Evolution of Multivalent Aptamer Corona for High‐Throughput Multiplexed Detection of Multiple Cancers

Clinical in vitro diagnosis is essential in early diagnosis and prognostic assessment, yet antibody-based assays face limitations in multiplexity and scalability. To address the growing demand for modern molecular diagnostics, a multivalent aptamer corona platform for high-throughput is introduced and multiplexed multi-cancer diagnosis. With clinical serum samples, ovarian cancer-, lung cancer-, and colorectal cancer-based aptamer coronas are obtained through several rounds of alternating positive and negative systematic evolution of ligands by exponential enrichment (SELEX). Leveraging a de novo ProteoFish-SELEX strategy, which integrates nanoparticle-protein corona technology, a multivalent aptamer corona is evolved. Proteomic profiling of protein coronas revealed cancer-associated protein signatures, while aptomic profiling of aptamer coronas identified high-affinity cancer-specific aptamers. With these aptamers, high diagnostic accuracy is demonstrated in multiplexed multi-cancer detection using clinical cohorts. Multivalent aptamer corona's outstanding diagnostic performance, multiplexed detection capability, and sequencing-enabled high-throughput potential position it as a promising versatile tool for novel biomarker discovery and a transformative advancement in precision oncology.