Sheathless elasto-inertial focusing of sub-25 nm particles in straight microchannels

Nanoscale biological particles, such as lipoproteins (10-80 nm) or extracellular vesicles (30-200 nm), play pivotal roles in health and disease, including conditions like cardiovascular disorders and cancer. Their effective analysis is crucial for applications in diagnostics, quality control, and nanomedicine development. While elasto-inertial focusing offers a powerful method to manipulate particles without external fields, achieving consistent focusing of nanoparticles (<500 nm) has remained a challenge. In this study, we experimentally demonstrate elasto-inertial focusing of nanoparticles as small as 25 nm using straight high-aspect-ratio microchannels in a sheathless flow. Systematic investigations reveal the influence of channel width, particle size, viscoelastic concentration, and flow rate on focusing behavior. Additionally, through numerical simulations and experimental validation, we provide insights into particle migration dynamics and viscoelastic forces governing nanoparticle focusing. Finally, we successfully focus biological particles, including liposomes (90-140 nm), extracellular vesicles (100 nm), and lipoproteins (10-25 nm), under optimized conditions, showcasing potential applications in medical diagnostics and targeted drug delivery. These findings mark a significant advancement toward size-based high-resolution particle separation, with implications for biomedicine and environmental sciences.