DNA circuits for biomarker detection: from signal amplification to molecular logic

Driven by the requirements of precision medicine, there is an urgent need for highly sensitive and specific biomarker detection in complex biological samples. Conventional molecular diagnostics are often limited by the necessity for thermal cycling and the vulnerability of natural enzymes. Consequently, DNA circuits-characterized by their high programmability, isothermal nature, and molecular-level information processing-have provided a transformative approach for novel bioanalytical systems. This review systematically evaluates the fundamental design principles and advanced applications of DNA circuits in precision diagnostics. We first summarize the mechanisms and performance of key signal amplification strategies, including both enzyme-assisted and enzyme-free systems. Next, we detail the construction of DNA logic circuits driven by toehold-mediated strand displacement (TMSD). Building on these concepts, we review recent advancements in applying DNA circuits to detect various biomarkers, such as nucleic acids and proteins. Finally, we critically discuss the existing challenges and future perspectives of DNA circuits, specifically addressing the maintenance of operational robustness in complex biological matrices, the expansion of computational dimensionality beyond Boolean logic, and the acceleration of clinical translation through standardized, automated POCT (point-of-care testing) integration.