(a, b) Signatures for miR-155 (miRNA) hybridized with an unlabeled probe (P0) (a) and a PEG24-labeled probe (P24) (b). The PEG label allows generating a distinct current profile compared with the block using unlabeled probe. (c) Histogram showing the current amplitude of each stage in the signature in panel b. (d) Molecular configurations for sequential stages in b. When a miR-155·P24 hybrid is trapped in the pore, the single-stranded lead first enters the β-barrel (Ia). As the lead threads in the pore, the PEG label moves into the β-barrel to further reduce the blocking level (Ib). The lead with the PEG label is pulled by the electric field to induce the unzipping of the miR-155·P24 hybrid and continuously slides in the β-barrel while unzipping occurs. The PEG label finally slides out of the pore, resulting in higher pore conductance (Ic). After unzipping and probe translocation, the dissociated miR-155 temporarily resides in the nanocavity (II) and finally translocates through the β-barrel (III) to terminate the block.