Catalytic Hairpin Assembly‐Propelled Weak‐Inputs‐Strong‐Outputs (CP‐WISO) DNA Logic Nanodevices with Orthogonal Design and Contrary Logic Responses

Abstract Developing innovative multi‐channel DNA logic systems with strong responses for weak inputs is of paramount significance for versatile molecular computing, information processing, smart biosensing, and early medical diagnostics. However, most previous works usually necessitate abundant inputs equivalent to signal probes or computing elements, and present only single‐channel outputs, causing DNAs’ over‐consumption, limited computing functions, flexibility, and maneuverability. Herein, assisted with a catalytic‐hairpin‐assembly (CHA) amplifier and rational orthogonal design, the first universal weak‐inputs‐strong‐outputs DNA system (named CP‐WISO) with contrary logic responses is reported, which exhibited noticeable advantages over previous works. 1) Excellent FRET effect of dual‐signal DNA probes (Cy3/Cy5) brought enriched contrary logic output channels; 2) One‐step CHA amplification avoided DNAs’ over‐consumption, high cost, and complexity; 3) A library of CP‐WISO DNA logic nanodevices with the manipulated orthogonal design is realized, accompanied with enhanced flexibility, maneuverability, and computing proficiency; 4) Even and odd parity generators/checkers (pG/pC) are concurrently operated based on the “XOR∧XNOR”‐type CP‐WISO nanodevice, ensuring the recognition of erroneous bits and secure molecular data transmission; 5) Additionally, taking miRNA‐499, miRNA‐21 and miRNA‐122 as alternative model targets, the “YES∧NOT” and “AND∧NAND” CP‐WISO nanodevices achieved intelligent identification and ratiometric fluorescent detection of miRNAs in human serums, promoting the early diagnostics of acute myocardial infarction and liver cancer.