Surface-enhanced Raman scattering (SERS) intensities for individual Au nanospheres, nanoshells, and nanosphere and nanoshell dimers coated with nonresonant molecules are measured, where the precise nanoscale geometry of each monomer and dimer is identified through in situ atomic force microscopy. The observed intensities correlate with the integrated quartic local electromagnetic field calculated for each specific nanostructure geometry. In this study, we find that suitably fabricated nanoshells can provide SERS enhancements comparable to nanosphere dimers.

Nearly monodisperse hollow gold nanospheres (HGNs) with tunable interior and exterior diameters have been synthesized by sacrificial galvanic replacement of cobalt nanoparticles. It is possible to tune the peak of the surface plasmon band absorption between 550 and 820 nm by carefully controlling particle size and wall thickness. Cobalt particle size is tunable by simultaneously changing the concentration of sodium borohydride and sodium citrate, the reducing and capping agent, respectively. The thickness of the gold shell can be varied by carefully controlling the addition of gold salt. With successful demonstration of ensemble as well as single HGN surface-enhanced Raman scattering, these HGNs have shown great potential for chemical and biological sensing applications, especially those requiring nanostructures with near-IR absorption.

We present the development of nanoscale pH sensors based on functionalized silver nanoparticles and surface-enhanced Raman scattering (SERS). The SERS spectrum from individual silver nanoparticle (50-80 nm in diameter) clusters functionalized with 4-mercaptobenzoic acid shows a characteristic response to the pH of the surrounding solution and is sensitive to pH changes in the range of 6-8. Measurements from nanoparticles incorporated in living Chinese hamster ovary cells demonstrate that the nanoparticle sensors retain their robust signal and sensitivity to pH when incorporated into a cell.

A unique gold nanoparticle aggregate (GNA) system has been shown to be an excellent substrate for surface-enhanced Raman scattering (SERS) applications. Rhodamine 6G (R6G), a common molecule used for testing SERS activity on silver, but generally difficult to detect on gold substrates, has been found to readily bind to the GNA and exhibit strong SERS activity due to the unique surface chemistry afforded by sulfur species on the surface. This GNA system has yielded a large SERS enhancement of 107−109 in bulk solution for R6G, on par with or greater than any previously reported gold SERS substrate. SERS activity has also been successfully demonstrated for several biological molecules including adenine, l-cysteine, l-lysine, and l-histidine for the first time on a gold SERS substrate, showing the potential of this GNA as a convenient and powerful SERS substrate for biomolecular detection. In addition, the SERS spectrum of R6G on single aggregates has been measured. We have shown that the special surface properties of the GNA, in conjunction with strong near-IR absorption, make it useful for SERS analysis of a wide variety of molecules.

We report the development of nanoprobes that exploit the surface-enhanced Raman scattering (SERS) from nonaggregated, hollow, gold nanospheres (HGNSs). The homogeneity of the HGNSs leads to a nearly 10-fold improvement in signal consistency over standard silver SERS substrates, which translates into a significant increase in sensitivity and dynamic range for the model application of pH sensing. Moreover, the small size (30-nm diameter) of these SERS-active nanoparticles represents a major step in advancing sensing technology based on SERS, making this technology more amenable to intracellular sensing.

Colloidal solutions of metal nanoparticles are currently among the most studied substrates for sensors based on surface-enhanced Raman scattering (SERS). However, such substrates often suffer from not being cost-effective, reusable, or stable. Here, we develop nanoporous Au as a highly active, tunable, stable, biocompatible, and reusable SERS substrate. Nanoporous Au is prepared by a facile process of free corrosion of AgAu alloys followed by annealing. Results show that nanofoams with average pore widths of ∼250nm exhibit the largest SERS signal for 632.8nm excitation. This is attributed to the electromagnetic SERS enhancement mechanism with additional field localization within pores.

We demonstrate the rapid optical characterization of large numbers of individual metal nanoparticles freely diffusing in colloidal solution by confocal laser spectroscopy to guide nanoparticle engineering and optimization. We use ratios of the Rayleigh and Raman scattering response and rotational diffusion timescales of individual nanoparticles to show that hollow gold nanospheres and solid silver nanoparticle dimers linked with a bifunctional ligand, both specifically designed nanostructures, exhibit significantly higher monodispersity than randomly aggregated gold and silver nanoparticles.

We demonstrate that optical trapping combined with confocal Raman spectroscopy using a single laser source is a powerful tool for the rapid identification of micrometer-sized particles in an aqueous environment. Optical trapping immobilizes the particle while maintaining it in the center of the laser beam path and within the laser focus, thus maximizing the collection of its Raman signals. The single particle is completely isolated from other particles and substrate surfaces, therefore eliminating any unwanted background signals and ensuring that information is collected only from the selected, individual particle. In this work, an inverted confocal Raman microscope is combined with optical trapping to probe and analyze bacterial spores in solution. Rapid, reagentless detection and identification of bacterial spores with no false positives from a complex mixed sample containing polystyrene and silica beads in aqueous suspension is demonstrated. In addition, the technique is used to analyze the relative concentration of each type of particle in the mixture. Our results show the feasibility for incorporating this technique in combination with a flow cytometric-type scheme in which the intrinsic Raman signatures of the particles are used instead of or in addition to fluorescent labels to identify cells, bacteria, and particles in a wide range of applications.