Electroporation is a technique that increases the cell membrane permeability by application of electric pulses and has a widespread use in different fields such as medicine, biotechnology as well as in the food industry. Electric pulses unavoidable cause electrochemical reactions at the electrode–electrolyte interface among others, metal release from the electrodes. Consequently, a challenge in developing electroporation treatments is in predicting and optimizing the factors affecting electrochemical reactions. Efficient tool for optimization of electroporation protocols is by modeling the reactions that take place close to the electrodes. Objectives: The aim of this work was to develop and validate a numerical model to describe electrochemical reactions, mainly metal dissolution taking place at the electrode–electrolyte interface during the application of electric pulses.
Methods:
The analysis was focused on modeling aluminum cuvette and stainless steel plate electrodes, as they are commonly used in electroporation research. A two-dimensional model was used with Nernst–Planck equations for ion transport and Butler–Volmer equations to describe electrode kinetics thus for the first time giving the possibilityto implement different electroporation protocols, that is, pulse waveforms as an input function to the numericalmodel. The developed model was validated using experimental study by Kotnik et al.
Results:
Numerical model shows that the pulse amplitude and polarity (monophasic vs. biphasic) greatly affects the dissolution of aluminum and iron ions from the electrodes.
Conclusions:
The presented model requires further improvements but can with its limitations be used to optimize electroporation pulse waveforms in medicine and biology.
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References
1.
MiklavčičD, MaliB, KosB, et al.Electrochemotherapy: From the drawing board into medical practice. Biomed Eng OnLine, 2014; 13(1):29; doi: 10.1186/1475-925X-13-29
2.
DavalosRV, MirILM, RubinskyB. Tissue ablation with irreversible electroporation. Ann Biomed Eng, 2005; 33(2):223–231; doi: 10.1007/s10439-005-8981-8
3.
GeboersB, SchefferHJ, GraybillPM, et al.High-voltage electrical pulses in oncology: Irreversible electroporation, electrochemotherapy, gene electrotransfer, electrofusion, and electroimmunotherapy. Radiology, 2020; 295(2):254–272; doi: 10.1148/radiol.2020192190
4.
SugrueA, MaorE, IvorraA, et al.Irreversible electroporation for the treatment of cardiac arrhythmias. Expert Rev Cardiovasc Ther, 2018; 16(5):349–360; doi: 10.1080/14779072.2018.1459185
5.
RosazzaC, Haberl MeglicS, ZumbuschA, et al.Gene electrotransfer: A mechanistic perspective. Curr Gene Ther, 2016; 16(2):98–129; doi: 10.2174/1566523216666160331130040
6.
KotnikT, FreyW, SackM, et al.Electroporation-based applications in biotechnology. Trends Biotechnol, 2015; 33(8):480–488; doi: 10.1016/j.tibtech.2015.06.002
7.
Mahnič-KalamizaS, VorobievE, MiklavcicD. Electroporation in food processing and biorefinery. J Membr Biol, 2014; 247(12):1279–1304; doi: 10.1007/s00232-014-9737-x
8.
KotnikT, RemsL, TarekM, et al.Membrane electroporation and electropermeabilization: Mechanisms and models. Annu Rev Biophys, 2019; 48(1):63–91; doi: 10.1146/annurev-biophys-052118-115451
9.
KotnikT, KramarP, PuciharG, et al.Cell membrane electroporation- Part 1: The phenomenon. IEEE Electr Insul Mag, 2012; 28(5):14–23; doi: 10.1109/MEI.2012.6268438
SachdevS, PotočnikT, RemsL, et al.Revisiting the role of pulsed electric fields in overcoming the barriers to in vivo gene electrotransfer. Bioelectrochemistry, 2022; 144:107994; doi: 10.1016/j.bioelechem.2021.107994
12.
CindričH, KosB, MiklavčičD. Ireverzibilna elektroporacija kot metoda ablacije mehkih tkiv: Pregled in izzivi pri uporabi v kliničnem okolju. Slov Med J, 2021; 90(1–2):38–53; doi: 10.6016/ZdravVestn.2954
13.
StewartMT, HainesDE, MiklavčičD, et al.Safety and chronic lesion characterization of pulsed field ablation in a Porcine model. J Cardiovasc Electrophysiol, 2021; 32(4):958–969; doi: 10.1111/jce.14980.
14.
SugrueA, VaidyaV, WittC, et al.Irreversible electroporation for catheter-based cardiac ablation: A systematic review of the preclinical experience. J Interv Card Electrophysiol, 2019; 55(3):251–265; doi: 10.1007/s10840-019-00574-3
Batista NapotnikT, PolajžerT, MiklavčičD. Cell death due to electroporation–A review. Bioelectrochemistry, 2021; 141:107871; doi: 10.1016/j.bioelechem.2021.107871
17.
LvY, ZhangY, RubinskyB. Molecular and histological study on the effects of electrolytic electroporation on the liver. Bioelectrochemistry, 2019; 125:79–89; doi: 10.1016/j.bioelechem.2018.09.007
18.
RubinskyL, GuentherE, MikusP, et al.Electrolytic effects during tissue ablation by electroporation. Technol Cancer Res Treat, 2016; 15(5):NP95–NP103; doi: 10.1177/1533034615601549
19.
PhillipsM, RubinskyL, MeirA, et al.Combining electrolysis and electroporation for tissue ablation. Technol Cancer Res Treat, 2015; 14(4):395–410; doi: 10.1177/1533034614560102
20.
BardyGH, ColtortiF, IveyTD, et al.Some factors affecting bubble formation with catheter-mediated defibrillator pulses. Circulation, 1986; 73(3):525–538; doi: 10.1161/01.CIR.73.3.525
21.
PerkonsNR, SteinEJ, NwaezeapuC, et al.Electrolytic ablation enables cancer cell targeting through pH modulation. Commun Biol, 2018; 1(1):48; doi: 10.1038/s42003-018-0047-1
22.
SaulisG, Rodaitė-RiševičienėR, DainauskaitėVS, et al.Electrochemical Processes During High-Voltage Electric Pulses and Their Importance in Food Processing Technology. In: Advances in Food Biotechnology. (RavishankarRV. ed.) John Wiley & Sons, Ltd.: Hoboken, NJ; 2016; pp. 575–592.
23.
NilssonE, BerendsonJ, FontesE. Electrochemical treatment of tumours: A simplified mathematical model. J Electroanal Chem, 1999; 460(1):88–99; doi: 10.1016/S0022-0728(98)00352-0
24.
FriedrichU, StachowiczN, SimmA, et al.High efficiency electrotransfection with aluminum electrodes using microsecond controlled pulses. Bioelectrochem Bioenerg, 1998; 47(1):103–111; doi: 10.1016/S0302-4598(98)00163-9
25.
AbreoK, GlassJ. Cellular, biochemical, and molecular mechanisms of aluminium toxicity. Nephrol Dial Transplant, 1993; 8(Supp1):5–11; doi: 10.1093/ndt/8.supp1.5
26.
CrisponiG, FanniD, GerosaC, et al.The meaning of aluminium exposure on human health and aluminium-related diseases. Biomol Concepts, 2013; 4(1):77–87; doi: 10.1515/bmc-2012-0045
27.
ExleyC, Derek BirchallJ. The cellular toxicity of aluminium. J Theor Biol, 1992; 159(1):83–98; doi: 10.1016/S0022-5193(05)80769-6
28.
SaulisG, Rodaitė-RiševičienėR, SaulėR. Cytotoxicity of a cell culture medium treated with a high-voltage pulse using stainless steel electrodes and the role of iron ions. Membranes, 2022; 12(2):184; doi: 10.3390/membranes12020184
29.
SousaL, OliveiraMM, PessôaMTC, et al.Iron overload: Effects on cellular biochemistry. Clin Chim Acta, 2020; 504:180–189; doi: 10.1016/j.cca.2019.11.029
30.
LapidotT, GranitR, KannerJ. Lipid peroxidation by “Free” iron ions and myoglobin as affected by dietary antioxidants in simulated gastric fluids. J Agric Food Chem, 2005; 53(9):3383–3390; doi: 10.1021/jf040402g
31.
YamamotoY, HachiyaA, MatsumotoH. Oxidative damage to membranes by a combination of aluminum and iron in suspension-cultured tobacco cells. Plant Cell Physiol, 1997; 38(12):1333–1339; doi: 10.1093/oxfordjournals.pcp.a029126
32.
Mahnič-KalamizaS, MiklavčičD. Scratching the electrode surface: Insights into a high-voltage pulsed-field application from in vitro & in silico studies in indifferent fluid. Electrochim Acta, 2020; 363:137187; doi: 10.1016/j.electacta.2020.137187
33.
PataroG, DonsìG, FerrariG.Modeling of Electrochemical Reactions During Pulsed Electric Field Treatment. In: Handbook of Electroporation. (MiklavcicD. ed) Springer International Publishing: Cham, 2016; pp. 1–30.
34.
KotnikT, MiklavčičD, MirLM. Cell membrane electropermeabilization by symmetrical bipolar rectangular pulses: Part II. Reduced electrolytic contamination. Bioelectrochemistry, 2001; 54(1):91–95; doi: 10.1016/S1567-5394(01)00115-3
35.
TurjanskiP, OlaizN, Abou-AdalP, et al.pH front tracking in the electrochemical treatment (EChT) of tumors: Experiments and simulations. Electrochim Acta, 2009; 54(26):6199–6206; doi: 10.1016/j.electacta.2009.05.062
36.
SaulisG, Rodaitė-RiševičienėR, SnitkaV. Increase of the roughness of the stainless-steel anode surface due to the exposure to high-voltage electric pulses as revealed by atomic force microscopy. Bioelectrochemistry, 2007; 70(2):519–523; doi: 10.1016/j.bioelechem.2006.12.003
37.
VižintinA, VidmarJ, ŠčančarJ, et al.Effect of interphase and interpulse delay in high-frequency irreversible electroporation pulses on cell survival, membrane permeabilization and electrode material release. Bioelectrochemistry, 2020; 134:107523; doi: 10.1016/j.bioelechem.2020.107523
38.
PataroG.On the modeling of electrochemical phenomena at the electrode-solution interface in a PEF treatment chamber: Methodological approach to describe the phenomenon of metal release. J Food Eng, 2015; 165:34–44.
39.
RichardsonG, KingJR. Time-dependent modelling and asymptotic analysis of electrochemical cells. J Eng Math, 2007; 59(3):239–275; doi: 10.1007/s10665-006-9114-6
40.
NilssonE, von EulerH, BerendsonJ, et al.Electrochemical treatment of tumours. Bioelectrochemistry, 2000; 51(1):1–11; doi: 10.1016/S0302-4598(99)00073-2
41.
PataroG, BarcaGMJ, PereiraRN, et al.Quantification of metal release from stainless steel electrodes during conventional and pulsed ohmic heating. Innov Food Sci Emerg Technol, 2014; 21:66–73; doi: 10.1016/j.ifset.2013.11.009
42.
Loomis-HusselbeeJW, CullenPJ, IrvineRF, et al.Electroporation can cause artefacts due to solubilization of cations from the electrode plates. Aluminum ions enhance conversion of inositol 1,3,4,5-tetrakisphosphate into inositol 1,4,5-trisphosphate in electroporated L1210 cells. Biochem J, 1991; 277(3):883–885; doi: 10.1042/bj2770883
43.
SaulisG, LapėR, PranevičiūtėR, et al.Changes of the solution pH due to exposure by high-voltage electric pulses. Bioelectrochemistry, 2005; 67(1):101–108; doi: 10.1016/j.bioelechem.2005.03.001
44.
StapulionisR.Electric pulse-induced precipitation of biological macromolecules in electroporation. Bioelectrochem Bioenerg, 1999; 48(1):249–254; doi: 10.1016/S0302-4598(98)00206-2
45.
MorrenJ, RoodenburgB, de HaanSWH. Electrochemical reactions and electrode corrosion in pulsed electric field (PEF) treatment chambers. Innov Food Sci Emerg Technol, 2003; 4(3):285–295; doi: 10.1016/S1466-8564(03)00041-9
46.
PataroG, FalconeM, DonsìG, et al.Metal release from stainless steel electrodes of a PEF treatment chamber: Effects of electrical parameters and food composition. Innov Food Sci Emerg Technol, 2014; 21:58–65.
47.
RoodenburgB, MorrenJ, Berg HE (Iekje), et al. Metal release in a stainless steel pulsed electric field (PEF) system. Innov Food Sci Emerg Technol, 2005; 6(3):337–345; doi: 10.1016/j.ifset.2005.04.004
48.
DickinsonEJF, EkströmH, FontesE. COMSOL Multiphysics®: Finite element software for electrochemical analysis. A mini-review. Electrochem Commun, 2014; 40:71–74; doi: 10.1016/j.elecom.2013.12.020
49.
PataroG, BarcaGM, FerrariG.Mathematical Modeling of Electrochemical Phenomena at the Electrode-Solution Interface in a PEF Treatment Chamber. In: 1st World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine and Food & Environmental Technologies. (JarmT, KramarP. eds.) IFMBE Proceedings Springer Singapore: Singapore, 2016; pp. 97–100.
50.
NilssonE, FontesE. Mathematical modelling of physicochemical reactions and transport processes occurring around a platinum cathode during the electrochemical treatment of tumours. Bioelectrochemistry, 2001; 53(2):213–224; doi: 10.1016/S0302-4598(01)00097-6
51.
MokhtareA, Shiv Krishna ReddyM, RoodanVA, et al.The role of pH fronts, chlorination and physicochemical reactions in tumor necrosis in the electrochemical treatment of tumors: A numerical study. Electrochim Acta, 2019; 307:129–147; doi: 10.1016/j.electacta.2019.03.148
52.
PatelBA.Chapter 1 - Introduction to Electrochemistry for Bioanalysis. In: Electrochemistry for Bioanalysis. (PatelB. ed.) Elsevier: Amsterdam, Netherlands; 2020; pp. 1–8.
53.
GusevaO, SchmutzP, SuterT, et al.Modelling of anodic dissolution of pure aluminium in sodium chloride. Electrochim Acta, 2009; 54(19):4514–4524; doi: 10.1016/j.electacta.2009.03.048
54.
Rodaite-RisevicieneR, SauleR, SnitkaV, et al.Release of iron ions from the stainless steel anode occurring during high-voltage pulses and its consequences for cell electroporation technology. IEEE Trans Plasma Sci, 2014; 42(1):249–254; doi: 10.1109/TPS.2013.2287499
55.
TurjanskiP, OlaizN, MagliettiF, et al.The role of pH fronts in reversible electroporation. PLoS One, 2011; 6(4):e17303; doi: 10.1371/journal.pone.0017303
56.
MiklavčičD, SeršaG, KryžanowskiM, et al.Tumor treatment by direct electric current-tumor temperature and pH, electrode material and configuration. Bioelectrochem Bioenerg, 1993; 30:209–220; doi: 10.1016/0302-4598(93)80080-E
57.
NilssonE, BerendsonJ, FontesE. Development of a dosage method for electrochemical treatment of tumours: A simplified mathematical model. Bioelectrochem Bioenerg, 1998; 47(1):11–18; doi: 10.1016/S0302-4598(98)00157-3
58.
ColomboL, GonzálezG, MarshallG, et al.Ion transport in tumors under electrochemical treatment: In vivo, in vitro and in silico modeling. Bioelectrochemistry, 2007; 71(2):223–232; doi: 10.1016/j.bioelechem.2007.07.001
59.
ScuderiM, Dermol-ČerneJ, Batista NapotnikT, et al.Characterization of experimentally observed complex interplay between pulse duration, electrical field strength, and cell orientation on electroporation outcome using a time-dependent nonlinear numerical model. Biomolecules, 2023; 13(5):727; doi: 10.3390/biom13050727
60.
RemsL, UšajM, KandušerM, et al.Cell electrofusion using nanosecond electric pulses. Sci Rep, 2013; 3(1):3382; doi: 10.1038/srep03382
WahabFMAE, KhedrMGA, DinAMSE. Effect of anions on the dissolution of Al in acid solutions. J Electroanal Chem Interfacial Electrochem, 1978; 86(2):383–393; doi: 10.1016/S0022-0728(78)80012-6
63.
PicardT, Cathalifaud-FeuilladeG, MazetM, et al.Cathodic dissolution in the electrocoagulation process using aluminium electrodes. J Environ Monit, 2000; 2(1):77–80; doi: 10.1039/a908248d
64.
SherifE-S.A comparative study on the electrochemical corrosion behavior of iron and X-65 steel in 4.0 wt % sodium chloride solution after different exposure intervals. Molecules, 2014; 19(7):9962–9974; doi: 10.3390/molecules19079962
65.
DebordeM, Von GuntenU. Reactions of chlorine with inorganic and organic compounds during water treatment—Kinetics and mechanisms: A critical review. Water Res, 2008; 42(1–2):13–51; doi: 10.1016/j.watres.2007.07.025
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