link to be spaced apart by larger distances than permitted in a conventional RF link. Furthermore, wireless communication between the BTE prosthetic device100and other external devices700may also preferably take place in the propagating far-field. An antenna tuned to the frequency range of operation is generally used for efficient communication using the EM-field. Whereas a magnetic induction link uses a coil or closed-wire antenna, transmission and reception by electromagnetic field propagation may be carried out with open-ended antennas. According to aspects of the present invention, an electromagnetic antenna is integrated with a mechanical connector which is used in BTE prosthetic device100to mechanically attach various components or other devices to the BTE prosthetic device. According to one embodiment of the invention, and referring toFIGS.1and2, an electromagnetic antenna can be incorporated into a connector, shown as connector170. In the specific illustrated embodiment ofFIGS.1and2, connector170of the BTE prosthetic device100is configured to mechanically attach an ear hook180to BTE prosthetic device100. Connector170may also be configured to operate as, or function as, as an electromagnetic antenna for transmission of, or reception of signals between BTE prosthetic device100and one or more other components of the implantable hearing system. Ear hook180provides a mounting means for holding BTE prosthetic device100behind the ear of the recipient. Connector170may include, for example, threaded attachment elements, a snap-lock or click-fit mechanism or any other removable mechanical fastening means now know or later developed for attaching connector170to BTE prosthetic device100. In certain embodiments, one or more conducting wires310provide an electrical coupling between connector170and components of BTE prosthetic device100, such as the printed circuit board of the BTE prosthetic device. As noted, connector170may also be configured for electrical connection with an auxiliary device. For example, connector170may be provided with, or comprise, for example, a socket accepting a plug410of an auxiliary device440, such as an earphone. Some possible embodiments of connector170are illustrated inFIG.3.FIG.3Aillustrates connector170as a coaxial electrical and mechanical connector type.FIG.3Billustrates connector170as a twin-axial electrical and mechanical connector type. In certain embodiments, connector170may comprise an outer body171which is cylindrical and may be made of an electrical conducting material. In the embodiments ofFIG.3A, coaxial connector170comprises one electrically conductive receptacle172, in addition to the conductive outer body171. Hence, the outer body171and the receptacle172, which are electrically shielded from each other, constitute an input or output jack for transmitting and/or receiving electrical signals, such as audio signals, to and from the attached auxiliary device440. Therefore, BTE prosthetic device100may comprise an audio or baseband transmitter and/or receiver (transceiver)150, linked at113to signal processor110. Audio/baseband transceiver150is connected to the outer body171and to the receptacle172of connector170. The outer body171is configured to operate as, or function as, as part of an electromagnetic antenna for transmitting or receiving signals. As noted, connector170may be used by BTE prosthetic device100to transmit, or receive signals from, one or more other components of the implantable hearing system. In certain embodiments, outer body171operates as an open-ended wire, a monopole, stub, helix or helical wound coil, meander or dipole electromagnetic antenna. The electromagnetic antenna is operable in a variety of frequency ranges, including above 100 KHz, and in some embodiments in a frequency range above 30 MHz or 3 GHZ. As such, in the illustrated embodiments, connector170is configured for electrical connection of an auxiliary device to BTE prosthetic device100and for transmission and/or reception of signals between components of the hearing aid system. BTE prosthetic device100may comprise an RF high band transceiver120, linked via link112to signal processor110. RF transceiver120is connected to the outer body171. In order to improve the reception or transmission of power efficiency of outer body171as an antenna, an impedance matching circuit130may be provided between transceiver120and outer body171. A high-pass or band-pass filter130and a low-pass or band-pass filter140ensure a separation of the radiated RF signals and the signals transferred over the jack combination171/172. Hence, filter140blocks high RF band signals and prevents them from propagating to the transceiver150and high-pass filter130blocks low band signals (e.g. audio, baseband) and prevents them from leaking into transceiver120. Connector170may comprise multiple separate electrical conduction paths for conductive transmission of electrical signals. Likewise, outer body171of connector170may or may not transfer electrical signals. In certain embodiments, connector170protrudes from BTE prosthetic device100. FIG.3Billustrates an additional embodiment of the present invention. As shown, the twin-axial connector170ofFIG.3Bcomprises two electrically conductive receptacles173, in addition to a conductive outer body171. Hence, the receptacles173, which are electrically shielded from each other, constitute a jack for transmitting and/or receiving electrical signals, such as audio signals, to and from an auxiliary device440attached thereto. Therefore, BTE prosthetic device100may comprise an audio or baseband transmitter and/or receiver (transceiver)150, linked at link113to signal processor110. Audio/baseband transceiver150is connected to the receptacles173. In the embodiments ofFIG.3B, the outer body171may operate as an electromagnetic antenna similar to that described above with reference toFIG.3A. Therefore, BTE prosthetic device100may comprise a high RF band transceiver120, linked at link112to signal processor110. RF transceiver120is connected to the outer body171. In certain embodiments, to improve receive or transmit power efficiency of the antenna, an impedance matching circuit130is provided between transceiver120and the antenna (outer body)171for making the impedance of the antenna, as seen by the transceiver, real. A high-pass or band-pass filter130and a low-pass or band-pass filter140may ensure a separation of the radiated RF signals and the signals transferred over the jack173. The low-pass and high-pass filters may be optional in the case ofFIG.3B, as the two types of signals (to/from transceivers150and120) may not share the same electrical paths as in the case ofFIG.3A. However, radiated RF signals may be captured by the receptacles173and may interfere with the operation of the baseband transceiver150. Likewise, the antenna171may capture low band signals. Hence, filter140blocks high RF band signals and prevents them from propagating to the transceiver150and high-pass filter130blocks low band signals and prevents them from leaking to transceiver120. A low band signal preferably comprises frequencies below or equal to about 100 KHz, while high RF band signals comprise signals situated in the radio spectrum above 100 KHz, such as, for example, 2.4 GHz. For the purposes of the present invention, high RF band signals are signals in the VHF (very high frequency), UHF (ultra high frequency), or higher frequency range. The low-pass filter140and the high-pass filter130may function as a band diplexer. The antenna170may be arranged to transmit or receive data such as telemetry, control data, signaling data and audio streaming. FIG.4illustrates a possible implementation of the impedance matching circuit and high-pass filter130and the low-pass filter140in accordance with embodiments of the present invention. As shown inFIG.4, such filters may comprise, for example, lumped resistors, capacitors and inductors, or other elements now know or later developed, the values of which may be chosen in function of the operating frequencies of the devices. The audio or baseband signals applied to or received from the auxiliary device are much lower in frequency than the RF signals radiated by the antenna. A third-order filtering may be sufficient in most cases. Antenna impedance matching circuit130may be used to alter the effective electrical length of an antenna by matching it with additional capacitance or inductance. Antenna impedance matching circuit130tunes the radiating system of the antenna at the operational radio frequency, in order to obtain resonance. In one such case, the RF transceiver120sees the antenna as a purely resistive load. Such a matching circuit is optional. As noted, antenna171may operate as an open-ended wire antenna, such as a monopole, a dipole, a groundplane, a helix, a helical wound, or a meander antenna.FIG.5shows a simplified representation of a quarter λ, a ⅝λ and a matched groundplane antenna. The physical construction of antenna171of the present invention can be considered as a groundplane antenna, with the housing of BTE prosthetic device or its printed circuit board as ground plane element and the connector170as radiating or receiving element. From an antenna-matching viewpoint, it is preferable to choose the total physical length of the antenna (e.g. the length of the outer body171of connector170) to λ/4 or ⅝λ with λ the wavelength of the operating frequency of the antenna. When the wavelength is very small, e.g. at 2.4 GHz, antenna matching is performed on the connector170. At lower frequencies, an antenna with increased physical length is used. This may be achieved by incorporating, for example, into the auxiliary device which is attached to the BTE prosthetic device, an extension of antenna170. Such an arrangement is illustrated inFIG.1with device300. In the illustrated embodiments, device300comprises all elements necessary for operation as an electromagnetic antenna, such as a ground plane and radiating/receiving elements. As such, device300is referred to as an auxiliary antenna device. The auxiliary antenna device300may be removably attached to the BTE prosthetic device100and comprises a connector plug410for acceptance by connector170, the auxiliary device440, a lead430between connector and auxiliary device and an optional antenna impedance matching circuit420. The lead430is a naturally preferred object for use as radiating/receiving element and lends itself as an extension of antenna170. When auxiliary antenna device300is coupled to connector antenna170, an antenna500is obtained with increased length over the antenna provided by connector antenna170alone. The total physical length of antenna500is the sum of the length Lm of the connector170(base antenna) and the length La of auxiliary antenna300. The auxiliary antenna device300may comprise a matching circuit420in additional to the matching circuit130of connector170. The integration of a removable auxiliary antenna allows to improve radiating efficiency due to a physical extension of the radiating element. The auxiliary antenna devices300may allow antennas matched for different operating frequencies. The auxiliary antenna devices300may additionally allow antennas of different physical lengths for a same operating frequency. In the latter case, because of the different physical lengths, different impedance matching circuits should be implemented. Such embodiments, allow BTE prosthetic device100to be very versatile in the field of wireless communication and communicate with different devices over different RF bands. FIGS.6A and6Bgenerally illustrates the components of auxiliary antenna device300in accordance with certain embodiments. Coaxial connector plug410ofFIG.6Ais arranged for fitting into coaxial connector socket170ofFIG.3A. The twin-axial connector plug410is configured to fit into twin-axial connector socket170ofFIG.3B. A lead430comprising two or more conductive wires links connector plug410and impedance matching circuit420, such as any of those shown inFIG.4, to the auxiliary device440. Lead430may conduct low-band electrical signals (e.g. audio signals) from BTE prosthetic device100to the auxiliary device440or vice versa. In the case of a coaxial connector system200, comprising socket170and plug410(FIGS.3aand6a), electrical connection with BTE prosthetic device100is obtained by electrical contact between receptacle172and plug412, and between the outer bodies171and411of the connectors. In the case of a twin-axial connector system200, comprising socket170and plug410(FIGS.3band6b), the electrical connection with the BTE prosthetic device is obtained by electrical contact between the two receptacles173and plugs413, and optionally additionally between the outer bodies171and411of the connectors. Returning toFIG.1, antenna170, or the extended antenna500, allows wireless communication in a radio frequency band between a BTE prosthetic device100and remote devices. Such devices may be a remote control unit700, provided with an antenna760for wireless communication in the same frequency band. A bidirectional wireless communication link710,720may be established between BTE prosthetic device100and remote control unit700. The BTE prosthetic device100may also communicate wirelessly with cochlear implant600, both through a magnetic induction link810,820by aid of headpiece116, and through a radio frequency electromagnetic link610,620by the use of antennas500or170of the BTE prosthetic device and RF antenna660of the cochlear implant. FIG.7illustrates an additional embodiment for an auxiliary antenna device450for use as extension of antenna170. Antenna450is constituted by a helically wound antenna, and is incorporated into ear hook180. In accordance with certain embodiments, an auxiliary device may comprise an external plug-in device, such as an in-the-ear speaker. According to other aspects of the present invention, an antenna device comprises a second connector for fitting into the connector of BTE prosthetic device100, an impedance matching circuit and a lead. The impedance matching circuit is tuned to the impedance of the lead, whereby the lead is operable as an extension of the electromagnetic antenna. The second connector is the counterpart of the connector of the hearing aid device. The second connector may be a plug or a socket. The antenna in accordance with embodiments of the present invention is not only restricted to connector170of an ear hook.FIG.8shows an alternative embodiment of the present invention wherein the antenna is incorporated into connector socket109of headpiece116. In such embodiments, connector socket109may be implemented in a substantially similar manner as that described above with reference to connector socket170. In the specific embodiments in which headpiece116is additionally used as an auxiliary RF antenna device, the removable device300may comprise an auxiliary connector410arranged for being accepted by connector109, an impedance matching unit420and a headpiece116, connected to the auxiliary connector410by a lead comprising two or more wires. As discussed above with reference toFIG.1, the BTE prosthetic device100may communicate wirelessly with an implant600, which is provided with both a magnetic induction coil antenna630and an RF EM-field antenna660. Coil antenna630may communicate with headpiece116when closely coupled. Communication over RF antennas 500and660may be established simultaneously, or consecutively in time with the communication over antennas116and630. In the case that an implant, such as implant800, is not provided with an RF antenna, wireless communication between BTE prosthetic device100and cochlear implant800may be established over a magnetic induction link810,820using coil antennas116and830, e.g. for transmitting stimuli signals to an electrode array840and/or actuator850. Simultaneously, the BTE prosthetic device may communicate over antenna500with other devices, such as remote control unit700. While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of example only, and not limitation. It will be apparent to persons skilled in the relevant art that various changes in form and detail can be made therein without departing from the spirit and scope of the invention. Thus, the breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents. For example, as one of ordinary skill in the art would appreciate, the present invention provides improved or at least alternative wireless communication possibilities compared to prior art devices and wireless communication methods. Active implantable medical devices envisaged by the present invention include, but are not limited to, cochlear implants, nerve stimulators, pace makers, glucose meters, and any other type of active implantable medical device requiring wireless communication. U.S. Provisional Patent Application No. 60/924,800, filed on May 31, 2007, and U.S. Provisional Application No. 60/924,807, filed on May 31, 2007, are hereby incorporated by reference in their entirely herein. Similarly, all other patents and publications discussed herein are incorporated in their entirety by reference thereto. The term “medical device” can refer to any instrument, apparatus, appliance, material or other article, whether used alone or in combination, together with any accessories or software for its proper functioning, intended to be used for human beings to, for example, diagnosis, prevention, monitoring, treatment or alleviation of disease or injury; to investigate, replace or modify of the anatomy or of a physiological process; or to control of conception, and which does not achieve its principal intended action by pharmacological, chemical, immunological or metabolic means, but which may be assisted in its function by such means. An ‘active medical device’ means any medical device relying for its functioning on a source of electrical energy or any source of power other than that directly generated by the human body or gravity. An ‘active implantable medical device’ is any active medical device which is intended to be totally or partially introduced, surgically or medically, into the human body or by medical intervention into a natural orifice, and which is intended to remain after the procedure. The increased use of wireless communication in and miniaturization of active implantable medical devices (AIMDs) demands innovative, consistent and reliable designs of radio frequency (RF) system blocks and antennas. Antennas should be placed by preference outside any electrical or ferromagnetic shielding encapsulation to obtain a high efficiency in power transfer and high reliability in data transfer. The antenna characteristics for receiving energy are essentially the same as for sending due to antenna reciprocity. AIMDs are often shielded with a screening of titanium or other biocompatible material to decrease their vulnerability for trauma. The titanium RF shielding forces to position any type of antenna outside its shielding encapsulation. A time-varying electrical current flowing in an antenna produces a corresponding electromagnetic field configuration that propagates through space in the form of electromagnetic waves. The total field configuration produced by an antenna can be decomposed into a far-field component, where the magnitudes of the electric and magnetic fields vary inversely with the distance from the antenna, and a near-field component with field magnitudes varying inversely with higher powers of the distance. The field configuration in the immediate vicinity of the antenna is primarily due to the near-field component (e.g. MI radio, Near Field Communication), while the field configuration at greater distances is due solely to the far-field component, also known as the electromagnetic far field propagation (electromagnetic radiation). The EM far field propagation can be physical explained by the decomposed E-field and H-field components of the EM field, maintaining each other and forming planar waves. The MI field is a non-propagating quasi-static magnetic field and has a very high field roll-off behaviour as a function of distance. Hence, the MI field is relevant only in the near-field. The electromagnetic (EM) field may be decomposed into a near-field component and a far-field component. The power of a plane wave in the EM far-field rolls off as one over the distance from the source squared. The EM near-field may further be decomposed into an EM reactive near-field and an EM radiating near-field. For the purpose of the present invention, the term “far-field” bears the meaning of “EM far-field”, the term “near-field” may mean both an MI near-field and an EM near-field and the term “reactive near-field” may mean both an MI field and a reactive EM near-field. A common type of antenna for active implantable medical devices is the coil antenna, also referred as closed-wire or loop antenna. An external coil antenna is coupled to the coil antenna of the implant to transfer upstream or downstream any required data such as telemetry, control data, signaling data and audio streaming. The data transfer with those types of antennas occurs in the MI near-field and at lower frequencies (<15 MHz). In the MI near-field coil antennas are closely coupled and may also provide the AIMD with a power supply which enables operation or enables to charge an implanted battery if present. U.S. Pat. No. 6,766,201 discloses an implantable medical device, such as a cardiac pacemaker, utilizing EM far-field data transfer by electromagnetic field propagation. Communication using far-field radiation can take place over much greater distances and makes the communication between the implant and external devices more convenient. The antenna of the implant is a classical open-ended monopole or dipole antenna. Communication in the far-field classically utilizes an open-ended antenna tuned at a higher frequency band (typically >>50 MHz), such as a monopole or dipole antenna, relying on the propagating electromagnetic field characteristics. An open-ended wire antenna most efficiently radiates energy if the length of the antenna is the sum of a quarter wavelength and an integral number of half-wavelengths of the driving signal. A dipole antenna, for example, is a conductor which has a total length equal to half the wavelength of the driving signal with its feed point in the middle. A monopole antenna can be a conductor with a length equal to one-quarter the wavelength of the driving signal situated with respect to a reflecting ground plane so that the total emitted and reflected field configuration resembles that of the dipole antenna. As will be discussed below, an antenna matching circuit may be used to alter the effective electrical length of an antenna by adapting it with additional capacitance or inductance. U.S. Pat. No. 6,924,773 discloses an integrated dual band antenna, to be used externally to a recipient's body and which combines a magnetic induction shielded loop antenna and an electromagnetic radiation antenna. The shielded loop antenna may be used for communicating with an AIMD, while the electromagnetic radiation antenna is used for wireless communication with other external devices. The integration of both types of antennas is achieved by unshielding a part of the shielded loop antenna, inserting a low-pass filter and connecting the electromagnetic radiation antenna, provided with a high-pass filter, to said unshielded part. The active implantable medical devices of the prior art either comprise means for wireless communication in the near-field (by magnetic induction) or means for wireless communication in the electromagnetic field. In the prior art, the problem of applying a wireless communication link with a medical implant both in the MI near-field and in the EM field is not tackled. Far-field communication may occur at higher frequency bands, which opens new possibilities and has additional benefits. The additional placement of open-ended antennas next to the existing MI coil antennas outside the encapsulated shielded body of the AIMD to exploit the higher frequency bands would increase the AIMD size and probably decrease reliability. Moreover, as both antennas would have to be provided outside of the shielding encapsulation of the AIMD, this would result in an increased number of through-passages in the encapsulation for the antenna leads. Providing a leak-tight closure at these passages, around the antenna leads is a difficult matter. In accordance with one embodiment of the present invention, an active implantable medical device is disclosed, comprising: an antenna and a band diplexer connected to the antenna, wherein the band diplexer comprises first filter means for a first signal to be transmitted and/or received in a first RF band and second filter means for a second signal to be transmitted and/or received in a second RF band, the second RF band being higher in frequency than the first RF band. The present invention is related to active implantable medical devices and methods of wireless communication between external devices and said active implantable medical devices, which provide improved or at least alternative wireless communication possibilities compared to prior art devices and wireless communication methods. Active implantable medical devices envisaged by the present invention are: cochlear implants, nerve stimulators, pace makers, glucose meters, and any other type of active implantable medical device requiring wireless communication. According to a first aspect of the invention, there is provided an active implantable medical device comprising an antenna and a band diplexer connected to said antenna. The band diplexer comprises first filter means for a first signal to be transmitted and/or received in a first RF band and second filter means for a second signal to be transmitted and/or received in a second RF band, said second RF band being higher in frequency than said first RF band. Preferably, the antenna comprises one or multiple windings. More preferably, the antenna is a closed-wire antenna. Preferably, the first filter means are connected in differential mode to the antenna and the second filter means are connected in common mode to the antenna. Preferably, in the active implantable medical device according to the invention, the first signal is applied to the antenna in differential mode and the second signal is applied to the antenna in common mode. More preferably, the first signal is a reactive near-field signal and the second signal is a far-field signal. Preferably, the antenna is arranged to transmit and/or receive the first signal over an MI near-field and arranged to transmit and/or receive the second signal over a radiating near-field or EM far-field. Preferably, the antenna is arranged to operate simultaneously for transmitting or receiving the first signal and transmitting or receiving the second signal. Preferably, the active implantable medical device according to the invention comprises: a first device arranged to receive said first signal in the first RF band and connected to said band diplexer, and a second device arranged to transmit said second signal in a second RF band and connected to said band diplexer. More preferably, the first device is connected to the band diplexer in differential mode and the second device is connected to the band diplexer in common mode. Even more preferably, in the active implantable medical device according to the invention the first device is further arranged for transmitting in the first RF band and the second device is further arranged for receiving in the second RF band. In a preferred embodiment of the active implantable medical device according to the invention, both the first and the second devices are arranged for transferring unidirectionally power from said antenna towards the active implantable medical device using the reactive near-field. Preferably, the second device is arranged to indicate MI and/or EM field level or radio signal strength. Preferably, in the active implantable medical device according to the invention, the frequencies of the first RF band are below or equal to 30 MHz and the frequencies of the second RF band are above 30 MHz. More preferably, the frequencies of the second RF band are above 50 MHz, even more preferably above 100 MHz. Preferably, the first signal is analogue and/or digital and the second signal is analogue and/or digital. Preferably, the active implantable medical device according to the invention comprises an antenna matching unit arranged for impedance matching said antenna to an open-ended antenna for operation in the second RF band. The antenna matching unit is preferably connected to said band diplexer. Preferably, in the active implantable medical device according to the invention, the first and/or second signal comprises one or more data from the group consisting of: telemetry, control data, signaling data and audio streaming. According to a preferred embodiment, the active implantable medical device of the invention is a cochlear implant. According to a second aspect of the invention, there is provided an external hearing aid device, comprising an antenna system and a band diplexer connected to said antenna system. Said band diplexer comprises first filter means for a first signal to be transmitted and/or received in a first RF band and second filter means for a second signal to be transmitted and/or received in a second RF band. Said second RF band is higher in frequency than said first RF band. Preferably, in the external hearing aid device according to the invention, the antenna system comprises a closed-wire antenna. More preferably, the first signal is applied to the antenna in differential mode and the second signal is applied to the antenna in common mode. According to a third aspect of the invention, there is provided a hearing aid system comprising: a cochlear implant of the invention and one or more external devices according to the invention. Preferably, said one or more external devices comprise a sound processor device for behind the ear (BTE device). The sound processor device may process (i.e. filter, encode, etc.) airborne auditory signals captured by a microphone and convert them into stimuli signals suitable for use with the cochlear implant. The converted signals are transferred via a transcutaneous link to the cochlear implant. More preferably, the sound processor device for behind the ear comprises a connector for a closed-wire antenna external to said device for behind the ear for transcutaneous power transfer to the cochlear implant. Preferably, in the hearing aid system according to the invention, said one or more external devices comprise a device for in the ear canal of a recipient. Preferably, in the hearing aid system according to the invention, said one or more external devices comprise a remote control or handheld device. According to a fourth aspect of the invention, there is provided a method of bidirectional wireless communication between an active implantable medical device and an external device, comprising the steps of: communicating unidirectionally from the external device to the implantable medical device over a first wireless link in a first RF band in the MI near-field and communicating unidirectionally from the implantable medical device to the external device over a second wireless link in a second RF band in the EM-field, preferably the EM far field. According to a fifth aspect of the invention, there is provided a method of bidirectional wireless communication between an external hearing aid device and a second external device, comprising the steps of: communicating unidirectionally from the second external device to the external hearing aid device over a first wireless link in a first RF band in the MI near-field and communicating unidirectionally from the external hearing aid device to the second external device over a second wireless link in a second RF band in the EM-field, preferably the EM far field. Preferably, in the methods according to the invention, said second RF band is higher in frequency than said first RF band. Embodiments of the present invention will now be described in detail with reference to the attached figures, the invention is not limited thereto but only by the claims. The drawings described are only schematic and are non-limiting. In the drawings, the size of some of the elements may be exaggerated and not drawn on scale for illustrative purposes. The dimensions and the relative dimensions do not necessarily correspond to actual reductions to practice of the invention. Those skilled in the art can recognize numerous variations and modifications of this invention that are encompassed by its scope. Accordingly, the description of preferred embodiments should not be deemed to limit the scope of the present invention. Furthermore, the terms first, second and the like in the description and in the claims are used for distinguishing between similar elements and not necessarily for describing a sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein. Moreover, the terms top, bottom, left, right, over, under and the like in the description and the claims are used for descriptive purposes and not necessarily for describing relative positions. The terms so used are interchangeable under appropriate circumstances and the embodiments of the invention described herein can operate in other orientations than described or illustrated herein. For example “left” and “right” from an element indicates being located at opposite sides of this element. It is to be noticed that the term “comprising”, used in the claims, should not be interpreted as being restricted to the means listed thereafter; it does not exclude other elements or steps. Thus, the scope of the expression “a device comprising means A and B” should not be limited to devices consisting only of components A and B. It means that with respect to the present invention, the only relevant components of the device are A and B. The present invention overcomes the shortcomings of prior art devices by integrating an open-ended (EM-field) antenna into a closed-wire (near-field) antenna so as to obtain one single physical antenna which is able to operate over two separate frequency bands. The combined antenna of the invention allows to establish bidirectional data communication links over a first, lower radio frequency band and over a second, upper radio frequency band. The two bands may be used simultaneously or consecutively in time for bidirectional communication between the AIMD and external devices operating in the lower RF band and the upper RF band. In an equally preferred embodiment of the invention, the combined antenna allows to establish a forward unidirectional data communication link over a first, lower RF band (e.g. towards an AIMD) and a backward unidirectional data communication link over a second, upper RF band (e.g. from the AIMD towards an external device). The first, lower radio frequency band lies preferably below 30 MHz, more preferably below 15 MHz. The second, upper frequency band lies preferably well above 15 MHz, more preferably well above 50 MHz (e.g. on the order of a few GHz). For the purposes of the present invention, the upper RF band signals are signals in the VHF (very high frequency), UHF (ultra high frequency), or higher frequency range. FIG.9shows an implantable antenna for an active implantable medical device1100. The antenna is physically formed by a closed electrical loop with one or multiple windings1160. The antenna has both the properties of a closed-wire loop antenna and of an open-ended wire antenna. The antenna is provided outside of a shielding encapsulation1150of the AIMD and is implanted beneath the skin200of a recipient. In order to perform its dual band role, the antenna1160is connected to a band diplexer1140. The antenna1160operates furthermore in combination with a ground plane1150, which may be the shielding encapsulation1150, an open-ended antenna matching unit1120, an upper band transceiver1110and lower band transceiver1130. A transceiver comprises a receiver and transmitter and processes the radio frequency signals that are received or that are to be transmitted. Transceivers1110and1130may be provided with inputs and outputs for receiving and transmitting analogue data, inputs and outputs for receiving and transmitting digital data and with an output for transmitting power signals to the implant. Either one or both the transceivers may also be a receiver or a transmitter only. For communication over the upper RF band, the antenna behaves as a kind of monopole element with an asymmetrical RF power hot-feed point at both coil ends and feeder ground attached to the ground plane1150. The ground plane could be the electrical shielding of the implant encapsulation or any printed circuit board (PCB) ground if the implant encapsulation is unshielded. The matching unit1120puts the antenna system for the upper RF band into resonance and optimum impedance. For communication over the lower RF band, the antenna behaves as a closed-wire loop preferably with a symmetrical feed point. A current from the lower RF band transmitter1130through the coil1160generates a magnetic field. The Biot-Savart law describes this magnetic field set up due to a steady flowing line current in a current wire element or steady current density (magneto-statics). The signal applied to the lower RF band receiver1130is a voltage induced in the loops of the coil1160that is proportional to the change of magnetic flux. This is based on Faraday's law. The band diplexer1140comprises a filter for the upper radio frequency band, such as a high-pass or a band-pass filter and a filter for the lower radio frequency band, such as a low-pass or a band-pass filter. That creates a separation or isolation between the low RF signals (lower RF band) and the high RF signals (upper RF band). This allows simultaneous operation over both frequency bands. Transmitted signals1510from the upper RF band transmitter1110towards external devices1600will not interfere with signals1320from external devices1400working in the lower RF band towards the lower RF band receiver1130. Transmitted signals1310from the lower RF band transmitter1130towards external devices1400will not interfere with signals1520from external devices1600working in the upper RF band towards the upper RF band receiver1110. This signal separation is illustrated inFIG.10as a frequency-amplitude characteristic. Referring toFIG.11, the band diplexer1140comprises upper RF band coupling elements, preferably two low-valued capacitors1144. These will block the lower RF signals for the upper RF transceiver system1110. Additionally, the band diplexer1140comprises lower RF band coupling elements, preferably two low-valued inductors1142. These will block the upper RF signals for the lower RF transceiver system1130. Optionally, a capacitor1141can be used to obtain resonance at the lower RF band for improving power and data transfer efficiency. The value of the capacitors and the inductors and other electrical elements may be chosen in function of the frequency bands used. A major benefit using this band diplexer topology is the existence of a common and differential mode. The differential mode is used for the closed-wire antenna system in the lower RF band, whereas the common mode is used for the open-ended antenna system in the upper RF band. Because of the different modes of operation, additional electrical isolation between the two transceiver systems1110and1130can be obtained. The communication link over the lower RF band (1310and1320ofFIG.9) is based on magnetic induction and is preferably below 30 MHz, more preferably below 15 MHz. This link utilizes the non-propagating quasi-static magnetic field. The magnetic field has a very high roll-off behavior as a function of distance. The communication link over the upper RF band (1510and1520ofFIG.9) is based on electromagnetic field propagation and is preferably higher than 30 MHz, more preferably much higher than 50 MHz. The power of a plane wave in the far-field rolls off as one over the distance from the source squared. The medical implant device1100is able to communicate wirelessly with other devices over an upper RF band and a lower RF band, simultaneously or consecutively in time. The communication link over the lower RF band is a magnetic induction link, operating in the reactive near-field. The communication link over the upper RF band may operate in the reactive near-field, the radiating near-field and/or in the propagating far-field. Operation in the reactive near-field necessitates that the antennas of the implant and the communicating device be arranged in close proximity. A power transfer from external devices1400and1600, operating in the reactive near-field at respectively lower RF bands and upper RF bands towards the AIMD1100, over the lower RF band1320or upper RF band1520, can be established with a coil antenna1160connected to a band diplexer1140, in combination with a ground plane for the upper RF band1150, an open-ended antenna-matching unit1120, an upper band transceiver1110and a lower band transceiver1130. In the reactive near-field, where coils are magnetically closely coupled, the external device1400could transfer sufficient power over the lower frequency band1320towards the AIMD to provide the implant with electrical energy enabling operation or charging of its implanted battery if present. According to another aspect of the invention, an external device may communicate with an active implantable medical device1100of the invention over a first, lower radio-frequency band and/or a second, upper radio frequency band. Referring toFIG.12andFIG.13, the communication link between implant device1100and external device1401over the lower RF band (1310,1320) is based on magnetic induction. The lower RF band communication link1310and1320utilizes the non-propagating quasi-static magnetic field (reactive near-field). The communication link1510and1520over the upper RF band may operate in the near-field and/or in the propagating far-field (electromagnetic field propagation). FIG.12shows an antenna1180for an external device1401(e.g. a behind-the-ear device), physically formed by a closed electrical loop with one or multiple windings. Antenna1180has the properties of both a closed-wire loop antenna and an open-ended wire antenna. The antenna1180is connected to a band diplexer2140. The antenna1180operates furthermore in combination with a ground plane2150, an open-ended antenna matching unit2120, an upper band transceiver2110and lower band transceiver2130. The ground plane can be the electrical shielding of the encapsulation of external device1401or a printed circuit board ground. The configuration of the band diplexer2140and antenna matching unit2120may be similar to that of band diplexer1140and antenna matching unit1120of the implant1100. Hence, band diplexer2140may comprise a filter for the lower RF band signals (differential mode signals) and a filter for the upper RF band signals (common mode signals). The antenna1180allows to establish bidirectional data communication links over a first, lower radio frequency band (1310,1320) and over a second, upper radio frequency band (1510,1520). The two bands may be used simultaneously or consecutively in time for bidirectional communication between external device1401and the AIMD1100or other devices. In order to use the lower RF band magnetic induction link, the antenna1180of the external device should preferably be located at short range of antenna1160. Lower RF band transceiver2130may be a transmitter or receiver only. Upper RF band transceiver2110may be a transmitter or receiver only. As shown inFIG.13, in order to communicate with the AIMD1100of the invention, an external device should comprise either one or both antennas1480or1610. Antenna1480is a closed-wire antenna and operates in a lower RF band according to a non-propagating quasi-static magnetic field (magnetic induction). Closed-wire antenna1480is connected to a closed-wire antenna matching unit2145for adjusting the impedance and resonance of the antenna and with a lower RF band transceiver2130. Transceiver2130may also be a transmitter or a receiver only. Antenna1610is an open-ended antenna and operates in a higher RF band according to electromagnetic field propagation. Open-ended antenna1610is connected to an open-ended antenna matching unit2120and to an upper RF band transceiver2110. Transceiver2110may also be a receiver or a transmitter only. The open-ended wire antenna1610operates in combination with a ground plane2150and may be a monopole, stub, helix or helical wound coil, meander or dipole antenna. In case of a dipole antenna, the use of a ground plane2150becomes optional. Transceivers2110and2130may be provided with inputs and outputs for receiving and transmitting analogue data, inputs and outputs for receiving and transmitting digital data and with an input for transmitting power signals to the implant. FIG.14illustrates an embodiment of the AIMD of the invention as a cochlear implant1100in a hearing aid system. The cochlear implant1100is an implantable hearing aid device comprising a cochlea stimulating electrode1170that stimulates by applying electrical signals the auditory nerves of the cochlea or brainstem. Depending on cause of recipient's deafness, a mechanical implantable actuator stimulating middle or inner parts of the ear can be placed in conjunction or as alternative. The cochlear implant is implanted beneath the human skin, near the left or right ear. The cochlear implant comprises a combined open-ended and closed-wire antenna1160, and an implantable battery (not shown). The implant communicates with several external devices (1401,1601,1602,1603) as summed hereafter. A first type of external device is behind-the-ear (BTE) device1401, which comprises a dual-band coil antenna1180according to the one ofFIG.12. Antenna1180is a combined open-ended and closed-wire antenna similar to the principle of the combined coil antenna of an implant. BTE device1401allows wireless bidirectional data transfer (1310,1320) over the lower RF band. Therefore, either coil antenna1180or headpiece1470may be used. Coil antenna1180creates a magnetic induction link with the dual-band coil antenna1160of the implant. Headpiece1470is a coil antenna, which may be connected externally to the BTE device1401. This allows to attach headpiece1470in close proximity to the combined coil antenna1160of the implant device1100. Attachment or fixation between headpiece1470and antenna coil1160of the implant may be done by a permanent magnet. Headpiece1470is particularly useful for wireless transcutaneous power transfer over the lower frequency band1320. The behind-the-ear device1401may further comprise a microphone system1440, human interface controls and buttons1420, a small display1430, in-the-ear speaker1460, digital and analogue inputs and outputs1450, signal processing circuits, memory and batteries. A second type of behind-the-ear device1601is capable of communicating wirelessly over an upper RF band. The bidirectional data transfer over that upper RF band uses electromagnetic field propagation (1510,1520). Therefore, BTE device1601comprises an open-ended antenna1610, e.g. of monopole or dipole type. BTE device1601may further comprise a microphone system1640, human interface controls and buttons1620, a small display1630, an in-the-ear speaker1660, digital and analogue inputs and outputs1650, signal processing circuits, memory and batteries. BTE device1401may equally well act as BTE device1601, as it comprises a dual band antenna1180of the invention. Another type of external device is a remote control or handheld device1602, which incorporates a receiver and transmitter system with antenna1610for bidirectional wireless communication (1510,1520) in the upper RF band. The remote control1602may comprise a microphone system1640, human interface controls and buttons1620, a display1630, digital and analogue inputs and outputs1650, signal processing circuits, memory and batteries. An additional type of external device is an in-the-ear device1603, comprising a transmitter system with antenna1610for unidirectional wireless communication1520in the upper RF band. The in-the-ear device1603may comprise a microphone system, human interface controls and buttons, signal processing circuits, memory and batteries. The radiating elements (antennas)1610of the second type of behind-the-ear device1601, the remote control1602and in-the-ear device1603are open-ended wire antennas such as monopole, stub, helix or helical wound coil, meander or dipole antennas. In case of a dipole antenna, no ground plane is needed. FIG.15illustrates other system combinations. A remote control1402, a BTE device1403and an in-the-ear device1404may communicate uni- or bidirectionally with implant1100over a lower RF band by using a coil antenna1480to create a magnetic induction link with the dual-band coil antenna1160of the implant. Therefore, remote control1402, BTE device1403and in-the-ear device1404each comprise a closed-wire antenna1480for wireless communication over a lower RF band. Since the implant can operate simultaneously in the lower and upper RF bands by implementation of two transceivers, bilateral or binaural communication between two BTEs or even two implants is supported in one RF band, whilst having a supplementary communication link in the other RF band. External devices1401,1402,1403and1404may also communicate with each other via the lower RF link. External devices1601,1602,1603may communicate with each other via the upper RF link. A remote unit1402or1602may communicate with the implant1100via a BTE device1401or respectively1403or1601. Bilateral communication comprises telemetry, control data, signaling data and audio streaming. The wireless communication links of the present invention may be used for controlling and programming medical implant devices. The two-band communication capabilities of the implant devices of the invention allow to obtain an energy optimization. Battery cells supply all kinds of implant devices with power, providing the recipient with limited duration autonomy. Since recipients and the market demand for longer system autonomy and miniaturization, an optimized design of the wireless communication link with very low power consumption is required. According to an additional aspect of the invention, a method of wireless communication is provided between any AIMD of the invention and an external device, such as a remote control unit or a remote programmable unit. The present method allows to reduce energy consumption of the AIMD. According to the method, the forward wireless communication from the external device to the AIMD operates over the lower band magnetic induction. link (near-field communication) and the backward wireless communication from the AIMD to the external device operates over the upper band electromagnetic field propagation link (far-field communication). Over a long range, an EM-field wireless communication uses a lower amount of energy resources than an MI field wireless communication. Hence, the method allows to reduce power consumption of the AIMD of the invention. Furthermore, in case that the forward communication takes place over the magnetic induction link only, an upper RF band receiver is not required on the AIMD. In case that the backward communication takes place over the electromagnetic field propagation link only, a magnetic induction transmitter is not required on the AIMD. This allows to save space on the AIMD. According to a further aspect of the invention, a method of wireless communication is provided between a fitting system and a hearing aid system. Since recipients of hearing aid systems have different auditory defects, each hearing aid device must be adjusted, “fitted” or “mapped” specifically to an individual's needs and his/her responses to sound. This fitting process requires an initial appointment with an audiologist at a clinical implant centre. The fitting process adjusts the “map” as the brain adapts to incoming sound. Wireless fitting or mapping offers benefit to the audiologist and to the recipients, especially when the recipient is a child. The method of the invention optimizes the power consumption at recipient's side during fitting sessions by selecting a dedicated wireless technology for forward link and another dedicated wireless technology for back-data link. The fitting system generally is a remote, external programmable unit, such as a PC, provided with a wireless communication link with the recipient's hearing aid system. The remote programmable unit can easily increase the magnetic field presented to the target devices (BTE device or cochlear implant). This reduces amplification and power consumption for the target (hearing aid) device. By way of example, the remote programming unit (RPU) is capable of supplying more power to its MI transmitter because the RPU is connected to the mains (electrical wired power distribution 110 Vac/230 Vac) and hence has the availability of quasi unlimited power. The power consumption of the transceiver of the hearing aid system (e.g. transceiver2110) hence can be made much lower than the power consumption of the transceiver of the fitting or RPU system. Moreover, due to the increased magnetic field, the target device need not be equipped with a highly selective receiving filter for the MI receiver, because a third party's MI interference field is strongly attenuated (inversely proportional to r3). This allows to save space on the target device (BTE device, cochlear implant). A further reduction in power consumption of the target device—the hearing aid device (e.g. a BTE device or a cochlear implant)—can be obtained by having the forward wireless communication link from the fitting system to the hearing aid device established through magnetic induction (near-field communication) and the backward wireless communication link from the hearing aid device to the fitting system established through electromagnetic field propagation (far-field communication). Moreover, in case the far-field communication is always established unidirectionally (i.e. backward), a far-field receiver and selective receiving filter may be absent on the hearing aid device. This allows to save space on the BTE device or the cochlear implant. The method of the invention can equally be applied more in general to BTE devices of the invention. In the case of wireless communication between a BTE device and a second external device, such as a remote control unit or a remote programmable unit, the forward wireless communication from the second external device to the BTE device operates over the lower band magnetic induction link (near-field communication) and the backward wireless communication from the BTE device to the second external device operates over the upper band electromagnetic field propagation link (far-field communication). Hence, the method also allows to reduce power consumption of the BTE device of the invention. Furthermore, in case that forward communication takes place over the magnetic induction link only, an upper RF band receiver is not required on the BTE device. In case that backward communication takes place over the electromagnetic field propagation link only, a magnetic induction transmitter is not required on the BTE device. This allows to save space on the BTE device. Primary benefits of different embodiments of the present invention may or may not include: One and the same coil is used for two simultaneous links of different type. Two antennas integrated in one component, this saves space. Additional electrical RF isolation between diplexer transceiver ports is obtained due to common and differential mode operation. Band diplexer contains physical small surface mount (SMT) elements, since the capacitor and inductance values are very small, e.g. 10 pF and 100 nH for lumped elements. Implanted battery can be charged over the lower RF band simultaneously in time with a bidirectional communication link in the upper RF band. Coexistence and simultaneous operation between the existing 5 MHz power/data link and any other wireless external devices. Magnetic induction technology is most optimized for power transfer towards the implant and bidirectional communication links ranging 30 cm or shorter, whereas electromagnetic bidirectional communication links reaches ranges of several meters. In certain aspects, an active implantable medical device (100) comprising an antenna (1160) and a band diplexer (1140) connected to the antenna is provided. The band diplexer comprises first filter means (1141,1142) for: a first signal to be transmitted and/or received in a first RF band and second filter means (1144) for a second signal to be transmitted and/or received in a second RF band, the second RF band being higher in frequency than the first RF band. In further aspects, the antenna comprises one or multiple windings. In further aspects, the first signal is applied to the antenna in differential mode and the second signal is applied to the antenna in common mode. In further aspects, the antenna is arranged to transmit and/or receive the first signal over an MI near-field and arranged to transmit and/or receive the second signal over a radiating near-field or EM far-field. In further aspects, the antenna is arranged to operate simultaneously for transmitting or receiving the first signal and transmitting or receiving the second signal. In further aspects, a first device (1130) is arranged to receive the first signal in the first RF band and connected to the band diplexer, and a second device (1110) is arranged to transmit the second signal in a second RF band and connected to the band diplexer. In further aspects, the first device is connected to the band diplexer in differential mode and the second device is connected to the band diplexer in common mode. In further aspects, the first device (1130) is further arranged for transmitting in the first RF band; and the second device (1110) is further arranged for receiving in the second RF band. In further aspects, both the first and the second devices are arranged for transferring unidirectionally power from the antenna towards the active implantable medical device using the reactive near field. In further aspects, the frequencies of the first RF band are below or equal to 30 MHz and the frequencies of the second RF band are above 30 MHz. In further aspects, the first signal is analogue and/or digital and the second signal is analogue and/or digital. In further aspects, an antenna matching unit (1120) is arranged for impedance matching of the antenna (1160) to an open-ended antenna for operation in the second RF band, wherein the antenna matching unit is connected to the band diplexer. In further aspects, the first and/or second signal comprises one or more data from the group consisting of: telemetry, control data, signaling data and audio streaming. In further aspects, the active implantable medical device is a cochlear implant. In certain aspects, external hearing aid device comprising an antenna system (1480) and a band diplexer (2140) connected to the antenna system is provided. The band diplexer comprises first filter means for a first signal to be transmitted and/or received in a first RF band and second filter means for a second signal to be transmitted and/or received in a second RF band, the second RF band being higher in frequency than the first RF band. In further aspects, the antenna system comprises a closed-wire antenna. In further aspects, the first signal is applied to the antenna in differential mode and the second signal is applied to the antenna in common mode. In further aspects, the hearing aid system comprises a cochlear implant and one or more external devices. In further aspects, the one or more external devices comprise a sound processor device for behind the ear (1401). In further aspects, the sound processor device for behind the ear comprises a connector for a closed-wire antenna (470) external to the device for behind the ear for transcutaneous power transfer to the cochlear implant. In further aspects, the one or more external devices comprise a device for in the ear canal of a recipient. In further aspects, the one or more external devices comprise a remote control or handheld device. In certain aspects, a method of bidirectional wireless communication between an active implantable medical device and an external device is provided. The method comprises the steps of: communicating unidirectionally from the external device to the implantable medical device over a first wireless link in a first RF band in the MI near-field and communicating unidirectionally from the implantable medical device to the external device over a second wireless link in a second RF band in the EM-field. In certain aspects, a method of bidirectional wireless communication between an external hearing aid device and a second external device is provided. The method comprises the steps of: communicating unidirectionally from the second external device to the external hearing aid device over a first wireless link in a first RF band in the MI near-field and communicating unidirectionally from the external hearing aid device to the second external device over a second wireless link in a second RF band in the EM-field. In further aspects, the second RF band is higher in frequency than the first RF band. | 67,831 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.