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.

Triangular silver nanoparticles ( approximately 100 nm wide and 50 nm high) have remarkable optical properties. In particular, the peak extinction wavelength, lambda(max) of their localized surface plasmon resonance (LSPR) spectrum is unexpectedly sensitive to nanoparticle size, shape, and local ( approximately 10-30 nm) external dielectric environment. This sensitivity of the LSPR lambda(max) to the nanoenvironment has allowed us to develop a new class of nanoscale affinity biosensors. The essential characteristics and operational principles of these LSPR nanobiosensors will be illustrated using the well-studied biotin-streptavidin system. Exposure of biotin-functionalized Ag nanotriangles to 100 nM streptavidin (SA) caused a 27.0 nm red-shift in the LSPR lambda(max). The LSPR lambda(max) shift, DeltaR/DeltaR(max), versus [SA] response curve was measured over the concentration range 10(-)(15) M < [SA] < 10(-)(6) M. Comparison of the data with the theoretical normalized response expected for 1:1 binding of a ligand to a multivalent receptor with different sites but invariant affinities yielded approximate values for the saturation response, DeltaR(max) = 26.5 nm, and the surface-confined thermodynamic binding constant K(a,surf) = 10(11) M(-)(1). At present, the limit of detection (LOD) for the LSPR nanobiosensor is found to be in the low-picomolar to high-femtomolar region. A strategy to amplify the response of the LSPR nanobiosensor using biotinylated Au colloids and thereby further improve the LOD is demonstrated. Several control experiments were performed to define the LSPR nanobiosensor's response to nonspecific binding as well as to demonstrate its response to the specific binding of another protein. These include the following: (1) electrostatic binding of SA to a nonbiotinylated surface, (2) nonspecific interactions of prebiotinylated SA to a biotinylated surface, (3) nonspecific interactions of bovine serum albumin to a biotinylated surface, and (4) specific binding of anti-biotin to a biotinylated surface. The LSPR nanobiosensor provides a pathway to ultrasensitive biodetection experiments with extremely simple, small, light, robust, low-cost instrumentation that will greatly facilitate field-portable environmental or point-of-service medical diagnostic applications.

The elucidation of the long range distance dependence of the localized surface plasmon resonance (LSPR) of surface-confined noble metal nanoparticles is the aim of this work. It was suspected that the linear distance dependence found in CH3(CH2) x SH self-assembled monolayer (SAM) formation was the thin shell limit of a longer range, nonlinear dependence. To verify this, multilayer SAM shells based on the interaction of HOOC(CH2)10SH and Cu2+ were assembled onto surface-confined noble metal nanoparticles and were monitored using UV−visible spectroscopy. Measurement of the LSPR extinction peak shift versus number of layers and adsorbate thickness is nonlinear and has a sensing range that is dependent on the composition, shape, in-plane width, and out-of-plane height of the nanoparticles. Theoretical calculations based on an accurate electrodynamics description of the metal nanoparticle plus surrounding layered material indicate plasmon resonance wavelength shifts that are in excellent agreement with the measurements. The calculations show that the sensing range is determined by falloff of the average induced electric field around the nanoparticle. This detailed set of experiments coupled with an excellent theory versus experiment comparison prove that the sensing capabilities of noble metal nanoparticles can be size tuned to match the dimensions of biological and chemical analytes by adjusting the aforementioned properties. The optimization of the LSPR nanosensor for a specific analyte will significantly improve an already sensitive nanoparticle-based sensor.

A nanoscale optical biosensor based on localized surface plasmon resonance (LSPR) spectroscopy has been developed to monitor the interaction between the antigen, amyloid-beta derived diffusible ligands (ADDLs), and specific anti-ADDL antibodies. Using the sandwich assay format, this nanosensor provides quantitative binding information for both antigen and second antibody detection that permits the determination of ADDL concentration and offers the unique analysis of the aggregation mechanisms of this putative Alzheimer's disease pathogen at physiologically relevant monomer concentrations. Monitoring the LSPR-induced shifts from both ADDLs and a second polyclonal anti-ADDL antibody as a function of ADDL concentration reveals two ADDL epitopes that have binding constants to the specific anti-ADDL antibodies of 7.3 x 10(12) M(-1) and 9.5 x 10(8) M(-1). The analysis of human brain extract and cerebrospinal fluid samples from control and Alzheimer's disease patients reveals that the LSPR nanosensor provides new information relevant to the understanding and possible diagnosis of Alzheimer's disease.

Silver and gold nanotriangles were fabricated by nanosphere lithography (NSL) and their localized surface plasmon resonance (LSPR) spectra were measured by UV-vis extinction spectroscopy. It is demonstrated that the short range (viz., 0-2 nm) distance dependence of the electromagnetic fields that surround these nanoparticles when resonantly excited can be systematically tuned by changing their size, structure, and composition. This is accomplished by measuring the shift in the peak wavelength, λ max , of their LSPR spectra caused by the adsorption of hexadecanethiol as a function of nanoparticle size (in-plane width, out-of-plane height, and aspect ratio), shape (truncated tetrahedron versus hemisphere), and composition (silver versus gold). We find that the hexadecanethiol-induced LSPR shift for Ag triangles decreases when in-plane width is increased at fixed out-of-plane height or when height is increased at fixed width. These trends are the opposite to what was seen in an earlier study of the long range distance dependence in which 30 nm thick layers were examined (Haes et al. J. Phys. Chem. B 2004, 108, 109), but both the long and short range results are confirmed by a theoretical analysis based on finite element electrodynamics. The theory results also indicate that the short range results are primarily sensitive to hot spots (regions of high induced electric field) near the tips of the triangles, so this provides an example where enhanced local fields play an important role in extinction spectra. Our measurements further show that the hexadecanethiol-induced LSPR peak shift is larger for nanotriangles than for hemispheres with equal volumes and is larger for Ag nanotriangles than for Au nanotriangles with the same in-plane widths and out-of-plane heights. The dependence of the alkanethiolinduced LSPR peak shift on chain length for Ag nanotriangles is approximately size-independent. We anticipate that the improved understanding of the short range dependence of the adsorbate-induced LSPR peak shift on nanoparticle structure and composition reported here will translate to significant improvements in the sensitivity of refractive-index-based nanoparticle nanosensors.