Intimate Interaction Between Nucleic Acid and Conjugated Polymers in Organic Electrochemical Transistors Enables Ultrasensitive Biomarker Detection

ABSTRACT Ultrasensitive biosensors are crucial for pandemic prevention and healthcare monitoring. The interactions between biomolecules and functional materials, such as metals and semiconductors, have led to the development of highly sensitive biosensors. Organic semiconductors, known for their unique mixed ion and electronic conduction properties in aqueous solutions, show promise in these applications. However, the interactions between organic semiconductors and biomolecules remain poorly understood. In this study, we investigate the interaction between nucleic acid and a conjugate polymer by analyzing the performance of organic electrochemical transistors (OECTs). For the first time, we demonstrate that negatively charged ribonucleic acid (RNA) can interact with the conjugate polymer, leading to a decrease in the volumetric capacitance of the polymer channel in aqueous solutions. Based on this effect, OECTs are employed to detect various RNA biomarkers with high sensitivity, achieving multiplexed and selective detections of multiple RNA biomarkers at a low detection limit down to 10 −17 M. This portable biosensing platform can facilitate rapid, low‐cost and point‐of‐care diagnostics for various diseases.