Efficient Evaluation of the Influence of Electric Pulse Characteristics on the Dynamics of Cell Trans-Membrane Voltage

This paper aims at presenting a systematic approach for evaluating the effects induced on the dynamics of the Trans-Membrane Voltage of a biological cell by the characteristics of the non-ideal (trapezoidal) applied electric pulses. The proposed methodology is based on a combined use of the Design of Experiments (DoE) and Response Surface Methodology that allows to put in evidence the self and mutual effects produced by the characteristic parameters of the pulse (slew rate, the total duration of the impulse and its amplitude) on the time evolution of the Trans-Membrane Voltage (TMV). In particular, the effects on the max instantaneous value of the TMV are analysed: its qualitative behaviour vs. the considered parameters, the combination of parameters leading to the highest amplitude and the most influencing parameter are identified with an efficient search based on an optimal set of numerical trials. The analysis concerning the dependence of the max value of TMV on the pulse parameters is performed by considering either a basic Hodgkin-Huxley (HH) circuit or a modified one taking also into account the electroporation phenomenon.