Study On The Mechanism Of The Response Of The Transmembrane Voltage Induced By Pulsed Electric Field

Cancer is one of the main diseases that are threatening human lives. Theconventional therapies are not satisfactory due to the limits of appropriateness,contraindication and side effects, etc. Electrical therapy (ECT), which is the joint name ofelectroporation therapy, intracellular electro-manipulation and steep pulsed electric fieldstherapy, is a new technology developed during the last three decades. With its stronglethal effect and controllable lethal area, ECT has shown a bright and broad prospect inlocal therapy of malignant tumor. Although the individual mechanisms of ECT therapiesare different, they have a common base: When transmembrane voltage induced by pulsedelectric field is beyond the critical value of breakdown voltage, an irreversible electricalbreakdown or a reversible electrical breakdown will be leaded, so that cancer can betreated alone or in an assistant way.After analyzing cell's biophysical and dielectric characteristics, a new morereasonable and practical 5-layer singular cell model, which takes nucleolus intoconsideration, is presented firstly based on the classical 3-layer model. Then analyticalexpressions of outer and inner membrane voltages induced by steady-state field arededuced. Method of calculating the transmembrane voltage induced by time-varying fieldis also given. Based on the calculation of the transmembrane voltage induced by an idealrectangular pulse, it can be concluded that with a reducing pulse width, both the outer andthe inner membrane voltage are decreasing, while the ratio of these two voltages areincreasing. This conclusion proved in a quantitative way that the narrower is a pulse, thestronger effect it has on the nucleolus and that inducing apoptosis by a narrow pulse ispossible. Based on the calculation of the transmembrane voltage induced by an actualexponential attenuation pulse with a rising edge, it can be concluded that within someextension the smaller is a rising time constant, the greater a transmembrane voltage can beinduced,while beyond the extension, there is no distinguishing effect can be found.Alsoit can be concluded that the descending time constant has a decisive influence on thevalue of the transmembrane voltage.Finally, based on analyzing electric characteristics of normal and tumor tissues, aphysical model of tumor tissue is presented. With FEMLAB, the electrical field intensitydistribution developed by the ordinary 2-electrode and our 7-electrode are simulated andcalculated. Influence of the needle diameter and the distance between needles on the fielddistribution are analyzed. Comparison between the field distribution of 2-electrode and7-electrode array proved that 7-electrode array is more reasonable and effective.