Membrane Geometric Confinement Reshapes the Lateral Electric Field Distribution and Intracellular Cargo Transport in Nanopore Electroporation

Nanopore electroporation (NanoEP) is an emerging transfection method that enables efficient and safe intracellular delivery and removal of biomolecular cargo for applications in disease modeling, tissue engineering, and therapeutic biologics manufacturing. Conventional device designs assume uniform vertical cargo flux across nanoporous membranes; however, we demonstrate that the lateral electric field distributions introduce a pronounced edge effect, with enhanced cargo delivery and depletion along the membrane perimeters. We identify and characterize the presence of this edge effect in NanoEP systems, and develop a modified Nernst–Planck model to guide the design of membrane geometries that either promote delivery uniformity or create prescribed spatial gradients within cell monolayers. By varying the internal angles formed by the membrane edges (60°C, 90°C, 120°C), we create predictable intracellular cargo gradients, while concave “serpentine” geometries with high perimeter-to-area ratios amplify delivery efficiency and minimize spatial heterogeneity compared to circular membranes. These findings establish membrane geometry as a tunable design parameter in NanoEP, enabling control over both uniform and patterned intracellular payload delivery or depletion. This geometric design principle offers a scalable strategy for next-generation transfection platforms and synthetic tissue constructs.