Retarded Translocation of Nucleic Acids through α‑Hemolysin Nanopore in the Presence of a Calcium Flux

Electrophysiological measurement of molecular translocation through a nanopore is the fundamental basis of nanopore sensing. Free translocation of nucleic acids however is normally so fast that the identities of the compounds are not clearly resolvable. Inspired by recent progress in fluorescence imaging based nanopore sensing, we found that during electrophysiology measurements, translocation of nucleic acids is also retarded whenever a calcium flux around the pore vicinity is established. The residence time of nucleic acids has been extended to tens of milliseconds, a result of the strong coupling between nucleic acids and free calcium ions. The methodology presented here is applicable to both DNAs and RNAs and is able to clearly discriminate between different RNA homopolymers. This offers new insights for calcium imaging based nanopore sensing and suggests a new strategy of electrophysiology-based nanopore sensing aimed at a retarded motion of nucleic acids.