A Smart Active Phase-Change Micropump Based on CMOS-MEMS Technology.

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.

Microelectromechanical System Measurement of Platelet Contraction: Direct Interrogation of Myosin Light Chain Phosphorylation.

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.

Sensing of joint and spinal bending or stretching via a retractable and wearable badge reel.

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.

Imperceptible energy harvesting device and biomedical sensor based on ultraflexible ferroelectric transducers and organic diodes.

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.

3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics.

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.

Inertial flow focusing: a case study in optimizing cellular trajectory through a microfluidic MEMS device for timing-critical applications.

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.

Fabrication, calibration, and preliminary testing of microcantilever-based piezoresistive sensor for BioMEMS applications.

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 Hg2+ 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).

CardioMEMSTM System in the Daily Management of Heart Failure: Review of Current Data and Technique of Implantation.

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 CardioMEMSTM 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 CardioMEMSTM system allows the provider to institute timely intensification of HF therapies to alter the course. In trial and registry data, the use of the CardioMEMSTM 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: CardioMEMSTM is relatively safe and cost-effective, reduces heart failure hospitalization rates, and fits into intermediate to high-value medical care.

Real-time Lissajous imaging with a low-voltage 2-axis MEMS scanner based on electrothermal actuation.

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.

Versatile Single-Element Ultrasound Imaging Platform using a Water-Proofed MEMS Scanner for Animals and Humans.

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 Modified Couple Stress Elasticity for Non-Uniform Composite Laminated Beams Based on the Ritz Formulation.

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.

Enhanced Heuristic Drift Elimination with Adaptive Zero-Velocity Detection and Heading Correction Algorithms for Pedestrian Navigation.

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.

An Improved Calibration Technique for MEMS Accelerometer-Based Inclinometers.

Micro-electro-mechanical system (MEMS) accelerometer-based inclinometers are widelyused to measure deformations of civil structures. To further improve the measurement accuracy, anew calibration technique was proposed in this paper. First, a single-parameter calibration modelwas constructed to obtain accurate angles. Then, an image-processing-based method was designedto obtain the key parameter for the calibration model. An ADXL355 accelerometer-basedinclinometer was calibrated to evaluate the feasibility of the technique. In this validationexperiment, the technique was proven to be reliable and robust. Finally, to evaluate theperformance of the technique, the calibrated MEMS inclinometer was used to measure thedeflections of a scale beam model. The experimental results demonstrate that the proposedtechnique can yield accurate deformation measurements for MEMS inclinometers. .

A Photoacoustic Imaging Device Using Piezoelectric Micromachined Ultrasound Transducers (PMUTs).

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 Vpp 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.

Biodegradable nanofiber-based piezoelectric transducer.

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.

MEMS-Based Sensor for Simultaneous Measurement of Pulse Wave and Respiration Rate.

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.

Design and Analyses of a Transdermal Drug Delivery Device (TD3) †.

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 × 10-5 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 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.

Light-Induced Molecular Adsorption of Proteins Using the PRIMO System for Micro-Patterning to Study Cell Responses to Extracellular Matrix Proteins.

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.

L-type voltage-gated calcium channel regulation of in vitro human cortical neuronal networks.

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.

A 0.35-V 240-µW Fast-Lock and Low-Phase-Noise Frequency Synthesizer for Implantable Biomedical Applications.

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.