Toward Quantitative Surface-Enhanced Raman Scattering with Plasmonic Nanoparticles: Multiscale View on Heterogeneities in Particle Morphology, Surface Modification, Interface, and Analytical Protocols

Abstract

Surface-enhanced Raman scattering (SERS) provides significantly enhanced Raman scattering signals from molecules adsorbed on plasmonic nanostructures, as well as the molecules' vibrational fingerprints. Plasmonic nanoparticle systems are particularly powerful for SERS substrates as they provide a wide range of structural features and plasmonic couplings to boost the enhancement, often up to >10 8 −10 10 . Nevertheless, nanoparticle-based SERS is not widely utilized as a means for reliable quantitative measurement of molecules largely due to limited controllability, uniformity, and scalability of plasmonic nanoparticles, poor molecular modification chemistry, and a lack of widely used analytical protocols for SERS. Furthermore, multiscale issues with plasmonic nanoparticle systems that range from atomic and molecular scales to assembled nanostructure scale are difficult to simultaneously control, analyze, and address. In this perspective, we introduce and discuss the design principles and key issues in preparing SERS nanoparticle substrates and the recent studies on the uniform and controllable synthesis and newly emerging machine learning-based analysis of plasmonic nanoparticle systems for quantitative SERS. Specifically, the multiscale point of view with plasmonic nanoparticle systems toward quantitative SERS is provided throughout this perspective. Furthermore, issues with correctly estimating and comparing SERS enhancement factors are discussed, and newly emerging statistical and artificial intelligence approaches for analyzing complex SERS systems are introduced and scrutinized to address challenges that cannot be fully resolved through synthetic improvements.

Combinatorial Approach to Find Nanoparticle Assemblies with Maximum Surface-Enhanced Raman Scattering

“…As a result, there is a significant fluctuation in the EF values obtained by different laboratories, even when studying the same nanoparticle system. 7 Despite the uncertainties in the measured EF values, it is widely accepted that the SERS signal of AuNP monomers is inherently weak (EF ≲ 10 3 ), 8,9 often falling below the detection limit. Significant Raman enhancement occurs only when two or more nanoparticles are assembled and form nanogaps.…”

“…However, accurate measurements of N SERS are challenging, making it necessary to rely on numerous approximations and assumptions for its estimation. As a result, there is a significant fluctuation in the EF values obtained by different laboratories, even when studying the same nanoparticle system …”

Branched Aluminum Nanocrystals with Internal Hot Spots: Synthesis and Single-Particle Surface-Enhanced Raman Scattering

“…The enhancement factors (EFs) were estimated by the approach employed by Nam’s group . The maximum EF of Al NHP-OHs was ∼1.40 × 10 8 , and the maximum EF of Al NHP-tOHs reached up to ∼1.79 × 10 8 (Table S2).…”

Amplified Plasmonic Forces from DNA Origami-Scaffolded Single Dyes in Nanogaps

“…The interplay of energy between a light emitter and its environment modifies its spontaneous emission rate through the Purcell effect. Placing a quantum emitter in a photonically structured environment such as an optical cavity or photonic crystal can enhance the light–matter interaction enough to enter the strong-coupling regime. − By using metallic nanostructures, light can be even more tightly confined to sub-diffraction-limited gaps, enhancing fluorescence and revealing (ultra)­strong light–matter coupling. − These arise from the localized surface plasmons supported on metal nanostructures, which create tightly confined electromagnetic hot spots. The localized plasmons couple to radiative electronic transitions of any chromophore placed in the proximity, such as dye molecules or semiconductor quantum dots. − , …”