Dekai Ye

The demand for rapid and highly sensitive sensing technologies is increasing across diverse fields, including precise disease diagnosis, early-stage screening, and real-time environmental monitoring. Field-effect transistor (FET)-based sensing platforms have shown tremendous potential for detecting target molecules at extremely low concentrations, owing to their ultrahigh sensitivity, label-free and amplification-free operation, and rapid response. In recent years, the rapid advancement of nucleic acid probe design and interfacial engineering has markedly accelerated the development of FET sensors, leading to the emergence of nucleic acid-based FET (NA-FET) biosensors. Beyond their fundamental role in nucleic acid detection, the integration of nucleic acid aptamers and framework nucleic acids has greatly expanded NA-FET biosensors’ applicability to a wide range of analytes and multiplexed detection. At the same time, advances in semiconductor materials have endowed the NA-FET biosensor with highly efficient signal transduction and diverse device architectures, enabling successful proof-of-concept demonstrations for various clinically and environmentally relevant molecular biomarkers. Furthermore, the integration into portable, wearable, and implantable devices has laid a solid foundation for their future development into real-world applications. This review summarizes recent cutting-edge progress in NA-FET biosensors, highlights key design strategies and performance improvements, and discusses current challenges, future development directions, and their prospects for practical applications.