A Programmable Nanopore Logic Platform with Bidirectional Amplification for PNK Detection and DNA‐Based Computation

Abstract The integration of nucleic acid amplification strategies with solid‐state nanopores has attracted increasing attention for trace analyte detection. Yet, studies on nanopore‐based logic gates remain rare due to the unidirectional nature of nanopore signal outputs and limited scalability, with most amplification‐assisted nanopore sensors still restricted to one‐way signal enhancement. Here, a nanopore logic device based on an autocatalytic hybridization reaction (AHR) that integrates catalytic hairpin assembly (CHA) with hybridization chain reaction (HCR). The initiator‐triggered HCR generates DNA duplexes and abundant CHA activators, while CHA releases sequences identical to the initiator, forming a mutual feedback loop for bidirectional amplification. This strategy drives efficient synthesis of DNA nanowires that adsorb onto G4‐PAMAM‐modified nanopores under an electric field, altering surface charges and enhancing ionic rectification. With an auxiliary hairpin, the system achieves ultrasensitive detection of PNK (0.0001 U mL −1 ). Moreover, diverse DNA‐based Boolean logic gates (OR, YES, AND, INHIBIT, NOR, NAND) can be constructed without complex sequence engineering. This label‐free nanopore platform offers a versatile and universal strategy for biomolecular logic gate construction and provides a promising foundation for large‐scale DNA computing circuits and advanced multi‐target biosensors.