Abstract

Extracellular vesicles (EVs) have been extensively exploited as diagnostic and therapeutic agents in life science and clinical diagnosis. Containing rich intracellular molecules, EVs hold great potential for understanding disease mechanisms, diagnostics, and drug development. However, effective isolation of EVs from complex samples remains challenging due to limitations in current methods, which often suffer from low yield, purity, and efficiency, hindering both basic research and clinical translation. In this study, we proposed a portable vortex tangential flow filtration (VTFF) system for automated separation of EVs by mimicking the structure of the gill arch in suspension-feeding fishes. Specifically, this study developed an efficient multi-stage filtration device with built-in herringbone baffles in the microchannel in order to achieve efficient separation and purification of EVs in continuous flow. By combining bio-inspired architecture with tangential flow filtration, this approach enables effective isolation and recovery of EVs. We demonstrated its utility by separating large and small EVs from plasma samples of patients with malignant and benign lung nodules, facilitating subsequent proteomic analysis and highlighting the system's applicability in biomedical research.