Recent Advances in the Synthesis of Intra-Nanogap Au Plasmonic Nanostructures for Bioanalytical Applications

Plasmonic nanogap-enhanced Raman scattering has attracted considerable attention in the fields of Raman-based bioanalytical applications and materials science. Various strategies have been proposed to prepare nanostructures with an inter- or intra-nanogap for fundamental study models or applications. This report focuses on recent advances in synthetic methods to fabricate intra-nanogap structures with diverse dimensions, with detailed focus on the theory and bioanalytical applications. Synthetic strategies ranging from the use of a silica layer to small molecules, the use of polymers and galvanic replacement, are extensively investigated. Furthermore, various core structures, such as spherical, rod-, and cube-shaped, are widely studied, and greatly expand the diversity of plasmonic nanostructures with an intra-nanogap. Theoretical calculations, ranging from the first plasmonic hybridization model that is applied to a concentric Au–SiO₂–Au nanosphere to the modern quantum corrected model, have evolved to accurately describe the plasmonic resonance property in concentric core–shell nanostructures with a subnanometer nanogap. The greatly enhanced and uniform Raman responses from the localized Raman reporter in the built-in nanogap have made it possible to achieve promising probes with an extraordinary high sensitivity in various formats, such as biomolecule detection, high-resolution cell imaging, and an in vivo imaging application.