Microfluidics is an emerging technology for buffer exchange in bioprocessing applications. However, achieving buffer exchange with simplicity of operation and high throughput in a straightforward channel design remains a challenge. This study presents a novel semicircular microchannel design that allows for the deterministic regulation of helical and Dean vortices through geometric confinement. By incorporating micro-obstacles into semicircular microchannels with large dimensions (900 μm wide and 100 μm high), we observe a substantial enhancement in secondary flows, leading to a unique fluid distribution across a wide range of flow rates. This design enables a high particle separation efficiency (>
96.27%) coupled with a low fluorescein purity (<
4.46%) at a high throughput of 3 × 10