Editor’s Choice Articles

Temporal lobe epilepsy (TLE) is a form of refractory focal epilepsy, which includes a latent period and a chronic period. Microelectrode arrays capable of multi-region detection of neural activities are important for accurately identifying the epileptic focus and pathogenesis mechanism in the latent period of TLE. Here, we fabricated multi-shank MEAs to detect neural activities in the DG, hilus, CA3, and CA1 in the TLE rat model. In the latent period in TLE rats, seizures were induced and changes in neural activities were detected. The results showed that induced seizures spread from the hilus and CA3 to other areas. Furthermore, interneurons in the hilus and CA3 were more excited than principal cells and exhibited rhythmic oscillations at approximately 15 Hz in grand mal seizures. In addition, the power spectral density (PSD) of neural spikes and local field potentials (LFPs) were synchronized in the frequency domain of the alpha band (9–15 Hz) after the induction of seizures. The results suggest that fabricated MEAs have the advantages of simultaneous and precise detection of neural activities in multiple subregions of the hippocampus. Our MEAs promote the study of cellular mechanisms of TLE during the latent period, which provides an important basis for the diagnosis of the lesion focus of TLE. Full article

Portability and low-cost analytic ability are desirable for point-of-care (POC) diagnostics; however, current POC testing platforms often require time-consuming multiple microfabrication steps and rely on bulky and costly equipment. This hinders the capability of microfluidics to prove its power outside of laboratories and narrows the range of applications. This paper details a self-contained microfluidic device, which does not require any external connection or tubing to deliver insert-and-use image-based analysis. Without any microfabrication, magnetorheological elastomer (MRE) microactuators including pumps, mixers and valves are integrated into one modular microfluidic chip based on novel manipulation principles. By inserting the chip into the driving and controlling platform, the system demonstrates sample preparation and sequential pumping processes. Furthermore, due to the straightforward fabrication process, chips can be rapidly reconfigured at a low cost, which validates the robustness and versatility of an MRE-enabled microfluidic platform as an option for developing an integrated lab-on-a-chip system. Full article

The Pacinian corpuscle is a highly sensitive mammalian sensor cell that exhibits a unique band-pass sensitivity to vibrations. The cell achieves this band-pass response through the use of 20 to 70 elastic layers entrapping layers of viscous fluid. This paper develops and explores a scalable mechanical model of the Pacinian corpuscle and uses the model to predict the response of synthetic corpuscles, which could be the basis for future vibration sensors. The −3dB point of the biological cell is accurately mimicked using the geometries and materials available with off-the-shelf 3D printers. The artificial corpuscles here are constructed using uncured photoresist within structures printed in a commercial stereolithography (SLA) 3D printer, allowing the creation of trapped fluid layers analogous to the biological cell. Multi-layer artificial Pacinian corpuscles are vibration tested over the range of 20–3000 Hz and the response is in good agreement with the model. Full article

In this study, we developed a radial artery pulse acquisition system based on finger-worn dense pressure sensor arrays to enable three-dimensional pulse signals acquisition. The finger-worn dense pressure-sensor arrays were fabricated by packaging 18 ultra-small MEMS pressure sensors (0.4 mm × 0.4 mm × 0.2 mm each) with a pitch of 0.65 mm on flexible printed circuit boards. Pulse signals are measured and recorded simultaneously when traditional Chinese medicine practitioners wear the arrays on the fingers while palpating the radial pulse. Given that the pitches are much smaller than the diameter of the human radial artery, three-dimensional pulse envelope images can be measured with the system, as can the width and the dynamic width of the pulse signals. Furthermore, the array has an effective span of 11.6 mm—3–5 times the diameter of the radial artery—which enables easy and accurate positioning of the sensor array on the radial artery. This study also outlines proposed methods for measuring the pulse width and dynamic pulse width. The dynamic pulse widths of three volunteers were measured, and the dynamic pulse width measurements were consistent with those obtained by color Doppler ultrasound. The pulse wave velocity can also be measured with the system by measuring the pulse transit time between the pulse signals at the brachial and radial arteries using the finger-worn sensor arrays. Full article

The recent advances in chip-size microscopy based on optical scanning with spatially resolved nano-illumination light sources are presented. This new straightforward technique takes advantage of the currently achieved miniaturization of LEDs in fully addressable arrays. These nano-LEDs are used to scan the sample with a resolution comparable to the LED sizes, giving rise to chip-sized scanning optical microscopes without mechanical parts or optical accessories. The operation principle and the potential of this new kind of microscope are analyzed through three different implementations of decreasing LED dimensions from 20 µm down to 200 nm. Full article

We investigate the direct writing properties of copper (Cu) patterns on glass and polydimethylsiloxane (PDMS) substrates using femtosecond laser pulse-induced thermochemical reduction of glyoxylic acid copper (GACu) complex. The films of the GACu complex coated on the substrates were irradiated by focused femtosecond laser pulses using a low numerical aperture of 0.45. Under the same conditions, such as laser scanning speed and pulse energy, the width of the line patterns fabricated on PDMS substrates was larger than that on glass substrates. X-ray diffraction peaks of the patterns on glass substrates corresponded to Cu without significant oxidation. By contrast, although Cu patterns were fabricated on PDMS substrates at a scanning speed of 10 mm/s and pulse energy of 0.49 nJ, Cu₂O was also generated under overheating conditions at a scanning speed of 1 mm/s and pulse energy of 0.37 nJ. All the patterns exhibited electrical conductivity. The minimum resistivity of the patterns on PDMS substrates is 1.4 × 10⁻⁵ Ωm, which is 10 times higher than that on glass substrates, indicating that microcracks formed by thermal shrinkage of the substrates during the laser irradiation increase the resistivity. This direct Cu writing technique on soft materials is useful for fabricating flexible microdevices. Full article

This work presents a comprehensive comparison of switchable electromechanical transducers in an AlN/GaN heterostructure toward the goal of reconfigurable RF building blocks in next-generation ad hoc radios. The transducers’ inherent switching was achieved by depleting a 2D electron gas (2DEG) channel, allowing an RF signal launched by interdigital transducers (IDTs) to effectively excite the symmetric (S_o) Lamb mode of vibration in the piezoelectric membrane. Different configurations for applying DC bias to the channel for electromechanical actuation in the piezoelectric are discussed. Complete suppression of the mechanical mode was achieved with the transducers in the OFF state. Equivalent circuit models were developed to extract parameters from measurements by fitting in both ON and OFF states. This is the first time that an extensive comparative study of the performance of different switchable transducers in their ON/OFF state is presented along with frequency scaling of the resonant mode. The switchable transducer with Ohmic IDTs and a Schottky control gate showed superior performance among the designs under consideration. Full article

In this paper, a new method to regulate the correlated color temperature (CCT) of white light-emitting diodes (LEDs) is proposed for the single-chip packaging structure, in which the blue light distribution emitted from the chip in the red/yellow phosphor layer was modulated through changing the paraffin-polydimethylsiloxane (PDMS) film transparence and haze. The results show that the transmittance of the paraffin-PDMS film can be modulated from 49.76% to 97.64%, while the haze of that ranges from 88.19% to 63.10%. When the thickness of paraffin-PDMS film is 0.6 mm, and the paraffin-PDMS film concentration is 30 wt%, the CCT of white LED decreases from 15177 K to 3615 K with the increase of thermal load in the paraffin-PDMS film. The modulating range of its CCT reaches 11562 K. The maximum CCT variation at the same test condition is only 536 K in the repeated experiments within one week. Full article

We demonstrate extremely high-throughput microfluidic cell sorting by making a parallel version of the vortex-actuated cell sorter (VACS). The set-up includes a parallel microfluidic sorter chip and parallel cytometry instrumentation: optics, electronics and control software. The result is capable of sorting lymphocyte-sized particles at 16 times the rate of our single-stream VACS devices, and approximately 10 times the rate of commercial cell sorters for an equivalent procedure. We believe this opens the potential to scale cell sorting for applications requiring the processing of much greater cell numbers than currently possible with conventional cell sorting. Full article

Motion capture of a robot and tactile sensing for a robot require sensors. Strain sensors are used to detect bending deformation of the robot finger and to sense the force from an object. It is important to introduce sensors in effective combination with actuators without affecting the original performance of the robot. We are interested in the improvement of flexible strain sensors integrated into soft microrobot fingers using a pneumatic balloon actuator (PBA). A strain sensor using a microchannel filled with liquid metal was developed for soft PBAs by considering the compatibility of sensors and actuators. Inflatable deformation generated by PBAs, however, was found to affect sensor characteristics. This paper presents structural reinforcement of a liquid metal-based sensor to solve this problem. Parylene C film was deposited into a microchannel to reinforce its structure against the inflatable deformation caused by a PBA. Parylene C deposition into a microchannel suppressed the interference of inflatable deformation. The proposed method enables the effective combination of soft PBAs and a flexible liquid metal strain sensor for use in microrobot fingers. Full article

In this article, we propose a new actuator named the modular bio-actuator (MBA). The MBA has two tendon structures made of polydimethylsiloxane (PDMS) at both ends of the bio-actuator. The MBA can be easily handled and fixed on an artificial micro-robot body to increase its design flexibility and output power. The tendon structures were connected to a bio-actuator in the form of a chain structure, and the connection between the tendon structures and the bio-actuator was maintained for more than three weeks. The contraction length of the MBA was linearly increased when the DC voltage applied to the MBA was increased. The MBA contracted over 200 µm when a DC voltage of 10 V and 1 Hz was applied to the bio-actuator. The output power of the MBA was measured using a PDMS cantilever, and the total output power of the MBA increased linearly when multiple MBAs were stacked on a PDMS cantilever. This study was aimed at improving the design flexibility and controllability of micro-robots and bionic systems. Full article

We developed a liquid crystal (LC) aptamer biosensor for the sensitive detection of amoxicillin (AMX). The AMX aptamer was immobilized onto the surface of a glass slide modified with a mixed self-assembled layer of dimethyloctadecyl [3-(trimethoxysilyl) propyl] ammonium chloride (DMOAP) and (3-aminopropyl) triethoxysilane (APTES). The long alkyl chains of DMOAP maintained the LC molecules in a homeotropic orientation and induced a dark optical appearance under a polarized light microscope (POM). In the presence of AMX, the specific binding of the aptamer and AMX molecules induced a conformational change in the aptamers, leading to the disruption of the homeotropic orientation of LCs, resulting in a bright optical appearance. The developed aptasensor showed high specificity and a low detection limit of 3.5 nM. Moreover, the potential application of the developed aptasensor for the detection of AMX in environmental samples was also demonstrated. Therefore, the proposed aptasensor is a promising platform for simple, rapid, and label-free monitoring of AMX in an actual water environment with high selectivity and sensitivity. Full article

We demonstrate a blood analysis routine by observing red blood cells through light and digital holographic microscopy in a microfluidic channel. With this setup a determination of red blood cell (RBC) concentration, the mean corpuscular volume (MCV), and corpuscular hemoglobin concentration mean (CHCM) is feasible. Cell count variations in between measurements differed by 2.47% with a deviation of $-0.26\times {10}^6$ μL to the reference value obtained from the Siemens ADVIA 2120i. Measured MCV values varied by 2.25% and CHCM values by 3.78% compared to the reference ADVIA measurement. Our results suggest that the combination of optical analysis with microfluidics handling provides a promising new approach to red blood cell counts. Full article

Accurate monitoring of motion and sleep states is critical for human health assessment, especially for a healthy life, early diagnosis of diseases, and medical care. In this work, a smart wearable sensor (SWS) based on a dual-channel triboelectric nanogenerator was presented for a real-time health monitoring system. The SWS can be worn on wrists, ankles, shoes, or other parts of the body and cloth, converting mechanical triggers into electrical output. By analyzing these signals, the SWS can precisely and constantly monitor and distinguish various motion states, including stepping, walking, running, and jumping. Based on the SWS, a fall-down alarm system and a sleep quality assessment system were constructed to provide personal healthcare monitoring and alert family members or doctors via communication devices. It is important for the healthy growth of the young and special patient groups, as well as for the health monitoring and medical care of the elderly and recovered patients. This work aimed to broaden the paths for remote biological movement status analysis and provide diversified perspectives for true-time and long-term health monitoring, simultaneously. Full article

A water droplet dispensed on a superhydrophobic ratchet surface is formed into an asymmetric shape, which creates a Laplace pressure gradient due to the contact angle difference between two sides. This work presents a magnetically actuated superhydrophobic ratchet surface composed of nanostructured black silicon strips on elastomer ridges. Uniformly magnetized NdFeB layers sputtered under the black silicon strips enable an external magnetic field to tilt the black silicon strips and form a superhydrophobic ratchet surface. Due to the dynamically controllable Laplace pressure gradient, a water droplet on the reported ratchet surface experiences different forces on two sides, which are explored in this work. Here, the detailed fabrication procedure and the related magnetomechanical model are provided. In addition, the resultant asymmetric spreading of a water droplet is studied. Finally, droplet impact characteristics are investigated in three different behaviors of deposition, rebound, and penetration depending on the impact speed. The findings in this work are exploitable for further droplet manipulation studies based on a dynamically controllable superhydrophobic ratchet surface. Full article

Measurement of ice nucleation (IN) temperature of liquid solutions at sub-ambient temperatures has applications in atmospheric, water quality, food storage, protein crystallography and pharmaceutical sciences. Here we present details on the construction of a temperature-controlled microfluidic platform with multiple individually addressable temperature zones and on-chip temperature sensors for high-throughput IN studies in droplets. We developed, for the first time, automated droplet freezing detection methods in a microfluidic device, using a deep neural network (DNN) and a polarized optical method based on intensity thresholding to classify droplets without manual counting. This platform has potential applications in continuous monitoring of liquid samples consisting of aerosols to quantify their IN behavior, or in checking for contaminants in pure water. A case study of the two detection methods was performed using Snomax^® (Snomax International, Englewood, CO, USA), an ideal ice nucleating particle (INP). Effects of aging and heat treatment of Snomax^® were studied with Fourier transform infrared (FTIR) spectroscopy and a microfluidic platform to correlate secondary structure change of the IN protein in Snomax^® to IN temperature. It was found that aging at room temperature had a mild impact on the ice nucleation ability but heat treatment at 95 °C had a more pronounced effect by reducing the ice nucleation onset temperature by more than 7 °C and flattening the overall frozen fraction curve. Results also demonstrated that our setup can generate droplets at a rate of about 1500/min and requires minimal human intervention for DNN classification. Full article

The capillary action between two solid surfaces has drawn significant attention in micro-objects manipulation. The axisymmetric capillary bridges and capillary forces between a spherical concave gripper and a spherical particle are investigated in the present study. A numerical procedure based on a shooting method, which consists of double iterative loops, was employed to obtain the capillary bridge profile and bring the capillary force subject to a constant volume condition. Capillary bridge rupture was characterized using the parameters of the neck radius, pressure difference, half-filling angle, and capillary force. The effects of various parameters, such as the contact angle of the spherical concave gripper, the radius ratio, and the liquid bridge volume on the dimensionless capillary force, are discussed. The results show that the radius ratio has a significant influence on the dimensionless capillary force for the dimensionless liquid bridge volumes of 0.01, 0.05, and 0.1 when the radius ratio value is smaller than 10. The effectiveness of the theorical approach was verified using simulation model and experiments. Full article

Non-contact manipulation technology has a wide range of applications in the manipulation and fabrication of micro/nanomaterials. However, the manipulation devices are often complex, operated only by professionals, and limited by a single manipulation function. Here, we propose a simple versatile optoelectronic tweezer (OET) system that can be easily controlled for manipulating microparticles with different sizes. In this work, we designed and established an optoelectronic tweezer manipulation system. The OET system could be used to manipulate particles with a wide range of sizes from 2 μm to 150 μm. The system could also manipulate micro-objects of different dimensions like 1D spherical polystyrene microspheres, 2D rod-shaped euglena gracilis, and 3D spiral microspirulina. Optical microscopic patterns for trapping, storing, parallel transporting, and patterning microparticles were designed for versatile manipulation. The sorting, rotation, and assembly of single particles in a given region were experimentally demonstrated. In addition, temperatures measured under different objective lenses indicate that the system does not generate excessive heat to damage bioparticles. The non-contact versatile manipulation reduces operating process and contamination. In future work, the simple optoelectronic tweezers system can be used to control non-contaminated cell interaction and micro-nano manipulation. Full article

In this paper, the characterization and analysis of a silicon micromachined Quad Mass Gyroscope (QMG) in the rate mode of operation are presented. We report on trade-offs between full-scale, linearity, and noise characteristics of QMGs with different Q-factors. Allan Deviation (ADEV) and Power Spectral Density (PSD) analysis methods were used to evaluate the performance results. The devices in this study were instrumented for the rate mode of operation, with the Open-Loop (OL) and Force-to-Rebalance (FRB) configurations of the sense mode. For each method of instrumentation, we presented constraints on selection of control parameters with respect to the Q-factor of the devices. For the high Q-factor device of over 2 million, and uncompensated frequency asymmetry of 60 $\mathrm{m}$$\mathrm{Hz}$, we demonstrated bias instability of $0.095$${}^{\circ }$/$\mathrm{h}$r and Angle Random Walk (ARW) of $0.0107$${}^{\circ }$/$\sqrt{\mathrm{hr}}$ in the OL mode of operation and bias instability of $0.065$${}^{\circ }$/$\mathrm{h}$r and ARW of $0.0058$${}^{\circ }$/$\sqrt{\mathrm{hr}}$ in the FRB mode of operation. We concluded that in a realistic MEMS gyroscope with imperfections (nearly matched, but non-zero frequency asymmetry), a higher Q-factor would increase the frequency stability of the drive axis resulting in an improved noise performance, but has challenges in implementation of digital control loops. Full article

In this work, a novel flexible electrically resistive-type MXene/Thermoplastic polyurethanes(TPU) based strain sensors was developed by a composite process of electrospinning (ES) and electrostatic spray deposition (ESD). Compared with other deposition processes, the sensing layer prepared by ESD has better adhesion to the ES TPU nanofiber membrane and is not easy to crack during the stretching process, thereby greatly improving the working range of the strain sensor. Furthermore, we obtained the sandwich structure easily by ES on the surface of the sensing layer again. This will help make the stress distribution more uniform during the stretching process and further increase the strain sensing range. The ESD-ES strain sensors were attached on skin to monitor various human motions. The results demonstrate that our ESD-ES strain sensors have wide application prospects in smart wearable device. Full article

The aim of this study is to determine the efficiency of loading and release of several zwitterionic, neutral, anionic and cationic dyes into/from mesoporous nanoparticles to find the optimum loading and release conditions for their application in detection protocols. The loading is carried out for MCM-41 type silica supports suspended in phosphate-buffered saline (PBS) buffer (pH 7.4) or in acetonitrile, involving the dyes (rhodamine B chloride, rhodamine 101 chloride, rhodamine 101 perchlorate, rhodamine 101 inner salt, meso-(4-hydroxyphenyl)-boron–dipyrromethene (BODIPY), sulforhodamine B sodium salt and fluorescein 27). As a general trend, rhodamine-based dyes are loaded with higher efficiency, when compared with BODIPY and fluorescein dyes. Between the rhodamine-based dyes, their charge and the solvent in which the loading process is carried out play important roles for the amount of cargo that can be loaded into the materials. The delivery experiments carried out in PBS buffer at pH 7.4 reveal for all the materials that anionic dyes are more efficiently released compared to their neutral or cationic counterparts. The overall best performance is achieved with the negatively charged sulforhodamine B dye in acetonitrile. This material also shows a high delivery degree in PBS buffer. Full article

Recently, grating-structured triboelectric nanogenerators (TENG) operating in freestanding mode have been the subject of intensive research. However, standard TENGs based on interdigital electrode structures are unable to realize real-time sensing of the direction of the freestanding electrode movement. Here, a newly designed TENG, consisting of one group of grating freestanding electrodes and three groups of interdigitated induction electrodes with the identical period, has been demonstrated as a self-powered vector angle/displacement sensor (SPVS), capable of distinguishing the real-time direction of the freestanding electrode displacement. Thanks to the unique coupling effect between triboelectrification and electrostatic induction, periodic alternating voltage signals are generated in response to the rotation/sliding movement of the top freestanding electrodes on the bottom electrodes. The output peak-to-peak voltage of the SPVS can reach as high as 300 V at the rotation rate of 48 rpm and at the sliding velocity of 0.1 m/s, respectively. The resolution of the sensor reaches 8°/5 mm and can be further enhanced by decreasing the width of the electrodes. This present work not only demonstrates a novel method for angle/displacement detection but also greatly expands the applicability of TENG as self-powered vector sensors. Full article

We demonstrate the hybrid integration of a lithium niobate microring resonator with a silicon nitride waveguide in the vertical configuration to achieve efficient light coupling. The microring resonator is fabricated on a lithium niobate on insulator (LNOI) substrate using photolithography assisted chemo-mechanical etching (PLACE). A fused silica cladding layer is deposited on the LNOI ring resonator. The silicon nitride waveguide is further produced on the fused silica cladding layer by first fabricating a trench in the fused silica while using focused ion beam (FIB) etching for facilitating the evanescent coupling, followed by the formation of the silicon nitride waveguide on the bottom of the trench. The FIB etching ensures the required high positioning accuracy between the waveguide and ring resonator. We achieve Q-factors as high as 1.4 × 10⁷ with the vertically integrated device. Full article

(1) Background: Dissolving microneedles (DMNs), a transdermal drug delivery system, have been developed to treat various diseases in a minimally invasive, painless manner. However, the currently available DMNs are based on burst release systems due to their hydrophilic backbone polymer. Although hydrophobic biodegradable polymers have been employed on DMNs for sustained release, dissolution in an organic solvent is required for fabrication of such DMNs. (2) Method: To overcome the aforementioned limitation, novel separable polycaprolactone (PCL) DMNs (SPCL-DMNs) were developed to implant a PCL-encapsulated drug into the skin. PCL is highly hydrophobic, degrades over a long time, and has a low melting point. Under thermal melting, PCL encapsulated capsaicin and could be fabricated into a DMN without the risk of toxicity from an organic solvent. (3) Results: Optimized SPCL-DMNs, containing PCL (height 498.3 ± 5.8 µm) encapsulating 86.66 ± 1.13 µg capsaicin with a 10% (w/v) polyvinyl alcohol and 20% (w/v) polyvinylpyrrolidone mixture as a base polymer, were generated. Assessment of the drug release profile revealed that this system could sustainably release capsaicin for 15 days from PCL being implanted in porcine skin. (4) Conclusion: The implantable SPCL-DMN developed here has the potential for future development of toxicity-free, sustained release DMNs. Full article

An essential method to investigate neuromodulation effects of an invasive neural interface (INI) is magnetic resonance imaging (MRI). Presently, MRI imaging of patients with neural implants is highly restricted in high field MRI (e.g., 3 T and higher) due to patient safety concerns. This results in lower resolution MRI images and, consequently, degrades the efficacy of MRI imaging for diagnostic purposes in these patients. Cubic silicon carbide (3C-SiC) is a biocompatible wide-band-gap semiconductor with a high thermal conductivity and magnetic susceptibility compatible with brain tissue. It also has modifiable electrical conductivity through doping level control. These properties can improve the MRI compliance of 3C-SiC INIs, specifically in high field MRI scanning. In this work, the MRI compliance of epitaxial SiC films grown on various Si wafers, used to implement a monolithic neural implant (all-SiC), was studied. Via finite element method (FEM) and Fourier-based simulations, the specific absorption rate (SAR), induced heating, and image artifacts caused by the portion of the implant within a brain tissue phantom located in a 7 T small animal MRI machine were estimated and measured. The specific goal was to compare implant materials; thus, the effect of leads outside the tissue was not considered. The results of the simulations were validated via phantom experiments in the same 7 T MRI system. The simulation and experimental results revealed that free-standing 3C-SiC films had little to no image artifacts compared to silicon and platinum reference materials inside the MRI at 7 T. In addition, FEM simulations predicted an ~30% SAR reduction for 3C-SiC compared to Pt. These initial simulations and experiments indicate an all-SiC INI may effectively reduce MRI induced heating and image artifacts in high field MRI. In order to evaluate the MRI safety of a closed-loop, fully functional all-SiC INI as per ISO/TS 10974:2018 standard, additional research and development is being conducted and will be reported at a later date. Full article

For the past two decades, many research groups have investigated new methods for reducing the size and cost of safe and arm-fire systems, while also improving their safety and reliability, through batch processing. Simultaneously, micro- and nanotechnology advancements regarding nanothermite materials have enabled the production of a key technological building block: pyrotechnical microsystems (pyroMEMS). This building block simply consists of microscale electric initiators with a thin thermite layer as the ignition charge. This microscale to millimeter-scale addressable pyroMEMS enables the integration of intelligence into centimeter-scale pyrotechnical systems. To illustrate this technological evolution, we hereby present the development of a smart infrared (IR) electronically controllable flare consisting of three distinct components: (1) a controllable pyrotechnical ejection block comprising three independently addressable small-scale propellers, all integrated into a one-piece molded and interconnected device, (2) a terminal function block comprising a structured IR pyrotechnical loaf coupled with a microinitiation stage integrating low-energy addressable pyroMEMS, and (3) a connected, autonomous, STANAG 4187 compliant, electronic sensor arming and firing block. Full article

3D printing has emerged as a powerful manufacturing technology and has attracted significant attention for the fabrication of microneedle (MN)-mediated transdermal systems. In this work, we describe an optimisation strategy for 3D-printed MNs, ranging from the design to the drug delivery stage. The key relationships between design and manufacturing parameters and quality and performance are systematically explored. The printing and post-printing set parameters were found to influence quality and material mechanical properties, respectively. It was demonstrated that the MN geometry affected piercing behaviour, fracture, and coating morphology. The delivery of insulin in porcine skin by inkjet-coated MNs was shown to be influenced by MN design. Full article

Additive, direct-write manufacturing via a focused electron beam has evolved into a reliable 3D nanoprinting technology in recent years. Aside from low demands on substrate materials and surface morphologies, this technology allows the fabrication of freestanding, 3D architectures with feature sizes down to the sub-20 nm range. While indispensably needed for some concepts (e.g., 3D nano-plasmonics), the final applications can also be limited due to low mechanical rigidity, and thermal- or electric conductivities. To optimize these properties, without changing the overall 3D architecture, a controlled method for tuning individual branch diameters is desirable. Following this motivation, here, we introduce on-purpose beam blurring for controlled upward scaling and study the behavior at different inclination angles. The study reveals a massive boost in growth efficiencies up to a factor of five and the strong delay of unwanted proximal growth. In doing so, this work expands the design flexibility of this technology. Full article

The production of energetic crystalized micro-patterns by using one-step printing has become a recent trend in energetic materials engineering. We report a direct ink writing (DIW) approach in which micro-scale energetic composites composed of 1,3,5-trinitro-1,3,5-triazinane (RDX) crystals in selected ink formulations of a cellulose acetate butyrate (CAB) matrix are produced based on a direct phase transformation from organic, solvent-based, all-liquid ink. Using the formulated RDX ink and the DIW method, we printed crystalized RDX micro-patterns of various sizes and shapes on silicon wafers. The crystalized RDX micro-patterns contained single crystals on pristine Si wafers while the micro-patterns containing dendrite crystals were produced on UV-ozone (UVO)-treated Si wafers. The printing method and the formulated all-liquid ink make up a simple route for designing and printing energetic micro-patterns for micro-electromechanical systems. Full article

Bone replacement implants for craniofacial reconstruction require to provide an adequate structural foundation to withstand the physiological loading. With recent advances in 3D printing technology in place of bone grafts using autologous tissues, patient-specific additively manufactured implants are being established as suitable alternates. Since the stress distribution of these structures is complicated, efficient design techniques, such as topology optimization, can deliver optimized designs with enhanced functionality. In this work, a two-scale topology optimization approach is proposed that provides multi-material designs for both macrostructures and microstructures. In the first stage, a multi-resolution topology optimization approach is used to produce multi-material designs with maximum stiffness. Then, a microstructure with a desired property supplants the solid domain. This is beneficial for bone implant design since, in addition to imparting the desired functional property to the design, it also introduces porosity. To show the efficacy of the technique, four different large craniofacial defects due to maxillectomy are considered, and their respective implant designs with multi-materials are shown. These designs show good potential in developing patient-specific optimized designs suitable for additive manufacturing. Full article

The fabrication of in vitro neuronal cell networks where cells are chemically or electrically connected to form functional circuits with useful properties is of great interest. Standard cell culture substrates provide ensembles of cells that scarcely reproduce physiological structures since their spatial organization and connectivity cannot be controlled. Supersonic Cluster Beam Deposition (SCBD) has been used as an effective additive method for the large-scale fabrication of interfaces with extracellular matrix-mimicking surface nanotopography and reproducible morphological properties for cell culture. Due to the high collimation of SCBD, it is possible to exploit stencil masks for the fabrication of patterned films and reproduce features as small as tens of micrometers. Here, we present a protocol to fabricate micropatterned cell culture substrates based on the deposition of nanostructured cluster-assembled zirconia films by stencil-assisted SCBD. The effectiveness of this approach is demonstrated by the fabrication of micrometric patterns able to confine primary astrocytes. Calcium waves propagating in the astrocyte networks are shown. Full article

CMOS-MEMS resonators have become a promising solution thanks to their miniaturization and on-chip integration capabilities. However, using a CMOS technology to fabricate microelectromechanical system (MEMS) devices limits the electromechanical performance otherwise achieved by specific technologies, requiring a challenging readout circuitry. This paper presents a transimpedance amplifier (TIA) fabricated using a commercial 0.35-µm CMOS technology specifically oriented to drive and sense monolithically integrated CMOS-MEMS resonators up to 50 MHz with a tunable transimpedance gain ranging from 112 dB to 121 dB. The output voltage noise is as low as 225 nV/Hz^1/2—input-referred current noise of 192 fA/Hz^1/2—at 10 MHz, and the power consumption is kept below 1-mW. In addition, the TIA amplifier exhibits an open-loop gain independent of the parasitic input capacitance—mostly associated with the MEMS layout—representing an advantage in MEMS testing compared to other alternatives such as Pierce oscillator schemes. The work presented includes the characterization of three types of MEMS resonators that have been fabricated and experimentally characterized both in open-loop and self-sustained configurations using the integrated TIA amplifier. The experimental characterization includes an accurate extraction of the electromechanical parameters for the three fabricated structures that enables an accurate MEMS-CMOS circuitry co-design. Full article

We designed a kirigami structure with a particular shape at both ends to provide a large uniform deformation region when stretched. When a kirigami structure is stretched, non-deformation regions, where the regions’ cuts do not open, and non-uniform deformation regions, where the regions’ cuts are not uniformly deformed, are produced. The extent of the non-deformation and non-uniform deformation regions increases in proportion to the number of cut cycles in the width direction n_w this reduces the percentage of the uniform deformation region. We propose a method that increases the uniform deformation region in a kirigami structure by deforming the shape of the ends from a rectangle to a trapezoid when stretched. The proposed kirigami structure has separation lines at both ends that separate cuts in the width direction, and the position of contacts at both ends are moved to the center. The proposed kirigami structure has a large uniform deformation region, even when n_w is large, as evidenced by calculating the area of open cuts under stretching. The product of our study realizes a stretchable electro device with a large area, which maintains the position of evenly mounted functional elements when stretched. Full article

A silicon-chip based double-deck three-dimensional (3D) solenoidal electromagnetic (EM) kinetic energy harvester is developed to convert low-frequency (<100 Hz) vibrational energy into electricity with high efficiency. With wafer-level micro electro mechanical systems (MEMS) fabrication to form a metal casting mold and the following casting technique to rapidly (within minutes) fill molten ZnAl alloy into the pre-micromachined silicon mold, the 300-turn solenoid coils (150 turns for either inner solenoid or outer solenoid) are fabricated in silicon wafers for saw dicing into chips. A cylindrical permanent magnet is inserted into a pre-etched channel for sliding upon external vibration, which is surrounded by the solenoids. The size of the harvester chip is as small as 10.58 mm × 2.06 mm × 2.55 mm. The internal resistance of the solenoids is about 17.9 Ω. The maximum peak-to-peak voltage and average power output are measured as 120.4 mV and 43.7 $\mathsf{\mu }\mathrm{W}$. The EM energy harvester shows great improvement in power density, which is 786 $\mathsf{\mu }\mathrm{W}/{\mathrm{cm}}^3$ and the normalized power density is 98.3 $\mathsf{\mu }\mathrm{W}/{\mathrm{cm}}^3/\mathrm{g}$. The EM energy harvester is verified by experiment to be able to generate electricity through various human body movements of walking, running and jumping. The wafer-level fabricated chip-style solenoidal EM harvesters are advantageous in uniform performance, small size and volume applications. Full article

Plant virus-like particles, and in particular, tobacco mosaic virus (TMV) particles, are increasingly being used in nano- and biotechnology as well as for biochemical sensing purposes as nanoscaffolds for the high-density immobilization of receptor molecules. The sensitive parameters of TMV-assisted biosensors depend, among others, on the density of adsorbed TMV particles on the sensor surface, which is affected by both the adsorption conditions and surface properties of the sensor. In this work, Ta₂O₅-gate field-effect capacitive sensors have been applied for the label-free electrical detection of TMV adsorption. The impact of the TMV concentration on both the sensor signal and the density of TMV particles adsorbed onto the Ta₂O₅-gate surface has been studied systematically by means of field-effect and scanning electron microscopy methods. In addition, the surface density of TMV particles loaded under different incubation times has been investigated. Finally, the field-effect sensor also demonstrates the label-free detection of penicillinase immobilization as model bioreceptor on TMV particles. Full article

The sneak path current (SPC) is the inevitable issue in crossbar memory array while implementing high-density storage configuration. The crosstalks are attracting much attention, and the read accuracy in the crossbar architecture is deteriorated by the SPC. In this work, the sneak path current problem is observed and investigated by the electrical experimental measurements in the crossbar array structure with the half-read scheme. The read margin of the selected cell is improved by the bilayer stacked structure, and the sneak path current is reduced ~20% in the bilayer structure. The voltage-read stress-induced read margin degradation has also been investigated, and less voltage stress degradation is showed in bilayer structure due to the intrinsic nonlinearity. The oxide-based bilayer stacked resistive random access memory (RRAM) is presented to offer immunity toward sneak path currents in high-density memory integrations when implementing the future high-density storage and in-memory computing applications. Full article

We show that by combining deterministic lateral displacement (DLD) with electrokinetics, it is possible to sort cells based on differences in their membrane and/or internal structures. Using heat to deactivate cells, which change their viability and structure, we then demonstrate sorting of a mixture of viable and non-viable cells for two different cell types. For Escherichia coli, the size change due to deactivation is insufficient to allow size-based DLD separation. Our method instead leverages the considerable change in zeta potential to achieve separation at low frequency. Conversely, for Saccharomyces cerevisiae (Baker’s yeast) the heat treatment does not result in any significant change of zeta potential. Instead, we perform the sorting at higher frequency and utilize what we believe is a change in dielectrophoretic mobility for the separation. We expect our work to form a basis for the development of simple, low-cost, continuous label-free methods that can separate cells and bioparticles based on their intrinsic properties. Full article

Microfluidic devices are used extensively in the development of new in vitro cell culture models like organs-on-chips. A typical feature of such devices is the patterning of biological hydrogels to offer cultured cells and tissues a controlled three-dimensional microenvironment. A key challenge of hydrogel patterning is ensuring geometrical confinement of the gel, which is generally solved by inclusion of micropillars or phaseguides in the channels. Both of these methods often require costly cleanroom fabrication, which needs to be repeated even when only small changes need be made to the gel geometry, and inadvertently expose cultured cells to non-physiological and mechanically stiff structures. Here, we present a technique for facile patterning of hydrogel geometries in microfluidic chips, but without the need for any confining geometry built into the channel. Core to the technique is the use of laminar flow patterning to create a hydrophilic path through an otherwise hydrophobic microfluidic channel. When a liquid hydrogel is injected into the hydrophilic region, it is confined to this path by the surrounding hydrophobic regions. The various surface patterns that are enabled by laminar flow patterning can thereby be rendered into three-dimensional hydrogel structures. We demonstrate that the technique can be used in many different channel geometries while still giving the user control of key geometric parameters of the final hydrogel. Moreover, we show that human umbilical vein endothelial cells can be cultured for multiple days inside the devices with the patterned hydrogels and that they can be stimulated to migrate into the gel under the influence of trans-gel flows. Finally, we demonstrate that the patterned gels can withstand trans-gel flow velocities in excess of physiological interstitial flow velocities without rupturing or detaching. This novel hydrogel-patterning technique addresses fundamental challenges of existing methods for hydrogel patterning inside microfluidic chips, and can therefore be applied to improve design time and the physiological realism of microfluidic cell culture assays and organs-on-chips. Full article

Integrated photonic quantum chip provides a promising platform to perform quantum computation, quantum simulation, quantum metrology and quantum communication. Femtosecond laser direct writing (FLDW) is a potential technique to fabricate various integrated photonic quantum chips in glass. Several quantum logic gates fabricated by FLDW have been reported, such as polarization and path encoded quantum controlled-NOT (CNOT) gates. By combining several single qubit gates and two qubit gates, the quantum circuit can realize different functions, such as generating quantum entangled states and performing quantum computation algorithms. Here we demonstrate the FLDW of integrated photonic quantum chips composed of one Hadamard gate and one CNOT gate for generating all four path-encoded Bell states. The experimental results show that the average fidelity of the reconstructed truth table reaches as high as 98.8 $\pm$ 0.3%. Our work is of great importance to be widely applied in many quantum circuits, therefore this technique would offer great potential to fabricate more complex circuits to realize more advanced functions. Full article

High accuracy measurement of size is essential in physical and biomedical sciences. Various sizing techniques have been widely used in sorting colloidal materials, analyzing bioparticles and monitoring the qualities of food and atmosphere. Most imaging-free methods such as light scattering measure the averaged size of particles and have difficulties in determining non-spherical particles. Imaging acquisition using camera is capable of observing individual nanoparticles in real time, but the accuracy is compromised by the image defocusing and instrumental calibration. In this work, a machine learning-based pipeline is developed to facilitate a high accuracy imaging-based particle sizing. The pipeline consists of an image segmentation module for cell identification and a machine learning model for accurate pixel-to-size conversion. The results manifest a significantly improved accuracy, showing great potential for a wide range of applications in environmental sensing, biomedical diagnostical, and material characterization. Full article

Micromodels are ideal candidates for microfluidic transport investigations, and they have been used for many applications, including oil recovery and carbon dioxide storage. Conventional fabrication methods (e.g., photolithography and chemical etching) are beset with many issues, such as multiple wet processing steps and isotropic etching profiles, making them unsuitable to fabricate complex, multi-depth features. Here, we report a simpler approach, femtosecond laser material processing (FLMP), to fabricate a 3D reservoir micromodel featuring 4 different depths—35, 70, 140, and 280 µm, over a large surface area (20 mm × 15 mm) in a borosilicate glass substrate. The dependence of etch depth on major processing parameters of FLMP, i.e., average laser fluence (${\mathrm{LF}}_{\mathrm{av}}$), and computer numerically controlled (CNC) processing speed (${\mathrm{PS}}_{\mathrm{CNC}}$), was studied. A linear etch depth dependence on ${\mathrm{LF}}_{\mathrm{av}}$ was determined while a three-phase exponential decay dependence was obtained for ${\mathrm{PS}}_{\mathrm{CNC}}$. The accuracy of the method was investigated by using the etch depth dependence on ${\mathrm{PS}}_{\mathrm{CNC}}$ relation as a model to predict input parameters required to machine the micromodel. This study shows the capability and robustness of FLMP to machine 3D multi-depth features that will be essential for the development, control, and fabrication of complex microfluidic geometries. Full article

Ion channel proteins play important roles in various cell functions, making them attractive drug targets. Artificial lipid bilayer recording is a technique used to measure the ion transport activities of channel proteins with high sensitivity and accuracy. However, the measurement efficiency is low. In order to improve the efficiency, we developed a method that allows us to form bilayers on a hydrogel bead and record channel currents promptly. We tested our system by measuring the activities of various types of channels, including gramicidin, alamethicin, α-hemolysin, a voltage-dependent anion channel 1 (VDAC1), a voltage- and calcium-activated large conductance potassium channel (BK channel), and a potassium channel from Streptomyces lividans (KcsA channel). We confirmed the ability for enhanced measurement efficiency and measurement system miniaturizion. Full article

Lung-on-a-chip devices could provide new strategies for a biomimetic lung cell microenvironment and construction of lung disease models in vitro, and are expected to greatly promote the development of drug evaluation, toxicological detection, and disease model building. In this study, we developed a novel poly (lactic-co-glycolic acid) (PLGA) nanofiber/polydimethylsiloxane (PDMS) microporous composite membrane-sandwiched lung-on-a-chip to perform anti-tumor drug testing. The composite membrane was characterized, and the results showed that it was permeable to molecules and thus could be used to study small-molecule drug diffusion. In addition, the microchip could apply perfusion fluids to simulate blood flow under extremely low fluid shear stress, and could also simulate the spherical-like shape of the alveoli by deformation of the composite membrane. Using this chip, we evaluated the anti-tumor drug efficacy of gefitinib in two kinds of non-small cell lung cancer cells, the lung adenocarcinoma NCI-H1650 cell line and the large cell lung cancer NCI-H460 cell line. We further probed the resistance of NCI-H460 cells to gefitinib under normoxic and hypoxic conditions. The established composite membrane-sandwiched lung chip can simulate more biochemical and biophysical factors in the lung physiological and pathological microenvironment, and it has important applications in the personalized treatment of lung tumors. It is expected to play a potential role in clinical diagnosis and drug screening. Full article

In this paper, we developed a spheroid culture device that can trap a spheroid in the trapping site sandwiched by two extracellular matrix gels located at the upper and lower side of the spheroid. This device can form different biochemical gradients by applying target biochemicals separately in upper and lower channels, allowing us to study the angiogenic sprouting under various biochemical gradients in different directions. In the experiments, we confirmed the trapping of the spheroids and demonstrate the investigation on the direction and extent of angiogenic sprouts under unidirectional or bidirectional biochemical gradients. We believe our device can contribute to understanding the pathophysiological phenomena driven by chemical gradients, such as tissue development and tumor angiogenesis. Full article

Transport-induced-charge (TIC) phenomena, in which the concentration imbalance between cations and anions occurs when more than two chemical potential gradients coexist within an ultrathin dimension, entail numerous nanofluidic systems. Evidence has indicated that the presence of TIC produces a nonlinear response of electroosmotic flow to the applied voltage, resulting in complex fluid behavior. In this study, we theoretically investigate thermal effects due to Joule heating on TIC phenomena in an ultrathin nanopore by computational fluid dynamics simulation. Our modeling results show that the rise of local temperature inside the nanopore significantly enhances TIC effects and thus has a significant influence on electroosmotic behavior. A local maximum of the solution conductivity occurs near the entrance of the nanopore at the high salt concentration end, resulting in a reversal of TIC across the nanopore. The Joule heating effects increase the reversal of TIC with the synergy of the negatively charged nanopore, and they also enhance the electroosmotic flow regardless of whether the nanopore is charged. These theoretical observations will improve our knowledge of nonclassical electrokinetic phenomena for flow control in nanopore systems. Full article

Five-dimensional (5D) recording and decoding is demonstrated by using femtosecond direct laser writing in a silver-containing commercial glass. In particular, laser intensities and ellipse orientations generated by anamorphic focusing are employed to produce 5D data storage unit (3D for XYZ, 1D for the orientation of the elliptically-shaped data storage unit and 1D for its fluorescence intensity). In the recording process, two different images of a 4-bit bitmap format were simultaneously embedded in the medium by multiplexing the elliptical orientation of the laser focus and its intensity so as to access oriented elliptical patterns with independent fluorescence intensity. In the decoding process, two merged original images were successfully reconstructed by comparing each data storage unit with a fabricated calibration matrix of 16 × 16 levels for elliptic orientations and fluorescence intensities. We believe this technique can be applied to semi-permanent high-density data storage device. Full article

Deterministic Lateral Displacement (DLD) is a label-free particle sorting method that separates by size continuously and with high resolution. By combining DLD with electric fields (eDLD), we show separation of a variety of nano and micro-sized particles primarily by their zeta potential. Zeta potential is an indicator of electrokinetic charge—the charge corresponding to the electric field at the shear plane—an important property of micro- and nanoparticles in colloidal or separation science. We also demonstrate proof of principle of separation of nanoscale liposomes of different lipid compositions, with strong relevance for biomedicine. We perform careful characterization of relevant experimental conditions necessary to obtain adequate sorting of different particle types. By choosing a combination of frequency and amplitude, sorting can be made sensitive to the particle subgroup of interest. The enhanced displacement effect due to electrokinetics is found to be significant at low frequency and for particles with high zeta potential. The effect appears to scale with the square of the voltage, suggesting that it is associated with either non-linear electrokinetics or dielectrophoresis (DEP). However, since we observe large changes in separation behavior over the frequency range at which DEP forces are expected to remain constant, DEP can be ruled out. Full article

Precise and quick measurement of samples’ flow velocities is essential for cell sorting timing control and reconstruction of acquired image-analyzed data. We developed a simple technique for the single-shot measurement of flow velocities of particles simultaneously in a microfluidic pathway. The speed was calculated from the difference in the particles’ elongation in an acquired image that appeared when two wavelengths of light with different irradiation times were applied. We ran microparticles through an imaging flow cytometer and irradiated two wavelengths of light with different irradiation times simultaneously to those particles. The mixture of the two wavelength transmitted lights was divided into two wavelengths, and the images of the same microparticles for each wavelength were acquired in a single shot. We estimated the velocity from the difference of its elongation divided by the difference of irradiation time by comparing these two images. The distribution of polystyrene beads’ velocity was parabolic and highest at the center of the flow channel, consistent with the expected velocity distribution of the laminar flow. Applying the calculated velocity, we also restored the accurate shapes and cross-sectional areas of particles in the images, indicating this simple method for improving of imaging flow cytometry and cell sorter for diagnostic screening of circulating tumor cells. Full article

Decellularized tissues are promising materials that mainly consist of extracellular matrices (ECMs) obtained by removing all cells from organs and tissues. High hydrostatic pressure (HHP) has been used for decellularization to remove cells physically from organs or tissues rather than by chemical methods. However, ultrahigh pressure induces denaturation of the ECM structure. In this study, we examined the effects of cyclic HHP at low and high pressures on the cell membrane structure to establish a novel decellularization method that enables decellularization without the denaturation of the ECM. A decellularization device using cyclic HHP (maximum pressure: 250 MPa, cycle number: 5) was developed. NB1RGB cell suspension was injected into a plastic bag to be subjected to cyclic HHP. After applying cyclic HHP, the amount of DNA inside the cells and the morphological changes of the cells were evaluated. As a result, the amount of DNA inside the cells decreased after the cyclic HHP compared to the static HHP. In addition, cyclic HHP was suggested to promote the destruction of the cell and nuclear membrane. In conclusion, it was revealed that the cell structure could be denatured and destroyed by cyclic HHP at a lower level than that of previous approaches. Full article

An active surface with an on-demand tunable topography holds great potential for various applications, such as reconfigurable metasurfaces, adaptive microlenses, soft robots and four-dimensional (4D) printing. Despite extensive progress, to achieve refined control of microscale surface structures with large-amplitude deformation remains a challenge. Moreover, driven by the demand of constructing a large area of microstructures with increased complexity—for instance, biomimetic functional textures bearing a three-dimensional (3D) gradient—novel strategies are highly desired. Here, we develop an active surface with a dynamic topography and three-tier height gradient via a strain-tunable mismatching-bonding process. Pneumatic actuation allows for rapid, reversible and uniform regulation of surface microstructures at the centimeter scale. The in-situ modulation facilitates large-amplitude deformation with a maximum tuning range of 185 μm. Moreover, the structural gradient can be modulated by programming the strain value of the bonding process. With our strategy, another two types of surfaces with a four-tier gradient and without gradient were also prepared. By providing active modulation and design flexibility of complicated microstructures, the proposed strategy would unlock more opportunities for a wealth of novel utilizations. Full article