Closed Cyclic DNA Machine for Sensitive Logic Operation and APE1 Detection

Abstract DNA self‐assembly has been developed as a kind of robust signal amplification strategy, but most of reported assembly pathways are programmed to amplify signal in one direction. Herein, based on mutual‐activated cascade cycle of hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA), a closed cycle circuit (CCC) based DNA machine is developed for sensitive logic operation and molecular recognition. Benefiting from the synergistically accelerated signal amplification, the closed cyclic DNA machine enabled the logic computing with strong and significant output signals even at weak input signals. The typical logic operations such as OR, YES, AND, INHIBIT, NOR, and NAND gate, are conveniently and clearly executed with this DNA machine through rational design of the input and computing elements. Moreover, by integrating the target recognition module with the CCC module, the proposed DNA machine is further employed in the homogeneous detection of apurinic/apyrimidinic endonuclease 1 (APE1). The precise recognition and exponential signal amplification facilitated the highly selective and sensitive detection of APE1 with limit of detection (LOD) of 7.8 × 10 −5 U mL −1 . Besides, the normal cells and tumor cells are distinguished unambiguously by this method according to the detected concentration difference of cellular APE1, which indicates the robustness and practicability of this method.