Rational Design of Plasmonic Nanostructures for Biomolecular Detection: Interplay between Theory and Experiments

In this work, we report a simple strategy to obtain ultrasensitive SERS nanostructures by self-assembly and bioconjugation of Au nanospheres (NSs). Homodimer aggregates with an interparticle gap of around 8 nm are generated in aqueous dispersions by the highly specific molecular recognition of biotinylated Au NSs to streptavidin (STV), while random Au NS aggregates with a gap of 5 nm are formed in the absence of STV due to hydrogen bonding among biotinylated NSs. Both types of aggregates depict SERS analytical enhancement factors (AEF) of around 10⁷ and the capability to detect biotin concentrations lower than 1 × 10^–12 M. Quite interesting, the AEF for an external analyte, Rhodamine 6G (RH6G), using the dimer aggregates is 1 order of magnitude greater (10⁵) than using random aggregates (around 10⁴). The dependence on the wavelength and the differences of the AEF for Au random aggregates and dimers are rationalized with rigorous electrodynamic simulations. The dimers obtained afford a new type of an <i>in situ</i> self-calibrated and reliable SERS substrate where biotinylated molecules can selectively be “trapped” by STV and located in the nanogap enhanced plasmonic field. Using this concept, powerful molecular-recognition-based SERS assays can be carried out. The capability of the dimeric structures for analytical applications is demonstrated using SPR spectroscopy to detect biotinylated immunoglobulin G at very low concentrations