A novel complex impedance flow cytometry method for single-cell electrical characterization toward biomedical applications

Electrical characterization analysis of single cells by impedance flow cytometry is emerging as a compact, low-cost, high-throughput method for analyzing cell population heterogeneity based on their electrophysiology. Cell analysis requires a combination of conventional biophysical methods based on microfluidic systems, including manipulating, identifying, and enumerating biological cells. However, measurements on large cell populations consisting of different cell lines provide only average information on cell numbers without distinguishing the difference in electrical properties between cell lines. Furthermore, cellular phenotypic heterogeneity is often evaluated based on differences in physiological properties such as cell size, shape and endoplasmic reticulum features, and nucleus size. In this study, a novel complex impedance flow cytometry method was proposed and numerically investigated, enabling the detection and differentiation of the electrical characteristics of individual cells. The complex impedance sensing structure modeled the configuration of cell-by-cell passing through patterned electrodes integrated into a microchannel, which allows the detection and differentiation of red blood cells (RBCs) and breast cancer cells (MCF-7). The results show that the change in resistance and reactance values for the MCF-7 cells is approximately 297.7 kO and 4.8 kO, respectively. Meanwhile, the change in resistance and reactance values for RBCs is approximately 9.2 kO and 2.6 kO, respectively. Besides, this study demonstrates that the impedance change is frequency-dependent and exhibits a specific dispersion for each region of RBCs and MCF-7 cells. This work verifies the effectiveness and feasibility of the proposed analysis method and also lays a strong foundation for the success of future experimental works on biological cell detection and enumeration for biomedical applications.