The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article.

Surface-enhanced Raman scattering (SERS) has become a powerful tool in chemical, material and life sciences, owing to its intrinsic features (i.e., fingerprint recognition capabilities and high sensitivity) and to the technological advancements that have lowered the cost of the instruments and improved their sensitivity and user-friendliness. We provide an overview of the most significant aspects of SERS. First, the phenomena at the basis of the SERS amplification are described. Then, the measurement of the enhancement and the key factors that determine it (the materials, the hot spots, and the analyte-surface distance) are discussed. A section is dedicated to the analysis of the relevant factors for the choice of the excitation wavelength in a SERS experiment. Several types of substrates and fabrication methods are illustrated, along with some examples of the coupling of SERS with separation and capturing techniques. Finally, a representative selection of applications in the biomedical field, with direct and indirect protocols, is provided. We intentionally avoided using a highly technical language and, whenever possible, intuitive explanations of the involved phenomena are provided, in order to make this review suitable to scientists with different degrees of specialization in this field.

Gold nanorods (Au NRs) are the archetype of a nanoantenna, enabling the directional capture, routing, and concentration of electromagnetic fields at the nanoscale. Solution-based synthesis methods afford advantages relative to top-down fabrication but are challenged by insufficient precision of structure, presence of byproducts, limited tunability of architecture, and device integration. This is due in part to an inadequate understanding of the early stages of Au NR growth. Here, using phase transfer via ligand exchange with monothiolated polystyrene, we experimentally demonstrate the complete evolution of seed-mediated Au NR growth in hexadecyltrimethylammonium bromide (CTAB) solution. Au NR size and shape progress from slender spherocylinders at short reaction times to rods with a dumbbell profile, flattened end facets, and octagonal prismatic structures at later stages. These evolve from a single mechanism and reflect the majority of reported Au NR morphologies, albeit reflecting different stages. Additionally, the fraction of nonrod impurities in a reaction is related to the initial distribution of the structure of the seed particles. Overall, the observations of early and intermediate stage growth are consistent with the formation of a surfactant bilayer on different crystal facets at different growth stages due to a fine balance between kinetic and thermodynamic factors.

We report a novel approach for fabricating gold nanostar-functionalized substrates for highly sensitive surface enhanced Raman spectroscopy (SERS)-based chemical sensing. Gold nanostars immobilized on a gold substrate via a Raman silent organic tether serve as the SERS substrate, and facilitate the chemical sensing of analytes that can either be chemisorbed or physisorbed on the nanostars. Our SERS substrates are capable of detecting chemisorbed 4-mercaptobenzoic acid at a concentration as low as 10 fM with a reproducible SERS enhancement factor of 10(9), and enable the semi-quantitative multiplexed identification of analytes from mixtures in which they have been dissolved in variable stoichiometry. Most importantly, they afford the detection of physisorbed analytes, such as crystal violet, with an excellent signal-to-noise ratio, hence serving as a versatile platform for the chemical identification of in principle any molecular analyte. These characteristics make a strong case for the use of our nanostar-based SERS substrate in practical chemical sensing applications.

Over the past decade the emphasis on single-molecule sensitivity of surface-enhanced Raman spectroscopy (SERS) has brought to prominence the special role played by so-called SERS hot spots, oftentimes nanometerscale junctions between nanoparticles (NPs). In this report, molecular linkers are used to mediate the assembly of NPs to dimers and small clusters. When the SERS enhancement is optimized, the aggregation process is quenched by polymer and protein stabilizers that subsequently act as encapsulants resulting in SERS substates with unprecedented enhancement uniformity, reproducibility, and stability. The polymer-stabilized NP junctions were then imprinted with a variety of small molecules that permeated the polymer coat and displaced the linker from the hot spot. The average SERS enhancement of these SERS "nanocapsules" was found to be at least 300× greater than for single NPs, while the Raman/Rayleigh scattering ratio was 10 4 higher for linked NPs versus nonoptimized aggregates. Single-particle statistics showed that almost every nanocapsule produced intense SERS, suggesting that they are NP dimers and small clusters with the probe molecule resident in a hot spot. Nanocapsules were functionalized and shown to compete successfully with fluorescence imaging in multiplexed identification of cancer cell epitopes at the single-cell and single-nanotag level.

Surface-directed corner-sharing MnO 6 octahedra within numerous manganese oxide compounds containing Mn 3+ or Mn 4+ oxidation states show strikingly different catalytic activities for water oxidation, paradoxically poorest for Mn 4+ oxides, regardless of oxidation assay (photochemical and electrochemical). This is demonstrated herein by comparing crystalline oxides consisting of Mn 3+ (manganite, γ-MnOOH; bixbyite, Mn 2 O 3 ), Mn 4+ (pyrolusite, β-MnO 2 ) and multiple monophasic mixed-valence manganese oxides. Like all Mn 4+ oxides, pure β-MnO 2 has no detectable catalytic activity, while γ-MnOOH (tetragonally distorted Mn 3+ O 6 , D 4h symmetry) is significantly more active and Mn 2 O 3 (trigonal antiprismatic Mn 3+ O 6 , D 3d symmetry) is the most active. γ-MnOOH deactivates during catalytic turnover simultaneous with the disappearance of crystallographically defined corner-sharing Mn 3+ O 6 and the appearance of Mn 4+ . In a comparison of 2D-layered crystalline birnessites (δ-MnO 2 ), the monovalent Mn 4+ form is catalytically inert, while the hexagonal polymorph, containing few out-of-layer corner-sharing Mn 3+ O 6 , has ∼10-fold higher catalytic activity than the triclinic polymorph, containing in-plane edge-sharing Mn 3+ O 6 . These electronic and structural correlations point toward the more flexible (corner-shared) Mn 3+ O 6 sites, over more rigid (edge-shared) sites as substantially more active catalytic centers. Electrochemical measurements show and ligand field theory predicts that, among corner-shared Mn 3+ O 6 sites, those possessing D 3d ligand field symmetry have stronger covalent Mn−O bonding to the six equivalent oxygen ligands, which we ascribe as responsible for more efficient and faster electrolytic water oxidation. In contrast, D 4h Mn 3+ O 6 sites have weaker Mn−O bonding to the two axial oxygen ligands, have separated electrochemical oxidation waves for Mn and O, and are catalytically less efficient and exhibit slower catalytic turnover. By controlling the ligand field geometry and strength to oxygen ligands, we have identified the key variables for tuning water oxidation activity by manganese oxides. We apply these findings to propose a mechanism for water oxidation by the CaMn 4 O 5 catalytic site of natural photosynthesis.

The preparation and properties of a series of gold nanoclusters protected by thiolated peptides based on the alpha-aminoisobutyric acid (Aib) unit are described. The peptides were devised to form 0-3 C=O...H-N intramolecular hydrogen bonds, as required by their 3(10)-helical structure. The monolayer-protected clusters (MPCs) were prepared, using a modified version of the two-phase Brust-Schiffrin preparation, and fully characterized with (1)H NMR spectrometry, IR and UV-vis absorption spectroscopies, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS). The MPCs were obtained with core diameters in the range of 1.1-2.3 nm, depending on the reaction conditions. Structured peptides formed smaller clusters. The smallest MPC obtained is in agreement with the average formula Au(38)Pep(18). The results showed that the chemical integrity of the peptide is maintained upon monolayer formation and that the average number of peptide ligands per gold cluster is typically 75-85% the value calculated for alkanethiolate MPCs of similar sizes. The IR and NMR spectra indicated that in the monolayer the peptides are involved in both intra- and interligand C=O...H-N hydrogen bonds.

Gold nanostars are one of the most fascinating anisotropic nanoparticles.