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

Abstract 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 st…