Generalized Approach to SERS-Active Nanomaterials via Controlled Nanoparticle Linking, Polymer Encapsulation, and Small-Molecule Infusion

Over the past decade the emphasis on single-molecule sensitivity of surface-enhanced Raman spectroscopy (SERS) has brought to prominence the special role played by so-called SERS hot spots, often times nanometerscale junctions between nanoparticles (NPs). In this report, molecular linkers are used to mediate the assembly of NPs to dimers and small clusters. When the SERS enhancement is optimized, the aggregation process is quenched by polymer and protein stabilizers that subsequently act as encapsulants resulting in SERS substates with unprecedented enhancement uniformity, reproducibility, and stability. The polymer-stabilized NP junctions were then imprinted with a variety of small molecules that permeated the polymer coat and displaced the linker from the hot spot. The average SERS enhancement of these SERS nanocapsules was found to be at least 300x greater than for single NPs, while the Raman/Rayleigh scattering ratio was 101 higher for linked NPs versus nonoptimized aggregates. Single-particle statistics showed that almost every nanocapsule produced intense SERS, suggesting that they are NT dimers and small clusters with the probe molecule resident in a hot spot. Nanocapsules were functionalized and shown to compete successfully with fluorescence imaging in multiplexed identification of cancer cell epitopes at the single-cell and single-nanotag level.