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NbN-Gated GaN Transistor Technology for Applications in Quantum Computing Systems

High-performance and scalable cryogenic electronics is an essential component of future quantum infor-mation systems, which typically operate below 4K. Su-perconducting qubits need advanced radio-frequency (RF) and pulse-shaping electronics, which typically oc-cupies large instrumentation racks operating at room temperature. This approach is not scalable to the mil-lions of qubits needed in future quantum systems.This work explores the use of wide band gap heterostructure electronics, specifically the AlGaN/GaN high electron mobility transistor (HEMT), for cryogenic low-noise applications. These structures take advantage of the polarization-induced two-dimensional electron gas to create a high mobility channel, hence eliminating the heavy doping needed in the other semiconductor technologies. Epitaxially-grown GaN-on-Silicon wafers have been demonstrated in large (12 inch / 300 mm) substrates, therefore making the technology an excellent candidate for scalable RF electronics in quantum computing systems.Furthermore, the use of electrodes of superconducting materials is proposed to significantly reduce the parasitic components and therefore push the RF performance of cryogenic devices. Short-channel transistors with NbN gates of length 250 nm have been demonstrated with promising performance.The next step will study the effect of the superconducting gate on RF characteristics of the transistors, with the eventual goal of pushing the frequency performance of these transistors to new limits. These transistors will be integrated into low-noise amplifier circuits for applications in readout and control electronics at cryogenic temperature. Furthermore, the demonstrated NbN-gated GaN transistor paves the way for the application of high-frequency GaN technology in cryogenic electronics, notably in scalable quantum computing systems. When combined with other highlights in GaN electronics, e.g., a GaN complementary metal-oxide-semiconductor (CMOS) platform, the reported technology brings usone step closer to an all-nitride integrated electronics-quantum device platform.

Metal Alloy Enables Reliable Silicon Memristor Synapses

In the age of artificial intelligence (AI), memristors have emerged as an artificial synapse for neuromorphic computing, overcoming the limitations of convention-al silicon (Si)-based digital synapses. Interestingly, Si has also been utilized to develop memristor synapses via combination with a silver (Ag) electrode. An electri-cal conductance of Si medium is reversibly modulated by Ag injection, corresponding to the synaptic weight changes. Owing to the thermodynamic instability of Ag in Si medium (Ag is immiscible in Si), injected Ag exhib-its high mobility, resulting in a high-weight modulation ratio and high switching endurance. Unfortunately, large switching variations and poor weight stability occur at the devices and are also induced by the ther-modynamic instability. Thus, to mitigate such dilem-mas in performance, the regulation of thermodynamic stability of Ag in Si medium would be the fundamental strategy. Here we have developed Ag alloy for precision tuning of thermodynamic interactions of Ag and Si, thereby achieving highly balanced synaptic performance. We selected copper (Cu) as an alloying element due to its (1) high diffusivity into Si and (2) favorable thermodynamic interactions with both Ag and Si. Our hypothesis was that Cu would migrate into Si simultaneously with Ag and enhance thermodynamic stability of Ag in Si (i.e., be a stabilizer). The device’s performance results clearly confirm our metallurgical strategy that switching uniformity and weight retention are significantly enhanced by a Ag-Cu alloyed electrode (Figure 1). It should be noted that other alloying elements such as Ni cannot improve the synaptic performance due to their repulsive interactions with Ag.With promising device performance test results, we have demonstrated 32 × 32 Si memristor array and successfully performed image storage (Figure 2) and image processing (Figure 3), which are only enabled by Ag-Cu active electrode (Figure 3). We believe our alloying strategy can be expanded to other memristive synapses to resolve performance issues in neuromorphic computing applications.

Highly Tunable Junctions in Magic Angle Twisted Bilayer Graphene Tunneling Devices

The recent observation of superconductivity and cor-related insulating states in “magic-angle” twisted bi-layer graphene (MATBG) featuring nearly flat bands at twist angles close to 1.1 degrees presents a highly tunable two-dimensional material platform capable of behaving as a metal, an insulator, or a superconduc-tor. Local electrostatic control over these phases may enable the creation of versatile quantum devices that were previously not achievable in other single materi-al platforms. Our research shows how we can exploit the electrical tunability of MATBG to engineer Joseph-son junctions and tunneling transistors all within one material, defined solely by electrostatic gates. Our multi-gated device geometry offers complete control over the Josephson junction, with the ability to inde-pendently tune the weak link, barriers, and tunneling electrodes. Utilizing the intrinsic bandgaps of MATBG, we also demonstrate monolithic edge tunneling spec-troscopy within the same MATBG devices and mea-sure the energy spectrum of MATBG in the supercon-ducting phase. Furthermore, inducing a double barrier geometry permits the devices to be operated as a sin-gle-electron transistor, exhibiting a Coulomb blockade. These MATBG tunneling devices, with versatile func-tionality encompassed within a single material, may find applications in graphene-based tunable supercon-ducting qubits, on-chip superconducting circuits, and electromagnetic sensing in next-generation quantum nanoelectroni

Electronic Cells: Autonomous Micromachines from 2D Materials

Electronic cells are micromachines encompassing au-tonomous on-board functions such as sensing, com-putation, communication, locomotion, and power management. Akin to their biological counterparts, electronic cells bring specialized capabilities to previ-ously inaccessible locations. Here, we present the de-sign and fabrication of the first-of-its-kind electronic cell composed of the nanoelectronic circuit on top of an SU-8 particle. Powered by a 2D material-based pho-todiode, the on-board circuit connects a chemiresistor element and a memristor element, enabling on-board detection and storage capabilities. We demonstrate how our cells sense and record information about the presence of ammonia and dispersed soot when aerosol-ized in the enclosed tubes, dispersed in a hydrodynamic flow of pipelines, or sprayed over large surfaces. Elec-tronic cells may find widespread application as probes in confined environments, such as the human digestive tract, oil and gas conduits, chemical and biosynthetic reactors, and autonomous environmental sensors.

Decoding Complexities in Relaxor Ferroelectrics Using Electron Microscopy

Relaxor ferroelectrics show slim hysteresis loops, low remanent polarization, high saturation polarization, and exceptional electromechanical coupling, finding applications in ultrasound imaging and energy storage devices. Developing a structure-property relationship in relaxors has been a seemingly intractable prob-lem due to the presence of nanoscale chemical and structural heterogeneities. We have employed aberra-tion-corrected scanning transmission electron micros-copy (STEM) to quantify the various contributions of nanoscale heterogeneity to relaxor ferroelectric prop-erties in a PMN-PT system. Specifically, we found three main contributions-- chemical ordering, oxygen octa-hedral tilting and oxygen octahedral distortion--that are difficult to otherwise differentiate. STEM reveals the elusive connection between chemical and struc-tural heterogeneity and local polarization variation. Further, the effects of strain and thickness on PMN-PT thin films has been examined. These measurements elucidate the design principles for next-generation re-laxor material.

Printed MEMS Membrane Electrostatic Microspeakers

This work reports the fabrication and operation of electrostatic microspeakers formed by contact-trans-fer of 125-nm-thick gold membranes over cavities pat-terned in a micron-thick silicon dioxide (SiO2) layer on a conducting substrate. Upon electrostatic actuation, the membranes deflect and produce sound. Addition-ally, membrane deflection upon pneumatic actuation can be used to monitor pressure. The microspeaker fabrication process reported enables fabrication of MEMS diaphragms without wet or deep reactive-ion etching, thus obviating the need for etch-stops and wafer-bonding. This process enables monolithic fab-rication of multiple completely-enclosed drum-like structures with non-perforated membranes to dis-place air efficiently, in both individual-transducer and phased-array geometries. We characterized the mechanical deflection of the gold membranes using optical interferometry. The membranes show a repeatable peak center deflection of 121±13 nm across gaps of ~25 microns at 1 kHz sinusoidal actuation with 60 V peak-to-peak amplitude and a 30 V DC bias (Figure 1). The acoustic performance of the microspeakers is characterized in the free field. Microspeaker sound pressure level increases with frequency at 40 dB/decade (Figure 2), indicating that its sound pressure output is proportional to the acceleration of its diaphragm, as expected in the spring-controlled regime for free field radiation. The microspeaker consumes 262 µW of real electric power under broadband actuation in the free field, and outputs 34 dB(SPL/Volt) of acoustic pressure at 10 kHz drive. The silicon wafer substrate (~500 μm thick) dominates the total thickness of the microspeakers; the active device thickness is less than 2 µm. These thin microspeakers have potential applications in hearing aids, headphones, and large-area phased arrays for directional sound sources.

Stretchable Pressure and Shear Sensitive Skin

In the fields of robotics and prosthesis design, there is need for inexpensive, wide-area pressure- and shear-sens-ing arrays that can be integrated into a flexible and stretchable skin analog. This project seeks to meet this need by building combined pressure and shear sensors based on the well-documented piezoresistive (strain de-pendent resistance) property of composites made from polydimethylsiloxane (PDMS) and carbon black (CB).The sensor skins are fabricated of three materials which are all PDMS-based: A CB/PDMS mixture is used as the active sensing material, a CB/PDMS and ~1 µm silver particle mixture is used to form strain-insensitive conductors into the skin, and pure PDMS is used to form the base of the skin. These materials are mixed, vacuum degassed, and then molded in custom-machined acytal and aluminum molds to fabricate the sensor arrays. Each sensor consists of a roughly hemispherical piece of CB/PDMS molded on top of a line of three conductors, thus allowing the resistance of each half of the CB/PDMS sensor to be measured independently. A schematic representation of a single sensor is shown in Figure 1. Our own characterization experiments performed on bulk (1 cm3) CB/PDMS samples have shown that the resistance of CB/PDMS increases under tensile, compressive, and shear strain but is much more sensitive to tensile strain then compressive strain. This symmetry allows the device to sense both pressure and shear. Under pressure, each half of the sensor has roughly equal compressive strain, and thus the resistance of each half of the device increases roughly equally. However, under shear, one half of the device is under tensile strain while the other half is under compressive strain. Due to the asymmetric response of the CB/PDMS, the resistance of the half of the sensor under tension increases much more than the half under compression, allowing a differentiation between pressure and shear; see Figure 2.

Tunneling Nanoelectromechanical Switches Based on Molecular Layers

Nanoelectromechanical (NEM) switches have emerged as a promising competing technology to the conventional complementary metal-oxide semicon-ductor (CMOS) transistors. NEM switches can exhibit abrupt switching behavior with large on-off current ratios and near-zero off-state leakage currents. How-ever, they typically require large operating voltages exceeding 1 V and suffer from failure due to stiction. To address these challenges, this work presents NEM switches utilizing metal-molecule-metal switching gaps. These switches operate by electromechanical modulation of the tunneling current through electro-statically-induced compression of the molecular film (Figure 1). The molecular layer helps define few-nano-meter-thick switching gaps to achieve low-voltage operation. In addition, the compressed molecules prevent direct contact between the electrodes while providing a restoring force to turn off the device once the applied voltage is removed, thereby preventing permanent adhesion between the electrodes and eliminating stiction. A prototype two-terminal tunneling NEM switch is fab-ricated as a laterally actuated cantilever using electron beam-lithography (Figure 2). A fluorinated decanethiol layer is deposited over the device area and into the gap between Electrodes 1 and 2 using self-assembly through thiol-chemistry. During the assembly process, Elec-trode 1 collapses onto the opposing electrode to form a metal-molecule-metal junction with a nanometer thickness. Experimental results based on a device with a self-assembled fluorinated decanethiol layer demon-strate repeatable switching, indicating the importance of the molecular film in alleviating stiction. Compari-son of these results to the theoretically expected device behavior suggests the compression of the molecular layer during the switching process, confirming the elec-tromechanical modulation of tunneling current as the switching mechanism. Our current research focuses on engineering the molecular layer and the device design to optimize the NEM switch performance to achieve stiction-free sub-1-V actuation with more than 6 orders of magnitude on-off current ratio.

Electrically-Tunable Organic Microcavities

The availability of a compact, single-system tunable visible light source would benefit a wide range of fields such as remote sensing, spectroscopy, and optical switches. Organic-based materials are attractive for visible light emission over a broad tunable spectrum. However, previously demonstrated frequency-tunable lasing devices required either complex fabrication techniques, external micro-actuated mirror stages, or manual switching between gain media. Tunable air-gap MEMS microcavity structures offer a scalable, inte-grated solution but their typical fabrication processes are incompatible with solvent- and temperature-sensi-tive organic gain materials. We have demonstrated a method for fabricating integrated organic optical microcavities that can be mechanically or electrostatically actuated to dynamically tune their output emission spectra. Fabrication of the micro-opto-electro-mechanical system (MOEMS) structures (as in Figure 1) is enabled by a solvent-free additive transfer-printing method for composite membranes that we have developed. The suspended membrane incorporates an organic laser gain medium, Alq3:DCM, into the microcavity, and the completed capacitive structure can be electrostatically actuated for dynamic tuning of the optical spectra (see Figure 2). Electrical actuation and optical characterization of a completed cavity structure show reversible resonance tuning greater than 20 nm for net membrane deflections of over 200 nm at 50 V. The device structure and transfer technique are easily scalable for large area fabrication with applications in tunable lasers as well as remote all-optical pressure sensing and low-power optical switches.

MEMS Tactile Displays

Providing information to people who are blind or have low vision is critical for enhancing their mobility and situational awareness. Although refreshable 2D graph-ical interfaces are preferred, it is challenging to create actuators that are compact enough to be arrayed into an unlimited number of rows and columns while still being robust, easy to sense, and rapidly switchable. Electroactive polymer actuators are small enough to be arrayed with a few- millimeter pitch and to provide quasistatic millimeter-scale actuations, but they typ-ically have actuation times on the order of seconds. An alternative integrates piezoelectric bending beam actuators perpendicular to the tactile sensing plane, enabling large bending beam actuators to be tightly packed for fully 2D displays. Ideally, the display’s resolution should be about one tactel (i.e., tactile element) per mm2 , which is the density of mechanoreceptors in human finger pads. It should be refreshable in real time (hundreds of Hz, i.e., the frequency response of human touch), allowing the contents of the display to keep up with rapidly changing inputs. Since humans are much more sensitive to motions and changing stimuli than to static patterns, the display should code information not only as static patterns, but also as simulated motion against the user’s finger pads. Finally, the power consumption of the display should be compatible with portable use. Although existing displays meet various subsets of these requirements, no existing display can meet all requirements simultaneously. We are developing tactile displays based on a new type of MEMS tactile actuator created to target these requirements. This new actuator concept uses an extensional piezoelectric actuator that operates a scissor amplifier that transforms the in-plane movement of the piezo into amplified out-of-plane movement (see Figure 1). We have shown these tactile elements to be effective at the milliscale. Their measured performance agrees with the models, with maximum deflections of greater than 10 µm and maximum forces above 45 mN (as in Figure 2) that place the devices well above the sensing threshold. Our analytical model based on ideal pinned hinges is shown to be useful for predicting the behavior of tactels with flexural hinges, especially when coupled with FEA to predict hinge failure. The analytical model validation provides support for further downscaling of the tactile elements to achieve 100 tactels/cm2. The measured performance confirms sensing thresholds of less than 4 µm and 2 mN for the most effective tactile devices.

Real-time Manipulation with Magnetically Tunable Structures

Responsive actuating surfaces have attracted signifi-cant attention as promising materials for liquid trans-port in microfluidics, cell manipulation in biological systems, and light tuning in optical applications via their dynamic regulation capability. Significant efforts have focused on fabricating static micro and nano-structured surfaces, even with asymmetric features to realize passive functionalities such as directional wet-tability and adhesion. Recent advances in utilizing ma-terials that mechanically respond to thermal, chemical or magnetic stimuli have enabled dynamic regulation. However, the challenges with these surface designs are associated with the tuning range, accuracy, response time, and multi-functionality for advanced systems. Here we report dynamically tunable micropillar arrays with uniform, reversible, continuous, and extreme tilt angles with precise control for real-time fluid and optical manipulation. Inspired by hair and motile cilia on animal skin and plant leaves for locomotion, liquid transportation, and thermal-optical regulation, our flexible uniform responsive microstructures (µFUR) consist of a passive thin elastic skin and active ferromagnetic microhair whose orientation is controlled by a magnetic field. We experimentally show uniform tilt angles ranging from 0° to 57° and developed a model to accurately capture the tilting behavior. Furthermore, we demonstrate that the µFUR can control and change liquid spreading direction on demand, manipulate fluid drag, and tune optical transmittance over a large range. The versatile surface developed in this work enables new opportunities for real-time fluid control, cell manipulation, drag reduction, and optical tuning in a variety of important engineering systems, including applications that require manipulation of both fluid and optical functions.

GaN MEMS Resonator Using a Folded Phononic Crystal Structure

We present a gallium nitride (GaN) Lamb-wave resona-tor using a phononic crystal (PnC) to selectively confine elastic vibrations with wide-band spurious mode sup-pression. A unique feature of the design demonstrated here is a folded PnC structure to relax energy confine-ment in the non-resonant dimension and to enable routing access of piezoelectric transducers inside the resonant cavity. This feature provides a clean spectrum over a wide frequency range and improves series resis-tance relative to transmission line or tethered resona-tors by allowing a low-impedance path for drive and sense electrodes. We demonstrate GaN resonators with wide-band suppression of spurious modes, f.Q product up to 3.06×1012, and resonator coupling coefficient keff2 up to 0.23% (filter BW up to 0.46%). Furthermore, these PnC GaN resonators exhibit record-breaking power han-dling, with IIP3 of +27.2dBm demonstrated at 993MHz.This work focuses on developing MEMS resonators for channel-select filtering in RF receiver front ends. For a MEMS band pass filter, the presence of spurious modes in the constituent resonators strongly impacts filter performance. Resonators with a clean frequency spectrum help reduce ripples in the pass-band and prevent interference from unwanted signals outside the pass-band. Conventional MEMS resonator designs with free mechanical boundaries are inherently prone to spurious modes, since free boundaries act as acoustic reflectors over all frequencies. To resolve this issue, the resonator boundary needs to be frequency selective. One way is by using PnCs, which involve periodic scatters to achieve highly reflective boundary conditions only for frequencies in a specific range. This acoustic band gap can be engineered based on the unit cell size and material configuration. While the acoustic band gap of these PnCs helps reduce resonance outside the band gap, these structures provide no spurious mode suppression inside the band gap. Further, transducers must be routed through the PnC in these configurations, leading to resistive loading of Q. In this work, we demonstrate a new resonant structure leveraging both PnC acoustic confinement and the electromechanical benefits of GaN. The proposed GaN folded PnC structure provides several important benefits:wide-band spurious mode suppression, both outside and inside the PnC band gap, through relaxed confinement in the non-resonant dimension,low-loss electrical routing to the resonant cavity, improved heat dissipation relative to other PnC or tethered resonators, androbust design that is immune to residual stress and handling.The folded PnC design achieves these improvements while maintaining quality factor and transducer cou-pling comparable to traditional tethered resonators.

GaN RF MEMS Resonators in MMIC Technology

As a wide bandgap semiconductor with large break-down fields and saturation velocities, gallium ni-tride (GaN) has been increasingly used in high-power, high-frequency electronics and monolithic microwave integrated circuits (MMICs). At the same time, GaN also has excellent electromechanical properties, such as high acoustic velocities and low acoustic losses. To-gether with a strong piezoelectric effect, these make GaN an ideal material for RF MEMS resonators. This work focuses on the optimization of L-band (1-2 GHz) GaN resonators in standard MMIC technology.For monolithically integrated resonators, various constraints of the technology must be considered, such as the thickness of the GaN MMIC heterostructure, residual stresses in the GaN film, and the lack of bottom electrodes. Residual stress due to high temperature growth can affect the mechanical properties of the resonators and even lead to cracking and breaking. To achieve high performance resonators with multiple frequencies on the same chip within this technology, we designed 5th-order extensional resonators driven piezoelectrically with a top metal interdigitated transducer (IDT) as shown in Figure 1. These resonators have achieved mechanical quality factors >5500 at 1GHz, with f·Q products >5.5×1012, the highest demonstrated in GaN to date. Enhanced signal-to-noise ratios (SNR)at high frequencies can be obtained by using active transistor sensing. We demonstrate the first mechanically-coupled Resonant Body Transistor, in which the drive transducer and sensing high electron mobility transistor (HEMT) are embedded in two separate cavities, as shown in Figure 1. This additional electrical isolation between drive and sense allows for an improvement in the SNR of >50× compared to previous designs. The large SNR, together with high Q (Figure 2), makes these resonators ideal for monolithically integrated low-phase noise oscillators, with applications in clocking and wireless communications.

Ion Energy Measurements of Dense Plasmas with a Microfabricated RPA

The energy of ions determines the efficiency of plasma propulsion systems and governs surface chemical reac-tions in plasma etching chambers. In plasma diagnostics, the instrument used to measure the ion energy distri-bution is the Retarding Potential Analyzer (RPA). How-ever, high-density plasmas of interest require tens- to hundreds-of-microns scale dimensions. Through MEMS processing techniques, our RPA achieves the small aper-ture sizes necessary to measure dense plasmas. Precise alignment between successive microfabricated grids is achieved through compliant support structures in the housing (as Figure 1 shows). The silicon spring tips mate with corresponding notches in the electrodes to provide robust alignment on the order of 1 µm and to increase the overall sensor’s ion transmission.Our previously reported RPA, deemed “hybrid” on account of incorporating microfabricated electrodes in a conventionally machined sensor, demonstrated improved performance over conventional RPAs. By reducing the aperture size while enforcing some degree of aperture alignment, we achieved a better resolution with no loss in signal strength compared to conventional mesh RPAs. Measurements of the ion energy distribution in a helicon plasma were obtained at MIT’s Plasma Science and Fusion Center using our sensors with microfabricated electrodes having 100 µm apertures. However, as a consequence of its larger apertures, the conventional RPA design was unable to effectively trap the plasma, and therefore no ion distribution could be extracted with this traditional device.Figure 2 shows ion energy distributions obtained with an ion source comparing the performance of a conventional RPA (with 152 µm apertures), the hybrid RPA (with 100 µm apertures), and MEMS RPA (with 150 µm apertures). The MEMS RPA design utilizes a fully microfabricated housing to improve upon the inter-grid aperture alignment over the hybrid sensor. Additionally, various aperture diameters are utilized in the electrode stack to mitigate current interception within the sensor. These RPA improvements result in an order of magnitude increase in signal strength over the conventional device and a threefold increase in energy distribution resolution.

High Throughput Electrospinning of Nanofibers from

Nanofibers promise to be a key engineering material in the near future due to their unique, nanoscale mor-phological properties. In particular, the large specific surface area of the porous webs they form make them highly desirable as scaffolds for tissue engineering; layers in multifunctional filters/membranes; and com-ponents in devices such as fuel cells, solar cells, and ul-tra-capacitors. However, their integration into almost all of these technologies is unfeasible as a result of the low throughput, high cost, and poor control of current production methods. The most common process for producing nanofibers involves applying strong elec-tric fields to polar, high-molecular-weight polymeric liquids pumped through a syringe in what is known as electrospinning. Electrospinning is the only known technique that can generate nanofibers of arbitrary length; it has tremendous versatility as it can create non-woven or aligned mats of polymer, ceramic, semi-conducting, and/or metallic fibers.We implement high throughput arrays of externally-fed, batch-microfabricated electrospinning emitters that are precise, simple, and scalable. We fabricate monolithic, linear emitter arrays that consist of pointed structures etched out of silicon using DRIE and assemble these into a slotted base to form a two-dimensional array. By alter-ing the surface chemistry and roughness of the emitters, we can modify their wetting properties to enable wicking of fluid through the micro-texture (as in Figure 1). The in-terplay between electric, viscoelastic, and surface tension forces governs the fluid transport and fiber formation. We achieve over 30 seconds of stable electrospinning of polyethylene oxide (2-4% w/v in 60/40 water/ethanol solu-tion) from 9 emitters in a two-dimensional array with a density of 11 emitters/cm2 using bias voltages around 10kV (see Figure 2). This density is 7 times greater than the emitter density achieved in similar array-based ap-proaches. Current work focuses on characterization of larger, denser arrays to demonstrate uniform emission.

Near-Monochromatic X-ray Sources Using a Nanostructured Field Emission Cathode and a Transmission Anode for Markerless Soft Tissue Imaging

A conventional X-ray generator consists of a thermion-ic cathode and a reflection anode inside of a vacuum chamber that has an X-ray transmission window. The cathode generates a beam of electrons that is acceler-ated towards the anode, which is biased at tens of kilo-volts above the cathode voltage. Some of the electrons collide with the anode and convert their kinetic energy into radiation, a fraction of which escapes the vacuum chamber through a transmission window made of a suitable material, such as beryllium. The X-ray emis-sion is a mix of bremsstrahlung radiation (broad, con-tinuous spectrum) and fluorescence (emission at spe-cific peaks corresponding to atomic shell transitions). Conventional X-ray technology requires high vacuum to operate, does not efficiently produce X-rays, and has overall low power efficiency. Conventional X-ray gen-erators cannot image well soft tissue unless contrast media, i.e., markers, are employed.We are developing efficient X-ray generators capable of soft tissue imaging using batch-microfabricated field emission cathodes composed of arrays of self-aligned, gated, and nanometer-sharp n-silicon tips, and a microstructured transmission anode (Figure 1). The nanostructured silicon cathode operates at low voltage and reliably achieves high-current emission with high transmission. The transmission anode efficiently generates X-rays while reducing the background radiation, resulting in emission of X-rays with narrow spectral linewidth for sharp imaging of biological tissue.Using our first-generation X-ray source (a tabletop apparatus), we have obtained absorption images of ex-vivo samples that clearly show soft tissue and fine bone structures (Figure 2). Current work focuses in miniaturizing the X-ray source into a portable system, and in improving the cathode and anode components to achieve generation of coherent X-rays to make possible phase contrast imaging at a low cost.

Multiplexed MEMS Electrospray Emitter Arrays with Integrated Extractor Grid and CNT Flow Control Structures for High-Throughput Generation of Ions

Electrospray is a process to ionize electrically conduc-tive liquids that relies on strong electric fields. Charged particles are emitted from sharp tips that serve as field enhancers to increase the electrostatic pressure on the surface of the liquid, overcome the effects of sur-face tension, and facilitate the localization of emission sites. Ions can be emitted from the liquid surface if the liquid is highly conductive and the emitter flowrate is low. Previous research has demonstrated successful operation of massive arrays of monolithic batch-mi-crofabricated planar electrospray arrays with an inte-grated extractor electrode using ionic liquids EMI-BF4 and EMI-Im—liquids of great importance for efficient nanosatellite propulsion and nanomanufacturing. The current design builds upon a previous electrospray array designs from our group by increasing the area density of the emitter tips and increasing the output current by custom-engineering nanofluidic structures for flow control.Our MEMS multiplexed electrospray source consists of an emitter die and an extractor grid die (Figure 1), both made of silicon and fabricated using deep reactive ion etching. The two dies are held together using a MEMS high-voltage packaging technology based on microfabricated springs that allows precision packaging of the two components with low beam interception. The emitter die contains dense arrays of sharp emitter tips with over 1,900 emitters in 1 cm2. A voltage applied between the emitter die and the extractor grid die creates the electric field necessary to ionize the ionic liquid. A carbon nanotube forest grown on the surface of the emitters transports the liquid from the base of the emitters to the emitter tips. Our electrospray arrays operate uniformly (Figure 2), and mass spectrometry of the emission demonstrates that our devices only produce ions.

Exploration of the Packing Limits of Ultrafast, Optically-triggered Silicon Field-emitter Arrays Using the Finite Element Method

Ultrafast optically-triggered field emission cathodes bypass several disadvantages demonstrated by current state-of-the-art ultrafast cathodes, such as requiring ultra-high vacuum to operate and short lifetime, and are a promising technology for implementing spatial-ly-structured electron sources for applications such as free-electron lasers, compact coherent X-ray sourc-es, and attosecond imaging. Ultrafast optically-trig-gered cathodes composed of massive arrays of high aspect-ratio silicon pillars capped by nano sharp tips and 5 µm pitch were fabricated at MIT MTL. The effect of the geometry and the morphology of the Si pillar ar-rays on the ultra-fast emission characteristics of such cathodes is now explored using the finite element mod-eling in 2D and 3D. Since the field-emitted current depends exponentially on the surface electric field, we are interested in studying how the electric field is enhanced by the geometry and the morphology of the Si pillar arrays. We selected COMSOL Multiphysics to simulate the electric field of the devices. The 3D model (see Figure 1) consists of a single tapered pillar 2.0 µm tall and 0.7 µm wide at the base with a 6-nm radius hemispherical cap. Perfectly matched layers (PMLs) are added on the top and bottom to absorb the excited and higher order modes. Floquet periodicity is applied on the four sides of the unit cell to simulate the infinite 2D array. The port boundary condition is applied on the interior boundary of the PML as the excitation port to simulate the 800-nm incident wave at a glancing angle of 84° from normal (the same experimental setup described in the third reading below). This model is validated by verifying the Fresnel equations between Si and vacuum before inserting the Si pillar. The 2D slice contour plot (see Figure 2) shows the simulated electric field from a 1 GV/m incident field on an emitter with 1-µm pitch using frequency domain analysis. The maximum electric field at the tip is about 4.2 GV/m, i.e., the emitter tip has an field enhancement factor of ~4.2. Both 2D and 3D models are utilized to explore the effect of the geometry and the morphology of the Si pillar arrays on the field enhancement.

High-Current Field Emission Cold Cathodes with Temporal and Spatial Emission Uniformity

Field emission arrays (FEAs) are an attractive alterna-tive to mainstream thermionic cathodes, which require high vacuum and high temperature to operate. Field emission of electrons consists of the following two processes: first, the transmission of electrons (tunnel-ing) through the potential barrier that holds electrons within the material (workfunction φ) when the barrier is deformed by a high electrostatic field and second, the supply of electrons from the bulk of the material to the emitting surface. Either the transmission process or the supply process could be the limiting step that de-termines the emission current of the field emitter. Due to the exponential dependence on the field factor, the emission current from the tips is extremely sensitive to tip radii variation. We have a process to achieve uni-form emission from nanosharp FEAs by both fabricat-ing highly uniform tip arrays and controlling the sup-ply of electrons to the emitting surface (see Figure 1). We have designed and fabricated FEAs in which each field emitter is individually ballasted using a vertical ungated field effect transistor (FET) made from a high aspect ratio (40:1) n-type silicon pillar. Each emitter has a proximal extractor gate that is self-aligned for maximum electron transmission to the anode (col-lector). Our modeling suggests that these cathodes can emit as much as 30 A.cm-2 uniformly with no deg-radation of the emitters due to Joule heating; also, these cathodes can be switched at microsecond-level speeds. The design process flow, mask set, and pil-lar arrays have been completed (as Figure 2 shows) with the self-aligned extractor gate. An ultra-high vacuum chamber has been built to test the devic-es. The chamber can test full 150mm wafers with six high voltage feed through and a step-down anode at 2x10-10 torr pressure while also imaging the electron emission on a phosphorus screen.

Photoactuated Ultrafast Silicon Nanostructured Electron Sources for Coherent X-ray Generation

Nanostructured cathodes that can be switched at an ultrafast time scale (<50 ps) have applications in free-electron lasers and coherent X-ray sources. This project is creating the theory, modeling, and exper-imental results for a compact coherent xray source for phase contrast medical imaging based on inverse Compton scattering of relativistic electron bunches. The X-ray system requires a low-emittance electron source that can be switched at timescales in the low femtosecond range. The focus of our work has been the design, fabrication, and characterization of massive arrays of a nanostructured high aspect-ratio silicon structures to implement low-emittance and high-brightness cathodes that are triggered using ultrafast laser pulses to produce spatially uniform electron bunches. Laser pulses at 35 fs, 800 nm and a 3 kHz repetition rate from a titanium sapphire laser at an 84º glancing angle, inside a vacuum chamber at ~10-8 torr bathe a highly uniform array of ~2200 silicon pillars with a 5-μm pitch. The cathode chip is connected to ground through a picoammeter while the anode, a 0.25-inch plate 3mm above the cathode, connects to a voltage supply (see Figure 1). The cathodes show stable emission and emit over 1.2 pC average charge for over 8-million pulses when excited with 9.5-μJ laser energy with no degradation of the emission characteristic of the cathode. This result shows that silicon-based photon-triggered cathodes processed with standard CMOS processes and operated at high vacuum can function for extended periods without performance degradation. The cathodes are fabricated from single-crystal <100> n-Si 1-10 Ω-cm wafers. The result is massive arrays of pillars (over half a million elements with 5-µm hexagonal packing) capped by tips with under-5-nm average tip radius and less than 1-nm standard deviation (see Figure 2). Through simulation and experiment we have demonstrated that the emitters operate in two distinctive regimens, i.e., the low-electric field multi-photon regime (similar to a typical photocathode), and the high-field quantum tunneling regime (similar to a field emission cathode). Actuation of the devices with laser pulses of 10 µJ or lower results in electron emission with no device degradation.

Field Emission Neutralizers for Electric Propulsion of Small Spacecraft in Low Earth Orbit

Electric propulsion (EP) systems are excellent candi-dates for small spacecraft since EP systems consume less propellant than chemical rockets. In EP systems such as field emission electric propulsion thrusters (FEEPs), ion engines, and hall thrusters, a beam of posi-tive ions is ejected at high speed to produce thrust. If the ejecting charge is not compensated, the operation of the EP system will negatively charge the spacecraft, reduc-ing the propulsion efficiency and eventually stopping the thruster. Hence, development of robust, low-pow-er, and high-current neutralizers that do not consume propellant is necessary to advance the state of the art of EP systems for small spacecraft. Field emission neutral-izers (FENs) are promising candidates because of their low power consumption, high specific current, small size, and lack of propellant consumption. For operation in LEO, neutralizers must withstand long-term opera-tion in environments with oxygen partial pressures of ~5×10-7 Torr. Carbon nanotube-based FENs could satisfy these requirements; however, they require biases higher than 600 V for 1 mA emission current.This work develops arrays of Pt-coated, self-aligned, gated tips as low-voltage FENs for electric propulsion of small spacecraft in low Earth orbit. The neutralizers consist of 320,000 tips with 10 µm pitch and 5-10 nm tip radii; they have an integrated self-aligned gate electrode with 3 µm apertures. The devices emit currents higher than 1 mA at bias voltages as low as 120 V, i.e., similar currents at five-fold less bias voltage and emission area than state-of-the-art CNT neutralizers. The devices have a 2.5-µm-thick gate dielectric to prevent device failure due to dielectric breakdown; the tips are coated with a 10-nm-thick Pt film to improve the tip resistance against ion bombardment and reactive gasses. Continuous emission for 3 hours at pressures of 5×10-6 Torr in air was demonstrated. Less than 60 V increase in the gate-emitter voltage was sufficient to maintain the emission current at 1 mA.

Field Emission Arrays with Integrated Vertical Current Limiters and Self-aligned Gate Apertures

Field emission cold cathodes are some of the bright-est electron sources ever reported, making them an ideal source in a variety of applications, including mi-croscopy, lithography, imaging, and the generation of terahertz and X-ray radiation. Field emission arrays (FEAs) suffer from emitter tip radius variation across the array and sensitivity to the state of the emitting surface, resulting in spatial and temporal variations of emission current. To address these issues, we previous-ly demonstrated that a high-aspect-ratio silicon ver-tical current limiter (VCL) that is connected in series with each field emitter in a field emission array could regulate the supply of electrons to each emitter and result in uniform emission; however, due to the lack of an integrated extractor gate, these devices operate at high extraction voltages and 99% of the total emitted current is intercepted by the extraction gate. Large ex-traction gate voltages are required due to the low field factor, β (cm-1), and result in a high Fowler-Nordheim (FN) slope bFN (V), arising from the large extractor gate−tip distance. To reduce the extractor voltage and enable low-voltage operation, we report Si FEAs with 1 million individual field emitters that have a 1-micron pitch with integrated VCLs poly-silicon extractor gates. These VCLs are Si pillars that have diameter less than 100 nm and are 10 microns tall, with tip radius under 20 nm. A schematic diagram and circuit diagram are shown in Figure 1 (a),(b). To fill in the gaps between the pillars and to support the self-aligned gate, a novel gap-filling process consisting of silicon dioxide and silicon-rich nitride deposition and chemical-mechanical planarization was employed, resulting in the structure shown in Figure 1 (c). The diameter of the extractor gate aperture is under 200 nm. As shown in Figure 1(d), these devices exhibit turn-on voltages less than 20 V and saturation currents of approximately 1 pA / emitter.

Low-Voltage High-Pressure Gas Field Ionizers

Low power consumption, soft-ionization capability, and the potential for operation at high pressures are characteristics desired in gas ionizers for application to portable analytical instruments. Unlike impact ion-ization techniques, field ionization provides an efficient method for producing stable molecular ions—even from complex organic compounds. Consequently, field ion sources can generate nonfragmented ions for exact measurement of the mass-to-charge ratio of an analyte. These devices are used in various analytical instru-ments such as field ion mass spectrometers (FIMS) and atom beam microscopes. Other applications include gas chromatography FIMS for analysis of petroleum prod-ucts and neutron generators for detection of shielded nuclear material and oil-well logging. Despite the attrac-tive features offered by field ion sources, long-term, reli-able, and high pressure operation has not been reported due to high voltages (> 500 V) needed for field ionization using the current state-of-the-art devices. We have developed low-voltage Torr-level gas field ion-izers with operating voltages as low as 150 V even for He, which has the highest ionization potential among mol-ecules. The ionizer consists of a large array of Pt-coat-ed self-aligned gated Si tips with radii <10 nm and gate apertures of 3 µm. The tips were designed to generate fields above 20 V/nm at gate-to-tip voltages lower than 200 V while the field at the edge of the gate remains be-low 0.2 V/nm. A 2.5-µm-thick stack of silicon oxide/sili-con nitride was employed as the gate dielectric to limit the field intensity inside the gate dielectric to less than 100 V/µm, allowing prolonged operation of the device. Continuous field ionization of He and N2 for 104 s was achieved at pressures as high as 10 Torr. A slow decay in ion current was observed over time, which can be explained by adsorption of particles at the tip surface. Nevertheless, the original device characteristics can be recovered by operating the device as field emitter in a high vacuum (<10-7 Torr).

Large-Area Field Emission Arrays for High-Current Applications

Gyrotrons, free electron lasers (FELs), and THz vac-uum electronic devices require intense high-current electron beams. High-current, high-current-density electron beams are also needed for X-ray generation, pumping of gaseous lasers, and surface treatment of materials. Field emission sources show great promise for these applications as they can produce current densities higher than 10 A/cm2 at voltages below 100 V. Despite these promising attributes, the state-of-the art devices have produced currents less than 300 mA due to limitated array size (1–10 mm2) because of fabrication issues that result in failure or severe sub-utilization of the array. The major challenges include low yield of fabrication, large variation in gate and tip dimensions across the array, and point defects in the gate dielectric.We have developed a high-yield process for fabrication of large-area, self-aligned, gated tip arrays with low sensitivity to processing conditions. The fabricated field emission arrays (FEAs) demonstrate average field factor >106 cm-1 using nanometer-scale tips (radii < 10 nm) surrounded by individual gates with 1.5 µm radius of aperture. This ensures low-voltage operation of the device and a turn-on voltage below 50 V. For reliability a thin Pt layer was deposited over the FEA and a SiOx/SiNx dielectric stack thicker than 2.5 µm was used as the gate insulator. The Pt coating ensures chemical resistivity of the tips against corrosive gasses/ions, and the thick insulator stack limits the field inside the gate dielectric to < 150 V/µm at Gate-Emitter voltages of < 300 V. Our FEAs consisting of 320,000 tips in 0.32 cm2 are capable of emitting currents as high as 350 mA at densities of ~1.1 A/cm2. The device operation at higher emission currents was prevented due to plasma ignition because of the excessive outgassing of the anode. At low pressures, long-term (~3 hrs) operation not only was possible but also lowered emission voltage and gate current.

Evaporation through Nanoporous Membranes for High Heat Flux

The development of ever more compact electronic cir-cuits has brought the demands for thermal management to unprecedented levels. Although there has been exten-sive research on single phase and multi-phase cooling in microchannels, evaporative cooling in the thin film regime has the potential to reach an even higher heat flux. We report the design and fabrication of a novel sil-icon-based evaporation device for direct integration into high power density electronics. We designed a micro-scale device, relying on the evaporation of a very thin liquid film to dissipate over 1000 W/cm2 with an overall temperature difference of less than 30 K. Evaporation occurs in a 200 nm thick silicon membrane patterned with 100 nm pores using interference lithography. The nanopores create a large thin-film evaporation area and generate a large capillary pumping pressure to supply fluid to the membrane. The membrane is thermally bonded to an arrayed supply network of 4 µm x 4 µm microchannels whose walls provide mechanical support and a thermal conduction pathway from the substrate. The substrate is resistively heated, and the temperature is measured with RTDs fabricated with a lift-off pattern. A finite element model is developed to optimize the microchannel and membrane geometry. The convective heat transfer coefficient is modeled by numerically solving governing equations of heat, mass, and momentum conservation at the pore level. Evaporation through nanoporous membranes has the potential for achieving ultra-high heat flux dissipation (5 kW/cm2) for high-performance electronic devices.

Experimental Investigation of Thin-film Evaporation from Microstructured Surfaces for Thermal Management

Thermal management is a primary design concern for numerous high power density devices such as in-tegrated circuits, electric vehicles, military avionics, photonic devices, and solar energy convertors. This is especially true in the microelectronics industry where the increase in the number of integrated circuits and operating speed has increased the waste heat that is generated at the device footprint from 30 W/cm2 in the 1970’s to 100 W/cm2. Moreover, this heat flux is projected to reach 300 W/cm2 in the next few years introducing new challenges in thermal management that has forced the industry to seek advanced cooling solutions. Unfortunately, the widely used convention-al single-phase cooling systems are inferior in perfor-mance and cannot be used for applications that require removal of high heat fluxes in excess of 100 W/cm2. As a result, state-of-the-art single-phase cooling systems are limited to low heat flux devices and the proposed solution is to use liquid-vapor phase change systems such as thin-film evaporation [1, 2] to make use of the high latent heat of vaporization that can be harnessed during the phase change process.In this experimental study, we investigated the com-plex fluidic and thermal transport processes when a thin-liquid film is evaporating from a microstructured surface. We fabricated well-defined microstructured surfaces using contact photolithography and deep reac-tive ion etching. In addition to offering rich opportuni-ties to manipulate the fluid dynamics, microstructured surfaces in combination with chemical functionaliza-tion have long been recognized for enhancing thermal performance in phase-change process. The induced roughness generates capillary pressure for passive liquid transport [3]. The liquid transport was further assisted by incorporating microchannels which reduce the overall flow resistance of the porous media. For in-tegrated heating and temperature measurement, we used electron-beam evaporation and acetone lift-off to create a thin-film heater and sensors. This work eluci-dates new and innovative techniques to utilize micro-structured surfaces for thermal management.

Scalable and Direct Water Purification Technology by Ion Concentration Polarization

We demonstrate a scalable and direct water purification technology using ion concentration polarization (ICP). Although nonlinear ICP was shown to generate a strong depletion zone near the ion exchange membrane (IEM), several challenges (power consumption, expandability, etc.) must be overcome for ICP to be a competitive technology in desalination. To resolve and improve them, we propose a modified ICP platform for water desalination by involving two identical cation exchange membranes (CEMs); it demonstrates better salt removal and energy efficiency than conventional electrodialysis (ED), as Figure 1 shows. Between two parallel CEMs, ion depletion/enrichment zones are generated near the CEMs under an electric field. As cations selectively transfer through the CEMs, anions relocate to achieve electro-neutrality, resulting in a decreased/increased concentration in the ion depletion/enrichment zone. Given that the desalted and brine flow streams form on the cathodic and anodic CEM in the main channel, respectively, we can separate and collect each desalted and brine flow by bifurcating the channel at the end. Our technique offers a significant advantage for reducing the number of water purification stages over other conventional technologies since we can obtain desalted flow delivering any charged particles (contaminants) to the brine channel simultaneously. To visualize the electrokinetic phenomena between the membranes, we fabricated a PDMS-based microfluidic chip with thin channel depth (~0.2mm) and injected a sodium chloride solution mixed with fluorescent dye, as in Figure 2(a). Additionally, to increase system throughput, we built a plastic-based desalination prototype (~1ml/min) by expanding the channel depth and successfully operated it over ten hours, as shown in Figures 2(b) and 2(c). Therefore, we expect our ICP desalination to be a practical technology for water purification, providing both lower energy cost and high throughput.

Electrostatic Precursor Films

When a liquid spontaneously spreads over a solid sur-face, a progressive microscopic structure—convention-ally known as van der Waals driven precursor film—de-velops ahead of the moving contact line. Here, we report a new class of electrostatically assisted precursors con-taining microscopic charged particles. This precursor manifests itself as the late stage of forced-spreading of a macroscopic dielectric film subjected to a unipolar ionic discharge in a gas containing particulates. We put a model forward to predict dynamic behavior of this electrostatic precursor dynamics. The spreading of the precursor film is predicted to be proportional to the square root of exposure time, which is consistent with the ellipsometric measurements.

Continuous-flow Microcalorimetry Using Silicon Microreactors and Off-the-shelf Components

Calorimetry is an important method for studying the kinetics and energy requirements of chemical and/or biological reactions. In particular, calorimetry can characterize the heats of reaction (ΔH) to determine the necessary heat transfer requirements when scaling up production, for example whether the system has the appropriate amount of heating/cooling elements to sustain its optimal reaction conditions. There are many products and devices capable of characterizing ΔH, such as differential scanning calorimeters, thermal activity monitors, and isothermal nanocalorimeters; however, these systems utilize fixed volumes of reac-tants and are inherently incapable of being run in-line with continuous flow without complex modifications. Unlike traditional calorimeters, this microcalorimeter is designed for continuous flow and to run in-line with an automated microfluidic reaction optimization system with little-to-no modifications. Previously, a similar microcalorimeter was proposed; however, the design had a high heat flux threshold (>50mW), limiting its usefulness to high-energy and/or high-concentration reactions (>1M for reactions where ΔH ≥ 50kJ/mol). This previous design had several other drawbacks including long thermal time constants due to its large thermal mass and requiring a control (baseline) reaction to be run sequentially with the sample reaction. Our design utilizes a parallel-reactor setup, enabling the baseline and sample reactions to run concurrently and allows for direct measurement between the parallel reactors. This parallel setup reduces the thermal mass and experimental time and results in a predicted 5x increase in thermal sensitivity. As such, the microcalorimeter is capable of characterizing ΔH’s faster than the previously mentioned design while at lower (<1M) concentrations. Currently, the continuous-flow microcalorimeter consists of two parallel silicon microreactors, one running the chemical reactions and the other running a baseline reaction. The microreactors are sandwiched in between a series of thermoelectric modules and a machined aluminum jig, and the ΔH is measured by heat flux between the microreactors. The microcalorimeter was used to characterize a Paal-Knorr reaction, resulting in the thermoelectric modules measuring a voltage of 3.70±0.27mV, corresponding to a heat flux of 170.7±12.5mW. When running the baseline reaction in both reactors, the system had a noise floor of 0.19mV. Extrapolating the signal to the noise floor, we predict that the microcalorimeter will be capable of measuring heat fluxes as low as 8.6mW.Our next step for the microcalorimeter is to continue refining the thermal control mechanisms to further improve the heat flux sensitivity. Additionally, we will designed and fabricate a specialized silicon microreactor for the ΔH characterization of solar thermal fuels, molecules designed by our collaborators that are capable of storing solar energy and subsequently releasing the solar energy as heat at a later date. Finally, the system will be inserted into an automated cycling setup to monitor to analyze the stability and cycling longevity of the solar thermal fuels.

MEMS Two-stage Diaphragm Vacuum Pump

Portable sensing devices such as microscale mass spec-trometers need vacuum pumping to lower samples at atmospheric pressure to the desired measurement pressure range. Further improvements for MEMS accelerometers, gyros, and other resonant sensors require internal pressures as low as a few microtorr, which is possible only with active vacuum pumping. While these pressures are easily achieved using mac-roscale vacuum pumps, the larger pumps are not por-table, negating the benefits gained from making small, low-power sensors in the first place. To realize the full potential of portable sensors, a chip-scale vacuum pump needs to be developed.We have developed what is to our knowledge the first two-stage MEMS displacement pump with integrated electrostatic actuation. Two pump stages, along with an efficient layout that minimizes dead volume and a new actuation scheme should enable it to reach pressures below 30 Torr. Actuation is achieved by electrostatically zipping a thin flexible membrane down onto a stiff curved electrode. This actuator topology allows for large displacements and large forces at relatively low voltages (< 100 V). An image of a fabricated two stage micropump is shown in Figure 1 below.We have developed two methods for producing curved electrodes in MEMS devices: 1) hot air trapped during wafer bonding expands with enough pressure to plastically deform thin silicon membrane and 2) strain induced when epoxy cures can pull a membrane into a curved shape. Using the plastically deformed electrodes, we have demonstrated that we can reliably and repeatably zip a thin membrane at low voltages and we have mapped out how the critical voltage depends on the deformation magnitude and the oxide thickness. This is shown in Figure 2 below. These accomplishments have helped us understand the fabrication process and physics of device operation. We plan in the next year to further examine the reliability of plastic deformation in our process, testing the actuators at low pressures, and we hope to fabricate a working micropump that is capable of achieving pressures as low as 30 Torr.

A Tabletop Fabrication System for MEMS Development and Production

A general rule of thumb for new semiconductor fabrica-tion facilities (fabs) is that revenues from the first year of production must match the capital cost of building the fab itself. With modern fabs routinely exceeding $1 billion to build, this rule serves as a significant barrier to entry for small entities seeking to develop or commercialize new semiconductor devices. The barrier is especially for-midable for those groups whose devices target smaller market segments or those which require exotic materials or nontraditional process sequences. The foundry fab model has arisen partially to overcome this inefficiency, but to remain profitable, these foundries typically offer only a few standardized processes that limit customer customization. The limited diversity afforded by these foundries can make some devices with smaller market sizes economically viable, but many devices (particularly in the MEMS sector) require process customization be-yond the level currently offered by commercial foundries.To address these problems, we are working to create a suite of tools that processes 1-2” substrates. This suite of tools (known colloquially as the 1” Fab) takes advantage of modern processing techniques, but at a fraction of the normal cost. We anticipate a full set of tools for product development and small-scale production to cost ~$1 million and require <50 ft2 of space (roughly a large conference table, see Figure 1 for a rendering), compared to >$1 billion and >50,000 ft2 for a typical 8” fab. In addition to the reductions in equipment cost and required space, a 1” Fab also uses significantly less total materials and reagents, requires far less energy to operate, and lessens the environmental impact of fabrication. The total throughput possible in a 1” Fab certainly cannot match a typical 8” fab, but the vast majority of devices that are unsuitable for traditional foundries simply do not require this advantage in production rate. For these devices, the cost savings of the 1” Fab platform and its ability to quickly prototype designs far outweigh any expansion in production schedules. We are currently developing a deep reactive ion etcher (DRIE) tool for the 1” Fab. DRIE tools are used to create highly anisotropic, high aspect-ratio trenches in silicon—a crucial element in many MEMS processes. The modularized design of our DRIE system can be easily adapted to produce other plasma-based etching and deposition tools (like PECVD and RIE). Our DRIE, shown in Figure 2, is the about the size of a large microwave oven and costs just a small fraction of a commercial system. We have demonstrated etch rates of >6 microns per minute and anticipate achieving etch rates of 10µm/min with further process tuning. In the coming year we will continue to optimize our DRIE design and begin developing PECVD and high-temperature process (e.g. oxidation and LPCVD) tools for the 1” fab.

A Double-gated CNF Tip Array for Electron-impact Ionization and Field Ionization

Carbon nanofibers have been investigated for a wide range of applications today. In particular, due to their remarkable conductivity, carbon nanofibers have generated a lot of interest for applications in vacuum microelectronic devices [1-2]. For example, the ionization sensor for gases is one of the most important applications since the conventional ionization sensors are bulky, require high-voltages, and consume high power. The purpose of this project is to fabricate carbon nanofiber field emission and field ionization arrays, which can be utilized in a micro-gas sensor. This device can help reduce the size of the sensor and operating voltages required for gas analysis.In this project, the PECVD method is used to grow vertically oriented carbon nanofibers. The number of carbon nanofibers per site is controlled by the Ni catalyst dot size. It has been demonstrated that the diameter of the Ni catalysts disk must be 300 nm or less to ensure the growth of only a single carbon nanofiber [3]. The 250-nm Ni dots used in this work were defined by ebeam lithography. Figure 1 shows a close-up SEM picture of vertically aligned single carbon nanofiber array grown by PECVD. Later, these vertically-aligned single carbon nanofibers will be integrated into a double-gated field emission/ionization structure developed by L. Dvorson [4]. Figure 2 shows the schematic drawing of the final device.Using the device shown in Figure 2, two approaches for ionizing gas molecules will be investigated for micro-gas sensors. One approach is electron impact ionization, which uses strong electric fields to emit electrons followed by collision between the energetic electrons and neutral gas molecules resulting in ionization. The second approach is field ionization, which is a gentler process in comparison to electron impact ionization. It results in molecular ionization and a simpler mass spectrum due to lower fragmentation of molecules.

Hand-assembly of an Electrospray Thruster Electrode Using Microfabricated Clips

This work [1] explores a method to precisely assemble two planar MEMS components. Our intended application is the assembly of the extractor electrode of an electrospray thruster, in which holes in the extractor must be aligned precisely with emitter needles or ridges (see [2] in this volume). In this method, the components can be accurately assembled by hand. Moreover, the assembly is made using a system of flexures, allowing considerable flexibility in the choice of materials and coatings for the components.Figure 1 shows a diagram of our device. The extractor electrode (red) needs to be assembled in a recess on the base of the electrospray thruster (blue). To do this, the extractor is placed by hand in its recess. This step is easy as there are a few hundred micrometers of slack. The extractor is then rotated. As it rotates, features around its periphery force it to align its center to within 50 micrometers of its final position. As it continues the rotation, flexible fingers on the base part get flexed by the extractor, until the fingertips fall into notches in the sidewalls of the extractor.Our devices, shown in Figure 2, were initially made out of Silicon using deep reactive-ion etching (DRIE). To show the flexibility of the method, we have also produced laser-cut polyimide extractors. The polyimide extractors have allowed us to achieve electrical insulation between the extractor and the rest of the device, which is vital for our intended application.We have measured front-to-back alignment on all our silicon devices and found that they are within 9 micrometers RMS of their intended location. However, multiple assembly/disassembly cycles on a specific device show that the position is repeatable to within 1.5 micrometers of standard deviation. This measurement suggests that much of the misalignment we are observing occurs due to misalignments during the various photolithography and bonding steps.

A Fully Microfabricated Planar Array of Electrospray Ridge Emitters for Space Propulsion Applications

Electrospray thrusters work by extracting ions or charged droplets directly from a liquid surface using an electrostatic field and accelerating them in that field to produce thrust. This method could lead to more efficient and precise thrusters for space propulsion applications. The propellant liquid is generally placed at the tip of a needle to enhance the electrostatic field. The electrospray process limits the thrust from a single emitter needle. To get into the millinewton range will require an array with thousands of emitters. Batch microfabrication is well suited to making such an array.We have designed and built a prototype thruster that consists of two silicon parts (Figure 1) made using deep reactive ion etching (DRIE) and SF6 plasma etching. The thruster base holds the electrospray emitters. Its surface is treated to control the areas where propellant can go. The extractor produces the electric field, which generates the electrospray. It is equipped with slits to allow the accelerated particles through. The two parts are positioned relative to each other using a kinematic mount, in which alumina balls rest in holes on the silicon dies (Figure 1). Alumina screws hold the assembly together.In this design, we have replaced the needles that are typically used in electrospray thrusters by ridge emitters: vertical slabs with sharp tips spaced along their length (Figure 2). We have shown that our process for needles [1] can be extended to ridge shapes, and a modeling effort is underway to better control the shapes of the emitters.Our thruster has been fired with the ionic liquid EMI-BF4. This experiment shows successful electrical insulation, even in the presence of the liquid. Challenges we now face are reducing the amount of emission that is intercepted by the extractor and determining where on the ridges the emission is coming from.

A Double-gated Silicon Tip, Electron-Impact Ionization Array

A device with the ability to ionize gases is needed for a variety of applications, of which the mass spectrometer (MS) [1-2] is one of the most important. The ionization method in the majority of gas analyzers in MS is electron-impact ionization, which uses a beam of electrons that collides with gas molecules. Through this collision process, energy is transferred from the electrons to the gas molecules, which causes electrons on the gas molecules to be stripped off (i.e., ionization of the gas molecules). Traditionally, thermionic emission, which consists of a filament that produces electrons when heated, is the most common way of generating electrons for MS using electron impact ionization. However, thermionic emission has several disadvantages: slow switch-on time, large power consumption, and lack of robustness. These disadvantages, however, are eliminated when field emission is used instead.In this project, a double-gated silicon field emission device is used to generate the electron source for electron impact ionization. Figure 1 shows a SEM picture of a double-gated silicon field emission device used here. Using this device, we have demonstrated the linear relationship between the emission current (IE) and the ion current (II) at a fixed pressure (10-4 torr) as shown in Figure 2.

A MEMS Electrometer for Gas Sensing

The DARPA-funded micro gas analyzer program aims to develop portable, low-power, fast, and reliable gas analyzer technology for a wide range of applications. The system architecture of the gas analyzer contemplates a MEMS electrometer at the end of the system. The electrometer characterizes the ionized species that are filtered by the quadrupole. The sensitive element of the electrometer is a MEMS structure embedded in a feedback loop of a precise oscillator circuit. The electrometer has a comb drive that sets the electrometer to oscillate. Shifts in the oscillation frequency are related to changes in the capacitance of the electrometer due to ion interception. The resolution of the device is estimated at 100 e/√Hz in vacuum [1]. Figure 1 shows a fabricated MEMS electrometer. Figure 2 shows the experimental data of one of these MEMS electrometers, in air. The experimental resonant frequency is 6.2 kHz, and the conversion gain was estimated at 2 × 109 V/C (theoretical value is 7 × 109 V/C). Current research focuses on implement lock-in detection, which will remove the noise from the drive signal because the output has twice the frequency of the input signal.

A Single-Gated CNT Field-Ionizer Array with Open Architecture

The micro gas analyzer project aims to develop the technology for portable, real-time sensors intended for chemical warfare and civilian air purity control. The device is composed of four micro-fabricated subsystems: an ionizer, a mass filter based on a quadrupole array [1], an electrometer [2], and a positive displacement pump [3]. We are developing a single-gated fieldionizer array based on gated carbon nanotubes (CNTs). The devices achieve species ionization by tunneling of outer shell electrons due to the presence of high electric fields that the device sets. We use CNTs as field enhancers because of their small radii and high aspect ratio while the gate proximity ensures high fields at low voltage. State-of-the-art ionizers use electron-impact ionization (thermionic cathodes), incurring in excessive power consumption, low current, current density, ionization efficiency, and short lifetime. The field-ionizer arrays (Figure 1) are able to soft-ionize species, thus achieving molecule ionization. The reliability and lifespan of the field-ionizer arrays are larger than the corresponding values for electron-impact ionizer arrays because the CNTs are biased at the highest potential in the circuit, thus making it unlikely for ionized molecules to back-stream. Figure 2 shows two SEM pictures of a single-gated CNT array that implements a selective CNT-growth process. This process reduces the fabrication complexity of the device because it grows CNTs from an un-patterned catalyst (Ni). Current research efforts concentrate on improving the device and data acquisition, including benchmarking the performance of the ionizer in low-pressure oxidizing environments.

A MEMS Quadrupole that Uses a Meso-scaled DRIE-patterned Spring Assembly System

The DARPA-funded micro gas analyzer program aims to develop portable, low-power, fast, and reliable gas analyzer technology for a wide range of applications. One of the subsystems of the gas analyzer is a mass filter. An array of micro-fabricated quadrupole mass filters is being developed for this purpose. The quadrupoles will sort out the ions based on their specific charge. Both high sensitivity and high resolution are needed over a wide range of ion masses, from 20 to 200 atomic mass units. In order to achieve this performance, multiple micro-fabricated quadrupoles, each operating at a specific stability region and mass range, are operated in parallel. The proof-of-concept device is a single, linear quadrupole that has a micro-fabricated mounting head with meso-scaled DRIE-patterned springs. The mounting head allows micron-precision hand assembly of the quadrupole rods [1]–critical for good resolution and ion transmission. The micro-fabricated mounting head can implement quadrupoles with a wide range of aspect ratios for a given electrode diameter. There are currently two versions of the mounting head, able to interact with rods of diameters equal to 1588 and 559 micrometers. The choice of electrode diameter results from pondering the dimensional uncertainties and alignment capabilities with respect to the expected resolution and transmission goals. Figure 1 shows an assembled MEMS quadrupole, including some detail of the spring structure near the quadrupole transmission region. The quadrupoles that have been implemented so far span the aspect ratio range from 30 to 60. Figure 2 shows the experimental data of one of these quadrupoles on a FC-43 sample, where a mass resolution of 2 amu and a full mass range of 200 amu are demonstrated, while using a 1.2-MHz RF power supply to drive the quadrupole. Current research efforts concentrate on developing RF power supplies of higher frequency to obtain better performance from the same device.

Digital Holographic Imaging of Micro-structured and Biological Objects

The need for understanding the trophodynamics of the ocean has led to the development of several instruments for monitoring plankton communities, critical indicators of the ocean’s health and the base of the aquatic food chain. The three competing methods for plankton observation utilize direct, acoustic, and optical sampling techniques; however none of the current systems can provide the complete data set required for predictive modeling capabilities. The goal of this project is to develop a small, low-power, digital holographic imaging (DHI) system that allows for in situ monitoring of plankton and other aquatic communities. This system allows microbiologists to collect high-resolution, spatio-temporal data on species-specific population structures. In addition to biological studies, the DHI camera can be utilized in diverse areas such as medical analysis, quality control inspection, and MEMS device characterization.DHI uses a digital sensor to record holograms, formed by the interference pattern between a reference wave and a field produced by scattered light from an illuminated object. The illumination source is coherent and typically provided by a laser. The recorded images are processed on a computer to reconstruct the original object field at a given axial location [1]. From the reconstructed images, information about the object such as morphology, topology, and 3D coordinates can be computed throughout a large sample volume. In addition, velocity and 3D trajectories are available under slightly modified methods.Experiments have focused on biological applications, including marine and microbial organisms ranging from 5 to 2000 microns. In addition to the inline configuration (Figure 1), several setups have been implemented to explore smaller scales, including the use of spherical reference waves, 4f telescopes, and microscope objectives. Figure 1 shows our compact benchtop prototype DHI camera, currently being developed to be used as a sea-going instrument for deep-sea microbiology. Using a lens-free spherical configuration with a working distance of 50 mm, all lines on a 1951 USAF resolution target can be resolved, down to 2.2 microns in width. A 4f system was used to track the trajectories of 7 micron algae over several seconds. Small plankton, 50 to 500 microns long, have been imaged using all three setups with excellent clarity. Figure 2 shows a reconstruction from an inline configuration of an adult copepod. Future work includes incorporating the DHI camera into an underwater vehicle. Additional work will focus on tracking small particles under turbulent flow conditions.

Aligning and Latching Nano-structured Membranes in 3D Micro-Structures

The 3D micro-electro-mechanical systems (MEMS) manufacturing is an emerging technology that promises to solve many of the problems in the microfabrication industry. In microelectronics, as the feature sizes of the components approach their physical limits, packing more transistors on a microprocessor or on a memory chip requires expanding the circuitry into the third dimension. In optical switches, the traditional 2D MEMS-based switches do not scale easily beyond 32 ports; to increase the number of ports, companies have been developing 3D micro-mirror arrays that can reflect light in multiple directions. The Nanostructured Origami™ 3D fabrication process is a two-step method for fabricating 3D MEMS; it involves patterning films on a surface and then folding the patterned films to create three-dimensional structures [1]. This method is advantageous because it uses state-of-the-art 2D patterning methods and it involves patterning all the parts of the structure in one step, eliminating problems of feature misalignment. However, in creating the 3D structures, two major challenges arise; the first is to accurately place the folded membranes in their desired positions and the second is to fix the membranes in those positions to maintain the final 3D configuration. Current positioning solutions involve the use of mechanical motion-limiters that prevent folded membranes from moving beyond a certain point [2]. We propose two methods for aligning and latching folded nano-patterned membranes in 3D microstructures. The first method uses photoresist pads to glue together two mating surfaces of the structure (Figure 1). What distinguishes this method from previous polymer gluing attempts is that we use dense gold patterns as a local heater to melt the photoresist pads. This allows us to control the membranes we latch and the time when we latch them. We use patterned gold wires to form the hinges that hold the membranes together. Thin dense gold patterns also serve as local heaters to melt the photoresist gluing pads. The surface tension in the molten pads aligns the surfaces and solidification of the photoresist latches them together. The second method uses mechanical alignment and latching features that allow edges-to-surface latching (Figure 2). One major advantage of this method is that the structural components and the alignment features are patterned in the same lithographic step, which lowers costs and minimizes misalignment errors. Another interesting aspect is the cascaded alignment; the alignment features are designed so that they function sequentially, starting from the features closest to the hinge. With proper design of those features, the alignment system can achieve accurate positioning using the features away from the hinge while tolerating a large initial positioning error range by virtue of the short radius sustaining the features closest to the hinge.

A Microfabricated Platform for Investigating Multicellular Organization in 3-D Microenvironments

Understanding how complex intrinsic and external cues are integrated to regulate cell behavior is crucial to the success of cell-based therapies in the treatment of human disease. Systematic and quantitative investigation of these microenvironment signals was first enabled by precise cell positioning using 2-D micropatterning tools [1]. However, cellular signaling is often altered in adherent tissue culture where structural cues are lacking (including tumor, stem, and differentiated cells), in contrast to 3-D culture systems that more closely resemble in vivo cell behavior [2]. Our goal was to develop new micropatterning tools capable of micron-scale cell patterning and organization within a 3-D hydrogel with tissue-like properties. We developed a technique for the rapid formation of reproducible, high-resolution, 3-D cellular structures within a photo-crosslinkable hydrogel using dielectrophoretic forces (Figure 1) [3]. We demonstrate parallel formation of ~20,000 cell clusters of precise size and shape within a 1 x 2 cm2 slab of tissue (Figure 2a), with high cell viability and differentiated cell function maintained over 2 weeks in culture. By modulating cell-cell interactions in clusters of various size (independent of hydrogel geometry, chemistry, or volumetric seeding density; Figure 2b), we present the first evidence that 3-D microscale tissue organization regulates chondrocyte behavior (Figure 2c) [3]. This dielectrophoretic cell patterning (DCP) technology enables further investigation of the role of tissue architecture in many other multicellular processes from embryogenesis to regeneration to tumorigenesis.

Microfluidic Hepatocyte Bioreactor

This project utilizes microfluidic systems to study how groups of liver cells acquire emergent tissue properties. Hepatocytes (the parenchymal cells of the liver) respond to many cues in their microenvironment: neighboring cells, growth factors, extracellular matrix, dissolved oxygen, and their interactions. One tissue property of interest is the compartmentalization of gene expression in multicellular domains along the liver sinusoid. This process, often described as “zonation,” underlies much of liver physiology and regional susceptibility to toxins. We have previously shown oxygen gradients can be used to compartmentalize mixed populations of hepatocytes in a large-scale reactor [1]. Here, we present a microdevice that enables one to explore the crosstalk between two inputs (oxygen gradients and soluble growth factors) in a systematic fashion. The device consists of a two-layer PDMS microfluidic network with an on-chip dilution tree bound to a glass slide with an array of microreactors. Hepatocyte zonation is induced in each microreactor through local oxygen concentration, which is modulated through gas channels separated from the bioreactor by a 100-µm PDMS layer as shown in Figure 1. The local oxygen concentration in the microchannels is quantified in Figure 2. Primary rat hepatocytes are seeded into microreactors together with 3T3 fibroblasts, which act to stabilize the hepatocyte phenotype as described previously. This device will be useful to further explore liver tissue biology in vitro including the dynamics of zonation, mechanisms of oxygen sensing, and the role of growth factors in zonal response.

Micromechanical Control of Cell-Cell Interaction

Cellular behavior within tissues is driven by environmental cues that vary temporally and spatially with granularity on the order of individual cells. Local cell-cell interactions via secreted and contact-mediated signals play a critical role in these pathways. In order to study these dynamic small-scale processes, we have developed a micromechanical platform to control microscale cell organization so that cell patterns can be reconfigured dynamically. This tool has been employed to deconstruct the mechanisms by which liver-specific function is maintained in hepatocytes upon co-cultivation with stromal support cells. Specifically, we examine the relative roles of cell contact and short-range soluble signals, duration of contact, and the possibility of bi-directional signaling.The device consists of two silicon parts that can be locked together either to allow cell-cell contact across the two parts or to separate the cells by a uniform gap of approximately 80 µm (Figs. 1 and 2). Switching between these two states is actuated simply by pushing the parts manually using tweezers; no micromanipulation machinery is necessary. Micron-scale precision is possible due to a 10:1 mechanical transmission ratio and microfabricated snap locks, both of which are monolithically incorporated into the silicon structure. The entire device is fabricated in a simple single-mask process using through-wafer deep reactive ion etching. To provide a surface compatible with cell culture, the surface is coated with a layer of polystyrene and plasma-treated, providing a standard tissue-culture surface.

Characterization and Modeling of Non-uniformities in DRIE

Our previous work on spatial non-uniformities in deep-reac-tive ion etch (DRIE) has provided a method by which an etch-ing tool and associated “recipes” of operating parameters may be pre-characterized [1]. That work allowed the wafer-average pattern opening density (or “loading”) to be related to wafer-scale etch rate variations. Such variations have been attributed to loading-dependent interactions of the flux densities of SxFy ions and F neutrals and to shifts in the gross flows of fluorine across the wafer [2]. Unlike some other approaches [3–5], our method captures asymmetries in the fluxes within the chamber. Our approach is now supplemented by an understanding of how uniformity depends on the localization of etched patterns within the wafer (Figure 1). A semi-physical model represents the diffusion of monatomic fluorine etchant parallel to the wa-fer’s surface, giving a two-dimensional filter which translates a discretized map of pattern density into a prediction of how etch rate will vary within and between dies [6]. This die-level mod-el is readily combined with the existing wafer-level model. To tune this combined model for a new recipe, a set of about five test wafers is etched, and fitting algorithms are run with etched-depth data. Collaborative experiments with Surface Technology Systems Ltd have demonstrated our approach in use with a prototype etch tool. Further experiments have compared the characteristics of different manufacturers’ tools. We have also quantified a memory effect whereby the aver-age pattern density of one etched wafer can affect the average rate and non-uniformity with which a subsequent wafer etches (Figure 2). In the future we aim to incorporate well-known fea-ture size or aspect ratio effects into our model [7]. We envisage our approach being integrated into computer-aided design systems for MEMS and believe that it will be of particular use when one is keen to preserve a fast-average etch rate and is thus loath to win uniformity by reducing the chamber pres-sure.

Understanding Uniformity and Manufacturability in MEMS Embossing

The hot embossing of thermoplastic materials, such as polymethylmethacrylate (PMMA) or cyclo- olefin copolymer (COC), is a promising way to manufacture microfluidic channels and networks [1]. Hot embossing potentially offers lower per-area cost than the micromachining of quartz or silicon and easier scaling-up of production than soft lithography using polydimethylsiloxane [2]. In hot embossing, a microfabricated mold (typically of silicon or nickel) is pressed into a flat sample of polymeric material that has been softened by heating it above its glass-transition temperature. We are particularly interested in how the spatial distribution of mold features—their diameters, shapes, and areal densities—may influence the quality of embossed patterns. We are developing a simulation approach whose building-block is a simple model in which, for given embossing conditions, a feature-sized disk of viscous polymer is compressed at a rate inversely proportional to the square of the radius of the disk [3] (Figure 1). Such a model implies that the mold will sink into the substrate at a spatially uniform rate when the product of the areal density of mold features and the square of their average radius remains constant across the mold. We aim to construct a reliable model that is computationally efficient and that can predict the combination of embossing pressure and duration required by any mold design. We are investigating the measurement of birefringence of embossed samples [4] as a way of monitoring the embossing process (Figure 2). We are also pursuing a technique for the bonding of polymer surfaces that promises minimal deformation of pre-embossed features: the polymer surfaces are exposed to an oxygen plasma for ~1 minute and then pressed together [5].

A MEMS Drug Delivery Device for the Prevention of Hemorrhagic Shock

Hemorrhagic shock is the number one cause of preventable death on today’s battlefield [1]. It is a hypotensive state of deficient organ perfusion caused by blood loss from wounds of the extremities or internal injuries. Hemorrhagic shock is normally treated by hemorrhage control, fluid replacement, and the injection of vasoconstrictors. Battlefield conditions, however, can prevent the timely administration of these measures. Hemostatic dressings developed for battlefield application are useful in controlling open wound hemorrhage but cannot stop internal bleeding or avert shock if too much blood has been lost [1]. Arginine vasopressin is a vasoconstrictor that causes peripheral and abdominal arteries to constrict, shunting blood to the vital organs in case of hemorrhage [2]. It improved survival by restoring blood pressure in pre-clinical experiments and clinical case studies of hemorrhagic shock when treatment was not immediately available [3-7]. This property makes it a perfect candidate for battlefield injection to keep wounded soldiers alive until they can be properly treated. Self-injection may not always be possible, however, due to the nature of these traumas.We are currently developing an implantable drug delivery microelectromechanical system (MEMS) to deliver vasopressin to wounded soldiers on the battlefield. This device consists of a silicon substrate in which pyramidal wells are etched using common MEMS processing techniques. The wells are capped by metallic membranes and the chip is hermetically bonded to a Pyrex macroreservoir (Figure 1). The macroreservoir can be injected with 25 µL of a vasopressin solution to be released on demand. Applying an electric pulse through a metallic membrane melts it by resistive heating, exposing the macroreservoir to the environment. We also observed the formation of multiple thermal bubbles inside the macroreservoir, which enabled rapid delivery of the solution. We are redesigning the device to better control this mechanism. Future challenges include insuring long-term hermeticity and wireless activation of the device.

Application of Input Shaping® and HyperBit™ Control to Improve the Dynamic Performance of a Six-axis MEMS Nano-positioner

We have recently demonstrated how Input Shaping® and HyperBitTM control may be used to obtain fine-resolution motion and minimize vibration errors in all six axes of a six-axis, MEMS nano-positioner [1]. The dynamic problems in MEMS positioners, e.g., ringing/overshoot, that are conventionally addressed by damping must be resolved using control techniques since it is difficult to incorporate damping into micro-scale devices. Secondly, a positioner’s range to resolution ratios has to be 1 million or larger and also its “on-chip” digital-to-analog converters would need to be minimized on the expensive silicon real estate. These issues will be resolved by the applying the Input Shaping and HyperBit control.We first study the dynamic characterization of the nanopositioner, the microHexFlex [2], including the natural frequencies and their corresponding mode shapes. We then demonstrate the effect of Input Shaping and HyperBit on the nano-positioner’s resolution and settling time. Using these techniques, it is possible to obtain ms settling times with sub-nanometer resolution. The practical implications of this work are that future small-scale precision devices will be able to use these techniques to provide low-cost, multi-axis positioning at high-speeds speed and with fine resolution.The micro-HexFlex nanopositioner possess a 2.5-mm footprint and consists of two layers of single crystalline silicon with one layer of silicon dioxide in between. The stage of the micro-HexFlex is supported by axi-symmetric micro-scale flexures. Thermomechanical actuators are used to drive the Micro-HexFlex. In our tests, the thermomechanical actuators were driven via a voltage that was preconditioned using an Input-shaping controller. The controller [3] is an implementation of a feed-forward technique that acts to remove ringing and overshoot by modifying the input signal to the actuators so as to obtain the best possible performance from the positioner.We also add HyperBit DAC technology, a recently developed technique [4] for extending the resolution of digital-to-analog converters (DACs), for instance using a 4- bit DAC to obtain 12-bit functionality. Since DAC update rate capabilities are significantly faster than the bandwidths of the devices being driven, this technique allows the idle time-domain capacity of “low-bit” DACs to emulate that of “high-bit” DACs. The improvement in resolution is therefore obtained with simpler DAC equipment/circuitry that is more easily fabricated and integrated with micro- and meso-scale devices. Experimental results indicate reduction in dynamic errors by two orders of magnitude when the positioner was given 100-Hz square wave commands.

Multi-Axis Electromagnetic Moving-Coil Microactuator

Electromagnetic (EM) micro-actuators are becoming increasingly important in micro-systems requiring moderate forces operating over a large range of motion. The applications that benefit from the performance advantages of EM micro-actuators include micro-scanning systems, micro-fluidic pumps, and positioning systems. Advantages of electromagnetic actuation over other classes of micro-actuators include low-voltage operation, moderate power density, large operating distances, linear response, multi-axis capability, and high bandwidth [1]. This work leverages the advantages of EM interactions to design a moving-coil micro-actuator that enables two-axes actuation with moderate forces (10+ mN) over large operating distances (10+ micrometers) at moderate mechanical frequencies (1+ kHz) using assembled permanent magnet field sources.The two-axes electromagnetic actuator consists of moving coils suspended on compliant silicon flexure springs above an array of 3 rectangular permanent magnets, as shown in Figure 1. The phase of the stacked coils results in Lorentz forces that are independently controllable in-the-plane and out-of-the-plane. The coil-spring fabrication scheme includes electroplating of copper coils, followed by a deep reactive-ion etch (DRIE) to pattern and release the compliant springs. Millimeter-sized permanent magnets are then aligned to the spring layer using an alignment chip. Successfully fabricated micro-coil structures have been shown to sustain current densities over 1000 Amps per square millimeter.A quasi-analytic electromagnetic force model for the device has been developed and experimentally validated against a centimeter-size bench-level prototype actuator. Figure 2 shows the predicted lateral-actuator force per coil-footprint versus current input for a typical actuator with 900-µm2 coil cross section. The actuator will be implemented in a high-speed meso-scale nano-positioner with applications in nano-fabrication and scanning-probe microscopy. When equipped with this micro-actuator, the nano-positioner is expected to be able to position millimeter-sized samples in six axes of motion (x, y, z, tip, tilt, yaw) with repeatability better than 10 nanometers at frequencies greater than 1 kHz.

Multiwell Cell Culture Plate Format with Integrated Microfluidic Perfusion System

Recent reports indicate that it takes nearly $800 million dollars and 10-15 years of development to bring a drug to market. Nearly 90% of the lead candidates identified by current in vitro screens fail to become marketable drugs. One of the reasons for the high failure rate of drug candidates is the lack of adequate models. To address the problem, we have developed a new cell culture analog amenable to routine use in drug development. It is based on the standard multiwell cell culture plate format but it provides perfused three-dimensional cell culture capability.The multiwell plate microbioreactor array [1, 2] consists of a fluidic and a pneumatic manifold with a diaphragm sandwiched in between them. The fluidic manifold contains an array of microbioreactor and reservoir pairs (Figure 1). Each microbioreactor/reservoir pair is fluidically isolated from all other microbioreactors on the plate. A key component of a microbioreactor is a scaffold for tissue morphogenesis (Figure 2). The scaffold is a thin wafer containing an array of channels in which cells self-assemble into 3D pieces of tissue. It is backed by a filter and a support scaffold. Tissue in the scaffold is perfused by cell culture medium. The medium is re-circulated between the reactor and reservoir by a diaphragm pump. The diaphragms of all pumps and rectifying valves are actuated in parallel via three pneumatic lines distributed by the pneumatic manifold. Fluidic capacitors control flow pulsatility.The system provides a means to conduct high throughput assays for target validation and predictive toxicology in the drug discovery and development process. It can be also used for evaluation of long-term exposure to drugs or environmental agents and as a model to study viral hepatitis, cancer metastasis, and other diseases and pathological conditions.

Characterization of Nanofilter Arrays for Biomolecule Separation

In the past decade, microfabricated devices have been developed that can separate, detect, and analyze various biomolecules [1]. In contrast to the sieving gels that are historically used in these studies, microfabricated devices are precisely designed and constructed. The deterministic structure of these devices facilitates experiment design and testing of theory. Periodic nanofilter arrays have been shown to separate DNA from 100 bp to 10 kbp [2]. These nanofilters consist of a regular sequence of free and constricted regions, with 50-100 nm being the characteristic dimension of the constricted region. In this context, the DNA is smaller than the constriction size, suggesting applicability of the Ogston sieving mechanism. Movement is characterized by the partitioning between the free and constricted regions due to steric constraints [3-4]. DNA has a persistence length of 50 nm (150 bp) and can be approximated as semi-rigid rods in this size range, facilitating theoretical analysis.We investigated the effects on separation efficiency and resolution of changing various device and experiment parameters. These parameters include the strength of the electric field; depth of the deep region; depth of the thin and deep regions, while maintaining their ratio; silicon substrate bias; buffer strength; and period of the nanofilter array.

Patterned Periodic Potential-energy Landscape for Fast Continuous-flow Biomolecule Separation

Manipulation of charged biomolecules through confining environments has broad applications in life science. Recent progress in fabricating well-defined spatial constraints allows direct observation of novel molecular dynamic behavior in molecular-sized confining structures. Further, it shows exceptional promise for providing regular sieving media with superior separation performance. Here we demonstrate a continuous-flow, biomolecule-separation device that makes use of a patterned anisotropic sieving matrix consisting of a two-dimensional periodic array of nanofilters. The electrophoretic drift of biomolecules in the sieving medium involves a differential bidirectional motion through two-dimensional, periodically modulated, free-energy landscapes that results in a vectorial apparent electrophoretic mobility that directs molecules of different sizes to follow radically different paths. This method provides a novel basis for dispersing small fluid-borne biomolecules into distinct fractions. A fluorescently labeled dsDNA mixture (50-766 bp) used to characterize the device was separated in 1 minute with a resolution of about 10%. The patterned anisotropic sieve was also used for size-fractionation of SDS-protein complexes of size ranging from 11 to 200 kDa in 1 minute. By virtue of its gel-free and continuous-flow operation, this device suggests itself as a key component of an integrated microsystem that prepares and analyzes biomolecule samples.

Fabrication of Massively-parallel Vertical Nanofluidic Membranes for High-throughput Applications

Nanofluidics has gained tremendous successes in the last few years because they provide unique capability in biomolecular manipulation and control. For nanofluidic applications, one critical issue is the availability of reliable, reproducible fabrication strategies for nanometer-sized structures. A simple technique, without nanolithography or special tools, has been developed to generate planar nanochannels with precise control of depths to the nanometer scale for many applications including separation [1] and preconcentration [2]. However, one big issue with these planar nanofluidic channels is the limited fluidic conductance that results in low throughput.Here we describe a novel fabrication approach to generate massively-parallel vertical nanochannels with the well-controlled gap size down to 100 nm [3]. We use anisotropic wet etching (KOH) to make deep, vertical trenches on Si (110) substrate (Figure 1A). Alternatively, conventional deep reactive ion etching (DRIE) can be performed to produce very deep trenches, and then the sidewalls can be smoothed by a short KOH etching. Then the width of the trench channel is further decreased to a desired thickness even below 50 nm (Figure 1B), by growing thermal oxide. Also, backside etching of the Si wafer can yield thin membranes over a wide area (~ 6-inch wafer) with well-defined membrane thickness, if needed. Our method requires neither expensive nanolithography expertise nor other tools and allows the integration of a large number of narrow, vertical nanofluidic filters with fluidic conductance 10~100 times higher than planar nanochannels. Furthermore, we have demonstrated efficient, high-throughput separation of large DNA molecules in our vertical nanofilter array device based on the entropic trapping mechanism (Figure 2). We believe that these membrane devices could be a key to the high-throughput nanofluidic sample-preparation microsystems.

Continuous-flow pI-based Sorting of Proteins and Peptides in a Microfluidic Chip Using Diffusion Potential

In this work, we have developed a simple microfluidic chip that can sort biomolecules based on their isoelectric point (pI) values in a simple buffer system. The new method differs from previous approaches such as transverse isoelectric focusing [1] or free-flow electrophoresis [2] in that this process involves no external power supply and no special ampholyte. Instead, we utilize the diffusion potential generated by the diffusion of different buffer ionic species in situ at the laminar flow junction. The use of diffusion potential in microfluidics was previously demonstrated with the mass transport of dye molecules between the two streams in [3]. However, they did not explicitly demonstrate a separation of two species. In our device, we establish a laminar flow junction between two buffers with different pH and concentrations. A potential gradient is developed across the liquid junction, generating a high-enough electric field to mobilize and to collect biomolecules at the boundary when their pI values fall between the two buffer pH values. The computational modeling shows a decreasing potential gradient from 17.1 V/cm to 6.9 V/cm along the 2-mm-long microchannel (20 µm deep, 100 µm wide), as the concentration gradient becomes shallower toward the end of the channel due to mixing (Figure 1). In our initial experiment, two pI-markers (Figure 2) as well as two proteins were successfully sorted in this device, with a flow rate of 5~10 µL/min. To characterize the accuracy of this pI-based sorting process, we tested sorting behavior of the device by changing the pH value of the sample buffer in 0.1 pH step. It was shown that a peptide can be sorted into a different output stream with a ~0.1pH unit resolution. We are currently working on the development of new buffer systems as well as on the hybrid approach with a superimposed external electric field to increase the sorting efficiency and resolution. Once fully developed, it can potentially be a pI-based sample fractionation tool for proteomic analysis of complex biomolecule samples.

Cell Stimulation, Lysis, and Separation in Microdevices

Quantitative data on the dynamics of cell signaling induced by different stimuli require large sets of self-consistent and dynamic measures of protein activities, concentrations, and states of modification. A typical process flow in these experiments starts with the addition of stimuli (cytokines or growth factors) to cells under controlled conditions of concentration, time, and temperature, followed at various intervals by cell lysis and the preparation of extracts. Microfluidic systems offer the potential to do this in a reproducible and automated fashion. Figure 1 shows quantification of the stimulation of a T-cell line with antibodies performed in a microfluidic device with integrated cell lysis. The device is capable of resolving the very fast kinetics of the cell pathways, with protein activation levels changing 4-fold in less than 15 seconds. The quantification of the lysate is currently performed off-chip using electrophoretic separation. To extract meaningful data from cellular preparations, many current biological assays require similar labor-intensive sample purification steps to be effective. Micro-electrophoretic separators have several important advantages over their conventional counterparts including shorter separation times, enhanced heat transfer, and the potential to be integrated into other devices on-chip. However, the high voltages required for these separations prohibit metal electrodes inside the microfluidic channel. A PDMS isoelectric focusing device with polyacrylamide gel walls has been developed to perform rapid separations by using electric fields orthogonal to fluid flow (Figure 2). This device has been shown to focus low molecular weight dyes, proteins, and organelles in seconds.

Thermal Management in Devices for Portable Hydrogen Generation

The development of portable-power systems employing hydrogen-driven solid oxide fuel cells continues to garner significant interest among applied science researchers. The technology can be applied in fields ranging from the automobile to personal electronics industries. This work focuses on developing microreaction technology that minimizes thermal losses during the conversion of fuels – such as light-end hydrocarbons, their alcohols, and ammonia – to hydrogen. Critical issues in realizing high-efficiency devices capable of operating at high temperatures have been addressed, specifically, thermal management, the integration of materials with different thermophysical properties, and the development of improved packaging and fabrication techniques.A new fabrication scheme for a thermally insulated, high temperature, suspended-tube microreactor has been developed. The new design improves upon a monolithic design proposed by Arana et al.[1]. In the new modular design (Figure 1), a high-temperature reaction zone is connected to a low-temperature (~50°C) package via the brazing of pre-fabricated, thin-walled glass tubes. The design also replaces traditional deep reactive ion etching (DRIE) with wet potassium hydroxide (KOH) etching, an economical and time-saving alternative. A brazing formulation that effectively accommodates the difference in thermal expansion between the silicon reactor and the glass tubes has been developed.

Autothermal Catalytic Micromembrane Devices for Portable High-Purity Hydrogen Generation

The high efficiency and energy density of miniaturized fuel cells provide an attractive alternative to batteries in the portable power generation market for consumer and military electronic devices [1-3]. The best fuel cell efficiency is typically achieved with hydrogen, but safety and reliability issues remain with current storage options. Consequently, there is continued interest in reforming liquid fuels to hydrogen. The process typically involves high temperature reforming of fuel to hydrogen combined with a low temperature PEM fuel cell, which implies significant thermal loss. Owing to its high hydrogen content (66%) and ease of storage and handling, methanol is an attractive fuel. However, partial oxidation of methanol also generates some CO, which may poison the fuel cell catalyst. Previously [4] we successfully demonstrated hydrogen purification using thin (~200 nm) Pd-Ag membranes using electrical heating. Further, integration of these devices with LaNiCoO3 catalyst allowed methanol reforming at 475oC with 47% fuel conversion [5]. Since microreactors possess high surface area to volume ratio, minimizing heat loss is important. Hydrogen flux across the Pd membranes is an equilibrium controlled process. Thus to achieve thermal management, the unextracted hydrogen, generated CO, and unreacted methanol can be completely oxidized in a separate reactor. In the current work, we explore the realization of autothermal hydrogen generation by fabricating silicon- based reactors using bulk micromachining techniques. The hydrogen generation unit comprises a 200-nm palladium-silver membrane coated with a reformer catalyst while the combustor is loaded with platinum catalyst. High thermal conductivity of silicon ensures autothermal operation. Upon thermal isolation using vacuum packaging [6], we characterize the performance of this integrated, autothermal hydrogen generation system in terms of energy efficiency and hydrogen production.

Multiphase Transport Phenomena in Microfluidic Systems

Fluid interfaces provide unique opportunities for microfluidic and nanofluidic systems. Applications range from microscale heat exchangers and miniature fuel cells to microreactors for materials synthesis. Multiphase flow in such devices can be challenging, as the interfacial forces naturally favor axisym-metric geometries that are difficult to microfabricate. The ad-vantages of surface tension dominated microfluidics include a much richer dynamic flow behavior and enhancement of heat and mass transfer by creating secondary flows. These advantages offer many uses beyond enabling gas-liquid and fluid-solid reactions [1]. In particular, we are interested in segmented flow of gas and liquid in hydrophilic channels. Figure 1 shows several key features of this flow for reaction purposes. The presence of bubbles reduces the amount of dispersion of liquid flowing through the channels, ensuring that reactants and products spend a uniform amount of time in the system. For nanopar-ticle synthesis in microfluidic networks, a uniform residence time distribution translates into narrowly distributed particle sizes [2-3]. Liquid segments are efficiently mixed by circula-tion motion and gas bubbles are separated from microchan-nel walls by only a thin film (thickness < 1 µm). Thin films re-duce mass transfer resistance to components immobilized on the walls, such as catalysts [4] or analytical reagents and anti-bodies. We are also interested in the dynamics of multiphase flow through microchannels that are populated with a forest of micropillars (diameters: 50 µm – 100 µm). The observed flow patterns (Figure 2) connect to fundamental studies of flow in porous media and to catalysis. Gas-liquid and liquid-liquid flow patterns and their dynamics are determined in pulse-laser fluorescent micrographs and with microscale par-ticle image velocimetry (PIV) measurements. Characteristics of such three-phase systems, such as persistent static fractions, axial dispersion and mixing, are compared with multiphase flow in macroscopic unstructured beds and porous media.

Microfluidic Synthesis and Surface Engineering of Colloidal Nanoparticles

Metal oxide colloidal particles such as silica (SiO2) and titania (TiO2) have many diverse applications ranging from catalysis, pigments and photonic band-gap materials to health care products. There has also been considerable research interest over the last decade in fabricating core-shell materials with tailored optical and surface properties. Core-shell particles such as titania-coated silica often exhibit improved physical and chemical properties over their single-component counterparts and hence are potentially useful over a broader range of applications. Newer methods of engineering such materials with controlled precision are required to overcome the difficulties with conventional production techniques, which are limited to multi-step batch processes. We have developed microfluidic routes for synthesis and surface-coating of colloidal silica and titania particles. The chief advantages of a microfluidic platform are precise control over reactant addition and mixing and continuous operation. Microfluidic chemical reactors for the synthesis and overcoating of colloidal particles are shown in Figure 1a and Figure 1b, respectively [1-2]. Figure 2a is an SEM micrograph of silica particles synthesized in a microreactor (Figure 1a) operated in segmented gas-liquid flow mode. Figure 2b shows a silica nanoparticle coated with a thick shell of titania. We have also fabricated integrated devices combining synthesis and overcoating to enable continuous multi-step synthesis of core-shell particles.

Microreactor Enabled Multistep Chemical Synthesis

As a demonstration of how microsystems can enable quantitative study and improved production of chemistries that have been too hazardous to pursue via traditional means, the kinetics of direct sodium nitrotetrazolate (NaNT) synthesis were characterized and a microsystem for its commercial production has been constructed (Figure 1). A PDMS modular microreactor system capable of both multi-step synthesis and rapid scale-out was constructed. This system minimized the necessary volume of the unstable diazonium intermediate, enabling the study of NaNT, an energetic material used in the construction of fire suppression systems that was too dangerous to test with traditional techniques. In the direct synthesis of NaNT, 5-aminotetrazole (5-AT) reacts with nitrous acid to produce the diazonium intermediate that, in a second reaction, undergoes a Sandmeyer type reaction that displaces the diazonium group by the nitrite ion. The rapid mixing and safety advantages of microsystems were incorporated into a flexible architecture, presenting an improved ability to safely probe the conditions of the reaction. The modular design of this system also enabled the same set of modules to be rearranged as parallel reactor chains for small-scale production. A second generation microsystem was constructed from silicon micromixer modules (Figure 2); this micro-system is not only more robust than the PDMS design but also capable of accommodating higher flow rates (>2 mL/min) and higher temperatures. This system allows higher throughput and longer operational lifetimes and is currently being optimized for use as a full-scale production platform.

Integrated Microreactor System

The realization of integrated microchemical systems will revolutionize chemical research by providing flexible tools for rapid screening of reaction pathways, catalysts, and materials synthesis procedures, as well as faster routes to new products and optimal operating conditions. Moreover, such microsystems for chemical production will require less space, use fewer resources, produce less waste, and offer safety advantages. The need for synthesizing sufficient quantities of chemicals for subsequent evaluation dictates that microchemical systems are operated as continuous systems. Such systems require fluid controls for adjusting reagent volumes and isolating defective units. The integration of sensors enables optimization of reaction conditions as well as the extraction of mechanistic and kinetic information.We are developing integrated microchemical systems that have reactors, sensors, and detectors with optical fibers integrated on one platform. We are exploring new approaches for connecting modular microfluidic components into flexible fluidic networks. Real-time control of reaction parameters using online sensing of flowrate, temperature, and concentration allows for precise attainment of reaction conditions and optimization over a wide range of temperatures and flow-rates. The multiple microreactors on the system can be used together to give higher throughputs or they can be used independently to carry out different reactions at the same time. Figure 1 shows a schematic of an integrated microreactor platform along with an early stage microreactor “circuit board” [1].

Crystallization in Microfluidic Systems

Microfluidic systems offer a unique toolset for discovering new crystal polymorphs and for studying the growth kinetics of crystal systems because of well-defined laminar flow profiles and online optical access for measurements. Traditionally, crystallization has been achieved in batch processes that suffer from non-uniform process conditions across the reactors and chaotic, poorly controlled mixing of the reactants, resulting in polydisperse crystal size distributions (CSD) and impure polymorphs. This reduces reproducibility and manufactures products with inhomogeneous properties. The short length scale in microfluidic devices allows for better control over the process parameters, such as the temperature and the contact mode of the reactants, creating uniform process conditions. Thus, these devices have the potential to produce crystals with a single morphology and a more uniform size distribution. In addition, microfluidic systems decrease waste, provide safety advantages, and require only minute amounts of reactants, which is most important when dealing with expensive materials such as pharmaceutical drugs. Figure 1 shows a microfluidic device used for crystallization and Figure 2 shows optical images of different shapes and sizes of glycine crystals produced in reactor channels. A key issue for achieving continuous crystallization in microsystems is to eliminate heterogeneous crystallization – irregular and uncontrolled formation and growth of crystals at the channel surface, which ultimately clogs the reactor channel. We have developed a sheath flow microcrystallizer using microfabrication and hot embossing of poly(dimethylsiloxane) (PDMS) and cyclic olefin copolymer (COC) to prevent heterogeneous crystallization. We are currently working on integrating an online spectroscopy tool for in situ polymorph detection. Our ultimate goal is to develop an integrated microfluidic system for continuous crystallization with the ability to control polymorphism and online detection.

Microreactors for Synthesis of Quantum Dots

We have fabricated a gas-liquid segmented flow reactor with multiple temperature zones for the synthesis of quantum dots (QDs). In contrast to single-phase flow reactors, the segmented flow approach enables rapid mixing and narrow residence-time distributions, factors which have a strong influence on the ultimate QD size distribution. The silicon-glass reactor accommodates a 1-m long reaction channel (hydraulic diameter ~400-µm) and two shallow side channels for collecting reaction aliquots (Figure 1). Two temperature zones are maintained, a heated reaction region (>260°C) and a cooled quenching region (<70°C). As a model system, monodisperse CdSe QDs with excellent optical properties were prepared using the reactor. Cadmium and selenium precursor solutions are delivered separately into the heated section. An inert gas stream is introduced further downstream to form a segmented gas-liquid flow, thereby rapidly mixing the precursors and initiating the reaction. The reaction is stopped when the fluids enter the cooled outlet region of the device. Under conditions for a typical synthesis, the gas and liquid segments are very uniform (Figure 2a-b), and the QDs produced in the reactor possess narrow spectral features, indicative of monodisperse samples. The narrow particle size distributions arise directly from the enhanced mixing and narrow residence-time distribution realized by the segmented flow approach. Furthermore, the QD size can be tuned without sacrificing monodispersity by varying the Cd and Se precursor flow rates. In Figure 2d, the Se/Cd molar ratio was varied while keeping the total liquid and gas flow rates constant. Decreasing Se/Cd results in a substantial red shift of the QD effective band-gap (first absorption feature and photoluminescence peak), corresponding to larger QD diameters.

Polymer-based Microbioreactors for High Throughput Bioprocessing

This project aims at developing high-throughput platforms for bioprocess developments. Based on the membrane-aerated microbioreactor [1], we have realized a microliter-volume, actively-mixed, and polymer-based microbioreactor by microfabrication and precision machining of PDMS and PMMA for batch [2] and continuous cultures [3] of microbial cells. Biological applications of microbioreactors, such as global gene expression of yeast cells [4], were demonstrated, and the parallel operation of multiple batch fermentations was realized by a multiplexed system [5].As a very important operation for bioprocess developments, fed-batch process allows extensive control over environmental conditions in fermentations. Fed-batch fermentations in the microbioreactor were made possible by applying water evaporation through the PDMS membrane as a fluidic exit, and by combining passive feeding of water and active feeding of base, acid, and glucose solutions. Commercial microvalves were used to control pressure-driven liquid feeds to realize closed-loop pH control in the microbioreactor. For Escherichia coli fermentations, the pH value was successfully maintained within a certain range (Figure 1). Cells were physiologically healthier and remained active for longer periods of time (as shown by the dissolved oxygen curve), which in return yielded significantly higher biomass concentration at the end of experiments.The microbioreactor was also integrated with the plug-n-pump microfluidic connectors [6], as well as incorporation of fabricated polymer micro-optical lenses and connectors for biological measurements to realize “cassettes” of microbioreactors (Figure 2). The fabrication process included precision machining and thermal bonding of PMMA devices. These integrations greatly simplified the setup and operation procedure and increased the signal-to-noise ratio for optical measurements for the cassettes, thus made the microbioreactors more compatible with high-throughput bioprocessing in multiplexed systems.

Micro-fluidic Bioreactors for Studying Cell-Matrix Interactions

Mechanical forces are important regulators of cell biology in health and disease. Cells in the vascular system are subjected to fluid shear stress, cyclic stretch, and differential pressure [1]. Numerous investigations have revealed the vast pathological and physical responses of endothelial cells to fluid shear stress by culturing the cells on the rigid surfaces of a flow chamber. This approach, however, fails to mimic the true environment of cells in vivo that grow on flexible, porous basement membranes with a defined microstructure [1-4]. In order to create an improved model for this in vivo condition, we developed a new microfluidic bioreactor system that enables us to study cell-matrix interactions on soft substrates made of gel under conditions of controlled shear stress and pressure difference. A gel cage consisting of three thin layers (Figure 1) is constructed from PDMS using a silicon master made by the deep RIE process. Flow chambers, also made of PDMS, are cured on an SU-8 patterned master. Separate channels are included that allow for filling this central chamber with a gel that mimics the extracellular matrix and also allows for independent control over the flows in the upper and lower channels. The assembled bioreactor is shown in Figure 2. To conduct experiments, we introduce a peptide solution into the gel cage, allow it to gel, and then seed cells on the gel surface exposed through the holes of gel cage. After cell adhesion, the flow chambers are sealed by the application of a vacuum to the top and bottom sides of the gel cage. Flows are then applied to each chamber with controlled pressures and flow rates. With this system, we will apply controlled shear stress and pressure on the cell layers. We plan to study the process of angiogenesis that entails the growth of vascular sprouts emanating from one endothelial surface and connecting with the other.

A Nanoscanning Platform for Biological Assays

An in-plane nanoscanning platform with switchable stiffness being developed at the Micro & Nano Systems Laboratory (MNSL) [1] can be an alternative to the existing atomic force microscope (AFM) system. The nanoscanning platform has a carbon nanotube (CNT) tip, which is known as one of the ideal candidates for AFM tips because of their superior mechanical and chemical properties. Raman Spectroscopy has gained a lot of interest as a tool for single molecule detection since it has easy and fast sample preparation and measurement compared to the existing technologies, such as X-ray crystallography and nuclear magnetic resonance. Among the several approaches attempted in order to enhance the weak Raman signals is tip enhanced raman spectroscopy (TERS). The enhancement of the electric field due to the plasmon resonance on the coated metal surface was predicted qualitatively [2]. The metal-coated CNT or CNT filled with Ag, Au, or Cu with a small diameter tip and high aspect ratio is ideal for TERS. The switchable stiffness AFM can work as a tool for imaging and placing the tip at the sub-nanometer proximity to a soft, molecular-scale biological sample, which would enhance the Raman signals.

A Large Strain, Arrayable Piezoelectric Microcellular Actuator

To provide a competitive actuating solution, micro-electromechanical-systems (MEMS)-based actuators need low operating power and form factors. Piezoelectrics provide substantially higher work-output/volume for a given voltage, when compared to other actuating solutions. A bow amplifier constructed of SU-8 beams and short length flexural pivots has been designed [1] and has demonstrated an amplification ratio of greater than 10:1. Current research focuses on increasing this amplification ratio and achieving the goal of 10% axial strain, while reducing parasitic out-of-plane bending inherent in the current fabrication process.The overall goal of this project is to array one such actuator massively in series and in parallel in order to create a macro-scale, muscle-like actuator. Such a device would have widespread applications in mobile robotics, medicine, and aero/astronautics, where low power, high efficiency, and small form factors might be required.

Self-powered Wireless Monitoring System Using MEMS Piezoelectric Micro Power Generator

A thin-film lead zirconate titanate Pb(Zr,Ti)O3 (PZT), MEMS Piezoelectric Micro Power Generator has been integrated with a commercial wireless sensor, Telos, to simulate a self-powered RF temperature monitoring system (Figure 1). Such a system has many important applications, ranging from structure to rotary system monitoring. Telos consumes 2270 µJ for 221 ms per measurement. The PMPG and power management module are designed to satisfy such power requirementsThe first prototype of PMPG provides an average 1 µW, with a natural frequency of 13.9 kHz (Figure 2). It has an energy density of 0.74 mW-h/cm2, which compares favorably to lithium ion batteries [1]. The second generation PMPG is designed to provide 0.173 mW of power at 3 V with a natural frequency of 150 Hz and maximum strain of 0.12% [2]. We increased the effective mass of the PMPG by adding a Si substrate with thickness of 525 µm to the beam structure. The increase in the effective mass increases the energy store in the device and its power output. The beam length is also increased to achieve a low resonant frequency. The third generation PMPG will use a serpentine structure, which can achieve a low frequency with minimum volume. Since PMPG offers limited power, a storage capacitor and a power management module are implemented to power the sensor node at discrete time intervals [3]. The PMPG is first connected to a rectifier that converts AC to DC voltage. Each cycle consists of a charging interval, in which PMPG charges the capacitor, and operation intervals, in which Telos uses the energy from capacitor. We developed a test bed, which mimics that of a liquid gas pipe used in the Alaska where the PMPG device will be used to generate power for temperature sensors. Scaling/dimension factors as well as cost and robustness are considered in the design.

MEMS Pressure-sensor Arrays for Passive Underwater Navigation

MEMS pressure sensors have had broad applications in fields such as mining, medicine, automobiles, and manufacturing. Another application to be explored is in underwater vehicular navigation. Objects within a flow generate pressure variations that characterize the objects’ shape and size. Sensing these pressure variations allows the unique identification and location of obstacles for navigation (Figure 1). This concept is inspired by existing biological systems. Fish have such a sensory lateral line, which they use to monitor all aspects of their hydrodynamic environment, including obstacles [2,5].We propose to develop low-power sensors that passively measure dynamic and static pressure fields with sufficient resolution to detect objects generating the disturbance. We will also develop processing schemes that use the information from the sensors to identify objects in the flow environment. These sensors and processing software emulate the capabilities of the lateral line in fish. While active acoustic means can be used for object detection, the process is power-intensive, and depends strongly on the acoustic environment. A simpler alternative is to use a passive system that can resolve the pressure signature of obstacles. The system consist of arrays of hundreds or thousands of piezoresistive pressure sensors fabricated on etched silicon and Pyrex wafers [1,3,4,6] with diameters around 1 mm; the sensors are arranged over a flat or curved surface in various configurations, such as a single line, a patch consisting of several parallel lines (Figure 2), or specialized forms to fit the hull shape of a vehicle or its fins. The sensors will be packaged close together at distances of a few millimeters apart in order to resolve pressure and flow features near the array spacing, which in turn can be used to identify the overall features of the flow.

An Integrated Multiwatt Permanent Magnet Turbine Generator

There is a need for compact, high-performance power sources that can outperform the energy density of modern batteries for use in portable electronics, autonomous sensors, robotics, and other applications. Previous research efforts on a micro-scale, axial-flux, permanent-magnet turbine generator [1-2] culminated in a spinning rotor test stand that delivered 8 W DC output power through a diode bridge rectifier with an overall generator system efficiency of 26.6%. In these experiments, the generator rotor was mounted via a steel shaft to an air-driven, ball-bearing supported spindle and spun to the desired operational speed.Current research efforts aim to fully integrate the permanent-magnet (PM) generator design into the silicon micro-turbine engine fabrication process and create devices that can deliver 10 W DC output power when driven by compressed air. The integrated generator will couple energy from the compressed air to the rotor through microfabricated turbine blades attached to the backside of the rotor. One important challenge in this integration process is the structural integrity of the magnetic rotor spinning at a tip speed near 300 m/s, or equivalently 450 krpm.Based on power requirements, a 300-µm thick circular NdFeB PM with an inner radius of 2.5 mm and an outer radius of 5 mm must be embedded into the silicon rotor on top of a 150 µm FeCoV back iron. FEA analysis shows that the maximum principle stress at 450 krpm in the silicon rotor, 900-µm thick and 12 mm in diameter, with bonded annular PM and back iron pieces, will be approximately 180 MPa through the entire structure. This stress is well below the tensile strength of silicon and FeCoV. However, because the PM is brittle and has a typical tensile strength around 83 MPa, it is unclear whether the material will fracture. Tests are currently underway to characterize the reference strength and Weibull modulus of the PM, and from these results, a working rotor design will be proposed.

Micro-scale Singlet Oxygen Generator for MEMS-based COIL Lasers

Conventional chemical oxygen iodine lasers (COIL) offer several important advantages for materials processing, including short wavelength (1.3 µm) and high power. However, COIL lasers typically employ large hardware and use reactants relatively inefficiently. This project is creating an alternative approach called microCOIL. In microCOIL, most conventional components are replaced by a set of silicon MEMS devices that offer smaller hardware and improved performance. A complete microCOIL system includes micro-chemical reactors, micro-scale supersonic nozzles, and micro-pumps. System models incorporating all of these elements predict significant performance advantages in the microCOIL approach [1]. Initial work focuses on the design, microfabrication, and demonstration of a chip-scale singlet oxygen generator (SOG), a micro-chemical reactor that generates singlet delta oxygen gas to power the laser. Given the extensive experience with micro-chemical reactors over the last decade [2-4], it is not surprising that a micro-SOG would offer a significant performance gain over large-scale systems. The gain stems from basic physical scaling; surface-to-volume ratio increases as the size scale is reduced, which enables improved mixing and heat transfer. The SOG chip demonstrated in this project, shown in Figure 1, employs an array of micro-structured packed-bed reaction channels interspersed with micro-scale cooling channels for efficient heat removal. Production of singlet oxygen has been confirmed via spontaneous emission (as shown in Figure 2) and mass spectrometry techniques. The yield (or fraction of singlet oxygen produced) is estimated at 70%, making the micro-SOG competitive with macro-scale alternatives.

Label-free Microelectronic PCR Quantification

The introduction of real-time monitoring of the polymerase chain reaction (PCR) represents a major breakthrough in specific nucleic acid quantification. This technique employs fluorescent intercalating agents or sequence-specific reporter probes to measure the concentration of amplified products after each PCR cycle. However, the need for optical components can limit the scalability and robustness of the measurement for miniaturization and field-uses. Moreover, the addition of external fluorescent reagents can induce inhibitory effects [1] and require extensive optimization [2].We have developed a robust and simple method for direct label-free PCR product quantification using an integrated microelectronic sensor (Figure 1) [3]. The field-effect sensor can sequentially detect the intrinsic charge of multiple unprocessed PCR products and does not require sample processing or additional reagents in the PCR mixture. The sensor measures nucleic acid concentration in the PCR relevant range and specifically detects the PCR products over reagents such as Taq polymerase and nucleotide monomers. The sensor can monitor the product concentration at various stages of PCR and can generate a readout that resembles that of a real-time fluorescent measurement using an intercalating dye but without its potential inhibition artifacts (Figure 2). The device is mass-produced using standard semiconductor processes, can be reused for months, and integrates all sensing components directly on-chip. As such, our approach establishes a foundation for the direct integration of PCR-based in vitro biotechnologies with microelectronics.

Atomic Force Microscopy with Inherent Disturbance Suppression for Nanostructure Imaging

Scanning probe imaging is often limited by disturbances, or mechanical noise, from the environment that couple into the microscope. We demonstrate on a modified commercial atomic force microscope that adding an interferometer as a secondary sensor to measure the separation between the base of the cantilever and the sample during conventional feedback scanning can result in real-time images with inherently suppressed out-of-plane disturbances (Figure 1) [1]. The modified microscope has the ability to resolve nanometer-scale features in situations where out-of-plane disturbances are comparable to or even several orders of magnitude greater than the scale of the topography. We present images of DNA in air from this microscope in tapping mode without vibration isolation, and show improved clarity using the interferometer as the imaging signal (Figure 2). The inherent disturbance suppression approach is applicable to all scanning probe imaging techniques.We do not claim that image improvement will be comparable to these results on all SPMs and in all imaging environments. At present, this technique will be most effective in very noisy environments, such as a microfabrication facility, where Z disturbances overwhelm sample topography. However, there are two significant implications of this work: 1) vibration isolation, which is costly and consumes space, can be rendered unnecessary for noisy environments; and, 2) this technique can potentially outperform vibration isolation in any environment with further reduction of the interferometer noise floor.

Vacuum-Packaged Suspended Microchannel Resonant Mass Sensor for Biomolecular Detection

Microfabricated transducers enable the detection of biomolecules in microfluidic systems with nanoliter size sample volumes. Their integration with microfluidic sample preparation into lab-on-a-chip devices can greatly leverage experimental efforts in systems biology and pharmaceutical research by increasing analysis throughput while dramatically reducing reagent cost. Microdevices can also lead to robust and miniaturized detection systems with real-time monitoring capabilities for point-of-use applications.We have recently fabricated, packaged, and tested a resonant mass sensor for the detection of biomolecules in a microfluidic format [1]. The transducer employs a suspended microchannel as the resonating element, thereby avoiding the problems of damping and viscous drag that normally degrade the sensitivity of resonant sensors in liquid (Figure 1). Our device differs from a vibrating tube densitometer in that the channel is very thin, which enables the detection of molecules that bind to the channel walls; this provides a path to specificity via molecular recognition by immobilized receptors. The fabrication is based on a sacrificial polysilicon process with low-stress LPCVD silicon nitride as the structural material, and the resonator is vacuum packaged on the wafer scale using glass frit bonding (Figure 2). Packaged resonators exhibit a sensitivity of 0.8 ppm/(ng•cm2) and a mechanical quality factor of up to 700. To the best of our knowledge, this quality factor is among the highest so far reported for resonant sensors with comparable surface mass sensitivity in liquid.

Microbial Growth in Parallel Integrated Bioreactor Arrays

Bioprocesses with microbial cells play an important role in producing biopharmaceuticals such as human insulin and human growth hormone and other products such as amino acids and biopolymers. Because bioprocesses involve the complicated interaction between the genetics of the microorganisms and their chemical and environmental conditions, hundreds or thousands of microbial growth experiments are necessary to develop and optimize them. In addition, efforts to develop models for bioprocesses require numerous growth experiments to study phenotypes of microorganism. We have designed and developed integrated arrays of microbioreactors that can provide the oxygen transfer and control capabilities of a stirred tank bioreactor in a high-throughput format. The devices comprise a novel peristaltic oxygenating mixer and microfluidic injectors (Figure 1), which are fabricated using a process that allows the combination of multiple scale (100 µm-1 cm) and multiple depth (100 µm-2 mm) structures in a single mold. The microbioreactors have a 100 µL working volume, a high oxygen-transfer rate (kLa ≈ 0.1s-1), and closed loop control over dissolved oxygen and pH (±0.1). Overall, the system supports eight simultaneous batch cultures in two parallel arrays with two dissolved oxygen thresholds, individual pH set points, and automated near real-time monitoring of optical density, dissolved oxygen concentration, and pH. These capabilities allowed the demonstration of multiple Escherichia coli aerobic fermentations with growth to high cell densities (>12g-dcw/L, Figure 2), and individual bioreactor performance on par with bench scale stirred tank bioreactors. The successful integration of diverse microfluidic devices and optical sensors in a scalable architecture opens a new pathway for continued development of parallel bioreactor systems.

Vacuum-Sealing Technologies for Micro-chemical Reactors

Current portable power sources may soon fail to meet the demand for increasingly larger power densities. To address this concern, our group has been developing MEMS power generation schemes that are focused around fuel cells and thermophotovoltaics. At the core of these systems is a suspended tube micro-reactor that has been designed to process chemical fuels [1]. Proper thermal management is critical for high reactor efficiency, but substantial heat loss is attributed to conduction through air. A straightforward solution is to eliminate the heat-loss pathways associated with air by means of a vacuum package. This work explores a glass-frit bonding method for vacuum sealing.Optimization of pre-sintering and bonding parameters of the glass frit produced a repeatable and robust hermetic seal. Encounters with outgassing issues prompted an alternate two-step packaging process illustrated in Figure 1. New capping dies were fabricated, test devices were packaged, and the final seal-off was attempted with various materials [2]. Several experimental results appear in Figure 2. The glass frits are undesirable since they produce holes from material breakdown when heated in a vacuum. The gold-indium solder appears promising but holes formed due to internal outgassing. Extended heating to assist outgassing resulted in the delamination of the solder from the wetting metal. Recent work has been conducted to evaluate oxidized caps and lead-tin solder as solutions to these problems. Enhancements through the incorporation of non-evaporable getters will be assessed once a vacuum package is achieved.

Direct Patterning of Organic Materials and Metals Using Micromachined Printheads

Organic optoelectronic devices are promising for many commercial applications if methods for fabricating them on large-area, low-cost substrates become available. Our project investigates the use of MEMS in the direct patterning of materials needed for such devices. By depositing the materials directly from the gas phase, without liquid phase coming in contact with the substrate, we aim to avoid the limitations of inkjet printing such materials.In our first demonstration, we used an electrostatically actuated micromachined shutter integrated with an x-y-z manipulator to modulate the flux of evaporated organic semiconductors and metals and to generate patterns of the deposited materials. We printed arbitrary patterns of organic semiconductor Alq3 (tris(8-hydroxyqunolinato) aluminum) and metal silver on glass substrates. We also printed pentacene/silver organic field effect transistor (OFET) and arrays of organic light emitting devices (OLED), as shown in Figure 1. This printing technique can pattern small-molecule organic light-emitting devices at high resolution (800 dpi).The next stage of this project investigates the use of a microporous layer with integrated heaters for local evaporation of the materials. The microfabricated device is shown in Figure 2. The material to be printed is delivered to the porous region in liquid or gas phase and deposits inside the pores. An integrated heater then heats up the porous area and the material is re-evaporated from the pores onto the substrate. Compared to the first generation of printheads, the problems of crashing and stiction are avoided, since there is no moving part. Clogging is also limited since most of the material is removed during each printing cycle. Other advantages include the smaller quantity of organic material used, and the reduced substrate heating. Such a printhead would ultimately be integrated with an ink-jet printer for the delivery of liquid phase material into the porous region.

A Thermophotovoltaic (TPV) MEMS Power Generator

For a number of years, batteries have not kept up with the fast development of microelectronic devices. The low energy densities of even the most advanced batteries are a major hindrance to lengthy use of portable consumer electronics such as laptops and of military equipment that most soldiers carry today. Furthermore, battery disposal constitutes an environmental problem. Hydrocarbon fuels exhibit very high energy densities in comparison, and micro-generators converting the stored chemical energy into electrical power at even modest levels are therefore interesting alternatives in many applications. This project focuses on building thermophotovoltaic (TPV) micro-generators, in which photocells convert radiation from a combustion-heated emitter into electrical power. TPV is an indirect conversion scheme that goes through the thermal domain and therefore does not exhibit very high efficiencies (10-15% max). However, because of its simple structure and because the combustor and photocell fabrication processes do not need to be integrated, the system is simpler to micro-fabricate than other generator types, e.g., thermoelectric systems and fuel cells. It is also a mechanically passive device that is virtually noiseless and less subject to wear than engines and turbines. In this TPV generator, a catalytic combustor, the suspended micro-reactor (SµRE) (Figure 1), is heated by combustion of propane and air, and the radiation emitted is converted into electrical energy by low-bandgap (GaSb) photocells. Net power production of up to 1 mW has been achieved [1], constituting a promising proof of concept. A new version of the SµRE is currently under fabrication. This new design (Figure 2) aims to address several problems existing in the earlier version, including fabrication difficulties, low burst pressure of the tubes, and low emitter surface area.

MEMS Vacuum Pump

There are many advantages to miniaturizing systems for chemical and biological analysis. Recent interest in this area has led to the creation of several research programs, including a micro gas analyzer (MGA) project at MIT. The goal of this project is to develop an inexpensive, portable, real-time, and low-power approach for detecting chemical and biological agents. Elements entering the MGA are first ionized, then filtered by a quadrupole array, and sensed using an electrometer. A key component enabling the entire process is a MEMS vacuum pump, responsible for routing the gas through the MGA and increasing the mean free path of the ionized particles so that they can be accurately detected. There has been a great deal of research done over the past 30 years in the area of micro pumping devices [1, 2]. We are currently developing a displacement micro-vacuum pump that uses a piezoelectrically driven pumping chamber and a pair of piezoelectrically driven active-valves; the design is conceptually similar to the MEMS pump reported by Li et al. [3]. We constructed accurate computer models for all aspects of the pump’s operation: a compressible mass flow model of the flow rates, the pressure, the density, and the Mach number in the different parts of the pump in both the sonic and subsonic regimes [4], and a nonlinear plate deformation model of the stresses experienced by the pistons, tethers, and walls of the pump during operation [5], for any chosen dimensions and material properties. Using these models we have defined a process flow for our first-generation MEMS vacuum pump designed to meet our first-term goals. A schematic of this pump that we started fabricating is shown in Figure 1 below. For ease in testing we have decided to fabricate only Layers 1-3 and constructed a testing platform that will drive the pistons pneumatically. This will allow for rapid characterization of pumping performance as well as chamber and valve designs for several dies at once without having to incorporate piezos in each case. The final device will be driven using low-voltage, low-loss, piezoelectric-stacks incorporated into Layer 4 and will include Layer 5 for structural support.

Rapid and Shape-Controlled Growth of Aligned Carbon Nanotube Structures

We present approaches for growth of aligned carbon nanotube (CNT) structures on silicon substrates, based on atmospheric pressure chemical vapor deposition (CVD) using a Fe/Al2O3 catalyst film in C2H4/H2. First, vertically-aligned films of small-diameter (5-10 nm) multi-walled CNTs (MWNTs) are grown to 0.9 mm thickness in 15 minutes and 1.8 mm in 60 minutes, using a conventional 1-inch-diameter tube furnace [1]. The catalyst is patterned by photolithography, and the growth rate of CNT microstructures depends on the local areal density of catalyst, which is analogous to loading effects in plasma etching process. Further, using a novel apparatus where the silicon substrate is resistively heated, we achieve CNT film thickness of 3 mm in just 20 minutes along with rapid (100oC/s) control of the substrate temperature and optically image the film during growth (Figure 1).By placing a weight on the catalyst-coated substrate, we measure the force which can be exerted by a growing CNT film and demonstrate that the film thickness after a fixed growth time and the alignment of CNTs within the film decrease concomitantly with increasing applied force [2]. We utilize this principle to fabricate three-dimensional structures of CNTs (Figure 2) that conform to the shape of a microfabricated template. This technique is a catalytic analogue to micromolding of polymer and metal microstructures; it enables growth of nanostructures in arbitrarily-shaped forms and does not require patterning of the catalyst.Finally, we perform combinatorial flow studies of CNT growth using an array of parallel microchannels fabricated by KOH etching of silicon [3]. We observe transitions in CNT yield and quality along the microchannels, grow CNT structures that are aligned by gas flows in the microchannels, and fabricate CNT-filled microchannels for applications such as microfluidic filters.

A Low Contact Resistance MEMS-Relay

A low contact resistance MEMS-relay featuring highly parallel and planar oblique contacts has been fabricated and is currently being tested. The contacts are etched in silicon using a potassium hydroxide (KOH) solution. An offset between the wafer-top and the wafer-bottom KOH masks produces the oblique contact geometry schematically shown in Figure 1A. In contrast, many prior art MEMS devices [1-3] have rough, non complementary contacts. As these surfaces touch, they do so in a small number of high points, as shown in Figure 1B, which significantly reduces the effective contact area and leads to a high contact resistance and a low current carrying capacity. Additionally, vertical contacts are prone to poor metallization, which further affects the device’s contact resistance. Our MEMS-relay, shown in Figure 2, is composed of a compliant mechanism (B), a pair each of engaging (C) and disengaging (D) rolling-point “Zipper” actuators [4-5], and a pair of planar and parallel contacts (E).The relay is fabricated by a combination of deep reactive ion etching (DRIE) and KOH etching. Nested masks are used to pattern both wafer-through etches. Low stress silicon nitride (Si3N4), which will later be used as a KOH mask, is patterned initially on both sides of the device wafer. A silicon oxide film is deposited on the KOH mask. The compliant mechanism and actuators are then etched through DRIE and a second Si3N4 film is deposited. The second Si3N4 film is patterned using a “shadow” (through-etched) wafer as a mask. The oxide is selectively etched to reveal the buried nitride mask. The contacts are etched in KOH solution. Both Si3N4 and oxide films are stripped and a thermal oxide, which insulates both the electrostatic actuators and the relay contacts from the rest of the device, is grown. Gold is evaporated over both sides of the insulated contacts and the device wafer is anodically bonded to a Pyrex handle wafer. Experimental pull-in and drop-out voltages of 70 V and 40 V, respectively, agree with the model. Contact travel of 50 µm prevents arcing as the load circuit is switched on and off. A contact resistance of 50 mΩ was demonstrated by our group using an externally actuated structure as a proof of concept for the contact design [4]. Our group continues to develop these MEMS relays for power applications.

Fast Three-Dimensional Electrokinetic Pumps for Microfluidics

Electrokinetic pumps are attractive for portable and flexible microfluidic analysis systems, since they operate without moving parts using low (battery-powered) alternating potentials. Since the discovery of AC electro-osmosis (ACEO) in the late 1990s, there has been much work in designing planar, periodic pumps, which exploit broken symmetry in electrode spacing and width to produce a streaming flow over a surface. Although surface-height modulation has been suggested as another means of breaking symmetry[1], it has never been numerically or experimentally pursued. Recently, Bazant and Squires described more general flows due to induced charge electro-osmosis (ICEO) around three-dimensional metal structures[2], which has since been realized experimentally in microfluidic systems[3]. Motivated by ICEO around raised electrodes, we are developing a variety of new three-dimensional AC electrokinetic pumps capable of much faster directional flows than planar ACEO pumps (for the same applied voltage and minimum feature size) by an order of magnitude according to the usual low-voltage model. This phenomena and an example microfabricated device are illustrated in Figure 1. We test and improve our theoretical designs experimentally in a microfluidic loop[4], as shown in Figure 2. Our pumps involve interdigitated planar electrodes with raised metal structures from a simple electroplating step, which leads to greatly enhanced pumping.

BioMEMS for Control of the Stem-cell Microenvironment

The stem-cell microenvironment is influenced by several factors including cell-media, cell-cell, and cell-matrix interactions. Although conventional cell-culture techniques have been successful, they offer poor control of the cellular microenvironment. To enhance traditional techniques, we have designed a microscale system to perform massively parallel cell culture on a chip.To control cell-matrix and cell-cell interactions, we use dielectrophoresis (DEP), which uses non-uniform AC electric fields to position cells on or between electrodes [1]. We present a novel microfabricated DEP trap designed to pattern large arrays of single cells (Figure 1, left). We have experimentally validated the trap using polystyrene beads and cells, showing excellent agreement with our model predictions [2]. In addition, by placing interdigitated electrodes between the traps, we can prevent cells from sticking to the substrate outside the traps (Figure 1, right).To control cell-media interactions, we have developed a microfluidic device for culturing adherent cells over a logarithmic range of flow rates (Figure 2, left) [3]. The device controls flow rates via a network of geometrically-set fluidic resistances connected to a syringe-pump drive. We use microfluidic perfusion to explore the effects of continuous flow on the soluble microenvironment. We have demonstrated logarithmically-scaled perfusion culture of mouse embryonic stem cells over 4 days, with flow rates varying > 300x across the array. Cells cultured at the slowest flow rate did not proliferate while colonies at higher flow rates demonstrated healthy round morphology (Figure 2, upper and lower right) and expressed the stem-cell marker Oct-4. These microfabricated platforms will enable precise and unique control over the cellular microenvironment, allowing novel cell biology experiments at the microscale.

Microfluidic/Dielectrophoretic Approaches to Selective Microorganism Concentration

This project focuses on the development of microfabricated microfluidic/dielectrophoretic devices capable of concentrating micron-size particles from complex liquids, for example water containing contaminants such as dust, sand, protein or soot. The concentrated particles of interest, such as pathogenic bacteria and spores, can then be delivered in small aliquots to the appropriate sensor for identification.The micro-concentrator exploits the phenomenon of dielectrophoresis–the force on polarizable particles in spatially non-uniform electric field [1]–to trap the particles from the flow stream in order to subsequently concentrate them by release into a smaller volume of liquid. Dielectrophoresis does not negatively affect the liquid or the particles on which it operates. In our device the non-uniform electric field is created by interdigitated electrodes (IDE) at the bottom of the channel through which the contaminated solution is passed (Figure 1). To maximize the exposure of particles to the DEP field, we mix the liquid using passive micro-fluidic mixers (Figure 1). Preliminary results with different fabricated micro-fluidic mixers exhibit up to 70% improvement in trapping efficiency as compared to devices without mixers (Figure 2). Although both the herringbone mixer (HM) and slanted groove mixer (SGM) show notable improvements over smooth channel configurations, the staggered herringbone mixer (SHM) provides the greatest enhancement in trapping efficiency. We believe that the chaotic mixing associated solely with the SHM exposes more particles to the concentrator’s bank of IDEs, thus resulting in higher trapping efficiency when compared to other mixer types.The magnitude and direction of the dielectrophoretic (DEP) force depends on the particle’s dielectric properties (i.e., conductivity and permittivity); therefore, when the operating frequency of the field and the conductivity of the medium are chosen, the DEP force can be selectively applied to trap and concentrate some particles (bacterial spores of interest) and not others (dust, soot, sand or protein). In our device, initial banks of interdigitated electrodes are driven to maximize interferent trapping, while final stages capture spores from a purified solution. Using this mode of operation, we demonstrated selective trapping of B. subtilis spores while rejecting interferents such as pollen, chitin, sand and depleting interferents such as soot and dust. Future work will focus on improving purity and efficiency of trapping.

Microfabricated Approaches for Sorting Cells Using Complex Phenotypes

We are developing microfabricated approaches to create sorting cytometers for genetic screening of complex phenotypes in biological cells. Our goal is to create technologies that combine the ability to observe with the ability to isolate individual mutant cells from a population under study. Such cytometry merges benefits of microscopy and flow-assisted cell sorting (FACS) to offer unique capabilities on a single platform. Biologists will be able to use these technologies to isolate cells based upon dynamic and/or intracellular responses, permitting creation of new types of genetic screens.We currently are developing optical and electrical approaches to enable image-based sorting. One of our current approaches uses an array of switchable traps (Figure 1) that rely upon the phenomena known as dielectrophoresis (DEP) [1]. The DEP-enabled traps allow for capturing and holding cells in defined spatial locations and then subsequently releasing a desired subpopulation for further study. The traps in our device are controlled using a series of row and column electrical connections. This setup avoids any need for separate connections to each of the traps in our arrays. Our chip-to-world interconnect needs thus scale only as 2√n for any n × n trap footprint. This condition enables site-specific addressing within arrays sized appropriately for bio-relevant assays (10,000 sites) using a minimal number of electrical ties (200 wires). To date, we have captured, held, and sorted small populations of individual HL60 human leukemia cells using a demonstrative 4 × 4 trap array [2]. Figure 2 shows a proof-of-concept assay where orange- and green-stained HL60 cells are first held in the 16-site array and then we sorted each of the green cells from the grid. Developing and scaling such a platform for screening applications requires performance characteristics that are easily met only by using quantitative modeling [3]. Using such an approach, we have developed updated trap geometries and system configurations for use in larger 20 × 20 array structures. Currently we are fabricating these enhanced devices, their affiliated control and automation systems, and specific RFP-tagged cell lines for planned complex phenotype-based sorting assays. In tandem with this design cycle, we are investigating the effects of DEP trapping on cell health and the impact that it may have on our ability to assess specific phenotypic behaviors. Complementary and alternative approaches for implementing these sorting functionalities are similarly under study in an attempt to lower the threshold for acceptance and use in biological laboratories.

A Continuous, Conductivity-Specific Micro-organism Separator

Increased throughput in the techniques used to engineer new metabolic pathways in unicellular organisms demands similarly high throughput tools for measuring the effects of these pathways on phenotype. For example, the metabolic engineer is often faced with the challenge of selecting the one genomic perturbation that produces a desired result out of tens of thousands of possibilities [1]. We propose a separation method–iso-dielectric separation, or IDS–which separates microorganisms continuously based on their dielectric properties. This technology would enable high-throughput screening of cells based upon electrically distinguishable phenotypes. Iso-dielectric separation uses dielectrophoresis (DEP) and media with spatially-varying conductivity to separate cells by their effective conductivity. It is similar to iso-electric focusing, except that it uses DEP instead of electrophoresis, and is thus applicable to uncharged particles, such as cells [2]. We apply this method to the separation of polystyrene beads (based on surface conductance), vesicles (based on the conductivity of the internal fluid), and cells (based on viability). Current efforts are focused on the separation of Escherichia coli based upon the amount of the intracellular polymer poly(hydroxybutyrate) that each cell contains.

MEMS Vibration Harvesting for Wireless Sensors

The recent development of “low power” (10’s-100’s of µW) sensing and data transmission devices, as well as protocols with which to connect them efficiently into large, dispersed networks of individual wireless nodes, has created a need for a new kind of power source. Embeddable, non-life-limiting power sources are being developed to harvest ambient environmental energy available as mechanical vibrations, fluid motion, radiation, or temperature gradients [1]. While potential applications range from building climate control to homeland security, the application pursued most recently has been that of structural health monitoring, particularly for aircraft.This SHM application and the power levels required favor the piezoelectric harvesting of ambient vibration energy. Current work focuses on harvesting this energy with MEMS resonant structures of various geometries. Coupled electromechanical models for uniform beam structures have been developed to predict the electrical and mechanical performance obtainable from ambient vibration sources. The uniform models have been validated by comparison to prior published results [2] and verified by comparison to tests on a macro-scale device [5]. Models of a uniform harvester with proof mass are currently undergoing macro-scale testing and validation. A non-optimized, uni-morph beam prototype (Figure 1) has been designed and modeled to produce 30 µW/cm3 [3]. A MEMS fabrication process for a prototype device is presented based on past work at MIT [4]. Dual optimal frequencies with equal peak powers and unequal voltages and currents are characteristic of the response of such coupled devices when operated at optimal load resistances (Figure 2). Design tools to allow device optimization for a given vibration environment have been developed for both geometries.Future work will focus on fabrication and testing of optimized uni-morph and proof-of-concept bi-morph prototype beams. System integration and development, including modeling the power electronics, will be included.

Fabrication and Structural Design of Ultra-thin MEMS Solid Oxide Fuel Cells

Microfabricated solid oxide fuel cells are being investigated for portable power applications requiring high energy densities [1-2]. Reducing the thickness of the fuel cell stack (anode, electrolyte, and cathode) improves the electrochemical performance over that of traditional devices. This motivation for thinner structures, combined with significant temperature excursions during processing and operation (~600-1000 °C), leads to a major challenge of thermomechanical stability of such membranes. Figure 1 shows a buckled electrolyte/SiN thin film. To predict and control structural stability and failure, the structural characterization of thin films is being investigated. Our group has characterized the residual stress and microstructure of the electrolyte layer. Complete studies were done on residual stress in sputter-deposited yttria-stabilized zirconia (YSZ) thin films (5 nm-1000 nm thickness) as a function of substrate temperature [3]. The results indicate variations in intrinsic stress from ~-0.5GPa to ~50 MPa as in Figure 2. Changes in microstructure are characterized using x-ray diffraction of as-deposited and annealed films and correlated with relevant mechanisms/models of residual stress evolution. Based on the design frameworks using the data above, a large-area full fuel cell stack (anode, electrolyte, and cathode) has been fabricated and tested to be thermomechanically stable at high operating temperatures. Tri-layers (Pt-YSZ/YSZ/Pt-YSZ, 50-200-µm wide, each 250-nm-thick) were sputter-deposited at high temperature (500-600C). Devices are being tested for electrochemical performance and power generation. In addition, proton-conducting electrolytes, typically capable of significant power generation at temperatures lower than YSZ are also being investigated in ultra-thin film form. Crack-free barium cerium-yttrium-oxide (BaCeYO) films with uniform thickness (300-500-nm thick) have been successfully sputter-deposited. Electrochemical and residual stress characterization for this material is currently underway. Additional ongoing work includes bulge-testing to determine the electrolyte’s elastic/thermal/fracture properties in ultra-thin membrane form, investigation of the mechanical and chemical properties of anode cathode materials, and nonlinear modeling of film postbuckling and failure.

Nanoscale Manipulation of Biological Entities Using Magnetic Particles and Fields

An increasing number of “lab-on-a-chip” technologies and therapeutic treatments rely on the rapid isolation of clinically or scientifically relevant proteins, cells, and nucleic acids. Magnetic fields and forces provide a useful means of sorting and manipulating such biological entities. Researchers have successfully used magnetic particles, often decorated with target-specific antibodies, for applications in human leukocyte antigen (HLA) diagnostics, cell enrichment or depletion, protein isolation, biomechanics measurements, and the electrophoresis of nucleic acids. The goal of our research is to use uniform and non-uniform magnetic fields in MEMS devices to manipulate magnetic particles or bound entities for the purpose of developing tools that can more rapidly and efficiently sort DNA, blood cells, and cellular organelles.We have previously demonstrated the electrophoresis of DNA in a microchannel using an array of self-assembled posts of magnetic particles [1]. We intend to investigate the effect of column spacing on separation efficiency and also the use of “blinking” magnetic fields (Figure 1) as a more rapid means to separate long-chain DNA, which tends to migrate very slowly in a static matrix. In addition, we have demonstrated, experimentally and through simulation, the ability to direct columns of magnetic beads laterally across a microfluidic channel, using patterned materials and a uniform magnetic field (Figure 2). This mechanism is the first step toward our development of a continuous, incubation-free cell-sorting device. Furthermore, we have utilized “saw-tooth” magnetic fields with aqueous ferrofluids to sort submicrometer (510 and 840nm) non-magnetic particles [2]. We believe this magnetophoresis will be useful in sorting subcellular, like-sized biological bodies, such as organelles and viruses.

Suspended Microchannel Resonators for Biomolecular Detection

We have demonstrated a new approach for detecting biomolecular mass in the aqueous environment. Known as the suspended microchannel resonator (SMR), target molecules flow through a suspended microchannel and are captured by receptor molecules attached to the interior channel walls [1]. As with other resonant mass sensors, the SMR detects the amount of captured target molecules via the change in resonance frequency of the channel during the adsorption (Figures 1,2). However, what separates the SMR from the myriad of existing resonant mass sensors is that the receptors, targets, and their aqueous environment are confined inside the resonator, while the resonator itself can oscillate at high Q in an external vacuum environment, thus, yielding extraordinarily high mass resolution. Figure 1: a) Suspended microchannel resonator (SMR); b) Cross-section of vibrating SMR; c) Targets bind to immobilized receptors (not shown), and the high surface concentration lowers the resonant frequency. Since biomolecules are more dense than solution (~1.4 g/cm3), the resonant frequency is reduce by ∆ω.Figure 2: a) Electron micrograph of three suspended microchannel resonators; b) Relative frequency shift for a 40 kHz resonant microchannel after injection of the following solutions: buffer (black), avidin (blue), bBSA (red), and avidin (blue). The adsorption of the biomolecules to the interior channel walls increases the overall mass and lowers the resonant frequency.

A Combined Microfluidic/Dielectrophoretic Microorganism Concentrator

This project focuses on the development of a microorganism concentrator for pathogen detection applications. A common problem in microfluidic systems is the mismatch between the volume of a sample and the volume that a device, such as a detector, can process in a reasonable amount of time. Concentrators can, therefore, be used in pathogen detection and other microfluidics applications to reduce sample sizes to the micro-scale without losing particles of interest.The concentrator, illustrated in Figure 1, is an active filter that uses dielectrophoresis to concentrate bacterial spores in low-conductivity solution. Dielectrophoresis uses spatially nonuniform, alternating electric fields to move particles by polarizing them and then acting on the induced dipole [1]. This concentrator uses positive dielectrophoresis, pulling particles toward electric field maxima. In operation, we set up the electric fields by lining the bottom of the channel with interdigitated electrodes. We combine a passive mixer [2] with these electrodes to enable trapping at high flowrates: the mixer circulates the liquid, bringing particles to the bottom of the channel where they are trapped by the electrodes. When enough particles have been collected, they are all released at once in a small volume, thereby producing a concentrated sample. Figure 2 shows a plot of output concentration over time as a sample of beads is released. The plot was produced by sampling discrete droplets at the output of the device and measuring their bead concentration using a spectrophotometer. This result shows a concentration enhancement of 25x between the input (C0) and output (Drop #5) concentrations.

single Molecule Analysis of DNA in Electric Fields

Recent advances in gene therapy and crime investigation have spurred a demand for rapid “gene mapping” of large (kbp-Mbp) DNA molecules. Because current electrophoresis technologies are inadequate for large DNA, several promising MEMS designs for DNA mapping have been recently proposed that require either: 1) a DNA molecule negotiating an obstacle course in a microchannel or 2) stretching a DNA coil for linear analysis. The goal of our research is to experimentally probe the fundamental physics that underlie these DNA mapping designs. In general, the governing physics is complex due to the confinement of the microchannel, the coiled-nature of long DNA molecules, and the induced electric field gradients from obstacles and changes in channel dimensions. With single molecule microscopy, we have demonstrated many of the governing physical mechanisms at play in these gene mapping microfluidic devices [1-3]. For example, we have shown the experimental scaling for the diffusion coefficient of DNA in a confined channel (Figure 1a) and the probability distribution for the “collision time” of a DNA molecule unhooking from a small obstacle (Figure 1c). In addition, we have thoroughly investigated DNA stretching in electric field gradients created by a contraction and an obstacle (Figure 2). Just as a flow gradient stretches a polymer, an electric field gradient can stretch a charged polymer like DNA. Because electric field gradients have no local rotational components, a charged polymer will experience purely extensional deformation. These findings will aid the design of DNA separation devices that contain many obstacles and contractions, and they also offer an attractive way to completely stretch DNA for linear analysis.

Microfabricated Mechanical Biosensor with Inherently Differential Readout

Intermolecular forces that result from adsorption of biomolecules can bend a micromachined cantilever and enable the detection of nucleic acids and proteins without any prior labeling of target molecules. Often, the cantilever deflection is detected using the optical lever method, i.e., by focusing a laser beam at the tip of the cantilever and measuring the changes in position of the reflected beam. Researchers have also shown that, by using the optical lever method to separately measure the bending of two identical cantilevers, the reliability of the signal resulting from the molecular binding reaction is improved by monitoring the relative or differential bending. [1]We developed an interferometric sensor that inherently measures the differential bending between two adjacent cantilevers, thereby eliminating the need for two separate optical setups and alignment steps. The two cantilevers constitute a sensor-reference pair, whereby only the sensing surface is functionalized with receptors that are specific to the ligand to be detected (Figure 1). The two cantilevers have closely matched responses to background disturbances. Hence, disturbance-induced nonspecific deflections are suppressed upstream, i.e., before the optical signal is measured. We have previously shown that in air, the resolution of the interferometric cantilever-based sensor at high frequencies (40-1000 Hz) is limited by its sub-angstrom thermomechanical noise (~0.2 ÅRMS). However, at lower frequencies, the sensor exhibits a flicker or 1/f-type behavior, which yields noise levels that are much higher (~10 ÅRMS) than the thermomechanical noise. For biological applications of cantilever-based sensors, it is the low-frequency behavior in liquid that governs the detection limit. We have measured the low-frequency behavior of the sensor in liquid and demonstrated that it can be improved by differential detection (Figure 2) [2].

Micromechanical Detection of Proteins Using Aptamer-Based Receptor Molecules

Numerous studies have been conducted on using antibodies as receptors for detecting proteins. Although antibodies can be used to detect proteins with high sensitivity and specificity, they are generally produced in vivo, which introduces difficulties in engineering their properties. In contrast, aptamers (nucleic-acid binding species) can be selected in vitro and have been produced against a wide range of targets, from small molecules, to proteins, to whole cells. Aptamers are DNA or RNA molecules, which can form tertiary structures that recognize and bind to their respective targets.We have investigated the capability of an aptamer-protein binding event to generate changes in surface stress that bend a flexible micromachined cantilever (Figure 1) [1]. We used a receptor-ligand system that was previously investigated and characterized in solution. The ligand, i.e. the target molecule, was Thermus aquaticus (Taq) DNA polymerase, an enzyme that is frequently used in polymerase chain reaction (PCR). The recognition element (receptor) of the sensor was an anti-Taq aptamer modified with a thiol group at one end to enable covalent linking onto a gold surface. The sensor cantilever was functionalized with aptamer molecules, and the reference cantilever was functionalized with oligonucleotides of nonspecific sequence. The differential bending between the two cantilevers was determined directly by using interferometry. We characterized the system in terms of its response to variation in ligand concentration, as well as, its ability to recognize a particular ligand in a complex mixture and to discriminate against nonspecific binding (Figure 2). Our results indicate that aptamers can be used with cantilever-based sensors for sensitive, specific, and repeatable protein detection.

Plasmon Microscopy on Gold and Gold/Oxide surfaces

Surface plasmon resonance has primarily been used as a technique for measuring the thicknesses of very thin organic and polymer films on metallic surfaces with low lateral resolution. Its ability to sense unlabeled molecules and its speed of measurement are advantageous when observing real-time adsorption, desorption, or reactions, of biological molecules.In this study, we will use the surface plasmon technique to create an imaging microscope to study planar lipid bilayers. We develop imaging optics that collect the plasmon reflectivity in a CCD (charged-coupled device) camera to provide real images of the optical thickness of absorbates as shown in Figure 1. To improve the lateral resolution, we will utilize protein barriers to restrict the motion of the lipids and to uniformly divide the observational field. We print these with a PDMS (polydimethylsiloxane) stamp made from photoresist masters created in the MTL Technology Research Laboratory. To provide a surface commensurate with other experimentation on the lipids, we coat the metallic interface with a 10 nm layer of silicon dioxide, which has a minimal effect on sensitivity. The metallic surface and the silicon dioxide coating are evaporated in the MTL Exploratory Materials Laboratory. In Figure 2, we show a static corral pattern with 50x50 µm2 areas of 40% 1,2-dioleoyl-sn-glyceri-3-phosphocholine (DOPC)/30% egg-sphingomyelin/30% cholesterol surrounded by 10 micrometer wide BSA (Bovine Serum Albumin) protein spacers. The width is foreshortened by the experimental setup.After improving the lateral resolution, this technique will be able to image the domain dynamics caused by enzyme reactions in a high throughput way.

Use of stamped Protein corrals in High Throughput studies of Lipid Membrane Model systems

Supported lipid bilayers are useful in vitro mimics for natural biological membranes, and various biotechnological applications are facilitated by their planar geometry. In this study, variable compositions or conditions will be created on supported planar lipid bilayers in order to study the coupled effects of enzyme, membrane, and solution composition on the sphingomyelinase enzymatic reaction. We combine gradients produced by microfluidic flows with membranes confined to surface patterned corrals in order to achieve a high throughput experimental system in which the preparation and measurement times can be greatly reduced. We employ poly(dimethylsiloxane) (PDMS) stamps, which are made from photoresist masters created in the MTL Technology Research Laboratory, to print proteins [1] onto glass surfaces to create barriers capable of restricting the motion of lipids to specific regions of the surface called corrals, as shown in Figure 1. The various membrane conditions in the corrals can be created by incorporating the patterned surface within a microfluidic device. The laminar flow in the micofluidic channel causes fluid elements to follow streamlines, mixing across the streamlines only by diffusion. To create varying lipid bilayer compositions, vesicles are deposited from solution and irreversibly stick to form a continuous bilayer within each corral. As a consequence, a particular vesicle composition in the microfluidic channel is captured by the surface and is restricted in each corral, as shown in Figure 2. Likewise, we can create gradients in the bulk solutions (e.g. enzyme concentration or buffer conditions) by varying the composition in neighboring laminar streams. The desired corralled lipid composition gradient or desired solution condition gradient upon corralled lipid can be adjusted by flow parameters and scale of corral size.

Use of Microfluidic Device to study Protein-Polymer Interactions

In recent years, the importance of polymer architecture on their physical properties has been recognized. We are studying the effect of a polymer’s macromolecular architecture on its ability to interact with other molecules, in particular with proteins. In order to study a variety of protein-polymer interactions we developed a microfluidic platform. We monitor polymer-protein interactions by means of fluorescence resonance energy transfer (FRET), where the polymer molecules are unlabeled and two populations of protein molecules are fluorescently labeled with a FRET donor and an acceptor pair. Because a FRET signal is highly distance-dependent, without interaction we observe little FRET, and upon complexation, we observe a strong FRET signal (Figure 1). We are interested in the effects of polymer branching on protein aggregation and have chosen a model system of different generations of Poly(amidoamine) PAMAM dendrimers and fluorescently labeled Streptavidin. We can manipulate the overall charge of PAMAM dendrimers either by selecting dendrimers generation (G0, G2, G4, etc) or by adjusting the solution pH.We create a microfluidic device from polydimethylsiloxane (PDMS). The laminar flow in these channels allows us to directly compare polymer or control solutions interacting with the protein solution by interdiffusion. Our initial results show qualitative differences between Streptavidin/PAMAM (G2) and Streptavidin/PAMAM (G4) interactions (Figure 2). As molecules move along the channel, they start interacting. We observe both a shift in peak position, as well as, changes in intensity profiles as the molecules move away from the junction point. The peak position shift indicates that, indeed, both polymers interact with Streptavidin and that changes in intensity profiles are not solely caused by diffusion. Differences between the intensity profiles of Streptavidin/PAMAM G2 and Streptavidin/PAMAM G4 show that indeed both polymers interact differently with Streptavidin molecules; we are currently analyzing these FRET profiles to provide a quantitative measure of protein-polymer interaction.

Super-Hydrophobic Surfaces for Hemocompatibility

It is well known that in fluid systems, as geometric scale decreases, the effect of surface forces increases relative to body forces. This property has been exploited to modify the wetting behavior of fluids on a surface by structuring the surface. By reducing feature size, surfaces have been developed that have a contact angle with water that approaches 180˚ when the flat-surface contact angle of the material is closer to 100˚ [1]. Our project focuses on making these so-called super-hydrophobic surfaces practical to manufacture. We have manufactured surfaces with water contact angles above 160˚ by casting poly-dimethylsiloxane (PDMS), a material with a flat-surface water contact angle of approximately 100˚. Our methods are limited by the size of a low temperature oven, not by wafer size. Thus, we can scale production size up beyond the limits of typical microfabrication techniques. Additionally, we are interested in the application of super-hydrophobic surfaces in bio-medical systems to improve hemocompatability. A material is hemocompatable if it does not react unfavorably in the presence of blood. Hemocompatible surfaces are crucial to the performance of many biomedical devices. One of the requirements for such surfaces is the ability to resist the coagulation of proteins from blood. The increase in contact angle for super-hydrophobic surfaces is driven by a reduction in the interaction between the fluid and the surface. We are investigating the hypothesis that reducing the fluid-surface interaction between blood and a surface by microstructuring will decrease protein deposition on the surface.

Electrical Properties of the Tectorial Membrane Measured with a Microfabricated Planar Patch clamp

The tectorial membrane (TM) is a mechanical structure in the cochlea that plays a critical role in hearing. Although its composition suggests that it contains an abundance of charged molecules–charges that may contribute to its mechanical properties–measuring the concentration of this fixed charge has been difficult. Since the TM lacks an insulating cell membrane, traditional micropipette techniques have not yielded stable measurements of the electrical potential of the TM. We have developed a microfabricated chamber that overcomes this problem by placing the TM as an electrochemical barrier separating two fluid baths. The chamber consists of a small aperture into a microfluidic channel (Figure 1), similar to previous planar patch clamp designs [1]. The aperture diameter was chosen to be small enough to be covered by the TM, while large enough to contribute little electrical resistance. The microfluidic channel allows perfusion of the fluid below the TM, so the ionic composition of fluids in both baths can be rapidly changed. Varying the ionic concentration of the baths changes the electrical potential between baths in a manner that depends on the fixed charge of the TM. The microfabricated chamber has enabled the first stable, repeatable measurements of this electrical potential (Figure 2). The results suggest that the TM contains sufficient charge to completely account for its mechanical rigidity.

Microfabricated shearing Probes for Measuring Material Properties of the Tectorial Membrane at Audio Frequencies

The tectorial membrane (TM) is ideally located to exert shearing forces on sensory hair cells in the cochlea in response to sound. Consequently, measuring the shear impedance of the TM is important for understanding the mechanical basis of hearing. However, few direct measurements of TM shear impedance exist, because the small size of the TM and the need to measure its properties at audio frequencies render traditional impedance measurement methods infeasible. We have overcome these limitations by designing and microfabricating shearing probes that are comparable in size to the TM and that can exert forces at audio frequencies. The probes consist of systems of cantilevers designed to apply forces in two dimensions (Figure 1). Forces applied to the base of the probe are coupled through the cantilevers to a shearing plate, which is brought into contact with the TM. By measuring the relative deflection of the base and plate and knowing the probe stiffness, we can determine the shear impedance of the TM. A variety of probes with different stiffnesses and geometries allow measurement of impedance over many orders of magnitude. Figure 2 shows a probe whose shearing plate is in contact with the TM. To determine TM impedance at audio frequencies, we have coupled these probes to a computer microvision system that allows measurements of nanometer-scale motions at high frequencies [1]. The probes were calibrated, and could exert forces with amplitudes in the range 3-300 nN at frequencies from 10-9000 Hz, a large fraction of the hearing range. Measurements of TM shear impedance, using these microfabricated probes, have helped to characterize this enigmatic component of the cochlea.

Implantable MEMs for Drug Delivery

We have developed an implantable silicon microelectrome-chanical system (MEMS) device for biomedical applications [1]. This device contains an array of wells that hermetically store its contents. Activation of the device electrochemically dissolves gold membranes covering the wells, by application of an anodic voltage through a wire-bonded connector (Figure 1). The well contents are then exposed to the surrounding en-vironment. This system allows temporal control of several acti-vations and the ability to store a variety of contents separately. Targeted application for this device is local drug delivery.We have focused our drug delivery efforts on carmustine (BCNU), a potent brain cancer drug. Local delivery of BCNU from an implanted device results in efficacious concentrations at the tumor site, coupled with reduced systemic toxicity, which is a major drawback of the systemic delivery of BCNU [2]. We have achieved successful in vitro and in vivo release of BCNU, and have shown it to significantly impede tumor growth in rats as a result of co-formulation with polyethylene glycol (PEG) to improve release kinetics, and of the development of a new, Pyrex-based package that increases the capacity of the device [3]. Combination therapy of BCNU with Interleukin-2 (IL-2), however, has been shown to be more effective than either alone against tumors [4]. We, therefore, plan to use our device to achieve combination releases, to fully utilize the advantages of our MEMS, i.e., temporal control and multi-drug releases.