This work aimed to investigate the potential selective effects of nano-pulse stimulation (NPS) on adherent cancer and normal cells using impedance spectroscopy. 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, D _cs, 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). Afterward, a Cole–Cole model was utilized to represent the impedance of cell monolayers. The model parameter, R ₀, representing resistance at low frequency, was related to the paracellular distance, D _cc. Results showed that cancer cells could suffer a higher degree of electroporation than normal cells when exposed to the same NPS. This selective NPS effect was reflected by a greater decrease of the Cole model parameter, α, and larger induced TMPs for cancer cells. D _cc was pulse number-dependent for both types of cells after exposure (four and eight pulses, 100 ns, 660 V). D _cs showed lingering effects even 24 h after exposure to 8 ns pulses for both cancer and normal cells, suggesting that intense NPS can induce long-term changes of the cell-to-substrate interface.

这项工作旨在利用阻抗谱研究纳秒脉冲刺激（NPS）对贴壁癌和正常细胞的潜在选择性作用。使用恒定相位元件将电极极化的阻抗与总的测量阻抗分开。它的振幅还与细胞到基底的距离D _cs有关，D _cs描述了细胞和基底之间的间隙。基于单个细胞的单壳介电模型提取亚细胞成分的介电特性，并随后将其用于计算诱导跨膜电位（TMP）。之后，使用Cole-Cole模型来表示细胞单层的阻抗。模型参数R ₀代表低频电阻，与细胞旁距离D _cc有关。结果显示，当暴露于相同的NPS时，癌细胞可能比正常细胞遭受更高程度的电穿孔。Cole模型参数α的更大降低和癌细胞的更大诱导TMP反映了这种选择性NPS效应。暴露后，两种类型的电池的D _cc均取决于脉冲数（四个和八个脉冲，100 ns，660 V）。D _cs甚至在暴露于癌细胞和正常细胞的8 ns脉冲后24小时仍表现出挥之不去的效果，这表明强NPS可以诱导细胞与底物界面的长期变化。