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Trimethylamine N -oxide (TMAO) has been recognized as a biomarker for the early detection of thrombosis. However, testing for TMAO typically requires expensive laboratory equipment and skilled technicians, making it unsuitable for home care pre-screening. To enable its widespread use in home applications, it is crucial to develop a scalable and sensitive device capable of catalyzing TMAO metabolism with a specific enzyme that is tailored for point-of-care use. This study presents an investigation of a MEMS-based two-tiered-tower biosensor array with a detection limit of 0.1 μM for TMAO, aiming to diagnose chronic metabolic diseases using urine or serum samples. Based on the augmented Cole-Cole model, the proposed parameters R _catalyzed , C _catalyzed , and R p_catalyzed can predict the catalytic impedance of enzymatic activities such as the redox effects of analytes and characterize the small-signal current caused by catalysis. The proposed MEMS biosensor, integrated with a readout circuitry, demonstrates a high sensitivity of 41 ADC counts per μM TMAO (or 4.5 mV μM -1 TMAO), a response time of 1 second, a repetition rate of 98.9%, and a drift over time of 0.5 mV. The sensor effectively distinguishes TMAO based on minute capacitance changes induced by the TorA enzyme, resulting in a discernible distinction of 10.6%. These measurements were successfully compared to conventional cyclic voltammetry (CV) results, showing a variance of only 0.024%. The proposed biosensor is well-suited for pre-screening thrombosis factors for the early detection and prevention of thrombosis in point-of-care applications. The device is cost-effective, lightweight, and demonstrates excellent performance, with a conversion rate of 88% of TMAO and a selectivity rate of 97% for the by-product TMA, allowing for the prediction of cardiovascular risks.

Purpose: The purpose of this study was to design an objective method for measurement of head positions as achieved with use of a microelectromechanical systems (MEMS) sensor. In addition, to use this system to observe the abnormal head position (AHP) in patients with congenital superior oblique palsy (SOP) before and after their surgery., Methods: An MEMS sensor was designed for recording of the pitch, roll, and yaw values of the head position in real time. The MEMS sensor was then fixed on the synoptophore from -30 degrees to +30 degrees positions horizontally and vertically to test the accuracy of these measurements. Then, we tested 13 participants with AHP using the MEMS method and the photographic method and compared their correlations. Finally, the pitch, roll, and yaw values of head positions were measured using this MEMS sensor in 31 patients with congenital SOP as performed before and after their surgery., Results: The MEMS sensor (LPMS-B2; Alubi, Guangzhou, China; 400 hertz [Hz]), as based on the theory of a gyroscope, was designed and connected to a smartphone via Bluetooth. It was able to conveniently record the patient's pitch, roll, and yaw head positions in real time, recordings which were consistent with the scales of the synoptophore (P > 0.05) and good correlations with the photographic method (P < 0.001). The main preoperative AHP in patients with SOP was roll (22/31, 71%). Pre- and postoperative vertical deviations were 16.4 ± 7.3 prism diopters (PD) and 4.1 ± 4.2 PD, respectively (P = 0.001). The AHP in patients with SOP was positively correlated with the angle of extorsion in the dominant eye (P = 0.01), rather than that of the vertical deviation., Conclusions: The MEMS sensor described in this report is a simple, practical, and accurate objective device for use in head position measurements. In patients with SOP, the AHP is related to the angle of extorsion in the dominant eye., Translational Relevance: The MEMS sensor was designed as a micro-wireless dynamic high-precision device for AHP measurement, which has the potential for use in a clinic.

Nanoelectromechanical systems (NEMS)-based mass spectrometry (MS) is an emerging technique that enables determination of the mass of individual adsorbed particles by driving nanomechanical devices at resonance and monitoring the real-time changes in their resonance frequencies induced by each single molecule adsorption event. We incorporate NEMS into an Orbitrap mass spectrometer and report our progress towards leveraging the single-molecule capabilities of the NEMS to enhance the dynamic range of conventional MS instrumentation and to offer new capabilities for performing deep proteomic analysis of clinically relevant samples. We use the hybrid instrument to deliver E. coli GroEL molecules (801 kDa) to the NEMS devices in their native, intact state. Custom ion optics are used to focus the beam down to 40 μm diameter with a maximum flux of 25 molecules/second. The mass spectrum obtained with NEMS-MS shows good agreement with the known mass of GroEL., (© 2024 Wiley-VCH GmbH.)

A label-free biosensor based on a tunable MEMS metamaterial structure is proposed in this paper. The adopted structure is a one-dimensional array of metamaterial gratings with movable and fixed fingers. The moving unit of the optical detection system is a component of the MEMS structure, driven by the surface stress effect. Thus, these suspended optical nanoribbons can be moved and change the grating pattern by the biological bonds that happened on the modified cantilever surface. Such structural variations lead to significant changes in the optical response of the metamaterial system under illuminating angled light and subsequently shift its resonance wavelength spectrum. As a result, the proposed biosensor shows appropriate analytical characteristics, including the mechanical sensitivity of S m = 11.55 μm/Nm -1 , the optical sensitivity of S o = Δλ/Δd = 0.7 translated to S o = Δλ/Δσ = 8.08 μm/Nm -1 , and the quality factor of Q = 102.7. Also, considering the importance of multi-biomarker detection, a specific design of the proposed topology has been introduced as an array for identifying different biomolecules. Based on the conducted modeling and analyses, the presented device poses the capability of detecting multiple biomarkers of disease at very low concentrations with proper precision in fluidic environments, offering a suitable bio-platform for lab-on-chip structures.

Flow-induced vibrations (FIV) were considered as unwanted vibrations analogous to noise. However, in a recent trend, the energy of these vibrations can be harvested and converted to electrical power. In this study, the potential of FIV as a source of renewable energy is highlighted through experimental and numerical analyses. The experimental study was conducted on an elastically mounted circular cylinder using helical and leaf springs in the wind tunnel. The Reynolds number (Re) varied between 2300-16000. The motion of the cylinder was restricted in all directions except the transverse direction. The micro-electromechanical system (MEMS) was mounted on the leaf spring to harvest the mechanical energy. Numerical simulations were also performed with SST k-ω turbulence model to supplement the experiments and were found to be in good agreement with the experimental results. The flow separation and vortex shedding induce aerodynamic forces in the cylinder causing it to vibrate. 2S vortex shedding pattern was observed in all of the cases in this study. The maximum dimensionless amplitude of vibration (A/D) obtained was 0.084 and 0.068 experimentally and numerically, respectively. The results showed that the region of interest is the lock-in region where maximum amplitude of vibration is observed and, therefore, the maximum power output. The piezoelectric voltage and power output were recorded for different reduced velocities (Ur = 1-10) at different resistance values in the circuit. It was observed that as the amplitude of oscillation of the cylinder increases, the voltage and power output of the MEMS increases due to high strain in piezoelectric transducer. The maximum output voltage of 0.6V was observed at Ur = 4.95 for an open circuit, i.e., for a circuit with the resistance value of infinity. As the resistance value reduced, a drop in voltage output was observed. Maximum power of 10.5μW was recorded at Ur = 4.95 for a circuit resistance of 100Ω., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Islam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Thin-film piezoelectric micromachined ultrasound transducers (PMUTs) are an increasingly relevant and well-researched field, and their biomedical importance has been growing as the technology continues to mature. This review article briefly discusses their history in biomedical use, provides a simple explanation of their principles for newer readers, and sheds light on the materials selection for these devices. Primarily, it discusses the significant applications of PMUTs in the biomedical industry and showcases recent progress that has been made in each application. The biomedical applications covered include common historical uses of ultrasound such as ultrasound imaging, ultrasound therapy, and fluid sensing, but additionally new and upcoming applications such as drug delivery, photoacoustic imaging, thermoacoustic imaging, biometrics, and intrabody communication. By including a device comparison chart for different applications, this review aims to assist microelectromechanical systems (MEMS) designers that work with PMUTs by providing a benchmark for recent research works. Furthermore, it puts forth a discussion on the current challenges being faced by PMUTs in the biomedical field, current and likely future research trends, and opportunities for PMUT development areas, as well as sharing the opinions and predictions of the authors on the state of this technology as a whole. The review aims to be a comprehensive introduction to these topics without diving excessively deep into existing literature.

The rational integration of many microfluidic chips and micropumps remains challenging. Due to the integration of the control system and sensors in active micropumps, they have unique advantages over passive micropumps when integrated into microfluidic chips. An active phase-change micropump based on complementary metal-oxide-semiconductor-microelectromechanical system (CMOS-MEMS) technology was fabricated and studied theoretically and experimentally. The micropump structure is simple and consists of a microchannel, a series of heater elements along the microchannel, an on-chip control system, and sensors. A simplified model was established to analyze the pumping effect of the traveling phase transition in the microchannel. The relationship between pumping conditions and flow rate was examined. Based on the experimental results, the maximum flow rate of the active phase-change micropump at room temperature is 22 µL/min, and long-term stable operation can be achieved by optimizing heating conditions.

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., (Copyright © 2021 by ASME.)

Myosin Light Chain (MLC) regulates platelet contraction through its phosphorylation by Myosin Light Chain Kinase (MLCK) or dephosphorylation by Myosin Light Chain Phosphatase (MLCP). The correlation between platelet contraction force and levels of MLC phosphorylation is unknown. We investigate the relationship between platelet contraction force and MLC phosphorylation using a novel microelectromechanical (MEMS) based clot contraction sensor (CCS). The MLCK and MLCP pair were interrogated by inhibitors and activators of platelet function. The CCS was fabricated from silicon using photolithography techniques and force was validated over a range of deflection for different chip spring constants. The force of platelet contraction measured by the clot contraction sensor (CCS) was compared to the degree of MLC phosphorylation by Western Blotting (WB) and ELISA. Stimulators of MLC phosphorylation produced higher contraction force, higher phosphorylated MLC signal in ELISA and higher intensity bands in WB. Inhibitors of MLC phosphorylation produced the opposite. Contraction force is linearly related to levels of phosphorylated MLC. Direct measurements of clot contractile force are possible using a MEMS sensor platform and correlate linearly with the degree of MLC phosphorylation during coagulation. Measured force represents the mechanical output of the actin/myosin motor in platelets regulated by myosin light chain phosphorylation.

Human motions, such as joint/spinal bending or stretching, often contain information that is useful for orthopedic/neural disease diagnosis, rehabilitation, and prevention. Here, we show a badge-reel-like stretch sensing device with a grating-structured triboelectric nanogenerator exhibiting a stretching sensitivity of 8 V mm -1 , a minimum resolution of 0.6 mm, a low hysteresis, and a high durability (over 120 thousand cycles). Experimental and theoretical investigations are performed to define the key features of the device. Studies from human natural daily activities and exercise demonstrate the functionality of the sensor for real-time recording of knee/arm bending, neck/waist twisting, and so on. We also used the device in a spinal laboratory, monitoring human subjects' spine motions, and validated the measurements using the commercial inclinometer and hunchback instrument. We anticipate that the lightweight, precise and durable stretch sensor applied to spinal monitoring could help mitigate the risk of long-term abnormal postural habits induced diseases.

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 .

Investigation of neural circuit dynamics is crucial for deciphering the functional connections among regions of the brain and understanding the mechanism of brain dysfunction. Despite the advancements of neural circuit models in vitro, technologies for both precisely monitoring and modulating neural activities within three-dimensional (3D) neural circuit models have yet to be developed. Specifically, no existing 3D microelectrode arrays (MEAs) have integrated capabilities to stimulate surrounding neurons and to monitor the temporal evolution of the formation of a neural network in real time. Herein, we present a 3D high-density multifunctional MEA with optical stimulation and drug delivery for investigating neural circuit dynamics within engineered 3D neural tissues. We demonstrate precise measurements of synaptic latencies in 3D neural networks. We expect our 3D multifunctional MEA to open up opportunities for studies of neural circuits through precise, in vitro investigations of neural circuit dynamics with 3D brain models.

Although microfluidic micro-electromechanical systems (MEMS) are well suited to investigate the effects of mechanical force on large populations of cells, their high-throughput capabilities cannot be fully leveraged without optimizing the experimental conditions of the fluid and particles flowing through them. Parameters such as flow velocity and particle size are known to affect the trajectories of particles in microfluidic systems and have been studied extensively, but the effects of temperature and buffer viscosity are not as well understood. In this paper, we explored the effects of these parameters on the timing of our own cell-impact device, the μHammer, by first tracking the velocity of polystyrene beads through the device and then visualizing the impact of these beads. Through these assays, we find that the timing of our device is sensitive to changes in the ratio of inertial forces to viscous forces that particles experience while traveling through the device. This sensitivity provides a set of parameters that can serve as a robust framework for optimizing device performance under various experimental conditions, without requiring extensive geometric redesigns. Using these tools, we were able to achieve an effective throughput over 360 beads/s with our device, demonstrating the potential of this framework to improve the consistency of microfluidic systems that rely on precise particle trajectories and timing.

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).

Introduction: Heart failure (HF) leads to significant morbidity and mortality and imposes a large economic burden. Although there have been several advances in HF monitoring and management, HF-rehospitalization remains a significant problem. Remote monitoring of HF to detect early signs of decompensation has emerged in past years as an option to prevent or reduce the incidence of HF rehospitalization. The CardioMEMS TM HF system is a wireless pulmonary artery (PA) pressure monitoring system that detects changes in PA pressure and transmits data to the healthcare provider. Since changes in PA pressure happen early in the course of HF decompensation, the CardioMEMS TM system allows the provider to institute timely intensification of HF therapies to alter the course. In trial and registry data, the use of the CardioMEMS TM HF system has been associated with reduction in HF hospitalization, improvement in quality of life, symptoms, and physical activity., Areas Covered: This review will focus on the available data supporting its utilization in patients with HF., Expert Opinion: CardioMEMS TM is relatively safe and cost-effective, reduces heart failure hospitalization rates, and fits into intermediate to high-value medical care.

Single-element transducer based ultrasound (US) imaging offers a compact and affordable solution for high-frequency preclinical and clinical imaging because of its low cost, low complexity, and high spatial resolution compared to array-based US imaging. To achieve B-mode imaging, conventional approaches adapt mechanical linear or sector scanning methods. However, due to its low scanning speed, mechanical linear scanning cannot achieve acceptable temporal resolution for real-time imaging, and the sector scanning method requires specialized low-load transducers that are small and lightweight. Here, we present a novel single-element US imaging system based on an acoustic mirror scanning method. Instead of physically moving the US transducer, the acoustic path is quickly steered by a water-proofed microelectromechanical (MEMS) scanner, achieving real-time imaging. Taking advantage of the low-cost and compact MEMS scanner, we implemented both a tabletop system for in vivo small animal imaging and a handheld system for in vivo human imaging. Notably, in combination with mechanical raster scanning, we could acquire the volumetric US images in live animals. This versatile US imaging system can be potentially used for various preclinical and clinical applications, including echocardiography, ophthalmic imaging, and ultrasound-guided catheterization.

A linear piezoelectric micromachined ultrasound transducer (PMUT) array was fabricated and integrated into a device for photoacoustic imaging (PAI) of tissue phantoms. The PMUT contained 65 array elements, with each element having 60 diaphragms of [Formula: see text] diameter and [Formula: see text] pitch. A lead zirconate titanate (PZT) thin film was used as the piezoelectric layer. The in-air vibration response of the PMUT array elements showed a first mode resonance between 6 and 8 MHz. Hydrophone measurements showed 16.2 kPa average peak ultrasound pressure output at 7.5 mm from one element excited with 5 V pp input. A receive sensitivity of ~0.48 mV/kPa was observed for a PMUT array element with 0 dB gain. The PMUT array was bonded to a custom-printed circuit board to enable compact integration with an optical fiber bundle for PAI. A broad photoacoustic bandwidth of ~89% was observed for the photoacoustic response captured from absorbing pencil lead targets. Linear scanning of a single element of a PMUT array was performed on different tissue phantoms embedded with light-absorbing targets to successfully demonstrate B-mode PAI using PMUTs.

Due to the large application of tapered beams in smart devices, such as scanning tunneling microscopes (STM), nano/micro electromechanical systems (NEMS/MEMS), atomic force microscopes (AFM), as well as in military aircraft applications, this study deals with the vibration behavior of laminated composite non-uniform nanobeams subjected to different boundary conditions. The micro-structural size-dependent free vibration response of composite laminated Euler-Bernoulli beams is here analyzed based on a modified couple stress elasticity, which accounts for the presence of a length scale parameter. The governing equations and boundary conditions of the problem are developed using the Hamilton's principle, and solved by means of the Rayleigh-Ritz method. The accuracy and stability of the proposed formulation is checked through a convergence and comparative study with respect to the available literature. A large parametric study is conducted to investigate the effect of the length-scale parameter, non-uniformity parameter, size dimension and boundary conditions on the natural frequencies of laminated composite tapered beams, as useful for design and optimization purposes of small-scale devices, due to their structural tailoring capabilities, damage tolerance, and their potential for creating reduction in weight.

Laser scanning based on Micro-Electro-Mechanical Systems (MEMS) scanners has become very attractive for biomedical endoscopic imaging, such as confocal microscopy or Optical Coherence Tomography (OCT). These scanners are required to be fast to achieve real-time image reconstruction while working at low actuation voltage to comply with medical standards. In this context, we report a 2-axis Micro-Electro-Mechanical Systems (MEMS) electrothermal micro-scannercapable of imaging large fields of view at high frame rates, e.g. from 10 to 80 frames per second. For this purpose, Lissajous scan parameters are chosen to provide the optimal image quality within the scanner capabilities and the sampling rate limit, resulting from the limited A-scan rate of typical swept-sources used for OCT. Images of 233 px × 203 px and 53 px × 53 px at 10 fps and 61 fps, respectively, are experimentally obtained and demonstrate the potential of this micro-scannerfor high definition and high frame rate endoscopic Lissajous imaging.

As pedestrian dead-reckoning (PDR), based on foot-mounted inertial sensors, suffers from accumulated error in velocity and heading, an improved heuristic drift elimination (iHDE) with a zero-velocity update (ZUPT) algorithm was proposed for simultaneously reducing the error in heading and velocity in complex paths, i.e., with pathways oriented at 45°, curved corridors, and wide areas. However, the iHDE algorithm does not consider the changes in pedestrian movement modes, and it can deteriorate when a pedestrian walks along a straight path without a pre-defined dominant direction. To solve these two problems, we propose enhanced heuristic drift elimination (eHDE) with an adaptive zero-velocity update (AZUPT) algorithm and novel heading correction algorithm. The relationships between the magnitude peaks of the y -axis angular rate and the detection thresholds were established only using the readings of the three-axis accelerometer and the three-axis gyroscopic, and a mechanism for constructing temporary dominant directions in real time was introduced. Real experiments were performed and the results showed that the proposed algorithm can improve the still-phase detection accuracy of a pedestrian at different movement motions and outperforms the iHDE algorithm in complex paths with many straight features., Competing Interests: The authors declare no conflict of interest.

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., Competing Interests: The authors declare no competing interest.

For implantable frequency synthesizers, realizing ultra-low voltage (ULV) and low power in addition to meeting PLL targets, fast lock and low phase noise, poses a difficult challenge. This paper presents techniques to achieve PLL targets as well as ULV and low power in the same chip through the use of a regular CMOS technology node. A curvature-PFD technique achieves both faster locking and lower jitter compared with conventional techniques. A two-step switching technique substantially reduces the power consumption in current mirrors and reduce noise when switching from a charge pump. Leakage analysis and subthreshold-leakage-reduction technique reduce reference spur and jitter to the voltage-controlled oscillator (VCO). A dither technique randomizes and averages reference spurs. The proposed chip was implemented in 90-nm CMOS technology; the 0.35-V medical-band frequency synthesizer consumes 238-μW power while generating output clock of 401.8 to 431.31-MHz and exhibiting a phase noise of -105.7 dBc/Hz at 1-MHz frequency offset with 20 μs locking time.

In this paper, we introduce a novel type of transdermal drug delivery device (TD 3 ) 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 TD 3 has shown to be capable of delivering a volumetric flow of 2.92 × 10 -5 cm 3 /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 µm in length fulfills the function of permeating skin, allowing that the fluid reaches the desired destination and avoiding any possible pain during the insertion.

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'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'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.

Cells sense a variety of extracellular cues, including the composition and geometry of the extracellular matrix, which is synthesized and remodeled by the cells themselves. Here, we present the method of Light-Induced Molecular Adsorption of Proteins (LIMAP) using the PRIMO system as a patterning technique to produce micro-patterned extracellular matrix (ECM) substrates using a single or combination of proteins. The method enables printing of ECM patterns in micron resolution with excellent reproducibility. We provide a step-by-step protocol and demonstrate how this can be applied to study the processes of neuronal pathfinding. LIMAP has significant advantages over existing micro-printing methods in terms of the ease of patterning more than one component and the ability to generate a pattern with any geometry or gradient. The protocol can easily be adapted to study the contribution of almost any chemical component towards cell fate and cell behavior. Finally, we discuss common issues that can arise and how these can be avoided.

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The combination of in vitro multi-electrode arrays (MEAs) and the neuronal differentiation of stem cells offers the capability to study human neuronal networks from patient or engineered human cell lines. Here, we use MEA-based assays to probe synaptic function and network interactions of hiPSC-derived neurons. Neuronal network behaviour first emerges at approximately 30 days of culture and is driven by glutamate neurotransmission. Over a further 30 days, inhibitory GABAergic signalling shapes network behaviour into a synchronous regular pattern of burst firing activity and low activity periods. Gene mutations in L-type voltage gated calcium channel subunit genes are strongly implicated as genetic risk factors for the development of schizophrenia and bipolar disorder. We find that, although basal neuronal firing rate is unaffected, there is a dose-dependent effect of L-type voltage gated calcium channel inhibitors on synchronous firing patterns of our hiPSC-derived neural networks. This demonstrates that MEA assays have sufficient sensitivity to detect changes in patterns of neuronal interaction that may arise from hypo-function of psychiatric risk genes. Our study highlights the utility of in vitro MEA based platforms for the study of hiPSC neural network activity and their potential use in novel compound screening.

Sound sensing finds wide applications in various fields, such as underwater detection, structural health monitoring, and medical diagnosis, to name just a few. Based on our previously developed MEMS-on-fiber sensors, showing the advantages of low cost, small volume, and high performance, a three-dimensional ultrasonic localization system employing four such sensors was established in this work. A time difference of arrival (TDOA) algorithm was utilized to analyze the acquired data and then calculate the accurate position of the ultrasonic signal source. Plenty of practical measurements were performed, and the derived localization deviation in the region of 2 m × 2 m × 1 m was about 2-5 mm. Outside this region, the deviation tended to increase due to the directional sensitivity existing in these sensors. As a result, for a more accurate localization requirement, more sensing probes are needed in order to depict a completely suitable application situation for MEMS technology.

Smartphone MEMS (Micro Electrical Mechanical System) accelerometers have relatively low sensitivity and high output noise density. Therefore, it cannot be directly used to track feeble vibrations such as structural vibrations. This article proposes an effective increase in the sensitivity of the smartphone accelerometer utilizing the stochastic resonance (SR) phenomenon. SR is an approach where, counter-intuitively, feeble signals are amplified rather than overwhelmed by the addition of noise. This study introduces the 2D-frequency independent underdamped pinning stochastic resonance (2D-FI-UPSR) technique, which is a customized SR filter that enables identifying the frequencies of weak signals. To validate the feasibility of the proposed SR filter, an iPhone device is used to collect bridge acceleration data during normal traffic operation and the proposed 2D-FI-UPSR filter is used to process these data. The first four fundamental bridge frequencies are successfully identified from the iPhone data. In parallel to the iPhone, a highly sensitive wireless sensing network consists of 15 accelerometers (Silicon Designs accelerometers SDI-2012) is installed to validate the accuracy of the extracted frequencies. The measurement fidelity of the iPhone device is shown to be consistent with the wireless sensing network data with approximately 1% error in the first three bridge frequencies and 3% error in the fourth frequency.

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.

The model of ultrasonic motor (USM) is the foundation of the analysis and control of the motor. Ultrasonic motor maintains nonlinear and complicated in dynamics due to its special structure and unique operating, which makes it difficult to establish a good model with traditional modeling. Moreover, the model should be established in line with strong nonlinearities. The nonlinear Hammerstein model of USM is established in this paper, which can better characterize the nonlinear motor. To adapt the model to the need of position control of ultrasonic motor, driving frequency and rotor position are considered as the input and output variables of the Hammerstein model respectively. To improve the accuracy of model and the efficiency of modeling process, model identification combined with differential evolution algorithm is designed. The comparison of model calculation results with the experimental data shows the accuracy of the established model and the validity of the proposed modeling., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

We present a methodology for building biologically inspired, soft microelectromechanical systems (MEMS) devices. Our strategy combines several advanced techniques including programmable colloidal self-assembly, light-harvesting with plasmonic nanotransducers, and in situ polymerization of compliant hydrogel mechanisms. We synthesize optomechanical microactuators using a template-assisted microfluidic approach in which gold nanorods coated with thermoresponsive poly(N-isopropylmethacrylamide) (pNIPMAM) polymer function as nanoscale building blocks. The resulting microactuators exhibit mechanical properties (4.8 ± 2.1 kPa stiffness) and performance metrics (relative stroke up to 0.3 and stress up to 10 kPa) that are comparable to that of bioengineered muscular constructs. Near-infrared (NIR) laser illumination provides effective spatiotemporal control over actuation (sub-micron spatial resolution at millisecond temporal resolution). Spatially modulated hydrogel photolithography guided by an experimentally validated finite element-based design methodology allows construction of compliant poly(ethylene glycol) diacrylate (PEGDA) mechanisms around the microactuators. We demonstrate the versatility of our approach by manufacturing a diverse array of microdevices including lever arms, continuum microrobots, and dexterous microgrippers. We present a microscale compression device that is developed for mechanical testing of three-dimensional biological samples such as spheroids under physiological conditions.

This paper reports the design, fabrication, and testing of a microfluidic MEMS biosensor for rapid sensing of low concentration Escherichia coli O157:H7. It consists of a specially designed focusing and sensing region, which enables the biosensor to detect low concentration of bacterial cells. The focusing region consists of a ramped vertical electrode pair made of electroplated gold along with tilted thin film finger pairs (45°) embedded inside a microchannel. The focusing region generates positive dielectrophoresis force, which moves the cells towards the edges of the tilted thin film electrode fingers, located at the center of the microchannel. The fluidic drag force then carries the focused cells to the sensing region, where three interdigitated electrode arrays (IDEAs) with 30, 20, and 10 pairs, respectively, are embedded inside the microchannel. This technique resulted in highly concentrated samples in the sensing region. The sensing IDEAs are functionalized with the anti- E. coli antibody for specific sensing of E. coli 0157:H7. As E. coli binds to the antibody, it results in an impedance change, which is measured across a wide frequency range of 100 Hz-10 MHz. The biosensor was fabricated on a glass substrate using the SU8 epoxy resist to form the microchannel, gold electroplating to form the vertical focusing electrode pair, a thin gold film to form the sensing electrode, the finger electrodes, traces and bonding pads, and polydimethylsiloxane to seal the device. The microfluidic impedance biosensor was tested with various low concentration bacterial samples and was able to detect bacterial concentration, as low as 39 CFU/ml with a total sensing time of 2 h.

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.

The paper presents a simulation study of breath analysis based on theoretical models of microelectromechanical structure (MEMS) cantilever sensor array. The purpose of this study is to suggest a methodology for the development of MEMS electronic nose (e-nose) for monitoring disease-specific volatiles in exhaled breath. Oxidative stress and diabetes are taken as case studies for the assessment of e-nose designs. The detection of ethane for general oxidative stress, isoprene for hypoxia, and acetone for diabetes are considered for targeted detection. A number of volatiles concurrently present in the exhaled breath are taken as interferents. The MEMS cantilevers are coated with volatile-selective polymers and are analyzed in both the static and dynamic modes. The sensor array is defined by polymer selections based on three data mining methods: principal component analysis (PCA), fuzzy c-means clustering (FCM), and fuzzy subtractive clustering (FSC). This utilizes vapor/polymer partition coefficients as a database. Analyses are carried out to find optimal combinations of the polymer selection method and cantilever sensing mode. Virtual breath analysis experiments are analyzed by PCA for target discrimination. It is found that no single combination works best in all conditions. The acetone (diabetes) detection is best in both sensing modes with the polymers selected by FSC; the isoprene (hypoxia) is detectable only in static sensing mode with polymers selected by FCM clustering; and the ethane (oxidative stress) detection is possible by all sensing modes and polymer selections, provided the breath samples are preconcentrated. This study suggests that it is difficult to realize a single general-purpose MEMS breath analyzer. The dedicated analyzers for specific disease indications can however be made with an optimal combination of sensing mode and polymer coatings.

Purpose: To evaluate the performance of micro-electromechanical systems (MEMS) switches against PIN diodes for switching a dual-tuned RF coil between 19 F and 1 H 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 19 F and 1 H 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 19 F and 1 H 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 19 F frequency and 12% at the 1 H frequency. The coil provides transmit field homogeneity of ±12.9% at the 1 H frequency and ±14.4% at the 19 F 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 19 F and 1 H resonances were demonstrated, despite the proximity of their Larmor frequencies., (© 2018 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

A micro/nanomotor (MNM), as miniaturized machinery, can potentially bridge the application gap between the traditional macroscale motor and the molecular motor to manipulate materials at the cellular scale. The fascinating biomedical potential application for these tiny robots has been long envisioned by science fiction, such as "Fantastic Voyage", where complicated surgery can be performed at single cell precision without any surgical incision. However, to enter the highly conservative biomedical and healthcare industry in practice, the MNM must provide unique advantages over existing technology without introducing additional health risk, which has not been fully materialized. As an emerging approach, light-driven micro/nanomotors (LMNMs) have demonstrated several unique advantages over other MNMs, which will be addressed in this Account. As a control signal, light promises additional degrees of freedom to manipulate MNMs by modulating the light intensity, frequency, polarization, and propagation direction with spatial and temporal precision, which enables excellent controllability and programmability of LMNMs. Additionally, the fruitful knowledge and catalysts from the well-studied photocatalysis can be readily transferred to LMNMs for photoelectrochemical reactions, which provides a rich materials inventory for the development of advanced LMNM systems. A model LMNM in general can be regarded as a miniaturized solar cell combined with electrokinetic propulsion parts, where electric current is provided by the photovoltaic effect and then converted to propulsion thrust through a variety of electrokinetic mechanisms. It can be envisioned that the electric current may be further regulated with the onboard electronic circuit for advanced logic-controlled nanorobots. Finally, because incident photons instead of active chemicals provide the energy for LMNM propulsion, the highly active but toxic chemical fuels can be avoided, which suggested their better biocompatibility. It is essential to emphasize that all of these promises rely on the in-depth understanding of the photoelectrochemical reaction as well as the physics of electrokinetic phenomena, which requires further investigations. As a persistent endeavor, the biomedical application is the most attractive but challenging target for MNMs. Currently, most of the MNMs are demonstrated with in vitro conditions largely deviating from the biological environment, and nontrivial in vivo studies and cytotoxicity experiments are rarely reported. As merits of MNMs, the efficiency, biocompatibility, ion tolerance, and controllability critically determine the future success of MNMs. In this Account, existing and prospective solutions in these aspects are systemically discussed for light-propelled MNMs. We believe that, with a better understanding of the fundamental photoelectrochemical and electrokinetic processes, the development of motor design strategies, and improved fabrication methods, the promised practical biomedical application, such as early disease diagnosis, interventional therapy, targeted therapy, and microsurgery, could be realized in the near future.

Three-dimensional (3D) printing now enables the fabrication of 3D structural electronics and microfluidics. Further, conventional subtractive manufacturing processes for microelectromechanical systems (MEMS) 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. Here, we demonstrate the ability to fabricate microfluidic-based acoustofluidic devices 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 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 devices generated bulk acoustic waves (BAWs) capable of size-selective manipulation, trapping, and separation of suspended particles in droplets and microchannels. Flow visualization studies in a 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.

Purpose: Integrated parallel reception, excitation, and shimming coil arrays with N shim loops per radio-frequency (RF) coil element (iPRES(N)) allow an RF current and N direct currents (DC) to flow in each coil element, enabling simultaneous reception/excitation and shimming of highly localized B 0 inhomogeneities. The purpose of this work was to reduce the cost and complexity of this design by reducing the number of DC power supplies required by a factor N, while maintaining a high RF and shimming performance., Methods: In the proposed design, termed adaptive iPRES(N) (iPRES(N)-A), each coil element only requires one DC power supply, but uses microelectromechanical systems switches to adaptively distribute the DC current into the appropriate shim loops to generate the desired magnetic field for B 0 shimming. Proof-of-concept phantom experiments with an iPRES(2)-A coil and simulations in the human abdomen with an 8-channel iPRES(4)-A body coil array were performed to demonstrate the advantages of this innovative design., Results: The iPRES(2)-A coil showed no loss in signal-to-noise ratio and provided a much more effective correction of highly localized B 0 inhomogeneities and geometric distortions than an equivalent iPRES(1) coil (88.2% vs. 32.2% lower B 0 root-mean-square error). The iPRES(4)-A coil array showed a comparable shimming performance as that of an equivalent iPRES(4) coil array (52.6% vs. 54.2% lower B 0 root-mean-square error), while only requiring 8 instead of 32 power supplies., Conclusion: The iPRES(N)-A design retains the ability of the iPRES(N) design to shim highly localized B 0 inhomogeneities, while drastically reducing its cost and complexity. Magn Reson Med 80:371-379, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Primary tumors of patients can release circulating tumor cells (CTCs) to flow inside of their blood. The CTCs have different mechanical properties in comparison with red and white blood cells, and their detection may be employed to study the efficiency of medical treatments against cancer. We present the design of a novel MEMS microgripper with rotatory electrostatic comb-drive actuators for mechanical properties characterization of cells. The microgripper has a compact structural configuration of four polysilicon layers and a simple performance that control the opening and closing displacements of the microgripper tips. The microgripper has a mobile arm, a fixed arm, two different actuators and two serpentine springs, which are designed based on the SUMMiT V surface micromachining process from Sandia National Laboratories. The proposed microgripper operates at its first rotational resonant frequency and its mobile arm has a controlled displacement of 40 µm at both opening and closing directions using dc and ac bias voltages. Analytical models are developed to predict the stiffness, damping forces and first torsional resonant frequency of the microgripper. In addition, finite element method (FEM) models are obtained to estimate the mechanical behavior of the microgripper. The results of the analytical models agree very well respect to FEM simulations. The microgripper has a first rotational resonant frequency of 463.8 Hz without gripped cell and it can operate up to with maximum dc and ac voltages of 23.4 V and 129.2 V, respectively. Based on the results of the analytical and FEM models about the performance of the proposed microgripper, it could be used as a dispositive for mechanical properties characterization of circulating tumor cells (CTCs).

Inflammable breath gases such as H₂ and CH₄ are used as bio markers for monitoring the condition of the colon. However, their typical concentrations of below 100 ppm pose sensitivity and selectivity challenges to current gas sensing systems without the use of chromatography. We fabricated a compact, gas-selective thermoelectric array sensor (TAS) that uses micro-machined sensor devices with three different combustion catalysts to detect gases such as H₂, CO, and CH₄ in breath. Using Pt/Pt-W thin-film micro-heater meanders, Pd/Al₂O₃, Pt,Pd,Au/Co₃O₄, and Pt/Al₂O₃ catalysts were heated to 320, 200, and 125 °C, respectively, and the gas sensing performances of the TAS for each gas and for a model breath gas mixture of 100 ppm H₂, 25 ppm CO, 50 ppm CH₄, and 199 ppm CO₂ in air were investigated. Owing to its high catalyst temperature, the Pd/Al₂O₃ catalyst burned all three gases, while the Pt,Pd,Au/Co₃O₄ burned CO and H₂ and the Pt/Al₂O₃ burned H₂ selectively. To calibrate the gas concentration of the mixture gas without the use of a gas separation tool, linear discriminant analysis was applied to measure the sensing performance of TAS. To enhance the gas selectivity against H₂, a double catalyst structure was integrated into the TAS sensor.

There is a growing interest in Nordic walking both from the fitness and medical point of views due to its possible therapeutic applications. The proper execution of the technique is an essential requirement to maximize the benefits of this practice. This is the reason why a monitoring system for outdoor Nordic walking activity was developed. Using data obtained from synchronized sensors, it is possible to have a complete overview of the users' movements. The system described in this paper is able to measure: the pole angle during the pushing phase, the arms cycle frequency and synchronization and the pushing force applied to the ground. Furthermore, data from a GPS module give an image of the environment where the activity session takes place, in terms of the distance, slope, as well as the ground typology. A heart rate sensor is used to monitor the effort of the user through his/her Beats Per Minute (BPM). In this work, the developed monitoring system is presented, explaining how to use the gathered data to obtain the main feedback parameters for Nordic walking performance analysis. The comparison between left and right arm measurements allowed validating the system as a tool for technique evaluation. Finally, a procedure to estimate the peak pushing force from acceleration measurements is proposed.

Microelectromechanical systems (MEMS)-based high-performance accelerometers are ubiquitously used in various electronic devices. However, there is an existing need to detect physical impacts using low-cost devices with no electronic circuits or a battery. We designed and fabricated an impact sensor prototype using a commercial stereolithography apparatus that only consists of a plastic housing and working fluids. The sensor device responds to the instantaneous acceleration (impact) by deformation and pinch off of a water droplet that is suspended in oil in a sensor cavity. We tested the various geometrical and physical parameters of the impact sensor to identify their relations to threshold acceleration values. We show that the state diagram that is plotted against the dimensionless Archimedes and Bond numbers adequately describes the response of the proposed sensor.

Novel drug delivery systems based on microtechnology have advanced tremendously, but yet face some technological and societal hurdles to fully achieve their potential. The novel drug delivery systems aim to deliver drugs in a spatiotemporal- and dosage-controlled manner with a goal to address the unmet medical needs from oral delivery and hypodermic injection. The unmet needs include effective delivery of new types of drug candidates that are otherwise insoluble and unstable, targeted delivery to areas protected by barriers (e.g. brain and posterior eye segment), localized delivery of potent drugs, and improved patient compliance. After scrutinizing the design considerations and challenges associated with delivery to areas that cannot be efficiently targeted through standard drug delivery (e.g. brain, posterior eye segment, and gastrointestinal tract), this review provides a summary of recent advances that addressed these challenges and summarizes yet unresolved problems in each target area. The opportunities for innovation in devising the novel drug delivery systems are still high; with integration of advanced microtechnology, advanced fabrication of biomaterials, and biotechnology, the novel drug delivery is poised to be a promising alternative to the oral administration and hypodermic injection for a large spectrum of drug candidates., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The presence of external elements is a major limitation of current hearing aids and cochlear implants, as they lead to discomfort and inconvenience. Totally implantable hearing devices have been proposed as a solution to mitigate these constraints, which has led to challenges in designing implantable sensors. This work presents a feasibility analysis of a MEMS piezoelectric accelerometer coupled to the ossicular chain as an alternative sensor. The main requirements of the sensor include small size, low internal noise, low power consumption, and large bandwidth. Different designs of MEMS piezoelectric accelerometers were modeled using Finite Element (FE) method, as well as optimized for high net charge sensitivity. The best design, a 2 × 2 mm 2 annular configuration with a 500 nm thick Aluminum Nitride (AlN) layer was selected for fabrication. The prototype was characterized, and its charge sensitivity and spectral acceleration noise were found to be with good agreement to the FE model predictions. Weak coupling between a middle ear FE model and the prototype was considered, resulting in equivalent input noise (EIN) lower than 60 dB sound pressure level between 600 Hz and 10 kHz. These results are an encouraging proof of concept for the development of MEMS piezoelectric accelerometers as implantable sensors for hearing devices.

Here, we demonstrate the advantages of the laser Doppler vibrometer (LDV) over conventional techniques (the network analyzer), as well as the techniques to create an application-based microelectromechanical systems (MEMS) filter and how to use it efficiently (i.e., tuning the tuning-capability and avoiding both failure and stiction). LDV enables crucial measurements that are impossible with the network analyzer, such as higher mode detection (highly sensitive biosensor application) and resonance measurement for very small devices (fast prototyping). Accordingly, LDV was used to characterize the frequency tuning range and resonance frequency at different modes of the MEMS filters built for this study. This wide range frequency tuning mechanism is based simply on Joule heating from the embedded heaters and relatively high thermal stress with respect to the temperature of a fixed-fixed beam. However, we demonstrate that another limitation of this method is the resulting high thermal stress, which can burn the devices. Further improvement was achieved and shown for the first time in this study, such that the tuning capability was increased by 32% through an increase in the applied DC bias voltage (25 V to 35 V) between the two adjacent beams. This important finding eliminates the need for the extra Joule heating at the wider frequency tuning range. Another possible failure is through stiction and requirement of structure optimization: We propose a simple and easy technique of low frequency square wave signal application that can successfully separate the beams and eliminates the need for the more sophisticated and complicated methods given in the literature. The above findings necessitate a design methodology, and so we also provide an application-based design.

Advances in micro-electromechanical systems have turned magnetic inertial measurement units (MIMUs) into a suitable tool for vertical jumping biomechanical evaluation. Thus, this study aimed to determine whether appropriate reliability and agreement reports could also be obtained when analyzing 20-m sprint mechanics. Four bouts of 20-m sprints were evaluated to determine whether the data provided by a MIMU placed at the lumbar spine could reliably assess sprint mechanics and to examine the validity of the MIMU sensor compared to force plate recordings. Maximal power (P 0 ), force (F 0 ), and velocity (V 0 ), as well as other mechanical determinants of sprint performance associated with the force-velocity, power-velocity, and ratio of forces-velocity, such as applied horizontal force loss (S fv ) and decrease in ratio of forces (D rf ), were calculated and compared between instrumentations. Extremely large-to-very large correlation levels between MIMU sensor-based sprint mechanics variables and force plate recordings were obtained (mean±SD, force plate vs MIMU; V 0, 8.61±0.85 vs 8.42±0.69; F 0 , 383±110 vs 391±103; P 0 , 873±246 vs 799±241; S fv, -44.6±12.7 vs -46.2±10.7), ranging from 0.88 to 0.94, except for D rf, which showed weak-to-moderate correlation level (r=.45; -6.32±1.08 vs -5.76±0.68). Step-averaged force values measured with both systems were highly correlated (r=.88), with a regression slope close to the identity (1.01). Bland and Altman graphical representation showed a no random distribution of measured force values. Finally, very large-to-extremely large retest correlation coefficients were found for the intertrial reliability of MIMU measurements of sprint performance variables (r value ranging from .72 to .96). Therefore, MIMUs showed appropriate validity and reliability values for 20-m sprint performance variables., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A microelectronic biosensor was subjected to in vivo exposure by implanting it in the vicinity of m. trapezii (Trapezius muscle) from cattle. The implant is intended for the continuous monitoring of glucose levels, and the study aimed at evaluating the biostability of exposed semiconductor surfaces. The sensor chip was a microelectromechanical system (MEMS) prepared using 0.25 µm complementary metal-oxide-semiconductor CMOS/BiCMOS technology. Sensing is based on the principle of affinity viscometry with a sensoric assay, which is separated by a semipermeable membrane from the tissue. Outer dimensions of the otherwise hermetically sealed biosensor system were 39 × 49 × 16 mm. The test system was implanted into cattle in a subcutaneous position without running it. After 17 months, the device was explanted and analyzed by comparing it with unexposed chips and systems. Investigations focused on the MEMS chip using SEM, TEM, and elemental analysis by EDX mapping. The sensor chip turned out to be uncorroded and no diminishing of the topmost passivation layer could be determined, which contrasts remarkably with previous results on CMOS biosensors. The negligible corrosive attack is understood to be a side effect of the semipermeable membrane separating the assay from the tissue. It is concluded that the separation has enabled a prolonged biostability of the chip, which will be of relevance for biosensor implants in general., Competing Interests: The authors declare no conflict of interest.

This paper presents a wireless capsule microsystem to detect and monitor the pH, pressure, and temperature of the gastrointestinal tract in real time. This research contributes to the integration of sensors (microfabricated capacitive pH, capacitive pressure, and resistive temperature sensors), frequency modulation and pulse width modulation based interface IC circuits, microcontroller, and transceiver with meandered conformal antenna for the development of a capsule system. The challenges associated with the system miniaturization, higher sensitivity and resolution of sensors, and lower power consumption of interface circuits are addressed. The layout, PCB design, and packaging of a miniaturized wireless capsule, having diameter of 13 mm and length of 28 mm, have successfully been implemented. A data receiver and recorder system is also designed to receive physiological data from the wireless capsule and to send it to a computer for real-time display and recording. Experiments are performed in vitro using a stomach model and minced pork as tissue simulating material. The real-time measurements also validate the suitability of sensors, interface circuits, and meandered antenna for wireless capsule applications.