Protein-Mediated Sandwich Strategy for Surface-Enhanced Raman Scattering: Application to Versatile Protein Detection

For surface-enhanced Raman scattering (SERS)-based protein identification, immunoassay, and drug screening, metal sandwich substrates bridged by proteins have been created in the present study. The sandwich architectures are fabricated based on a layer-by-layer (LbL) technique. The first gold monolayer is prepared by the self-assembling of gold nanoparticles on a poly(diallyldimethylammonium chloride) (PDDA)-coated glass slide. The second gold or silver layer is produced by the interactions between proteins in the middle layer of the sandwich architecture and the metal nanoparticles. Highly reproducible surface-enhanced resonance Raman scattering (SERRS) and SERS spectra can be obtained by the present gold-protein-gold (Au/Au) and gold-protein-silver (Au/Ag) sandwiches, and we find that the latter yields about 7 times stronger SERRS than the former. Because of contributions from the two metal layers to the SERS, this sandwich strategy holds great potential in highly sensitive and reproducible protein detections.