A Fluid Multivalent Magnetic Interface for High‐Performance Isolation and Proteomic Profiling of Tumor‐Derived Extracellular Vesicles

Isolation and analysis of tumor‐derived extracellular vesicles (T‐EVs) are important for clinical cancer management. Here, we develop a fluid multivalent magnetic interface (FluidmagFace) in a microfluidic chip for high‐performance isolation, release, and protein profiling of T‐EVs. The FluidmagFace increases affinity by 105‐fold with fluidity‐enhanced multivalent binding to improve isolation efficiency by 13.9 % compared with a non‐fluid interface. Its anti‐adsorption property and microfluidic hydrodynamic shear minimize contamination, increasing detection sensitivity by two orders of magnitude. Moreover, its reversibility and expandability allow high‐throughput recovery of T‐EVs for mass spectrometric protein analysis. With the chip, T‐EVs were detected in all tested cancer samples with identification of differentially expressed proteins compared with healthy controls. The FluidmagFace opens a new avenue to isolation and release of targets for cancer diagnosis and biomarker discovery. A fluid multivalent magnetic interface was engineered in a microfluidic chip to improve the kinetics and thermodynamics of biomolecular recognition for efficient isolation of tumor‐derived extracellular vesicles (T‐EVs). With the assistance of magnetic and flow fields, this interface balanced affinity, selectivity, reversibility, and extendibility, enabling high‐throughput recovery of T‐EVs for protein profiling.