Plasmonic Microneedle Arrays for in Situ Sensing with Surface-Enhanced Raman Spectroscopy (SERS).

Surface-enhanced Raman spectroscopy (SERS) is a sensitive, chemically specific, and short-time response probing method with significant potential in biomedical sensing. This paper reports the integration of SERS with microneedle arrays as a minimally invasive platform for chemical sensing, with a particular view toward sensing in interstitial fluid (ISF). Microneedle arrays were fabricated from a commercial polymeric adhesive and coated with plasmonically active gold nanorods that were functionalized with the pH-sensitive molecule 4-mercaptobenzoic acid. This sensor can quantitate pH over a range of 5 to 9 and can detect pH levels in an agar gel skin phantom and in human skin in situ. The sensor array is stable and mechanically robust in that it exhibits no loss in SERS activity after multiple punches through an agar gel skin phantom and human skin or after a month-long incubation in phosphate-buffered saline. This work is the first to integrate SERS-active nanoparticles with polymeric microneedle arrays and to demonstrate in situ sensing with this platform.

Physicochemical Trapping of Neurotransmitters in Polymer-Mediated Gold Nanoparticle Aggregates for Surface-Enhanced Raman Spectroscopy.

Because of the sharp distance dependence of surface-enhanced Raman spectroscopy (SERS), analyte molecules that do not exhibit strong affinity for Au/Ag often elude detection. New methods of integrating such analytes with SERS substrates are required to circumvent this limitation and expand the sensitivity of SERS to new molecules and applications. We communicate here a solution-phase, capture agent-free method of aggregating Au nanospheres in the presence of five neurotransmitters (dopamine, epinephrine, norepinephrine, serotonin, and histamine) and preventing sedimentation by encapsulating the aggregated nanospheres with polyvinylpyrrolidone, thereby trapping the neurotransmitters in close proximity to the Au nanospheres and enabling SER detection. The primary advantages of this physicochemical trapping method, which is generalizable to analytes beyond the scope of this work, are the high signal-to-noise ratio and spectral consistency down to nM levels. Normal Raman spectra and density functional theory calculations corroborate the accuracy of the spectra. Spectra collected over a wide range of concentrations were used to construct adsorption isotherms for all five neurotransmitters, from which adsorption dissociation constants were calculated, spanning from 5.7 × 10-4 M to 1.7 × 10-10 M. We expect this method to produce high quality SER spectra of any molecule with an Au affinity known or expected (based on functional groups) to be within that range. Our results have implications for plasmonic detection of these neurotransmitters, particularly for mixtures of those that exhibited disparate Au affinity in our study. We also present evidence that this method produces spectra of sufficient resolution to explore hypotheses related to surface adsorption behavior.

Single-Molecule Chemistry with Surface- and Tip-Enhanced Raman Spectroscopy.

Single-molecule (SM) surface-enhanced Raman spectroscopy (SERS) and tip-enhanced Raman spectroscopy (TERS) have emerged as analytical techniques for characterizing molecular systems in nanoscale environments. SERS and TERS use plasmonically enhanced Raman scattering to characterize the chemical information on single molecules. Additionally, TERS can image single molecules with subnanometer spatial resolution. In this review, we cover the development and history of SERS and TERS, including the concept of SERS hot spots and the plasmonic nanostructures necessary for SM detection, the past and current methodologies for verifying SMSERS, and investigations into understanding the signal heterogeneities observed with SMSERS. Moving on to TERS, we cover tip fabrication and the physical origins of the subnanometer spatial resolution. Then, we highlight recent advances of SMSERS and TERS in fields such as electrochemistry, catalysis, and SM electronics, which all benefit from the vibrational characterization of single molecules. SMSERS and TERS provide new insights on molecular behavior that would otherwise be obscured in an ensemble-averaged measurement.

Ultrahigh-Vacuum Tip-Enhanced Raman Spectroscopy.

Molecule-surface interactions and processes are at the heart of many technologies, including heterogeneous catalysis, organic photovoltaics, and nanoelectronics, yet they are rarely well understood at the molecular level. Given the inhomogeneous nature of surfaces, molecular properties often vary among individual surface sites, information that is lost in ensemble-averaged techniques. In order to access such site-resolved behavior, a technique must possess lateral resolution comparable to the size of surface sites under study, analytical power capable of examining chemical properties, and single-molecule sensitivity. Tip-enhanced Raman spectroscopy (TERS), wherein light is confined and amplified at the apex of a nanoscale plasmonic probe, meets these criteria. In ultrahigh vacuum (UHV), TERS can be performed in pristine environments, allowing for molecular-resolution imaging, low-temperature operation, minimized tip and molecular degradation, and improved stability in the presence of ultrafast irradiation. The aim of this review is to give an overview of TERS experiments performed in UHV environments and to discuss how recent reports will guide future endeavors. The advances made in the field thus far demonstrate the utility of TERS as an approach to interrogate single-molecule properties, reactions, and dynamics with spatial resolution below 1 nm.

Spiers Memorial Lecture. Surface-enhanced Raman spectroscopy: from single particle/molecule spectroscopy to ångstrom-scale spatial resolution and femtosecond time resolution.

Four decades on, surface-enhanced Raman spectroscopy (SERS) continues to be a vibrant field of research that is growing (approximately) exponentially in scope and applicability while pushing at the ultimate limits of sensitivity, spatial resolution, and time resolution. This introductory paper discusses some aspects related to all four of the themes for this Faraday Discussion. First, the wavelength-scanned SERS excitation spectroscopy (WS-SERES) of single nanosphere oligomers (viz., dimers, trimers, etc.), the distance dependence of SERS, the magnitude of the chemical enhancement mechanism, and the progress toward developing surface-enhanced femtosecond stimulated Raman spectroscopy (SE-FSRS) are discussed. Second, our efforts to develop a continuous, minimally invasive, in vivo glucose sensor based on SERS are highlighted. Third, some aspects of our recent work in single molecule SERS and the translation of that effort to ångstrom-scale spatial resolution in ultrahigh vacuum tip-enhanced Raman spectroscopy (UHV-TERS) and single molecule electrochemistry using electrochemical (EC)-TERS will be presented. Finally, we provide an overview of analytical SERS with our viewpoints on SERS substrates, approaches to address the analyte generality problem (i.e. target molecules that do not spontaneously adsorb and/or have Raman cross sections <10-29 cm2 sr-1), SERS for catalysis, and deep UV-SERS.

High-Resolution Distance Dependence Study of Surface-Enhanced Raman Scattering Enabled by Atomic Layer Deposition.

We present a high-resolution distance dependence study of surface-enhanced Raman scattering (SERS) enabled by atomic layer deposition (ALD) at 55 and 100 °C. ALD is used to deposit monolayers of Al2O3 on bare silver film over nanospheres (AgFONs) and AgFONs functionalized with self-assembled monolayers. Operando SERS is used to measure the intensities of the Al-CH3 and C-H stretches from trimethylaluminum (TMA) as a function of distance from the AgFON surface. This study clearly demonstrates that SERS on AgFON substrates displays both a short- and long-range nanometer scale distance dependence. Excellent agreement is obtained between these experiments and theory that incorporates both short-range and long-range terms. This is a high-resolution operando SERS distance dependence study performed in one integrated experiment using ALD Al2O3 as the spacer layer and Raman label simultaneously. The long-range SERS distance dependence should make it possible to detect chemisorbed surface species located as far as ∼3 nm from the AgFON substrate and will provide new insight into the surface chemistry of ALD and catalytic reactions.

Bisboronic Acids for Selective, Physiologically Relevant Direct Glucose Sensing with Surface-Enhanced Raman Spectroscopy.

This paper demonstrates the direct sensing of glucose at physiologically relevant concentrations with surface-enhanced Raman spectroscopy (SERS) on gold film-over-nanosphere (AuFON) substrates functionalized with bisboronic acid receptors. The combination of selectivity in the bisboronic acid receptor and spectral resolution in the SERS data allow the sensors to resolve glucose in high backgrounds of fructose and, in combination with multivariate statistical analysis, detect glucose accurately in the 1-10 mM range. Computational modeling supports assignments of the normal modes and vibrational frequencies for the monoboronic acid base of our bisboronic acids, glucose and fructose. These results are promising for the use of bisboronic acids as receptors in SERS-based in vivo glucose monitoring sensors.

Surface-Enhanced Raman Spectroscopy Biosensing: In Vivo Diagnostics and Multimodal Imaging.

This perspective presents recent developments in the application of surface-enhanced Raman spectroscopy (SERS) to biosensing, with a focus on in vivo diagnostics. We describe the concepts and methodologies developed to date and the target analytes that can be detected. We also discuss how SERS has evolved from a "point-and-shoot" stand-alone technique in an analytical chemistry laboratory to an integrated quantitative analytical tool for multimodal imaging diagnostics. Finally, we offer a guide to the future of SERS in the context of clinical diagnostics.

Structure enhancement factor relationships in single gold nanoantennas by surface-enhanced Raman excitation spectroscopy.

Determining the existence of any direct spectral relationship between the far-field scattering properties and the near-field Raman-enhancing properties of surface-enhanced Raman spectroscopy (SERS) substrates has been a challenging task with only a few significant results to date. Here, we prove that hot spot dominated systems show little dependence on the far-field scattering properties because of differences between near- and far-field localized surface plasmon resonance (LSPR) effects as well as excitation of new plasmon modes via a localized emitter. We directly probe the relationship between the near- and far-field light interactions using a correlated LSPR-transmission electron microscopy (TEM) surface-enhanced Raman excitation spectroscopy (SERES) technique. Fourteen individual SERS nanoantennas, Au nanoparticle aggregates ranging from dimers to undecamers, coated in a reporter molecule and encased in a protective silica shell, were excited using eight laser wavelengths. We observed no correlation between the spectral position of the LSPR maxima and the maximum enhancement factor (EF). The single nanoantenna data reveal EFs ranging from (2.5 ± 0.6) × 10(4) to (4.5 ± 0.6) × 10(8) with maximum enhancement for excitation wavelengths of 785 nm and lower energy. The magnitude of maximum EF was not correlated to the number of cores in the nanoantenna or the spectral position of the LSPR, suggesting a separation between near-field SERS enhancement and far-field Rayleigh scattering. Computational electrodynamics confirms the decoupling of maximum SERS enhancement from the peak of the scattering spectrum. It also points to the importance of a localized emitter for radiating Raman photons to the far-field which, in nonsymmetric systems, allows for the excitation of radiative plasmon modes that are difficult to excite with plane waves. Once these effects are considered, we are able to fully explain the hot spot dominated SERS response of the nanoantennas.

Immobilized nanorod assemblies: fabrication and understanding of large area surface-enhanced Raman spectroscopy substrates.

We describe the fabrication of optimized plasmonic substrates in the form of immobilized nanorod assemblies (INRA) for surface-enhanced Raman spectroscopy (SERS). Included are high-resolution scanning electron micrograph (SEM) images of the surface structures, along with a mechanistic description of their growth. It is shown that, by varying the size of support microspheres, the surface plasmon resonance is tuned between 330 and 1840 nm. Notably, there are predicted optimal microsphere sizes for each of the commonly used SERS laser wavelengths of 532, 633, 785, and 1064 nm.

Silver colloidal pastes for dye analysis of reference and historical textile fibers using direct, extractionless, non-hydrolysis surface-enhanced Raman spectroscopy.

Surface-enhanced Raman spectroscopy (SERS) is an ideal tool for analyzing dyes on historical textiles because it requires very little sample compared to other available analytical methods and analysis can be done directly on the fiber. This paper reports on the first systematic study of the use of citrate-reduced silver colloidal pastes for the direct, extractionless, non-hydrolysis detection of dyes directly on wool, silk, cotton, and flax fibers. This type of study provides greater insight into the optimal conditions required for accurate analysis of dyes in historical samples. In this work, Ag colloidal pastes were characterized using localized surface plasmon resonance and scanning electron microscopy. The pastes were then employed for SERS analysis of twelve reference samples of different vegetal and animal fibers dyed with cochineal and eleven dyed with brazilwood. Furthermore, six historical textiles from an important collection of Mariano Fortuny (1871-1949) textiles at the Art Institute of Chicago were also examined, to test the efficacy of the paste on aged samples, and to shed light on Fortuny's fascinating production techniques. A mixture of cochineal and brazilwood was detected in some of the historical samples demonstrating, for the first time, simultaneous identification of these colorants used in combination. In addition, the findings give substance to the claim that Fortuny kept using natural dyes at a time when many new and attractive synthetic products became available.

Single nanoparticle plasmonics.

Interest in nanotechnology is driven by the unique and novel properties of nanoscale materials such as the strong interaction of metal particles with light, caused by localized surface plasmon resonances (LSPRs). In this perspective article we review and discuss prominent advantages and advances in single particle studies of plasmonic nanostructures. Common techniques and recent improvements in spatial and spectral resolution will first be outlined, covering both far-field and near-field phenomena. Then, new insight and information uniquely obtained from single particle approaches will be overviewed, including several fundamental studies of plasmonic behaviour, as well as applications using single particle tracking and chemical reaction monitoring. Finally, highly interdisciplinary future directions and experiments are discussed.

Creating, characterizing, and controlling chemistry with SERS hot spots.

In this perspective we discuss the roles of hot spots in surface-enhanced Raman spectroscopy (SERS). After giving background and defining the hot spot, we evaluate a variety of SERS substrates which often contain hot spots. We compare and discuss the differentiating properties of each substrate. We then provide a thorough analysis of the hot spot contribution to the observed SERS signal both in ensemble-averaged and single-molecule conditions. We also enumerate rules for determining the SERS enhancement factor (EF) to clarify the use of this common metric. Finally, we present a forward-looking overview of applications and uses of hot spots for controlling chemistry on the nanoscale. Although not exhaustive, this perspective is a review of some of the most interesting and promising methodologies for creating, controlling, and using hot spots for electromagnetic amplification.

Structure-activity relationships in gold nanoparticle dimers and trimers for surface-enhanced Raman spectroscopy.

Understanding the detailed relationship between nanoparticle structure and activity remains a significant challenge for the field of surface-enhanced Raman spectroscopy. To this end, the structural and optical properties of individual plasmonic nanoantennas comprised of Au nanoparticle assemblies that are coated with organic reporter molecules and encapsulated by a SiO(2) shell have been determined using correlated transmission electron microscopy (TEM), dark-field Rayleigh scattering microscopy, surface-enhanced Raman scattering (SERS) microscopy, and finite element method (FEM) calculations. The distribution of SERS enhancement factors (EFs) for a structurally and optically diverse set of nanoantennas is remarkably narrow. For a collection of 30 individual nanoantennas ranging from dimers to heptamers, the EFs vary by less than 2 orders of magnitude. Furthermore, the EFs for the hot-spot-containing nanoparticles are uncorrelated to aggregation state and localized surface plasmon resonance (LSPR) wavelength but are crucially dependent on the size of the interparticle gap. This study demonstrates that the creation of hot spots, where two particles are in subnanometer proximity or have coalesced to form crevices, is paramount to achieving maximum SERS enhancements.

Gold nanoparticle dimer plasmonics: finite element method calculations of the electromagnetic enhancement to surface-enhanced Raman spectroscopy.

Finite element method calculations were carried out to determine extinction spectra and the electromagnetic (EM) contributions to surface-enhanced Raman spectroscopy (SERS) for 90-nm Au nanoparticle dimers modeled after experimental nanotags. The calculations revealed that the EM properties depend significantly on the junction region, specifically the distance between the nanoparticles for spacings of less than 1 nm. For extinction spectra, spacings below 1 nm lead to maxima that are strongly red-shifted from the 600-nm plasmon maximum associated with an isolated nanoparticle. This result agrees qualitatively well with experimental transmission electron microscopy images and localized surface plasmon resonance spectra that are also presented. The calculations further revealed that spacings below 0.5 nm, and especially a slight fusing of the nanoparticles to give tiny crevices, leads to EM enhancements of 10(10) or greater. Assuming a uniform coating of SERS molecules around both nanoparticles, we determined that regardless of the separation, the highest EM fields always dominate the SERS signal. In addition, we determined that for small separations less than 3% of the molecules always contribute to greater than 90% of the signal.

Surface-Enhanced Femtosecond Stimulated Raman Spectroscopy.

Surface-enhanced Raman spectroscopy (SERS) and femtosecond stimulated Raman spectroscopy (FSRS) have revolutionized the Raman spectroscopy field. SERS provides spectroscopic detection of single molecules, and FSRS enables the acquisition of Raman spectra on the ultrafast time scale of molecular motion. Here, we present the first successful combination of these two techniques, demonstrating surface-enhanced femtosecond stimulated Raman spectroscopy (SE-FSRS) using gold nanoantennas with embedded reporter molecules. Using a picosecond Raman and femtosecond probe pulse, the time- and ensemble-averaged enhancement factor is estimated to be in the range of 10(4)-10(6). We report the line shapes, power dependence, and magnitude of the SE-FSRS signal and discuss contributions to sample degradation on the minute time scale. With these first successful proof-of-principle experiments, time-resolved SE-FSRS techniques can now be rationally attempted with the goals of investigating the dynamics of plasmonic materials as well as examining the contributions of environmental heterogeneities by probing more homogeneous molecular subsets.

Ellipsometric identification of collective optical properties of silver nanocrystal arrays.

The optical properties of silver nanocrystal arrays are investigated using spectroscopic ellipsometry in combination with polarized reflection measurements. Analysis of the ellipsometry and reflectometry spectra in terms of the "thin island film" theory enables a transparent identification of the contribution of collective effects to the optical response. Negligible image charge effects imply that only dipole contributions have to be considered. The interactions between the hexagonally ordered silver nanocrystals give rise to an effective modification of the spherical response to oblate entities with different polarizabilities parallel and perpendicular to the substrate, expressed in terms of corresponding depolarization factors. The effect of nanocrystal ordering, nearest-neighbor distance, size distribution, surrounding ambient, and the optical properties of the single nanocrystals on the optical response are analyzed. The extent of plasmon resonance peak splitting as a function of surface coverage is discussed.