Equivalent Circuit Modeling and Analysis for Microfluidic Electrical Impedance Monitoring of Single-Cell Growth

Microfluidics has significantly advanced the field of single-cell analysis, particularly in studies related to cell growth, division, and heterogeneity. Electrical impedance spectroscopy (EIS), a label-free and non-invasive biosensing technique, has been integrated into microfluidic devices for high-throughput and long-term monitoring of single budding yeast cells. Accurate interpretation of EIS measurements of cell growth dynamics necessitates the establishment of theoretical equivalent circuit models for the single-cell sensing system. Here, we report on the development of equivalent circuit models of an in situ EIS sensing system to elucidate cell growth. Firstly, finite element modeling and simulation of an EIS measurement of cell growth in the EIS sensing unit were performed, guiding the fittings of electrical components for an established equivalent circuit model (ECM). From the ECM, we extracted an equivalent volume fraction applicable to various cell and sensing unit geometries to describe the geometry-dependent sensing characteristics corresponding to the electrical response in the model. Then, EIS measurements of an immobilized cell in a microfluidic device were conducted via peripheral circuits. A lumped parameter model for the entire EIS measurement system was established, with electrical components determined by fitting to experimental data. The rationality of the proposed theoretical model was validated through the long-term impedance variation induced by cell growth in experiments, demonstrating its feasibility in linking EIS data with the bio-physics underlying the experimental phenomenon.