Direct Measurement of Single-Molecule DNA Hybridization Dynamics with Single-Base Resolution

Abstract Herein, we report label‐free detection of single‐molecule DNA hybridization dynamics with single‐base resolution. By using an electronic circuit based on point‐decorated silicon nanowires as electrical probes, we directly record the folding/unfolding process of individual hairpin DNAs with sufficiently high signal‐to‐noise ratio and bandwidth. These measurements reveal two‐level current oscillations with strong temperature dependence, enabling us to determine the thermodynamic and kinetic properties of hairpin DNA hybridization. More importantly, successive, stepwise increases and decreases in device conductance at low temperature on a microsecond timescale are successfully observed, indicating a base‐by‐base unfolding/folding process. The process demonstrates a kinetic zipper model for DNA hybridization/dehybridization at the single base‐pair level. This measurement capability promises a label‐free single‐molecule approach to probe biomolecular interactions with fast dynamics.