A multichannel thermal bubble-actuated impedance flow cytometer with on-chip TIA based on CMOS-MEMS

Electrochemical impedance spectroscopy(EIS)flow cytometry offers the advantages of speed,affordability,and portability in cell analysis and cytometry applications.However,the integration challenges of microfluidic and EIS read-out circuits hinder the downsizing of cytometry devices.To address this,we developed a thermal-bubble-driven impedance flow cytometric application-specific integrated circuit(ASIC).The thermal-bubble micropump avoids external piping and equipment,enabling high-throughput designs.With a total of 36 cell counting channels,each measuring 884×220μm^(2),the chip significantly enhances the throughput of flow cytometers.Each cell counting channel incorporates a differential trans-impedance amplifier(TIA)to amplify weak biosensing signals.By eliminating the parasitic parameters created at the complementary metal-oxidesemiconductor transistor(CMOS)-micro-electromechanical systems(MEMS)interface,the counting accuracy can be increased.The on-chip TIA can adjust feedback resistance from 5 to 60 kΩto accommodate solutions with different impedances.The chip effectively classifies particles of varying sizes,demonstrated by the average peak voltages of 0.0529 and 0.4510 mV for 7 and 14μm polystyrene beads,respectively.Moreover,the counting accuracies of the chip for polystyrene beads and MSTO-211H cells are both greater than 97.6%.The chip exhibits potential for impedance flow cytometer at low cost,high-throughput,and miniaturization for the application of point-of-care diagnostics.

微纳流体光波导及其在生物传感器中的应用

微纳流体光波导融合了微观流体与微光学特征,能够在相同物理空间实现流体介质和微光学信息功能及结构的集成,是生物化学分析及生物传感器的关键器件。本文综述了微纳流体光波导研究现状及其在生物传感器和生物化学分析中的应用实例。论述了实现微纳流体光波导的全反射机理、多层干涉效应,抗谐振反射机理,以及基于上述机理实现的各种流体波导形式。重点分析了基于微纳流体层流效应的全流体波导,基于多层干涉效应的Bragg光波导、空心光子晶体波导、狭缝光流体波导、抗谐振反射光波导等多种波导的特点。指出狭缝光流体波导和抗谐振反射光波导具有更好的设计灵活性,且检测灵敏度高、可靠性好、易于集成制造,可望在生物传感器及微纳流体光学系统中得到更广泛的应用。

A NOVEL TECHNIQUE FOR MULTIPLE FAULTS AND THEIR LOCATIONS DETECTION AND START ELECTRODE SELECTION IN MICROFLUIDIC DIGITAL BIOCHIP

A device,that is used for biomedical operation or safety-critical applications like point-of-care health asssment,massive parallel DNA analysis,automated drug discovery,air-quality monitoring and food-safety testing,must have the attributes like relia bility,dependability and correctness.As the biochips are used for these purposes;therefore,these devices must be fault free all the time.Naturally before usi ng these chips,they must be well tested.We are proposing a novel technique that can detect mutiple fults,locate the fault positions within the biochip,as well as calculate the traversal time if the biochip is fault free.The proposed technique also highlights a new idea how to select the appropriate base node or pseudo source(start electrode).The main idea of the proposed technique is to form multiple loops with the neighboring electrode arrays and then test each loop by traversing test droplet to check whether there is any fault.If a fault is detected then the propoed technique also locates it by backtracking the test droplet.In case,no fault is detected,the biochip is fault free then the proposed technique also calculates the time to traverse the chip.The result suggests that the proposed technique is eficient and shows significant improvement to ca lculate fault-free biochip traversal time over existing method.

On-chip classification of micro-particles using laser light scattering and machine learning

The rapid detection of microparticles exhibits a broad range of applications in the field of science and technology. The proposed method differentiates and identifies the 2 μm and 5 μm sized particles using a laser light scattering. The detection method is based on measuring forward light scattering from the particles and then classifying the acquired data using support vector machines. The device is composed of a microfluidic chip linked with photosensors and a laser device using optical fiber. Connecting the photosensors and laser device using optical fibers makes the device more diminutive in size and portable. The prepared sample containing microspheres was passed through the channel, and the surrounding photosensors measured the scattered light. The time-domain features were evaluated from the acquired scattered light, and then the SVM classifier was trained to distinguish the particle’s data. The real-time detection of the particles was performed with an overall classification accuracy of 96.06%. The optimum conditions were evaluated to detect the particles with a minimum concentration of 0.2 μg/m L. The developed system is anticipated to be helpful in developing rapid testing devices for detecting pathogens ranging between 2 μm to 10 μm.

Microfluidic chip enables single-cell measurement for multidrug resistance in triple-negative breast cancer cells

Aims:Triple-negative breast cancer patients are commonly treated with combination chemotherapy.Nonetheless,outcomes remain substandard with relapses being of a frequent occurrence.Among the several mechanisms that result in treatment failure,multidrug resistance,which is mediated by ATP-binding cassette proteins,is the most common.Regardless of the substantial studies conducted on the heterogeneity of cancer types,only a few assays can distinguish the variability in multidrug resistance activity between individual cells.We aim to develop a single-cell assay to study this.Methods:This experiment utilized a microfluidic chip to measure the drug accumulation in single breast cancer cells in order to understand the inhibition of drug efflux properties.Results:Selection of single cells,loading of drugs,and fluorescence measurement for intracellular drug accumulation were all conducted on a microfluidic chip.As a result,measurements of the accumulation of chemotherapeutic drugs(e.g.,daunorubicin and paclitaxel)in single cells in the presence and absence of cyclosporine A were conducted.Parameters such as initial drug accumulation,signal saturation time,and fold-increase of drug with and without the presence cyclosporine A were also tested.Conclusion:The results display that drug accumulation in a single-cell greatly enhanced over its same-cell control because of inhibition by cyclosporine A.Furthermore,this experiment may provide a platform for future liquid biopsy studies to characterize the multidrug resistance activity at a single-cell level.