Fig. 2: Simulation model of intracellular AP recordings and cell-electrode interface for simulated micro-electroporation.

a, b Schematic diagrams of equivalent circuit models for extracellular recorded from unperforated cells and intracellular recorded from perforated cells, respectively. The passive circuits were based on RC (resistor-capacitor parallel) elements, including non-junctional RC (Rnj, Cnj), conjunctional RC (Rj, Cj), seal resistor (Rseal), microelectrode RC (Re, Ce), and amplifier RC (Cstary). c (i) Recorded typical original AP, (ii) simulated extracellular FP and (iii) simulated intracellular AP based on original AP. d Schematic diagram of an equivalent circuit model of intracellular AP recorded by one microelectrode perforating two cardiomyocytes simultaneously. e (i) and (ii) were the original APs of neighboring cardiomyocytes, respectively; there was a time difference (Δt) in the APs of neighboring cells due to the propagation of the electrical signals, and the appearance of two spikes in the simulated AP in (iii) was due to the superposition of the intracellular signals of the two cardiomyocytes that had a time difference. f Microscope images of cardiomyocytes coupled on Au microelectrodes defined by SU-8 insulating patterns. g Schematic diagram of the cell-electrode interface model. Model types include cell coupled to small-sized microelectrode surface, cell coupled to medium-sized microelectrode surface and cell coupled to large-sized microelectrode surface. h A three-dimensional cell-microelectrode interface model constructed by COMSOL Multiphysics software was used to simulate the potential distribution, current density and electric field distribution during micro-electroporation. i–k Heatmap of the potential in the cell section during perforation at 3 V. l–n To quantitatively analyze the effects of different electrode sizes (e.g., small size: 80 μm, medium size: 100 μm, and large size: 120 μm) on the transmembrane potential during micro-electroporation. We uniformly set five reference lines 80 μm away from the bottom of the substrate at 10 μm intervals, named 1–5, respectively; and labelled the sites where the five reference lines penetrate the cell membrane, named a-j, respectively. o–q The bottom-up along the set reference lines potential magnitude. m–o Statistical transmembrane potentials at the sites where the reference lines penetrated the cardiomyocyte membrane. r–t Current densities and electric field modes of cell cross sections during perforation at 3 V. Higher densities of current lines and electric field lines represent higher current densities and electric field modes