Turning up the lights - fabrication of brighter SERRS nanotags

Brighter SERRS nanotags ideal for improved SERRS imaging were prepared by the controlled addition of electrolyte producing a dimer enriched solution, which was incubated with a Raman reporter before being stabilised by a polyethylene glycol (PEG) shell

Surface enhanced optical spectroscopies for bioanalysis

Surface enhancement can provide improved detection sensitivity in a range of optical spectroscopies. When applied to bioanalysis these enhanced techniques allow for the detection of disease biomarkers at lower levels, which has a clear patient benefit. However, to achieve widespread clinical use of surface enhanced techniques there remain several "grand challenges". In this review we consider the substrates employed to achieve enhancement before reviewing each enhanced optical technique in detail; surface plasmon resonance, localised surface plasmon resonance, surface enhanced fluorescence, surface enhanced infrared absorption spectroscopy and surface enhanced (resonance) Raman spectroscopy. Finally we set out the "grand challenges" currently facing the field

Enhancing the SERS properties of nanoworms by matrix formation

A highly SERS-active substrate was fabricated by trapping gold "nanoworms" on commercially available filter membranes providing significant enhancement of the Raman signal as a result of the remarkable electromagnetic couplings induced by the dense packing. The resultant substrate provides a simple and cost-effective porous SERS surface for use and quantitative analytical procedures

The optimisation of facile substrates for surface enhanced Raman scattering through galvanic replacement of silver onto copper

A fast and cost-effective approach for the synthesis of substrates used in surface enhanced Raman scattering (SERS) has been developed using galvanic displacement. Deposition of silver onto commercially available Cu foil has resulted in the formation of multiple hierarchical structures, whose morphology show dependence on deposition time and temperature. Analysis of the surface structure by scanning electron microscopy revealed that the more complex silver structures correlated well with increased deposition time and temperature. Using Rhodamine 6G (R6G) as a model Raman probe it was also possible to relate the substrate morphology directly with subsequent SERS intensity from the R6G analyte as well as the reproducibility across a total of 15 replicate Raman maps (20 x 20 pixels) consisting of 400 spectra at a R6G concentration of 10(-4) M. The substrate with the highest reproducibility was then used to explore the limit of detection and this compared very favourably with colloidal-based SERS assessments of the same analyte

Design Consideration for Surface-Enhanced (Resonance) Raman Scattering Nanotag Cores

Surface-enhanced (resonance) Raman spectroscopy (SE­(R)­RS) holds great promise for the in vivo detection of multiple disease markers. Nanotags consisting of a metallic nanoparticle decorated with reporter molecules encapsulated in either an inert or biofunctionalized shell, for inactive or active targeting, have been developed. To improve the tissue depth from which the signal can be detected, it is preferable to operate with excitation in the near-infrared wavelengths; however, this reduces the inherent Raman signal intensity. The signal strength can be reestablished by matching the absorbance of the nanoparticle with the laser excitation. However, nanoparticles must get physically larger to support absorbances in the near-infrared region, which can have an adverse affect on cellular uptake. In this paper we compare the use of silver nanoparticles with plasmon absorbances at longer wavelengths with clusters (2–4 nanoparticles) formed from much smaller nanoparticles which support so-called “hot spots”. We find that the small clusters outperform the resonant single nanoparticles with respect to the observed SE­(R)­RS signal. It has also previously been shown in the literature that small nanoparticles are more readily taken up into cells than larger nanoparticles. This knowledge combined with the results reported here highlight an important design consideration in that new SE­(R)­RS active nanotags should be made from coupled small dimensional nanoparticles rather than large single nanoparticles that support absorbances in the near-infrared region

Positively charged silver nanoparticles and their effect on surface-enhanced Raman scattering of dye-labelled oligonucleotides

Improved positively charged nanoparticles are described to provide a simplified SERS substrate for DNA detection. Complete flocculation of the nanoparticles is prevented due to the controlled analyte induced aggregation. This provides a stable aggregation state which significantly extends the analysis window simplifying DNA detection by SERS

SERS Primers and Their Mode of Action for Pathogen DNA Detection

SERS primers have been used to directly detect specific PCR products utilizing the difference in adsorption of single-stranded and double-stranded DNA onto nanoparticle surfaces. Herein, seven parameters important for improved positive SERS assays for real applications were investigated. First, we applied a model system for optimization experiments, followed by a PCR assay to detect pathogen DNA, and then the introduction of a new assay that utilizes the 5′→3′ exonuclease activity of <i>Taq</i> DNA polymerase to partly digest the SERS probe, generating dye-labeled single-stranded DNA increasing the SERS signals for detection of pathogen DNA. Applying the model system, it was found that uni-molecular SERS primers perform better than bi-molecular SERS primers. However, within the PCR assays, it was found that uni- and bi-molecular SERS primers performed very similarly, and the most reproducible results were obtained using the 5′→3′ exonuclease digestion assay. These SERS-based assays offer new routes over conventional fluorescence-based techniques without compromising sensitivity or selectivity

Raman Analysis of Dilute Aqueous Samples by Localized Evaporation of Submicroliter Droplets on the Tips of Superhydrophobic Copper Wires

Raman analysis of dilute aqueous solutions is normally prevented by their low signal levels. A very general method to increase the concentration to detectable levels is to evaporate droplets of the sample to dryness, creating solid deposits which are then Raman probed. Here, superhydrophobic (SHP) wires with hydrophilic tips have been used as supports for drying droplets, which have the advantage that the residue is automatically deposited at the tip. The SHP wires were readily prepared in minutes using electroless galvanic deposition of Ag onto copper wires followed by modification with a polyfluorothiol (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-1-decanethiol, HDFT). Cutting the coated wires with a scalpel revealed hydrophilic tips which could support droplets whose maximum size was determined by the wire diameter. Typically, 230 μm wires were used to support 0.6 μL droplets. Evaporation of dilute melamine droplets gave solid deposits which could be observed by scanning electron microscopy (SEM) and Raman spectroscopy. The limit of detection for melamine using a two stage evaporation procedure was 1 × 10^–6 mol dm^–3. The physical appearance of dried droplets of sucrose and glucose showed that the samples retained significant amounts of water, even under high vacuum. Nonetheless, the Raman detection limits of sucrose and glucose were 5 × 10^–4 and 2.5 × 10^–3 mol dm^–3, respectively, which is similar to the sensitivity reported for surface-enhanced Raman spectroscopy (SERS) detection of glucose. It was also possible to quantify the two sugars in mixtures at concentrations which were similar to those found in human blood through multivariate analysis

Synthesis and NIR optical properties of hollow gold nanospheres with LSPR greater than one micrometer

Optical analysis in the near infrared region is of significant biological importance due to better tissue penetration and reduced autofluorescence. In this work, an improved synthesis of hollow gold nanospheres (HGNs), which provides a tunable localized surface plasmon resonance (LSPR) from 610 nm up to 1320 nm, is demonstrated. The scattering properties of these nanoparticles are shown using surface enhanced Raman scattering (SERS) at 1064 nm excitation wavelength and are compared to citrate reduced gold and silver nanoparticles of similar physical sizes and surface properties. After the addition of salts, a strong signal was observed from hollow gold with a LSPR of 650 nm and a weaker, yet observable, signal from HGNs with a LSPR of 775 nm. However, no obvious signals were observed in the case of standard citrate reduced gold, silver or HGNs with a LSPR of 1080 nm. The absorption properties of HGNs were investigated by monitoring their photothermal activity. In this case, different nanoparticle suspensions including citrate reduced gold, silver, and HGNs were illuminated by a continuous laser at 785 nm excitation wavelength and the absorption efficiency of HGNs with a LSPR of 775 nm was calculated to be 0.81% which is more than 5 times higher than the absorption efficiency of citrate reduced gold nanoparticles under similar conditions