Study on effect of electroporation combining high- and low-frequency harmonics

The effects of electroporation are highly influenced by the shape of the applied waveform. This waveform shape can modify the transmitted energy and current flow patterns, impacting the electric field distribution, temperature rise among others. These interactions, along with their synergies with electroporation, are being explored across various industrial and research domains. For instance, in the biomedical field, high-frequency waveforms such as nanosecond pulses offer distinct advantages, while in the food industry, controlled temperature increases combined with electroporation are beneficial. However, in the medical field, the effects of combining high-frequency waveforms (in the MHz range) with low-frequency waveforms (in the kHz range commonly used in clinical electroporation) have not been thoroughly studied, though hypotheses have been proposed regarding their potential effects. In this paper, proof of concept of the effect of the combination of two harmonics is presented using three different strategies to investigate new electroporation protocols. To support this study, a specialized electrical and thermal test bench was developed to control and evaluate the feasibility and potential of possible synergy between high- and low-frequency waveforms to electroporation using an in vitro model.