SERS discrimination of single amino acid residue in single peptide by plasmonic nanocavities

TL;DR

This study demonstrates a highly sensitive plasmonic nanocavity-based SERS method capable of discriminating single amino acid residues within individual peptides, advancing single-molecule proteomics.

Contribution

The paper introduces a novel electroplasmonic nanocavity technique that enables SERS discrimination of single amino acids in peptides, including non-aromatic residues, at the single-molecule level.

Findings

Achieved discrimination of 10 amino acids using SERS in nanocavities.

Successfully identified amino acid sequences of biomarkers Vasopressin and Oxytocin.

Demonstrated differentiation between peptides with specific amino acid variations.

Abstract

Surface-enhanced Raman spectroscopy (SERS) is a sensitive label-free optical method that can provide fingerprint Raman spectra of biomolecules such as DNA, amino acids and proteins. While SERS of single DNA molecule has been recently demonstrated, Raman analysis of single protein sequence was not possible because the SERS spectra of proteins are usually dominated by signals of aromatic amino acid residues. Here, we used electroplasmonic approach to trap single gold nanoparticle in a nanohole for generating a plasmonic nanocavity between the trapped nanoparticle and the nanopore wall. The giant field generated in the nanocavity was so sensitive and localized that it enables SERS discrimination of 10 distinct amino acids at single-molecule level. The obtained spectra are used to analyze the spectra of 2 biomarkers (Vasopressin and Oxytocin) made of a short sequence of 9 amino-acids. Significantly, we demonstrated identification of single non-aromatic amino acid residues in a single short peptide chain as well as discrimination between two peptides with sequences distinguishable in 2 specific amino-acids. Our result demonstrate the high sensitivity of our method to identify single amino acid residue in a protein chain and a potential for further applications in proteomics and single-protein sequencing.