Bipolar Electrode-based Sheath-Less Focusing and Continuous Acoustic Sorting of Particles and Cells in an Integrated Microfluidic Device.

Sheath-less focusing and sorting of cells or particles is an important preprocessing step in a variety of biochemical applications. Most of the previous sorting methods depend on the use of sheath flows to realize efficient cell focusing. The sheath flow dilutes the sample and requires precise flow control via additional channels. We, for the first time, reported a method of bipolar electrode (BPE)-based sheath-less focusing, switching, and tilted-angle standing surface acoustic wave-based sorting of cells and particles in continuous flow. The device consists of a piezoelectric substrate with a pair of BPEs for focusing and switching, and a pair of interdigitated transducers for cell sorting. Smaller cells experience a weak acoustic force and reach the lower outlet, whereas larger cells are subjected to a strong acoustic force such that they are propelled toward the upper outlet. We first validate the device functionality by sorting 5 and 8 µm PS beads with a high sorting efficiency. The working and deflection regions were increased by propelling the particle beam toward the bottom edge of BPE via changing the applied voltage of BPE, further improving the sorting performance with high efficiency (94%) and purity (92%). We then conducted a verification for sorting THP-1 and yeast cells, and the efficiency and purity reached 90.7 and 91.5%, respectively. This integrated device eliminates the requirement of balancing the flow of several sheath inlets and provides a robust and unique approach for cell sorting applications, showing immense promise in various applications, such as medical diagnosis, drug delivery, and personalized medicine.

The Nonvolatile Memory and Neuromorphic Simulation of ReS2/h-BN/Graphene Floating Gate Devices Under Photoelectrical Hybrid Modulations.

The floating gate devices, as a kind of nonvolatile memory, obtain great application potential in logic-in-memory chips. The 2D materials have been greatly studied due to atomically flat surfaces, higher carrier mobility, and excellent photoelectrical response. The 2D ReS2 flake is an excellent candidate for channel materials due to thickness-independent direct bandgap and outstanding optoelectronic response. In this paper, the floating gate devices are prepared with the ReS2/h-BN/Gr heterojunction. It obtains superior nonvolatile electrical memory characteristics, including a higher memory window ratio (81.82%), tiny writing/erasing voltage (±8 V/2 ms), long retention (>1000 s), and stable endurance (>1000 times) as well as multiple memory states. Meanwhile, electrical writing and optical erasing are achieved by applying electrical and optical pulses, and multilevel storage can easily be achieved by regulating light pulse parameters. Finally, due to the ideal long-time potentiation/depression synaptic weights regulated by light pulses and electrical pulses, the convolutional neural network (CNN) constructed by ReS2/h-BN/Gr floating gate devices can achieve image recognition with an accuracy of up to 98.15% for MNIST dataset and 91.24% for Fashion-MNIST dataset. The research work adds a powerful option for 2D materials floating gate devices to apply to logic-in-memory chips and neuromorphic computing.

Controlled generation of droplets using an electric field in a flow-focusing paper-based device.

Droplet-based microfluidics is a modular platform in high-throughput single-cell and small sample analyses. However, this droplet microfluidic system was widely fabricated using soft lithography or glass capillaries, which is expensive and technically demanding for various applications, limiting use in resource-poor settings. Besides, the variation in droplet size is also restricted due to the limitations on the operating forces that the paper-based platform is able to withstand. Herein, we develop a fully integrated paper-based droplet microfluidic platform for conducting droplet generation and cell encapsulation in independent aqueous droplets dispersed in a carrier oil by incorporating electric fields. Through imposing an electric field, the droplet size would decrease with increasing the electric field and smaller droplets can be produced at high applied voltage. The droplet diameter can be adjusted by the ratio of inner and outer flow velocities as well as the applied electric field. We also demonstrated the proof of concept encapsulation application of our paper device by encapsulating yeast cells under an electric field. Using a simple wax printing method, carbon electrodes can be integrated on the paper. The integrated paper-based microfluidic platform can be fabricated easily and conducted outside of centralized laboratories. This microfluidic system shows great potential in drug and cell investigations by encapsulating cells in resource-limited environments.

Label-Free Multitarget Separation of Particles and Cells under Flow Using Acoustic, Electrophoretic, and Hydrodynamic Forces.

Multiplex separation of mixed biological samples is essential in a considerable portion of biomedical research and clinical applications. An automated and operator-independent process for the separation of samples is highly sought after. There is a significant unmet need for methods that can perform fractionation of small volumes of multicomponent mixtures. Herein, we design an integrated chip that combines acoustic and electric fields to enable efficient and label-free separation of multiple different cells and particles under flow. To facilitate the connection of multiple sorting mechanisms in tandem, we investigate the electroosmosis (EO)-induced deterministic lateral displacement (DLD) separation in a combined pressure- and DC field-driven flow and exploit the combination of the bipolar electrode (BPE) focusing and surface acoustic wave (SAW) sorting modules. We successfully integrate four sequential microfluidic modules for multitarget separation within a single platform: (i) sorting particles and cells relying on the size and surface charge by adjusting the flow rate and electric field using a DLD array; (ii) alignment of cells or particles within a microfluidic channel by a bipolar electrode; (iii) separation of particles based on compressibility and density by the acoustic force; and (iv) separation of viable and nonviable cells using dielectric properties via the dielectrophoresis (DEP) force. As a proof of principle, we demonstrate the sorting of multiple cell and particle types (polystyrene (PS) particles, oil droplets, and viable and nonviable yeast cells) with high efficiency. This integrated microfluidic platform combines multiple functional components and, with its ability to noninvasively sort multiple targeted cells in a label-free manner relying on different properties, is compatible with high-definition imaging, showing great potential in diverse diagnostic and analysis applications.

A T-shaped gate tunneling field effect transistor with negative capacitance, super-steep subthreshold swing.

With the development of semiconductor technology, the size of traditional metal oxide semiconductor field effect transistor devices continues to decrease, but it cannot meet the requirements of high performance and low power consumption. Low power tunneling field effect transistor (TFET) has gradually become the focus of researchers. This paper proposes a novel T-shaped gate TFET based on the silicon with the negative capacitance (NC-TGTFET). On the basis of TGTFET, ferroelectric material (HZO) is used as gate dielectric. The simulation results show that, compared with the traditional TGTFET, the opening order and sensitivity of the two tunneling junctions are different. The influences of thickness and the doping concentration of pocket and ferroelectric material properties on the characteristics of NC-TGTFET is also discussed by Sentaurus simulation tool. Furthermore, the negative capacitance of ferroelectric material makes NC-TGTFET have a very steep subthreshold swing (18.32 mV/dec) at the range of drain current from 1 × 10-15to 1 × 10-7Aµm-1. And the on-state current (Vg= 0.5 V,Vd= 0.5 V) is 1.52 × 10-6Aµm-1.

High-Throughput Separation, Trapping, and Manipulation of Single Cells and Particles by Combined Dielectrophoresis at a Bipolar Electrode Array.

Microfluidic systems have been developed widely in scaled-down processes of laboratory techniques, but they are usually limited in achieving stand-alone functionalities. It is highly desirable to exploit an integrated microfluidic device with multiple capabilities such as cell separation, single-cell trapping, and cell manipulation. Herein, we reported a microfluidic platform integrated with actuation electrodes, for separating cells and microbeads, and bipolar electrodes, for trapping, rotating, and propelling single cells and microbeads. The separation of cells and microbeads can be first achieved by deflective dielectrophoresis (DEP) barriers. Trapping experiments with yeast cells and polystyrene (PS) microbeads suspended in aqueous solutions with different conductivities were then conducted, showing that both cells and particles can be trapped at the center of wireless electrodes by negative DEP force. Upon application of a rotating electric field, yeast cells exhibit translational movement along the electrode edges, and self-rotation is seen at an array of bipolar electrodes when electrorotational torque and traveling wave DEP force are applied on the cells. The current approach allows us to switch the propulsion and rotation direction of cells by varying the frequency of the applied electric field. Beyond the achievements of single-cell manipulation, this system permits effective control of several particles or cells simultaneously. The integration of parallel sorting and single trapping stages within a microfluidic chip enables the prospect of high-throughput cell separation, single trapping, and large-scale cell locomotion and rotation in a noninvasive and disposable format, showing great potential in single-cell analysis, targeted drug delivery, and surgery.

Enhanced model-based design of a high-throughput three dimensional micromixer driven by alternating-current electrothermal flow.

We propose a 3D microfluidic mixer based on the alternating current electrothermal (ACET) flow. The ACET vortex is produced by 3D electrodes embedded in the sidewall of the microchannel and is used to stir the fluidic sample throughout the entire channel depth. An optimized geometrical structure of the proposed 3D micromixer device is obtained based on the enhanced theoretical model of ACET flow and natural convection. We quantitatively analyze the flow field driven by the ACET, and a pattern of electrothermal microvortex is visualized by the micro-particle imaging velocimetry. Then, the mixing experiment is conducted using dye solutions with varying solution conductivities. Mixing efficiency can exceed 90% for electrolytes with 0.2 S/m (1 S/m) when the flow rate is 0.364 µL/min (0.728 µL/min) and the imposed peak-to-peak voltage is 52.5 V (35 V). A critical analysis of our micromixer in comparison with different mixer designs using a comparative mixing index is also performed. The ACET micromixer embedded with sidewall 3D electrodes can achieve a highly effective mixing performance and can generate high throughput in the continuous-flow condition.

Large-Scale Single Particle and Cell Trapping based on Rotating Electric Field Induced-Charge Electroosmosis.

We propose a simple, inexpensive microfluidic chip for large-scale trapping of single particles and cells based on induced-charge electroosmosis in a rotating electric field (ROT-ICEO). A central floating electrode array, was placed in the center of the gap between four driving electrodes with a quadrature configuration and used to immobilize single particles or cells. Cells were trapped on the electrode array by the interaction between ROT-ICEO flow and buoyancy flow. We experimentally optimized the efficiency of trapping single particles by investigating important parameters like particle or cell density and electric potential. Experimental and numerical results showed good agreement. The operation of the chip was verified by trapping single polystyrene (PS) microspheres with diameters of 5 and 20 µm and single yeast cells. The highest single particle occupancy of 73% was obtained using a floating electrode array with a diameter of 20 µm with an amplitude voltage of 5 V and frequency of 10 kHz for PS microbeads with a 5-µm diameter and density of 800 particles/µL. The ROT-ICEO flow could hold cells against fluid flows with a rate of less than 0.45 µL/min. This novel, simple, robust method to trap single cells has enormous potential in genetic and metabolic engineering.

Enhanced particle trapping performance of induced charge electroosmosis.

By increasing the number of floating electrodes or enlarging the width of single floating electrode, this work provides effective ways to strongly improve the particle trapping performance of induced charge electroosmosis (ICEO). Particle trapping with double or triple separate narrow floating electrodes increases the effective actuating range of ICEO flow and therefore enhance the optimum trapping ability to be 1.63 or 2.34 times of that with single narrow electrode (width of L=200µm), and the ideal trapping frequency is independent of the electrode number due to the mutual independence of electrochemical ion relaxation over each electrode. Furthermore, using a single wide floating electrode with the effective width equal to three separate narrow floating electrodes (L=600µm) instead of a single narrow one slightly lowers the ideal trapping frequency due to an increase in the characteristic polarization length, but the trapping performance is only up to 1.59 times of that with original single narrow electrode, implying that vertical channel confinement effect may severely suppresses the effective actuating range of ICEO flow and renders the trapping performance not as expected. Trapping experiments over wide floating electrode with different channel height were carried out, showing that the trapping performance increases by correctly increasing the channel height.

Bidirectional and Stepwise Rotation of Cells and Particles Using Induced Charge Electroosmosis Vortexes.

The rotation of cells is of significant importance in various applications including bioimaging, biophysical analysis and microsurgery. Current methods usually require complicated fabrication processes. Herein, we proposed an induced charged electroosmosis (ICEO) based on a chip manipulation method for rotating cells. Under an AC electric field, symmetric ICEO flow microvortexes formed above the electrode surface can be used to trap and rotate cells. We have discussed the impact of ICEO and dielectrophoresis (DEP) under the experimental conditions. The capabilities of our method have been tested by investigating the precise rotation of yeast cells and K562 cells in a controllable manner. By adjusting the position of cells, the rotation direction can be changed based on the asymmetric ICEO microvortexes via applying a gate voltage to the gate electrode. Additionally, by applying a pulsed signal instead of a continuous signal, we can also precisely and flexibly rotate cells in a stepwise way. Our ICEO-based rotational manipulation method is an easy to use, biocompatible and low-cost technique, allowing rotation regardless of optical, magnetic or acoustic properties of the sample.

Three-dimensional rotation of deformable cells at a bipolar electrode array using a rotating electric field.

Three-dimensional rotation of cells is imperative in a variety of applications such as biology, medicine, and chemistry. We report for the first time a versatile approach for executing controllable 3D rotation of cells or particles at a bipolar electrode (BPE) array using a rotating electric field. The versatility of this method is demonstrated by 3D rotating various cells including yeast cells and K562 cells and the cells can be rotated to a desired orientation and immobilized for further operations. Our results demonstrate how electrorotation torque, induced charge electroosmosis (ICEO) flow and dielectrophoresis can be exerted on certain cells for modulating the rotation axis, speed, and direction. ICEO-based out-of-plane rotation is capable of rotating various cells in a vertical plane regardless of their shape and size. It can realize cell orientation by rotating cells toward a specific angle and enable cell rotation by steadily rotating multiple cells at a controllable speed. The rotation spectrum for in-plane rotation is further used to extract the cellular dielectric properties. This work offers a flexible method for controllable, contactless and precise rotation of different cells or particles, offering a rapid, high-throughput, and nondestructive rotation method for cell analysis and drug discovery.

Label free and high-throughput discrimination of cells at a bipolar electrode array using the AC electrodynamics.

BACKGROUND: Cell characterization and manipulation play an important role in biological and medical applications. Cell viability evaluation is of significant importance for cell toxicology assay, dose test of anticancer drugs, and other biochemical stimulations. The electrical properties of cells change when cells transform from healthy to a pathological state. Current methods for evaluating cell viability usually requires a complicated chip and the throughput is limited. RESULTS: In this paper, a bipolar electrode (BPE) array based microfluidic device for assessing cell viability is exploited using AC electrodynamics. The viability of various cells including yeast cells and K562 cells, can be evaluated by analyzing the electro-rotation (ROT) speed and direction of cells, as well as the dielectrophoresis (DEP) responses of cells. Firstly, the cell viability can be identified by the position of the cell captured on the BPE electrode in terms of DEP force. Besides, cell viability can also be evaluated based on both the cell rotation speed and direction using ROT. Under the action of travelling wave dielectric electrophoresis force, the cell viability can also be distinguished by the rotational motion of cells on bipolar electrode edges. SIGNIFICANCE: This study demonstrates the utility of BPEs to enable scalable and high-throughput AC electrodynamics platforms by imparting a flexibility in chip design that is unparalleled by using traditional electrodes. By using BPEs, our proposed new technique owns wide application for cell characterization and viability assessment in situ detection and analysis.

Enhancement of Binding Kinetics on Affinity Substrates Using Asymmetric Electroosmotic Flow on a Sinusoidal Bipolar Electrode.

In the context of the COVID-19 epidemic, enhancing the transport of analyte to a sensor surface is crucial for rapid detection of biomolecules since common conditions, including low diffusion coefficients, cause inordinately long detection times. Integrated microfluidic immunoassay chips are receiving increasing attention for their low sample volume and fast response time. We herein take advantage of asymmetric ICEO flow at a bipolar sinusoidal electrode to improve the rate of antibody binding to the reaction surface based on finite element modeling. Three different microfluidic cavities are proposed by changing the positions of the surface reaction area. We further investigate the relationship between binding enhancement and reaction surface positions, Damkohler number, and the voltage and frequency of the AC signal applied to the driving electrodes. Furthermore, the influence of the AC signal applied to the sinusoidal bipolar electrode on antigen-antibody-binding performance is studied in detail. Above all, the simulation results demonstrate that the microfluidic immune-sensor with a sinusoidal bipolar electrode could not only significantly improve the heterogeneous immunoassays but also enable efficient enhancement of assays in a selected reaction region within the micro-cavity, providing a promising approach to a variety of immunoassay applications, such as medical diagnostics and environmental and food monitoring.

Generation of droplets with adjustable chemical concentrations based on fixed potential induced-charge electro-osmosis.

The effective control of the sample concentration within droplets is essential in a broad range of assays in chemistry and biochemistry. Here we provide an electrical method for producing batches of aqueous droplets with various chemical concentrations by exploiting fixed-potential induced-charge electroosmosis (ICEO) flow around a bipolar electrode. By applying an AC electric signal to the bipolar electrode and changing the zeta potential on it, the bipolar electrode acts as a gate electrode for generating asymmetric ICEO flow. The ICEO flow induced transverse vortexes interact with two parallel laminar streams with different chemical compositions. Controlled mixing of the aqueous solutions can be achieved by adjusting the shape and size of the asymmetric vortexes via altering the electric signal applied to the gate electrode. The mixed streams are split at a bifurcation, and one of the streams with a desired controlled concentration is pumped into a flow-focusing geometry to generate droplets with adjustable chemical concentrations. The in-droplet concentration increases in the range of 0.412-1.404 mM, as the applied voltage increases in the range of 0-70 mV at 15 kHz. This approach offers a promising method for on-chip control of chemical concentrations within droplets without labor-intensive dilutions while minimizing the sample consumption, showing great potential for next generation droplet-based applications.

Association of Formal and Informal Social Support With Health-Related Quality of Life Among Chinese Rural Elders.

Objectives: To explore the association of formal and informal social support with health-related quality of life (HRQOL) among Chinese rural elders and further investigate the influence of quantity and quality of social support on their HRQOL. Methods: The sample of 4189 Chinese rural elders over 60 years old was acquired from the 2015 China Health and Retirement Longitudinal Study (CHARLS). The HRQOL was evaluated by EQ-5D-3L questionnaire. The social support assessment was mainly based on the social support rating scale (SSRS), and Tobit regression analysis was used to explore the impact of social support on HRQOL. Results: The average EQ-5D index score (0 to 1) of the Chinese rural elders was 0.78 ± 0.16. Participants who were male or with better education were found to have higher scores. Those elders living alone, suffering from chronic diseases or disabled acquired lower scores. As for formal social support, higher medical or pension insurance and more social activities statistically significantly possessed higher scores. As for informal social support, higher number of offspring had a significant association with lower scores, while more contact with children and financial support from family were shown to be statistically significantly associated with higher scores after controlling for sociodemographic characteristics. The quality of social support is more important than its quantity. An interesting finding was that the EQ-5D index scores did not support the Chinese traditional belief that 'the more children, the more blessings'. Conclusions: The EQ-5D index scores of the rural elders in China is above the median level based on the scores of EQ-5D. Social support is significantly associated with elderly peoples' quality of life. The results would be significant for accurately improving the life quality of Chinese rural elders from the perspective of social support.

Three-dimensional paper based platform for automatically running multiple assays in a single step.

Paper based assays are paving the way to automated, simplified, robust and cost-effective point of care testing (POCT). We propose a method for fabricating three dimensional (3D) microfluidic paper based analytical devices (µPADs) via combining thin adhesive films and paper folding, which avoids the use of cellulose powders and the complex folding sequence and simultaneously permits assays in several layers. To demonstrate the effectiveness of this approach, a 3DµPADs was designed to conduct more assays on a small footprint, allowing dual colorimetric and electrochemical detections. More importantly, we further developed a 3D platform for implementing automated and multiplexed ELISA in parallel, since ELISA, a routine and standard laboratory method, has rarely been used in practical analyses outside of the laboratory. In this configuration, complex and multistep diagnostic assays can be carried out with the addition of the sample and buffer in a simple fashion. Using Troponin I as model, the device showed a broad dynamic range of detection with a detection limit of 0.35 ng/mL. Thus, the developed platforms allow for various assays to be cost-effectively carried out on a single 3D device, showing great potential in an academic setting and point of care testing under resource-poor conditions.

A novel micromixer based on the alternating current-flow field effect transistor.

Induced-charge electroosmosis (ICEO) phenomena have been attracting considerable attention as a means for pumping and mixing in microfluidic systems with the advantage of simple structures and low-energy consumption. We propose the first effort to exploit a fixed-potential ICEO flow around a floating electrode for microfluidic mixing. In analogy with the field effect transistor (FET) in microelectronics, the floating electrode act as a "gate" electrode for generating asymmetric ICEO flow and thus the device is called an AC-flow FET (AC-FFET). We take advantage of a tandem electrode configuration containing two biased center metal strips arranged in sequence at the bottom of the channel to generate asymmetric vortexes. The current device is manufactured on low-cost glass substrates via an easy and reliable process. Mixing experiments were conducted in the proposed device and the comparison between simulation and experimental results was also carried out, which indicates that the micromixer permits an efficient mixing effect. The mixing performance can be further enhanced by the application of a suitable phase difference between the driving electrode and the gate electrode or a square wave signal. Finally, we performed a critical analysis of the proposed micromixer in comparison with different mixer designs using a comparative mixing index (CMI). The novel methods put forward here offer a simple solution to mixing issues in microfluidic systems.