Light-Nucleotide versus Ion-Nucleotide Interactions for Single-Nucleotide Resolution.

Several parallel reads of ionic currents through multiple CsgG nanopores provide information about ion-nucleotide interactions for sequencing single-stranded DNA (ss-DNA) using base-calling algorithms. However, the information in ion-nucleotide interactions seems insufficient for single-read nanopore DNA sequencing. Here we report discriminative light-nucleotide interactions calculated from density functional theory (DFT), which are compared with ionic currents obtained from molecular dynamics (MD) simulations. The MD simulations were performed on a system containing a transverse nanochannel and a longitudinal solid state nanopore. We show that both of the transverse and longitudinal ionic currents during the translocation of A16, G16, T16, and C16 through the nanopore, overlapped widely. On the other hand, the UV-vis and Raman spectra of different types of single nucleotides, nucleosides, and nucleobases show relatively higher resolution than the ionic currents. Light-nucleotide interactions provide better information for characterizing the nucleotides in comparison to ion-nucleotide interactions for nanopore DNA sequencing. This can be realized by using optical techniques including surface-enhanced Raman spectroscopy (SERS) or tip-enhanced Raman spectroscopy (TERS), while plasmon excitation can be used to localize light and control the rate of nucleotide flow.