Simulation Of Single Cell Electroporation Characteristics Under High-frequency Nanosecond Pulse Bursts Based On Mesh Transport Network Method Model

In order to solve the problems in the treatment of tumor technology using pulsed electric field,and combine the direct and rapid killing effect of microsecond pulsed electric field(?sPEF)and the indirect and slow regulation effect of nsPEF,we creatively proposed a very new research idea,which is that the high-frequency nanosecond pulse train electric field can be used to induce intracellular and extracellular membrane electroporation.However,there have not been a complete and mature electroporation theoretical system to support this idea.Therefore,the goal of this thesis is to further study the dynamic development of extracellular and nuclear membrane electroporation and their accumulation rule under high-frequency nanosecond pulse bursts,and the effects of different pulse bursts parameters on electroporation characteristics.Based on the domestic and foreign electroporation simulation,this paper adopts Mesh Transport Network Method(MTNM),which is the most mature and suitable for High-frequency nanosecond pulse bursts until now.We use this model to simulate electroporation characteristics directly and molecular transport indirectly.Considering this type of pulse lasts too much long in the time domain.Therefore,we divided the time domain into 3 parts: single pulse period,single pulse burst period,and multiple pulse bursts period,whose corresponding electroporation and molecular transport properties will be studied respectively.The main work and results of this paper are as follows:(1)The interested single cell area including nuclear membrane was discretized by MATLAB firstly,then the Mesh Transport Network Method model was established after electric transport and pore transport properities were given to the nodes of this model.The voltage of all the nodes and the pore density under different discretization pore radius of those membrane nodes are set to be unknown quantities.And the ordinary differential equations were established and then solved by ode15 s in MATLAB.The perforation characteristics of intracellular and extracellular membranes under high frequency nanosecond pulse bursts were studied in terms of spatial potential distribution,transmembrane voltage curve and pore radius distribution.We found that during the course of a single pulse,the radius of the membrane transition region is larger and the density of the pore is smaller,the density of the pore at the right electrode is larger,but the radius of the pore is smaller.And the higher the electric field intensity is,electroporation appears earlier and the number of pores will be much higher when the pulse is removed.Comparing with the nuclear membrane,extracellular membrane has more pore density.(2)Based on the MTNM model above,molecular transport was coupled with electric and pore transport.And then the molecular concentration distributaion and transmembrane flux has been solved and be used to analyze molecular transport properties and the effect of electric field on them under single pulse.We found that during the course of a single pulse,the transmembrane transport velocity is quite faster than the period when the pulse is removed.And the transition region has the optimal pore density distribution for maximum transmembrane flux.Besides,the increase of the field strength can promote the molecular transmembrane transport to a certain extent,but if the field strength is increased further,it will not promote the transmembrane transport a lot.(3)Based on the study of single pulse,this paper made a further study about the electroporation chararcteristics among different pulses and different pulse bursts,and the effects of different pulse number and pulse frequcency on them.We found that when multiple pulses are applied,the pore number is basically unchanged,but the pore radius has a cumulative effect.The effect of repetitive pulse trains is to make the electroporation presents a certain periodicity,that is to say,the action of next pulse train is almost the same as that of a series of pulses before.In addition,increasing the number of pulses in the train can increase the number of extracellular membrane pores,but not affect the number of nuclear pores.And increasing the number of intra pulse frequency does not affect the number of extracellular membrane pores,but can greatly increase the number of nuclear pores.(4)Then a futher study was made about the molecular transmembrane transport under different pulses and different pulse bursts,and the effects of different pulse number and pulse frequcency on them.We found that both the single pulse burst and the pulse bursts can promote molecular transmembrane transport.In terms of extracellular membrane,the increase of pulse number or pulse frequency in the pulse train can contribute to the molecular into the membrane.And in terms of nuclear membrane,increasing the pulse number cannot help molecular transport a lot,but a higher intra frequency will greatly improve the efficiency of molecular transmembrane transport.(5)Applying the same pulse parameters with the transmembrane transport experimental literature in the simulation model,then comparing the simulation with the experimental data,we can found that although there are still errors in numerical values with each other,both of them can illustrate the same conclusions.In summary,this paper studied the electroporation and transmembrane transport properties of single cell exposed to high frequency nanosecond pulse trains,and gave the influence rules of different pulse parameters on electroporation and molecular transport characteristics,which were used to provide theoretical guidance of parameters choosing for experimental research in cancer therapy.