Hybrid Microtubule–Solid-State Nanopores for Single-Molecule Analysis

Abstract

We demonstrate a hybrid microtubule–solid-state nanopore (MT–SSN) platform that enables label-free single-molecule analysis. Under continuous voltage bias, individual taxol-stabilized MTs are electrostatically anchored into an SSN to form a stable conduit for ionic current. We measured ionic current through MT–SSNs under two distinct configurations, one in which the SSN constricts ionic flow, and the other where the MT itself serves as the primary conduction channel. The geometrical asymmetry of the hybrid MT–SSN leads to a pronounced current–voltage asymmetry, that is, current rectification. Compared to bare SSNs, the hybrid MT–SSN slows double-stranded DNA translocation by up to ∼3.5× and enhances event-level signal contrast by increasing the relative current blockade, despite an increase in baseline low-frequency noise. By repurposing the hollow, charged nanotubule of MTs to establish a novel framework for probing nanoscale ionic transport at the single-molecule level, this study provides insight into the broader use of cytoskeletal proteins for bioelectronics sensing.