Single-molecule DNA Bases Discrimination in Oligonucleotides by Controllable Trapping in Plasmonic Nanoholes

TL;DR

This paper introduces a method to control the residence time of DNA molecules in plasmonic hot spots, enabling single-molecule SERS detection and discrimination of DNA bases within oligonucleotides, advancing nanopore sequencing technology.

Contribution

The authors develop a technique to trap nanoparticles in plasmonic nanoholes, significantly increasing the time for SERS detection of single DNA bases and oligonucleotides.

Findings

Successful discrimination of all four DNA bases at the single-molecule level.

Extended trapping times up to minutes improve SERS signal quality.

Potential extension to label-free sensing of amino acids and proteins.

Abstract

Surface-enhanced Raman spectroscopy (SERS) sensing of DNA sequences by plasmonic nanopores could pave a way to new generation single-molecule sequencing platforms. The SERS discrimination of single DNA bases depends critically on the time that a DNA strand resides within the plasmonic hot spot. However, DNA molecules flow through the nanopores so rapidly that the SERS signals collected are not sufficient for single-molecule analysis. In this work, we report an approach to control the time that molecules reside in the hot spot by physically adsorbing them onto a gold nanoparticle and then trapping the single nanoparticle in a plasmonic nanohole. By trapping the nanoparticle for up to minutes, we demonstrate single-molecule SERS detection of all 4 DNA bases as well as discrimination of single nucleobases in a single oligonucleotide. Our method can be extended easily to label-free sensing of single-molecule amino acids and proteins.