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

Abstract

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 × 220 μm2, 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-oxide-semiconductor 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 kΩ to 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 14 μm 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.