Small Molecule‐Driven Organic Electrochemical Transistors for Rapid, Ultrasensitive and Amplification‐Free Detection of RNA Biomarkers
Abstract
Abstract RNA biomarkers are vital for diagnosing infections, cancer, and neurodegenerative diseases. RT‐qPCR is sensitive but complex and equipment‐intensive, limiting point‐of‐care 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‐free detection of RNA. The biosensor leverages “click chemistry” 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‐molecule ligand that selectively binds SARS‐CoV‐2 RNA. The resulting biosensor achieves real‐time, amplification‐free 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‐term 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‐molecule recognition, electrochemical transduction and AC field enhancement for next‐generation rapid diagnostics.
Article Details
Authors (17)
Jiacheng Yu
Molecular Medicine Program, The Hospital for Sick Children
Qitong Feng
Monash Institute of Pharmaceutical Sciences (MIPS) Monash University Parkville VIC 3052 Australia
Jintao Zheng
Han Liu
Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong SAR 999077, P. R. China
Hui Liu
Runzhi Zhou
Faculty of Biotechnology and Food Engineering Guangdong Technion‐Israel Institute of Technology (GTIIT) Shantou China
Xiaohong Jiang
Haoyang Yan
Faculty of Biotechnology and Food Engineering Guangdong Technion‐Israel Institute of Technology (GTIIT) Shantou China
Zheng Liang
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering
Mingxi Chen
Omer Yehezkeli
Faculty of Biotechnology and Food Engineering Technion‐Israel Institute of Technology (IIT) Haifa 3200003 Israel
Haifeng Dong
Marshall Laboratory of Biomedical Engineering, Precision Medicine and Health Research Institute, Shenzhen Key Laboratory for Nano-Biosensing Technology, Guangdong Key Laboratory of Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Medical School
Lin Li
Bo Peng
Nicolas H. Voelcker
Melbourne Centre for Nanofabrication
Jiacan Su
Institute of Translational Medicine School of Medicine Shanghai University Shanghai China
Keying Guo
Key Lab for Special Functional Materials of Ministry of Education, National & Local Joint Engineering Research Center for High-efficiency Display and Lighting Technology, School of Nano Science and Materials Engineering, Collaborative Innovation Center of Nano Functional Materials and Applications