Hierarchically Structured Plasmonic Nanoparticle Assemblies with Dual-Length Scale Electromagnetic Hot Spots for Enhanced Sensitivity in the Detection of (Bio)Molecular Analytes

High sensitivity in plasmon-enhanced spectroscopies results not only from high electromagnetic (EM) field enhancements at the vicinity of nanostructured metal surfaces but also the ability to leverage on these enhancements via analyte colocalization with the EM hot spots. However, promising configurations for EM hot spots such as metal nanogaps are spatially restrictive for adsorption of larger analytes such as proteins. This results in an adverse spatial trade-off in the design of EM hot spots, viz., increasingly confined geometries sought to drive high EM enhancements and space necessary to accommodate binding of large biomolecular analytes. In this direction, we demonstrate gold nanoparticle cluster arrays (NCAs) exhibiting interparticle (<1 nm wide) and intercluster (<10 nm wide) EM hot spots, with cluster size and densities engineered to enhance the leverage of biomolecular analytes over EM hot spots. Surface-enhanced Raman and fluorescence assays of streptavidin–dye conjugates on biotinylated NCAs show higher sensitivity to be achieved using NCA geometry exhibiting greater density of intercluster hot spots. Quartz crystal microbalance measurements reveal the higher sensitivity to be achieved despite lower nanoparticle as well as analyte surface densities as compared to less sensitive NCA geometries. The results are aligned with the expectation that the large dimensions of protein analytes allow better leverage of intercluster rather than interparticle hot spots and consequently be detected with better sensitivity on NCAs presenting higher intercluster hot-spot densities. The investigation supports the need to factor in the size of the analyte into the design of the EM hot spots to achieve high sensitivity in plasmon-enhanced spectroscopic sensors.