The chemical origin of enhanced signals from tip-enhanced Raman detection of functionalized nanoparticles

Here we present results that investigate the origins of signals observed in tip-enhanced Raman (TERS) measurements of functionalized nanoparticles. Surface enhanced Raman scattering (SERS) is known to give the largest enhancements in gap junctions. Similarly, gap-mode TERS also produces significant enhancements. The methodology developed here provides gap-mode like enhancements in TERS measurements without the need for a metal surface. Using a combination of aggregated nanoparticle SERS and TERS detection of functionalized nanoparticles, we assess the chemical origins of the observed peaks and show that molecules outside of gap junctions are also enhanced using our methodology. Our experiments use biotin and streptavidin as a model system for protein-ligand binding. Different size functionalized nanoparticles (20, 50, 80 nm) show changes in intensity in both SERS and TERS measurements. SERS measurements indicate that streptavidin has a larger Raman cross-section than biotin and is preferentially observed. The specific streptavidin peaks observed by TERS vary depending on whether streptavidin is attached to the nanoparticle and located in the gap or bound to the substrate surface. This methodology suggests a route to enhancing TERS signals associated with protein receptors in biological systems that cannot be isolated to a metallic surface.