Tim4‐Functionalized ^HB EV‐Chip by Isolating Plasma‐Derived Phosphatidylserine‐Positive Small Extracellular Vesicles for Pan‐Cancer Screening

Thanks to containing tumor-related molecules, small extracellular vesicles (sEVs) are emerging as biomarkers in tumor liquid biopsy and commonly employed diagnose a specific cancer. However, pan-cancer screening method for pre-symptomatic patients is crucial achieving the early cancer detection. Herein, lipid-protein capture system on herringbone (HB) microfluidic chip (HBEV-Chips) isolate multiple tumor-derived sEVs constructed. Phosphatidylserine (PS) abnormally surface-supposed binds T-cell immunoglobulin domain mucin domain-containing protein 4 (Tim4) calcium-dependent manner. PS+ isolated by HBEV-Chips perform chromatography electrospray ionization tandem mass spectrometry it found that highly correlated with pathway (P < 0.05), such Cdc42 signal transduction, neuropilin signaling pathway, Wnt pathway. And further validated clinical sample PS+sEV number shows statistical difference between healthy donors plasma 0.01) has efficient diagnostic power (area under curve = 0.86), suggesting potential biomarker screening. The Tim-4 functionalized device facilitates detection, providing be used rapid-screening tool setting.