Engineering hot spots on plasmonic nanopillar arrays for SERS: A review

Highly intense surface-enhanced Raman scattering (SERS) is featured as label-free non-destructive detection of biochemical molecules at extremely low concentration. Localized surface plasmon resonance (LSPR) enhances SERS signals by amplifying both the excitation and scattering process. However, aligning molecules near the hotspots of SERS substrate is still challenging to reach stable preconcentration and confinement of free electrons without inhibition of LSPR. This work presents electrophoretic preconcentration on plasmonic nanopillar arrays for highly intense surface-enhanced Raman scattering. The device includes silver nanoislands coated glass nanopillar arrays (GNA) on a transparent electrode and a cavity between top and bottom electrodes. The results show the enhancement of SERS signals over two orders of magnitudes. This enhancement enables SERS measurement of low Raman active biochemical molecules like neurotransmitters. Moreover, selective SERS measurement between oppositely charged molecules was demonstrated. The combination of strong LSPR metal nanostructure and electrophoretic preconcentration suggests not only enhancement of SERS signals even for low Raman active molecules but also active control of molecules for selective SERS detection of oppositely charged molecules.

Controlling the electromagnetic hot-spot generation is essential for surface-enhanced Raman scattering (SERS) assays. Current hot-spot-based SERS assays have been extensively studied in solutions or on substrates. However, probing biospecies by controlling the hot-spot assembly in living systems has not been demonstrated thus far. Herein, we report a background-free SERS probe for imaging pyrophosphate (PPi), a biochemically significant anion, in living cells. Intracellular PPi is able to induce the nanoparticle dimerization, thus creating an intense electromagnetic hot spot and dramatically enhancing the signal of the Raman reporters residing in the hot spot. More impressively, the reporter we used in this study provides a strong and sharp single peak in the cellular Raman-silent region (1800-2800 cm-1), thus eliminating the possible background interference. This strategy could be readily extended to detect other biomarkers by only replacing the recognition ligands.

This work presents a novel method for fabricating repeatable, uniform, large-area, highly sensitive, surface-enhanced resonance Raman scattering (SERRS) substrates combined with silicon nanopillar arrays and silver nanoparticles. The proposed method consists of two steps: (1) induce periodic ripples in deionized water using a linearly polarized femtosecond laser; and (2) generate dense 80-nm-diameter nanopillar arrays with silver nanoparticles in silver nitrate solution with a 90° rotated polarization, femtosecond double-pulse train. As the pulse delay increases from 0 to 1000 fs, the mean size of the silver nanoparticles reduces, and the average number of nanoparticles increases, which, in turn, increases the enhancement factor of SERRS signals up to 1.1×10(9). Furthermore, melamine (down to 125 ppb) was detected by the fabricated SERRS substrates.

In this study, we developed a simple surface-enhanced Raman Scattering (SERS) composite substrate, composed of an all-metal metasurface and on-surface random distributing silver nanoparticles (AgNPs), to enhance the performance of SERS sensing. The metasurface is made up of gold (Au) nanopillars array on aluminum (Al), it can localize the electromagnetic field energy with a resonant absorption peak near the 630 nm wavelength, which contributes to the SERS performance of AgNPs deposited into the structure. The composite substrate can significantly improve the sensing performance, and the SERS Enhancement Factor (EF) reaches 2.81 × 106. The substrate also has good stability and reproducibility. The research is based on the combination of Localized Surface Plasmon Resonance (LSPR) and SERS effects, providing a method and idea for improving the sensitivity of SERS detection, and achieving the trace detection of Rhodamine 6G (R6G) and Thiram at 10−10 M, respectively.

Photo-induced in-situ synthesized nanocellulose-based SERS substrate integrated with molecularly imprinted polymer for selective detection of pesticide residues.

As a bio/chemical sensing technique, surface enhanced Raman spectroscopy (SERS) offers sensitivity comparable to that of fluorescence detection while providing highly specific information about the analyte. Although single molecule identification with SERS was demonstrated over a decade ago, today a need exists to develop practical solutions for point-of-sample and point-of-care SERS systems. In recent years, optofluidic SERS has emerged, in which microfluidic functions are integrated to improve the performance of SERS. Advancements in optofluidic SERS are leading towards portable analytical systems, but the devices are currently too expensive and too cumbersome for limited resource settings. Recently, we demonstrated the fabrication of SERS substrates by inkjet printing silver nanostructures onto paper. Using a low-cost commercial inkjet printer, we chemically patterned cellulose paper to form hydrophobic regions, which can control the aqueous sample on the paper microsystem. Additionally, we inkjet-printed silver nanoparticles with micro-scale precision to form SERS-active biosensors. Using these devices, we have been able to achieve detection limits comparable to conventional nanofabricated substrates. Furthermore, we leverage the fluidic properties to enhance the performance of the SERS devices while also enabling unprecedented ease of use. Paper dipsticks concentrate a relatively large sample volume into a small SERS-active detection region at the tip. Likewise, paper swabs collect samples from a large surface area and concentrate the collected molecules into a SERS sensor on the paper. We will summarize the progress in the fabrication and use of these paper-based optofluidic devices, and will describe their use in practical applications for point-of-sample detection.

Experimental and theoretical investigation for a hierarchical SERS activated platform with 3D dense hot spots

Polymer-nanoimprinting route for the construction of large-area Au@Ag plasmonic arrays using as highly-uniform SERS platforms

This paper presents a simple strategy for the formation of surface-enhanced Raman scattering (SERS) hot spots, or regions with extraordinary large electric-field enhancements, by depositing a silver nanocube on a metal substrate. Our experimental and theoretical results show that hot spots form at the corners of a nanocube in contact with the substrate and the hot spots derived from a single silver nanocube are capable of detecting SERS from a single molecule. By varying the electrical property of the substrate, and the distance between the nanoparticle and the substrate, we show that the substrate can dramatically affect the SERS from a supported nanoparticle. In addition, by comparing the SERS for nanocubes and nanospheres of similar sizes, we show that this effect is also sensitive to the shape of the supported nanoparticle, and enhancement factors of 9.7×106 and 2.1×108 were obtained for a nanosphere and a nanocube on a metal substrate, respectively. This new approach requires minimum fabrication efforts and offers great simplicity for the formation of robust and fully accessible hot spots, providing an effective SERS platform for single-molecule detection.

Applicable surface enhanced Raman scattering (SERS) active substrates require high enhancement factor (EF), excellent spatial reproducibility, and low-cost fabrication method on a large area. Although several SERS substrates with high EF and relative standard deviation (RSD) of signal less than 5% were reported, reliable fabrication for large area SERS substrates with both high sensitivity and high reproducibility via low-cost routes remains a challenge. Here, we report a facile and cost-effective fabrication process for large-scale SERS substrate with Ag inter-nanoparticle (NP) gaps of 5 nm based on ultrathin alumina mask (UTAM) surface pattern technique. Such closely packed Ag NP arrays with high density of electromagnetic field enhancement ("hot spots") on large area exhibit high SERS activity and excellent reproducibility, simultaneously. Rhodamine 6G molecules with concentration of 1 × 10(-7) M are used to determine the SERS performance, and an EF of ∼10(9) is obtained. It should be noted that we obtain RSDs about 2% from 10 random spots on an area of 1 cm(2), which implies the highly reproducible signals. Finite-difference time-domain simulations further suggest that the enhanced electric field originates from the narrow gap, which agrees well with the experimental results. The low value of RSD and the high EF of SERS signals indicate that the as-prepared substrate may be promising for highly sensitive and uniform SERS detection.

A versatile generation of plasmonic nanoparticle dimers for surface-enhanced Raman scattering (SERS) is presented by combining a DNA origami nanofork and spherical and nonspherical Au or Ag nanoparticles. Combining different nanoparticle species with a DNA origami nanofork to form DNA origami nanoantennas (DONAs), the plasmonic nanoparticle dimers can be optimized for a specific excitation wavelength in SERS. The preparation of such nanoparticle dimers is robust enough to enable the characterization of SERS intensities and SERS enhancement factors of dye-modified DONAs on a single dimer level by measuring in total several thousands of dimers from five different dimer designs, each functionalized with three different Raman reporter molecules and measured at four different excitation wavelengths. Based on these data, SERS enhancement factor (EF) distributions have been determined for each dimer design and excitation wavelengths. The structures and measurement conditions with the highest EFs are suitable for single-molecule SERS (SM-SERS), which is realized by placing single dye molecules into hot spots. We demonstrate that the probability of placing single molecules in a strongly enhancing hot spot for SM-SERS can be increased by using anisotropic nanoparticles with several sharp edges, such as nanoflowers. Combining a Ag nanoparticle with a Au particle in one dimer structure allows for a broadband excitation covering almost the whole visible range. The most versatile plasmonic dimer structure for SERS combines a spherical Ag nanoparticle with a Au nanoflower. Employing the discontinuous Galerkin time domain method, we numerically investigate the bare, symmetric dimers with respect to spectral and near-field properties, showing that, indeed, the nanoflowers induce multiple hot spots located at the edges which surpass the intensity of the spherical dimers, indicating the possibility for SM-SERS. The presented DONA structures and SERS data provide a robust basis for applying such designs as versatile SERS tags and as substrates for SM-SERS measurements.

The research reported in this thesis focuses on the fundamental science and engineering required for the fabrication and optimization of nanoparticles functionalized paper as Surface Enhanced Raman Scattering (SERS) bio-diagnostics platform. It addresses the current Sensitivity, Selectivity, Simplicity and Strength (4S) limitations of bioactive paper. The research vision is to develop a nanoparticles treated paper as a generic diagnostic platform to identify and quantify low concentrations of a specific (bio)analyte in aqueous solutions. The product concept is a “dipstick sensor” based on functionalized gold nanoparticle treated paper (AuNP paper) for SERS detection. Such AuNP paper test would allow the direct, rapid and easy detection of (bio)analyte molecules at very low concentrations (below the nanomolar range), making it suitable for biomedical analysis, such as in cancer detection. It also eliminates the tedious preparation of multiple reactants and washing steps involved in current technology such as the Enzyme-Linked Immunosorbent Assay (ELISA) based bioactive paper. Three parallel research length scales are investigated: nano, micro and macro. This involves quantifying the distribution and adsorption state of nanoparticles on paper (nanoscale). The effects of gold nanoparticles (AuNPs) concentration and 3-dimensional (3D) distribution profile on their adsorption and aggregation states on paper were explored. The surface coverage of AuNPs on paper scaled linearly with their concentration profile in solutions. The SERS performances of the AuNPs-treated papers were evaluated with a model Raman molecule, 4-aminothiophenol (4-ATP), and their SERS intensities increased linearly with the density of AuNPs on paper. The role of z-distribution of AuNPs within the bulk of paper was highlighted; their three-dimensional (3D) architecture was able to quench the background noise through interlayer plasmon coupling, thus amplifying the SERS signal. The retention and aggregation state of nanoparticles on paper was controlled to drastically optimize the SERS performance (microscale). Paper substrates were pre-treated with a series of cationic polyacrylamide (CPAM) solutions to control the AuNPs adsorption and aggregation state on paper. The CPAM pre-treated paper produced a more uniform distribution of AuNPs compared to untreated paper. CPAM chains which adsorbed on paper in a high loops and tails conformation promotes efficient bridging of AuNPs to achieve higher surface coverage and aggregation of AuNPs on paper. This configuration is favored by CPAM solutions of higher concentration, charge density and molecular weight. A simple approach to form and visualize polyelectrolyte-nanoparticles chaplet like structures on paper was developed by using negatively-charged gold nanoparticles (AuNPs) to decorate polymer chain of CPAM. AuNP chaplets were adsorbed in an opposite direction to the cellulose fibers and along the length of the CPAM molecules which were draped over the fibers. The effects of CPAM polymer concentration, charge density and molecular weight on the dimension of AuNP chaplets were quantified. Assembling nanometer-scale components (AuNPs) into micrometer-scale arrays (chaplets) on a porous paper substrate can be a promising strategy for low-cost nanoelectronics applications The SERS properties of nanoparticles functionalized paper were quantified and optimized (macroscale). The effect of CPAM concentration, charge density and molecular weight on the aggregation and surface coverage of AuNPs on paper and ultimately the SERS signal of 4-ATP was quantified. The optimized AuNPs-CPAM paper showed a higher sensitivity and Raman enhancement factor (EF), which was almost an order of magnitude higher than the untreated AuNPs paper. The effect of CPAM dissolution kinetic on the SERS reproducibility was also quantified. SERS reproducibility of AuNPs on CPAM pre-treated paper both increase with dissolution time of CPAM, as the heterogeneity of AuNP distribution and aggregate size decreases; increasing CPAM charge density accentuated this tendency. After the SERS efficiency towards the detection of model Raman molecule (4-ATP) was proven, AuNPs paper was upgraded by functionalizing the AuNPs with biotin/streptavidin assemblies for the detection of antibody-antigen binding. The modification of antibody local structure due to the interaction with antigen was detected. Evidence of antigen binding was elucidated from the SERS spectra, confirming the presence of antigen. Reproducible spectra features were observed for the functionalized AuNP papers which were exposed to different concentration of antigen; their intensity increased as a function of antigen concentration. By conducting these studies and merging these three length scales of research, a novel strategy to engineer AuNPs functionalized paper as a low-cost and generic SERS platform for bio-diagnostic applications was developed.

Surface-enhanced Raman spectroscopy (SERS) is undoubtedly one of the most useful physical chemistry techniques for highly sensitive molecular detection. It is now well understood that the plasmonic coupling effect at the nanometer gap junction between particles induces enormous electromagnetic enhancement that allows SERS signal to be detected with single-molecule sensitivity. However, the applications of SERS in quantitative detection are still far from well established, due to the difficulty in obtaining reproducible SERS substrates, and hence the SERS signal intensities. Therefore, fabrication of highly reliable SERS substrates is a significant part of SERS development. In this study, we provide a simple, low-cost method, based on the production process of nanoporous anodic aluminum oxide (AAO), to fabricate polymeric nanopillar structure which can be used as high sensitivity SERS substrate. In details, the nanoporous anodic aluminum oxide was used as the template for the fabrication of uniform nanopillar array. The ordered nanopillar array was successfully realized by pouring acrylate monomer into the AAO template and subsequential curing. The shape of nanopillar was carefully controlled by periodical modulation of anodizing and pore widening. And, to produce electric field for SERS, Ag nanoparticles were coated on the nanopillar array. Various chemicals, such as rhodamine 6G and some proteins, on the Ag-coated nanopillar array were detected by SERS. The Ag-coated polymeric nanopillar substrate provided higher sensitivity of SERS spectra for various chemicals than Ag-coated flat polymeric substrate (without nanopillar). As the diameter of nanopillar was controlled by anodizing voltage accordingly, changes of nanogap size caused different SERS signal sensitivity. Furthermore, the shape of nanopillar, thickness of Ag-coated layer, and aging temperature were interestingly crucial factors for the improvement of sensitivity and reproducibility of SERS signal.

A Ag@AuNP-functionalized capillary-based surface-enhanced Raman scattering (SERS) sensing platform for the interference-free detection of glucose using SERS tags with a built-in nitrile signal has been proposed in this work. Capillary-based SERS capture substrates were prepared by connecting 4-mercaptophenylboronic acid (MBA) to the surface of the Ag@AuNP layer anchored on the inner wall of the capillaries. The SERS tags with a built-in interference-free signal could then be fixed onto the Ag@AuNP layer of the capillary-based capture substrate based on the distinguished feature of glucose, which can form a bidentate glucose-boronic complex. Thus, many "hot spots" were formed, which produced an improved SERS signal. The quantitative analysis of glucose levels was realized using the interference-free SERS intensity of nitrile at 2222 cm-1, with a detection limit of about 0.059 mM. Additionally, the capillary-based disposable SERS sensing platform was successfully employed to detect glucose in artificial urine, and the new strategy has great potential to be further applied in the diagnosis and control of diabetes.

The remarkably high electromagnetic fields that can be induced by the optical stimulation of surface plasmons in plasmonic nanostructures can induce large enhancements to Raman scattering. The Surface-enhanced Raman Scattering (SERS) effect offers great potential for the development of molecular sensors with low false alarm rates and high sensitivity. Although research in this field has grown at a very fast pace in recent years, most of this work has focused on attaining the highest enhancements at highly localized hot-spots, which while providing large peak enhancements, exhibit very low average enhancement factors, making their use for most sensing applications unlikely. Here we report on Au-coated Si nanopillar arrays where we probe the dependence of the SERS enhancement on both the nanopillar diameter and the interpillar gap over a range extending from 30 to 245 nm and 20 to 165 nm, respectively. This approach allows for the optimization of the SPR condition relative to the incident laser wavelength chosen, enabling an optimized SERS sensor. As the interparticle gaps approach 20 nm, we also explored arrays of nanopillars where interparticle plasmonic coupling should exist, however, it remains unclear if any such collective effects are present. The arrays created do illustrate very large highly uniform (<30% deviation) SERS enhancement factors (G), with G in excess of 1x10⁷ being reported. In addition, we explored the role of the nanoparticle geometry, where we determined that a higher G is observed for circle in comparison to square nanopillars of similar dimensions. The SERS enhancement was found to have a very distinct dependence on the nanopillar diameter, while only a monotonic increase was observed with increasing interpillar gap. These results suggest great suitability of plasmo-photonic large-area nanopillar arrays for SERS vapor and liquid sensor applications.