Single-Blood-Draw-Based Screening of Cancer Histotypes via Homologous Adhesion between Tumor Extracellular Vesicles and Bionic Microspheres.

Precise cancer diagnosis boosts survival rates, but liquid biopsy struggles to identify the tumor histotype from a single blood draw. We propose a Homologous Adhesion Identification (HAI) method that enables specific recognition between tumor extracellular vesicles (tEVs) and homologous tumor cell membrane-coated silica microsphere (TMS). The functionalized TMS exhibits an effective HAI property with high binding strength, speed, and biospecificity between tEVs and TMS, and their similar membrane structures facilitate efficient, rapid, and selective cancer diagnosis. The HAI method can effectively distinguish extracellular vesicles from normal and tumor sources and from different tumor histotypes and subtypes using just 10 μL of serum. It is versatile with replaceable cell membranes and lanthanide ions and supports diverse detection techniques like fluorescence, ultraviolet-visible spectrophotometry, electrochemistry, and electrochemiluminescence (ECL), with a minimum detection limit of 10 tEVs/mL. It accurately differentiates healthy and tumor blood samples in five animal models and shows significant potential for rapid cancer classification and therapeutic monitoring in clinical serum testing, both pre- and postoperatively.