Impedimetric Characterization of Normal and Cancer Cell Responses after Nano-pulse Stimulation

This work aimed to investigate the potential selective effects of nano-pulse stimulation (NPS) on adherent cancer and normal cells by means of impedance spectroscopy (IS). A constant phase element was used to separate the impedance of electrode polarization from the overall measured impedance. Its amplitude was further related to cell-to-substrate distance, Dcs, which describes the gap between cells and substrate. Dielectric properties of subcellular components were extracted based on a single-shell dielectric model for individual cells and were consequently used to calculate the induced transmembrane potentials (TMPs). Afterwards, a Cole-Cole model was utilized to represent the impedance of cell monolayers. The model parameter, R0, representing resistance at low frequency was related to the paracellular distance, Dcc. Results showed that cancer cells could suffer higher degree of electroporation than normal cells when exposed to the same NPS. Such selective NPS-effect was reflected by a greater decrease of the Cole model parameter, α, and larger induced TMPs for cancer cells. Dcc exhibited a pulse number-dependent manner for both types of cells after exposures (4 and 8 pulses, 100 ns, 660V). Dcs showed lingering effects even 24 h after exposure to 8 nanosecond pulses for both cancer and normal cells, suggesting intense NPS can induce long-term changes of the cell-to-substrate interface.