Integrated electrical modeling of circulating tumor cells for enhanced dielectrophoretic trapping and electroporation

Abstract

This study presents a comprehensive computational and experimental investigation of the integrated dielectrophoresis (DEP) and electroporation framework for the selective manipulation and controlled treatment of circulating tumor cells (CTCs), white blood cells (WBCs), and platelets (PLTs) within a unified microfluidic platform. A multiphysics mathematical model, implemented in COMSOL Multiphysics, is developed to simulate the complete sequence of DEP-driven cell trapping followed by pulsed electric field electroporation, capturing the dynamic processes of membrane charging, pore nucleation, growth, and resealing under short-duration 2 µs electric pulses. The key electroporation parameters, including transmembrane potential, pore radius, pore density, and membrane conductivity, are systematically characterized for each cell type to define cell-specific optimal pulse protocols that maximize treatment efficacy while preserving cell viability and minimizing thermal effects. The DEP mechanism provides stable spatial confinement of target cells between electrode pairs, enabling precise and reproducible exposure to calibrated electric fields with reduced off-target perturbations. Comparative computational analysis across the three cell types reveals that the requisite electric field strength must be tailored to cell dimensions, with 1–4 kV/cm identified as appropriate for CTCs and WBCs and 10–40 kV/cm required for platelets owing to their substantially smaller diameter and correspondingly higher membrane charging threshold. The simulation results demonstrate spatially heterogeneous pore dynamics and electric displacement field distributions across the cell membrane, with the most pronounced effects concentrated at the hyperpolarized pole, underscoring the critical influence of cell geometry and electric field distribution on electroporation outcomes. To experimentally validate the computational predictions, a dedicated microfluidic platform integrating microfabricated electrode arrays with real-time impedance sensing and optical monitoring was developed and applied to THP-1 monocytic cells as a representative model system. The device comprises a central impedance sensor defining the active sensing zone and surrounding focusing electrodes with lateral dimensions of $$L = w = 600$$ µm and an inter-electrode spacing of 200 µm, electrically routed through via connections for independent excitation and measurement. Impedance spectroscopy was performed over a frequency range of $$10^{3}$$–$$10^{6}$$ Hz under applied voltages from 1 to 25 V across the 200 µm sensing gap. The impedance magnitude (|Z|) exhibited a clear monotonic decrease with increasing applied voltage, with the most pronounced reductions observed in the mid-frequency range (10–100 kHz), confirming enhanced membrane permeability and increased effective conductivity of the cell suspension under stronger electric fields. The reactive impedance component ($$X_s$$) demonstrated progressive suppression of negative reactance with increasing voltage, indicating systematic loss of membrane capacitive behavior, while the series resistance ($$R_s$$) decreased and stabilized at higher voltages, reflecting a transition from capacitance-dominated to conductivity-dominated electrical transport.