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

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.