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RT\u2010qPCR is sensitive but complex and equipment\u2010intensive, limiting point\u2010of\u2010care use. Herein, for the first time, an organic electrochemical transistor (OECT) biosensor is reported utilizing small molecules as recognition elements for rapid, ultrasensitive and amplification\u2010free detection of RNA. The biosensor leverages \u201cclick chemistry\u201d to precisely immobilize screened and chemically edited small molecules to the OECT gate, enabling efficient target RNA binding. To further enhance sensitivity and reduce detection time, a rapid sample incubation module utilizing alternating current (AC) electrokinetic acceleration without the influence of electric currents and thermal effects strategy is employed to accelerate biomolecule transport and increase binding kinetics. This approach is validated using a model system incorporating C5, a chemically optimized small\u2010molecule ligand that selectively binds SARS\u2010CoV\u20102 RNA. The resulting biosensor achieves real\u2010time, amplification\u2010free RNA detection within three minutes, and the results are transmitted to electronic devices via Bluetooth. Notably, it shows impressive sensitivity (0.3 aM) and excellent long\u2010term stability, retaining functional sensitivity for five months under ambient storage. This work establishes a new paradigm for RNA biosensing, demonstrating the power of integrating small\u2010molecule recognition, electrochemical transduction and AC field enhancement for next\u2010generation rapid diagnostics.<\/jats:p>","DOI":"10.1002\/adma.202515338","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T07:36:26Z","timestamp":1765179386000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Small Molecule\u2010Driven Organic Electrochemical Transistors for Rapid, Ultrasensitive and Amplification\u2010Free Detection of RNA Biomarkers"],"prefix":"10.1002","volume":"38","author":[{"given":"Jiacheng","family":"Yu","sequence":"first","affiliation":[{"name":"Biotechnology and Food Engineering Guangdong Technion\u2010Israel Institute of Technology (GTIIT)  Shantou 515063 China"},{"name":"Faculty of Biotechnology and Food Engineering Technion\u2010Israel Institute of Technology (IIT)  Haifa 3200003 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qitong","family":"Feng","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences (MIPS) Monash University  Parkville VIC 3052 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Biotechnology and Food Engineering Guangdong Technion\u2010Israel Institute of Technology (GTIIT)  Shantou 515063 China"},{"name":"Faculty of Biotechnology and Food Engineering Technion\u2010Israel Institute of Technology (IIT)  Haifa 3200003 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine Shanghai University  Shanghai 200444 China"},{"name":"MedEng\u2010X Insititutes Shanghai University  Shanghai 200444 China"},{"name":"Organoid Research Center Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Flexible Electronics (LoFE) &amp; 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