Si Microanemones Integrated Microfluidic Chip for Highly Efficient Isolation of Extracellular Vesicles

Abstract Liquid biopsy has emerged as a transformative approach for early cancer detection and treatment monitoring, offering significant potential to improve patient outcomes. However, isolating tumor‐derived extracellular vesicles (EVs) from body fluids is often impeded by background noise, making subsequent analysis challenging. Herein, a bio‐inspired 3D silicon microanemone (SMA) microfluidic chip is reported. This innovative structure is prepared by a two‐step lithographic method combined with nanosphere lithography, achieving an impressive isolation efficiency of 89.4%. Simulation results reveal that the hierarchical structure not only provides more antibody binding sites but also synergizes with an integrated chaotic mixer to amplify fluid perturbations, while inducing a flow around circular cylinder phenomenon to enhance EV‐antibody interactions. Finally, the SMA chip's performance is assessed with clinical samples and combined with RT‐qPCR‐based β‐actin ( ACTB ) mRNA quantification in purified EVs. The results demonstrate its high sensitivity and specificity in isolating cancer‐related EV subgroups, enabling non‐invasive and precise detection of cancer biomarkers in blood samples.