Programming Ion Gating and Dynamic Response of Nanopores with Responsive Tetrahedral DNA Nanostructures

Mimicking ion-gating function with artificial nanopores empowered by well-designed responsive DNA architectures represents one of the leading maneuvers in the nanopore sensing field. However, due to the rarely preponderant orientation and uncontrollable assembly of conventional DNA constructs at heterogeneous interfaces, the recognition ability and gating efficiency remain a considerable challenge. Here, we show that manipulating the ion-gating efficiency can be readily achieved by the assembly of responsive tetrahedral DNA nanostructures in glass nanopipettes. We design a set of 3D-DNA nanostructures consisting of size-tunable DNA tetrahedrons and Pb²⁺-dependent DNAzyme structural domain in the nanopipettes, which served as the ion gate and recognition element, respectively, and thus enabled the sensing of Pb²⁺ in a label-free manner. Using the constructed 3D-DNA-nanostructured ion-gating systems, we can program stimulus-response capacity and ionic current rectification behaviors in the Pb²⁺ sensing events. We found that larger-size DNA tetrahedrons resulted in more efficient ion gating and importantly could achieve dynamic linear response to Pb²⁺, with the concentration spanning from 10 pM to 10 μM. Finite element simulations revealed that steric hindrance, rather than surface charge, may be a principal cause for regulating trans-pore ion transport. This work opens an avenue for the design of DNA nanostructure-based responsive nanopores for sensing applications.