A Duplex Polymerization Strategy for General, Programmable and High‐Resolution Nanopore‐Based Sensing

Abstract Nanopore sensing is highly promising in single molecular analysis but their broad applications have been challenged by the limited strategies that can transduce a target‐of‐interest into a specific and anti‐false/inference signal, especially for solid‐state nanopores with relatively lower resolution and higher noise. Here we report a high‐resolution signal‐production concept named target‐induced duplex polymerization strategy (DPS). Through linking the same or different duplex substrates (DSs) with a special linker (L) and an optional structure tag (ST), the DPS can generate target‐specific DS polymers with highly controllable duration times, duration intervals and even distinguished secondary tagging currents. Experimentally, DPS mono‐polymerization of single DS and co‐polymerization of multiple DSs has verified the duration time of a DPS product is the sum of those for each DS monomer. Tetrahedron‐DNA structures with different sizes are used as the STs to provide needle‐like secondary peaks for further resolution enhancement and multiplex assay. With these examples DPS represents a general, programmable and advanced strategy that may simultaneously provide size‐amplification, concentration amplification, and signal‐specificity for molecular recognition. It is also promisingly in various applications regarding to single molecular investigation, such as polymerization degree, structure/side chain conformation, programmable multiplex decoding and information index.