Deciphering Immediate Post-Pulse Membrane Resealing from 4-Electrode Impedance Measurements by Numerical Modeling

Background: The present article proposes a numerical strategy to decipher the dynamics of the cell membranes exposed to an electroporating electric field from bioimpedance measurements. In particular, we aim at discriminating between the increase of membrane conductivity due to electroporation from the increase of buffer conductivity due to ion exchange between buffer and cells.Methods: We propose first a robust calibration procedure that enables to account for the complexity of the 4-electrode experimental setup. Thanks to this robust calibration, we deduce the impedance of the sample from the measurements. Then we propose a simple electrical circuit model of the setup, which is calibrated into two steps.Results: First, we estimate the model parameters before the electroporating electric field, to obtain the cell parameters. The dynamic of the membrane resistance after the pulses is then calibrated simultaneously with the increase of the buffer conductivity due to ion exchanges. Interestingly, our model and our calibration strategy enable us to capture the dynamics of the cell membranes within a few seconds after the pulse. For longer times, we explain how additional measurements of the buffer conductivity should be performed to track the dynamics of the membrane resealing more accurately.Conclusions: The combination of the robust calibration with the well-designed equivalent circuit model enables us to capture the dynamics of ions exchange and membrane permeabilization within the few seconds after the electric pulse.