Raman sequential readout through nanopores for RNA and protein sequencing

Abstract

Inspired by nanopore sequencing technology, we developed a plasmonic device capable of operating in a flow-through configuration to detect individual molecules as they pass through the plasmonic hotspot. This device consists of permeable plasmonic films, through which single molecules are sequentially delivered via electrophoresis, while Raman spectra are recorded in real time. We successfully captured the Raman spectra of the four DNA nucleotides as well as multiple amino acids while passing through the nanopores at single monomer level with time resolution down to 10us. For nucleotides we achieved a discrimination accuracy of 89% at single molecole level and of 99.9% for few tens of translocations. Also, we demonstrated a spatial resolution on the order of a few angstroms, suggesting clear potential for Raman based identification and sequencing of nucleic acids and proteins.