The illusion of sharp boundaries: unresolved issues in reversible and irreversible electroporation

Electroporation has birthed two massive parallel universes of applications: medicine and food processing. Despite operating on the same fundamental physics, these fields fail to crosspollinate, limiting their advancement. The classical “aqueous pore” model and threshold-based definitions fail to explain the highly complex, multiparameter realities of molecular transport, cell death mechanisms, and tissue-level physiological responses. The fields often struggle to translate in vitro findings—where even varying cell lines yield conflicting results—into predictive clinical and industrial outcomes. Upscaling from small animals to humans, as well as from laboratory to industrial scale, often fails due to increasing biological complexity and variability. This translational chasm is exacerbated by a lack of multiscale and multiphysics modeling that couples electric fields with thermodynamics, fluid dynamics, and electrochemistry and most of all downstream effects of electroporation like cell death and changes in mass transport. Emerging clinical applications like Pulsed Field Ablation and therapies based on gene delivery represents a perplexing, multiparameter optimization problem that must balance electrical, thermal, and electrochemical constraints. This paper highlights critical deficiencies, explores the sharp boundary between reversible and irreversible electroporation, and calls for better reporting, standardized nomenclature, and interdisciplinary collaboration to elevate electroporation from an empirical to a universally predictive, robust science.