SCRATCHING THE ELECTRODE SURFACE: INSIGHTS INTO A HIGH-VOLTAGE PULSED-FIELD APPLICATION FROM IN VITRO & IN SILICO STUDIES IN INDIFFERENT FLUID

Abstract Electroporation is employed ever more frequently and broadly to deliver energy to tissues and liquid media in various applications, thus answering questions on the associated electrochemistry and electrode material alteration is becoming important. The aim of the present study is firstly to introduce and elucidate the basic relations between voltage, current, electrical impedance, and heat generation in the medium, and secondly, to characterize electrode material alteration due to pulse delivery, both by performing an in vitro and an in-silico study. Saline was used as a(n) (over)simplified model medium representing biological tissue, and exposed to high-amplitude, high-current electroporation pulses of varying duration, polarity, and pulse repetition rate. The controlled experiment was conducted by using seven different electrode metals of high purity, delivering pulses using three different protocols, and concurrently or sequentially measuring as many physical properties as available (electric current, voltage, electrode-electrolyte impedance, temperature). The intent is to present a multi-physics approach to what is occurring during procedures such as in vivo electrochemotherapy, gene delivery and in vitro gene transfection, intracardiac irreversible electroporation/pulsed-field ablation, or indeed electroporation in liquid food products such as juice. Modelling is also used to see whether it is possible to detect, via electrical measurements, any alterations in medium properties (e.g. composition) due to electrochemical effects, and if any such effects can be decoupled from the ohmic and thermal effects. Water electrolysis was observed indirectly (gas production), but not detected by electrical measurements during pulse application. Reactions at the electrodes alter the electrode electrical properties depending on the electrode material as expected, which might be important especially in applications where the same electrodes are used for delivery of electroporation pulses and also for sensing small electrical signals such as ECG for example. The demonstrated approach using saline as a model medium allows for rapid validation, and can more easily be developed further, as compared to experiments with more complex electrode materials (e.g. alloys), media (e.g. fluids, growth media, biological cell suspensions), or tissues.