Plasma-SELEX for Acute Myocardial Infarction Biomarker Discovery and Diagnosis.

Early diagnosis of acute diseases is fundamentally constrained by the lack of chemically tractable methods for biomarker discovery directly from a complex plasma. Here, we report PSABD (plasma-SELEX-enriched aptamer-based biomarker discovery and diagnosis), a chemical platform that integrates carboxylate magnetic-bead-mediated plasma protein capture within situ aptamer SELEX, enabling molecular-recognition-driven identification of disease-associated biomarkers. With this strategy, enriched aptamers not only serve as affinity probes but also function as structurally programmable molecular handles to pull down their targets, thereby linking selection chemistry with proteomic discovery. With acute myocardial infarction (AMI) as a model, PSABD identified malate dehydrogenase 2 (MDH2) as an unexpected AMI-associated plasma protein, which was significantly elevated in AMI patient samples and exhibited a high binding affinity to selected aptamers. On the basis of this interaction, we developed an aptamer-based analytical platform capable of distinguishing AMI patients from healthy individuals. Collectively, PSABD establishes a general chemical strategy that bridges molecular recognition, biomarker discovery, and diagnostic development, highlighting aptamers as programmable chemical probes for the acute disease diagnosis and clinical translation.