Gold Nanorod Array-Bridged Internal-Standard SERS Tags: From Ultrasensitivity to Multifunctionality

Bimetallic gold core-silver shell (Au@Ag) surface-enhanced Raman scattering (SERS) tags draw broad interest in the fields of biological and environmental analysis. In reported tags, silver coating tended to smooth the surface and merge the original hotspot of Au cores, which was disadvantageous to signal enhancement from the aspect of surface topography. Herein, we developed gold nanorod (AuNR)-bridged Au@Ag SERS tags with uniform three-dimensional (3D) topography for the first time. This unique structure was achieved by selecting waxberry-like Au nanoparticles (NPs) as cores, which were capped by vertically oriented AuNR arrays. Upon selective surface blocking with thiol-ligands, Ag NPs were controlled to anisotropically grow on the tips of the AuNRs, producing high-density homo- (Ag-Ag) and hetero- (Au-Ag) hotspots in a single NP. The 3D hotspots rendered this NP extraordinary SERS enhancement ability (an analytical enhancement factor of 3.4 × 10⁶) 30 times higher than the counterpart with a smooth surface, realizing signal detection from a single NP. More importantly, multiplexing signals ("blank" or multiplex "internal standard") can be achieved by simply changing thiol-ligands, as exemplified in the synthesis of NPs with 8 signatures. Furthermore, the multifunctionality has been demonstrated in living cell/in vivo imaging, photothermal therapy, and SERS substrates for ratiometric quantitative analysis, relying on the inherent internal standard signal. The prepared Au@Ag NPs have great potential as standard tools in many SERS-related fields.