Heterogeneous micro-architectonic integration of SU-8 and highly entangled polyacrylamide hydrogel to realize cut-resistant soft superhydrophobic surfaces
This paper presents a novel idea to create cut-resistant superhydrophobic (SHPo) surfaces by integrating an array of SU-8 micropillars on a highly entangled polyacrylamide (PAAm) hydrogel substrate. We begin by demonstrating that this highly entangled PAAm hydrogel exhibits superior resistance to cutting while being as transparent, flexible, and stretchable as other polymeric substrates like polydimethylsiloxane (PDMS). Currently, there are no well-known methods or chemicals to directly integrate SU-8 and PAAm with a covalent bond. To overcome this challenge, we introduce a thin layer of chemically modified PDMS between the SU-8 and PAAm so that covalent bonds can be formed between both the SU-8/PDMS interface and the PDMS/PAAm interface. After validating the reliability of the bonding in our experiments, we develop a heterogeneous integration process to fabricate the desired SHPo surface. To demonstrate the critical role of PAAm hydrogel in achieving the cut-resistant SHPo surface, we contrast this new SHPo surface with a reference version that uses a PDMS substrate instead. We conduct microscopic inspections using scanning electron microscopy (SEM) and a contact angle goniometer before and after cutting the two surfaces. These evaluations show significant differences in their structural integrity and behavior in water interaction.
The UmboMic: A PVDF Cantilever Microphone
We present the "UmboMic," a prototype piezoelectric cantilever microphone designed for future use with totally-implantable cochlear implants.
Effects of Micromachining on Anti-oxidant Elution from a Mechanically-Adaptive Polymer
Intracortical microelectrodes (IMEs) can be used to restore motor and sensory function as a part of brain-computer interfaces in individuals with neuromusculoskeletal disorders. However, the neuroinflammatory response to IMEs can result in their premature failure, leading to reduced therapeutic efficacy. Mechanically-adaptive, resveratrol-eluting (MARE) neural probes target two mechanisms believed to contribute to the neuroinflammatory response by reducing the mechanical mismatch between the brain tissue and device, as well as locally delivering an antioxidant therapeutic. To create the mechanically-adaptive substrate, a dispersion, casting, and evaporation method is used, followed by a microfabrication process to integrate functional recording electrodes on the material. Resveratrol release experiments were completed to generate a resveratrol release profile and demonstrated that the MARE probes are capable of long-term controlled release. Additionally, our results showed that resveratrol can be degraded by laser-micromachining, an important consideration for future device fabrication. Finally, the electrodes were shown to have a suitable impedance for single-unit neural recording and could record single units .
Characterization of thin film Parylene C device curvature and the formation of helices via thermoforming
In microfabricated biomedical devices, flexible, polymer substrates are becoming increasingly preferred over rigid, silicon substrates because of their ability to conform to biological tissue. Such devices, however, are fabricated in a planar configuration, which results in planar devices that do not closely match the shape of most tissues. Thermoforming, a process which can reshape thermoplastic polymers, can be used to transform flat, thin film, polymer devices with patterned metal features into complex three-dimensional (3D) geometries. This process extends the use of planar microfabrication to achieve 3D shapes which can more closely interface with the body. Common shapes include spheres, which can conform to the shape of the retina; cones, which can be used as a sheath to interface with an insertion stylet; and helices, which can be wrapped around nerves, blood vessels, muscle fibers, or be used as strain relief feature. This work characterizes the curvature of thin film Parylene C devices with patterned metal features built with varying Parylene thicknesses and processing conditions. Device curvature is caused by film stress in each Parylene and metal layer, which is characterized experimentally and by a mathematical model which estimates the effects of device geometry and processing on curvature. Using this characterization, an optimized process to thermoform thin film Parylene C devices with patterned metal features into 0.25 mm diameter helices while preventing cracking in the polymer and metal was developed.
MEMS piezoelectric resonant microphone array for lung sound classification
This paper reports a highly sensitive piezoelectric microelectromechanical systems (MEMS) resonant microphone array (RMA) for detection and classification of wheezing in lung sounds. The RMA is composed of eight width-stepped cantilever resonant microphones with Mel-distributed resonance frequencies from 230 to 630 Hz, the main frequency range of wheezing. At the resonance frequencies, the unamplified sensitivities of the microphones in the RMA are between 86 and 265 mV Pa, while the signal-to-noise ratios (SNRs) for 1 Pa sound pressure are between 86.6 and 98.0 dBA. Over 200-650 Hz, the unamplified sensitivities are between 35 and 265 mV Pa, while the SNRs are between 79 and 98 dBA. Wheezing feature in lung sounds recorded by the RMA is more distinguishable than that recorded by a reference microphone with traditional flat sensitivity, and thus, the automatic classification accuracy of wheezing is higher with the lung sounds recorded by the RMA than with those by the reference microphone, when tested with deep learning algorithms on computer or with simple machine learning algorithms on low-power wireless chip set for wearable applications.
Regulatory Effects of Gradient Microtopographies on Synapse Formation and Neurite Growth in Hippocampal Neurons
Among approaches aiming toward functional nervous system restoration, those implementing microfabrication techniques allow the manufacture of platforms with distinct geometry where neurons can develop and be guided to form patterned connections in vitro. The interplay between neuronal development and the microenvironment, shaped by the physical limitations, remains largely unknown. Therefore, it is crucial to have an efficient way to quantify neuronal morphological changes induced by physical or contact guidance of the microenvironment. In this study, we first devise and assess a method to prepare anisotropic, gradient poly(dimethylsiloxane) micro-ridge/groove arrays featuring variable local pattern width. We then demonstrate the ability of this single substrate to simultaneously profile the morphologcial and synaptic connectivity changes of primary cultured hippocampal neurons reacting to variable physical conditons, throughout neurodevelopment, in vitro. The gradient microtopography enhanced adhesion within microgrooves, increasing soma density with decreasing pattern width. Decreasing pattern width also reduced dendritic arborization and increased preferential axon growth. Finally, decreasing pattern geometry inhibited presynaptic puncta architecture. Collectively, a method to examine structural development and connectivity in response to physical stimuli is established, and potentially provides insight into microfabricated geometries which promote neural regeneration and repair.
Use of liquid lithography to form intestinal crypts with varying microcurvature surrounding the stem cell niche
The role of the crypt microarchitecture and surrounding tissue curvature on intestinal stem/proliferative cell physiology is unknown. The utility of liquid lithography in creating polydimethylsiloxane (PDMS) micropillar stamps with controlled tip curvature was assessed. Using these stamps, the impact of microcurvature at the crypt base on intestinal cell and cytoskeletal behavior was studied.
Irreversible, Self-Aligned Microfluidic Packaging for Chronic Implant Applications
Packaging is an often overlooked component in microfluidic devices for biomedical implant applications. Robust and reliable connectors to interface microscale and macroscale features are especially critical for chronic implant applications. Existing microfluidic packaging methods are incompatible with emerging polymeric materials designed to enhance device integration with the surrounding tissue. A microfluidic connector scheme was developed to promote compatibility with novel materials and implant applications. The connectors and an adhesive wax were printed on a scaffold via additive manufacturing processes. The low-temperature packaging process entailed bonding the connector to a polymer nanocomposite-based intracortical microfluidic probe using an adhesive wax. The robustness of the packaging was assessed by measuring the tensile and shear bond strengths of the connector-adhesive wax-polymer film interface. After soak testing for 4 weeks, the bond strength continued to exceed the force required to infuse fluids through the microfluidic channel. Further, the shear bond strength exceeded typical probe insertion forces by at least 10-fold. These results support the use of the connector and thermal bonding method as a viable option for chronic implant applications.
Bonding methods for chip integration with Parylene devices
Flexible electronics require more compact interconnects for next-generation devices. Polymer devices can be bonded to integrated circuit chips, but combining flexible and rigid substrates poses unique technical challenges. Existing technologies either cannot achieve the density required for modern chips or employ specialized equipment and complex processes to do so. Here, we adapt several approaches to achieve fine-pitch bonding between rigid and flexible substrates including epoxy, ultrasonic wire, and anisotropic conductive film bonding and also introduce a novel technique called polymer ultrasonic on bump (PUB) bonding. Using Parylene C devices and various rigid substrates as our model testbed systems, we investigate these four methods across a range of bond pad size and pitch by measuring yield and resistance and by subjecting devices to thermomechanical reliability tests. We demonstrate that all methods are capable of bonding fine pitch interconnects (100 m) at low temperature (<100 °C). Additionally, we focus on PUB bonding and join a packaged chip and a bare die to Parylene devices.
Hybrid Electrical and Optical Neural Interfaces
Neural interfaces bridge the nervous system and the outside world by recording and stimulating neurons. Combining electrical and optical modalities in a single, hybrid neural interface system could lead to complementary and powerful new ways to explore the brain. It has gained robust and exciting momentum recently in neuroscience and neural engineering research. Here, we review developments in the past several years aiming to achieve such hybrid electrical and optical microsystem platforms. Specifically, we cover three major categories of technological advances: transparent neuroelectrodes, optical neural fibers with electrodes, and neural probes/grids integrating electrodes and microscale light-emitting diodes. We discuss examples of these probes tailored to combine electrophysiological recording with optical imaging or optical neural stimulation of the brain and possible directions of future innovation.
Microfluidic fabrication of stable collagen microgels with aligned microstructure using flow-driven co-deposition and ionic gelation
The controlled biofabrication of stable, aligned collagen hydrogels within microfluidic devices is critically important to the design of more physiologically accurate, longer-cultured on-chip models of tissue and organs. To address this goal, collagen-alginate microgels were formed in a microfluidic channel by calcium crosslinking of a flowing collagen-alginate solution through a cross-channel chitosan membrane spanning a pore allowing ion diffusion but not convection. The gels formed within seconds as isolated islands in a single channel, and their growth was self-limiting. Total gel thickness was controlled by altering the concentration of calcium and collagen-alginate flow rate to reach an equilibrium of calcium diffusion and solution convection at the gel boundary, for a desired thickness of 30-200 m. Additionally, less calcium and higher flow produced greater compression of the gel, with regions farther from the pore compressing more. An aligned, stable collagen network was demonstrated by collagen birefringence, circumferential texture orientation, and little change in gel dimensions with de-chelation of calcium from alginate by prolonged flow of EDTA in the channel. Resultant gels were most stable and only slightly asymmetric when formed from solutions containing 8 mg ml collagen. Diffusion of 4 kDa and 70 kDa fluorescently-labeled dextran indicated size-dependent diffusion across the gel, and accessibility of the construct to appropriately-sized bioactive molecules. This work demonstrates the physicochemical parameter control of collagen gel formation in microfluidic devices, with utility toward on-chip models of dense extracellular matrix invasion, cancer growth and drug delivery to cells within dense extracellular matrix bodies.
Analysis of mechanical deformation effect on the voltage generation of a vertical contact mode triboelectric generator
One of the associated factors that controls the performance of a triboelectric generator (TEG) is the mechanical deformation of the dielectric layer. Therefore, a good contact model can be a prominent tool to find a more realistic and efficient way of determining the relationships between the contact and electrical output of the generator. In this study, experiments are conducted on a vertical contact mode triboelectric generator under an MTS machine. The open-circuit voltages are measured at different loads imposed by the MTS by controlling the cyclic displacement of the top tribo layer of the generator. A finite-element-based theoretical model is developed to explain the behavior of the generator during the experiments. The 2D-contact problem of the micro-structured tribo layers is simulated and then the contact results are integrated into 3D to find the actual contact area between the two surfaces. These numerical contact results improve the existing theoretical model by evaluating the correct surface charge density and contact area as a function of the input parameters. The excellent agreement between our experimental and theoretical results illustrates that theoretical modeling could be used as a robust approach to predict the mechanical and electrical performance of TEGs. In addition, some parametric studies of the harvester are presented here for different geometrical parameters of the microstructures.
Extracellular matrix micropatterning technology for whole cell cryogenic electron microscopy studies
Cryogenic electron tomography is the highest resolution tool available for structural analysis of macromolecular organization inside cells. Micropatterning of extracellular matrix (ECM) proteins is an established cell culture technique used to control cell shape. Recent traction force microscopy studies have shown correlation between cell morphology and the regulation of force transmission. However, it remains unknown how cells sustain increased strain energy states and localized stresses at the supramolecular level. Here, we report a technology to enable direct observation of mesoscale organization in epithelial cells under morphological modulation, using a maskless protein photopatterning method (PRIMO) to confine cells to ECM micropatterns on electron microscopy substrates. These micropatterned cell culture substrates can be used in mechanobiology research to correlate changes in nanometer-scale organization at cell-cell and cell-ECM contacts to strain energy states and traction stress distribution in the cell.
Low Temperature CMUT Fabrication Process with Dielectric Lift-off Membrane Support for Improved Reliability
This paper reports an improved CMOS compatible low temperature sacrificial layer fabrication process for Capacitive Micromachined Ultrasonic Transducers (CMUTs). The process adds the fabrication step of silicon oxide evaporation which is followed by a lift-off step to define the membrane support area without a need for an extra mask. This simple addition improves reliability by reducing the electric field between the top and bottom electrodes everywhere except the moving membrane without affecting the vacuum gap thickness. Furthermore, the parasitic capacitance which degrades the CMUT receive performance is reduced. A 1-D CMUT array suitable for Intracardiac Echocardiography (ICE) imaging with 9MHz center frequency is fabricated using this method. Detailed electrical and acoustic testing indicates adequate performance of the devices for ICE in agreement with simulations. Long term output pressure testing with more than 2×10 pulsing cycles and environmental testing demonstrate the efficacy of the approach for improved reliability as compared to devices without the additional membrane support layer.
Acoustic Actuation of Fabricated Artificial Cilia
We present on-chip acoustic actuation of fabricated artificial cilia. Arrays of cilia structures are UV polymerized inside a microfluidic channel using a photocurable polyethylene glycol (PEG) polymer solution and photomasks. During polymerization, cilia structures are attached to a silane treated glass surface inside the microchannel. Then, the cilia structures are actuated using acoustic vibrations at 4.6 kHz generated by piezo transducers. As a demonstration of a practical application, DI water and fluorescein dye solutions are mixed inside a microfluidic channel. Using pulses of acoustic excitations, and locally fabricated cilia structures within a certain region of the microchannel, a waveform of mixing behavior is obtained. This result illustrates one potential application wherein researchers can achieve spatiotemporal control of biological microenvironments in cell stimulation studies. These acoustically actuated, fabricated, cilia structures can be used in many on-chip applications in biological, chemical and engineering studies.
Dynamics of Thin-film Piezoelectric Microactuators with Large Vertical Stroke Subject to Multi-axis Coupling and Fabrication Asymmetries
The high performance and small size of MEMS based scanners has allowed various optical imaging techniques to be realized in a small form factor. Many such devices are resonant scanners, and thus their linear and nonlinear dynamic behaviors have been studied in the past. Thin-film piezoelectric materials, in contrast, provide sufficient energy density to achieve both large static displacements and high-frequency resonance, but large deformation can in turn influence dynamic scanner behavior. This paper reports on the influence of very large stroke translation of a piezoelectric vertical actuator on its resonant behavior, which may not be otherwise explained fully by common causes of resonance shift such as beam stiffening or nonlinear forcing. To examine the change of structural compliance over the course of scanner motion, a model has been developed that includes internal forces from residual stress and the resultant additional multi-axis coupling among actuator leg structures. Like some preceding vertical scanning micro-actuators, the scanner of this work has four legs, with each leg featuring four serially connected thin-film PZT unimorphs that allow the scanner to generate larger than 400μm of vertical displacement at 14V. Using an excitation near one or more resonances, the input voltage can be lowered, and complementary multi-axis rotations can be also generated, but change of the resonant frequencies with scanner height needs to be understood to maximize scanner performance. The presented model well predicts the experimental observation of the decrease of the resonant frequencies of the scanner with the increase of a dc bias voltage. Also, the effects of the magnitude and uniformity of residual stress across the scanner structure on the natural frequencies have been studied.
Acoustofluidic bacteria separation
Bacterial separation from human blood samples can help with the identification of pathogenic bacteria for sepsis diagnosis. In this work, we report an acoustofluidic device for label-free bacterial separation from human blood samples. In particular, we exploit the acoustic radiation force generated from a tilted-angle standing surface acoustic wave (taSSAW) field to separate from human blood cells based on their size difference. Flow cytometry analysis of the separated from red blood cells (RBCs) shows a purity of more than 96%. Moreover, the label-free electrochemical detection of the separated displays reduced non-specific signals due to the removal of blood cells. Our acoustofluidic bacterial separation platform has advantages such as label-free separation, high biocompatibility, flexibility, low cost, miniaturization, automation, and ease of in-line integration. The platform can be incorporated with an on-chip sensor to realize a point-of-care (POC) sepsis diagnostic device.
Rise Time Reduction of Thermal Actuators Operated in Air and Water through Optimized Pre-Shaped Open-Loop Driving
Electrothermal actuators have many advantages compared to other actuators used in Micro-Electro-Mechanical Systems (MEMS). They are simple to design, easy to fabricate and provide large displacements at low voltages. Low voltages enable less stringent passivation requirements for operation in liquid. Despite these advantages, thermal actuation is typically limited to a few kHz bandwidth when using step inputs due to its intrinsic thermal time constant. However, the use of pre-shaped input signals offers a route for reducing the rise time of these actuators by orders of magnitude. We started with an electrothermally actuated cantilever having an initial 10-90% rise time of 85 μs in air and 234 μs in water for a standard open-loop step input. We experimentally characterized the linearity and frequency response of the cantilever when operated in air and water, allowing us to obtain transfer functions for the two cases. We used these transfer functions, along with functions describing desired reduced rise-time system responses, to numerically simulate the required input signals. Using these pre-shaped input signals, we improved the open-loop 10-90% rise time from 85 μs to 3 μs in air and from 234 μs to 5 μs in water, an improvement by a factor of 28 and 47, respectively. Using this simple control strategy for MEMS electrothermal actuators makes them an attractive alternative to other high speed micromechanical actuators such as piezoelectric stacks or electrostatic comb structures which are more complex to design, fabricate, or operate.
MEMS device for applying shear and tension to an epithelium combined with fluorescent live cell imaging
Mechanical forces play important roles in the biological function of cells and tissues. While numerous studies have probed the force response of cells and measured cell-generated forces, they have primarily focused on tensile, but not shear forces. Here, we describe the design, fabrication, and application of a silicon micromachined device that is capable of independently applying and sensing both tensile and shear forces in an epithelial cell monolayer. We integrated the device with an upright microscope to enable live cell brightfield and fluorescent imaging of cells over many hours following mechanical perturbation. Using devices of increasing stiffness and the same displacement input, we demonstrate that epithelia exhibit concomitant higher maximum resistive tensile forces and quicker force relaxation. In addition, we characterized the force response of the epithelium to cyclic shear loading. While the maximum resistive forces of epithelia under cyclic shear perturbation remained unchanged between cycles, cyclic loading led to faster relaxation of the resistive forces. The device presented here can be applied to studying the force response of other monolayer-forming cell types and is compatible with pharmacological perturbation of cell structures and functions.
Elastic-plastic properties of mesoscale electrodeposited LIGA nickel alloy films: microscopy and mechanics
The elastic-plastic properties of mesoscale electrodeposited LIGA Ni alloy specimens are investigated as a function of specimen size, strain rate, and material composition. Two material compositions are studied: a high-strength fine-grained Ni-Fe alloy and a high-ductility coarse-grained Ni-Co alloy. The specimens have thicknesses of approximately 200 m and gauge widths ranging from 75 m to 700 m. Tensile tests are conducted at strain rates of 0.001/s and 1/s using tabletop loading apparatuses and digital image correlation (DIC) for strain measurement. For each test condition, the apparent Young's modulus, yield strength, ultimate tensile strength, and strain hardening exponent and strength coefficient are extracted from the tensile tests. The true strains to failure are also assessed from fractography. Size, rate, and composition effects are discussed. For most properties, the statistical scatter represented by the standard deviation exceeds the measurement uncertainty; the notable exceptions to these observations are the apparent Young's modulus and yield strength, where large measurement uncertainties are ascribed to common experimental factors and material microplasticity.
Metrology and characterization of SU-8 microstructures using autofluorescence emission
Sophisticated three-dimensional microstructures fabricated using the negative tone SU-8 photoresist are used in many biomedical and microfluidic applications. Scanning electron microscopy (SEM) and profilometry are commonly used metrological techniques for the dimensional characterization of fabricated SU-8 microstructures but are not viable for non-destructive measurements and characterization of subsurface features like hidden microchannels. In this study, we report a unique methodology for the non-destructive dimensional characterization of SU-8 microstructures using the emitted autofluorescence radiation from fabricated SU-8 microstructures to generate depth profiles. The relationship between autofluorescence emission intensities and the thicknesses of the microstructures measured using SEM was determined and used to characterize the dimensions of unknown SU-8 microstructures based on their autofluorescence intensities. Lateral dimensions were also measured. This relationship was used to create highly accurate depth profiles for different types of microstructures including hidden subsurface features. These results were validated by comparison with SEM. The results suggest a feasible and accurate non-destructive, low cost, metrological technique to characterize SU-8 surface and subsurface microstructures using autofluorescence emission intensities.