Detecting weakly adsorbing molecules via label-free surface-enhanced Raman scattering is addressed through the development of tricomponent substrates using dual-rim nanorings made of Au, Ag, and CuO, each with distinct functionalities. The CuO nanorings provide strong adsorption of carboxylates via chelating bonds, while Au and Ag nanorings enhance Raman scattering signals through strong coupling effects. These tricomponent assemblies allow effective Raman-based analysis of biomolecules, including amino acids, proteins, nucleobases, and nucleotides, demonstrating their potential for sensitive detection applications.

This study introduces annular Au nanotrenches, a novel class of nanoparticles with narrow circular nanogaps (~1 nm), designed for near-field focusing in surface-enhanced Raman scattering immunoassays for detecting SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). These nanotrenches achieved an exceptionally low detection limit of 1 fg/mL for spike glycoproteins, outperforming enzyme-linked immunosorbent assays by six orders of magnitude. Clinical testing on 50 samples demonstrated a sensitivity of 96% and a selectivity of 100%, representing the superior sensing capabilities of this approach compared to existing diagnostic methods.

This study presents a highly sensitive and selective method for protein screening using surface-enhanced Raman scattering facilitated by octahedral Au nanotrenches, a novel class of nanoparticles with narrow trench-like excavations in the facets of Au octahedrons. The unique geometry of these nanotrenches maximizes electromagnetic near-field focusing by confining and reflecting light within the trenches, enhancing detection sensitivity. Using Ni ions and molecular linkers for selective binding of His-tagged proteins, the approach achieved 100% sensitivity and selectivity in distinguishing His-tagged human serum albumin from native human serum albumin, demonstrating its exceptional protein screening capabilities.