Nanofluidic biosensing for beta-amyloid detection using surface enhanced Raman spectroscopy

Trace detection of the conformational transition of beta-amyloid peptide (Abeta) from a predominantly alpha-helical structure to beta-sheet could have a large impact in understanding and diagnosing Alzheimer's disease. We demonstrate how a novel nanofluidic biosensor using a controlled, reproducible surface enhanced Raman spectroscopy active site was developed to observe Abeta in different conformational states during the Abeta self-assembly process as well as to distinguish Abeta from confounder proteins commonly found in cerebral spinal fluid.     

One-step synthesis of star-like gold nanoparticles for surface enhanced Raman spectroscopy

In this paper we present a new protocol for the synthesis of Star-Like Gold Nanoparticles (SGNs) by a simple one-step, room temperature procedure not involving the use of seeds or surfactants, that can be performed in seconds in any laboratory without the need of special technologies. These particles exhibited excellent properties for Surface Enhanced Raman Spectroscopy (SERS) and, when compared with spherical nanoparticles with similar size and concentration, showed enhancing factors from 10 to 50 times higher depending on the dye and on the wavelength employed. SGNs could be used directly in suspension as single, non-aggregating particles and were shown to be active in a remarkably broad range of the light spectrum from green to near infrared. Moreover, SGNs were adsorbed on the surface of a silicon slide to prepare SERS active solid substrate. Despite the fact that the surface of the solid substrate was not perfectly homogeneous, the signals recorded from different positions acquired through DuoScan averaging mode show excellent reproducibility, demonstrating how this simple and cheap protocol can be applied in order to generate reliable and homogeneous SERS substrates.     

Investigation into a surface plasmon related heating effect in surface enhanced Raman spectroscopy

The irreversible loss of surface enhanced Raman spectroscopy (SERS) intensity derived from electrostatically immobilized Au colloidal substrate is studied. The total intensity of the SERS scattering from crystal violet molecules adsorbed onto the substrate was monitored for up to 240 s under continuous laser irradiation. The rate of signal decay was found to depend upon the thickness of the liquid layer over the coated substrate. On the basis of this observation, we propose a plausible mechanism in which surface plasmon related heating induced a small but significant lateral particle diffusion in closely spaced Au particles. The result of the shifting is an increase in the average interparticle distance, which subsequently reduces the electromagnetic coupling between the Au nanoparticles, and in turn causes a reduction in the SERS activity. Finally, a three-state model is proposed and shown to satisfactorily describe the observed decays.     

Large area fabrication of leaning silicon nanopillars for surface enhanced Raman spectroscopy

Using a simple two step fabrication process substrates with a large and uniform Raman enhancement, based on flexible free standing nanopillars can be manufactured over large areas using readily available silicon processing equipment.     

Guided-mode-resonance-coupled plasmonic-active SiO(2) nanotubes for surface enhanced Raman spectroscopy

We demonstrate a surface enhanced Raman scattering (SERS) substrate by integrating plasmonic-active SiO(2) nanotubes into Si(3)N(4) gratings. First, the dielectric grating that is working under guided mode resonance (GMR) provides enhanced electric field for localized surface plasmon polaritons on the surface of metallic nanoparticles. Second, we use SiO(2) nanotubes with densely assembled silver nanoparticles to provide a large amount of "hot spots" without significantly damping the GMR mode of the grating. Experimental measurement on Rhodamine-6G shows a constant enhancement factor of 8?～?10 in addition to the existing SERS effect across the entire surface of the SiO(2) nanotubes.     

Inkjet printed surface enhanced Raman spectroscopy array on cellulose paper

A novel, ultra low-cost surface enhanced Raman spectroscopy (SERS) substrate has been developed by modifying the surface chemistry of cellulose paper and patterning nanoparticle arrays, all with a consumer inkjet printer. Micro/nanofabrication of SERS substrates for on-chip chemical and biomolecular analysis has been under intense investigation. However, the high cost of producing these substrates and the limited shelf life severely limit their use, especially for routine laboratory analysis and for point-of-sample analysis in the field. Paper-based microfluidic biosensing systems have shown great potential as low-cost disposable analysis tools. In this work, this concept is extended to SERS-based detection. Using an inexpensive consumer inkjet printer, cellulose paper substrates are modified to be hydrophobic in the sensing regions. Synthesized silver nanoparticles are printed onto this hydrophobic paper substrate with microscale precision to form sensing arrays. The hydrophobic surface prevents the aqueous sample from spreading throughout the paper and thus concentrates the analyte within the sensing region. A SERS fingerprint signal for Rhodamine 6G dye was observed for samples with as low as 10 femtomoles of analyte in a total sample volume of 1 μL. This extraordinarily simple technique can be used to construct SERS microarrays immediately before sample analysis, enabling ultra low-cost chemical and biomolecular detection in the lab as well as in the field at the point of sample collection.     

Monolayer detection on flat metal surface via surface enhanced Raman spectroscopy and sum frequency generation spectroscopy

Monolayer detection on metal surface requires ultra high sensitivity. Sum Frequency Generation Spectroscopy (SFG) and Surface Enhanced Raman Spectroscopy (SERS) are regarded as two powerful techniques with submolecular sensitivity to detect adsorbents on metal surface. However, in some cases it's still challenge to characterize molecules or groups with relatively high intramolecular symmetry, such as 4-Nitrothiophenol (4NTP), on flat metal surface even combining these two techniques. Basically, this is due to that 4NTP with para-substituted phenol groups is SFG insensitive while flat metal surface is unfavorable to yield strong SERS enhancement. In this concern, a simple and efficient method, silver mirror method, was employed to facilitate the detection of 4NTP SAM on flat gold surface. Silver nanopheres with diameters around 300 nm was fabricated through silver mirror reaction and in situ formed milky overlayer on top of 4NTP SAM adsorbed on gold surface. Significant enhancement on SERS signal can be achieved with such special assembly structure of the "metal-molecule-metal" system. Generally, the silver mirror method provided a complementary approach to facilitate the spectroscopic applications of molecule level detection on various metal surfaces in situ.     

Fabrication of large area nanoprism arrays and their application for surface enhanced Raman spectroscopy

This work demonstrates the fabrication of metallic nanoprism (triangular nanostructure) arrays using a low-cost and high-throughput process. In the method, the triangular structure is defined by the shadow of a pyramid during angle evaporation of a metal etching mask. The pyramids were created by nanoimprint lithography in polymethylmethacrylate (PMMA) using a mould having an inverse-pyramid-shaped hole array formed by KOH wet etching of silicon. Silver and gold nanoprism arrays with a period of 200?nm and an edge length of 100?nm have been fabricated and used as effective substrates for surface enhanced Raman spectroscopy (SERS) detection of rhodamine 6G (R6G) molecules. Numerical calculations confirmed the great enhancement of electric field near the sharp nanoprism corners, as well as the detrimental effect of the chromium adhesion layer on localized surface plasmon resonance. The current method can also be used to fabricate non-equilateral nanoprism and three-dimensional (3D) nanopyramid arrays, and it can be readily extended to other metals.     

Redox potential dependence of peptide structure studied using surface enhanced Raman spectroscopy

We describe a novel surface enhanced Raman spectroscopy (SERS) sensing approach utilizing modified gold nanoshells and demonstrate its application to analysis of critical redox-potential dependent changes in antigen structure that are implicated in the initiation of a human autoimmune disease. In Goodpasture's disease, an autoimmune reaction is thought to arise from incomplete proteolysis of the autoantigen, α3(IV)NC1(67-85) by proteases including Cathepsin D. We have used SERS to study conformational changes in the antigen that correlate with its oxidation state and to show that the antigen must be in the reduced state in order to undergo proteolysis. Our results demonstrate that a redox potential of ～-200 mV was sufficient for reduction and subsequent productive processing of the antigenic fragment α3(IV)NC1(67-85). Moreover, we demonstrate that the peptide bonds subsequently cleaved by Cathepsisn D can be identified by comparison with a SERS library of short synthetic peptides.     

Directivity enhanced Raman spectroscopy using nanoantennas

Directing the emission from optical emitters is highly desired for efficient detection and, by reciprocity, efficient excitation as well. As a scattering process, Raman benefits from directivity enhancements in both excitation and emission. Here we demonstrate directivity enhanced Raman scattering (DERS) using a nanoantenna fabricated by focused ion beam milling. The nanoantenna uses a resonant ring-reflector to shape the emitted beam and achieve DERS-this configuration is most similar to a waveguide antenna. The ring reflector boosts the measured Raman signal by a factor of 5.5 (as compared to the ground plane alone), and these findings are in quantitative agreement with comprehensive numerical simulations. The present design is nearly optimal in the sense that almost all the beam power is coupled into the numerical aperture of the microscope. Furthermore, the emission is directed out of the plane, so that this design can be used to achieve DERS using conventional Raman microscopes, which has yet to be achieved with Yagi-Uda and traveling wave antenna designs.     

A nanoporous metallic mat showing excellent and stable surface enhanced Raman spectroscopy activities

A novel nanoporous mat structure was made of gold nanoparticles through a simple, inexpensive self-assembly process as a bottom-up approach to produce an affordable and high-quality SERS substrate. This nanostructure mat shows an excellent SERS reproducibility, physical stability, and strong Raman enhancement, which may satisfy all the criteria as a universal-type SERS substrate. The limit of detection for crystal violet dye on the nanostructured substrates is estimated to reach ppb levels and the SERS enhancement factor is found to be two orders of magnitude higher than that from conventional de-alloy nanoporous films. Mechanical strength of the nano-cluster network can be increased by a post-assembly annealing process. The nanoparticle-based SERS substrate holds promise in practical sensing applications toward a rapid determination of harmful substances or contaminants in food and environment.     

Lab-on-a-bubble surface enhanced Raman indirect immunoassay for cholera

We describe a novel sandwich assay based on surface enhanced Raman scattering (SERS) comprised of buoyant silica microspheres coated with antibodies against the β subunit of the cholera toxin (CT), and gold nanoparticles tagged with a Raman reporter, shelled with silica and coated with antibodies against the β subunit of the CT. Together these components couple to form a sandwich which, after incubation, floats on the surface of the sample. The buoyant silica microparticle/nanoparticle reporter combination has been coined a lab on a bubble (LoB). LoB materials may provide a platform for rapid detection of antigen in solution and offers advantages over lateral flow or magnetic pull-down assays. The Raman reporter provides a unique and intense signal to indicate a positive analysis. Our limit of detection for the β subunit of the CT in a buffer based system is 1100 ng.     

Plasmonic dimer antennas for surface enhanced Raman scattering

Electron beam induced deposition (EBID) has recently been developed into a method to directly write optically active three-dimensional nanostructures. For this purpose a metal-organic precursor gas (here dimethyl-gold(III)-acetylacetonate) is introduced into the vacuum chamber of a scanning electron microscope where it is cracked by the focused electron beam. Upon cracking the aforementioned precursor gas, 3D deposits are realized, consisting of gold nanocrystals embedded in a carbonaceous matrix. The carbon content in the deposits hinders direct plasmonic applications. However, it is possible to activate the deposited nanostructures for plasmonics by coating the EBID structures with a continuous silver layer of a few nanometers thickness. Within this silver layer collective motions of the free electron gas can be excited. In this way, EBID structures with their intriguing precision at the nanoscale have been arranged in arrays of free-standing dimer antenna structures with nanometer sized gaps between the antennas that face each other with an angle of 90°. These dimer antenna ensembles can constitute a reproducibly manufacturable substrate for exploiting the surface enhanced Raman effect (SERS). The achieved SERS enhancement factors are of the order of 10? for the incident laser light polarized along the dimer axes. To prove the signal enhancement in a Raman experiment we used the dye methyl violet as a robust test molecule. In future applications the thickness of such a silver layer on the dimer antennas can easily be varied for tuning the plasmonic resonances of the SERS substrate to match the resonance structure of the analytes to be detected.     

Online-calibration for reliable and robust lab-on-a-chip surface enhanced Raman spectroscopy measurement in a liquid/liquid segmented flow

Concerning the usability of lab-on-a-chip surface enhanced Raman spectroscopy (LOC-SERS) for analytical tasks applying chemometric data evalutation, a secure, reproducible, and stable data output independent of inconsistent ambient conditions has to be accomplished. In this contribution, we present a new approach to achieve reliable and robust measurements based on segmented flow LOC-SERS via online-wavenumber calibration.     

Metal-coated magnetic nanoparticles for surface enhanced Raman scattering studies

We report the optimization and usage of surfactantless, water dispersible Ag and Au-coated gboldsymbolgamma–Fe₂_{boldsymbol 2}O₃_{boldsymbol 3} nanoparticles for applications in surface-enhanced Raman scattering (SERS). These nanoparticles, with plasmonic as well as super paramagnetic properties exhibit Raman enhancement factors of the order of 10⁶ (10⁵) for Ag (Au) coating, which are on par with the conventional Ag and Au nanoparticles. Raman markers like 2-naphthalenethiol, rhodamine-B and rhodamine-6G have been adsorbed to these nanoparticles and tested for nonresonant SERS at low concentrations. Further, to confirm the robustness of Ag-coated nanoparticles, we have performed temperature-dependent SERS in the temperature range of 77–473 K. The adsorbed molecules exhibit stable SERS spectra except at temperatures $boldsymbol >$boldsymbol >323 K, where the thermal desorption of test molecule (naphthalenethiol) were evident. The magnetic properties of these nanoparticles combined with SERS provide a wide range of applications.     

Two particle enhanced nano Raman microscopy and spectroscopy

The distance- and polarization-dependent near-field enhancement of two coupling metal nanoparticles (MNPs) is analyzed by means of the novel scanning particle enhanced Raman spectroscopy (SPRM) technique. In contrast to single MNP Raman experiments, the near-field coupling between two dissimilar MNPs as followed here leads to a Raman hot spot yielding an extra enhancement factor of 17.6 and 20, as proven here both in experiment and in theory. Three-dimensional electric field calculations for our two-particle arrangements were performed using the semianalytical multiple-multipole method. An excellent agreement is found to our experiments, in which we inspect the interaction between a "scanning" 30 nm gold MNP (Au30) and a "fixed" 80 nm Au MNP (Au80). The Au80 MNP is attached to the apex of an optical fiber manipulator and exposed to the Gaussian focus of a high NA = 1.45 objective at lambda = 532 nm. A monolayer of 1-octanethiol molecules covering the Au80 MNP serves as the electric field prober when scanning the Au30 MNP through the optical focus. This constellation allows recording the Raman signatures from a very low number of well-confined molecules. Moreover, also the spectral and spatial dependence could be explored with a superb sensitivity and very low integration time.     

Butterfly-wing hierarchical metallic glassy nanostructure for surface enhanced Raman scattering

Nano Research - The surface-enhanced Raman spectroscopy (SERS) is a technique for the detection of analytes on the surface with an ultrahigh sensitivity down to the atomic-scale, yet the...     

Sensitive carbohydrate detection using surface enhanced Raman tagging

Glycomic analysis is an increasingly important field in biological and biomedical research as glycosylation is one of the most important protein post-translational modifications. We have developed a new technique to detect carbohydrates using surface enhanced Raman spectroscopy (SERS) by designing and applying a Rhodamine B derivative as the SERS tag. Using a reductive amination reaction, the Rhodamine-based tag (RT) was successfully conjugated to three model carbohydrates (glucose, lactose, and glucuronic acid). SERS detection limits obtained with a 633 nm HeNe laser were ～1 nM in concentration for all the RT-carbohydrate conjugates and ～10 fmol in total sample consumption. The dynamic range of the SERS method is about 4 orders of magnitude, spanning from 1 nM to 5 μM. Ratiometric SERS quantification using isotope-substituted SERS internal references allows comparative quantifications of carbohydrates labeled with RT and deuterium/hydrogen substituted RT tags, respectively. In addition to enhancing the SERS detection of the tagged carbohydrates, the Rhodamine tagging facilitates fluorescence and mass spectrometric detection of carbohydrates. Current fluorescence sensitivity of RT-carbohydrates is ～3 nM in concentration while the mass spectrometry (MS) sensitivity is about 1 fmol, achieved with a linear ion trap electrospray ionization (ESI)-MS instrument. Potential applications that take advantage of the high SERS, fluorescence, and MS sensitivity of this SERS tagging strategy are discussed for practical glycomic analysis where carbohydrates may be quantified with a fluorescence and SERS technique and then identified with ESI-MS techniques.     

Temperature dependence of silver nanostructure for surface enhanced Raman scattering application

We study the fabrication and application of the fractal silver nanostructure using an electrochemical process. Scanning electron microscope and high resolution transmission electron microscope images show the morphology of silver nanostructure can be well controlled via the various reaction times. The surface enhanced Raman scattering of 10 microM aqueous Rhodamine 6G (R6G) solutions conducted in as-fabricated silver nanostructure achieved an enhancement factor approximately 10(5) at room temperature. Meanwhile, an approximately 10(4) enhancement factor of SERS signal can be kept under 200 degrees C in present study. This study can help us to integrate the nano-metals and nano-particles for advanced nano devices.