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Contact-printed MEMS Membranes

It is desirable to extend the functionality of MEMS to different form factors including large-area arrays of sensors and actuators, and to various substrate materials, by developing a means to fabricate large-area suspended thin films. Conventional photolithography-based MEMS fabrication methods limit the device array size and are incompatible with flexible polymeric substrates.A new method for additive fabrication of thin (125±15-nm-thick) gold membranes on cavity-patterned silicon dioxide substrates using contact-transfer printing is presented for MEMS applications. The deflection of these membranes, suspended over cavities in a silicon dioxide dielectric layer atop a conducting electrode, can be used to produce sounds or monitor pressure. The fabrication process employs a novel technique of dissolving an underlying organic film using acetone to transfer membranes onto the substrates. The process avoids fabrication of MEMS diaphragms via wet or deep reactive-ion etching, which in turn removes the need for etch-stops and wafer bonding. Membranes up to 0.78 mm2 in area are fabricated, and their deflection is measured using optical interferometry. The membranes have a maximum deflection of about 150 nm across 28-μm-diameter cavities, as shown in Figure 1. Using the membrane deflection data, Young’s modulus of these gold films is extracted (74±17 GPa), and it is comparable to that of bulk gold. Additionally, a 15 Hz sinusoidally varying voltage of 15 V peak-to-peak amplitude is applied to the MEMS device to demonstrate that the large membrane deflection is a repeatable deflection (Figure 2).These films can be utilized in microspeakers, pressure sensors, microphones, deformable mirrors, tunable optical cavities, and large-area arrays of these devices.

An On-Chip Test Circuit for Characterization of MEMS Resonator

Electromechanical resonators such as quartz crystals, surface acoustic wave (SAW) resonators, and ceramic resonators have become essential components in electronic systems. However, due to their large footprint and difficulty in integrating with CMOS processes, there has been much development in realizing microelectromechanical system (MEMS) resonators that achieve comparable performance yet have smaller footprint and are compatible with CMOS. As with other semiconductor devices, with increasing frequency and with decreasing device size into the submicron scale, variability has started to become a critical issue in MEMS resonators. However, one of the critical challenges is the lack of a characterization method that is accurate but efficient enough to be used for testing the large number of devices necessary to acquire accurate statistical distribution of the parameters of interest. This project proposes an on-chip test circuit that can accurately characterize a large number of resonators for variation analysis and that is general enough that it can be used with a wide range of resonators, not limited to specific frequencies or other properties. The proposed test circuit is based on a transient step response method using a voltage step that can accurately measure the resonant frequencies and the quality factor of devices [1] . The circuit employs a sub-sampling method to capture the high-frequency decay signal [2] and a simple analog-to-digital converter (ADC) [3] allowing complete digital interface, an important feature for test automation. SPICE level simulation combined with a behavioral simulation tool that was developed showed acceptable extraction errors of <1% for RS, <0.1% for Lx, <0.1% for Cx, <100 ppm for fs, and <1% for Qs. A test chip implementing the proposed test circuit has been designed and fabricated in NSC 0.18-um CMOS process.

DNA-templated Assembly of Droplet-derived Microtissues

Paracrine and autocrine cell signaling are critical factors guiding tissue development and maintenance, and dysregulation of these cues contributes to the pathogenesis of diseased states such as cancer. Patterning multiple cell types is thus a critical step for engineering functional tissue [1] , but current “top-down” approaches such as dielectrophoresis and photopatterning are challenging to scale-up for the construction of mesoscale tissues. On the other hand, “bottom-up” methods wherein small tissue building blocks are assembled into larger structures have potential for constructing multicellular tissues in a facile, scalable fashion. Synthetic microtissues composed of cell-laden hydrogels in this size range represent appropriate fundamental building blocks of such bottom-up methods [2] .To specify the placement of many different microtissues relative to one another, we have developed a “bottom-up” approach for fabricating multicellular tissue constructs that utilizes DNA-templated assembly of 3D cell-laden hydrogel microtissues (Figure 1a). A microfluidic flow focusing-generated emulsion of photopolymerizable prepolymer is used to produce 100-µm monodisperse microtissues at a rate of 100 Hz (105/hr) (Figure 1b-d). Multiple cell types, including suspension and adherently cultured cells, can be encapsulated into the microtissues with high viability (~97%) (Figure 1e). We then use a DNA coding scheme to self-assemble microtissues “bottom-up” from a template that is defined using “top-down” techniques. The microtissues are derivatized with single-stranded DNA using a biotin-streptavidin linkage to the polymer network and are assembled by sequence-specific hybridization onto spotted DNA microarrays. Using orthogonal DNA codes, we have achieved multiplexed patterning of multiple microtissue types with high binding efficiency and >90% patterning specificity (Figure 2a). We have also demonstrated the ability to organize multicomponent constructs composed of epithelial and mesenchymal microtissues while preserving each cell type in a 3D microenvironment (Figure 2b).

AC Variability Characterization of MOSFETs

The high-frequency variability characterization of MOSFETs is becoming more necessary due to new process developments such as high-K metal gates, elevated source-drain junctions, strained silicon, and others. Some of the effects of these variability sources can be seen at low frequencies by characterizing MOSFET parameters such as threshold voltage or saturation current. However, the nature of some of these sources of variability may manifest itself only at high frequencies. Two circuits have been designed and implemented to assess the potential manifestations of these short time-scale, or AC, variation sources.The first circuit is a simple array-based test structure consisting of 128 devices under test (DUTs) whose relative delays are characterized using a logic gate-based delay detector circuit, as shown in Figure 1 [1] . The delay measurement technique only requires a single off-chip DC voltage measurement for each DUT. A design-time optimization is performed on each DUT array to ensure that the measured delays of each DUT primarily reflect its AC, or short time-scale, characteristics rather than previously well-studied DC characteristics such as saturation current, threshold voltage, and channel length.The second circuit, shown in Figure 2, is a ring oscillator (RO)-based test structure which transforms small delay variations into easily measurable digital and DC quantities [2] . This enables the calculation of a parameter that primarily reflects the AC, or short time-scale, characteristics of the DUT. An array of such ROs is designed in order to obtain statistics on the DUTs. The array-based circuit and RO-based circuit occupy areas of 400 um x 20 um and 1600 um x 20 um, respectively, and are both implemented in an advanced CMOS PD-SOI technology. Simulations show that both circuits exhibit good sensitivity towards potential AC variation sources in transistors.

An On-Chip Test Circuit for Characterization of MEMS Resonators

Electromechanical resonators such as quartz crystals, surface acoustic wave (SAW) resonators, and ceramic resonators have become essential components in electronic systems. However, due to their large footprint and difficulty in integrating with CMOS processes, there has been much interest in developing microelectromechanical systems (MEMS) resonators that achieve comparable performance yet have smaller footprint and are compatible with CMOS. Recently, MEMS resonators have been proposed that overcome physical limitations in traditional resonators to reach frequencies in the GHz range. In addition, they have the potential for compatibility with CMOS, opening up possibilities for new circuits and systems [1] . As with other semiconductor devices, with increasing frequency and with decreasing device size into the submicron scale, variability has started to become a critical issue in MEMS resonators. Thus vigorous characterization of important device parameters such as resonant frequencies, quality factors, and variations associated with them has become necessary. However, one of the critical challenges is the lack of a characterization method that is accurate but efficient enough to be used for testing of the large number of devices necessary to acquire accurate statistical distribution of the parameters of interest. This project proposes an on-chip test circuit that can accurately characterize a large number of resonators for variation analysis. The desired test circuit is general enough that it can be used with a wide range of resonators, not limited to specific frequencies or other properties. Previous works have attempted to achieve similar goals, but most of them were restricted to characterization of a single device or a narrow range of properties. The proposed test circuit is based on a transient step response method using a voltage step that can accurately measure the resonant frequencies and the quality factor of devices [2] . The circuit employs a sub-sampling method to capture the high-frequency decay signal [3] and a simple analog-to-digital converter (ADC) [4] allowing complete digital interface, an important feature for test automation.

Micro-contact Printed MEMS

It is desirable to extend the functionality of MEMS to different form factors including large area arrays of sensors and actuators, and to various substrate materials, by developing a means to fabricate large-area suspended thin films. Conventional photolithography-based MEMS fabrication methods limit the device array size and are incompatible with flexible polymeric substrates. We present a new method for fabricating thin (140-nm-thick) suspended metal films in MEMS using micro-contact printing. These films can be utilized in pressure sensors, microphones, deformable mirrors, tunable optical cavities, and large-area arrays of MEMS sensors.Our approach to MEMS fabrication involves the use of a stamp and a donor viscoelastic transfer pad that is coated with an organic release layer and a thin film of metal. The stamp consists of a layer of patterned polydimethylsiloxane (PDMS) atop a glass slide that is coated with a layer of electrically conducting indium tin oxide (ITO). The surface of this patterned PDMS stamp is placed in contact with the thin metal film on the donor transfer pad, and then the stamp is rapidly peeled away, picking up the metal film. The metal film ends up bridging the gaps in the patterns of the PDMS stamp, forming a capacitive MEMS structure. A continuous film of metal is lifted onto the stamp only if the stamp is peeled off the transfer pad rapidly.This process avoids the use of solvents and etchants, eliminating the need for deep reactive-ion etching and other harsh chemical treatments. Solvent absence during fabrication also avoids the detrimental effects of MEMS stiction that can result during wet processing. MEMS fabrication on flexible polymeric substrates is also possible due to the absence of elevated temperature processing.Thin films up to 0.78 mm2 in area have been fabricated using the aforementioned process, as shown in Figure 1. These MEMS devices are actuated electrostatically to demonstrate the deflection of 25-μm-diameter films (see Figure 2).

Malaria-diagnostic System Based on Electric Impedance Spectroscopy

Malaria prevails mainly in the countries that lack proper medical facilities, and it kills about a million people worldwide a year. This parasitic disease invades human red blood cells (RBCs), and it is life-threatening unless treated immediately [1] .This work focuses on utilizing a single cell analysis technique to develop a rapid malaria diagnostic test system among various approaches to diagnose the disease in its early stage. Single cell analysis based on electronics enables high throughput tests of biological cells. The specific analysis method used in this research is electric impedance spectroscopy (EIS), which measures the electric impedance of biological cells flowing continuously over a pair of electrodes, so that it can differentiatecells whose impedance is highly correlated to cell size and cytoplasm permittivity [2] [3] [4] [5] [6] .The system consists of two parts: a MEMS probe and a reader circuit. To investigate one cell at a time and to achieve enough sensitivity to tiny (<10 µm) human red blood cells, a MEMS device consisting of a microfluidic channel and micro-electrodes is fabricated. The probe MEMS device is made of transparent materials except the electrodes for convenience of monitoring. In addition, a printed-circuit-board using a commercial impedance-to-digital chip is made to continuously measure electric impedance in high-speed manner. The circuit board generates a sinusoidal voltage signal, measures the DFT of the resulting current, and calculates the impedance from DFT. We are seeing this system as a possible solution for developing a low-power, highly sensitive, and cost-effective malaria diagnostic device.

Automated Passive Dynamical Model Extraction of Thin Film Bulk Acoustic Resonators (FBAR) for Time Domain Simulations

Thin Film Bulk Acoustic Resonators (FBARs) are widely used in the design of modern radio frequency components including duplexers, filters, and oscillators. The overall goal of this project is to incorporate the performance parameters of these resonators into the design flow of the overall system. As a first step, the frequency response of the fabricated devices is measured. Traditionally, an equivalent circuit is then built based on least squares fitting of the frequency response of a simple RLC network to the measured data [1] . Such a technique is fairly simple, and the resulting equivalent model does capture important performance parameters, such as quality factor and resonant frequency. However, this technique cannot capture spurious resonances and other second order effects, which quite often play a significant role in the overall performance of the device.In this work, we are developing tools that will automatically generate accurate, compact, and passive dynamical models for FBARs. Given measured transfer function samples, we identify a rational transfer function model that minimizes the mismatch at the given frequencies. These dynamical models can be interfaced with commercial circuit simulators for time domain simulations of a larger interconnected system. To guarantee the stability of the overall simulation, we ensure the passivity of our generated models by enforcing semidefinite constraints during the fitting process as proposed in [2] . Figure 1 shows the 3D layout of an FBAR. Numerical results are presented for resonators configured to constitute a bandpass frequency response. Figure 2 compares the output of our identified models with the given measured data.

Single-cell Trapping and DNA Damage Analysis Using Microwell Arrays

DNA damage has been found to play critical roles in cancer, aging, and heritable disease. There is rising interest in studying DNA damage and repair kinetics in cells, but the lack of a robust, inexpensive, and high-throughput device for quantitative DNA damage analysis makes such investigations far from routine. The single cell gel electrophoresis or “comet” assay is one of the best-established methods for detection of DNA lesions and strand breaks. Based on the principle that relaxed loops and fragments of damaged DNA migrate farther under the influence of an electrical field in agarose gel than undamaged DNA, the level of DNA damage can be assessed by measuring the relative amount of DNA migration. Although extremely versatile and inexpensive, the comet assay is restrained from wider acceptance due to its low throughput, poor reproducibility and laborious and potentially biased analysis methods. Through incorporation of microfabrication techniques, we have developed a microarray platform to perform high throughput single cell electrophoresis with improved consistency. Different from randomly dispersed cells in the traditional comet assay, cells on our platform are patterned into spatially registered microscopic wells. These microwells are formed by direct stamping of hydrated gels with molds that contain patterned microposts fabricated through Su-8 photolithography (Figure 1). Cells are arrayed through passive settling into the microwells and can then undergo treatment and analysis. We have also developed software that utilizes the unique patterning feature to automatically analyze images with high accuracy and reproducibility (Figure 1). By sandwiching our patterned agarose gel between a bottomless 96-well plate and glass plate, we have transformed our assay into a multiwell version, referred to as “the CometChip.” This 96-well format enables simultaneous investigation of different chemical conditions among different cells samples, as well as analysis of repair kinetics. Importantly, the CometChip is compatible with standard automated liquid handling and imaging. The efficacy and increased throughput of the CometChip for DNA damage analysis is demonstrated by comparing an irradiation dose response to the traditional comet assay (Figure 2). All doses and replicates were assayed on a single CometChip in significantly shorter time and with less labor. Our research has demonstrated a significant technological advance to traditional methodology and opened countless possibilities in epidemiology and drug development applications.

Continuous Signal Enhancement for Sensitive Aptamer Mobility Shift Assay Using Electrokinetic Concentration

Aptamers are emerging as popular alternatives to antibodies as affinity probes in immunoassays. From a point-of-care diagnostics standpoint, aptamers have an advantage over antibodies since they are stable over a wide range of conditions and can be chemically synthesized at low cost. Affinity probe capillary electrophoresis (CE) [1] [2] is a promising platform with which to perform aptamer-based biomarker detection as it features fast homogeneous reaction kinetics and requires only one affinity probe species, although sensitivity is still limited due to band dispersion, complex dissociation and lack of amplification reaction.We have previously demonstrated microfabricated nanofluidic preconcentration devices that can continuously accumulate a charged biomolecule species at a specified location [3] [4] [5] . In this work, we showed that these devices can also efficiently separate biomolecules with different mobilities by focusing them at different locations. This phenomenon lends itself well to aptamer affinity probe CE, where aptamers undergo a significant mobility shift upon binding to larger target proteins. The important advantage of this scheme compared to conventional CE is that aptamer-protein dissociation and band broadening effects are counteracted by electrokinetic focusing. By simultaneously focusing and separating free aptamers from aptamer-protein complex in this device, we can obtain highly sensitive and quantitative measurement of target biomarkers using aptamers.With this scheme, we showed enhanced detection sensitivity for IgE and HIV-1 RT in simple buffer solution. The limits of detection obtained (4.5 pM for IgE and 9 pM for HIV-1 RT) are among the lowest reported in the literature. The limit of detection for IgE in 10% serum was 10-fold higher due to nonspecific interactions between aptamers and serum proteins. Due to the simple readout for this assay, multiple samples can be assayed in parallel. As the assay is driven by gravitational flow, uses low voltages (30 V), and does not require multiple processing steps, it is well-suited towards low-cost point-of-care analysis.

Dynamic Cell Deformability Study in Microfluidic Devices

The mechanical properties of tissues and cells have important implications on their differentiated state, functions and responses to injury. Altered cell deformability is both a cause of and biomarker for potentially severe diseases, such as cancer, sickle cell anemia and malaria. In the past, several techniques have been developed to measure single-cell deformability including micropipette aspiration, atomic force microscopy, and optical tweezers. However, many of these measurements assess only static cell deformations which often fail to reflect in vivo situation when cells are in microcirculation. Additionally, the low throughput of the techniques limits sampling size per experiment, which may potentially lead to misrepresentation of population-wide trait. Therefore, we aim to develop a microfluidic device which measures cell dynamic deformability with high sensitivity and high throughput.In this project, the relation between cell dynamic deformability and disease state is aimed to be established for several representative cell lines including human erythrocytes, breast cancer cells, and mesenchymal stem cells. The impact of microenvironmental controls such as temperature fluctuation and drug treatment on the deformability of malaria infected cells is also investigated.

An Integrated Microfluidic Probe for Concentration-enhanced Selective Single Cell Kinase Activity Measurement

We present an integrated microfluidic probe that captures the contents of selected single adherent cells from standard tissue culture platforms and directly measures specific protein kinase activities in the captured lysate using either a fluorimetric assay in a small isolated chamber or a concentration-enhanced mobility-shift assay in an integrated nanofluidic concentrator. We demonstrate the use of the probe by measuring kinase activity in a single human hepatocellular carcinoma (HepG2) cell.Traditional cellular assays measure average properties of 103-106 of cells, missing differences (e.g., drug responses) between individual cells in supposedly homogenous populations that have consequences for treatment of diseases [1] . Recent microfluidic or traditional tools [2] have studied genetic differences between single cells using nucleic acid amplification. These tools fail to capture important non-genetic sources of heterogeneity that create unique proteomes in different cells. Direct measurement of protein activities from single cells remains difficult due to limited assay sensitivity. In addition, difficulties in interfacing with adherent cells in a standard culture have led to the use of cell suspensions in microfluidic single cell assays [2] .The integrated device (Figure 1) reported here interfaces with standard tissue culture plates using a microfluidic probe [3] that creates a limited, tunable lysis zone at its tip by simultaneously dispensing and collecting lysis agents and lyses and collects contents of selected single cells from adherent cell populations. The captured cytosol is mixed with assay reagents and flowed into a small reaction chamber, which is isolated for observation, using pneumatic micro-valves. The integrated ion-selective hydrogel-based nanofluidic concentrator [4] is then used to trap/concentrate the proteins/reaction products in the mixture to yield very high kinase assay sensitivity [5] , sufficient to probe proteins from single cells. This single cell detection platform is agnostic to specific sensing chemistry, so other biochemical assays can also be implemented with minimal modification.

Microfluidic Platforms for Studying the Role of the Biophysical and Cellular Microenvironment in Tumor Invasion

Tumor invasion has received considerable attention as a critical step in cancer metastasis, and is a promising target for developing new cancer drugs. Current understanding of the role of the biophysical and cellular microenvironment in tumor invasion is limited, because of the lack of appropriate in vitro and in vivo models. We have adapted our previous microfluidic platforms [1] for studying the role of the endothelium on tumor intravasation (entry into the vascular system) and the effects of interstitial flow on tumor cell migration, along with the development of new hard plastic devices for commercial transition.Recent results from the tumor-endothelial interaction assay demonstrated the capability to form a confluent endothelial monolayer on collagen type I matrices, in the presence of invading tumor cells in 3D (Figure 1). Stimulating the layer with inflammatory cytokines, we demonstrated an increase in diffusive permeability to fluorescent dextrans, in agreement with a measured increase in the number of intravasation events. These results demonstrate the utility of this assay for studying the role of the endothelial barrier function in tumor cell intravasation.We also developed a microfluidic system for investigating the role of interstitial flow in tumor cell migration (Figure 2). Tumor cells exposed to interstitial flow preferentially migrated along streamlines, and the relative percentage of cells migrating upstream and downstream was found to be a function of chemokine receptor activity and cell density. Interstitial flow stimulated downstream tumor cell migration through CCR7-mediated autocrine signaling. However, flow also stimulated upstream cell migration through a competing, mechanically mediated pathway, as evidenced by significant increases in FAK activation in devices with flow. Relative strengths of the autocrine and mechanical stimuli determine whether cells migrate upstream or downstream.We applied known commercially-viable manufacturing methods to a cyclic olefin copolymer (COC) to fabricate a microfluidic device with controlled surface properties and improved potential for high-volume applications. Culture of cells in the new COC device indicated no adverse effects. Therefore, this transition of platform demonstrates a capability of using microfludic devices for 3D cell culture across the range from the scientific research to applications with broad clinical impact.

Thermal Ink Jet Printing of PZT Thin Films

We recently demonstrated a process of thermal ink jet printing of PZT thin films for MEMS applications [1] [2] . Previous methods for deposition of solution-based PZT were painstaking and low-yield; they also imposed significant processing and design constraints. Thermal ink jet printing allows for rapid, low-cost deposition of patterned PZT films over a wide range of geometries and provides for greater flexibility in process sequencing. With this technique, PZT may be easily integrated into devices with large out-of-plane features after the micro-machining process, which enables the formation of more complex device structures. In 2010-2011 the printing process was modeled in detail, including the dynamics of droplet formation as well as the internal flows that occurring during film drying. Models proposed by others were extended to include printed PZT films [3] . Experiments were carried out to confirm the modeling. Specifically, high-speed camera images (Figure 1) were taken to visualize the droplet formation, and the effects of surface tension and temperature were investigated through droplet drying tests. As a result the conditions required for highly repeatable and uniform printed films were determined. Further development work focused on the integration of printed PZT into a range of micro-machined structures including cantilevers and bridges with energy harvester applications as well as resonators for ultrasonic transduction (Figure 2). These devices provide a proof of concept for a fully integrated PZT device fabrication process. In the future we plan to produce devices that utilize the full capabilities of this process to reach energy densities and acoustic coupling greater than those of devices based on current deposition techniques.

Piezoelectric Transducers for Advanced Ultrasound Imagining Systems and Energy Harvesting

In this project, a piezoelectric 2-D array of ultrasound transducers will be developed for compact, portable 3-D ultrasound imaging systems. Piezoelectric materials have been used for macro-scale ultrasound systems due to their high polarization density. However, making tiny 2-D array of transducers with conventional piezoelectric materials (all ceramic or polymeric composite) has been extremely difficult. Dicing and bonding of crystallized piezoelectric ceramic bulk and subsequent delicate assembly operations require a lot of manual effort, which limits production yield, rate, and quality. In addition, piezo-ceramics inherently have high acoustic impedance, which is difficult to match in liquid or air medium. Capacitive Micromachined Ultrasonic Transducers (CMUTs) have been developed to leverage the MEMS fabrication techniques for small form factor transducer fabrication and to mitigate the acoustic impedance mismatch [1] . A CMUT consists of metallized silicon nitride membranes suspended above highly doped silicon bulk. These membranes vibrate when an electrostatic charge is generated under each membrane. Each membrane can also detect the reflected sound wave by measuring the capacitance change at the gap under each membrane. CMUTs offer greater bandwidth than piezoelectrics and are tunable [2] . Moreover, many of the available MEMS processing technologies could be used to make micro-scale arrays of CMUT elements effectively. However, CMUTs still have some technical issues such as high voltage requirement, which makes them not suitable for in vivo operations, result in insulator breakdown, and cause static charge accumulation at the membrane surface.This research project will focus on developing PZT micromachined ultrasound transducers (PMUTs) and designing novel 2-D array PMUTs with a reliable PZT process technique of PZT. The initial goal of this project is to study the PZT structure appropriate for a 64×64 array and actuation voltage less than 10 volts. A prototype PZT structure will be fabricated and characterized to demonstrate the feasibility of the technology. In addition, the low voltage limits, potential efficiency, and sensitivity will be determined and optimized. Fabricating an array of PZT pillars with size less than 50 mm is one of the major challenges of this project. A new and flexible on-demand deposition process for high quality PZT thin films developed by Bathurst et al. will be used to solve this problem [3] .In addition to the advanced medical applications, the core technology developed in this project will be applied to further improve the ultra-wide bandwidth of energy harvesters. This will lead energy harvesters to be deployable in real world applications including sensors for energy efficient buildings, structural monitoring devices of crude oil pipelines, and leak detectors in water supply networks.

Design of Low-frequency, Low-g, Nonlinear Resonating Piezoelectric Energy Harvesters

To overcome the limitations of piezoelectric energy harvesters such as narrow bandwidth and low power density, our group has recently demonstrated a broadband harvester, which is based on amplitude-stiffened Duffing mode resonance. This nonlinear resonance greatly increases the bandwidth by keeping the harvester resonant until jumping down to a low energy state. Furthermore, the stretching strain of the nonlinear beam produces much higher maximum extractable electrical energy than that of a linear bending-based harvester. This design has been fabricated into a compact MEMS device, which is about the size of a US quarter coin. The test results show more than one order of magnitude improvements in both bandwidth (~20% of the peak frequency) and power density (up to 2W/cm3) in comparison to the devices previously reported. To make the energy harvester better scavenge energy from ambient vibrations, which typically have low frequency spectra and low-g excitation, we are exploring new designs based on the nonlinear resonance. We have found that it is possible to bring the working frequency down to the range of 100 Hz to several hundred Hz, and lower the excitation level to ~0.5 g, by tuning the design parameters such as the dimensions of the resonator and external proof mass. The new low frequency, low-g designs will be implemented and tested soon. We anticipate that the broadband, low frequency, low-g piezoelectric energy harvesters will be used to power a wide range of devices including portable electronic devices and self-powered wireless sensors.

MEMS Pressure-sensor Arrays for Passive Underwater Navigation

A novel sensing technology for unmanned undersea vehicles (UUVs) is under development. The project is inspired by the lateral line sensory organ in fish, which enables some species to form three-dimensional maps of their surroundings [1] [2] . The canal subsystem of the organ can be described as an array of pressure-sensors [3] . The lateral line allows fish to perform a variety of actions, from tracking prey [4] to recognizing nearby objects [2] [5] . Similarly, by measuring pressure variations on a vehicle surface, an engineered pressure-sensor array allows the identification and location of obstacles for navigation. Several strain-gauge-based approaches to the sensing element are being tested. The two types presented here are silicon- and polymer-based technologies.Both sensor designs share the following features. The array consists of thin diaphragms. Each sensor has an empty cavity behind the membrane connected via a common backplane to the others. A set of strain gauge resistors on the diaphragms responds to pressure changes. When the sensor is placed in a Wheatstone bridge, the resulting output voltage can be used to determine the change in resistance in the strain gauges and thus the pressure difference between the two sides of the diaphragm. The two technologies differ chiefly in how strain is measured. In the silicon-based approach, the shape of the resistor is altered slightly by strain. In the polymer-based approach, the distances between conducting particles embedded in the material adjusts as strain is applied.The amplified voltage output bridges with strain-gauge resistors on diaphragms of various sizes as was measured as a function of applied pressure. Generally, larger diaphragms are more stable and more sensitive, whereas small diaphragms maintain linearity over a wider range and are more physically robust. The deflections of the centers of silicon diaphragms are measured as functions of applied pressure. Although larger diaphragms exhibit non-linear behavior, there are no hysteretic effects, thus enabling their usage for static and dynamic pressure sensing.For the conductive polymer strain-gauge patterned onto a PDMS membrane, the resistances of the strain gauges are measured against the segment length. The resulting linear fit demonstrates consistency of resistivity across the patterned structure. Finally, observing output voltage in response to dynamic pressure applied with a syringe connected to the sensor indicates a bandwidth fast enough for underwater sensing.

MEMS Space Thrusters: The ion Electrospray Propulsion System (iEPS)

Electric Propulsion (EP) brings benefits for space missions requiring relatively large changes in satellite velocity, for example by reducing the propellant mass compared to traditional, less fuel-efficient chemical engines. Introducing EP in small satellites would enable them to perform interesting missions, such as long term attitude control/drag cancellation, orbital modification and, perhaps, deep space travel [1] . However, most EP technologies are challenging to miniaturize to the required levels, especially for nano/pico-satellites. Our group has developed an ion Electrospray Propulsion System (iEPS) as a candidate of an EP technology amenable for efficient miniaturization. The thruster core is based on a porous metal structure, which is bonded to an oxidized silicon package frame, followed by masking of the metal with a pattern of circles. The metal is then electrochemically etched in a regime that prevents material removal inside the pores, thus forming an array of porous tips [2] , as shown in Figure 1. To finalize the device, an extractor silicon grid with a matching array of holes and coated with a gold film is aligned and bonded to the frame holding the porous metal. Electrical isolation is provided by the bonding material and grown silicon oxide layers. A zero vapor pressure ionic liquid (the propellant) is then injected to the device from the back through a port in the silicon frame. The liquid wicks through the porous structure reaching the tips. Ion emission is the produced when applying a voltage of about 1kV between the metal and extractor grid. Figure 2 shows a typical I-V curve and a picture finished devices on a CubeSat [3] . A thruster pair should be able to produce 60-70 micro-N, enough to raise the orbit of a 1 kg CubeSat by 400 km in about 25 days of operation consuming 6-7 grams of propellant with 1W of power.

Suspended Microchannel Resonators with Piezoresistive Sensors

Precision frequency detection has enabled the suspended microchannel resonator (SMR) to weigh single living cells, single nanoparticles, and adsorbed protein layers in fluid. To date, the SMR resonance frequency has been determined optically, which requires the use of an external laser and photodiode and cannot be easily arrayed for multiplexed measurements. Here we demonstrate the first electronic detection of SMR resonance frequency by fabricating piezoresistive sensors using ion implantation into single crystal silicon resonators [1] . To validate the piezoresistive SMR, buoyant mass histograms of budding yeast cells and a mixture of 1.6-, 2.0-, 2.5-, and 3.0-mm-diameter polystyrene beads are measured. Figure 1 shows our experimental setup. For piezoresistive detection, a Wheatstone bridge is built with the piezoresistor and three external resistors. The bias voltage (5 V) is selected to maximize the signal while limiting the temperature increase in the piezoresistor due to resistive heating. Figure 6 shows mass resolution derived from mass sensitivity and Allan variance. In summary, the mass resolution achieved with piezoresistive detection is comparable to what can be achieved by the conventional optical-lever detector in 1 kHz bandwidth. Eliminating the need for expensive and delicate optical components will enable new uses for the SMR in both multiplexed and field deployable applications.

Continuous Microbioreactors

For systems biology, the models are more often limited by the absence of reliable experimental data than by available computational resources. Unfortunately, there is still great difficulty in making the leap from genetic and biochemical analysis to accurate verification with conventional culture growth experiments due to variations in culture conditions. Measurements of metabolic activity through substrate and product interactions or cellular activity through fluorescent interactions are highly dependent on environmental conditions and cellular metabolic state. For such experiments to be feasible, continuous cultures [1] [2] utilizing control strategies must be developed to measure chemical concentrations, introduce chemical inputs, and remove waste. An integrated microreactor system with built-in fluid metering will enable environmental control and programmable experiments capable of generating reproducible data.The chip shown in Figure 1 is fabricated out of a rigid plastic polycarbonate, utilizing PDMS membranes for actuation and pumping [3] . The fabrication process for bonding plastic-PDMS hybrid devices has been described previously [4] . Mixing and oxygen delivery are performed through membranes between the fluidic and actuation layers of the growth chamber sections. A growth volume of 1 mL ensures the ability to couple sampled volume to offline chemical analysis. Culture experiments are performed using E. coli strain FB21591 grown on defined media. The glucose input is separated to provide input control. As shown in Figure 2, various metabolic states are observable through continuous flow control. Cell density is directly dependent on glucose input, and acid production is proportional to cell density in chemostat mode. In turbidostat mode, cell density can be kept constant and glucose utilization can be observed, demonstrating the direct observation of overflow metabolism.

Controlling the Intrinsic Stresses in Polycrystalline Metallic Films for N/MEMS Applications

Polycrystalline metallic thin films are vital in a wide variety of applications, including microelectronics, plasmonics, magnetic storage, N/MEMS and catalysis. Because mechanical properties strongly influence their reliability and performance, understanding and controlling the intrinsic stresses in as-deposited films are of great importance. When the capacitance or multi-beam laser technique is used, real-time stress measurements can be performed during thin film deposition. The measurement results do not only provide a useful tool to define the stress evolution history but also an insightful picture for the study of structure evolution processes. When combining the in situ stress measurement with other characterization techniques and theoretical modeling, we are able to move towards a comprehensive understanding of the underlying atomic processes during Volmer-Weber growth.We have experimentally studied the intrinsic stress evolution at different homologous temperatures. Figure 1 shows the general trend—compressive stress is favored at higher temperatures and tensile stress is favored at lower temperatures. This trend indicates that the compressive stress generation processes are thermally activated. Furthermore, we found the incremental stress changes from compressive to tensile during growth at intermediate homologous temperatures, e.g., Ni at 398K. The origin of the compressive-tensile transition is not known exactly. None of the previous models [1] [2] [3] are able to explain the transition behavior. We have also studied the stress behaviors during long interruptions of gold films. Particularly, we studied the long interruptions of gold films with different thicknesses. Figure 2 demonstrates that the total released stress is dependent on the film thickness during long interruptions. This result strongly suggests that the stress relaxation during long interruptions is a bulk process. Meanwhile, we found abnormal grain growth occurs in as-deposited gold film at room temperature. By calculating the densification stress due to grain growth and comparing its value with the measured bulk relaxation stress, we conclude that grain growth is the main process of bulk stress relaxation.

MEMS Langmuir Probes for Atmospheric Reentry Plasma Diagnostics

One of the most fundamental technical problems concerning spacecraft design is preparing the vehicle to survive the extreme conditions encountered during reentry into the Earth’s atmosphere [1] . When a hypersonic vehicle travels through the atmosphere, a high-density, low-temperature plasma sheath forms around it [2] . The reentry plasma sheath affects heat transfer to the spacecraft, aerodynamics, and perhaps most notably, communications. A communications blackout is a major threat, bringing about a complete loss of RF signal strength between the reentry vehicle and the ground. A thorough knowledge of reentry plasma sheath properties is needed to effectively develop systems capable of maintaining communications during reentry. However, the reentry plasma sheath occurs due to processes that are not well understood. Furthermore, the conditions of the plasma sheath rapidly change throughout reentry, which introduces additional complications. Analytical approaches alone are not sufficient to gain a complete understanding of the plasma sheath. Therefore, instrumentation must be developed to measure properties of the plasma sheath during reentry [3] .We propose a novel approach to reentry plasma diagnostics, utilizing planar arrays of MEMS Langmuir probes to perform real-time measurements of the electron temperature and number density of the reentry plasma sheath. The MEMS Langmuir probes, shown in Figure 1, consist of an array metallic vias in a high temperature-resistant dielectric substrate, which can be blended onto the outer surface of a reentry vehicle (i.e., as a sensorial skin). Figure 2 shows one of the early prototypes we made as proof of concept of the device process flow. The MEMS Langmuir probes are made using electroplated gold and an ultrasonic drilled Pyrex substrate. The performance of the MEMS probes will be validated experimentally in laboratory plasmas similar to those encountered by spacecraft during reentry.

Scaling of High Aspect Ratio Current Limiters for the Individual Ballasting of Large Arrays of Field Emitters

Field Emitter Arrays (FEAs) are excellent cold cathodes, but they have not found widespread adoption in demanding device applications because of several major challenges, including spatial/temporal current variations emanating from emitter tip radius distribution and the work function fluctuation. A consequence of tip radius variation is that the sharper emitters burn out from Joule heating before duller emitters turn on, reducing the current attainable from FEAs.Addressing these challenges, groups have incorporated current limiting (ballasting) elements including large resistors [1] , diodes [2] , and MOSFETs [3] into FEAs, but none of these simultaneously provide high current, high emitter density, and high current density. Velasquez-Garcia et al. demonstrated silicon vertical ungated FETs integrated with FEAs, resulting in a Si tip on Si pillar structure [4] . The ungated FET has a current-source-like I-V characteristic, providing effective individual ballasting of emitters while allowing uniform and high current emission without thermal runaway [4] . To limit emission current, the device uses pinch-off and velocity saturation of carriers in a Si high aspect ratio channel. Their pillars have a diameter of 1 µm, height of 100 µm, and 10-µm pitch, resulting in a density of 106 emitters/cm2. However, a consequence of tip radius variation and ballasting is that the energy distribution of emitted electrons is larger when compared to un-ballasted FEAs.To obtain FEAs with higher current densities, lower operating voltages, and reduced energy spread while retaining current uniformity, we expanded on previous work by scaling their tip on Si pillar structure. We developed vertical ungated FET current limiters 100 nm in diameter, 8 µm tall, and with 1-µm pitch, increasing the density to 108 emitters/cm2 (Figure 1). These devices demonstrate excellent current saturation of 15 pA / pillar with a linear conductance of 2.6×10-10 S/pillar and an output conductance under 10-13 S/pillar. The current saturates at a drain to source voltage under 0.2 V. These are the highest density, smallest diameter, and lowest operating voltage Si vertical ungated FETs ever reported.

Batch-micromachined RPAs for Plasma and Ion Measurements

Retarding potential analyzers (RPAs) were first developed in the 1960’s. RPAs find widespread application including characterization of near-spacecraft environments and assessment of the propulsion efficiency of plasma-based space thrusters. In this project we are exploring the multiplexing and scaling-down limits of RPAs using micro and nanotechnology. Miniaturized RPAs will weigh visibly less, which will reduce the cost of a nanosatellite-based mission. Also, miniaturized RPAs will provide better diagnostics of spacecraft plasma plumes as smaller projected area will be less disruptive to plasma under observation. In addition, batch-fabricated miniaturized RPAs can be used as part of a spacecraft “sensorial skin” that provides detailed local information of the plasma surrounding the spacecraft, particularly during re-entry, when monitoring exterior conditions is essential to ensuring safety during the mission.An improvement of our work from the state-of-the-art RPAs is the introduction of enforced aperture alignment. When the apertures of each successive grid are aligned, the optical transparency of the sensor increases, which should result in improved signal strength. We recently developed a first-generation prototype of a hybrid microRPA (Figure 1). The hybrid microRPA has micromachined electrodes and a stainless steel housing. Internal dynamics of this type of energy analyzer, however, are more complex than simple transmission or reflection of the various ion species [1] [2] . This fact is made evident by the experimental characterization of the microRPA using a commercial thermionic ion source for mass spectrometry. Figure 2 shows that the measured data reveal a peak in the energy distribution function around 5.4 V of retarding potential when the ionization region is at 10 V. Therefore, the observed ion energy distribution (dotted) deviates from the expected (continuous line) by approximately 4.6 V, a shift that is constant for a wide range of ionization region potentials. We speculate that changes in the internal dynamics due to enforced aperture alignment, sources of error in the applied voltages due to the materials selected, or a combination thereof are cause for this anomaly. Exploration of these potential sources of error continues, as well as the manufacturing of a fully batch-microfabricated RPA sensor with housing based on 3D HV packaging technology [3] [4] .

Electron-impact-ionization Pump Using Double-gated Isolated Vertically Aligned Carbon Nanotube Arrays

There is a need for microscale vacuum pumps that can be readily integrated with other MEMS and electronic components at the chip-scale level. Vacuum pumps exhibit favorable scaling and are promising for a variety of applications such as portable mass spectrometers [1] and vacuum amplifiers. This project aims to develop the technology for a micro-fabricated electron-impact-ionizer pump. The micropump consists of a field-emission electron source that is an array of double-gated isolated vertically aligned carbon nanotubes (VA-CNTs), an electron-impact-ionization region, and an ion implantation getter, as shown in Figure 1. The pump works as follows: first, electrons are field-emitted from the VA-CNT array; then, the electrons are accelerated at a bias voltage that maximizes the probability of collision with neutral gas molecules, this way achieving ionization by fragmentation of the molecules; finally, ions are implanted into the getter.In a double-gated field-emitter array, the first gate (extractor) is used to modulate the tunneling of electrons out of the tip, while the second gate (focus) is biased at a lower voltage than the first gate to focus the emitted electrons and to collect the back-streaming ions, thus protecting the tip [2] . As part of this work, we designed and fabricated single-gated isolated VA-CNT field-emission arrays, shown in Figure 2(a), to quantify the effectiveness of the field emitter-extractor diode to enhance the electric field on the emitter tip (i.e., estimate the extractor field factor), through experiments and simulations using the commercial software COMSOL. Figure 2(b) shows the solution of electric field using the same geometry of the device we fabricated. Each emitter has a 15-nm tip radius and 2-µm height with a 1-µm aperture from a single gate. From the simulation results we obtain an extractor field factor of 7.35×105V/cm. Figure 2(c) is the experimental FN plot of an array of ~10,000 single-gated emitters. From the slope of the plot we estimate a field factor of 7.8×105V/cm, which is in good agreement with the prediction of the extractor field factor from the COMSOL simulation.

Near-ultraviolet Sensor Based on Horizontal Low-Temperature Solution-Grown Zinc Oxide Nanowires

A near-ultraviolet (UV) sensor based on zinc oxide (ZnO) nanowires (NWs) that is sensitive to photo excitation at or below 400-nm wavelength has been fabricated and characterized. The device uses a single optical lithography step, and the NWs are grown at a low temperature from solution. ZnO is a wide direct band gap (3.37 eV) semiconductor whose absorption edge is in the near-UV range, making it an ideal near-UV photodetector. This is the first reported ZnO NW near-UV sensor that is insensitive to visible light (visible blind) and fabricated using a low temperature solution process [1] . At a voltage bias of 1V across the device, a 29-fold increase in current is observed in comparison to dark current when the NWs are photo excited by 400-nm light-emitting diode (LED), 8.91 µA (photo excitation current) vs. 311 nA (dark current).The fabrication of the near-UV sensor device is based on a single optical lithography step with no processing steps that exceed 100°C. The devices are compressed of a thin ZnO film with a metal cap. The sidewall of the ZnO film within the material stack acts as a seed for lateral growth of ZnO NWs. The metal cap restricts vertical growth of the NWs and doubles as the device electrodes. The symmetric devices have multiple electrode shapes and gaps between the electrodes ranging from 1-20 µm. The horizontally grown ZnO NWs bridge the gap between the two electrodes. The wires vary in length from 0.8 to 8.4 µm and diameter from 80 to 300 nm, depending on growth time. The result is a self-aligned ZnO NW ‘visible blind’ near-UV sensor that utilizes a low temperature process and a simple one-mask optical lithography step that can be integrated on a flexible substrate.

Massively Parallel Microfluidic Cell-pairing Platform for the Statistical Study of Immunological Cell-cell Interactions

Many immune responses are mediated by cell-cell interac­tions. In particular, cytotoxic T cells form conjugates with pathogenic and cancer cells in order to fight disease. More­over, T cell maturation and activation is governed by direct cell interactions with antigen-presenting cells (APCs). Er­rors in these processes can lead to the progression of severe diseases, such as multiple sclerosis (MS) and type 1 diabe­tes. The study of these intricate cell-cell interactions at the molecular scale is therefore crucial for understand­ing the dynamics and specificity of the immune response. One important feature of these interactions is the variability of response across populations. Cell-to-cell variability in pre­sumably homogeneous populations exposed to the same environmental conditions is ubiquitous, yet has long been neglected in immunology due to the limitations of conven­tional assay methods [1] [2] . Traditional methods to study cell-cell interactions, such as bulk measurements [3] or im­mobilization of cell pairs on a dish [4] [5] , suffer from both the inability to control cell-pairing at the single cell lev­el and the inability to study dynamic cell-cell interaction processes with high spatial and temporal resolution. We have overcome these limitations by developing a platform that can control cell pairing across thousands of individual immune cell pairs simultaneously while allowing visual­ization of the resulting responses. This approach enables us to quantify and understand variations in cell-cell inter­actions within large cell populations at the resolution of individual cell pairs. Previously, we developed a microflu­idic device with the capability to create thousands of such single cell pairs for the study of stem cell reprogramming (Figure 1, [6] ). To adapt the approach to work with smaller primary immune cells, we performed hydrodynamic mod­eling to guide redesign of the trap geometry (Figure 2). The modeling was used to determine how to adjust the trap ge­ometry to maximize flow through the center of the cups, which is crucial to the loading process. We determined that altering the cup-to-cup spacing transverse to the flow had the greatest impact on flow through the cups. We fabricated redesigned traps and are in the process of test­ing their pairing efficiency with primary immune cells.

Cell-based Sensors for Measuring Impact of Microsystems on Cell Physiology

The use of microsystems to manipulate and study cells in microenvironments is continually increasing. However, along with such increase in usage is also a growing concern regarding the impact of these microsystems on cell physiology. In this project, we are developing a set of cell-based fluorescent sensors to measure the impact of common stresses experienced in microsystems on cell physiology. We are including stress agents commonly found in microsystems (e.g., UV exposure, heat shock, fluid flow, etc.). Each sensor is designed to respond to one particular stress agent but can also be combined for multiplexed analysis of multiple stresses at once, as might be experienced in a typical microsystem. Designed to ease multiplexed analysis, each sensor will use different colors to both indicate the type of sensor and the strength of the signal.One sensor in the system will be a heat shock sensor that responds to activation of the heat shock pathway, which is a generalized stress pathway in cells. We are adapting a version of this sensor that we previously reported [1] [2] , which coupled fluorescent protein expression to activation of heat shock factor 1, from green fluorescent protein (EGFP) to a red fluorescent protein (RFP) and from red (DsRed) to yellow (YPet) for the constitutive color. Figure 1 shows the heat shock sensor response to 15 min heating at 42 ºC. Alongside this effort, we are using a multi-flow microfluidic device that can simultaneously apply different flows to cells across a 1000× range to understand the behavior of cells in flow [3] . Figure 2 is an image of the multi-flow device used to test NIH3T3 mouse fibroblast cells. Cells are seeded in 6 chambers concurrently and exposed to flow for 24 hrs, after which we can extract PCR from each chamber to study the cell response.

Microfluidic Perfusion for Modulating Stem Cell Diffusible Signaling

Stem cell phenotype and function are influenced by microenvironmental cues that include cell-cell, cell-extracellular matrix (ECM), and cell-media interactions, as well as mechanical forces. Our research focuses on developing microscale systems for controlling the cellular microenvironment of mouse embryonic stem cells (mESCs), in particular mechanical forces (i.e., shear stress) and cell-media interactions (i.e., diffusible signaling).Many emerging technologies used for ESC expansion or differentiation require perfusion culture, an example being pluripotent stem cell expansion in bioreactors for clinical applications [1] . We employ a multiplex microfluidic perfusion array to study the effects of shear stress on mESCs across a wide range of flow rates in a graded, quantitative manner. Using this device, we are able to show that perfusion elicits phenotypic changes and that the specific shear-responsive phenotype is due to mechanosensing by heparan sulfate proteoglycans (HSPGs, Figure 1A-C). This is the first study describing the ESC machinery capable of responding to shear stress, thus providing a foundation for further shear mechanotransduction studies [2] .Cells are constantly secreting and responding to soluble signals, the removal of which can be mediated by modulating flow properties at the microscale. To assess the contribution of cell-secreted factors to mESC differentiation and self-renewal, we utilized a two-layer microfluidic perfusion device allowing for parallel comparison of different cell culture conditions (Figure 2A) [3] . Our results demonstrate that mESCs do not grow in differentiation conditions with minimal autocrine signaling, even with supplementation by Fgf4, a signal that has been shown to be a crucial factor in differentiation toward a neuronal stem cell fate (Figure 2B). Conversely, under self-renewal conditions, mESCs proliferate but lose self-renewal markers and upregulate differentiation markers (Figure 2C). These results, together with signaling and downstream differentiation assays, indicate that a differentiation towards an epiblast-like early differentiation state under conditions that had previously been shown as sufficient for self-renewal. Together, these results indicate the importance of cell-secreted signals for mESC growth and self-renewal.

Micropatterning of Cells to Study Autocrine Signaling

Autocrine signaling is a mode of chemical signaling that occurs when cells can capture self-secreted diffusive factors. Apart from its major role in sustaining cancer growth, autocrine signaling is also involved in the positive-feedback regulation of various physiological processes. Due to the closed-loop nature and complex interplay of this signaling with other signaling cues, it is difficult to validate the presence and function of autocrine loops. Studying these loops typically requires the use of specific inhibitors to perturb the underlying ligand/receptor pairing, limiting investigation of poorly characterized autocrine loops.To promote the examination of autocrine signaling in broader biological systems, we have developed a general method for modulating autocrine activity using cell patterning. In addition to capturing self-secreted ligands, cells with autocrine loops also acquire ligands from their neighbors. By modulating the relative positioning between cells, we are able to modulate capture of autocrine ligands without needing specific inhibitors. In particular, we use stencil cell patterning to organize cells as square-latticed arrays of circular patches of varying array spacing (Figures 1A & B). We found that the cell-patterning platform can maintain uniform local cell density at all array spacings, in contrast to randomly plated cells, which exhibit increasing local cell density (Figure 1C). By reducing the influence of these other environmental cues, we are able to more explicitly study the effect of autocrine signaling on cell phenotype.In addition to studying the direct role of autocrine signaling, the cell-patterning platform can also be used to investigate the interplay of autocrine signaling with other signaling cues and to evaluate its contribution towards cell-to-cell variability. To determine the concurrent role of cell-cell contacts, we can compare cell responses between single patches and multiple patches where the cell number of both designs is equal (Figures 2A & B). To evaluate the contribution of autocrine loops in causing cell-to-cell variability, we can determine how the inclusion of a large cell patch will perturb the response of an array of small patches (Figure 2C). These innovative cell-patterning designs provide us novel tools for characterizing the impact of autocrine signaling without prior knowledge of the underlying ligand/receptor interactions.

Iso-dielectric Separation of Cells and Particles

The development of new techniques to separate and characterize cells with high throughput has been essential to many of the advances in biology and biotechnology over the past few decades. Continuing or improving upon this trend – for example, by developing new avenues for performing genetic and phenotypic screens – requires continued advancements in cell sorting technologies. Towards this end, we are developing a novel method for the simultaneous separation and characterization of cells based upon their electrical properties. This method, iso-dielectric separation (IDS), uses dielectrophoresis (the force on a polarizable object [1] ) and a medium with spatially varying conductivity to sort electrically distinct cells while measuring their effective conductivity (Figure 1). It is similar to iso-electric focusing, except that it uses DEP instead of electrophoresis to concentrate cells and particles to the region in a conductivity gradient where their polarization charge vanishes [2] [3] [4] .Previously, we have demonstrated the ability to perform continuous-flow, label-free, non-binary separations using IDS on a wide variety of cells and particles, while simultaneously extracting quantitative information from these samples as they are sorted [4] . In order to make IDS discovery more unknown cell types, dynamically changing the conductivity gradient is crucial for increasing the efficiency of finding the optimal separation condition. Therefore, we are developing a tri-syringe pump system to dynamically control conductivity gradients. We have verified the stability of the tri-syringe pump system via quantitative fluorescence imaging. Combining this gradient control system with a computer-controlled function generator and automated microscope, we plan to fully automate IDS separation and electrical profile screening (Figure 2).

Image-based Sorting of Cells

Microfabricated/microfluidic approaches to cell sorting, include purely dielectrophoretic (DEP) trap arrays [1] , passive hydrodynamic trap arrays with active DEP-based cell release [2] , and passive microwell arrays with optical cell release to permit sorting of non-adhered cells [3] . As these proceeding technologies were best suited to operate with non-adherent cells, we are developing a solution for adherent cells. Our approach to sorting adherent cells based on the morphological features uses a photolithography-inspired method, illustrated in Figure 1 (a). We first plated adherent cells into a dish and imaged cells using a microscope. Machine learning algorithm-based software CellProfiler [4] was used to quantitatively characterize the morphological features of the imaged cells, covering the cell area, shape, fluorescent intensity, and texture. As shown in Figure 1 (b), four classes were defined according to the fluorescent intensity difference in cell cellular compartments. A set of judging rules was generated by iteratively training the classifier based on hundreds of quantitative cell feature measurements to cluster the cells of similar phenotypes into a particular class. Desired cells were identified according to the classification. An alignment mark image was generated, with black features corresponding to locations of desired cells. Aligning the transparency mask to the back of the cell culture dish showed that opaque mask features resided beneath desired cells. We then mixed a prepolymer solutizon consisting of cell culture media, a UV-photoinitiator, and poly(ethylene glycol) diacrylate (PEGDA) monomer. We added the prepolymer to the cell culture dish and shined ultraviolet (UV) light from a standard fluorescence microscope fluorescence source through the transparency and into the dish. The prepolymer then crosslinked into a hydrogel in all unmasked locations, encapsulating undesired cells. The desired cells, which were not encapsulated, can be enzymatically released from the substrate and recovered, as shown in Figure 2. The overall technique requires standard equipment found in biological labs and inexpensive reagents (<$10 per experiment), encouraging widespread adoption.

Flexible Multi-site Electrodes for Moth Flight Control

Significant interest exists in creating insect-based Micro-Air-Vehicles (MAVs) [1] [2] [3] that would combine advantageous features of insects—small size, effective energy storage, navigation ability—with the benefits of MEMS and electronics—sensing, actuation and information processing. The key part of the insect-based MAVs is the multi-site electrode, which interfaces with the nervous system of the insect to bias the insect’s flight path by controlling insect’s abdominal motions.In this work, we have developed a flexible multi-site electrode (FME) for insect flight control that directly interfaces with the animal’s central nervous system as shown in Figure 1b. The FMEs are made of two layers of polyimide with gold sandwiched in-between in a split-ring geometry using standard MEMS processing [3] . The FMEs have a novel split-ring design that incorporates the anatomical bi-cylinder structure of the nerve cord of the Moth Manduca Sexta (Figure 1b) and allows for an efficient surgical process for implantation (Figure 1d). Additionally, we have integrated carbon nanotube (CNT)-Au nanocomposites into the FMEs to enhance the charge injection capability of the electrode.To quantify the performance of the FME, we have developed a custom stimulation and measurement system that allows computer-controlled stimulation and automated image analysis of the resulting abdominal motion (Figure 2a). We measured the magnitude (r) and direction (q) of the abdominal movement by the position of the red dot on the abdomen tip of the moths (Figure 2 b) versus the stimulations signal delivered at various magnitude and across various site pair. Moreover, we measured the voltage and current across pairs of stimulation sites during stimulation signal delivery (Figure 2c); hence, we could estimate the power consumption and injection charge density for the FME stimulations. Finally, we have integrated the FMEs into a wireless system (Figure 1a). In the flight control experiment, we can force a freely flying animal to perform turning motions via the FME stimulations.

High-flux Pool Boiling with Micro-engineered Surfaces

The mechanism of critical heat flux (CHF) is commonly attributed to two limits during boiling behavior: 1) the hydrodynamic limit due to Helmholtz instability and 2) the capillary limit determined by surface wettability [1] . In recent years, a significant amount of research has been focused on CHF enhancement by utilizing micro/nanostructured surfaces to improve wettability [2] [3] [4] , with CHF of ~200 W/cm2 being demonstrated [4] . While most works are focused on making small structure sizes to improve surface wettability, the effect of this roughness-augmented wettability on CHF is poorly understood. The limit of CHF enhancement with roughness-augmented wettability, where hydrodynamic instability becomes the dominant mechanism for CHF, has not been investigated. In addition, boiling on nanostructured surfaces suffers from the requirement of high superheat due to bubble geometries closer to the homogeneous nucleation limit. As a result, the heat transfer coefficient (HTC) on nanostructured surfaces is sacrificed [3] , which impairs the heat removal capability especially for applications demanding small temperature difference.In this study, micro/nanopillar arrays are fabricated with a series of pitch and diameter size, as shown in Figure 1. The sizes of pillar are designed to ensure that bubbles in the Cassie state, where vapor bubbles are suspended on the pillars, are energetically favorable such that bubble detachment is enhanced. The series of sizes of the structured arrays generate various capillary forces, which allow the study on the mechanism for CHF and the limit of CHF enhancement with roughness-augmented wettability. Furthermore, the investigation on surface roughness, where hydrodynamic instability dominants, gives the optimal size of structures for CHF enhancement and explores the feasibility of heterogeneous bubble nucleation on surfaces with proper structure geometry to reduce superheat.

Acoustic Bragg Reflectors for Q-enhancement of Unreleased MEMS Resonators

Two of the greatest challenges in MEMS are those of packaging and integration with CMOS technology. Development of unreleased MEMS resonators at the transistor level of the CMOS stack will enable direct integration into front-end-of-line (FEOL) processing and minimal or no packaging, making these devices an attractive choice for on-chip signal generation.Toward this goal, the authors have previously demonstrated the first fully unreleased MEMS resonator operating at 39 GHz with a quality factor (Q) of 129 [1] . The Si bulk acoustic resonator, surrounded on all sides by SiO2, demonstrates the feasibility of unreleased resonators, providing a Q that is only 4x lower than its released counterpart [2] . At mm-wave frequency in the Landau-Rumer regime, resonator Q is limited primarily by anchor loss [3] . In the case of fully-clad resonators, the quality factor can be significantly improved by localization of acoustic energy using acoustic Bragg reflectors [4] .The HybridMEMS lab has performed a study of fully unreleased resonator surrounded by lithographically defined ABRs, embedded in a homogeneous cladding layer (Figure 1). This one-mask design enables resonator banks of various frequencies on the same chip, providing multiple degrees of freedom in ABR design. With the goal of direct integration into FEOL CMOS processing, resonator performance is investigated for materials commonly found in the CMOS stack. The characteristics of these unreleased structures are compared with freely suspended resonators, released resonators isolated with lithographically defined ABRs [5] , and phononic crystal [6] based unreleased resonators (Figure 2).

MEMS RESONATOR OSCILLATOR DESIGN AND VARIATION STUDY

Electromechanical resonators such as quartz crystals, surface acoustic wave (SAW) resonators, and ceramic resonators have become essential components in electronic systems. However, due to their large footprint and difficulty in integrating with CMOS process, there has been much interest in developing MEMS resonators that achieve comparable performance yet have a smaller footprint and are compatible with CMOS. Recently, MEMS resonators have been proposed that overcome physical limitations in traditional resonators to reach frequencies in the GHz range. In addition, they have the potential for compatibility with CMOS, opening up possibilities for new circuits and systems [1].As with other semiconductor devices, with increasing frequency into the SHF and EHF range and with decreasing device size into the submicron scale, variability has started to become a critical issue in electromechanical resonators. Also, integration with CMOS process makes it more difficult or impossible to use the conventional frequency trimming methods employed for traditional resonators. Thus, in order for wider use of these resonators, more accurate characterization of important parameters and variations associated with these parameters is necessary. Some of these parameters include resonant frequency, the quality factor, and series resistance.This work aims to characterize and model the variation in resonant frequency of Si-based MEMS bulk acoustic resonators. The test structure consists of an array of resonators, multiplexing structures, and an oscillator loop. During measurement, each resonator is connected into a self-sustained oscillation loop through the multiplexing structure and the oscillation frequency is measured through a digital counter. On-chip measurement circuits such as this make it possible to measure a large number of devices, otherwise difficult to do with the traditional test methods of individual device probing, thus allowing more accurate characterization and modeling of critical device parameters and variations associated with them.

A COMPUTATIONALLY SIMPLE, WAFER-TO-FEATURE-SCALE MODEL OF ETCH-RATE VARIATION IN DEEP REACTIVE ION ETCHING

Modeling etch-rate variation in Deep Reactive Ion Etching (DRIE) helps to identify possible defects in MEMS and IC devices arising from sub-optimal etching depths and times. Besides tool-specific properties, such as the chamber design, another cause for the observed non-uniformity effects is the particular wafer pattern employed, which causes distinctive effects at the wafer-, die-, and feature-scales [1]. We present a model to capture these pattern-dependencies by tracking the spatial and temporal distribution of the ion and radical species within the DRIE chamber. The model implementation uses a time-stepped algorithm with three levels – corresponding to the three different length scales – and a coarse-grained approach whereby multiple features in a given region are characterized by a particular shape, size, and density. The local radical species concentration distribution above the wafer is determined at each time step using current feature geometries to compute their Knudsen transport coefficient, which is linked to the radical transport mechanisms within other areas in the chamber. At the end of each time step, etch-rate estimates based on this radical concentration distribution and current feature geometries are used to update feature depth information for the next time interval. At the wafer scale, our modeling results, shown in part in Figure 1, achieve a success comparable to that of previously-developed wafer-level models with an etch-rate RMS error percentage between 2.1% and 8.2%. The results also show that feature-level etch evolution substantially impacts the wafer-level fluorine concentration and thereby modifies the wafer and die etch-rate uniformity. We expect a similar model could be incorporated into CAD software tools to evaluate masks and correct potential design issues before they are made. Our results also shed light on possible tool and process modifications to allow users the capability of altering across-wafer etch-rate variability.

SIZE-SELECTIVE SORTING OF CELLS USING TEMPLATED ASSEMBLY BY SELECTIVE REMOVAL

This work presents the size-selective sorting of single biological cells using Templated Assembly by Selective Removal (TASR). We have demonstrated the selective self-assembly of single SF9 cells (clonal isolate derived from Spodoptera frugiperda IPLB-Sf21-AE cells) into patterned hemispherical sites on rigid assembly templates using TASR. Experimental success with SF9 cells, which are nearly spherical and resistant to shear, suggests that self-assembly using TASR can also be extended to other cells and biological materials that are spherical. Examples include white blood cells and, in general, cells that maintain a well-defined morphology for short durations when dispersed in culture media, agitated mildly using megasonic excitation, and allowed to settle on a patterned substrate. Therefore, TASR-based biological self-assembly holds potential for several applications, such as cell-sorting for medical research or diagnostics, or isolation of single cells for studying their biological and mechanical behavior.In TASR, the system’s free energy is minimized when objects assemble in holes that match their shapes and sizes on the template’s surface (Figure 1). A combination of chemical and mechanical effects selectively removes objects from poorly matched holes. Previous work on TASR has shown that microcomponents made from relatively rigid materials such as silica [1] [2] and deformable materials like polystyrene [3] can be assembled effectively on similarly rigid patterned templates using this technique. In an extension of the application of TASR to biological systems, SF9 cells (which come in a range of sizes with a mean diameter of 15 microns) were successfully assembled using TASR onto patterned silicon templates. The assembly sites comprised holes with nearly hemispherical profiles etched in a silicon substrate using DRIE. Figure 2 shows optical micrographs of the assembly and demonstrates the size-selectivity of the process as well as the high yield of cell assembly using this technique.

MEMS TUNABLE ORGANIC LASER CAVITIES

Standard photolithography-based methods for fabricating micro-electromechanical systems (MEMS) present several drawbacks including incompatibility with flexible substrates and limitations to wafer-sized device arrays. Recently our group has demonstrated a new method for rapid fabrication of metallic MEMS that breaks the paradigm of lithographic processing using an economically and dimensionally scalable, large-area microcontact printing method to define 3D electromechanical structures. Here we utilize this MEMS printing method to create tunable optical cavities, with the ultimate goal of creating an electrically color-tunable organic laser. The device concept is shown in Figure 1. The bottom half of the optical cavity is fabricated by forming ridges of polydimethylsiloxane (PDMS) on a dielectric mirror using a silicon master. The top half of the cavity is independently fabricated by thermally evaporating an organic release layer on a planar PDMS substrate followed by layers of Au and Ag, which act both as the top mirror of the cavity and as the flexible MEMS element. The organic lasing medium (DCM) is evaporated on the metallic layers. This layer structure is stamped onto the PDMS ridges followed by a rapid peel-off, forming the structure shown in Figure 1b.The photoluminescence from the DCM gain layer under 532-nm excitation shows clear evidence of a vertical optical cavity formed between the dielectric mirror and the Ag flexible membrane, demonstrating an optical microcavity formed by a scalable MEMS printing method. The optical resonances of the device can be varied by applying a bias voltage to the top flexible membrane, thus changing the distance between the mirrors (Figure 1a). This structure paves the way to developing color-tunable organic lasers on flexible substrates over large areas using an economical MEMS fabrication technique.

MICROFLUIDIC PERFUSION FOR MODULATING STEM CELL DIFFUSIBLE SIGNALING

Stem cell phenotype and function are influenced by microenvironmental cues comprised of the cell-cell, cell-extracellular matrix (ECM), cell-media interactions, and mechanical forces. Our research focuses on developing microscale systems for controlling the cellular microenvironment of mouse embryonic stem cells (mESCs), in particular mechanical forces (i.e., shear stress) and cell-media interactions (i.e., diffusible signaling).The use of embryonic stem cells (ESCs) for clinical therapeutic applications requires expansion of the pluripotent cells in bioreactors, where the cells are subjected to fluid shear stresses [1]. In comparison to macroscale bioreactors, microfluidic perfusion systems allow for study of shear stress effects on mESCs across a wide range of flow-rates. We demonstrate the utilization of a multiplex microfluidic perfusion device as a powerful experimental tool to probe shear stress effects in a graded, quantitative manner, allowing us to identify a shear-modulated marker, Fgf5 (Figure 1A-C). Such approach facilitates further targeting of molecular players implicated in shear stress mechanotransduction.Flow properties at the microscale enable fine-tuning of soluble factors transport, which plays a crucial role in determining ESC fate. To modulate cell-media interactions in mESCs self-renewal and differentiation, we utilized a two-layer microfluidic perfusion device allowing for parallel comparison of different cell culture conditions (Figure 2A) [2]. Our results demonstrate that mESCs under conditions of reduced autocrine signaling in self-renewing culture conditions express decreased levels of self-renewal markers and at the same time upregulated levels of early differentiation markers. In contrast, an interruption of cell-ECM interactions yields opposite results (Figure 2B). Similarly, we demonstrated that mESCs failed to proliferate under conditions of minimized autocrine signaling during neuronal differentiation. In addition, we found that autocrine Fgf4 signaling is implicated as a crucial factor in acquiring neuronal identity of mESCs, while alone it cannot restore the growth of mESCs undergoing differentiation (Figure 2C).

CONTINUOUS-FLOW DEFORMABILITY-BASED SORTING OF P. FALCIPARUM-INFECTED RED BLOOD CELLS USING A MICRO-FILTER ARRAY

Change in cell stiffness is a characteristic of several blood cell diseases, such as sickle cell anemia [1], malaria [2], and leukemia [3]. In humans, the spleen acts like a filter to remove these more rigid cells by pushing blood through slits between endothelial cells and removing cells that cannot pass. In this work, we create a microfluidic device that mimics the architecture of the spleen to achieve continuous-flow fractionation of cells based on their rigidity. We demonstrate successful operation of this device by separating malaria-infected from normal, uninfected red blood cells (RBCs). Applications include disease diagnosis and sample preparation for downstream analysis. Figure 1 illustrates device operation and presents details regarding device design.The device fabrication process involves the use of photo-curable polyurethane, NOA 81. The high Young’s modulus of this material enables the creation of high aspect ratio slits in an inexpensive and simple manner, as contrasted with PDMS and silicon-glass. Fabrication details have been presented elsewhere [4].We separated schizont-stage malaria-infected RBCs from uninfected RBCs. Figure 2A presents a snapshot from a video showing an infected cell sliding along the edge of a slit and uninfected cells following the direction of the fluid flow. Figure 2B presents a histogram showing the separation sensitivity of the device. As shown, this device was able to separate 4-infected cells from 164 uninfected cells.Applications of this device include sample preparation for biochemical and cell culture assays. Deformability-based cell sorting can also be useful for situations when cell surface markers are not clearly identified for FACS. Lastly, the low-cost aspect of this device makes it ideal for on-site disease (e.g., malaria) screening in resource-poor settings.

INCREASE OF SENSITIVITY OF ELISA USING A MULTIPLEXED ELECTROKINETIC PRECONCENTRATOR

Enzyme-Linked Immunosobent Assay (ELISA) is the gold standard in biodetection due to its high reproducibility and sensitivity. Still, the ultimate detection sensitivity of ELISA is not good enough to tackle the challenges of biomarker detection. This led to the development of many novel ultra-high-sensitivity immunoassay platforms. However, additional sensitivity comes with the cost of added complexity in amplification chemistry or complicated devices. Being able to measure analytes at concentrations below the current detection limits, without modifying the basic workflow of ELISA, would be very useful.We utilized a nanofluidic preconcentration device to continuously accumulate enzymatic product molecules from ELISA into a much smaller volume and increase its local concentration significantly, therefore achieving a lower limit of detection. An important advantage of this scheme is that the enzymatic product being concentrated is the same, and thus the same device setup is applicable regardless of the antigen. We also demonstrated multiplexing capability by assaying five samples simultaneously in a single device.We showed enhanced detection sensitivity in two cases: 1) when the enzymatic reaction is on-chip and 2) when the enzymatic reaction is off-chip. In the first case, immunobinding was performed using beads as a solid phase, and the beads were physically trapped in a microfluidic channel. When fresh substrate solution was flown through the bead pack, it was enzymatically converted into fluorescence product and accumulated downstream. In the second case, the complete ELISA workflow, including substrate conversion, was performed in a 96-well plate. After that, the converted molecules were injected into the device and electrokinetically concentrated. Using the first method, we demonstrated a 65-fold lower limit of detection for CA 19-9, a human pancreatic cancer marker, in control serum. The detection limit for human prostate specific antigen (PSA) in donkey serum was 100 times lower using the second method.

IMPROVEMENTS TO A CHIP-SCALE QUADRUPOLE MASS FILTER FOR PORTABLE MASS SPECTROMETRY

Mass spectrometers are powerful analytical instruments that are known to be the gold standard for chemical analysis. The Micro-Gas Analyzer Project attempts to leverage the cost reduction, performance enhancement, and increased portability associated with MEMS to create a microfabricated mass spectrometer for chemical species detection. One of the key components of the mass spectrometer is the mass analyzer, which functions to separate ionized species by their mass-to-charge ratios (m/z). There are various types of mass analyzer with respective advantages and disadvantages, but our group decided to utilize the quadrupole mass filter due to its inherent robustness.Various attempts at making MEMS-based linear quadrupoles have met with varying degrees of success [1] [2] [3] [4]. Our group devised a new class of chip-scaled quadrupole mass filter that utilizes square electrodes to address the issue of mass producibility, a property not readily achieved with the other technologies. The proof-of-concept device demonstrated a mass range of 250 amu when operated in the first stability region and a maximum resolution of ~40 when operated in the second stability region [5].A new improved version of the device demonstrated an increased mass range of up to 650 amu in the first stability region and a resolution of ~90 when operated in the second stability region [6]. Additionally, we demonstrated the functionality of integrated ion optics. The major improvement in the new version was a different process flow that raised the yield, electrical breakdown voltage, and structural robustness of the device. In future work, we plan on modifying the mask layout and device dimensions to further improve the performance through using a smaller device radius, minimizing the parasitic capacitances, and including prefilters for enhanced transmission.

COMPONENT INTEGRATION OF A MICRO-GAS ANALYZER

The Micro-Gas Analyzer Project attempts to leverage the cost reduction, performance enhancement, and increased portability associated with MEMS to create a microfabricated mass spectrometer for chemical species detection. Mass spectrometers are powerful analytical instruments that are mainly comprised of an ionizer, a mass analyzer, a detector, and a vacuum pump. Our group and collaborators have made substantial progress on these various components, spanning carbon-nanotube-based electron impact ionizers [1], chip-scaled quadrupole mass filters with square electrodes [2], and time-modulated capacitance electrometers [3]. Each component functions and performs adequately on its own, but a complete system requires the integration of these three parts, as demonstrated by other researchers [4] [5].An integration plan was conceived to sequentially combine the various components in a logical manner. A testing jig was designed and machined so the electron impact ionizers would have electrical connections to the power supplies and compatibility with our in-house characterization system. After validating the functionality of the ionizer with a macro-scaled quadrupole and a Channeltron electron multiplier, we plan to use our chip-scaled quadrupole instead of the macro-version. Once these two vital components are well characterized, we will check the functionality of the electrometer with a commercial ion source and a macro-scaled quadrupole. Finally, we will put all three components together to be tested and characterized in a vacuum chamber.

MANIPULATION OF LIQUID SPREADING ON ASYMMETRIC NANOSTRUCTURED SURFACES

The manipulation of liquid spreading is important for a broad range of microfluidic, biological, and thermal management applications [1] [2] [3]. In this work, we investigated the ability to manipulate droplet spreading to a single direction on-demand on asymmetric nanostructured surfaces using electrowetting. Asymmetric nanopillar arrays were fabricated with diameters of 500 to 750 nm and deflection angles of 3 to 52 degrees. Figure 1 shows scanning electron micrographs (SEMs) of three representative asymmetric nanopillar arrays with deflection angles, φ, (as defined in the Figure 1 inset) ranging from 7°-25°. A Cartesian coordinate system is defined for convenience, as shown in Figure 1, where the pillars deflect in the positive X (+X) direction. In the presence of asymmetric nanostructures, the spreading behavior can be dynamically controlled with electrowetting, which utilizes an electric potential, V, across the droplet and nanostructured surface to change the surface energy (Figure 2a). With this approach, different droplet-spreading directionalities can be achieved based on the magnitude of the electric potential. If we apply V= 1.5 V to an initially static symmetric droplet, the liquid pins in the –X direction and spreads in +X, i.e. uni-directionally (Figure 2b). In the case of an applied V= 2.1 V, the liquid unpins in –X and spreads bi-directionally. The spreading, however, is asymmetric: the rate is three times faster in +X as compared to –X (Figure 2c). Moreover, with increasing applied V, the asymmetry decreases. In the case of an applied V> 2.5V, the liquid spreading is nearly symmetric, i.e. the rates in +X and –X are approximately equal (Figure 2d). The study provides design guidelines to tune the droplet’s behavior from uni-directional to asymmetric or symmetric bi-directional spreading using both nanostructure design and applied electric fields for a variety of microfluidic applications.

MEMS STEAM GENERATORS FOR EJECTOR PUMPS

Microscale ejector pumps offer the potential for high-flow-rate pumping of gases, a functionality that is greatly needed in MEMS technology [1]. These pumps have many additional characteristics, such as their simplicity of design and their lack of moving parts, which favor them over other MEMS gas pumps. One of the challenges associated with driving ejector pumps, however, is providing a compact source of motive fluid. This fluid is the high-speed gas that drives the pumping action. The current work delivers a MEMS device capable of generating steam at speeds suitable for driving an ejector pump in a compact fashion. To that end, the device utilizes the homogeneous catalytic decomposition of hydrogen peroxide. Analysis shows that a MEMS ejector pump driven by this device is capable of achieving mass flow rates per unit pump volume on the order of 10-2 g/s/cm3, which is two orders of magnitude higher than the rates of state-of-the-art MEMS gas pumps. In addition to pumping, the steam generator may also be used for microrocket thrust generation in micropropulsion applications.This work involves the design, fabrication, and testing of the MEMS steam generator. To our knowledge, this device is the first of its kind in the literature that works successfully, and it achieves results that have been sought by other groups for over a decade. The device consists of a mixing section for the peroxide and catalyst streams, a reactor section where the peroxide decomposes, and finally a nozzle section where the gaseous products of the decomposition are accelerated to the required velocities. A schematic is shown in Figure 1. To design the device, multidomain (chemical, thermal, and fluidic) numerically-implemented modeling is used to study the underlying physics and arrive at an optimized, microfabricatable design. The modeling takes into account the key challenges of thermal management, achieving fast mixing [2], and boundary layer compensation. The device is then fabricated from a stack of four silicon wafers and one Pyrex wafer using deep-reactive-ion etching and wafer bonding. A photograph of a microfabricated device is shown in Figure 2. The modeling also guides the design of a mica-based ceramic package which provides both thermal insulation and piping ports. The system is then experimentally tested using 90% high-test hydrogen peroxide and ferrous chloride tetrahydrate solution as the catalyst. The device is characterized using temperature measurements, refractive index analysis, and visual inspection during operation. Successful performance is demonstrated via the full decomposition of the peroxide and the complete vaporization of the water produced. The experimental results are also compared with those from the simulation. Good agreement is observed between experiment and theory, providing comprehensive model verification.

DESIGN AND DEMONSTRATION OF INTEGRATED MICRO-ELECTRO-MECHANICAL (MEM) RELAY CIRCUITS FOR VLSI APPLICATIONS

Silicon CMOS circuits have a well-defined lower limit on their achievable energy efficiency due to subthreshold leakage. Once this limit is reached, power constrained applications will face a cap on their maximum throughput independent of their level of parallelism. Avoiding this roadblock requires an alternate device with steeper sub-threshold slope – i.e., lower VDD/Ion for the same Ion/Ioff ((H. Kam, et al., “Circuit Level Requirements for MOSFET Replacement Devices,” in IEDM Tech. Dig., 2008, pp. 427.)). One promising class of such devices is electro-statically actuated micro-electro-mechanical (MEM) relays with nearly ideal Ion/Ioff characteristics. Although mechanical movement makes MEM relays significantly slower than CMOS, they can be useful for a wide range of VLSI applications by reexamining traditional system- and circuit-level design techniques to take advantage of the electrical properties of the device. Unlike in CMOS circuit design, logic functions in MEMS circuit design should be implemented as a single complex gate with minimum-sized relays, resulting in significantly reduced logic complexity. We have recently shown that with optimized circuit topologies MEM relays may potentially enable ~10x lower energy over CMOS at up to ~0.1-1GHz frequencies [1]. This work takes initial steps towards experimental validation of these principles by leveraging recently developed relay technology and reliability enhancements [2] [3] to demonstrate several monolithically integrated MEM relay-based building blocks. Specifically, our chip includes logic, memory, I/O, and clocking structures, and we demonstrate successful basic functionality and circuit composition [4]. These relay circuits illustrate a range of important functions necessary for the implementation of integrated VLSI systems, and give insight into circuit design techniques that leverage the physical properties of these devices.

MEMS SIC LANGMUIR PROBES FOR PLASMA DIAGNOSTICS OF SPACECRAFT DURING REENTRY

During reentry, the formation of a high-density, low-temperature plasma sheath around a spacecraft results in a communications blackout [1]. Advanced plasma sensors onboard a reentry-bound spacecraft will enhance this spacecraft’s ability to maintain communications through the plasma sheath. We propose cost-effective and reliable batch fabricated MEMS-based silicon carbide (SiC) Langmuir probe arrays to provide real-time diagnosis of plasma conditions surrounding a spacecraft during reentry. The Langmuir probe array provides data associated with specific parameters of the plasma, including plasma temperature and plasma density. The Langmuir probe array operates so that each probe in the array is individually addressable. Our MEMS-based Langmuir probe arrays are fabricated from SiC, a semiconductor material that is relatively inexpensive and very resistant to hostile environments such as spacecraft reentry [2]. Current research efforts to develop SiC-based MEMS intended for harsh environments include transistors, and transducers to measure pressure, acceleration, temperature, and strain [3] [4] [5]. Langmuir probe densities as large as 106/cm2 have been demonstrated (Figure 1). Also, fabrication experiments using plasma-enhanced chemical-vapor-deposited (PECVD) SiC coatings have been conducted (Figure 2). Future research includes the development of MEMS-based Langmuir probe arrays fabricated from SiC substrate materials and micromolded SiC. Langmuir probe performance will be validated experimentally in laboratory plasma sources that generate plasma densities similar to those encountered by spacecraft during reentry.

MONITORING CELL PHYSIOLOGY IN MICROBIOREACTORS

Mammalian cell culture dominates the biopharmaceutical industry for biotherapeutics including monoclonal antibodies, vaccines, and growth factors. However, mammalian cells are also the most sensitive to changes in the culture environment, e.g., mechanical agitation, nutrient depletion, and waste byproduct accumulation. Hence, maintaining cell viability in mammalian cell cultures for an extended period of time is an important limiting factor for mammalian cell cultures [1]. Currently, state-of-the-art micro-bioreactors estimate cell density by measuring the turbidity of the culture using an Optical Density (OD) sensor [2]. Unfortunately, OD sensors measure light scattered by cells which may not be accurate due to cell aggregation and the influence of cell shape. Additionally, biomass measurements do not discriminate between live and dead cells. An online sensor that explicitly measures viable cells in a micro-bioreactor is necessary.Dielectric spectroscopy is a promising online sensor for cell viability in micro-bioreactors [3]. The difference between the low-frequency and high-frequency capacitance measurements (ΔC = CLF – CHF) in the radio frequency regime gives the capacitance contributed by the cells to the total capacitance of the suspension. Due to the fact that most dead cells no longer have an intact membrane, defined as a membrane that is selectively impermeable to ions in the solution, they do not contribute to the capacitance reading (ΔC). By calibrating the measured capacitance with cell suspensions of known cell densities, the number of live cells in the culture can be determined, shown in Figure 1. When dielectric spectroscopy is combined with OD measurements, the percent cell viability can be utilized to optimize the yield of a mammalian cell culture in a micro-bioreactor. The first part of our project involves designing and calibrating a dielectric spectroscopy sensor for a micro-scale bioreactor, shown in Figure 2.

A MEMS SINGLET OXYGEN GENERATOR FOR POWERING CHEMICAL LASERS

Singlet delta oxygen (O2(a)) may be synthesized through the highly exothermic multiphase reaction of gaseous Cl2 with an aqueous mixture of concentrated H2O2 and KOH. Among other applications, O2(a) may be used to drive a chemical oxygen iodine laser. The laser application of O2(a) generation requires a high yield (i.e., a high fraction of product oxygen in the O2(a) state) and conversion of Cl2 to O2(a) to sustain laser emission; the high yield is achieved in part by effective mixing of the gas and liquid reagents. Modeling suggests that the MEMS singlet-oxygen generator (SOG) has key advantages as compared with fully macroscale implementations [1]. These advantages include smaller hardware size for the same power level, higher yield, more efficient reactant utilization, gravity independence, and feasible batch manufacturing.Previously, the MIT microSOG team has demonstrated working microSOG devices [2] [3]. These devices produced O2(a) with yields of up to 78% and O2(a) flows per unit volume of up to 0.067mol/s/L; this yield was a significant improvement and the flows per unit volume were comparable to macroscale counterparts. Building on recent successes in this area of innovation [2] [3], we are creating new microSOG chips to improve the Cl2 utilization and O2(a) flow rate by optimizing the mixing, flow distribution systems, and device packaging. Mixing is promoted by an array of microstructured posts that fill the reaction channels; the size of these posts is reduced as compared with earlier systems to enable more compact microSOG chips and a higher contact area per unit volume, which enables high Cl2 utilization (more than 95%) and O2(a) yield (more than 70%). The new device is predicted to operate at a maximum O2(a) flow rate of 1000sccm, for a 7x increase in output flow per unit volume from 0.067mol/L/s [3] to 0.50 mol/L/s. The chip was fabricated from a stack of two silicon wafers and one Pyrex wafer using bulk micromachining (primarily DRIE and bonding technology). An SEM image of the generator and the finished chip are shown in Figures 1 and 2, respectively. Testing is underway.

METALLIC AND OTHER GLASSES FOR MEMS

Chalcogenide glasses are widely used as “phase change materials” for optical data storage media in rewrit­able compact discs (CD±RW) and rewritable digital video disks (DVD±RW, DVD-RAM). Recently, they have also shown high potential for use in phase-change random ac­cess memories (PC-RAMs or PRAMs), which might replace flash memories in the future. In these applications, information storage is accomplished by reversible amorphization and crystallization. Metallic glasses have also recently generated interest because of their having a combination of high elastic moduli and fracture strengths. They have been used, for example, as torsional springs in micro-mirror arrays. In both types of applications, the mechanical properties of films in the glassy state are important in determining their functionality and reliability. Of particular interest is the stability in the glassy state and stress changes associated with crystallization, both of which can be studied through measurements of cantilever displacements associated with crystallization.In prior work we have shown that the stress change associated with crystallization of chalcogenides depends strongly on the thickness of films, and on whether or not the films are capped with materials with high stiffness (Figure 1). This large dependence is the result of inelastic accommodation of a component of the large volume change (~6%). The yield stress of the glasses is strongly thickness- and encapsulation-dependent [1] [2].In more recent studies we have focused on metallic glasses, both for applications as memory media and as mechanical components in MEMS devices. We have used combinatorial deposition on cantilever arrays to characterize the volume change on crystallization in the binary Cu-Zr [3] and ternary Cu-Zr-Al systems [4]. We found significant and complex dependences of the volume/stress change on composition (Figure 2). These variations were also found to correlate with the ease with which these alloys of specific compositions could be deposited or quenched into the glassy state. We are now measuring the compositional dependence of the elastic modulus, thermal expansion coefficient, and hardness of as-deposited and annealed metallic glasses.

ULTRA-WIDE-BANDWIDTH MICRO ENERGY-HARVESTER

A novel ultra-wide-band resonating thin-film PZT MEMS energy-harvester has been developed. It harvests energy from parasitic ambient vibration at a wide range of amplitude and frequency via the piezoelectric effect. Up to this point, the designs of most piezoelectric energy devices have been based on high-Q linear cantilever beams that use the bending strain to generate electrical charge via the piezoelectric effect [1] [2]. They suffer from very small bandwidth and low power density, which prohibit practical use. Contrary to the traditional designs, our new design utilizes the tensile stretching strain in doubly-anchored beams [3]. The resultant stiffness nonlinearity due to the stretching provides a passive feedback and consequently an ultra-wideband resonance [4]. This wide bandwidth of resonance enables a robust power generation amid the uncertainty of the input vibration spectrum. This work includes the design, microfabrication, and testing of a MEMS-scale prototype that aims to harvest up to 0.1mW electrical power in a wide range of excitation frequencies. Mechanical testing has shown 10-fold improvements in the displacement bandwidth. Our simulation predicts 100-fold improvement in the electrical power bandwidth compared to the conventional linear designs. Currently, a new generation of the device is under fabrication and testing at MTL and MNSL facilities.

SCALE-DOWN CELL CULTURE FOR BIOPHARMACUETICALS

Developing highly productive cell-culture processes is an essential step in the production of biopharmaceutical products. Process development involves experimentally determining the combination of cell line, culture medium composition, and process parameters that will produce the highest quality and quantity of product. Scale-down models for large-scale bioreactors are essential for cell-culture process development in order to achieve the throughput necessary to conduct a sufficient number of experiments for a reasonable cost. Bioreactor systems based on 24 well plates [1] and a highly automated robotic system with passive microreactors [2] have recently been developed in order to overcome the shortcomings of traditional shake-flask and bench-scale stirred-tank-based scale-down models. However, in these systems mixing and fluid-handling require external machinery/robotics or manual intervention. We are using an alternative approach that integrates fluid-handling and mixing capabilities into the bioreactor device utilizing previously developed fluid injectors and mixing devices [3]. Figure 1 shows a schematic view and photographs of the mammalian-cell-culture reactor. It is fabricated with injection-molded and machined biocompatible polycarbonate layers and an actuated silicone membrane. Initial CHO cell cultures show comparable growth and viability to shake flask cultures.

DEVELOPMENT OF A MICROMACHINED RETARDING POTENTIAL ANALYZER FOR SENSING PLASMA CONDITIONS AT SPACECRAFT RE-ENTRY

To ensure safe operation during space missions, NASA is sponsoring research on advanced sensing systems. In this endeavor, one particular facet is the development of a sensing skin that would monitor the spacecraft re-entry conditions. A retarding potential analyzer (RPA) is a device that would provide useful information about the ion energy distribution of the plasma that forms around the spacecraft while it re-enters the atmosphere. As a consequence of the harsh conditions during re-entry, the sensor must be made of suitable materials such as silicon carbide or tungsten. We are currently developing a hybrid MEMS-macro RPA that uses grids made of either bulk silicon coated with SiC or W. Design constraints of the RPA require closely packed holes with large aspects ratios. Therefore, the grids are etched using deep-reactive-ion-etching (DRIE). We plan to investigate the effects that various probe parameters have on the RPA’s performance, which is driven mainly by the Debye length of the plasma [1]. To this extent, the hybrid sensor has been designed to allow variations in grid hole diameter, pitch, and transparency. Limitations in grid-to-grid spacing will also be examined. The modular assembly of the device is shown in Figure 1. Based on this experimental exploration, a fully micromachined RPA will be built using a MEMS 3D packaging technology that we pioneered for multiplexed high voltage MEMS [2] [3]. An example of what this MEMS RPA may eventually look like is given in Figure 2, where the first grid is shown on the left and the collector plate is displayed on the right. The proposed MEMS RPA has five electrodes to insure proper data collection. Future work will further reduce the footprint of this final design as well as explore the possibility of machining the grids using bulk SiC.

MICROFLUIDIC CONTROL OF CELL PAIRING AND FUSION

Cell fusion has been used for many purposes, including generating hybridomas and reprogramming somatic cells. The fusion step is the key event in initiating these procedures. Standard fusion techniques, however, provide poor and random cell contact, leading to low yields. While different approaches can be used successfully for reprogramming, the cell lines generated are not yet suitable for potential therapeutic applications in humans, and many questions remain about the process of nuclear reprogramming. A more efficient cell-pairing and fusion method could answer these questions. Skelley et al. have therefore developed a microfluidic device to trap and properly pair thousands of cells [1] (Figures 1 and 2). Using this device, the pairing efficiency for different cell types, including fibroblasts, mouse embryonic stem cells and myeloma cells, is as high as 70%. The device is compatible with both chemical and electrical fusion protocols, with membrane reorganization efficiencies of up to 89%. These properties render the device particularly suitable for our current study of the underlying mechanism of fusion-based reprogramming.Having established the basis for high-yield cell-pairing measurements using stem cells, we are developing a similar device for the statistical, kinetic study of immune cell populations. Immune responses are largely mediated by cell-cell interactions. In particular, natural killer cells and cytotoxic T cells form conjugates with pathogenic and cancer cells in order to fight disease Errors in these and other immune cell-cell interactions can lead to fatal immune diseases. The study of these intricate cell-cell interactions at the molecular scale is crucial for understanding the dynamics and specificity of the immune response. Conventional techniques, such as bulk measurements or immobilization of cell pairs on a dish, preclude gathering of sufficient data on single cell pairs for meaningful statistics of cell-cell interactions. We propose to overcome the limitations of traditional methods by visualizing and controlling the pairing of thousands of individual immune cell pairs simultaneously. Primary mouse lymphocytes (~6 μm diameter), a common model system in immunology, are significantly smaller than stem cells (~18 μm diameter), making a device redesign necessary. We have employed a numerical, finite- element fluid- dynamic model as a guide to optimize pairing efficiencies by altering geometric properties (Figure 3). Our device is furthermore compatible with standard staining methods, such as antibody staining and ratiometric calcium flux measurements. The next step will be to fabricate the new devices and evaluate their pairing efficiency.

MICROFLUIDIC STUDIES OF CANCER INVASION: NEW HIGH-THROUGHPUT ASSAYS TO STUDY MICROENVIRONMENTAL EFFECTS

Microfluidics offer a unique platform for screening the effects of the biochemical and biophysical microenvironment on cellular phenotype, while allowing for increasing the experimental throughput compared to traditional assays. In this work we study the effect of interstitial flow on tumor cell migration and the interactions between tumor and endothelial cells during tumor cell entry into a blood vessel (intravasation) in a 3D extracellular matrix. Based upon previous work over the past years in our lab [1] [2], we recently developed a new design with a 10-fold increase in the number of matrix regions allowing for increased data collection capabilities. The design consists of independently addressable microfluidic channels interconnected through 3D matrices, wherein tumor and endothelial cells can be seeded, while establishing interstitial flow and/or chemoattractant gradients through the matrix. We have also developed a protocol for applying fluid-flow induced shear stress on the endothelial monolayer on the channel for studying its effects on tumor cell intravasation. After applying a shear stress of 3 dynes/cm2 for 24 hours, we observed alignment of the endothelial cells in the flow direction consistent with previous studies. Using live cell imaging and in the absence of any directional microenvironmental cues, we observed both a quiescent and sprouting endothelium, while some tumor cells invaded in 3D randomly and others reached towards the endothelial monolayer.Tumor cells exposed to interstitial flow preferentially migrated along streamlines, and the relative percentage of cells migrating upstream and downstream was a function of chemokine receptor activity and intercellular distance. At low seeding densities, cells preferentially migrated upstream. However, at high intercellular distances, cells preferentially migrated downstream but reverted to upstream migration with blocking of a single cell receptor, CCR7. These data provide supporting evidence to the autologous chemotaxis model and suggest that a competing paracrine pathway provides a stimulus for upstream migration.

SINTERED METAL WICKS FOR LOOP HEAT PIPES

Loop heat pipes (LHPs) are a widely-used component in the thermal management of high-power electronics. LHPs transfer heat by utilizing the latent heat of a working fluid, which is circulated by the capillary pumping of a porous wick. A typical design consists of an evaporator and condenser connected in a closed loop. As the capillary wick, located in the evaporator, influences the operating characteristics and limits of the LHP, much work has been devoted to optimizing the wick’s capillarity and permeability to extend the range of LHP operation [1] [2] [3].This work investigates the wick characteristics necessary to operate a novel, multi-condenser LHP. To ensure controlled condensation and full utilization of all condensers, an additional wick must be integrated into the condensers. Condensation occurs on the wick’s surface, and the wick is used to separate the vapor and liquid phases. The wick must therefore have high capillary pressure at the interface to separate the phases and high bulk permeability for ease of liquid flow.To achieve high capillary pressure at the wick surface and high bulk permeability, a bi-layer sintered wick structure was fabricated in two steps (Figure 1). The bulk wick was first made by sintering coarse (120-140 µm) copper powder at 850 °C for 30 minutes. The sintering was performed in a tube furnace under a hydrogen-nitrogen atmosphere. A thin layer of high-capillarity wick was then fabricated on top of the bulk wick by layering fine (5-15 µm) copper powder and sintering at 650 °C for 30 minutes. A controlled fabrication procedure resulted in a repeatable thickness of the fine layer of approximately 100 µm. The bi-layer wick showed improvement over the single-layer coarse wick, matching the permeability (10-11 m2) of the coarse wick in the bulk while increasing the surface capillary pressure from 100 to 680 Pa for the advancing meniscus.

DIRECT SEAWATER DESALINATION BY ION-CONCENTRATION POLARIZATION

The shortage of fresh water is a serious global problem, and an energy-efficient desalination strategy can provide a substantial solution for the water-crisis [1]. Current desalination methods utilizing reverse-osmosis and electrodialysis mechanisms require high power consumption or large-scale infrastructures, which are not suitable for resource-limited settings. This work elucidates a novel desalination process utilizing ion-concentration polarization (ICP) [2].Often called ion depletion or enrichment, ICP occurs due to the mismatch of the charge carriers at the nanoporous membrane. Once ICP is triggered, the concentrations of both cations and anions decrease on the anodic side of the membrane (ion depletion) and increase on the cathodic side (ion enrichment) [3]. With a strong ICP, both anions and cations are depleted near the nanojunctions. If ICP is combined with a pressure-driven flow, a steady-state depletion zone is obtained using the device depicted in Figure 1(a). In the experiments done with seawater obtained from Crane Beach, MA in Figure 1(b), the depletion zone was formed to divert charged ions (represented by dyes) into the “salted” stream. It was also shown the ICP layer acts as a virtual barrier for all charged particles, including most solid particles and biomolecules found in water. Therefore, both small salt ions and large microorganisms can be removed from the “desalted” stream, significantly reducing membrane fouling. Figure 1(c) shows in situ conductivity measurement of “desalted” stream. Measurements of the desalted stream indicate the seawater’s conductivity dropped from ~50mS/cm to ~0.5mS/cm, which corresponds to ~3mM salinity. This level of salinity is below the 10mM threshold required for potable water.The steady-state current required was found to be ~30µA, equating power consumption of ~3.5Wh/L. This technology could be applied to small-scale desalination systems, possibly with the option of battery/solar cell-powered operation. The footprint of the device is small, potentially allowing ~3X104 parallelization on the wafer scale for a total throughput of ~300mL/min.

IMAGE-BASED CELL SORTING

This research involves the development of architectures for screening complex phenotypes in biological cells. We augment microscopy with the ability to retrieve cells of interest. This capability will permit cell isolation on the basis of dynamic and/or intracellular responses, enabling new avenues for screening. Currently, such sorts require expensive specialized equipment, widely prohibiting such sorts.We previously reported a technique for selective hydrogel-based photoencapsulation of undesired cells in cell cultures to enable sorting [1]. We have increased the resolution of this technique, improving purification and enrichment performance. We have also adapted this approach into an even simpler technique that permits sorting via photopatterned free-radical toxicity termed radical-activated cell sorting, or RACS [2] (Figure 1). Here we plate adherent cells into a dish, assay them using microscopy, and note the positions of cells of interest. We then use an inexpensive inkjet printer to print a transparency mask with opaque features corresponding to locations of cells of interest. After we align the mask to the dish, features reside beneath target cells. We then add a solution to the dish containing a UV-photoinitiator. We expose the dish through the mask with UV light, which causes the photoinitiator to split into toxic radicals that attack and kill unmasked, undesired cells, leaving behind live, desired cells (Figure 2). The method permits culture on arbitrary substrates and requires standard hardware found in biology labs and an inexpensive photoinitiator, facilitating dissemination.We have demonstrated the ability to pattern viability with resolution < 500 μm as well as the functional sorting of mixed MCF7 cell cultures predicated on microscopy-based selection. Further development will increase the range of cell types that can be sorted using this technique and resolution. The straightforward operation and low cost of RACS will especially appeal to biologists, bringing straightforward image-based cell-sorting technology to individual labs.

MICROSCALE CONTROLLED CONTINUOUS CELL CULTURE

For systems biology, the models are more often limited by the absence of reliable experimental data than by available computational resources. Unfortunately, there is still great difficulty in making the leap from genetic and biochemical analysis to accurate verification with conventional culture growth experiments due to variations in culture conditions. Measurements of metabolic activity through substrate and product interactions or cellular activity through fluorescent interactions are highly dependent on environmental conditions and cellular metabolic state. For such experiments to be feasible, continuous cultures [1] [2] utilizing control strategies must be developed to measure chemical concentrations, introduce chemical inputs, and remove waste. An integrated microreactor system with built-in fluid metering will enable environmental control and programmable experiments capable of generating reproducible data.The chip shown in Figure 1 is fabricated out of a rigid plastic, polycarbonate, utilizing PDMS membranes for actuation and pumping [3] The fabrication process for bonding plastic-PDMS hybrid devices has been described previously [4]. Mixing and oxygen delivery is performed through membranes between the fluidic and actuation layers of the growth chamber sections. Chip reliability is demonstrated over a 2-week culture where multiple steady states are reached. Culture experiments are performed with E. coli ATCC31883 in 5 g/L glucose minimum-salts defined medium supplemented with 100 ug/ml ampicillin. Cell density is measured through forward-scattering with an optical sensor at 585 nm in a path length of 0.8 mm. Multiple operation modes are shown in Figure 2 including batch, fed batch, oxystat, chemostat, and turbidostat. Full control is demonstrated under turbidostatic steady state, where the cell density is closed-loop-controlled at a cell density of 2, by dynamically varying the flow rate. Turbidostatic steady state also allows the extraction of the cell maximum growth rate of 0.79 h-1 in minimum salts medium.

USING BUOYANT MASS TO MEASURE THE GROWTH OF SINGLE CELLS

Understanding how the rate of cell growth changes during the cell cycle and in response to growth factors and other stimuli is of fundamental interest. Over the decades, various approaches have been developed for describing cellular growth patterns, but different studies have often reached irreconcilable conclusions, even for the same cell types. Several factors may contribute to the discrepancies between different growth models: i) cells are minute, irregularly shaped objects; ii) proliferating cells increase their size only by a factor of two, so distinguishing between different cell growth models with mathematical rigor requires highly precise measurements; iii) a wide variety of methods have been used to measure growth, including approaches that average across populations as well as those that monitor individual cells; and iv) a cell’s size includes both volume and mass, which can change at different rates. An ideal method for measuring cell growth rates would directly and continuously monitor the mass and volume accumulation of single unperturbed cells with high precision. In recent years, optical microscopy has been the closest match to this ideal, but volume determination by microscopy has lacked the precision to conclusively distinguish between cell-growth models. Potential alternatives include using fluorescent protein reporters that are correlated with cell size5 or using phase microscopy to measure dry mass during cell growth. We have developed a system that can precisely monitor the growth of single cells in terms of buoyant mass and show that bacteria, yeast, and mammalian lymphoblast cells grow at a rate that is proportional to their buoyant mass (Figures 1 and 2). Buoyant mass is dependent on the amount of biomass in the cell, most of which is denser than water, and so is analogous to the dry mass of the cell.

NONMONOTONIC ENERGY DISSIPATION IN MICROFLUIDIC RESONATORS

Micro- and nanomechanical cantilevers are widely used as sensitive probes for physical measurements in materials science, engineering, and biology. In vacuums and air, detecting shifts in the resonance frequency enables exquisitely sensitive measurements of mass and detection of single DNA molecules, single viral particles, and single bacterial cells. However, numerous applications in nanotechnology and the life sciences require samples to be contained in liquid. Recently, measurements have demonstrated that viscous damping is substantially reduced by confining the (liquid) sample to a microfluidic channel embedded inside a cantilever beam surrounded by vacuum (Figure 1). Such devices enable mass measurements of nanoparticles, single bacterial cells, and submonolayers of adsorbed proteins with femtogram sensitivity in liquid. A key outstanding question is how energy dissipation, and hence sensitivity, scales with the size of the resonator and the density and viscosity of the fluid. This is of particular interest since two of the most intriguing size regimes for these devices remain to be explored: (i) where the resonators are small enough to acquire mass spectra of viruses, protein complexes, and ultimately single molecules directly in solution and (ii) where the channel is large enough to measure the growth of mammalian cells by monitoring their mass with high precision. We have addressed this question through theory and through measurements; our results reveal surprising connections between the fluid properties, energy dissipation, and the device dimensions in liquid-filled microcantilevers. While the quality factor of conventional cantilever sensors submersed in fluid always degrades with increasing viscosity, we show that damping in liquid-filled cantilevers can increase or decrease as viscosity increases (Figure 2).

RF MEMS RESONATORS FOR BODY-AREA NETWORK TRANSCEIVERS

Traditionally, RF circuits for wireless communications have used large-sized and low-quality-factor (Q) electrical RF components such as oscillators and filter banks, which create a bottleneck to miniaturization. Silicon-based micromechanical resonators can complement or even replace their electrical counterparts in existing wireless technology by providing RF building blocks with small size, low power, high-Q and multi-GHz frequency (high speed) functionality.In this project, we are developing bulk acoustic resonators for use in low-power transceivers in Body-area Networks (BAN), as part of the Healthy Radios project sponsored by MARCO IFC/MSD. These networks will transmit data from multiple sensors for parallel monitoring of medical or environmental variables. An integrated solution for transceiver design employing multiple channels separated by 1 MHz in the 2.36 to 2.4 GHz Medical BAN band requires a bank of RF resonators with quality factors greater than those achievable using conventional LC tanks. We explore high-Q micromechanical resonators using lateral dielectric transduction [1] [2] at multi-GHz frequencies to achieve channel-select filtering and narrow-bandwidth frequency sources in the BAN transceivers. These devices are compared to piezoelectrically transduced devices, successfully demonstrated in the multi-GHz domain [3].The coupling coefficients of piezoelectric transducers are in general greater than those of their electrostatic counterparts. However, piezoelectric devices have limited quality factor due to mechanical losses in the piezoelectric material. Unlike piezoelectrics, dielectric transducers provide high Q and compatibility with CMOS for monolithic transceiver design. To this end, we scale Si-based lateral dielectrically transduced resonators to the BAN band at 2.4 GHz (Figure 1). The nth harmonic of longitudinal vibration in the bar is driven and sensed on alternate fingers of an interdigitated electrode design. Figure 2 provides the analytical frequency-dependence of motional impedance (Rx) and nominal capacitance (C0) for various harmonics with 20 nm of HfO2 transduction film on a 340-nm Si device layer. A motional impedance of ~10 kΩ is obtained for a 48-um device operating at the 15th harmonic but it is necessary to optimize for the nominal capacitance for these specifications. Optimization of Rx and C0 allows for integration of the resonators into the transceiver circuitry by making a feedback loop possible for an oscillator and providing low insertion loss for a bandpass filter.

MICROFABRICATED DEVICES FOR PORTABLE POWER-GENERATION

The development of portable power-generation systems remains an important goal, with applications ranging from the automobile industry to the portable electronics industry. The focus of this work is to develop microreaction technology that converts the chemical energy stored in fuels– such as light hydrocarbons and their alcohols— directly into electricity or into a different energy vector such as hydrogen. Developing devices with high energy-conversion efficiency requires addressing difficulties in high-temperature operation: specifically, thermal management, material integration, and improved packaging techniques.We have developed a catalytic combustion-based device intended for the direct conversion of thermal energy to electricity. The combustor has been designed to achieve attractive energy and power densities while addressing system challenges such as mechanically robust fluidic connections and minimal parasitic power losses related to pressurization of air. The channels of the combustor are etched using wet potassium hydroxide, which is the most economical etch technique available. Straight channels (1mm by 1mm in cross-section) are arranged in parallel and separated by 100-μm –thick silicon walls, in order to achieve low pressure drop (< 300 Pa at 10 SLPM gas flow) with significant surface area (~1 cm2 per channel) for catalyst deposition. Two identical reactors are stacked to increase reactor volume without a significant increase in exposed surface area. External gas distribution manifolds are compression-sealed to the reactor, eliminating the need for glass brazing of tubes, increasing the mechanical robustness of the device, and avoiding large pressure losses associated with flow constrictions. Platinum-on-alumina catalyst has been washcoated on the channel surfaces for the catalytic combustion of butane with air.The catalytic combustor has been shown to transfer up to 360 W of heat through surfaces intended for thermoelectric power generation, at a maximum surface temperature of 465°C and a thermal transfer efficiency in the range of 73 – 78% (based on fuel lower heating value). The experiments have been performed using conductive heat sinks designed to have a thermal resistance similar to that of a thermoelectric module. As designed, the reactor could also be used for heat integration of multiple reactions, such as catalytic combustion and steam reforming of alcohol for hydrogen production.

MODEL-BASED DESIGN OF MEMS VIBRATION-ENERGY-HARVESTERS FOR WIRELESS SENSORS

The recent development of “low power” (10s-100s 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. While potential applications range from building climate control to homeland security, the application pursued most recently has been that of structural health monitoring (SHM), 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 optimized models have been verified by comparison to tests on a macro-scale device both without [1] and with a proof mass at the end of the structure (Figure 1) [2]. A non-optimized, uni-morph beam prototype (Figure 2) has been designed and fabricated [3] [4]. Design tools to allow device optimization for a given vibration environment have been under detailed investigation considering various geometries of the device structures and fabrication constraints, especially in microfabrication. Future work will focus on fabrication and testing of optimized unimorph beams for not only the {3-1} mode but also the {3-3} mode of operation using an interdigitated electrode configuration. System integration and development, including modeling the power electronics, will be included.

STUDYING AUTOCRINE SIGNALING FOR GROWTH IN TUMOR AND STEM CELLS

Autocrine signaling plays a key role in tumorigenesis and in the maintenance of various physiologic states. Our research involves the use of cell-patterning techniques to investigate the role of autocrine signaling during in vitro expansion of embryonic stem cells and cancer cells.Expanding on our previous experimental work, recently we have also developed numerical models of autocrine signaling. Cells act as sources for autocrine factors. However, cells also possess receptors that the factors can bind to. Finally, in addition to protein transport, uptake of nutrients and production of metabolites are also important processes to account for, especially for longer culture periods. We have previously found an optimal density for 2-day culture of mouse embryonic stem cells. Our models suggest that the positive feedback on growth provided by autocrine signaling combined with the negative feedback provided by nutrient depletion can account for the presence of such an optimal density (Figure 1).For our study of autocrine signaling in tumor cells, we continued to investigate the role of autocrine signaling on heterogeneity in tumor growth. Using A431 epidermoid carcinoma cells as our model, we used stencil-cell patterning to position cells as square-latticed arrays of circular cell patches of varying size and spacing (Figure 2). Unlike randomly-plated cell culture where cells experience differing amounts of cell-cell contacts and irregular intercellular spacing, our platform ensures the direct modulation of autocrine signaling while keeping other contributing signals intact. We are investigating the use of the developed platform as a novel tool to quantify the spatial operation of autocrine signaling. Existing methods require prior knowledge of the underlying autocrine loops and therefore cannot be applied to less characterized biological systems. Our technique will be useful for in vitro investigation of cancer therapeutics and enables the systematic modulation of autocrine-promoted growth.

ISO-DIELECTRIC SEPARATION OF CELLS AND PARTICLES

The development of new techniques to separate and characterize cells with high throughput has been essential to many of the advances in biology and biotechnology over the past few decades. Continuing or improving upon this trend – for example, by developing new avenues for performing genetic and phenotypic screens – requires continued advancements in cell-sorting technologies. Towards this end, we are developing a novel method for the simultaneous separation and characterization of cells based upon their electrical properties. This method, iso-dielectric separation (IDS), uses dielectrophoresis (DEP, the force on a polarizable object [1]) and a medium with spatially varying conductivity to sort electrically distinct cells while measuring their effective conductivity. It is similar to iso-electric focusing, except that it uses DEP instead of electrophoresis to concentrate cells and particles to the region in a conductivity gradient where their polarization charge vanishes [2] [3].Previously, we have demonstrated the ability to perform continuous-flow, label-free, non-binary separations using IDS on a wide variety of cells and particles, while simultaneously extracting quantitative information from these samples as they are sorted [4]. We are currently focusing on extending these capabilities to perform genome-wide characterizations of electrical properties in the budding yeast Saccharomyces cerevisiae. The most recent implementation of the device uses a valve scheme that enables real-time control of the conductivity gradient, along with the ability to rapidly switch samples for sorting and characterization (Figure 1). These developments increase the throughput of the device, making the systematic characterization of both pooled and unpooled cell libraries feasible. To date, we have applied IDS to a pooled screen of the yeast deletion collection, identifying several genes associated with distinct electrical properties (Figure 2). The improved understanding of the relationship between a cell’s genotype and its physical properties enabled by IDS suggests its potential as a new high-content screening platform.

CHARACTERIZING IMMOBILIZED CATALYSTS USING PACKED-BED MICROREACTORS

Catalyst immobilization on heterogeneous supports affords several advantages over homogeneous catalysts for chemical synthesis in continuous flow processes. The use of packed beds in flow systems offers built-in catalyst separation from the effluent while allowing for high catalyst loadings. However, heterogeneous catalysts typically suffer from two problems: 1) reduced activity compared to the homogeneous analogue and 2) loss of activity over time due to deactivation or leaching. A requirement for using immobilized catalysts in continuous processes is an understanding of the activity and stability of the catalyst over long periods.Towards this end, we have developed a platform for characterizing immobilized catalysts using silicon microreactors. These devices have void volumes of 28-140 µL, which allow complete characterization using milligram quantities of material. The devices are fabricated using deep reactive-ion-etching (DRIE), coated with silicon nitride to enhance chemical compatibility, and capped with pyrex to allow visual access. The microfabricated weir has 25 µm wide channels (Figure 1); thus, particles larger than 25 µm can be retained. Fluidic connections are made using a compression packaging scheme that was recently developed in our group [1] (Figure 2). Both polymer beads and silica gel have been loaded and retained, though polymer beads offer challenges due to their tendency to swell in organic solvents. Application of this system to studying covalently bound catalysts and physisorbed catalysts [2] is ongoing.

DESIGN OF A THREE-AXIS MEMS FORCE-SENSOR

Multi-axis force-sensing at the micro-scale is necessary for a wide range of applications in biology, materials science, and nanomanufacturing. A three-degree-of-freedom force-sensor (Figure 1) was designed that is capable of accurately and precisely measuring the adhesion forces (nanoNewtons) between biologically active surfaces. This force sensor is positioned and actuated using a Hexflex nanopositioner and Lorenz force actuators. The fabricated device is shown in Figure 2.In order to design high-accuracy, high-precision, multi-axis MEMS force sensors, a closed-form model was developed to optimize the strain-sensitivity of the MEMS force-sensor. This model first sets constraints on the system due to package size, fabrication techniques, desired degrees of freedom, and force range. The layout of the flexure system is optimized to meet the kinematic and manufacturing constraints of the MEMS force-sensor. The geometry of the flexures is set to maximize the strain at the sensor locations.This model was incorporated into a thermal/electric model to fully characterize all of the inputs to the system. The resolution of the force-sensor is a function of the noise from the strain-sensors, the noise in the electronics, the thermomechanical noise, and the sensitivity of the strain-sensors to a force input. Based on this model, the dominant noise sources are identified and the sensor system is optimized to reduce these noise sources. The thermal/electric model is also used to determine the major factors limiting accuracy of the force-sensor. In most cases, the drifts in both the electronics and sensors caused by fluctuations in room temperature were the major sources of accuracy errors. Therefore, an environmental enclosure with closed-loop control over temperature was designed to reduce the thermal variation. Overall, the final design of the force sensor is capable of producing sub-nanoNewton-resolution force measurements with nanoNewton-level accuracy.

LIQUID PROPAGATION IN MICROPILLAR ARRAYS

Prediction and optimization of liquid propagation rates in micropillar arrays are important for various lab-on-chip [1], biomedical [2], and thermal management applications [3]. We developed a semi-analytical model based on the balance between capillary pressure and viscous resistance to predict liquid propagation rates in micropillar arrays with height-to-period ratios greater than 1 and diameter-to-period ratios less than 0.57. These geometries represent the most useful regimes for practical applications requiring large propagation rates. The capillary pressure was obtained using an energy approach in which the meniscus shape was predicted using Surface Evolver simulations and verified by interference microscopy. The interference microcopy image of the liquid meniscus is shown in Figure 1. The viscous resistance was determined using Brinkman’s equation [4] with a numerically obtained permeability [5] and corroborated with finite element simulations. The model shows excellent agreement with one-dimensional propagation experiments of de-ionized water in silicon micropillar arrays, which highlights the importance of capturing the details of the meniscus shape and the viscous losses. Furthermore, an effective propagation coefficient was obtained through dimensionless analysis that is functionally dependent only on the micropillar geometry. The relationship is plotted in Figure 2. The work offers design guidelines to obtain optimal liquid propagation rates on micropillar surfaces.The current model obtained an average driving pressure during the propagation process. More specifically, two distinct time scales were observed as the liquid front advanced on the bottom surface between pillars or wetting the sides of the pillars. When the height of the pillars is smaller than the period of the pillar array, the former time scales dominate and our model overestimates the propagation rate. Future work will focus on the detailed dynamics of the liquid front.

NANOFABRICATED REFLECTION AND TRANSMISSION GRATINGS

Diffraction gratings and other periodic patterns have long been important tools in research and manufacturing. Diffraction occurs due to the coherent superposition of waves and is a phenomenon with many useful properties and applications. Waves of many types can be diffracted, including visible and ultraviolet light, x-rays, electrons, and even atom beams. Periodic patterns have many useful applications in fields such as optics and spectroscopy; filtering of beams and media; metrology; high-power lasers; optical communications; semiconductor manufacturing; and nanotechnology research in nanophotonics, nanomagnetics, and nanobiology.A long-standing problem with transmission gratings in the extreme ultraviolet (EUV) and soft x-ray bands has been the strong absorption of photons upon transmission and thus a low diffraction efficiency in this important wavelength band. We have recently solved this problem with the invention and fabrication of critical-angle transmission (CAT) gratings. This new design for the first time combines the high broadband efficiency of blazed grazing-incidence reflection gratings with the superior alignment and figure tolerances and the low weight of transmission gratings [1] [2]. The CAT gratings consist of ultrahigh-aspect-ratio, nm-thin freestanding grating bars with sub-nm smooth sidewalls that serve as efficient mirrors for photons incident at graze angles below the angle for total external reflection (see Figures 1 and 2). Blazing can concentrate diffracted power into a single or a few desired diffraction orders and has been confirmed through x-ray tests. Blazing also enables the use of higher diffraction orders and leads to manifold increases in spectral [3] and spatial resolution in spectrometer or focusing applications, respectively. We have achieved grating bar aspect ratios of ~ 150 in 6-micron-deep, 200-nm-period CAT gratings and are currently focusing on the minimization of internal support structures.Work on high-resolution (R ~ 10,000 – 100,000) applications is also ongoing in the areas of high-precision patterning of silicon-immersion echelle gratings in infrared telescopes for astronomy [4] and blazed reflection gratings for high-resolution EUV and soft x-ray synchrotron applications [5].

FREE-FLOW ZONE ELECTROPHORESIS OF PEPTIDES AND PROTEINS IN PDMS MICROCHIP FOR NARROW ISOELECTRIC-POINT (PI) RANGE SAMPLE PREFRACTIONATION COUPLED WITH MASS SPECTROMETRY

Isoelectric point (pI)-based fractionation is ideally suited for the first-dimensional separation because the pI value of any peptide or protein can be simply estimated from the sequence information. Therefore, the pI-based fractionation techniques can be highly specific to target peptides and proteins. Due to this benefit, there have been previous efforts to integrate isoelectric focusing (IEF) into mass spectrometry (MS)-based proteome analysis processes [1] [2] [3] [4]. While the physical coupling between capillary IEF and ESI-MS is straightforward, the buffer systems for IEF separation (carrier ampholytes, a complex mixture of amphoteric small molecules) have low compatibility with electrospray (ESI)-MS interfaces. In view of this current deficit, we have developed an ampholyte-free, two-step cascaded microfluidic sorting technique based on free-flow zone electrophoresis that isolates the molecules of interest from a small sample volume of 100 mL within a narrow and freely adjustable pI range (£ 1 pH units), even below pH 3 and beyond pH 10 [5]. To create a salt bridge for free-flow electrophoresis in PDMS chips, we printed a submicron-thick hydrophobic layer on a glass substrate and created an electrical junction gap for free-flow zone electrophoresis. With this sorting device, as shown in Figure 1, we demonstrated binary sorting of peptides and proteins in standard buffer systems and validated the sorting result with liquid chromatography (LC)/MS. In Figure 2, the sorting result of the acidic peptides < pH 7 is shown as an example. Furthermore, we coupled two sorting steps via off-chip titration and isolated peptides within specific pI ranges from sample mixtures, where the pI range was simply set by the pH values of the buffer solutions. This pI-based binary sorting device, with its simplicity of fabrication and a sorting resolution of 0.5 pH unit, can potentially be a high-throughput sample fractionation tool for targeted proteomics using LC/MS.

STENCIL-AND-FLIP CELL PATTERNING FOR GENERATION OF DUAL STEM CELL MICROENVIRONMENTS

Embryonic development is a complex dynamic process, whereby spatial organization of molecular signals instructs stem cells to adopt various differentiation fates at different locations [1]. Recapitulating this process in vitro will greatly facilitate the mechanistic understanding of embryonic development. However, current in vitro models are unable to reproduce the developmental environment adequately. To realize the aim of building a complex developmental model, we developed the Stencil-and-Flip Cell Patterning (SAF-CP) technique to present multiple spatially organized microenvironments to a single population of stem cells [2]. SAF-CP combines two established patterning technologies i.e., stencil and Bio Flip Chip (BFC) [3] but uses them in a sequentially aligned format to create spatially organized stem cell microenvironments in vitro (Figure 1). To validate that spatial organization of microenvironments translates to differential instruction of stem cell fates, we used SAF-CP to selectively present self-renewing (STO fibroblast feeder + N2B27 medium) (Figure 2A) and neuronal differentiating (gelatin + N2B27 medium) (Figure 2B) microenvironments to a single mouse embryonic stem cell (mESC) colony. (Figure 2C) After one week of culture, we observed that self-renewal (Sox2) and neuronal precursor (Nestin) markers had a spatial distribution coinciding with the patterned dual microenvironments (Figure 2D). The ratio of self-renewal-to-neuronal phenotypes within a colony was observed to be dependent on the relative extent of the two microenvironments presented to the colony (quantifiable by the percentage colony area on STO and gelatin, respectively) (Figure 2E). Our results demonstrate the utility of the SAF-CP in building in vitro models that recapitulate the organizational-instructive traits of stem cell niches, allowing us to emulate stem cell development more realistically.

FLEXIBLE MULTI-SITE ELECTRODES FOR MOTH FLIGHT CONTROL

Significant interest exists in creating insect-based Micro-Air-Vehicles (MAVs) [1] [2] [3] that would combine advantageous features of insects—small size, effective energy storage, navigation ability—with the benefits of MEMS and electronics—sensing, actuation and information processing. The key part of the insect-based MAVs is the stimulation system which interfaces with the nervous system of the insect to bias the insect’s flight path.In this work, we have developed a flexible multi-site electrode (FME) for insect flight control that directly interfaces with the animal’s central nervous system. The FMEs are made of two layers of polyimide with gold sandwiched in-between in a split-ring geometry using standard MEMS processing [3]. The FMEs have a novel split-ring design that incorporates the anatomical bi-cylinder structure of the nerve cord of the Moth Manduca Sexta and allows for an efficient surgical process for implantation (Figure 1). Additionally, we have integrated carbon nanotube (CNT)-Au nanocomposites into the FMEs to enhance the charge injection capability of the electrode.We are able to elicit graded and multi-direction abdominal movements in both the pupae and adult moths using FME stimulation.Moreover, the CNT coated FMEs are able to elicit abdominal motion of the moths with a stimulation voltage significantly less (1.0 V vs. 2.0 V, p < 0.001, n=10 moths) than that of uncoated FMEs. Finally, we have integrated the FMEs into a wireless system and in the flight control experiment, we are able to force a freely flying animal to perform turning motions (Figure 2a) using the abdominal ruddering with these elicited abdomen motions. These turning motions are well repeatable and the changes in the yaw angle of the moth with 4 successive stimulations are shown in Figure 2b.

ORIGIN AND CONTROL OF INTRINSIC STRESSES IN METALLIC THIN FILMS FOR N/MEMS APPLICATIONS

The mechanical properties of thin films, especially residual stresses in as-deposited films, strongly influence the reliability and performance of microelectromechanical devices and systems. Residual stresses can be as high as 1GPa and can be tensile or compressive, depending on the material, deposition technique, and, very sensitively, deposition conditions. When evaporative deposition is used, the two broad categories of behavior occur (Figure 1). Type I is characterized by development of a high tensile stress that is retained during and after continued deposition. This behavior is common when materials are deposited at low temperatures relative to their melting temperature, e.g. among refractory metals and semiconductors. In Type II behavior, a tensile stress develops as the film first forms, but compressive stresses (as high as 200MPa) develop during continued deposition. This behavior is characteristic of materials with relatively low melting temperatures such as Au, Ag, and Al.The tensile rise seen in both behaviors is thought to arise as islands coalesce to form a film. The origin of post-coalescence compressive stress has been debated extensively over the past decade. Models associated with adatom-surface [1] [2] and adatom-grain boundary [3] interactions have been proposed to explain the compressive-stress generation during deposition and its reversible relaxation during growth interruptions.We use in-situ stress measurements to follow stress evolution as films are deposited. The measurements can be done with sensitivity to variations associated with sub-monolayer deposition and can be carried out at high sampling frequencies. Through correlation of stress and microstructural evolution, we have shown that reversible stress relaxations that occur during interruptions of growth of Au films vary with the grain size, in general agreement with the model given in reference [3] [4]. However, we also find that the temperature dependence of the reversible stress change is too weak to be consistent with any proposed models. To further characterize stress evolution phenomenology, especially with respect to deposition temperature, we have begun studies of a range of materials. Figure 2 shows results for Ni films deposited at room temperature and 200C. Two observations are noteworthy: the observed behavior is intermediate to Type I and II, and the behavior depends strongly on the deposition temperature. Those results show that the processes leading to the development of compressive stresses are temperature-dependent, even if the process involved in reversible stress relaxations is not.Through these and other studies, we aim for a comprehensive understanding of factors that affect the residual stress in thin films, so that this stress can be better controlled.

POROUS IONIC-LIQUID-ION-SOURCE EMITTER ARRAYS FOR SPACECRAFT PROPULSION

Ionic Liquid Ion Sources (ILIS) are a subset of electrospray emitters characterized by pure ion emission from room-temperature ionic liquids. Previously these sources have been shown to be a simple and efficient source of both positive and negative ions that could be used, amongst other applications, for spacecraft propulsion [1]. However, the low (<1µN) thrust levels per emitter require practical thrusters to employ arrays of emitters. At modest packing densities, a few tips per square millimeter, the thrust per unit area approaches that of more traditional plasma based ion thrusters [2]. Initial efforts focused on creating arrays of externally wetted emitters from silicon [3]. These studies were plagued by poor and/or inconsistent wetting. As an alternative, we are developing arrays fabricated from bulk porous materials. Here capillarity alone provides passive and consistent wetting of the emission sites. We have observed that this feed mechanism can yield a larger current range than externally wetted emitters while continuing to operate in the purely ionic regime [2]. Using porous emitters, a thruster configuration as in Figure 1 is envisioned.Fabricating arrays using bulk porous material has resulted in a number of inherent challenges. Electrochemical etching has been a useful tool for fabricating ILIS in the past [1], and our recent findings suggest it may be well suited for etching the surface of a porous material. Specifically, when etching is used with an appropriate tool, a transport limited etch rate can be achieved that promotes smooth, near-isotropic etching of the surface of a porous material with minimal penetration into the pores. Figure 2 demonstrates the results for both porous and solid nickel samples. Additionally, we are beginning to investigate the feasibility of high-pressure molding of powder metals to fabricate the emitters and substrate with molds fabricated using more traditional techniques. To date, basic extraction and acceleration grids have been fabricated from silicon with die-level alignment; however, we plan to move towards a more complete and optimized package within the near future.

PECVD CNT-ENABLED ELECTRON-IMPACT GAS IONIZERS FOR PORTABLE MASS SPECTROMETRY

Research efforts on MEMS-based analytical instrumentation have focused on the development of rugged gas chromatography and mass spectrometry (GC/MS) systems that are smaller, lighter, cheaper, faster, and more power-efficient [1]. The power consumption, size, and weight of these systems are driven by the pump requirements. Therefore, relaxation of the pressure level at which the system components can operate would enable the systems’ portability. Portable GC/MS systems, either as individual units or as parts of massive networks, can be used in a wide range of applications including in-situ geological surveys, law enforcement, environmental monitoring, and space exploration [2].The ionizer is one of the core components of an MS system. We have developed a carbon nanotube (CNT)-based MEMS/NEMS electron-impact gas ionizer with integrated extractor gate for portable mass spectrometry. The ionizer achieves low-voltage ionization using sparse forests of plasma-enhanced chemical-vapor-deposited (PECVD) CNTs as field-emitters and a proximal extractor grid with apertures aligned to the CNT forests to facilitate electron transmission. The extractor gate is integrated into the ionizer by using a high-voltage MEMS packaging technology based on Si springs defined by deep-reactive-ion etching (DRIE) [3]. The ionizer also includes a high aspect-ratio silicon structure (μfoam) that facilitates sparse CNT growth and also enables uniform current emission. The experimental data show that the MEMS extractor gate transmits up to 66% of the emitted current, and that the ionizers are able to produce up to 0.139 mA of ion current with up to 19% ionization efficiency at 22 mtorr while consuming 0.39 W [4]. Figure 1 shows a cross-section schematic and a picture of a fabricated ionizer; Figure 2 shows experimental data that demonstrate that the ionizers work as described by the electron-impact-ionization model.

MEMS PRESSURE-SENSOR ARRAYS FOR PASSIVE UNDERWATER NAVIGATION

A novel sensing technology for unmanned undersea vehicles (UUVs) is under development. The project is inspired by the lateral line sensory organ in fish, which enables some species to form three-dimensional maps of their surroundings [1] [2]. The canal subsystem of the organ can be described as an array of pressure-sensors [3]. Interpreting the spatial pressure gradients allows fish to perform a variety of actions, from tracking prey [4] to recognizing nearby objects [2]. It also aids schooling [5]. Similarly, by measuring pressure variations on a vehicle surface, an engineered dense pressure-sensor array allows the identification and location of obstacles for navigation (Figure 1). We are demonstrating proof-of-concept by fabricating such MEMS pressure sensors by using KOH etching techniques on SOI wafers to construct strain-gauge diaphragms.The system consists of arrays of hundreds of pressure-sensors spaced about 2 mm apart on etched silicon and Pyrex wafers. The sensors are arranged over a surface in various configurations (Figure 2). The target pressure resolution for a sensor is 1 Pa, which corresponds to the noiseless disturbance created by the presence of a 0.1-m radius cylinder in a flow of 0.5 m/s at a distance of 1.5 m. A key feature of a sensor is the flexible diaphragm, which is a thin (20-μm) layer of silicon attached at the edges to a silicon cavity. The strain on the diaphragm due to pressure differences across the diaphragm is measured. At this stage, the individual MEMS pressure sensors are being constructed and tested.In parallel to the construction of a sensor array, techniques are being developed to interpret the signals from a dense pressure array by detecting and characterizing wake structures such as vortices and building a library of pressure distributions corresponding to basic flow obstructions. In order to develop these algorithms, experiments are being performed on coarse arrays of commercial pressure-sensors.

PROTEIN DYNAMICS INVOLVED IN THE CYTOKINESIS OF FISSION YEAST

Cytokinesis is the final stage of cell division when eukaryotes assemble a contractile acto-myosin ring to physically divide their cytoplasm and genetic material to create two daughter cells. Global and local concentrations of protein components involved in the contractile ring assembly of fission yeast have been using quantitative fluorescence microscopy [1]. However, the dynamics of the ring protein remains unknown due to the limitations of conventional imaging and image analysis approaches. In this project, we use highly integrated computational-experimental research approaches that consist of high-resolution imaging with the assistance of micro-well arrays manufactured in MTL, computational image analysis (using an image-correlation spectroscopy algorithm) [2] [3], and data-driven computational modeling. Our goal is to establish a molecular-level model that describes mechanistically how the core set of ring proteins in fission yeast is organized prior to, as well as during, its constriction in cytokinesis. Specifically, the summer project includes an experimental imaging part and a computational modeling part.