A Nonlinear Size-Dependent Equivalent Circuit Model for Single-Cell Electroporation on Microfluidic Chips

Abstract

Electroporation (EP) is a process of applying a pulsed intense electric field on the cell membrane to temporarily induce nanoscale electropores on the plasma membrane of biological cells. A nonlinear size-dependent equivalent circuit model of a single-cell electroporation system is proposed to investigate dynamic electromechanical behavior of cells on microfluidic chips during EP. This model consists of size-dependent electromechanical components of a cell, electrical components of poration media, and a microfluidic chip. A single-cell microfluidic EP chip with 3D microelectrode arrays along a microchannel is designed and fabricated to experimentally analyze the permeabilization of a cell. Predicted electrical current responses of the model are in good agreement (average error of 6%) with that of single-cell EP. The proposed model can successfully predict the time responses of transmembrane voltage, pore diameter, and pore density at four different stages of permeabilization. These stages are categorized based on electromechanical changes of the lipid membrane. The current-voltage characteristic curve of the cell membrane during EP is also investigated at different EP stages in detail. The model can precisely predict the electric breakdown of different cell lines at a specific critical cell membrane voltage of the target cell lines.