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.

Elevated type I IFN signalling directly affects CD8+ T-cell distribution and autoantigen recognition of the skeletal muscles in active JDM patients.

The link between type I IFN and adaptive immunity, especially T-cell immunity, in JDM still remained largely unclear. This study aimed to understand the effect of elevated type I IFN signaling on CD8+ T cell-associated muscle damage in juvenile dermatomyositis (JDM). This study used flow cytometry (FC) and RT‒PCR were used to examine the circulating cell ratio and type I IFN response. And scRNA-seq was used to examine peripheral immunity in 6 active JDM patients, 3 stable JDM patients, 3 juvenile IMNM patients and 3 age-matched healthy children. In vivo validation experiments were conducted using a mouse model induced by STING agonists and an experimental autoimmune myositis model (EAM). In vitro experiments were conducted using isolated CD8+ T-cells from JDM patients and mice. We found that active JDM patients showed an extensive type I IFN response and a decreased CD8+ T-cell ratio in the periphery (P < 0.05), which was correlated with muscle involvement (P < 0.05). Both new active JDM patients and all active JDM patients showed decreased CD8+ TCM cell ratios compared with age and gender matched stable JDM patients (P < 0.05). Compared with new pediatirc systemic lupus erythematosus (SLE) patients, new active JDM patients displayed decreased CD8+ T-cell and CD8+ TCM cell ratios (P < 0.05). Active JDM patient skeletal muscle biopsies displayed an elevated type I IFN response, upregulated MHC-I expression and CD8+ T-cell infiltration, which was validated in EAM mice. sc-RNAseq demonstrated that type I IFN signalling is the kinetic factor of abnormal differentiation and enhances the cytotoxicity of peripheral CD8+ T cells in active JDM patients, which was confirmed by in vivo and in vitro validation experiments. In summary, the elevated type I IFN signalling affected the differentiation and function of CD8+ T cells in active JDM patients. Skeletal muscle-infiltrating CD8+ T cells might migrate from the periphery under the drive of type I IFN and increased MHC I signals. Therapies targeting autoantigen-specific CD8+ T cells may represent a potential new treatment direction.

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.

Low power consumption photoelectric coupling perovskite memristor with adjustable threshold voltage.

Organic-inorganic halide perovskites (OHPs) have been proven to possess unique optical and electrical properties, and achieved more extensive application as excellent materials for memristors in recent years. Based on the traditional OHP-based memristors, the intermediate layer of the memristor was prepared using yttrium oxide (Y2O3)/OHP stacking structure in this manuscript. The potential barrier between Y2O3and perovskite is relatively high (ΔEC = 2.13 eV) which leads to comparatively low current of the memristor, thus the power consumption can be reduced. Besides, by changing the external light conditions, one can realize sharp or slow switch between high resistance state (HRS) and low resistance state (LRS), so as to meet the requirement of multilevel data storage, which indicates its promising application prospect in information storage and biological simulation. In addition, based on characteristics of photoelectric coupling, the Y2O3/OHP memristor can also achieve the advantage of adjustable threshold voltage. The transition of HRS and LRS can be realized by changing the illumination condition at any voltage, which means the set and reset voltage are not fixed, so that the memristor with adjustable threshold voltage can adapt to various working conditions.

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.

Element Regulation and Dimensional Engineering Co-Optimization of Perovskite Memristors for Synaptic Plasticity Applications.

Capitalizing on rapid carrier migration characteristics and outstanding photoelectric conversion performance, halide perovskite memristors demonstrate an exceptional resistive switching performance. However, they have consistently faced constraints due to material stability issues. This study systematically employs elemental modulation and dimension engineering to effectively control perovskite memristors with different dimensions and A-site elements. Compared to pure 3D and 2D perovskites, the quasi-2D perovskite memristor, specifically BA0.15MA0.85PbI3, is identified as the optimal choice through observations of resistive switching (HRS current < 10-5 A, ON/OFF ratio > 103, endurance cycles > 1000, and retention time > 104 s) and synaptic plasticity characteristics. Subsequently, a comprehensive investigation into various synaptic plasticity aspects, including paired-pulse facilitation (PPF), spike-variability-dependent plasticity (SVDP), spike-rate-dependent plasticity (SRDP), and spike-timing-dependent plasticity (STDP), is conducted. Practical applications, such as memory-forgetting-memory and recognition of the Modified National Institute of Standards and Technology (MNIST) database handwritten data set (accuracy rate reaching 94.8%), are explored and successfully realized. This article provides good theoretical guidance for synaptic-like simulation in perovskite memristors.

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.

Highly efficient cell-microbead encapsulation using dielectrophoresis-assisted dual-nanowell array.

Recent advancements in micro/nanofabrication techniques have led to the development of portable devices for high-throughput single-cell analysis through the isolation of individual target cells, which are then paired with functionalized microbeads. Compared with commercially available benchtop instruments, portable microfluidic devices can be more widely and cost-effectively adopted in single-cell transcriptome and proteome analysis. The sample utilization and cell pairing rate (∼33%) of current stochastic-based cell-bead pairing approaches are fundamentally limited by Poisson statistics. Despite versatile technologies having been proposed to reduce randomness during the cell-bead pairing process in order to statistically beat the Poisson limit, improvement of the overall pairing rate of a single cell to a single bead is typically based on increased operational complexity and extra instability. In this article, we present a dielectrophoresis (DEP)-assisted dual-nanowell array (ddNA) device, which employs an innovative microstructure design and operating process that decouples the bead- and cell-loading processes. Our ddNA design contains thousands of subnanoliter microwell pairs specifically tailored to fit both beads and cells. Interdigitated electrodes (IDEs) are placed below the microwell structure to introduce a DEP force on cells, yielding high single-cell capture and pairing rates. Experimental results with human embryonic kidney cells confirmed the suitability and reproducibility of our design. We achieved a single-bead capture rate of >97% and a cell-bead pairing rate of >75%. We anticipate that our device will enhance the application of single-cell analysis in practical clinical use and academic research.

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.

A Review of Capillary Pressure Control Valves in Microfluidics.

Microfluidics offer microenvironments for reagent delivery, handling, mixing, reaction, and detection, but often demand the affiliated equipment for liquid control for these functions. As a helpful tool, the capillary pressure control valve (CPCV) has become popular to avoid using affiliated equipment. Liquid can be handled in a controlled manner by using the bubble pressure effects. In this paper, we analyze and categorize the CPCVs via three determining parameters: surface tension, contact angle, and microchannel shape. Finally, a few application scenarios and impacts of CPCV are listed, which includes how CPVC simplify automation of microfluidic networks, work with other driving modes; make extensive use of microfluidics by open channel, and sampling and delivery with controlled manners. The authors hope this review will help the development and use of the CPCV in microfluidic fields in both research and industry.

Auxin-induced AUXIN RESPONSE FACTOR4 activates APETALA1 and FRUITFULL to promote flowering in woodland strawberry.

Flowering time is known to be regulated by numerous pathways, such as the autonomous, gibberellin, aging, photoperiod-mediated, and vernalization pathways. These regulatory mechanisms involve both environmental triggers and endogenous hormonal cues. Additional flowering control mechanisms mediated by other phytohormones, such as auxin, are less well understood. We found that in cultivated strawberry (Fragaria × ananassa), the expression of auxin response factor4 (FaARF4) was higher in the flowering stage than in the vegetative stage. Overexpression of FaARF4 in Arabidopsis thaliana and woodland strawberry (Fragaria vesca) resulted in transgenic plants flowering earlier than control plants. In addition, FveARF4-silenced strawberry plants showed delayed flowering compared to control plants, indicating that FaARF4 and FveARF4 function similarly in regulating flowering. Further studies showed that ARF4 can bind to the promoters of the floral meristem identity genes APETALA1 (AP1) and FRUITFULL (FUL), inducing their expression and, consequently, flowering in woodland strawberry. Our studies reveal an auxin-mediated flowering pathway in strawberry involving the induction of ARF4 expression.

Anti-metastasis activity of curcumin against breast cancer via the inhibition of stem cell-like properties and EMT.

BACKGROUND: Curcumin is a polyphenolic compound with potent chemopreventive and anti-cancer efficacy. PURPOSE: To explore the potential anti-metastasis efficacy of curcumin in breast cancer stem-like cells (BCSCs), which are increasingly considered to be the origin of the recurrence and metastasis of breast cancer. METHODS: A CCK8 assay was performed to evaluate cell viability, and a colony formation assay was conducted to determine cell proliferation in MCF-7 and MDA-MB-231 adherent cells. Transwell and wound healing assays were used to detect the effect of curcumin on cell migration and invasion in MDA-MB-231 cells. Mammospheres were cultured with serum free medium (SFM) for three generations and the BCSC surface marker CD44+CD24-/low subpopulation was measured by flow cytometry. Mammosphere formation and differentiation abilities were determined after cell treatment with curcumin. Then, a reverse transcription-quantitative polymerase chain reaction assay was conducted to detect the relative mRNA level of epithelial-mesenchymal transition (EMT) marker genes and western blot analysis was performed to determine the protein expression of stem cell genes in mammospheres treated with curcumin. RESULTS: Curcumin exhibited anti-proliferative and colony formation inhibiting activities in both the MCF-7 and MDA-MB-231 cell lines. It also suppressed the migration and invasion of MDA-MB-231 cells. The CD44+CD24-/low subpopulation was larger in mammospheres when MCF-7 and MDA-MB-231 adherent cells were cultured with SFM. Further studies revealed that curcumin inhibited mammosphere formation and differentiation abilities. Moreover, curcumin down-regulated the mRNA expression of Vimentin, Fibronectin, and ß-catenin, and up-regulated E-cadherin mRNA expression levels. Western blot analysis demonstrated that curcumin decreased the protein expression of stem cell genes including Oct4, Nanog and Sox2. CONCLUSION: The results of the present study suggest that the inhibitor effects of curcumin on breast cancer cells may be related to resistance to cancer stem-like characters and the EMT process. These data indicate that curcumin could function as a type of anti-metastasis agent for breast cancer.

3D Integrated Circuit Cooling with Microfluidics.

Using microfluidic cooling to achieve thermal management of three-dimensional integrated circuits (ICs) is recognized as a promising method of extending Moore law progression in electronic components and systems. Since the U.S. Defense Advanced Research Projects Agency launched Intra/Inter Chip Enhanced Cooling thermal packaging program, the method of using microfluidic cooling in 3D ICs has been under continuous development. This paper presents an analysis of all publications available about the microfluidic cooling technologies used in 3D IC thermal management, and summarized these research works into six categories: cooling structure design, co-design issues, through silicon via (TSV) influence, specific chip applications, thermal models, and non-uniform heating and hotspots. The details of these research works are given, future works are suggested.

Identification and characterization of known and novel microRNAs in strawberry fruits induced by Botrytis cinerea.

MicroRNAs are endogenous small non-coding RNAs that negatively regulate mRNAs, mainly at the post-transcriptional level, and play an important role in resistance response of plants. To date, there are few reports on resistance response of strawberry miRNAs to pathogens. In this study, using high-throughput sequencing, 134 conserved and 35 novel miRNAs were identified in six libraries within the treatment of Botrytis cinerea. A total 497 potential target genes were predicted using Fragaria vesca genome. Most of the differential expressed miRNAs in strawberry fruits were up-regulated in early libraries and down-regulated in late libraries. PIRL, the target gene of miR5290a, showed the opposite expressed trend compared with miR5290 from T1 to T3 libraries, and functional analysis of the PIRL gene shows that it has obvious resistance to B. cinerea in the strawberry fruits with overexpressed PIRL gene. We speculate that miR5290a negatively regulates its target gene PIRL to increase resistance to pathogen infection, and further analysis of PIRL function is meaningful for studying the plant-pathogen relationship and improving strawberry fruit quality and yield.