Advances in Fabrication and Biomedical Integration of Precision Electroporation Devices

Electroporation, a biophysical method that transiently permeabilizes cell membranes via externally applied electric pulses, has evolved from bulk, low-resolution approaches to highly controlled micro- and nano-electroporation (MEP/NEP) platforms. By inducing a transmembrane potential exceeding a critical threshold (≈0.5–1.5 V), nanoscale pores form, enabling delivery of nucleic acids, proteins, drugs, and probes without viral vectors or chemical carriers. Early work demonstrated efficient plasmid uptake in mouse lyoma cells using high-intensity, short-duration pulses, establishing the foundation for modern gene transfer applications. Contemporary MEP devices improve spatial and temporal field control, reducing voltage requirements and cellular damage, while NEP systems focus the electric field onto subcellular regions, magnifying the electrophoretic component of transport, which contributes to a lesser, cargo- and parameter-dependent degree in bulk and micro-electroporation as well, to achieve rapid, high-efficiency cargo delivery. Advances in device architecture, including microchannels, high aspect ratio nanostructures, nanochannel arrays, and nanofountain probes, have expanded capabilities across gene delivery, tissue engineering, drug screening, cell lysis, and cell fusion. Beyond cargo transport, the applied field is increasingly used as a biological stimulus, modulating extracellular vesicle secretion and cargo content for cell engineering and biomanufacturing. Nevertheless, challenges persist: achieving uniform pore geometry, preserving viability, scaling throughput, and translating in vitro designs to in vivo contexts. Ongoing innovations in electrode materials, fabrication techniques, and integrated microfluidic systems promise to overcome these barriers, positioning MEP/NEP as a versatile platform for accelerating biomedical research and therapeutic development.