Diffusion‐Limited Microfluidic Focusing: Oscillatory Electro‐Viscoelastic Migration of Nanoparticles and Extracellular Vesicles

ABSTRACT Inertial and viscoelastic microfluidics have emerged as strategies for high‐throughput particle handling in micro‐scale systems. However, these methods are predominantly constrained to micron‐sized particles due to the weak lift forces at the nanoscale. Nanoparticle focusing in microfluidic devices requires long channels and extreme pressures to have a practical output. This study presents oscillatory electro‐viscoelastic migration (Osc‐EVM), which overcomes these limitations, enabling the focusing of particles as small as 20 nm in conventional micron‐sized channels, achieving an unprecedented blockage ratio of 4 × 10 −4 . We investigate the parameters driving particle focusing, including the interplay between focusing and diffusion, and determine the particle focusing limits on this system. The system's applicability was demonstrated by focusing extracellular vesicles (EVs) within a canonical 50 µm × 50 µm microfluidic channel, highlighting its potential for nanoscale biomedical applications. Additionally, we propose an electric field threshold as a novel mechanism for size‐based separation of nanoparticles. These findings present Osc‐EVM as a competent separation strategy for nanoscale particles and expand the applicability of microfluidic sorting in clinical and research contexts.