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Objective Laparoscopic renal denervation (LRDN) ablates sympathetic nerves on the outer wall of a renal artery to treat autonomic nervous system disorders such as hypertension and arrhythmia. Here, we developed a new circular radio frequency (RF) electrode for LRDN using micro-electro-mechanical systems (MEMS) technology. Methods The electrode consists of a parallel bipolar MEMS electrode, two MEMS thermocouples, and a shape-memory alloy (SMA) substrate. The electrode is automatically wrapped and unwrapped under actuation controlled by the heat generated by RF energy on the electrodetissue interface. The electrode was designed through a computational simulation analysis, and its actuation and temperature-sensing performance were tested in laboratory experiments and a porcine animal study. Results In an in-vivo study of porcine renal arteries, the electrode could automatically wrap and unwrap around an artery during LRDN. The bipolar MEMS electrode required 13 Vrms for heat generation up to 60 C, while the two MEMS thermocouples reliably measured the temperature without noise signals (a temperature coefficient of 38.3 or 38.5 V/C and an accuracy of 0.44 or 0.49 C). As revealed in a histological analysis using hematoxylin and eosin staining and Massons trichrome staining, the renal artery was intact after LRDN. Conclusion The circular RF electrode improves the safety of LRDN by reliably measuring the electrode temperature of the electrode during RDN and enhances the effectiveness of LRDN by reducing the complicated manipulations of the surgical instrument. Significance The developed circular RF electrode will pave the way for LRDN treatment of autonomic nervous system disorders.

Energy autonomy and conformability are essential elements in the next generation of wearable and flexible electronics for healthcare, robotics and cyber-physical systems. This study presents ferroelectric polymer transducers and organic diodes for imperceptible sensing and energy harvesting systems, which are integrated on ultrathin (1-µm) substrates, thus imparting them with excellent flexibility. Simulations show that the sensitivity of ultraflexible ferroelectric polymer transducers is strongly enhanced by using an ultrathin substrate, which allows the mounting on 3D-shaped objects and the stacking in multiple layers. Indeed, ultraflexible ferroelectric polymer transducers have improved sensitivity to strain and pressure, fast response and excellent mechanical stability, thus forming imperceptible wireless e-health patches for precise pulse and blood pressure monitoring. For harvesting biomechanical energy, the transducers are combined with rectifiers based on ultraflexible organic diodes thus comprising an imperceptible, 2.5-µm thin, energy harvesting device with an excellent peak power density of 3 mW·cm−3., Next-generation energy autonomous biomedical devices must easily conform to human skin, provide accurate health monitoring and allow for scalable manufacturing. Here, the authors report ultraflexible ferroelectric transducers and organic diodes for biomedical sensing and energy harvesting. Ultraflexible ferroelectric transducers based on P(VDF:TrFE) co-polymer with optimised crystalline structure by thermal annealing are utilised as sensors for vital parameters detection and as piezoelectric nanogenerators (PENG). The PENGs were incorporated in an energy harvesting system including OTFT-based rectifying circuits and thin film capacitors on a single ultrathin substrate. Both developments could pave the way towards self-powering, imperceptible e-health systems.

This article reports on the mechanical strength analysis and flow characteristics of square tip and circular tip microneedles by employing highly potent drugs that are given in extremely little quantity (microlitres) using MEMS technology, which proves to be a significant component of micropump in the application of Bio‐MEMS. These microneedles are well suitable for a MEMS‐based micropump in the drug delivery systems. It is an essential part of the micropump through which the drug is released into the patient’s body. The proposed microneedles can withstand a stress of 23 MPa and 20 KPa. An extensive investigation on selection of material for the microneedle is carried out to meet the requirements of the biocompatibility and high yield, as well as tensile strength. As mighty drugs such as vasopressin, atropine and digoxin are administered in large quantities, the microneedle is designed so as to deliver 800 µl of drug, with each microneedle delivering 90 µl. in a 3 3 array. 3 × 3 array releasing 90 µl.

In this study, the authors demonstrate the fabrication, calibration, and testing of a piezoresistive microcantilever‐based sensor for biomedical microelectromechanical system (BioMEMS) application. To use any sensor in BioMEMS application requires surface modification to capture the targeted biomolecules. The surface alteration comprises self‐assembled monolayer (SAM) formation on gold (Au)/chromium (Cr) thin films. So, the Au/Cr coating is essential for most of the BioMEMS applications. The fabricated sensor uses the piezoresistive technique to capture the targeted biomolecules with the SAM/Au/Cr layer on top of the silicon dioxide layer. The stiffness (k) of the cantilever‐based biosensor is a crucial design parameter for the low‐pressure range and also influence the sensitivity of the microelectromechanical system‐based sensor. Based on the calibration data, the average stiffness of the fabricated microcantilever with and without Au/Cr thin film is 141.39 and 70.53 mN/m, respectively, which is well below the maximum preferred range of stiffness for BioMEMS applications. The fabricated sensor is ultra‐sensitive and selective towards Hg(2+) ions in the presence of other heavy metal ions (HMIs) and good enough to achieve a lower limit of detection 0.75 ng/ml (3.73 pM/ml).

Although volatile organic compound samples can be detected by gas nanosensors in adsorption principles, extreme concentrations of target gases imply the excessive adsorption, which would lead to a long recovery time and even a shortened lifetime. Herein, we report the observations of the ionization current sensing behavior on the volatile organic compounds in an ionization gas sensor with silicon-based nanostructures. The micro ionization gas sensor consists of a pair of silicon microneedle array electrodes covered by nanolayer structures and a microdischarge gas gap. The dynamic response behaviors of the sensors to the exposure of ethanol, acetone, and 2-chloroethyl ethyl sulfide have been carefully scrutinized. The sensor exhibits sound performances to the high-concentration volatile organic compounds with a fast-recovery property and could generate effective responses well at 36 V, namely, the safety operation voltages. It could be well understood by the Jesse effect where small proportion of impurities in gases could lead to an intensive increase in the overall ionization probability. Besides, the reproducibility, recovery time, sensitivity, and selectivity properties have been systematically characterized.

Piezoelectric materials, a type of “smart” material that generates electricity while deforming and vice versa, have been used extensively for many important implantable medical devices such as sensors, transducers, and actuators. However, commonly utilized piezoelectric materials are either toxic or nondegradable. Thus, implanted devices employing these materials raise a significant concern in terms of safety issues and often require an invasive removal surgery, which can damage directly interfaced tissues/organs. Here, we present a strategy for materials processing, device assembly, and electronic integration to 1) create biodegradable and biocompatible piezoelectric PLLA [poly(l-lactic acid)] nanofibers with a highly controllable, efficient, and stable piezoelectric performance, and 2) demonstrate device applications of this nanomaterial, including a highly sensitive biodegradable pressure sensor for monitoring vital physiological pressures and a biodegradable ultrasonic transducer for blood–brain barrier opening that can be used to facilitate the delivery of drugs into the brain. These significant applications, which have not been achieved so far by conventional piezoelectric materials and bulk piezoelectric PLLA, demonstrate the PLLA nanofibers as a powerful material platform that offers a profound impact on various medical fields including drug delivery, tissue engineering, and implanted medical devices.

Here we propose a bio‐MEMS device designed to evaluate contractile force and conduction velocity of cell sheets in response to mechanical and electrical stimulation of the cell source as it grows to form a cellular sheet. Moreover, the design allows for the incorporation of patient‐specific data and cell sources. An optimized device would allow cell sheets to be cultured, characterized, and conditioned to be compatible with a specific patient's cardiac environment in vitro, before implantation. This design draws upon existing methods in the literature but makes an important advance by combining the mechanical and electrical stimulation into a single system for optimized cell sheet growth. The device has been designed to achieve cellular alignment, electrical stimulation, mechanical stimulation, conduction velocity readout, contraction force readout, and eventually cell sheet release. The platform is a set of comb electrical contacts consisting of three‐dimensional walls made of polydimethylsiloxane and coated with electrically conductive metals on the tops of the walls. Not only do the walls serve as a method for stimulating cells that are attached to the top, but their geometry is tailored such that they are flexible enough to be bent by the cells and used to measure force. The platform can be stretched via a linear actuator setup, allowing for simultaneous electrical and mechanical stimulation that can be derived from patient‐specific clinical data.

We developed a Complementary Metal-Oxide-Semiconductor Bio-Microelectromechanical Systems (CMOS-BioMEMS) based piezoresistive microcantilever sensor for detecting gentamicin, a peritonitis therapeutic small-molecule drug. In recent years, the patient-centric concept has been emphasized. In such a trend, therapeutic drug monitoring (TDM) is especially crucial for patients with peritonitis to avoid adverse reactions from a high concentration of gentamicin in the blood. With the aid of a commercialized semiconductor manufacturing process, the microcantilever sensing platform can serve as a portable, low-cost device and offer real-time detection. With chemical surface modification and capture antibody immobilization, the sensor can detect the small-molecule (2 kDa) gentamicin directly. We also modified the pH value of the buffer solution and applied an external electric field to promote sensor sensitivity. Comparing the change of the signals in a non-electric field of antibody immobilization and a 60-volt electric field of antibody immobilization showed that the average signal response increased 1.8 times. In the detection of gentamicin with different concentrations of 10-200 μg/mL, the limit of detection (LOD) of the sensor was 9.44 µg/mL. Finally, the detecting result of a microrcantilever sensor was compared with the one measured by a common instrument in hospital, and the high correlation was expressed between them in gentamicin detection. The CMOS-BioMEMS-based piezoresistive microcantilever sensor has been demonstrated to have great potential as a point-of-care (POC) device for real-time drug concentration monitoring.

CMOS–MEMS microresonators have become excellent candidates for developing portable chemical VOC sensing systems thanks to their extremely large mass sensitivity, extraordinary miniaturization capabilities, and on-chip integration with CMOS circuitry to operate as a self-sustained oscillator. This paper presents two 4-anchored MEMS plate resonators, with a resonance frequency of 2.2 MHz and 380 kHz, fabricated together with the required circuitry using a commercial 0.35 μm CMOS technology and then coated with poly-4-vinylheduorocumyl alcohol (P4V) via inkjet deposition. Such P4V constitutes a functionalization layer for specific acetone detection as a key step in the development of an integrated device for non-invasive diabetes diagnosis through exhaled human breath. The coated sensor system has been proven to increase the acetone injection response by 6-times compared to the uncoated platform and shows a cross-sensitivity to butane of 1 : 11. Experimental data show an acetone sensitivity of −0.012 ppm Hz−1 in the best case that, together with a measured frequency Allan deviation of 0.32 ppm, provides an expected limit of detection as low as 20 ppb of acetone. Additionally, this work presents an alternative resonator design with folded flexure anchors that provide a drastic reduction of the sensor temperature sensitivity and mitigate the impact of a fluid flow inherent to the calibration system.

An electrothermal piezoresistive cantilever (EPC) sensor is a low-cost MEMS resonance sensor that provides self-actuating and self-sensing capabilities. In the platform, which is of MEMS-cantilever shape, the EPC sensor offers several advantages in terms of physical, chemical, and biological sensing, e.g., high sensitivity, low cost, simple procedure, and quick response. However, a crosstalk effect is generated by the coupling of parasitic elements from the actuation part to the sensing part. This study presents a parasitic feedthrough subtraction (PFS) method to mitigate a crosstalk effect in an electrothermal piezoresistive cantilever (EPC) resonance sensor. The PFS method is employed to identify a resonance phase that is, furthermore, deployed to a phase-locked loop (PLL)-based system to track and lock the resonance frequency of the EPC sensor under cigarette smoke exposure. The performance of the EPC sensor is further evaluated and compared to an AFM-microcantilever sensor and a commercial particle counter (DC1100-PRO). The particle mass–concentration measurement result generated from cigarette-smoke puffs shows a good agreement between these three detectors.

In this paper, small-sized acoustic horns, the sensitivity enhancement package for the MEMS-based thermal acoustic particle velocity sensor, have been designed and optimized. Four kinds of acoustic horns, including tube horn, double cone horn, double paradox horn, and exponential horn, were analyzed through numerical calculation. Considering both the amplification factor and effective length of amplification zone, a small-sized double cone horn with middle tube is designed and further optimized. A three-wire thermal acoustic particle velocity sensor was fabricated and packaged in the 3D printed double cone tube (DCT) horn. Experiment results show that an amplification factor of 6.63 at 600 Hz and 6.93 at 1 kHz was achieved. A good 8-shape directivity pattern was also obtained for the optimized DCT horn with the lateral inhibition ratio of 50.3 dB. No additional noise was introduced, demonstrating the DCT horn’s potential in improving the sensitivity of acoustic particle velocity sensors.

From ultrasensitive detectors of fundamental forces to quantum networks and sensors, mechanical resonators are enabling next-generation technologies to operate in room-temperature environments. Currently, silicon nitride nanoresonators stand as a leading microchip platform in these advances by allowing for mechanical resonators whose motion is remarkably isolated from ambient thermal noise. However, to date, human intuition has remained the driving force behind design processes. Here, inspired by nature and guided by machine learning, a spiderweb nanomechanical resonator is developed that exhibits vibration modes, which are isolated from ambient thermal environments via a novel “torsional soft-clamping” mechanism discovered by the data-driven optimization algorithm. This bioinspired resonator is then fabricated, experimentally confirming a new paradigm in mechanics with quality factors above 1 billion in room-temperature environments. In contrast to other state-of-the-art resonators, this milestone is achieved with a compact design that does not require sub-micrometer lithographic features or complex phononic bandgaps, making it significantly easier and cheaper to manufacture at large scales. These results demonstrate the ability of machine learning to work in tandem with human intuition to augment creative possibilities and uncover new strategies in computing and nanotechnology.

One of the most effective treatments for type 1 and 2 diabetes is the administration of Insulin. Single needle mechanical insulin pumps are heavy and painful. Microneedle-based MEMS drug delivery devices can be an excellent solution for insulin dosing. The stackable structure provides minimum dimensions and the final product can be in the form of a patch that can be applied to any flat area of human skin. The use of microneedle array provides a safe, painless, and robust injection application. The design of positive volumetric insulin pump is a Multiphysics problem where the volumetric changes of the main pump chamber and the pumped fluid are directly coupled. We use a Multiphysics simulation system to investigate the performance of a MEMS-based insulin micropump with a piezoelectric actuator pumping a viscous Newtonian fluid. The model captures the accumulated out-flow, the netflow, or flow fluctuations based on deflection of piezoelectric diaphragm actuator. Different input voltages and different excitation frequencies cause movement of piezoelectric actuator, which moves the diaphragm disk in positive–negative directions thereby inducing discharge pressures at the microneedle array. In this study, we address various aspects of design and simulation of a MEMS-based piezoelectric insulin micropump including polydimethylsiloxane microvalves and microneedle array. We investigate the micropump performance at human skin interfacial pressure to match minimum to maximum delivery targets/requirements for total range of diabetic patient's expected operating parameters. comsolmultiphysics is used for this study.

Implantable medical devices, such as cardiac pacemakers and defibrillators, rely on batteries for operation. However, conventional batteries only last for a few years, and additional surgeries are needed for replacement. Harvesting energy directly from the human body enables a new paradigm of self-sustainable power sources for implantable medical devices without being constrained by the battery's limited lifetime. Here, we report the design of a multibeam cardiac energy harvester using polydimethylsiloxane (PDMS)-infilled microporous P(VDF-TrFE) composite films. We first added ZnO nanoparticles and multiwall carbon nanotubes into microporous P(VDF-TrFE) films to increase the energy output. The mixing ratios of 30% ZnO and 0.1% MWCNTs yielded 3.22 ± 0.24 V output, which resulted in a voltage output 46 times higher than that of pure P(VDF-TrFE) films. Next, we discovered that the voltage generated by the composite film with PDMS is approximately 105% higher than that of the one without PDMS. For the application in cardiac pacemakers, we developed a facile fabrication method by building a cylindrical multibeam device that resides on the pacemaker lead to harvest energy from the complex motion of the lead driven by the heartbeat. Since the energy harvesting component is integrated into the pacemaker, it significantly reduces the risks and expenses associated with pacemaker-related surgeries. This work paves the way toward the new generation of energy harvesters that will benefit patients with a variety of implantable biomedical devices.

As scientific and technical knowledge advances, research on biomedical micro-electromechanical systems (bio-MEMS) is also developing towards lab-on-a-chip (LOC) devices. A digital microfluidic (DMF) system specialized for an electrowetting- on-dielectric (EWOD) mechanism is a promising technique for such point-of-care systems. EWOD microfluidic biochemical analytical systems provide applications over a broad range in the lab-on-a-chip field. In this report, we treated extraction of cell-free DNA (cf-DNA) at a small concentration from a mouse embryo culture medium (2.5 days & 3.5 days) with electro-wetting on a dielectric (EWOD) platform using bio-reagents of micro-scale quantity. For such extraction, we modified a conventional method of genomic-DNA (g-DNA) extraction using magnetic beads (MB). To prove that extraction of cf-DNA with EWOD was accomplished, as trials we extracted designed-DNA (obtained from Chang Gung Memorial Hospital (CGMH), Taiwan which shows properties similar to that of cf-DNA). Using that designed DNA, extraction with both conventional and EWOD methods has been performed; the mean percentage of extraction with both methods was calculated for a comparison. From the cycle threshold (Ct) results with a quantitative polymerase chain reaction (q-PCR), the mean extraction percentages were obtained as 14.8 percent according to the conventional method and 23 percent with EWOD. These results show that DNA extraction with EWOD appears promising. The EWOD extraction involved voltage 100 V and frequency 2 kHz. From this analysis, we generated a protocol for an improved extraction percentage on a EWOD chip and performed cf-DNA extraction from an embryo-culture medium (KSOM medium) at 3.5 and 2.5 days. The mean weight obtained for EWOD-extracted cf-DNA is 0.33 fg from the 3.5-day sample and 31.95 fg from the 2.5-day sample. All these results will pave a new path towards a renowned lab-on-a-chip concept.

In the last few years, there have been an increasing number of reports where different energy harvesters are directly combined with charge storing devices, based on dual-function electrodes able to convert and store electrical energy in the same volume. This includes (bio)fuel cells harvesting chemical energy, (bio)solar cells harvesting solar energy, tribo- and piezoelectric devices harvesting mechanical energy, and thermoelectrics harvesting thermal energy, which now have been intimately combined with batteries and electrochemical capacitors. These new types of hybrid electric devices show great promise especially for the design of self-powered electronics where an integrated hybrid power system is preferable to separated ones, capable of scavenging ambient energy and simultaneously store it and in this way increasing the efficiency and enabling further miniaturization. This paper details the recent emergence of hybrid energy systems, reviewing the progress made using widely different energy harvesting techniques, which have so-far not been described in a single body of work.

We demonstrated an optical interferometer-based surface-stress immunosensor using freestanding polymethyl methacrylate (PMMA)/parylene-C nanosheet with high sensitivity for detection of biomolecules. PMMA/parylene-C nanosheets were transferred onto a silicon substrate with microcavities to fabricate freestanding submicron-thick membrane with a sealed cavity structure. The adhesive force between the transferred parylene-C and binder parylene-C layer was measured to be 1.06–2.4 N/10 mm by tape test. Evading Debye shielding, these nanomechanical sensors allow detection of the adsorption on the membrane surface through changes in surface stress transduced by the electric charge. We optimized the density of receptors and mode of immobilization for high sensitivity. To evaluate the selectivity of the sensor, membrane deflections induced by various proteins were measured and the spectral shifts showed high selectivity only for the target antigen. The minimum limit of detection (LOD) of the sensor for human serum albumin antigen was 0.1–1 fg/mL (1.5–15 aM), which was 20,000 times lower than that of the conventional micro-cantilever sensor.

Thermal methods are indispensable for the characterization of most materials. However, the existing methods require bulk amounts for analysis and give an averaged response of a material. This can be especially challenging in a biomedical setting, where only very limited amounts of material are initially available. Nano- and microelectromechanical systems (NEMS/MEMS) offer the possibility of conducting thermal analysis on small amounts of materials in the nano-microgram range, but cleanroom fabricated resonators are required. Here, we report the use of single drug and collagen particles as micro mechanical resonators, thereby eliminating the need for cleanroom fabrication. Furthermore, the proposed method reveals additional thermal transitions that are undetected by standard thermal methods and provide the possibility of understanding fundamental changes in the mechanical properties of the materials during thermal cycling. This method is applicable to a variety of different materials and opens the door to fundamental mechanistic insights., Eliminating the need for cleanroom fabrication for thermomechanical characterization of organic samples in a biomedical setting remains a challenge. Here, the authors propose the use of a single drug and collagen particles as resonators, enabling direct measurements on a material during thermal cycling.

The present work attempts to enhance the sensitivity of a folded beam microelectromechanical systems (MEMS) capacitive accelerometer by optimising the device geometry. The accelerometer is intended to serve as a microphone in the fully implantable hearing application which can be surgically implanted in the middle ear bone structure. For the efficient design of the accelerometer as a fully implantable biomedical device, the design parameters such as size, weight and resonant frequency have been considered. The geometrical parameters are varied to obtain the optimum sensitivity considering the design constraints and the stability of the structure. The optimised design is simulated and verified using COMSOL MULTIPHYSICS 4.2. The stability of the device is ensured using eigenfrequency analysis. Optimised results of the device geometry are presented and discussed. The accelerometer has a sensing area of 1 mm2 and attains a nominal capacitance of 5.3 pF and an optimum sensitivity of 6.89 fF.

Purpose To evaluate the performance of micro‐electromechanical systems (MEMS) switches against PIN diodes for switching a dual‐tuned RF coil between 19F and 1H resonant frequencies for multi‐nuclear lung imaging. Methods A four‐element fixed‐phase and amplitude transmit–receive RF coil was constructed to provide homogeneous excitation across the lungs, and to serve as a test system for various switching methods. The MR imaging and RF performance of the coil when switched between the 19F and 1H frequencies using MEMS switches, PIN diodes and hardwired configurations were compared. Results The performance of the coil with MEMS or PIN diode switching was comparable in terms of RF measurements, transmit efficiency and image SNR on both 19F and 1H nuclei. When the coil was not switched to the resonance frequency of the respective nucleus being imaged, reductions in the transmit efficiency were observed of 32% at the 19F frequency and 12% at the 1H frequency. The coil provides transmit field homogeneity of ±12.9% at the 1H frequency and ±14.4% at the 19F frequency in phantoms representing the thorax with the air space of the lungs filled with perfluoropropane gas. Conclusion MEMS and PIN diodes were found to provide comparable performance in on‐state configuration, while MEMS were more robust in off‐state high‐powered operation (>1 kW), providing higher isolation and requiring a lower DC switching voltage than is needed for reverse biasing of PIN diodes. In addition, clear benefits of switching between the 19F and 1H resonances were demonstrated, despite the proximity of their Larmor frequencies.

Finite Element Modeling of the peculiarities of the trapping energy phenomenon in application to the piezoelectric layered structure (PLS) “Al/(0 0 1) AlN/Mo/(1 0 0) diamond” has been fulfilled. The resonant properties of longitudinal bulk acoustic waves (BAW) as well as frequency dependence of impedance within the 1 – 6 GHz band have been studied. The investigation of distribution of elastic energy flow and elastic displacements in a PLS cross-section allowed us to obtain an important information on energy trapping (ET) in PLS. Experimentally and as a result of modeling, it has been found that Q minimums are observed in PLS at quarter-wave resonance in the thin-film piezoelectric transducer (TFPT). Maximal Q value was observed at half-wave resonance in TFPT. It has been established that the ET-effect depends considerably on the mutual location of the n-th overtone’s antiresonant frequency fa,n and cut-off frequencies of substrate fs,n−k−1 and fs,n−k where fs,n−k−1 fs,n−k, when the BAW energy excites the symmetrical or antisymmetrical Lamb waves.

Goal: This research aims to validate a new biomarker of breast cancer by introducing electromechanical coupling factor of breast tissue samples as a possible additional indicator of breast cancer. Since collagen fibril exhibits a structural organization that gives rise to a piezoelectric effect, the difference in collagen density between normal and cancerous tissue can be captured by identifying the corresponding electromechanical coupling factor. Methods: The design of a portable diagnostic tool and a microelectromechanical systems (MEMS)-based biochip, which is integrated with a piezoresistive sensing layer for measuring the reaction force as well as a microheater for temperature control, is introduced. To verify that electromechanical coupling factor can be used as a biomarker for breast cancer, the piezoelectric model for breast tissue is described with preliminary experimental results on five sets of normal and invasive ductal carcinoma (IDC) samples in the 25–45 $^{\circ }{\text C}$ temperature range. Conclusion: While the stiffness of breast tissues can be captured as a representative mechanical signature which allows one to discriminate among tissue types especially in the higher strain region, the electromechanical coupling factor shows more distinct differences between the normal and IDC groups over the entire strain region than the mechanical signature. From the two-sample $t$ -test, the electromechanical coupling factor under compression shows statistically significant differences ( $p\leq$ 0.0039) between the two groups. Significance: The increase in collagen density in breast tissue is an objective and reproducible characteristic of breast cancer. Although characterization of mechanical tissue property has been shown to be useful for differentiating cancerous tissue from normal tissue, using a single parameter may not be sufficient for practical usage due to inherent variation among biological samples. The portable breast cancer diagnostic tool reported in this manuscript shows the feasibility of measuring multiple parameters of breast tissue allowing for practical application.

Three-dimensional (3D) printing now enables the fabrication of novel 3D structural electronics and microfluidics. However, conventional subtractive manufacturing processes for MEMS fabrication relatively limit device structure to two dimensions and require post-processing steps for interface with microfluidics. Thus, the objective of this work is to create an additive manufacturing approach for fabrication of 3D microfluidic-based MEMS devices that enables 3D configurations of electromechanical systems and simultaneous integration of microfluidics in a one-pot manufacturing process. Here, we demonstrate the ability to fabricate microfluidic-based 3D microelectromechanical systems (MEMS) that contain orthogonal out-of-plane piezoelectric sensors and actuators using additive manufacturing. The devices were fabricated using a microextrusion 3D printing system that contained integrated pick-and-place functionality. Additively assembled materials and components included 3D printed epoxy, polydimethylsiloxane (PDMS), silver nanoparticles, and eutectic Gallium-Indium as well as robotically embedded orthogonal out-of-plane piezoelectric chips (lead zirconate titanate (PZT)). Electrical impedance spectroscopy and finite element modeling studies showed the embedded PZT chips exhibited multiple resonant modes of varying mode shape over the 0 – 20 MHz frequency range. Flow visualization studies using neutrally buoyant particles (diameter = 0.8 – 70 μm) confirmed the 3D printed MEMS devices generate bulk acoustic waves (BAWs) capable of size-selective manipulation, trapping, and separation of suspended particles in droplets and microchannels. Flow visualization studies in continuous flow format showed suspended particles could be moved toward or away from the walls of microfluidic channels based on selective actuation of in-plane or out-of-plane PZT chips. This work suggests additive manufacturing potentially provides new opportunities for the design and fabrication of acoustofluidic and microfluidic devices.

Introduction An electromechanical device was used to experimentally characterize the movement of a single tooth within the periodontal ligament space. The force magnitude leading to the complete compression of the periodontal ligament is considered a critical force and is designated Fc. We investigated the effectiveness of the electromechanical device to repeatedly determine the critical force magnitude Fc. Methods The study comprised 12 tests conducted on 11 subjects. Alternating labial and lingual forces were applied to a maxillary incisor by the device. The resulting immediate intra-alveolar tooth displacement was recorded in real time. Data processing was used to determine the tooth mobility curve for 193 push-pull cycles. The critical force Fc was mathematically determined for both the labial and lingual displacements of the tooth. Results The tooth mobility curve could be characterized for all 12 tests. A total of 386 values of Fc were calculated for the 12 different teeth. Values of Fc for each test ranged from 10.47 to 20.18 g in the lingual direction, and from 12.56 to 21.72 g in the labial direction. Conclusions The electromechanical appliance was successful in repeatedly determining Fc in vivo. The ability to experimentally determine the extent of periodontal ligament compression at a given force magnitude could shed new light on the question of an optimal orthodontic force and open new avenues of orthodontic research and treatment.

Soft actuators with complex range of motion lead to strong interest in applying devices like biomedical catheters and steerable soft pipe inspectors. To facilitate the use of soft actuators in devices where controlled, complex, precise, and fast motion is required, a structurally controlled Omni directional soft cylindrical actuator is fabricated in a modular way using multilayer composite of polylactic acid based conductive Graphene, shape memory polymer, shape memory alloy, and polyurethane. Multiple fabrication techniques are discussed step by step that mainly include fused deposition modeling based 3D printing, dip coating, and UV curing. A mathematical control model is used to generate patterned electrical signals for the Omni directional deformations. Characterizations like structural control, bending, recovery, path, and thermal effect are carried out with and without load (10 g) to verify the new cylindrical design concept. Finally, the application of Omni directional actuator as a steerable catheter is explored by fabricating a scaled version of carotid artery through 3D printing using a semitransparent material.

Noninvasive measurement of tissue viscoelastic properties is gaining more attention for screening and diagnostic purposes. Recently, measuring dynamic response of tissue under a constant force has been studied for estimation of tissue viscoelastic properties in terms of retardation times. The essential part of such a test is an instrument that is capable of creating a controlled axial force and is suitable for clinical applications. Such a device should be lightweight, portable, and easy to use for patient studies to capture tissue dynamics under external stress. In this paper, we present the design of an automated compression device for studying the creep response of materials with tissue-like behaviors. The device can be used to apply a ramp-and-hold force excitation for a predetermined duration of time and it houses an ultrasound probe for monitoring the creep response of the underlying tissue. To validate the performance of the device, several creep tests were performed on tissue-mimicking phantoms, and the results were compared against those from a commercial mechanical testing instrument. Using a second-order Kelvin–Voigt model and surface measurement of the forces and displacements, retardation times ${\boldsymbol{T}_1}$ and ${\boldsymbol{T}_2}$ were estimated from each test. These tests showed strong agreement between our automated compression device and the commercial mechanical testing system, with an average relative error of 2.9% and 12.4%, for ${\boldsymbol{T}_1}$ and ${\boldsymbol{T}_2}$ , respectively. Also, we present the application of compression device to measure local retardation times for four different phantoms with different size and stiffness.

Biomechanical tissue properties have been hypothesized to play a critical role in the quantification of prosthetic socket production for individuals with limb amputation. In this investigation, a novel indenter platform is presented and its performance evaluated for the purposes of residual-limb tissue characterization. The indenter comprised 14 position- and force-controllable actuators that circumferentially surround a biological residuum to form an actuator ring. Each indenter actuator was individually controllable in position ( ${{97.1}}~\mu {\text {m}}$ accuracy) and force (330 mN accuracy) at a PC controller feedback rate of 500 Hz, allowing for a range of measurement across a residual stump. Data were collected from 162 sensors over an EtherCAT fieldbus to characterize the mechanical hyperviscoelastic tissue response of two transtibial residual-limbs from a study participant with bilateral amputations. At five distinct anatomical locations across the residual-limb, force versus deflection data—including hyperviscoelastic tissue properties—are presented, demonstrating the accuracy and versatility of the multi-indenter platform for residual-limb tissue characterization.

Monitoring blood coagulation is an important issue in the surgeries and the treatment of cardiovascular diseases. In this work, we reported a novel strategy for the blood coagulation monitoring based on a micro-electromechanical film bulk acoustic resonator. The resonator was excited by a lateral electric field and operated under the shear mode with a frequency of 1.9GHz. According to the apparent step-ladder curves of the frequency response to the change of blood viscoelasticity, the coagulation time (prothrombin time) and the coagulation kinetics were measured with the sample consumption of only 1μl. The procoagulant activity of thromboplastin and the anticoagulant effect of heparin on the blood coagulation process were illustrated exemplarily. The measured prothrombin times showed a good linear correlation with R2=0.99969 and a consistency with the coefficient of variation less than 5% compared with the commercial coagulometer. The proposed film bulk acoustic sensor, which has the advantages of small size, light weight, low cost, simple operation and little sample consumption, is a promising device for miniaturized, online and automated analytical system for routine diagnostics of hemostatic status and personal health monitoring.

Micro Electro Mechanical Systems (MEMS) and microfluidic devices have found numerous applications in the industrial sector. However, they require a fast, cost-effective and reliable manufacturing process in order to compete with conventional methods. Particularly, at the sub-micron scale, the manufacturing of devices are limited by the dimensional complexity. A proper bonding and stiction prevention of these sub-micron channels are two of the main challenges faced during the fabrication process of low aspect ratio channels. Especially, in the case of using flexible materials such as polydimethylsiloxane (PDMS). This study presents a direct laser microfabrication method of sub-micron channels using an infrared (IR) ultrashort pulse (femtosecond), capable of manufacturing extremely low aspect ratio channels. These microchannels are manufactured and tested varying their depth from 0.5 µm to 2 µm and width of 15, 20, 25, and 30 µm. The roughness of each pattern was measured by an interferometric microscope. Additionally, the static contact angle of each depth was studied to evaluate the influence of femtosecond laser fabrication method on the wettability of the glass substrate. PDMS, which is a biocompatible polymer, was used to provide a watertight property to the sub-micron channels and also to assist the assembly of external microfluidic hose connections. A 750 nm depth watertight channel was built using this methodology and successfully used as a blood plasma separator (BPS). The device was able to achieve 100% pure plasma without stiction of the PDMS layer to the sub-micron channel within an adequate time. This method provides a novel manufacturing approach useful for various applications such as point-of-care devices

Overdrainage in upright position is one of the most prevalent issues in treating hydrocephalus with a cerebrospinal fluid (CSF) shunt. Anti-siphon devices (ASDs) are employed to reduce this problem. A novel microelectromechanical system (MEMS)-based valve, termed Chronoflow device, aims to regulate CSF drainage indifferently of the body posture. With this study, the suitability of this MEMS-based valve is evaluated regarding its use for the treatment of hydrocephalus, particularly for the prevention of overdrainage and blockage. In total, four Chronoflow devices were tested. An established in-vitro hardware-in-the-loop (HIL) test bed was used to investigate the valves regarding their pressure-flow characteristics, their behaviors towards CSF dynamics, and their capabilities to prevent CSF overdrainage in upright position. Additionally, a contamination test was conducted to evaluate the susceptibility of the device to blockage due to particles. All valves tested regulated the drainage rate at similar nominal flows and independently of posture. The pressure-flow relation measured, however, was notably higher than numerically calculated. Regarding the CSF dynamics, the first three valves tested led to a decreased steady-state intracranial pressure in supine position and showed stable drainage rate in upright position. During the transitional phase from supine to upright and vice versa, the valves continuously adjusted the outflow resistance, which resulted in a stable transitional phase preventing overdrainage. Yet, the fourth valve showed continuous overdrainage in upright position due to an increased nominal flow. However, after several test iterations the nominal flow decreased and stabilized at a level similar to that of the first three valves tested. The contamination test showed that most particles initially adhere to the pillars and spread throughout the cavity of the valve as the concentration of particles increases, thereby affecting the displacement of the membrane. The devices generally provide a stable flow regulation and prevent overdrainage in upright position. Specifically, their drainage behaviors during the posture changes are very effective. However, they also showed high hysteresis and sensitivity towards particle contamination, which resulted in initial increased and altering nominal flows after many test iterations. This result suggests that the MEMS design presented lacks robustness. Yet, an upstream filter and specific coatings on the fluid pathway may increase significantly its reliability.

The sensitivity and response time of glutamate sensors based on glutamate oxidase immobilized on planar platinum microelectrodes have been improved to near the theoretical performance limits predicted by a detailed mathematical model. Microprobes with an array of electroenzymatic sensing sites have emerged as useful tools for the monitoring of glutamate and other neurotransmitters in vivo; and implemented as such, they can be used to study many complex neurological diseases and disorders including Parkinson’s disease and drug addiction. However, less than optimal sensitivity and response time has limited the spatiotemporal resolution of these promising research tools. A mathematical model has guided systematic improvement of an electroenzymatic glutamate microsensor constructed with a 1-2 μm-thick crosslinked glutamate oxidase layer and underlying permselective coating of polyphenylenediamine and Nafion reduced to less than 200 nm thick. These design modifications led to a nearly 6-fold improvement in sensitivity to 320 ± 20 nA μM(−1) cm(−2) at 37 °C and a ~10-fold reduction in response time to 80 ± 10 ms. Importantly, the sensitivity and response times were attained while maintaining a low detection limit and excellent selectivity. Direct measurement of the transport properties of the enzyme and polymer layers used to create the biosensors enabled improvement of the mathematical model as well. Subsequent model simulations indicated that the performance characteristics achieved with the optimized biosensors approach the theoretical limits predicted for devices of this construction. Such high-performance glutamate biosensors will be more effective in vivo at a size closer to cellular dimension and will enable better correlation of glutamate signaling events with electrical recordings.

Conversion of vacuum fluctuations into real particles was first predicted by L. Parker considering an expanding universe, followed in S. Hawking's work on black hole radiation. Since their experimental observation is challenging, analogue systems have gained attention in the verification of this concept. Here we propose an experimental set-up consisting of two adjacent piezoelectric semiconducting layers, one of them carrying dynamic quantum dots (DQDs), and the other being p-doped with an attached gate on top, which introduces a space-dependent layer conductivity. The propagation of surface acoustic waves (SAWs) on the latter layer is governed by a wave equation with an effective metric. In the frame of the DQDs, this space- and time-dependent metric possesses a sonic horizon for SAWs and resembles that of a two dimensional non-rotating and uncharged black hole to some extent. The non-thermal steady state of the DQD spin indicates particle creation in form of piezophonons., 9 pages, 2 figures, reinterpration of results and new conclusion

Detection of thermal activities of biological cells is important for biomedical and pharmaceutical applications because these activities are closely associated with the conformational change processes. Calorimetric measurements of biological systems using bimaterial microcantilevers (BMC) have increasingly been reported with the ultimate goal of developing highly sensitive and inexpensive techniques with real-time measurement capability techniques for the characterization of dynamic thermal properties of biological cells. BMCs have been established as highly sensitive calorimeters for the thermal analysis of cells and liquids. In this paper, we present a simulation model using COMSOL Multiphysics and a mathematical method to estimate the heat capacity of objects (treated here as a biological cell) placed on the surface of a microcantilever. By measuring the thermal time constant, which is obtained from the deflection curve of a BMC, the heat capacity of a sample can be evaluated. With this model, we can estimate the heat capacity of single biological cells using a BMC, which can potentially be used for the thermal characterization of different biological samples.

The continuous measurements of vital signs (body temperature, blood pressure, pulse wave, and respiration rate) are important in many applications across various fields, including healthcare and sports. To realize such measurements, wearable devices that cause minimal discomfort to the wearers are highly desired. Accordingly, a device that can measure multiple vital signs simultaneously using a single sensing element is important in order to reduce the number of devices attached to the wearer&rsquo, s body, thereby reducing user discomfort. Thus, in this study, we propose a device with a microelectromechanical systems (MEMS)-based pressure sensor that can simultaneously measure the blood pulse wave and respiration rate using only one sensing element. In particular, in the proposed device, a thin silicone tube, whose inner pressure can be measured via a piezoresistive cantilever, is attached to the nose pad of a pair of eyeglasses. On wearing the eyeglasses, the tube of sensor device is in contact with the area above the angular artery and nasal cavity of the subject, and thus, both pulse wave and breath of the subject cause the tube&rsquo, s inner pressure to change. We experimentally show that it is possible to extract information related to pulse wave and respiration as the low-frequency and high-frequency components of the sensor signal, respectively.

Photoacoustic microscopy (PAM) can be classified as optical resolution (OR)-PAM and acoustic resolution (AR)-PAM depending on the type of resolution achieved. Using microelectromechanical systems (MEMS) scanner, high-speed OR-PAM system was developed earlier. Depth of imaging limits the use of OR-PAM technology for many preclinical and clinical imaging applications. Here, we demonstrate the use of a high-speed MEMS scanner for AR-PAM imaging. Lateral resolution of 84 μm and an axial resolution of 27 μm with ~2.7 mm imaging depth was achieved using a 50 MHz transducer-based AR-PAM system. Use of a higher frequency transducer at 75 MHz has further improved the resolution characteristics of the system with a reduction in imaging depth and a lateral resolution of 53 μm and an axial resolution of 18 μm with ~1.8 mm imaging depth was achieved. Using the two-axis MEMS scanner a 2 × 2 .5 mm2 area was imaged in 3 seconds. The capability of achieving acoustic resolution images using the MEMS scanner makes it beneficial for the development of high-speed miniaturized systems for deeper tissue imaging.

MEMS-based skin friction sensors are used to measure and validate skin friction and its distribution, and their advantages of small volume, high reliability, and low cost make them very important for vehicle design. Aiming at addressing the accuracy problem of skin friction measurements induced by existing errors of sensor fabrication and assembly, a novel fabrication technology based on visual alignment is presented. Sensor optimization, precise fabrication of key parts, micro-assembly based on visual alignment, prototype fabrication, static calibration and validation in a hypersonic wind tunnel are implemented. The fabrication and assembly precision of the sensor prototypes achieve the desired effect. The results indicate that the sensor prototypes have the characteristics of fast response, good stability and zero-return, the measurement ranges are 0&ndash, 100 Pa, the resolution is 0.1 Pa, the repeatability accuracy and linearity are better than 1%, the repeatability accuracy in laminar flow conditions is better than 2% and it is almost 3% in turbulent flow conditions. The deviations between the measured skin friction coefficients and numerical solutions are almost 10% under turbulent flow conditions, whereas the deviations between the measured skin friction coefficients and the analytical values are large (even more than 100%) under laminar flow conditions. The error resources of direct skin friction measurement and their influence rules are systematically analyzed.

Photoacoustic microscopy (PAM) is a fast-growing biomedical imaging technique that provides high-resolution in vivo imaging beyond the optical diffusion limit. Depending on the scalable lateral resolution and achievable penetration depth, PAM can be classified into optical resolution PAM (OR-PAM) and acoustic resolution PAM (AR-PAM). The use of a microelectromechanical systems (MEMS) scanner has improved OR-PAM imaging speed significantly and is highly beneficial in the development of miniaturized handheld devices. The shallow penetration depth of OR-PAM limits the use of such devices for a wide range of clinical applications. We report the use of a high-speed MEMS scanner for both OR-PAM and AR-PAM. A high-speed, wide-area scanning integrated OR-AR-PAM system combining MEMS scanner and raster mechanical movement was developed. A lateral resolution of 5 μm and penetration depth ∼0.9-mm in vivo was achieved using OR-PAM at 586 nm, whereas a lateral resolution of 84 μm and penetration depth of ∼2-mm in vivo was achieved using AR-PAM at 532 nm.

We present a novel FMT endoscope by using a MEMS scanning mirror and an optical fiberscope. The diameter of this highly miniaturized FMT device is only 5 mm. To our knowledge, this is the smallest FMT device we found so far. Several phantom experiments based on indocyanine green (ICG) were conducted to demonstrate the imaging ability of this device. Two tumor-bearing mice were systematically injected with tumor-targeted NIR fluorescent probes (ATF-PEG-IO-830) and were then imaged to further demonstrate the ability of this FMT endoscope for imaging small animals.

Efficient manipulation of micro biological cells has always been a very important task in healthcare sector for which a Micro Electro Mechanical System (MEMS) based impedance flow cytometry has been proven to be a promising technique. This technique utilise the advantage of dielectrophoresis (DEP) force which is generated by non-uniform electric field in a microfluidic channel using an appropriate external AC supply at certain frequency range. The DEP forces generated in micro-channel depend upon various biological and physical parameters of cell and suspending medium. Apart from that design parameters of microfluidic channel and dimension of electrodes used for generating DEP action also plays major role in micro cell/bead manipulation. This article give remarks on the operating parameters which affects the cell manipulation and interrogates the currently accepted various electrode orientations in microfluidic MEMS flow cytometer technologies for effective manipulation of micro entities like healthy human cells (T-lymphocytes, B- lymphocytes, Monocytes, Leukocytes erythrocytes and human kidney cells HEK293), animal cells (neuroblastoma N115 and sheep red blood cells), cancer cells (MCF-7, MDA-435 and CD34+), yeast cells (saccharomyces cerevisiae, listeria innocua and E. coli) and micro particles (polystyrene beads) based on their dielectric properties using DEP action. Article focuses on the key electrode orientations for generation of non-uniform electric field in microfluidic flow cytometer like tapered electrodes, trapezoidal electrode arrays, Interdigitated electrodes, curved microelectrode and 3D electrode orientations and give remarks on their advantages and limitations. The cell manipulation with current MEMS impedance flow cytometry orientations targeting possibilities of implementation of the lab-on-chip devices has been discussed.

We propose a new packaging process for an implantable blood pressure sensor using ultrafast laser micro-welding. The sensor is a membrane type, passive device that uses the change in the capacitance caused by the membrane deformation due to applied pressure. Components of the sensor such as inductors and capacitors were fabricated on two glass (quartz) wafers and the two wafers were bonded into a single package. Conventional bonding methods such as adhesive bonding, thermal bonding, and anodic bonding require considerable effort and cost. Therefore CO2 laser cutting was used due to its fast and easy operation providing melting and bonding of the interface at the same time. However, a severe heat process leading to a large temperature gradient by rapid heating and quenching at the interface causes microcracks in brittle glass and results in low durability and production yield. In this paper, we introduce an ultrafast laser process for glass bonding because it can optimize the heat accumulation inside the glass by a short pulse width within a few picoseconds and a high pulse repetition rate. As a result, the ultrafast laser welding provides microscale bonding for glass pressure sensor packaging. The packaging process was performed with a minimized welding seam width of 100 &mu, m with a minute. The minimized welding seam allows a drastic reduction of the sensor size, which is a significant benefit for implantable sensors. The fabricated pressure sensor was operated with resonance frequencies corresponding to applied pressures and there was no air leakage through the welded interface. In addition, in vitro cytotoxicity tests with the sensor showed that there was no elution of inner components and the ultrafast laser packaged sensor is non-toxic. The ultrafast laser welding provides a fast and robust glass chip packaging, which has advantages in hermeticity, bio-compatibility, and cost-effectiveness in the manufacturing of compact implantable sensors.

Peptides have attracted considerable attention due to their biocompatibility, functional molecular recognition and unique biological and electronic properties. The strong piezoelectricity in diphenylalanine peptide expands its technological potential as a smart material. However, its random and unswitchable polarization has been the roadblock to fulfilling its potential and hence the demonstration of a piezoelectric device remains lacking. Here we show the control of polarization with an electric field applied during the peptide self-assembly process. Uniform polarization is obtained in two opposite directions with an effective piezoelectric constant d33 reaching 17.9 pm V−1. We demonstrate the power generation with a peptide-based power generator that produces an open-circuit voltage of 1.4 V and a power density of 3.3 nW cm−2. Devices enabled by peptides with controlled piezoelectricity provide a renewable and biocompatible energy source for biomedical applications and open up a portal to the next generation of multi-functional electronics compatible with human tissue., Piezoelectricity in diphenylalanine peptide nanotubes (PNTs) suggests an avenue towards green piezoelectric devices. Here the authors show ‘smart' PNTs whose polarization can be controlled with an electric field, and a resultant power generator which harvests biomechanical energy with high power density.

We have developed a micro electromechanical systems (MEMS) device which enables plasma treatment for cells cultured in media. The device, referred to as the plasma-on-chip, comprises microwells and microplasma sources fabricated together in a single chip. The microwells have through-holes between the microwells and microplasma sources. Each microplasma source is located on the backside of each microwells. The reactive components generated by the microplasma sources pass through the through-holes and reach cells cultured in the microwells. In this study, a plasma-on-chip device was modified for a stable plasma treatment. The use of a dielectric barrier discharge (DBD) technique allowed a stable plasma treatment up to 3 min. The plasma-on-chip with the original electrode configuration typically had the maximum stable operation time of around 1 min. Spectral analysis of the plasma identified reactive species such as O and OH radicals that can affect the activity of cells. Plasma treatment was successfully performed on yeast (Saccharomyces cerevisiae) and green algae (Chlorella) cells. While no apparent change was observed with yeast, the treatment degraded the activity of the Chlorella cells and decreased their fluorescence. The device has the potential to help understand interactions between plasma and cells.

The higher performance of relaxor-based piezocrystals compared with piezoceramics is now well established, notably including improved gain-bandwidth product, and these materials have been adopted widely for biomedical ultrasound imaging. However, their use in other applications, for example as a source of focused ultrasound for targeted drug delivery, is hindered in several ways. One of the issues, which we consider here, is in shaping the material into the spherical geometries used widely in focused ultrasound. Unlike isotropic unpoled piezoceramics that can be shaped into a monolithic bowl then poled through the thickness, the anisotropic structure of piezocrystals make it impossible to machine the bulk crystalline material into a bowl without sacrificing performance. Instead, we report a novel faceted array, inspired by the geodesic dome structure in architecture, which utilizes flat piezocrystal material and maximizes fill factor. Aided by 3D printing, a prototype with f# ≈ 1.2, containing 96 individually addressable elements was manufactured using 1-3 connectivity PMN-PT piezocrystal - epoxy composite. The fabrication process is presented and the array was connected to a 32-channel controller to shape and steer the beam for preliminary performance demonstration. At an operating frequency of 1 MHz, a focusing gain around 30 was achieved and the side lobe intensities were all at levels below -12 dB compared to main beam. We conclude that, by taking advantage of contemporary fabrication techniques and driving instrumentation, the geodesic array configuration is suitable for focused ultrasound devices made with piezocrystal.

Objective: Presbyopia is a common age-related condition that prevents people from focusing on near objects. The etiology of presbyopia continues to be debated, but the end effect of all postulated mechanisms is the lack of deformation of the human lens. Using our understanding of the biomechanical properties of the natural human lens, we created a unique accommodating intraocular lens. Although this lens can be used for lenticular disease such as myopia and hyperoperopia, this study addresses the needs of cataract patients with presbyopia. Methods: The lens was implanted into presbyopic human cadaver eyes. Focal length of the lens was measured with simulated muscle contraction. Lens dimensions were measured using artificial tissue and a finite-element analysis (FEA) to simulate accommodation. Lens power was measured at various fill volumes. Accelerated soak testing for an equivalent of 7.4 years was performed and lens weight and optical transmittance were measured. Results: Previously presbyopic human eyes were able to accommodate between 2.0 and 7.4 diopters after lens implantation. FEA and lens measurements demonstrated a change in curvature of the anterior and posterior portions of the lens during accommodation. After accelerated aging, lens weight remained unchanged and optical transmission was 96%. Lens power increased with fill volume. Conclusion: A deformable liquid lens reversed presbyopia, can be individualized by optically adjusting for each patient, is stable for long periods of time, and is compatible with minimally invasive surgical techniques. Significance: A deformable liquid-filled lens can significantly improve accommodation over the presbyopic natural lens.

Electrochemical aptamer-based (E-AB) sensors employing electrode-immobilized, redox-tagged aptamer probes have emerged as a promising platform for the sensitive and quick detection of target analytes ranging from small molecules to proteins. Signal generation in this class of sensor is linked to change in electron transfer efficiency upon binding-induced change in flexibility/conformation of the aptamer probe. Because of this signaling mechanism, signal gains of these sensors can be improved by employing a displacement-based recognition system, which links target binding with a large-scale flexibility/conformation shift from the aptamer-DNA duplex to the single-stranded DNA or the native aptamer. Despite the relatively large number of displacement-based E-AB sensor samples, little attention has been paid to the structure variation of the aptamer-DNA duplex probe. Here we detail the effects of complementary length and position of the aptamer-DNA duplex probe on the performance of a model displacement-based E-AB sensor for ATP. We find that, greater background suppression and signal gain are observed with longer complementary length of the aptamer-DNA duplex probe. However, sensor equilibration time slows monotonically with increasing complementary length; and with too many target binding sites in aptamer sequence being occupied by the complementary DNA, the aptamer-target binding does not occur and no signal gain observed. We also demonstrate that signal gain of the displacement-based E-AB sensor is strongly dependent on the complementary position of the aptamer-DNA duplex probe, with complementary position located at the electrode-attached or redox-tagged end of the duplex probe, larger background suppression and signal increase than that of the middle position are observed. These results highlight the importance of rational structure design of the aptamer-DNA duplex probe and provide new insights into the optimization of displacement-based E-AB sensors.

A blended FC-V-50 and TZ-001 polymer-based microdisk laser was fabricated by the ink-jet printing method and used for biosensing applications. The FC-V-50 polymer has a negative charge due to the presence of carboxyl functional groups, and the TZ-001 polymer has a positive charge due to the tertiary amine group at a pH of seven. In biosensing applications, non-specific adsorption due to opposite charges of biomolecules and microdisk surfaces can adversely affect the performance of the biosensor. By mixing FC-V-50 and TZ-001 polymers in different ratios, the microdisk surface charge was controlled, and the non-specific adsorption of bovine serum albumin and lysozyme was studied. In addition, the label-free biosensing of streptavidin was demonstrated using a blended polymer-based microdisk laser. This work reports, to the best of our knowledge, the first demonstration of a blended polymer microdisk laser for controlling the non-specific adsorption of biomolecules.

High-precision microelectromechanical system (MEMS) accelerometers have wide application in the military and civil fields. The closed-loop microaccelerometer interface circuit with switched capacitor topology has a high signal-to-noise ratio, wide bandwidth, good linearity, and easy implementation in complementary metal oxide semiconductor (CMOS) process. Aiming at the urgent need for high-precision MEMS accelerometers in geophones, we carried out relevant research on high-performance closed-loop application specific integrated circuit (ASIC) chips. According to the characteristics of the performance parameters and output signal of MEMS accelerometers used in geophones, a high-precision closed-loop interface ASIC chip based on electrostatic time-multiplexing feedback technology and proportion integration differentiation (PID) feedback control technology was designed and implemented. The interface circuit consisted of a low-noise charge-sensitive amplifier (CSA), a sampling and holding circuit, and a PID feedback circuit. We analyzed and optimized the noise characteristics of the interface circuit and used a capacitance compensation array method to eliminate misalignment of the sensitive element. The correlated double sampling (CDS) technology was used to eliminate low-frequency noise and offset of the interface circuit. The layout design and engineering batch chip were fabricated by a standard 0.35 &mu, m CMOS process. The active area of the chip was 3.2 mm &times, 3 mm. We tested the performance of the accelerometer system with the following conditions: power dissipation of 7.7 mW with a 5 V power supply and noise density less than 0.5 &mu, g/Hz1/2. The accelerometers had a sensitivity of 1.2 V/g and an input range of &plusmn, 1.2 g. The nonlinearity was 0.15%, and the bias instability was about 50 &mu, g.

Microelectromechanical system (MEMS) liquid sensors may be used under large acceleration conditions. It is important to understand the deformation of the liquid droplets under acceleration for the design and applications of MEMS liquid sensors, as this will affect the performance of the sensors. This paper presents an investigation into the deformation of a mercury droplet in a liquid MEMS sensor under accelerations and reports the relationship between the deformation and the accelerations. The Laminar level set method was used in the numerical process. The geometric model consisted of a mercury droplet of 2 mm in diameter and an annular groove of 2.5 mm in width and 2.5 mm in height. The direction of the acceleration causing the droplet to deform is perpendicular to the direction of gravity. Fabrication and acceleration experiments were conducted. The deformation of the liquid was recorded using a high-speed camera. Both the simulation and experimental results show that the characteristic height of the droplets decreases as the acceleration increases. At an acceleration of 10 m/s2, the height of the droplet is reduced from 2 to 1.658 mm, and at 600 m/s2 the height is further reduced to 0.246 mm. The study finds that the droplet can deform into a flat shape but does not break even at 600 m/s2. Besides, the properties of the material in the domain surrounding the droplet and the contact angle also affect the deformation of the droplet. This work demonstrates the deformation of the liquid metal droplets under acceleration and provides the basis for the design of MEMS droplet acceleration sensors.

A handheld line-scanned dual-axis confocal (LS-DAC) microscope has been developed for high-speed (16 frames/s) fluorescence imaging of tissues with sub-nuclear resolution. This is the first miniature fluorescence LS-DAC system that has been fully packaged for handheld clinical use on patients. A novel micro-electro-mechanical system scanning mechanism, with synchronized tilting and pistoning, is used to achieve flat-field en face imaging. We show that this facilitates video mosaicking to generate images that sample an extended lateral field of view.

In this paper, we introduce a novel type of transdermal drug delivery device (TD3) with a micro-electro-mechanical system (MEMS) design using computer-aided design (CAD) techniques as well as computational fluid dynamics (CFD) simulations regarding the fluid interaction inside the device during the actuation process. For the actuation principles of the chamber and microvalve, both thermopneumatic and piezoelectric principles are employed respectively, originating that the design perfectly integrates those principles through two different components, such as a micropump with integrated microvalves and a microneedle array. The TD3 has shown to be capable of delivering a volumetric flow of 2.92 &times, 10&minus, 5 cm3/s with a 6.6 Hz membrane stroke frequency. The device only needs 116 Pa to complete the suction process and 2560 Pa to complete the discharge process. A 38-microneedle array with 450 &micro, m in length fulfills the function of permeating skin, allowing that the fluid reaches the desired destination and avoiding any possible pain during the insertion.