Engineering positive feedback in nucleic acid circuit Biosensors: Design and applications

Positive feedback refers to a process in which a system's output signal redirected to its input and superimposed in the same direction, causing progressive amplification. Integrating positive feedback loops into biosensor design has become a powerful strategy for efficient sensitivity improvement, enabling trace biomarkers detection. Recent advancements have applied cutting-edge technologies, such as DNAzymes, nucleic acid-modifying enzymes, and CRISPR/Cas systems, to engineer positive feedback loop in nucleic acid circuit biosensors with exceptional detection capability, cost-effectiveness, and robustness. This review first explained the mechanism of positive feedback-driven signal amplification and deconstructs the design principles of positive feedback nucleic acid circuit biosensors. It then systematically reviews representative studies, highlighting design innovations and comparing their performance. Finally, the current challenges and future directions were discussed. This review aims to clarify the design logic of positive feedback biosensors and inspire the development of next-generation biosensors with enhanced detection performance.