Ag Plasmonic Nanopore-Enabled Single-Molecule SERS Identification of Amino Acids

Accurate identification of amino acids within peptides and proteins is essential for understanding physiological and pathological mechanisms. While nanopore-based ionic current measurements have enabled single-molecule discrimination of the 20 proteinogenic amino acids, this approach offers limited insight into the chemical structure of analytes. Here, we present a novel strategy for fabricating silver plasmonic nanopores via liquid-liquid interface-confined chemical reduction within quartz nanopipettes. The resulting tapered porous Ag nanostructures are precisely positioned at the pipet tip and exhibit strong surface-enhanced Raman scattering (SERS) activity. Characteristic SERS spectra are obtained from single molecules of tryptophan and aspartic acid as they translocate through the plasmonic nanopore, allowing for statistical spectral analysis. This Ag plasmonic nanopore architecture provides a platform for integrating dynamic SERS detection into single-molecule analysis, thereby bridging the gap between single-molecule sensing and structural identification.