Single-Molecule Surface-Enhanced Raman Spectroscopy

Abstract

Single-molecule surface-enhanced Raman spectroscopy (SM-SERS) has the potential to detect single molecules in a non-invasive, label-free manner with high-throughput. SM-SERS can detect chemical information of single molecules without statistical averaging and has wide application in chemical analysis, nanoelectronics, biochemical sensing, etc. Recently, a series of unprecedented advances have been realized in science and application by SM-SERS, which has attracted the interest of various fields. In this review, we first elucidate the key concepts of SM-SERS, including enhancement factor (EF), spectral fluctuation, and experimental evidence of single-molecule events. Next, we systematically discuss advanced implementations of SM-SERS, including substrates with ultra-high EF and reproducibility, strategies to improve the probability of molecules being localized in hotspots, and nonmetallic and hybrid substrates. Then, several examples for the application of SM-SERS are proposed, including catalysis, nanoelectronics, and sensing. Finally, we summarize the challenges and future of SM-SERS. We hope this literature review will inspire the interest of researchers in more fields.

Keywords: nanoparticle; single-molecule detection; surface plasmon resonance; surface-enhanced Raman spectroscopy.

Figure 2

High-reproducibility substrates for SM-SERS. (a) Nanogap-engineered SERS-active GSND. (b) NPoM configuration. Figure reproduced from [46]. (c) The enhancement map of the quadrumer substrate. (d) Nanoparticle dimer assembled on the DNA origami nanofork. Figure reproduced from [57]. (e) Tunneling-controlled TERS. (f) Schematic diagram of FM-TERS. Figure reproduced from [64]. (g) Nanoantenna chip for SM-SERS. Figure reproduced from [66]. (h) The SEM image of the nanoslit device. Scale bar, 1 μm. Scanning electron microscopy, SEM. Figure reproduced from [15].

Figure 1

Schematic diagram of SM-SERS. Center: SPR effect of nanoparticles; Inset: (a) dimetric nanostructure; (b) plasmonic single-molecule junction; (c) plasmonic tip; (d) plasmonic nanopore.

Figure 3

Strategies to improve the probability of molecules in hotspots. (a) FDTD simulation for a Ag nanoparticle on a warped Au substrate. Figure reproduced from [72]. Inset: the schematic of the NPoM with warped substrate. FDTD, finite difference time domain. (b) The SERS substrate with programmable localized electrodynamic precipitation. Figure reproduced from [73]. PR, patterned photoresist layer. (c) Schematic of the setup for nanoslit SERS. Figure reproduced from [15]. WE, working electrode. (d) Electro–plasmonic trapping due to the balance between the electrophoretic (F_EP), electroosmotic (F_EO), and plasmonic gradient force (F_OF). Figure reproduced from [74].

Figure 4

Monitoring of catalytic reactions by SM-SERS. (a) The Au dimers, consisting of two nanoparticles sized 200 nm and 13 nm. Figure reproduced from [95]. Inset: an SEM image of the Au dimers. L-GNP, large gold nanoparticles. S-GNP, small gold nanoparticles. ITO, indium tin oxide. (b) Self-assembled 80 nm NPoM for eliciting EF for SM-SERS. Figure reproduced from [96]. (c) SHINERS, Au core SiO₂ shell nanoparticles.

Figure 5

Characterization of molecular nanoelectronics by SM-SERS. (a) The schematic of the Au–4bipy–Au junction with low/high bias voltage. Figure reproduced from [64]. (b) Simultaneous SERS and conductance measurements for single-molecule junction. Figure reproduced from [100]. Right: three metastable states in BDT junctions. (c) SERS of C₆₀ in an electromigrated junction. Figure reproduced from [102]. Inset: an SEM image of an electromigrated junction.

Figure 6

Biochemical sensing by SM-SERS. (a) Identification of single-stranded DNA by single-molecule TERS. Figure reproduced from [107]. The DNA molecules are deposited on the Au substrate. (b) The schematic of the plasmonic nanopore in the nanoporous film. NPG, nanoporous gold. Figure reproduced from [109]. (c) DNA sequence trapped in plasmonic nanopore. The base pairs are numbered in ascending order from tail to front of the molecule. Figure reproduced from [110].