This paper presents a monolithically integrated aptasensor composed of a piezoresistive microcantilever array and an on-chip signal processing circuit. Twelve microcantilevers, each of them embedded with a piezoresistor, form three sensors in a Wheatstone bridge configuration. The on-chip signal processing circuit consists of a multiplexer, a chopper instrumentation amplifier, a low-pass filter, a sigma-delta analog-to-digital converter, and a serial peripheral interface. Both the microcantilever array and the on-chip signal processing circuit were fabricated on the single-crystalline silicon device layer of a silicon-on-insulator (SOI) wafer with partially depleted (PD) CMOS technology followed by three micromachining processes. The integrated microcantilever sensor makes full use of the high gauge factor of single-crystalline silicon to achieve low parasitic, latch-up, and leakage current in the PD-SOI CMOS. A measured deflection sensitivity of 0.98 × 10−6 nm−1 and an output voltage fluctuation of less than 1 μV were obtained for the integrated microcantilever. A maximum gain of 134.97 and an input offset current of only 0.623 nA were acquired for the on-chip signal processing circuit. By functionalizing the measurement microcantilevers with a biotin-avidin system method, human IgG, abrin, and staphylococcus enterotoxin B (SEB) were detected at a limit of detection (LOD) of 48 pg/mL. Moreover, multichannel detection of the three integrated microcantilever aptasensors was also verified by detecting SEB. All these experimental results indicate that the design and process of monolithically integrated microcantilevers can meet the requirements of high-sensitivity detection of biomolecules.

High-precision microelectromechanical system (MEMS) gyroscopes are significant in many applications. Bias instability (BI) is an important parameter that indicates the performance of a MEMS gyroscope and is affected by the 1/f noise of the MEMS resonator and readout circuit. Since the bandgap reference (BGR) is an important block in the readout circuit, reducing its 1/f noise is key to improving a gyroscope’s BI. In a traditional BGR, the error amplifier is applied to provide a virtual short-circuit point, but it introduces the main low-frequency noise sources. This paper proposes an ultralow 1/f noise BGR by removing the error amplifier and applying an optimized circuit topology. In addition, a simplified but accurate noise model of the proposed BGR is obtained to optimize the BGR’s output noise performance. To verify this design, the proposed BGR has been implemented in a 180 nm CMOS process with a chip area of 545 × 423 μm. The experimental results show that the BGR’s output integrated noise from 0.1 to 10 Hz is 0.82 μV and the thermal noise is 35 nV/√Hz. Furthermore, bias stability tests of the MEMS gyroscope fabricated in our laboratory with the proposed BGR and some commercial BGRs are carried out. Statistical results show that reducing the BGR’s 1/f noise can nearly linearly improve the gyroscope’s BI.

Computational power density and interconnection between transistors have grown to be the dominant challenges for the continued scaling of complementary metal–oxide–semiconductor (CMOS) technology due to limited integration density and computing power. Herein, we designed a novel, hardware-efficient, interconnect-free microelectromechanical 7:3 compressor using three microbeam resonators. Each resonator is configured with seven equal-weighted inputs and multiple driven frequencies, thus defining the transformation rules for transmitting resonance frequency to binary outputs, performing summation operations, and displaying outputs in compact binary format. The device achieves low power consumption and excellent switching reliability even after 3 × 103 repeated cycles. These performance improvements, including enhanced computational power capacity and hardware efficiency, are paramount for moderately downscaling devices. Finally, our proposed paradigm shift for circuit design provides an attractive alternative to traditional electronic digital computing and paves the way for multioperand programmable computing based on electromechanical systems.

Miniaturized gas pumps based on electromagnetic effect have been intensively studied and widely applied in industries. However, the electromagnetic effect-based gas pumps normally have large sizes, high levels of noises and high power consumption, thus they are not suitable for wearable/portable applications. Herein, we propose a high-flowrate and high-pressure load valveless piezoelectric micropump with dimensions of 16 mm*16 mm*5 mm. The working frequency, vibration mode and displacement of the piezoelectric actuator, the velocity of gas flow, and the volume flowrate of the micropump are analyzed using the finite element analysis method. The maximum vibration amplitude of the piezoelectric actuator reaches ~29.4 μm. The output gas flowrate of the pump is approximately 135 mL/min, and the maximum output pressure exceeds 40 kPa. Then, a prototype of the piezoelectric micropump is fabricated. Results show that performance of the micropump is highly consistent with the numerical analysis with a high flowrate and pressure load, demonstrated its great potential for wearable/portable applications, especially for blood pressure monitoring.

By manipulating the geometry and surface chemistry of microfluidic channels, capillary-driven microfluidics can move and stop fluids spontaneously without external instrumentation. Furthermore, complex microfluidic circuits can be preprogrammed by synchronizing the capillary pressures and encoding the surface tensions of microfluidic chips. A key component of these systems is the capillary valve. However, the main concern for these valves is the presence of unwanted diffusion during the valve loading and activation steps that can cause cross-contamination. In this study, we design and validate a novel diffusion-free capillary valve: the π-valve. This valve consists of a 3D structure and a void area. The void acts as a spacer between two fluids to avoid direct contact. When the valve is triggered, the air trapped within the void is displaced by pneumatic suction induced from the capillary flow downstream without introducing a gas bubble into the circuit. The proposed design eliminates diffusive mixing before valve activation. Numerical simulation is used to study the function and optimize the dimensions of the π-valve, and 3D printing is used to fabricate either the mould or the microfluidic chip. A comparison with a conventional valve (based on a constriction-expansion valve) demonstrates that the π-valve eliminates possible backflow into the valve and reduces the mixing and diffusion during the loading and trigger steps. As a proof-of-concept, this valve is successfully implemented in a capillary-driven circuit for the determination of benzodiazepine, achieving the successive release of 3 solutions in a 3D-printed microfluidic chip without external instrumentation. The results show a 40% increase in the fluorescence intensity using the π-valve relative to the conventional value. Overall, the π-valve prevents cross-contamination, minimizes sample use, and facilitates a sophisticated preprogrammed release of fluids, offering a promising tool for conducting automated immunoassays applicable at point-of-care testing.

Particle migration dynamics in viscoelastic fluids in spiral channels have attracted interest in recent years due to potential applications in the 3D focusing and label-free sorting of particles and cells. Despite a number of recent studies, the underlying mechanism of Dean-coupled elasto-inertial migration in spiral microchannels is not fully understood. In this work, for the first time, we experimentally demonstrate the evolution of particle focusing behavior along a channel downstream length at a high blockage ratio. We found that flow rate, device curvature, and medium viscosity play important roles in particle lateral migration. Our results illustrate the full focusing pattern along the downstream channel length, with side-view imaging yielding observations on the vertical migration of focused streams. Ultimately, we anticipate that these results will offer a useful guide for elasto-inertial microfluidics device design to improve the efficiency of 3D focusing in cell sorting and cytometry applications.

A novel technology for the precise fabrication of quartz resonators for MEMS applications is introduced. This approach is based on the laser-induced chemical etching of quartz. The main processing steps include femtosecond UV laser treatment of a Cr-Au-coated Z-cut alpha quartz wafer, followed by wet etching. The laser-patterned Cr-Au coating serves as an etch mask and is used to form electrodes for piezoelectric actuation. This fabrication approach does not alter the quartz’s crystalline structure or its piezo-electric properties. The formation of defects, which is common in laser micromachined quartz, is prevented by optimized process parameters and by controlling the temporal behavior of the laser-matter interactions. The process does not involve any lithography and allows for high geometric design flexibility. Several configurations of piezoelectrically actuated beam-type resonators were fabricated using relatively mild wet etching conditions, and their functionality was experimentally demonstrated. The devices are distinguished from prior efforts by the reduced surface roughness and improved wall profiles of the fabricated quartz structures.

A nanofabricated superconducting quantum interference device (nano-SQUID) is a direct and sensitive flux probe used for magnetic imaging of quantum materials and mesoscopic devices. Due to the functionalities of superconductive integrated circuits, nano-SQUIDs fabricated on chips are particularly versatile, but their spatial resolution has been limited by their planar geometries. Here, we use femtosecond laser 3-dimensional (3D) lithography to print a needle onto a nano-SQUID susceptometer to overcome the limits of the planar structure. The nanoneedle coated with a superconducting shell focused the flux from both the field coil and the sample. We performed scanning imaging with such a needle-on-SQUID (NoS) device on superconducting test patterns with topographic feedback. The NoS showed improved spatial resolution in both magnetometry and susceptometry relative to the planarized counterpart. This work serves as a proof-of-principle for integration and inductive coupling between superconducting 3D nanostructures and on-chip Josephson nanodevices.

Demands for neural interfaces around functionality, high spatial resolution, and longevity have recently increased. These requirements can be met with sophisticated silicon-based integrated circuits. Embedding miniaturized dice in flexible polymer substrates significantly improves their adaptation to the mechanical environment in the body, thus improving the systems’ structural biocompatibility and ability to cover larger areas of the brain. This work addresses the main challenges in developing a hybrid chip-in-foil neural implant. Assessments considered (1) the mechanical compliance to the recipient tissue that allows a long-term application and (2) the suitable design that allows the implant’s scaling and modular adaptation of chip arrangement. Finite element model studies were performed to identify design rules regarding die geometry, interconnect routing, and positions for contact pads on dice. Providing edge fillets in the die base shape proved an effective measure to improve die-substrate integrity and increase the area available for contact pads. Furthermore, routing of interconnects in the immediate vicinity of die corners should be avoided, as the substrate in these areas is prone to mechanical stress concentration. Contact pads on dice should be placed with a clearance from the die rim to avoid delamination when the implant conforms to a curvilinear body. A microfabrication process was developed to transfer, align, and electrically interconnect multiple dice into conformable polyimide-based substrates. The process enabled arbitrary die shape and size over independent target positions on the conformable substrate based on the die position on the fabrication wafer.

COVID-19 has seriously threatened public health, and transdermal vaccination is an effective way to prevent pathogen infection. Microneedles (MNs) can damage the stratum corneum to allow passive diffusion of vaccine macromolecules, but the delivery efficiency is low, while iontophoresis can actively promote transdermal delivery but fails to transport vaccine macromolecules due to the barrier of the stratum corneum. Herein, we developed a wearable iontophoresis-driven MN patch and its iontophoresis-driven device for active and efficient transdermal vaccine macromolecule delivery. Polyacrylamide/chitosan hydrogels with good biocompatibility, excellent conductivity, high elasticity, and a large loading capacity were prepared as the key component for vaccine storage and active iontophoresis. The transdermal vaccine delivery strategy of the iontophoresis-driven MN patch is “press and poke, iontophoresis-driven delivery, and immune response”. We demonstrated that the synergistic effect of MN puncture and iontophoresis significantly promoted transdermal vaccine delivery efficiency. In vitro experiments showed that the amount of ovalbumin delivered transdermally using the iontophoresis-driven MN patch could be controlled by the iontophoresis current. In vivo immunization studies in BALB/c mice demonstrated that transdermal inoculation of ovalbumin using an iontophoresis-driven MN patch induced an effective immune response that was even stronger than that of traditional intramuscular injection. Moreover, there was little concern about the biosafety of the iontophoresis-driven MN patch. This delivery system has a low cost, is user-friendly, and displays active delivery, showing great potential for vaccine self-administration at home.

Microfluidics has demonstrated high versatility in the analysis of in-flow particles and can even achieve mechanical properties measurements of biological cells by applying hydrodynamic forces. However, there is currently no available technique that enables the direct measurement and tracking of these hydrodynamic forces acting on a flowing particle. In this work, we introduce a novel method for the direct measurement of the hydrodynamic force actuating on an in-flow particle based on the analysis of the induced resonance changes of suspended microchannel resonators (SMRs). This hydrodynamic force sensitivity depends on the device used; therefore, we considered the geometry and materials to advance this dependency on the SMR resonance frequency.

Real-time transformation was important for the practical implementation of impedance flow cytometry. The major obstacle was the time-consuming step of translating raw data to cellular intrinsic electrical properties (e.g., specific membrane capacitance Csm and cytoplasm conductivity σcyto). Although optimization strategies such as neural network-aided strategies were recently reported to provide an impressive boost to the translation process, simultaneously achieving high speed, accuracy, and generalization capability is still challenging. To this end, we proposed a fast parallel physical fitting solver that could characterize single cells’ Csm and σcyto within 0.62 ms/cell without any data preacquisition or pretraining requirements. We achieved the 27000-fold acceleration without loss of accuracy compared with the traditional solver. Based on the solver, we implemented physics-informed real-time impedance flow cytometry (piRT-IFC), which was able to characterize up to 100,902 cells’ Csm and σcyto within 50 min in a real-time manner. Compared to the fully connected neural network (FCNN) predictor, the proposed real-time solver showed comparable processing speed but higher accuracy. Furthermore, we used a neutrophil degranulation cell model to represent tasks to test unfamiliar samples without data for pretraining. After being treated with cytochalasin B and N-Formyl-Met-Leu-Phe, HL-60 cells underwent dynamic degranulation processes, and we characterized cell’s Csm and σcyto using piRT-IFC. Compared to the results from our solver, accuracy loss was observed in the results predicted by the FCNN, revealing the advantages of high speed, accuracy, and generalizability of the proposed piRT-IFC.

Water-in-oil droplets have emerged as promising microreactors for high-throughput biochemical analysis due to their features of reduced sample consumption and automated operation. For a typical screening application, droplets are often trapped for continuous monitoring of the reaction over an extended period, followed by the selective retrieval of targeted droplets based on the after-effect of biochemical reactions. While techniques for droplet trapping are well developed, retrieval of targeted droplets mainly demands complicated device fabrication or sophisticated control. Herein, facile and rapid selective droplet release is achieved by utilizing a new class of photoresponsive fluorosurfactant based on plasmonic nanoparticles. The intense photothermal response provided by this novel photoresponsive fluorosurfactant is capable of vaporizing the fluorocarbon oil at the droplet interface under laser illumination, resulting in a bubble releasing a trapped droplet on demand. A fully automated fluorescence-activated droplet release platform has also been developed to demonstrate its potential for droplet-based large-scale screening applications.

Projection micro stereolithography (PµSL) is a digital light processing (DLP) based printing technique for producing structured microparts. In this approach there is often a tradeoff between the largest object that can be printed and the minimum feature size, with higher resolution generally reducing the overall extent of the structure. The ability to produce structures with high spatial resolution and large overall volume, however, is immensely important for the creation of hierarchical materials, microfluidic devices and bioinspired constructs. In this work, we report a low-cost system with 1 µm optical resolution, representing the highest resolution system yet developed for the creation of micro-structured parts whose overall dimensions are nevertheless on the order of centimeters. To do so, we examine the limits at which PµSL can be applied at scale as a function of energy dosage, resin composition, cure depth and in-plane feature resolution. In doing so we develop a unique exposure composition approach that allows us to greatly improve the resolution of printed features. This ability to construct high-resolution scalable microstructures has the potential to accelerate advances in emerging areas, including 3D metamaterials, tissue engineering and bioinspired constructs.

The ability to control high-voltage actuator arrays relies, to date, on expensive microelectronic processes or on individual wiring of each actuator to a single off-chip high-voltage switch. Here we present an alternative approach that uses on-chip photoconductive switches together with a light projection system to individually address high-voltage actuators. Each actuator is connected to one or more switches that are nominally OFF unless turned ON using direct light illumination. We selected hydrogenated amorphous silicon (a-Si:H) as our photoconductive material, and we provide a complete characterization of its light to dark conductance, breakdown field, and spectral response. The resulting switches are very robust, and we provide full details of their fabrication processes. We demonstrate that the switches can be integrated into different architectures to support both AC and DC-driven actuators and provide engineering guidelines for their functional design. To demonstrate the versatility of our approach, we demonstrate the use of the photoconductive switches in two distinctly different applications—control of µm-sized gate electrodes for patterning flow fields in a microfluidic chamber and control of cm-sized electrostatic actuators for creating mechanical deformations for haptic displays.

Vaccines are used to protect human beings from various diseases. mRNA vaccines simplify the development process and reduce the production cost of conventional vaccines, making it possible to respond rapidly to acute and severe diseases, such as coronavirus disease 2019. In this study, a universal integrated platform for the streamlined and on-demand preparation of mRNA products directly from DNA templates was established. Target DNA templates were amplified in vitro by a polymerase chain reaction module and transcribed into mRNA sequences, which were magnetically purified and encapsulated in lipid nanoparticles. As an initial example, enhanced green fluorescent protein (eGFP) was used to test the platform. The expression capacity and efficiency of the products were evaluated by transfecting them into HEK-293T cells. The batch production rate was estimated to be 200–300 μg of eGFP mRNA in 8 h. Furthermore, an mRNA vaccine encoding the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein was produced by this platform. The proposed integrated platform shows advantages for the universal and on-demand preparation of mRNA products, offering the potential to facilitate broad access to mRNA technology and enable the development of mRNA products, including the rapid supply of new mRNA-based vaccines in pandemic situations and personalized mRNA-based therapies for oncology and chronic infectious diseases, such as viral hepatitis and acquired immune deficiency syndrome.

Thin-film PMUTs have been important research topics among microultrasound experts, and a concise review on their research progress is reported herein. Through rigorous surveying, scrutinization, and perception, it has been determined that the work in this field began nearly 44 years ago with the primitive development of functional piezoelectric thin-film materials. To date, there are three major companies commercializing thin-film PMUTs on a bulk scale. This commercialization illustrates the extensive contributions made by more than 70 different centers, research institutes, and agencies across 4 different continents regarding the vast development of these devices’ design, manufacturing, and function. This review covers these important contributions in a short yet comprehensive manner; in particular, this paper educates readers about the global PMUT outlook, their governing design principles, their manufacturing methods, nonconventional yet useful PMUT designs, and category-wise applications. Crucial comparison charts of thin-film piezoelectric material used in PMUTs, and their categorically targeted applications are depicted and discussed to enlighten any MEMS designer who plans to work with PMUTs. Moreover, each relevant section features clear future predictions based on the author’s past knowledge and expertise in this field of research and on the findings of a careful literature survey. In short, this review is a one-stop time-efficient guide for anyone interested in learning about these small devices.

The study of flow and particle dynamics in microfluidic cross-slot channels is of high relevance for lab-on-a-chip applications. In this work, we investigate the dynamics of a rigid spherical particle in a cross-slot junction for a channel height-to-width ratio of 0.6 and at a Reynolds number of 120 for which a steady vortex exists in the junction area. Using an in-house immersed-boundary-lattice-Boltzmann code, we analyse the effect of the entry position of the particle in the junction and the particle size on the dynamics and trajectory shape of the particle. We find that the dynamics of the particle depend strongly on its lateral entry position in the junction and weakly on its vertical entry position; particles that enter close to the centre show trajectory oscillations. Larger particles have longer residence times in the junction and tend to oscillate less due to their confinement. Our work contributes to the understanding of particle dynamics in intersecting flows and enables the design of optimised geometries for cytometry and particle manipulation.

In this paper, an electrostatic compliant mechanical amplifier intended for force-compensated displacement amplification in MEMS sensor applications is described. Usually, mechanical transformers that enhance a small input displacement into a large output displacement generate large forces at the input of the transformer. The microsystem proposed here allows for the reduction and compensation of the input stiffness of the amplifier and any mechanical components connected to it while providing a constant amplification ratio at the same time. The amplifying mechanism features bidirectional electrostatic anti-springs enabling the control of the stiffness by applying a constant DC voltage. The electrode design of the anti-springs and its influence on the force-displacement characteristic, the side instability and the maximal displacement are studied through analytical approaches and supported by FEA and by experiments. Based on the derived models, a compliant electromechanical amplifier is developed, featuring an amplification ratio of 50. For this amplifier the initial input stiffness of 422 N/m could be reduced to 6.8 N/m by applying a voltage of 100 V. As an additional application, we show how the amplifier can be used as a mechanical force sensor with tuneable sensitivity, where the forces at the input are transformed into large output displacements. Through experiments, we show how the sensitivity can be adjusted and increased by a factor of 25 by applying a voltage at the anti-springs.

Advancements in microscale electrode technology have revolutionized the field of neuroscience and clinical applications by offering high temporal and spatial resolution of recording and stimulation. Flexible neural probes, with their mechanical compliance to brain tissue, have been shown to be superior to rigid devices in terms of stability and longevity in chronic recordings. Shuttle devices are commonly used to assist flexible probe implantation; however, the protective membrane of the brain still makes penetration difficult. Hidden damage to brain vessels during implantation is a significant risk. Inspired by the anatomy of the mosquito mouthparts, we present a biomimetic neuroprobe system that integrates high-sensitivity sensors with a high-fidelity multichannel flexible electrode array. This customizable system achieves distributed and minimally invasive implantation across brain regions. Most importantly, the system’s nonvisual monitoring capability provides an early warning detection for intracranial soft tissues, such as vessels, reducing the potential for injury during implantation. The neural probe system demonstrates exceptional sensitivity and adaptability to environmental stimuli, as well as outstanding performance in postoperative and chronic recordings. These findings suggest that our biomimetic neural-probe device offers promising potential for future applications in neuroscience and brain-machine interfaces. A mosquito mouthpart-like bionic neural probe consisting of a highly sensitive tactile sensor module, a flexible microelectrode array, and implanted modules that mimic the structure of mosquito mouthparts. The system enables distributed implantation of electrode arrays across multiple brain regions while making the implantation minimally invasive and avoiding additional dural removal. The tactile sensor array can monitor the implantation process to achieve early warning of vascular damage. The excellent postoperative short-term recording performance and long-term neural activity tracking ability demonstrate that the system is a promising tool in the field of brain-computer interfaces.