Cyclodextrin-Based Synthesis and Host–Guest Chemistry of Plasmonic Nanogap Particles with Strong, Quantitative, and Highly Multiplexable Surface-Enhanced Raman Scattering Signals

We developed a synthetic strategy to form cyclodextrin-based intrananogap particles (CIPs) with a well-defined ∼1 nm interior gap in a high yield (∼97%), and were able to incorporate 10 different Raman dyes inside the gap using the cyclodextrin-based host-guest chemistry, leading to strong, reproducible, and highly multiplexable surface-enhanced Raman scattering (SERS) signals. The average SERS enhancement factor (EF) for CIPs was 3.0 × 109 with a very narrow distribution of the EFs that range from 9.5 × 108 to 9.5 × 109 for ∼95% of the measured particles. Remarkably, 10 different Raman dyes can be loaded within the nanogap of CIPs, and 6 different Raman dye-loaded CIPs with little spectral overlaps were distinctly detected for cancer cell imaging applications with a single excitation source. Our synthetic strategy provides new platforms in precisely forming plasmonic nanogap structures with all key features for widespread use of SERS including strong signal intensity, reliability in quantification of signal and multiplexing capability.