Quantitative surface-enhanced Raman spectroscopy

The purpose of this tutorial review is to show how surface-enhanced Raman (SERS) and resonance Raman (SERRS) spectroscopy have evolved to the stage where they can be used as a quantitative analytical technique. SER(R)S has enormous potential for a range of applications where high sensitivity needs to be combined with good discrimination between molecular targets, particularly since low cost, compact spectrometers can read the high signal levels that SER(R)S typically provides. These advantages over conventional Raman measurements come at the cost of increased complexity and this review discusses the factors that need to be controlled to generate stable and reproducible SER(R)S calibrations.     

Surface enhanced vibrational spectra of thymine

Surface-enhanced vibrational spectroscopy (SEVS) is discussed using 5-methyluracil (thymine) as a model compound. Surface-enhanced Raman scattering (SERS) and surface-enhanced infrared (SEIR) are reported and a characterization of thymine adsorbed onto silver island films is provided. The thymine SERS spectra obtained using silver colloids, silver roughened electrodes and silver island films are remarkably different due to several binding possibilities of thymine during chemical adsorption onto a silver surface. It is shown that laser induced photo dissociation may lead to further changes in the recorded spectra of the adsorbate. The surface enhanced-infrared (SEIR) spectra of thymine on silver island are reported here for the first time. The infrared spectra of thymine films were also been obtained to help the assignment of molecular vibrations in the surface enhanced spectra.     

A nanoscale DNA-Au dendrimer as a signal amplifier for the universal design of functional DNA-based SERS biosensors

The use of a nanoscale DNA-Au dendrimer as a signal amplifier was proposed for the universal design of functional DNA-based ultra-sensitive SERS biosensors. This novel design combines the high specificity of functional DNA with the high sensitivity of surface-enhanced Raman scattering (SERS) spectroscopy, resulting in sensitivity superior to that of previously reported sensors.     

Tracking Bisphosphonates through a 20 mm Thick Porcine Tissue by Using Surface-Enhanced Spatially Offset Raman Spectroscopy

Track it down: A recognized surface-enhanced Raman scattering (SERS) nanotag signal was monitored from a thin, dispersed layer of bisphosphonate-functionalized nanotags on a bone sample, through a 20?mm thick specimen of porcine muscle tissue by surface-enhanced spatial offset Raman spectroscopy (SESORS; see picture). The result demonstrates the great potential for non-invasive in?vivo bisphosphonate drug tracking.     

In situ dynamic measurements of the enhanced SERS signal using an optoelectrofluidic SERS platform

A novel active surface-enhanced Raman scattering (SERS) platform for dynamic on-demand generation of SERS active sites based on optoelectrofluidics is presented in this paper. When a laser source is projected into a sample solution containing metal nanoparticles in an optoelectrofluidic device and an alternating current (ac) electric field is applied, the metal nanoparticles are spontaneously concentrated and assembled within the laser spot, form SERS-active sites, and enhance the Raman signal significantly, allowing dynamic and more sensitive SERS detection. In this simple platform, in which a glass slide-like optoelectrofluidic device is integrated into a conventional SERS detection system, both dynamic concentration of metal nanoparticles and in situ detection of SERS signal are simultaneously possible with only a single laser source. This optoelectrofluidic SERS spectroscopy allows on-demand generation of 'hot spots' at specific regions of interest, and highly sensitive, reliable, and stable SERS measurements of the target molecules in a tiny volume (～500 nL) of liquid sample without any fluidic components and complicated systems.     

Raman Spectra of Molecules Adsorbed on Ag Centers in Sol-Gel Matrices

Silica monoliths and submicron spheres containing silver nanoparticles have been obtained using the sol gel technology. The Ag inclusions were synthesized via the counterdiffusion method. The silver-doped matrices were immersed in solutions of an organic dye (indocyanine green) enabling the solute molecules to interact with surface of the Ag-doped silica matrices. Raman spectra of free solutions of the organic molecules under investigation, the impregnated Ag-doped matrices and the impregnated Ag-free matrices have been measured. The impregnated silica matrices which did not contain silver nanoparticles were used as a reference. These experiments have been performed in order to establish if Raman signal enhancement could be obtained by adsorption of organic molecules on the surface of Ag inclusions in the sol-gel matrices analogously to the standard surface-enhanced Raman spectroscopy (SERS) method.     

Surface-enhanced Raman scattering of 4-aminobenzenethiol on silver nanoparticles substrate

Active surface-enhanced Raman scattering (SERS) silver nanoparticles substrate was prepared by multiple depositions of Ag nanoparticles on glass slides. The substrate is based on five depositions of Ag nanoparticles on 3-aminopropyl-trimetoxisilane (APTMS) modified glass slides, using APTMS sol–gel as linker molecules between silver layers. The SERS performance of the substrate was investigated using 4-aminobenzenethiol (4-ABT) as Raman probe molecule. The spectral analyses reveal a 4-ABT Raman signal enhancement of band intensities, which allow the detection of this compound in different solutions. The average SERS intensity decreases significantly in 4-ABT diluted solutions (from 10⁻⁴ to 10⁻⁶ mol L⁻¹), but the compound may still be detected with high signal/noise ratio. The obtained results demonstrate that the Ag nanoparticles sensor has a great potential as SERS substrate.     

Diterpenoic Acids Analysis Using a Coupled TLC-Surface-Enhanced Raman Spectroscopy System

Hyphenation of thin layer chromatography (TLC) with surface-based spectral methods requires a homogeneous surface for direct and quantitative analysis on the chromatographic plate after separation. Since most chromatographic materials do not produce strong background signals in Raman spectroscopy (RS) or surface-enhanced RS (SERS), we tested the suitability of two different chromatographic substrates and one interface for coupling SERS with TLC. This was carried out by using a chromatographic thin layer, specially produced for RS measurements, and a monolithic silica thin layer. A typical TLC plate with a modified aluminium backplate foil on one side was used as an interface. Three biologically active diterpenes, namely gibberellic acid (GA), abietic acid (AA) and kaurenoic acid (KA), were used as test analytes. Stock solutions were applied directly onto the surface, followed by the addition of silver colloid and measurements were taken by SERS. The strongest signal (excitation at 514.5 nm) was obtained for GA using a Raman treated thin layer where the enhancement factor value was determined to be 10². Several fundamental Raman bands for GA were found at 1622, 1593, 1570, 1542, 1366 and 1236 cm⁻¹. When the monolithic silica layer was used, no useful SERS signals were observed. The SERS spectra on modified aluminium backplate for AA and GA were quite similar and no SERS spectrum was obtained for KA. Future research will be concerned towards the use of nanostructured surfaces for SERS analysis. An erratum to this article can be found at     

Recent progress in SERS biosensing

This perspective gives an overview of recent developments in surface-enhanced Raman scattering (SERS) for biosensing. We focus this review on SERS papers published in the last 10 years and to specific applications of detecting biological analytes. Both intrinsic and extrinsic SERS biosensing schemes have been employed to detect and identify small molecules, nucleic acids, lipids, peptides, and proteins, as well as for in vivo and cellular sensing. Current SERS substrate technologies along with a series of advancements in surface chemistry, sample preparation, intrinsic/extrinsic signal transduction schemes, and tip-enhanced Raman spectroscopy are discussed. The progress covered herein shows great promise for widespread adoption of SERS biosensing.     

Rapid detection of Rosa laevigata polysaccharide content by near-infrared spectroscopy

We have investigated surface-enhanced Raman spectroscopy (SERS) spectrum of Omethoate (O,O-dimethyl-S-methylcarbamoylmethylthiophosphate). It is found significant signals in the ordinary Raman spectrum for solid-state Omethoate as well as strong vibrational signals absorbed on the silver sol surface which is prepared by γ-irradiation technique at a very low concentration. Effects of pH and anions (Cl-, Br-, I-) on the adsorption orientation are investigated as well. Two different adsorption mechanisms are deduced, depending on the experimental conditions. The sulfur atom or the sulfur and two oxygen atoms are adsorbed onto the silver sol surface. Among halide ions, Br- and I- are more strongly adsorbed onto the silver sol surface. As a result, the adsorption of Omethoate is less effective due to their steric hindrance.     

Advances in surface-enhanced Raman spectroscopy for analysis of pharmaceuticals: A review

Recently, Raman spectroscopy become a popular and potential analytical technique for the analysis of pharmaceuticals as a result of its advancement. The innovation of laser technology, Fourier Transform-Raman spectrometers with charge coupled device (CCD) detectors, ease of sample preparation and handling, mitigation of sub-sampling problems using different geometric laser irradiance patterns and invention of different optical components of Raman spectrometers are contributors of the advancement of Raman spectroscopy. Transmission Raman Spectroscopy is a useful tool in pharmaceutical analysis to address the problems related with sub-sampling in conventional Raman back scattering. More importantly, the development of surface-enhanced Raman scattering (SERS) has been a prominent advancement for Raman spectroscopy to be applied for pharmaceuticals analysis as it avoids the inherent insensitivity and fluorescence problems. As the active pharmaceutical ingredients (APIs) contain aromatic or conjugated domains with strong Raman scattering activity, Raman spectroscopy is an attractive alternative conventional analytical method for pharmaceuticals. Coupling of Raman spectroscopy with separation techniques is also another advancement applied to reduce or avoid possible spectral interferences. Therefore, in this review, transmission Raman spectroscopy, SERS, and SERS coupled with various separation techniques for pharmaceutical analysis are presented.     

Rapid monitoring of antibiotics using Raman and surface enhanced Raman spectroscopy

Comparatively few studies have explored the ability of Raman spectroscopy for the quantitative analysis of microbial secondary metabolites in fermentation broths. In this study we investigated the ability of Raman spectroscopy to differentiate between different penicillins and to quantify the level of penicillin in fermentation broths. However, the Raman signal is rather weak, therefore the Raman signal was enhanced using surface enhanced Raman spectroscopy (SERS) employing silver colloids. It was difficult by eye to differentiate between the five different penicillin molecules studied using Raman and SERS spectra, therefore the spectra were analysed by multivariate cluster analysis. Principal components analysis (PCA) clearly showed that SERS rather than the Raman spectra produced reproducible enough spectra to allow for the recovery of each of the different penicillins into their respective five groups. To highlight this further the first five principal components were used to construct a dendrogram using agglomerative clustering, and this again clearly showed that SERS can be used to identify which penicillin molecule was being analysed, despite their molecular similarities. With respect to the quantification of penicillin G it was shown that Raman spectroscopy could be used to quantify the amount of penicillin present in solution when relatively high levels of penicillin were analysed (>50 mM). By contrast, the SERS spectra showed reduced fluorescence, and improved signal to noise ratios from considerably lower concentrations of the antibiotic. This could prove to be advantageous in industry for monitoring low levels of penicillin in the early stages of antibiotic production. In addition, SERS may have advantages for quantifying low levels of high value, low yield, secondary metabolites in microbial processes.     

Label-free and direct protein detection on 3D plasmonic nanovoid structures using surface-enhanced Raman scattering

In this paper we use surface-enhanced Raman spectroscopy (SERS) on 3D metallic structures for label-free detection and characterization of proteins of interest at low concentrations. The substrates are prepared via nanopatterning with latex nano/microparticles and Cr and Ag sputtering, yielding stable, tunable, and mechanically flexible plasmonic structures. The nanovoids generate a SERS signal of the proteins of interest that is background free and independent of the protein charge. Concentrations as low as 0.05 μg mL⁻¹ could be detected for 4 different proteins. The proteins also exhibit significantly different SERS spectra on these substrates, which is an important feature for future label-free direct detection schemes.     

Rapid ultrasensitive monitoring the single-particle surface-enhanced Raman scattering (SERS) using a dark-field microspectroscopy assisted system

The observation of single-particle surface-enhanced Raman scattering(SERS) has generated considerable interest both in the nanomaterials filed and in the single-particle spectroscopy community.It is a challenge to realize rapid,facile,and high throughput SERS at single nanoparticle level.Here,without the complex experimental device and difficult experimental operations,a general single-particle SERS technique has been achieved by using dark-field-assisted surface-enhanced Raman spectroscopy(DFSERS).This advanced method provides in-situ characterization of the chemical reaction performance at single gold nanorod.     

DNA碱基与高氯酸根共吸附行为的表面增强拉曼光谱研究

共吸附有助于实现弱吸附分子或离子的高灵敏表面增强拉曼光谱(SERS)检测.本文研究了四种脱氧核糖核酸(DNA)碱基,即腺嘌呤、鸟嘌呤、胞嘧啶、胸腺嘧啶与高氯酸根(ClO4-)在金纳米粒子表面的共吸附行为,并考察了吸附能力、电位、共存阴离子等因素的影响.研究发现四种碱基在质子化后都可以与ClO4-发生共吸附,但在金表面吸附能力弱的胸腺嘧啶与ClO4-共吸附所获得的ClO4-信号最弱.另外,负电位下电极的排斥作用,以及较正电位下基底SERS增强效应减小等因素都会导致ClO4-信号衰减.此外,Cl-、NO3-、SO24-等阴离子可以与ClO4-发生可逆动态竞争共吸附,同时引起ClO4-信号减弱.以上结果将为提高共吸附法检测弱吸附离子的灵敏度提供重要参考.     

Interaction of DNA bases with silver nanoparticles: assembly quantified through SPRS and SERS

Colloidal silver nanoparticles were prepared by reducing silver nitrate with sodium borohydride. The synthesized silver particles show an intense surface plasmon band in the visible region. The work reported here describes the interaction between nanoscale silver particles and various DNA bases (adenine, guanine, cytosine, and thymine), which are used as molecular linkers because of their biological significance. In colloidal solutions, the color of silver nanoparticles may range from red to purple to orange to blue, depending on the degree of aggregation as well as the orientation of the individual particles within the aggregates. Transmission electron microscopy (TEM), X-ray diffraction (XRD), and absorption spectroscopy were used to characterize the assemblies. DNA base-induced differential silver nanoparticle aggregation was quantified from the peak separation (relates to color) of surface plasmon resonance spectroscopy (SPRS) and the signal intensity of surface-enhanced Raman scattering (SERS), which rationalize the extent of silver-nucleobase interactions.     

Convenient formation of nanoparticle aggregates on microfluidic chips for highly sensitive SERS detection of biomolecules

Microfluidic chips combined with surface-enhanced Raman spectroscopy (SERS) offer an outstanding platform for rapid and high-sensitivity chemical analysis. However, it is nontrivial to conveniently form nanoparticle aggregrates (as SERS-active spots for SERS detection) in microchannels in a well-controlled manner. Here, we present a rapid, highly sensitive and label-free analytical technique for determining bovine serum albumin (BSA) on a poly(dimethylsiloxane) (PDMS) microfluidic chip using SERS. A modified PDMS pneumatic valve and nanopost arrays at the bottom of the fluidic microchannel are used for reversibly trapping gold nanoparticles to form gold aggregates, creating SERS-active spots for Raman detection. We fabricated a chip that consisted of a T-shaped fluidic channel and two modified pneumatic valves, which was suitable for fast loading of samples. Quantitative analysis of BSA is demonstrated with the measured peak intensity at 1,615 cm⁻¹ in the surface-enhanced Raman spectra. With our microfluidic chip, the detection limit of Raman can reach as low as the picomolar level, comparable to that of normal mass spectrometry.     

银胶体系中的平衡因素对表面增强拉曼散射的影响

分析银胶体系中样品分子的平衡因子有器壁、银胶、水和杂质，并试验了某此样品的表面增强拉曼散射强度对这些因素的响应，指出全面分析影响对于表面增强拉曼散射的分应用的重要性。     

Silver nanoparticle aggregates on copper foil for reliable quantitative SERS analysis of polycyclic aromatic hydrocarbons with a portable Raman spectrometer

Silver nanoparticle aggregates were synthesized on copper foil, which was used for the surface-enhanced Raman spectroscopy (SERS) detection of polycyclic aromatic hydrocarbons (PAHs) with a portable Raman spectrometer. Silver nanoparticle aggregates were prepared by immersing copper foil in the solution of Sn(2+) and AgNO(3) in a cyclic fashion. A four-cycle process was selected for the following experiments due to its high enhancement and relatively convenient experimental procedure. The substrate has greater temporal stability under continuous laser radiation, good uniformity and reproducibility, which indicated that the substrate could provide reliable measurements. The relationship between SERS intensity and concentrations of PAHs was studied. Quantitative analysis of PAHs in aqueous solution was further performed based on the prepared substrate. The log-log plot of normalized SERS intensity to PAHs concentration exhibited a good linear relationship, with the detection limits in the range of 5-500 μg L(-1). Thus, due to the stability, reproducibility and quantitative results, the prepared substrate could be used as a potential SERS sensor for the analysis of environmental pollutants.