Surface-enhanced Raman scattering: realization of localized surface plasmon resonance using unique substrates and methods

Surface-enhanced Raman scattering (SERS) enhancement and the reproducibility of the SERS signal strongly reflect the quality and nature of the SERS substrates because of diverse localized surface plasmon resonance (LSPR) excitations excited at interstitials or sharp edges. LSPR excitations are the most important ingredients for achieving huge enhancements in the SERS process. In this report, we introduce several gold and silver nanoparticle-based SERS-active substrates developed solely by us and use these substrates to investigate the influence of LSPR excitations on SERS. SERS-active gold substrates were fabricated by immobilizing colloidal gold nanoparticles on glass slides without using any surfactants or electrolytes, whereas most of the SERS-active substrates that use colloidal gold/silver nanoparticles are not free of surfactant. Isolated aggregates, chain-like elongated aggregates and two-dimensional (2D) nanostructures were found to consist mostly of monolayers rather than agglomerations. With reference to correlated LSPR and SERS, combined experiments were carried out on a single platform at the same spatial position. The isolated aggregates mostly show a broadened and shifted SPR peak, whereas a weak blue-shifted peak is observed near 430 nm in addition to broadened peaks centered at 635 and 720 nm in the red spectral region in the chain-like elongated aggregates. In the case of 2D nanostructures, several SPR peaks are observed in diverse frequency regions. The characteristics of LSPR and SERS for the same gold nanoaggregates lead to a good correlation between SPR and SERS images. The elongated gold nanostructures show a higher enhancement of the Raman signal than the the isolated and 2D samples. In the case of SERS-active silver substrates for protein detection, a new approach has been adopted, in contrast to the conventional fabrication method. Colloidal silver nanoparticles are immobilized on the protein functionalized glass slides, and further SERS measurements are carried out based on LSPR excitations. A new strategy for the detection of biomolecules, particularly glutathione, under aqueous conditions is proposed. Finally, supramolecular J-aggregates of ionic dyes incorporated with silver colloidal aggregates are characterized by SERS measurements and correlated to finite-difference time-domain analysis with reference to LSPR excitations. Figure SPR and SERS images for isolated, elongated and two-dimensional gold nanostructures     

Optofluidic microsystem with quasi-3 dimensional gold plasmonic nanostructure arrays for online sensitive and reproducible SERS detection

Practical applications of chemical and biological detections through surface-enhanced Raman scattering (SERS) require high reproducibility, sensitivity, and efficiency, along with low-cost, straightforward fabrication. In this work, we integrated a poly-(dimethylsiloxane) (PDMS) chip with quasi-3D gold plasmonic nanostructure arrays (Q3D-PNAs), which serve as SERS-active substrates, into an optofluidic microsystem for online sensitive and reproducible SERS detections. The Q3D-PNA PDMS chip was fabricated through soft lithography to ensure both precision and low-cost fabrication. The optimal dimension of the Q3D-PNA in PDMS was designed using finite-difference time-domain (FDTD) electromagnetic simulations with a simulated enhancement factor (EF) of 1.6 × 10⁶. The real-time monitoring capability of the SERS-based optofluidic microsystem was investigated by kinetic on/off experiments through alternatively flowing Rhodamine 6G (R6G) and ethanol in the microfluidic channel. A switch-off time of ∼2 min at a flow rate of 0.3 mL min⁻¹ was demonstrated. When applied to the detection of low concentration malathion, the SERS-based optofluidic microsystem with Q3D-PNAs showed high reproducibility, significantly improved efficiency and higher detection sensitivity via increasing the flow rate. The optofluidic microsystem presented in this paper offers a simple and low-cost approach for online, label-free chemical and biological analysis and sensing with high sensitivity, reproducibility, efficiency, and molecular specificity.     

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.     

SERS活性光纤光谱微探针研究

用真空蒸镀银岛膜和银溶胶自组装膜两种方法对光纤探针进行表面增强拉曼(SERS)活性修饰,构造了圆锥型SERS活性光纤光谱微探针.选取几个有代表性的分子作为检测样品,得到了低浓度样品的SERS光谱,对样品BVPP的检测下限达到10^-9mol/L.比较两种修饰光纤探针的检测结果可知,银溶胶自组装膜修饰更有优势.     

Chemical analysis of polycyclic aromatic hydrocarbons by surface-enhanced Raman spectroscopy

The use of surface-enhanced Raman spectroscopy (SERS) for trace determination of polycyclic aromatic hydrocarbons (PAHs) is described. This paper focuses on the development of SERS-active substrates that are specific for the characterization and spectroscopic study of PAHs. The SERS-active substrates are based on thin gold films evaporated on a glass surface previously treated with a mercaptoalkylsilane. SERS of PAHs was investigated over uncoated gold island films and over such films coated with a self-assembled monolayer (SAM) of 1-propanethiol. Adsorption of PAHs on a plain SERS-active Au-film led to a surface-induced decomposition of PAHs, due to catalytic properties of nanostructured gold. Thus, the functionalization of the SERS-active substrates by means of SAM was done aiming at a specific chemical interaction toward PAHs. Thus, in addition to preventing decomposition of the PAHs, the coating also concentrates the hydrophobic PAHs close enough to the SERS-active interface. Results show that high sensitivity, SERS-active nanostructured gold substrates that show selectivity towards PAHs were obtained, with the following properties: strong intensification of the Raman signal, reproducibility, and stability over time. The employed methodology enables the observation of excellent Raman spectra of PAHs in aqueous environment at ppm levels.     

Immobilization of silver nanoparticles into POEGMA polymer brushes as SERS‐active substrates

Surface‐enhanced Raman scattering (SERS) has attracted a great deal of interest during the past four decades and emerged as an ultrasensitive optical technique for chemical and biomedical analysis. It is widely accepted that the facile fabrication of SERS substrates with high activity and good reproducibility is of crucial importance for their applications. Herein, we report on a fast and robust method for the synthesis and immobilization of silver nanoparticles (AgNPs) into poly(oligo(ethylene glycol) methacrylate) (POEGMA) brushes under mild conditions without using any reducing agents. POEGMA brushes of different chain lengths were synthesized directly on silicon wafers by surface‐initiated atom transfer radical polymerization with various reaction time. X‐ray photoelectron spectroscopy and field emission scanning electron microscope measurements indicated that the AgNPs were firmly and homogeneously embedded into POEGMA brushes. The resulting POEGMA–AgNP hybrid films were employed as SERS substrates for the detection of 4‐aminothiophenol, giving rise to an enhancement factor of up to 1.9 × 10⁶. The influence of the POEGMA's chain length on SERS performance was also investigated. Copyright © 2016 John Wiley & Sons, Ltd.     

Highly reproducible surface-enhanced Raman scattering-active Au nanostructures prepared by simple electrodeposition: Origin of surface-enhanced Raman scattering activity and applications as electrochemical substrates

The fabrication of effective surface-enhanced Raman scattering (SERS) substrates has been the subject of intensive research because of their useful applications. In this paper, dendritic gold (Au) rod (DAR) structures prepared by simple one-step electrodeposition in a short time were examined as an effective SERS-active substrate. The SERS activity of the DAR surfaces was compared to that of other nanostructured Au surfaces with different morphologies, and its dependence on the structural variation of DAR structures was examined. These comparisonal investigations revealed that highly faceted sharp edge sites present on the DAR surfaces play a critical role in inducing a high SERS activity. The SERS enhancement factor was estimated to be greater than 10⁵, and the detection limit of rhodamine 6G at DAR surfaces was 10⁻⁸ M. The DAR surfaces exhibit excellent spot-to-spot and substrate-to-substrate SERS enhancement reproducibility, and their long-term stability is very good. It was also demonstrated that the DAR surfaces can be effectively utilized in electrochemical SERS systems, wherein a reversible SERS behavior was obtained during the cycling to cathodic potential regions. Considering the straightforward preparation of DAR substrates and the clean nature of SERS-active Au surfaces prepared in the absence of additives, we expect that DAR surfaces can be used as cost-effective SERS substrates in analytical and electrochemical applications.     

Microspectrometric investigation of active substrates for surface enhanced Raman scattering

The results of investigations of several new active silver substrates and some previously reported active silver substrates for surface enhanced Raman spectrometry (SERS) using a Raman microprobe are given. Filter-papers of different composition and porosity, silver membranes and glass slides are evaluated as supports for SERS active substrates. Methods of silver preparation include evaporation and chemical reduction. The Raman microprobe facilitates the acquisition of SER spectra of the adsorbate over the metal microstructure being observed on a TV monitor. This capability allows the establishment of practical relationships between the surface morphology and SERS activity which can be used as guidelines for SERS experiments with the microprobe. For the most monodisperse substrates, it is possible to establish a linear relationship between SERS intensity and adsorbate concentration. In the lower extreme of the calibration graph, the amount of adsorbate being observed under the microscope objective is only 0.3 amol or 1.9 × 10⁵ molecules.     

Surface-enhanced Raman scattering-active silver nanostructures with two domains

Generally, a controllable and reproduced surface roughness for surface-enhanced Raman scattering (SERS) studies can be generated through control of the electrochemical oxidation–reduction cycles (ORC) procedure. In this work, we propose a new sonoelectrochemical approach to prepare SERS-active substrates with two domain-Ag nanostructures. The method is based on a strategy of deposition–dissolution cycles (DDCs) by using a cathodic overpotential and an anodic overpotential from open circuit potential (OCP) in turn under sonication. The prepared SERS-active substrate demonstrates large Raman scattering enhancement for adsorbed Rhodamine 6G (R6G) with an enhancement factor of 2.3 × 10⁸ and a limit of detection of 2 × 10⁻¹³ M. The improved SERS performances can be successfully explained from the viewpoints of electromagnetic (EM) and chemical (CHEM) enhancements.     

Novel fabrication of silver-coated glass capillaries for ready SERS-based detection of dissolved chemical species

A novel method to deposit a highly surface-enhanced Raman scattering (SERS) active silver film onto the inside surface of a glass capillary is developed. Firstly, Ag sol was synthesized by the reaction of AgNO₃ with poly-(ethylenimine) (PEI), and then toluene and benzenethiol (BT) were added into the sol. The mixture was flowed through the glass capillary to obtain the SERS-active Ag film-coated glass capillary. The SERS activity of the Ag-coated capillary was dependent on the amount of PEI and BT used. In addition, BT could be easily desorbed from the Ag surface by treating it with a borohydride solution, maintaining the initial SERS activity. The SERS enhancement factor at 632.8-nm excitation was estimated to be on the order of 10⁶. The detection limits of adenine and dipicolinic acid were then as low as 1.0 × 10⁻⁸ and 1.0 × 10⁻⁷ M, respectively, based on an S/N ratio of 3. This clearly suggests that the Ag-coated capillary is an invaluable device for the analysis of effluent chemicals by SERS.     

Silver Nanostructures on Graphene Oxide as the Substrate for Surface-Enhanced Raman Scattering (SERS)

Nanosized surface-enhanced Raman scattering (SERS) substrates fabricated by the controlled growth of metal nanostructures on water-dispersed two-dimensional nanomaterials can open a new avenue for SERS analysis of liquid samples in biological fields. In this work, regular and uniform Ag nanostructures were grown on the surface of graphene oxide (GO) through a microwave-assisted hydrothermal method. Polyamidoamine (PAMAM) dendrimers were assembled on the surface of GO to form GO/PAMAM templates for growing Ag nanostructures, which are primarily comprised of Ag dimers and trimers. The prepared Ag/GO nanocomposites are highly dispersed and stable in aqueous solution and may be used as substrates for enhanced Raman detection of rhodamine 6?G (R6G) in aqueous solution. This special substrate provides high-performance SERS and suppresses R6G fluorescence in aqueous solution and is promising as a nanosized material for the enhanced Raman detection of liquid samples in biological diagnostics.     

Using a photochemical method and chitosan to prepare surface-enhanced Raman scattering–active silver nanoparticles

In this paper, we report a new strategy for the preparation of surface-enhanced Raman scattering (SERS)-active silver nanoparticles (Ag NPs), using a photochemical method and the presence of chitosan (Ch). First, Ag substrates were subjected to electrochemical oxidation/reduction cycles (ORCs) in deoxygenated aqueous solutions containing 0.1 M HNO₃ and 1 g L⁻¹ Ch (pH 6.9, adjusted by adding 1 M NaOH), resulting in Ag⁺–Ch complexes. These substrates were then irradiated with UV light at various wavelengths to yield the SERS-active Ag NPs. A stronger SERS effect was observed on the SERS-active Ag NPs prepared by using UV irradiation at 310 nm. The pH of the solution and the presence of Ch during the preparation process both affected the resulting SERS activities.     

Identification and classification of respiratory syncytial virus (RSV) strains by surface-enhanced Raman spectroscopy and multivariate statistical techniques

There is a critical need for a rapid and sensitive means of detecting viruses. Recent reports from our laboratory have shown that surface-enhanced Raman spectroscopy (SERS) can meet these needs. In this study, SERS was used to obtain the Raman spectra of respiratory syncytial virus (RSV) strains A/Long, B1, and A2. SERS-active substrates composed of silver nanorods were fabricated using an oblique angle vapor deposition method. The SERS spectra obtained for each virus were shown to posses a high degree of reproducibility. Based on their intrinsic SERS spectra, the four virus strains were readily detected and classified using the multivariate statistical methods principal component analysis (PCA) and hierarchical cluster analysis (HCA). The chemometric results show that PCA is able to separate the three virus strains unambiguously, whereas the HCA method was able to readily distinguish an A2 strain-related G gene mutant virus (ΔG) from the A2 strain. The results described here demonstrate that SERS, in combination with multivariate statistical methods, can be utilized as a highly sensitive and rapid viral identification and classification method.     

Aptameric SERS sensor for Hg~(2+) analysis using silver nanoparticles

Aptamer–silver nanoparticles (AgNPs) based surface-enhanced Raman scattering (SERS) sensor has been developed for Hg²⁺ detection by employing the structure-switching aptamer in the presence of spermine. This simple method shows excellent sensitivity and selectivity owing to the sensitive SERS detection technique and high specificity of aptamer for binding Hg²⁺.     

Surface-enhanced Raman scattering for protein detection

Proteins are essential components of organisms and they participate in every process within cells. The key characteristic of proteins that allows their diverse functions is their ability to bind other molecules specifically and tightly. With the development of proteomics, exploring high-efficiency detection methods for large-scale proteins is increasingly important. In recent years, rapid development of surface-enhanced Raman scattering (SERS)-based biosensors leads to the SERS realm of applications from chemical analysis to nanostructure characterization and biomedical applications. For proteins, early studies focused on investigating SERS spectra of individual proteins, and the successful design of nanoparticle probes has promoted great progress of SERS-based immunoassays. In this review we outline the development of SERS-based methods for proteins with particular focus on our proposed protein-mediated SERS-active substrates and their applications in label-free and Raman dye-labeled protein detection. Figure Protein-mediated SERS-active substrates for protein detection     

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.     

Simple and rapid surface-enhanced Raman Spectroscopy assay for safranine T and its application in highly sensitive determination of mercury (Ⅱ)

A simple and sensitive surface-enhanced Raman spectroscopy (SERS) method for the detection of safranine T (ST) and Hg²⁺ using silver nanoparticles (AgNPs) as substrate was developed. ST can absorb on the surface of AgNPs through electrostatic interaction, the electromagnetic effect combined with chemical adsorption effect give a notable Raman enhancement for ST. The presence of Hg²⁺ well decreased the absorbed ST molecules on AgNPs, leading to a significant decrease of SERS signals thus enabling to detect Hg²⁺. The determination conditions for SERS, including the amount of AgNPs, the concentration of NaCl, the concentration of HCl, the concentration of ST and the reaction time, were optimised. Under the optimised experimental conditions, good linear responses were obtained for ST and Hg²⁺ in the concentration ranges of 0.01–4.0 μmol L^?1 (3.5–1403.4 ng mL^?1) and 0.01–2.0 μmol L^?1 (2.0–401.2 ng mL^?1), the limit of detection were 3.0 nmol L^?1 (1.1 ng mL^?1) and 2.0 nmol L^?1 (0.4 ng mL^?1), respectively. The present method was subsequently applied to the determination of ST in tomato sauces and Hg²⁺ in environmental waters, the recoveries of ST and Hg²⁺ in spiked samples are 95.5–107.8% and 91.4–110.8 %, respectively.     

Surface-enhanced Raman scattering (SERS) optrodes for multiplexed on-chip sensing of nile blue A and oxazine 720

The fabrication and on-chip integration of surface-enhanced Raman scattering (SERS) optrodes are presented. In the optrode configuration, both the laser excitation and the back-scattered Raman signal are transmitted through the same optical fiber. The SERS-active component of the optrode was fabricated through the self-assembly of silver nanoparticles on the tip of optical fibers. The application of SERS optrodes to detect dyes in aqueous solution indicated a limit of quantification below 1 nM, using nile blue A as a molecular probe. Using the optrode-integrated microfluidic chip, it was possible to detect several different dyes from solutions sequentially injected into the same channel. This approach for sequential detection of different analytes is applicable to monitoring on-chip chemical processes. The narrow bandwidth of the vibrational information generated by SERS allowed solutions of different compositions of two chemically similar dyes to be distinguished using a dilution microfluidic chip. These results demonstrate the advantages of the SERS-optrode for microfluidics applications by illustrating the potential of this vibrational method to quantify components in a mixture.     

Surface-enhanced Raman spectroscopy based on conical holed enhancing substrates

In this contribution, surface-enhanced Raman spectroscopy (SERS) based on conical holed glass substrates deposited with silver colloids was reported for the first time. It combines the advantages of both dry SERS assays based on plane films deposited with silver colloids and wet SERS assays utilizing cuvettes or capillary tubes. Compared with plane glass substrates deposited with silver colloids, the conical holed glass substrates deposited with silver colloids exhibited five-to ten-folds of increase in the rate of signal enhancement, due to the internal multiple reflections of both the excitation laser beam and the Raman scattering photons within conical holes. The application of conical holed glass substrates could also yield significantly stronger and more reproducible SERS signals than SERS assays utilizing capillary tubes to sample the mixture of silver colloids and the solution of the analyte of interest. The conical holed glass substrates in combination with the multiplicative effects model for surface-enhanced Raman spectroscopy (MEM_SERS) achieved quite sensitive and precise quantification of 6-mercaptopurine in complex plasma samples with an average relative prediction error of about 4% and a limit of detection of about 0.02 μM using a portable i-Raman 785H spectrometer. It is reasonable to expect that SERS technique based on conical holed enhancing substrates in combination with MEM_SERS model can be developed and extended to other application areas such as drug detection, environmental monitoring, and clinic analysis, etc.