Portable Coulter counter with vertical through-holes for high-throughput applications

Abstract

A high-throughput Coulter counter for point-of-care (POC) applications has been developed, which measures the concentration and size distribution of cells in suspension at a single cell resolution. Vertical channels (silicon-based through-holes), instead of conventional planar ones, were employed to achieve a higher density of sensing channels for a high-throughput operation. The crosstalk from the multiple sensing channels was minimized by potentiometric measurement based on a three-electrode configuration, decoupling the neighboring channels electrically. The through-hole array and potentiometric sensing increased throughput up to 8000 cells/s in the prototype (designed with four channels). To secure the sensitivity over a wide range of cell sizes in a limited setting (a portable device powered by a battery power, <5 V), a non-inverting preamplifier with a feedback capacitor was adopted, which amplifies only transient potential change. The enhanced sensitivity by the AC gain extended the measurement range from 6-15 mu m to 4-20 mu m. The functionality of the prototypes was evaluated by gauging size and concentration of a mixture of microbeads (6, 10, 15 mu m) as well as diverse cancer cells spiked in diluted blood. The measurement results were validated with the data obtained from FACS (fluorescence activated cell sorting). (C) 2015 Elsevier B.V. All rights reserved.