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 structures with all key features for widespread use of SERS including strong signal intensity, reliability in quantification of signal and multiplexing capability.

Synthesis, Assembly, Optical Properties, and Sensing Applications of Plasmonic Gap Nanostructures

“…Overall, a key challenge is the ultra-precise synthesis of the targeted PGNs in a very high yield, and this could be easily translated into highly reliable and quantitative plasmonic response including SERS, as shown by various plasmonic nanogap particles formed and controlled by thiolated DNA, dealloying, silica/polymer interlayer, and host-guest chemistry. [9,15,19,27,28,34,48,54,56] While recently advanced top-down methods, such as electron-beam lithography, allow the versatile fabrication of PGNs with various morphologies, the reproducible synthesis of welldefined ultrasmall (1 nm or less) nanogaps in high yields has been mainly realized by the bottom-up approach. In particular, the high local field enhancements in ultrasmall nanogaps imply that subtle changes in this region significantly alter the plasmonic response.…”

“…Recently, Kim et al expanded the palette of Raman dyes for highly multiplexed sensing and imaging and incorporated 10 different within a plasmonic intragap by adopting cyclodextrin(CD)-based host-guest chemistry while forming CD-based intrananogap particles (CIPs). [48] Around 95% of the measured SERS EFs from individual CIPs were narrowly distributed between 9.5 × 10 8 to 9.5 × 10 9 with a high average EF value (3.0 × 10 9 ) due to the uniformly synthesized intragap particles with a clear gap morphology in a high yield (≈97%). It was shown that 10 different Raman dye-coded CIPs were clearly distinguishable with fingerprint SERS peaks.…”

“…A recent report regarding cyclodextrin (CD)-based intrananogap particles (CIPs) shows creation of a narrow and uniform ≈1 nm gap inside a plasmonic particle by nucleation on the CD-modified core particle surface (Figure 2c). [48] It was found that CDs play a key role in the formation of intragap, and the number of modified CDs per each core affects Au shell growth and gap formation and morphology. Densely modified nano meter-sized macrocyclic oligosaccharides (CD in this case) on the Au core induce a small number of budding Au nanostructures and leads to the incomplete shell formation.…”

“…Multiplexed SERS-based cell imaging with distinguishable SERS peaks for six different CIPs (right). Reproduced with permission [48]. Copyright 2020, American Chemical Society.…”

Biologically-Inspired Water-Swelling-Driven Fabrication of Centimeter-Level Metallic Nanogaps

“…Typically, the metallic nanogap can generate surface plasma resonance that will strongly enhance the localized electromagnetic field. This effect has great prospects in SERS (surface enhanced Raman scattering) [ 12 , 13 , 14 , 15 ] and sensing [ 16 , 17 , 18 ]. In these application scenarios, fabricating large-area metallic nanogaps in a low-cost manner is of great importance.…”