Quantification of cell death using an impedance-based microfluidic device

Abstract

Dielectric spectroscopy is a nondestructive method to characterize dielectric properties by measuring impedance data over a frequency spectrum. This method has been widely used for various applications such as counting, sizing, and monitoring biological cells and particles. Recently, utilization of this method has been suggested in various stages of the drug discovery process due to low sample consumption and fast analysis time. In this study, we used a previously developed microfluidic system to confine single PC-3 cells in microwells using dielectrophoretic forces and perform the impedance measurements. PC-3 cells are treated with 100 μM Enzalutamide drug, and their impedance response is recorded until the cells are totally dead as predicted with viability tests. Four different approaches are used to analyze the impedance spectrum. Equivalent circuit modeling is used to extract the cell electrical properties as a function of time. Principal component analysis (PCA) is used to quantify cellular response to drug as a function of time. Single frequency measurements are conducted to observe how the cells respond over time. Finally, opacity ratio is defined as an additional quantification method. This device is capable of quantitatively measuring drug effects on biological cells and detecting cell death. The results show that the proposed microfluidic system has the potential to be used in early stages of the drug discovery process.