A Tyndall Effect-Based Visible Aptasensing Platform Enables Sensitive and Isolation-Free Profiling of Small Extracellular Vesicle Surface Proteins

Rapid and portable profiling of surface proteins on small extracellular vesicles (sEV) is crucial for noninvasive cancer screening but remains technically challenging. Here, we present a Tyndall effect (TE)-based visible aptasensing platform (TEVAP) for direct, low-cost, and isolation-free detection of sEV surface proteins from complex biological samples. Aptamer-conjugated gold nanoparticles specifically bind to sEV, forming large-scale composites that enhance the TE signal. This enables the identification of five tumor-associated proteins with a detection limit of 6.5 × 10 6 particles mL –1 without enzyme catalysis or signal amplification strategies, comparable to other instrument-dependent methods. Applied to clinical samples (e.g., 5 μL of plasma), TEVAP generated distinct signal patterns and effectively distinguished liver and breast cancer patients from healthy controls. With further validation in larger cohorts, this platform holds strong potential for convenient cancer screening and postoperative monitoring.