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.

Automated summary

The study develops a microfluidic chip named FluidmagFace for efficient isolation, release, and protein profiling of tumor-derived extracellular vesicles (T-EVs). The FluidmagFace increases affinity by 105-fold and improves isolation efficiency by 13.9% compared to a non-fluid interface. It minimizes contamination and increases sensitivity by two orders of magnitude. With the chip, T-EVs were detected in all tested cancer samples and differentially expressed proteins were identified compared to healthy controls. The FluidmagFace opens a new avenue for cancer diagnosis and biomarker discovery.