Experimental Study On Tumor Ablation Using Nanosecond Pulsed Electric Field

Currently,development of Cancer therapy is still a major challenge in global public health,the more effective and safer therapy is urgently required to obtain a longer tumor-free survival and a better quality of life.Compared with traditional local ablation methods generated by the thermal ablation,Irreversible electroporation(IRE)uses intense microsecond electrical pulses to induce irreversible electroporation on the cell membranes,resulting in direct cell necrosis or apoptosis without any chemical drugs.In addition,IRE technology has a better applicability due to less influences on the adjacent blood vessels,bile ducts and nerves.The tumor ablation by nanosecond pulsed electric field(nsPEF)required smaller energy injected into the tissue than that of microsecond electrical pulses,which has been already confirmed by the square wave nanosecond pulses based on the Blumlein transmission line.However,maintaining the square wave waveform requires that the load resistance is closely matched with the characteristic impedance of the energy storing in transmission line,furthermore,the large size of the pulse generator limits its clinical application.In this paper,based on spark switch and transmission line transformer(TLT)technologies,a nanosecond pulsed electric field system was developed to study the effect and controllability of tumor ablation by nanosecond exponential pulse generated by the RC circuit.This work provides the preliminary test for the development of a new non-thermal pulsed source for tumors ablation.The main work and conclusions are as follows:(1)The theoretical analysis,discharge characteristic analysis and stability evalutions of the nsPEF system circuit were carried out.The results show that the system can stably generate nanosecond exponential electric pulses with a 15-ns rising edge,a 30-ns main-pulse width.In addition,the maximum voltage peak reaches 30 kV,the repetition frequency ranges from 0 to 100 pps(pulses per second).(2)Experimental studies were carried out on ablating liver tissues in vivo and pancreatic carcinoma in situ with the nsPEF system.The results show that the system can ablate 1-cm3 liver tissue under 14.7-kV voltage peak and electrodes pairs with E[0.5,5.0,10].The experimental results confirm the safety and feasibility of ablating situ pancreatic cancer as well.(3)The influences of electrical parameters and electrode configurations on the ablation area were investigated,where the B16 melanoma cells adhered at the inside walls of the six-well plate.The results show that voltage peak,pulse number and electrode diatance have obvious infuluences on the ablation area,whereas negligible influence could be observed produced by the repetition frequency;Taking the B16 tumor cell suspension in the cuvette as the research object,the cell activity after treatment using CCK-8 detection method has been studied.The electric field intensity threshold and the optimal pulse number are determined as 6.8 kV/cm and 500 pulses,respectively.Moreover,according to the experimental and simulation results,we proposed a fitting relationship between the ablation area,and the electrode distance under different voltage peak,which is helpful for parameter optimization of nsPEF tumor ablation.