Recent Advancements in Electroporation Technologies: From Bench to Clinic

Abstract

Over the past decade, the increased adoption of electroporation-based technologies has led to an expansion of clinical research initiatives. Electroporation has been utilized in molecular biology for mammalian and bacterial transfection; for food sanitation; and in therapeutic settings to increase drug uptake, for gene therapy, and to eliminate cancerous tissues. We begin this article by discussing the biophysics required for understanding the concepts behind the cell permeation phenomenon that is electroporation. We then review nano- and microscale single-cell electroporation technologies before scaling up to emerging in vivo applications.

Keywords: electrochemotherapy; gene therapy; microfluidics; pulsed field ablation; transfection.

Figure 1

Equivalent cell models may be used to represent the electrical pathways of the intact cell (a) prior to pulsing, (b) while exposed to a low-frequency unipolar pulse prior to membrane disruption, and (c) following electroporation leading to membrane impedance reduction with low-frequency unipolar bursts. In all cases, current travels down the paths of least resistance. Abbreviations: $C_{\mathrm{m}}$, capacitance of the cellular membrane; $I$, current; $R_{\mathrm{e}}$, extracellular resistance; $R_{\mathrm{e}\mathrm{p}}$, resistance of the membrane undergoing electroporation; $R_{\mathrm{e}\mathrm{p}\text{-Lf}}$, reduced resistance of electroporated membrane under low-frequency current; $R_{\mathrm{i}}$, intracellular resistance; $R_{\mathrm{m}}$, resistance of the intact cell membrane. Figure adapted from images created with BioRender.com.

Figure 2

(a–d) Representative flow-through, microfluidics-based electroporation techniques and (e–h) nanostructure-mediated electroporation techniques at the single-cell level.

Figure 3

An overview of in vivo electroporation-based techniques. Reversible techniques include electrochemotherapy as an adjuvant to therapeutics and electrogene transfer for gene manipulation to treat a variety of conditions. Irreversible techniques include tissue ablation as a monotherapy for targeting malignant tissues and cardiac ablation for treating arrhythmias. Figure adapted from images created with BioRender.com.

Figure 4

(a) Schematic demonstrating the insertion of six electrodes around the margin of tumor thrombosis for electrochemotherapy treatment of the right portal vein. (b) Percutaneous insertion of electrode needles via (c) ultrasound guidance in a minimally invasive procedure. Figure adapted from Reference (CC BY 4.0).