Ultrasensitive detection of 1,4-Bis(4-vinylpyridyl)phenylene in a small volume of low refractive index liquid by surface-enhanced Raman scattering-active light waveguide

This paper reports a novel surface-enhanced Raman scattering (SERS)-active light waveguide method for ultrasensitive detection of a sample dissolved in a small volume of low refractive index liquid. The SERS-active light waveguide demonstrated in this study was constructed via the light-guiding silica capillary. The surface of its inner wall was modified with SERS-active silver nanoparticles that can remarkably enhance Raman signals. The capillary with SERS-active modified layer was filled with the sample solution to form the SERS-active liquid core (LC) fiber. The incident laser beam travels through the waveguide in a totally reflective mode within the fiber wall and penetrates a small distance into the sample solution by the evanescent wave field. The Raman scattering of the analytes adsorbed onto the surface of the SERS-active modified layer can be excited by the laser beam and refracted into the fiber wall. Thus, a sample dissolved in low index liquid, e.g., methanol, can be quantitatively monitored by Raman spectroscopy and detection limit of its concentration is lower than 10(-9) mol/L.     

Minimally invasive surface-enhanced Raman scattering detection with depth profiles based on a surface-enhanced Raman scattering-active acupuncture needle

To obtain depth profiles of surface-enhanced Raman scattering (SERS) information in living systems, a SERS-active needle was structured by acupuncture needles, gold nanoshells (GNSs), and polystyrene, which were used as carriers, SERS-active elements to be absorbed on the carriers, and coatings to protect the absorbed GNSs from being erased during insertion, respectively. The SERS-active needle is minimally invasive for entering and exiting the body. The interspaces between the GNSs became vessels to collect diffused fluids at different depths after a SERS-active needle was inserted into an agarose gel, and the SERS intensity profile on the SERS-active needle coincided with the concentration profile of Nile Blue A (NBA) in the gel. SERS detection in vitro avoided the signal attenuation in gels, and the SERS detection at different spots of the SERS-active needle provided a depth profile of the NBA molecule in the gel. In vivo experiments of NBA and 6-mercaptopurine confirmed that the SERS-active needle could collect fluids in living systems easily with minimal invasion and provide information about depth profiles of target molecules in tissues.     

Gold coated zinc oxide nanonecklaces as a SERS substrate

Faceted zinc oxide nanonecklace (ZnO NN) arrays were grown on r-plane sapphires along one direction (ZnO [0001] II sapphire [10-11] and ZnO (-12-10) II sapphire (01-12)) using chemical vapor deposition. After coated with 45 nm gold films and annealed at 250 degrees C for 30 seconds, the coated ZnO NNs exhibit satisfactory and stable surface enhanced Raman scattering (SERS) effects when tested with melamine and other chemicals. The limit of detection of melamine is 10(-5) mol/L and the analytical enhancement factor is 10(4), which is competitive to a commercial substrate. This study indicates that gold coated ZnO NN substrates have a great potential as SERS-active substrates in rapid detection of trace amount food contaminants such as melamine and other chemicals.     

Silver nanorod arrays as a surface-enhanced Raman scattering substrate for foodborne pathogenic bacteria detection

Surface-enhanced Raman scattering (SERS) using novel silver nanorod array substrates has been used for the detection of pathogenic bacteria. The substrate consists of a base layer of 500 nm silver film on a glass slide and a layer of silver nanorod array with a length of approximately 1 microm produced by the oblique angle deposition method at a vapor incident angle of 86 degrees . Spectra from whole cell bacteria, Generic Escherichia coli, E. coli O157:H7, E. coli DH 5alpha, Staphylococcus aureus, S. epidermidis, and Salmonella typhimurium, and bacteria mixtures have been obtained. This SERS active substrate can detect spectral differences between Gram types, different species, their mixture, and strains. Principal component analysis (PCA) has been applied to classify the spectra. Viable and nonviable cells have also been examined, and significantly reduced SERS responses were observed for nonviable cells. SERS detection of bacteria at the single cell level, excited at low incident laser power (12 micro W) and short collection time (10 s), has also been demonstrated. These results indicate that the SERS-active silver nanorod array substrate is a potential analytical sensor for rapid identification of microorganisms with a minimum of sample preparation.     

Removal of surface contamination and self-assembled monolayers (SAMs) from silver (Ag) nanorod substrates by plasma cleaning with argon

Surface contamination of surface-enhanced Raman (SERS)-active metallic substrates has been a limitation to the utility of SERS as an analytical technique, potentially affecting surface coverage, spectral reproducibility, and analytical limits of detection. We have developed a simple and versatile cleaning method for SERS-active Ag nanorod arrays that consists of a short (4 min) exposure of the substrate to an Ar(+) plasma in a low-pressure environment. The findings presented here demonstrate that this cleaning procedure essentially eliminates organic background contamination. This procedure works equally well for self-assembled monolayers of thiolates that strongly adsorb onto Au and Ag surfaces. For SERS-active surfaces composed of arrays of Ag nanorods prepared by oblique-angle vapor deposition, we investigated the (1) Raman band intensities, (2) nanorod morphology via scanning electron microscopy, and (3) surface hydrophobicity via static contact angle measurements, as a function of exposure time of the Ag nanorods to the Ar(+) plasma. Short (4 min) exposure to Ar(+) plasma eliminated background contamination but decreased the observed SERS intensity for re-adsorbed analytes by approximately a factor of 2 while leaving the nanorod morphology essentially unchanged. Prolonged exposure to Ar(+) plasma (>10 min) resulted in substantial morphological changes of the Ag nanorod lattice and led to a decrease in the observed SERS intensities by a factor of 10. The results presented here suggest that Ar(+) plasma cleaning is an efficient process for removing carbonaceous and organic contamination as well as thiolate monolayers from SERS-active Ag surfaces, as long as the plasma conditions and exposure times are carefully monitored.     

Preparation and application of microfluidic SERS substrate:Challenges and future perspectives

Surface-enhanced Raman spectroscopy(SERS), as a highly sensitive molecular analysis technique, can realize fast and non-destructive detection of the information of molecular bonds to identify the component of analytes by "fingerprint" identification. The preparation of SERS substrates plays an extremely important role in the development of SERS technology and the application of SERS detection. By integrating SERS enhancement substrates into microfluidic chips, researchers have developed the microfluidic SERS chips which expand the function of microfluidic chips and provide an efficient platform for on-site biochemical analysis equipped with the powerful sensing capability of SERS technique. In this paper, we will first briefly give a review of the current microfluidic SERS-active substrates preparation technology and present the perspective on the application prospects of microfluidic SERS-active substrates. And then the challenges in the preparation of microfluidic SERS-active substrates will be pointed out, as well as realistic issues of using this technology for biochemical application.     

Nanoparticle-functionalized porous polymer monolith detection elements for surface-enhanced Raman scattering

The use of porous polymer monoliths functionalized with silver nanoparticles is introduced in this work for high-sensitivity surface-enhanced Raman scattering (SERS) detection. Preparation of the SERS detection elements is a simple process comprising the synthesis of a discrete polymer monolith section within a silica capillary, followed by physically trapping silver nanoparticle aggregates within the monolith matrix. A SERS detection limit of 220 fmol for Rhodamine 6G is demonstrated, with excellent signal stability over a 24 h period. The capability of the SERS-active monolith for label-free detection of biomolecules was demonstrated by measurements of bradykinin and cytochrome c. The SERS-active monoliths can be readily integrated into miniaturized micrototal-analysis systems for online and label-free detection for a variety of biosensing, bioanalytical, and biomedical applications.     

Localized oblique-angle deposition: Ag nanorods on microstructured surfaces and their SERS characteristics

In this paper, we demonstrate a simple and convenient method of depositing Ag nanorods on a substrate inside a standard evaporation chamber with the substrate resting on a leveled stage. Microstructuring the substrate prior to the deposition imparts a large incidence angle (>70°) between the collimated vapor atoms and the local surface normal, which is essential to induce the shadowing effect. Thereby, a localized oblique-angle deposition (LOAD) is realized, forming nanorods selectively on the steep sidewalls of surface microcavities patterned via standard photolithography and silicon dry etching. We also demonstrate that these nanorods can boost SERS activity of the underlying substrate and thus perform comparable to those fabricated via advanced patterning techniques or conventional OAD whereby the entire substrate has to be tilted with respect to the incident vapor atoms. Our results suggest the viability of decorating microchannel sidewalls with SERS-active nanorods for integrated sample processing and SERS detection.     

On-line monitoring of airborne chemistry in levitated nanodroplets: in situ synthesis and application of SERS-active Ag-Sols for trace analysis by FT-Raman spectroscopy

We report a new strategy for on-line monitoring of chemical reactions in ultrasonically levitated, nanoliter-sized droplets by Raman spectroscopy. A flow-through microdispenser connected to an automated flow injection system was used to dose picoliter droplets into the node of an ultrasonic trap. Taking advantage of the flow-through characteristics of the microdispenser and the versatility of the automated flow system, a well-defined sequence of reagents could be injected via the microdispenser into the levitated droplet placed in the focus of the collection optics of the Fourier transform Raman spectrometer. In that way, chemical reactions could be carried out and monitored on-line. The developed system was used for fast, reproducible, in situ synthesis of a highly active surface enhanced Raman scattering (SERS) sol resulting from the reduction of silver nitrate with hydroxylamine hydrochloride in basic conditions. With this chemical system, SERS substrate preparation could be achieved at room temperature and in short time. The in situ prepared silver sol was used for trace analysis of several organic test molecules that were injected into the levitated SERS-active droplet again using the microdispenser. The concentration dependence of the SERS spectra was studied using 9-aminoacridine, revealing that down to the femtogram region high-quality SERS spectra could be obtained. Additionally, SERS spectra of 6-mercaptopurine, thiamine, and acridine were recorded in the levitated drop as well.     

Carbon nanowalls amplify the surface-enhanced Raman scattering from Ag nanoparticles

We report surface-enhanced Raman scattering (SERS) from Ag nanoparticles decorated on thin carbon nanowalls (CNWs) grown by microwave plasma chemical vapor deposition. The Ag morphology is controlled by exposing the CNWs to oxygen plasma and through the electrodeposition process by varying the number of deposition cycles. The SERS substrates are capable of detecting low concentrations of rhodamine 6G and bovine serum albumin, showing much higher Raman enhancement than ordinary planar HOPG with Ag decoration. The major factors contributing to this behavior include: high density of Ag nanoparticles, large surface area, high surface roughness, and the underlying presence of vertically oriented CNWs. The relatively simple procedure of substrate preparation and nanoparticle decoration suggests that this is a promising approach for fabricating ultrasensitive SERS substrates for biological and chemical detection at the single-molecule level, while also enabling the study of fundamental SERS phenomena.     

New surface-enhanced Raman spectroscopy substrates via self-assembly of silver nanoparticles for perchlorate detection in water

Perchlorate (ClO4-) has recently emerged as a widespread contaminant in drinking water and groundwater supplies in the United States, and a need exists for rapid detection and monitoring of this contaminant. In this study, surface-enhanced Raman spectroscopy (SERS) was studied as a means of ClO4- detection, and new sol-gel-based SERS substrates were developed by self-assembly of silver colloidal nanoparticles with various functionalized silane reagents. These substrate materials were tailored to allow detection of ClO4- in water with improved sorptivity, stability, and sensitivity and with the ability to detect ClO4- at concentrations as low as 10(-6) M (or 100 microg/L) with good reproducibility. Similar techniques were used to fabricate capillary SERS flow cells by assembling functionalized silver nanoparticles capable of attracting ClO4- to the SERS surface or the internal wall of glass capillaries. These capillary flow cells could be readily configured to allow for in situ, nondestructive detection of ClO4- via fiber optics.     

Vapor deposition method for sensitivity studies on engineered surface-enhanced Raman scattering-active substrates

The design and optimization of a vapor-phase analyte deposition method for limit of detection (LOD) studies on engineered surface-enhanced Raman scattering (SERS)-active substrates is presented. The vapor deposition method was designed to overcome current challenges in quantitative analysis of lithographically produced SERS substrates that are relatively small (hundreds of square micrometers). A custom-built flow cell was used to deposit benzenethiol from the vapor phase onto SERS-active Ag thin films, as the control substrates, and nanoaperture arrays that were generated by electron-beam lithography. The surface coverage of benzenethiol as a function of time was monitored using the ring stretching mode 1070-cm(-1) band and the trend was fit to Langmuir adsorption kinetics. The method was deemed reliable based on agreement between the LOD determined on the control substrates and previously reported values for those substrates. Application of the new method to a 20 x 20 microm(2) nanoaperture array yielded a LOD of 4.2 +/- 0.3 amol.     

Controlled fabrication of surface-enhanced-Raman scattering-active silver nanostructures on polypyrrole films

Different kinds of silver nanostructures have been deposited on the surface of the polypyrrole (PPy) films by silver-mirror reaction. The morphology of silver nanostructures can be controlled by modulating the reaction conditions. The application of the as-prepared PPy–silver composites in surface-enhanced Raman scattering (SERS) was studied using 4-mercaptopyridine (4-Mpy) as probe molecules. The results showed that PPy–silver composites exhibited excellence SERS ability and could be used as SERS-active substrates for detection of trace molecules.     

Surface-enhanced Raman spectroscopy of the growth of ultra-thin organosilicon plasma polymers on nanoporous Ag/SiO2-bilayer films

A new method for the synthesis of thin bilayer films as surface-enhanced Raman spectroscopy (SERS) active substrates was developed which is based on the combination of plasma polymerization, plasma calcination and Ag-film deposition by means of physical vapor deposition. The surface morphology of prepared substrates was characterized by field emission scanning electron microscopy, atomic force microscopy and electrochemical impedance spectroscopy. These substrates lead to high surface enhancement factors proven by the spectroscopic analysis of adsorbed Trans-1,2 bis-(4-pyridyl) ethylene molecules. By this preparation technique, SERS-active films can be deposited on any substrate. The new SERS substrates were successfully applied to study the growth of ultra-thin hexamethyldisiloxane plasma polymer films. The Raman intensity of the CH-stretching vibration was studied as a function of the film thickness. The surface enhancement decreased sharply at about 20 nm. The resulting increase in the intensity of Raman peaks for thin adsorbed plasma polymer films was observed to be a combination of the electromagnetic enhancement mechanism and the high surface area increase of the rough Ag-surface.     

Portable surface-enhanced Raman scattering sensor for rapid detection of aniline and phenol derivatives by on-site electrostatic preconcentration

A portable surface-enhanced Raman scattering (SERS) sensor is developed and applied to simultaneous detection of aniline and phenol derivatives in a label-free way with an electrostatic preconcentration technique to amplify the signals. A SERS-active substrate, silver-electrodeposited screen-printed electrodes (Ag-SPEs), is used for qualification and quantification of polar organic pollutants. Observation of SERS spectra at different potentials indicates that polar pollutants are selectively adsorbed on the Ag-SPEs at a given potential, suggesting that Ag-SPEs could selectively attract polar pollutants to an oppositely charged electrode at different potentials. Optimum SERS-active substrate was obtained when a potential of -0.15 V vs Ag/AgCl was applied on the SPEs in 0.1 M AgNO(3) solution for 10 min. Moreover, the effects of experimental variables such as the electrodeposition time and potential of Ag and preconcentration time of polar molecules on the SERS signals are presented. Under optimum conditions and with a 785 nm laser, the method is effective over a wide range of concentration (1 nM to 1 μM) for aniline and phenol derivatives. The novel method described herein presents a new detection regime for environmental pollutant analysis and also demonstrates simultaneous multiplexed detection of polar organic pollutants using convenient Ag-SPEs.     

A new approach to solution-phase gold seeding for SERS substrates

Surface-enhanced Raman scattering (SERS) vastly improves signal-to-noise ratios as compared to traditional Raman scattering, making sensitive assays based upon Raman scattering a reality. However, preparation of highly stable SERS-active gold substrates requires complicated and expensive methodologies and instrumentation. Here, a general and completely solution-phase, seed-based approach is introduced, which is capable of producing gold films for SERS applications on a variety of substrates, not requiring surface modification or functionalization. SERS enhancement factors of ≈10(7) were observed. Moreover, solution-phase gold film deposition on highly complex surfaces, such as protein-coated bioassays, is demonstrated for the first time. Protein bioassays coated with such SERS-active gold films are combined with bioconjugated single-walled carbon nanotube Raman labels, affording highly sensitive detection of the cancer biomarker, carcinoembryonic antigen in serum, with a limit of detection of ≈5 fM (1 pg mL(-1) ).     

Portable electrochemical surface-enhanced Raman spectroscopy system for routine spectroelectrochemical analysis

A simple, portable electrochemical surface-enhanced Raman spectroscopy (SERS) system is reported, consisting of a small benchtop Raman spectrometer, a laptop computer, and a portable USB potentiostat. Screen printed electrodes modified with silver colloidal nanoparticles are used as the SERS-active electrode, which exhibit long-term stability once prepared. Spectroelectrochemical analyses of para-aminothiophenol and melamine as model systems was conducted. In both cases, an increase in SERS signal is observed upon modulation of the applied voltage, indicating an inherent benefit of such a system wherein the surface charge can be easily tuned. Given the low cost, rapid analysis time, and good sensitivity of this system, this simple setup could be implemented for many on-site sensing applications, ranging from food and drug analysis to environmental monitoring and to chemical and biological warfare agent detection.     

Recyclable SERS substrates based on Au-coated ZnO nanorods

Vertically aligned Au-coated ZnO nanorods (Au-ZnO NRs) were investigated as cheap, efficient and recyclable SERS-active substrates. The ZnO NRs were prepared through a simple, low-temperature hydrothermal route and made SERS-active through deposition of gold nanoislands by sputtering at room temperature. Optimized samples were able to detect methylene blue over a wide range of low concentrations (from 1 × 10(-4) to 1 × 10(-12) M), with good reproducibility. The photocatalytic properties of Au-ZnO NRs were exploited to recycle these substrates through UV-assisted cleaning. The experimental results showed that these substrates are characterized by high reproducibility and long shelf life, which make them promising as SERS platforms for multiple detection of different molecular species.     

Flower-shaped gold nanoparticles: synthesis, characterization and their application as SERS-active tags inside living cells

The detection of Raman signals inside living cells is a topic of great interest in the study of cell biology mechanisms and for diagnostic and therapeutic applications. This work presents the synthesis and characterization of flower-shaped gold nanoparticles and demonstrates their applicability as SERS-active tags for cellular spectral detection. The particles were synthesized by a facile, rapid new route that uses ascorbic acid as a reducing agent of gold salt. Two triarylmethane dyes which are widely used as biological stains, namely malachite green oxalate and basic fuchsin, were used as Raman-active molecules and the polymer mPEG-SH as capping material. The as-prepared SERS-active nanoparticles were tested on a human retinal pigment epithelial cell line and found to present a low level of cytotoxicity and high chemical stability together with SERS sensitivity down to picomolar particle concentrations.     

Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gap

An ideal surface-enhanced Raman scattering (SERS) nanostructure for sensing and imaging applications should induce a high signal enhancement, generate a reproducible and uniform response, and should be easy to synthesize. Many SERS-active nanostructures have been investigated, but they suffer from poor reproducibility of the SERS-active sites, and the wide distribution of their enhancement factor values results in an unquantifiable SERS signal. Here, we show that DNA on gold nanoparticles facilitates the formation of well-defined gold nanobridged nanogap particles (Au-NNP) that generate a highly stable and reproducible SERS signal. The uniform and hollow gap (～1 nm) between the gold core and gold shell can be precisely loaded with a quantifiable amount of Raman dyes. SERS signals generated by Au-NNPs showed a linear dependence on probe concentration (R(2) > 0.98) and were sensitive down to 10 fM concentrations. Single-particle nano-Raman mapping analysis revealed that >90% of Au-NNPs had enhancement factors greater than 1.0 × 10(8), which is sufficient for single-molecule detection, and the values were narrowly distributed between 1.0 × 10(8) and 5.0 × 10(9).