Research progress of surface-enhanced Raman scattering and its application in detecting nitrite

Preface to the special issue dedicated to Professor Richard P. Van Duyne (1945–2019)

Surface Enhanced Raman Scattering (SERS) is a technique that is increasingly being used to detect trace amounts of various types of molecules, especially organic and biological molecules. The SERS effect is available mainly due to the SERS substrate - a noble metal surface that is rough at the nano level or a set of noble metal nanoparticles in a certain arrangement. Such a SERS substrate acts as an analyte Raman signal amplifier and can provide amplification up to millions of times and even more. The amplification coefficient of the SERS substrate is determined mainly by the number of ‘hot spots’ it contains as well as the ‘hotness’ of these spots. In turn, a ‘hot spot’ is a certain space around the tips or a nanogap between particles, where the local electromagnetic field is intensely enhanced, while the ‘hotness’ is determined by the sharpness of the tips (the sharper the hotter) and tightness of the gaps (the narrower the hotter). This report presents an overview of the research results of fabricating a type of SERS substrate with a high enhancement factor, which is the SERS substrate made from silver nanostructures coated on the silicon surface. With the aim of increasing the number of ‘hot spots’ and their quality, as well as ensuring uniformity and reproducibility of the SERS substrate, silver nanostructures have been fabricated in various forms, such as nanoparticles, nanodendrites and nanoflowers. In addition, the report also mentions the use of the above silver nanostructures as SERS substrates to detect trace amounts of some pesticides and other toxic agents such as paraquat, pyridaben, thiram, cyanide...

One-step chemical reaction triggered surface enhanced Raman scattering signal conversion strategy for highly sensitive detection of nitrite

The accurate determination of nitrite in food samples is of great significance for ensuring people’s health and safety. Herein, a rapid and low-cost detection method was developed for highly sensitive and selective detection of nitrite based on a surface-enhanced Raman scattering (SERS) sensor combined with electrochemical technology and diazo reaction. In this work, a gold nanoparticle (AuNP)/indium tin oxide (ITO) chip as a superior SERS substrate was obtained by electrochemical self-assembled AuNPs on ITO with the advantages of good uniformity, high reproducibility, and long-time stability. The azo compounds generated from the diazotization-coupling reaction between nitrite, 4-aminothiophenol (4-ATP), and N-(1-naphthyl) ethylenediamine dihydrochloride (NED) in acid condition were further assembled on the surface of AuNP/ITO. The detection of nitrite was realized using a portable Raman spectrometer based on the significant SERS enhancement of azo compounds assembled on the AuNP/ITO chip. Many experimental conditions were optimized such as the time of electrochemical self-assembly and the concentration of HAuCl4. Under the optimal conditions, the designed SERS sensor could detect nitride in a large linear range from 1.0 × 10−6 to 1.0 × 10−3 mol L−1 with a low limit of detection of 0.33 μmol L−1. Additionally, nitrite in real samples was further analyzed with a recovery of 95.1−109.7%. Therefore, the proposed SERS method has shown potential application in the detection of nitrite in complex food samples.

Optical excitation of coupled plasmonic nanoparticles supports intense localized electromagnetic "hot-spots" which enable a variety of surface enhanced spectroscopies with the best known example being surface enhanced Raman scattering (SERS), currently of great interest for sensing applications. In this study, we present a novel SERS and electrical dual transduction chemical sensor based on gas-phase generated, negatively charged, silver nanoparticles self-assembled on glass slide forming a close-packed plasmonic monolayer thin-film that supports both SERS and electrical sensing. We demonstrate broad tunability of the localized surface plasmon resonance (LSPR) of the close-packed plasmonic nanoparticle monolayer thin-film sensors through control of the nanoparticle (NP) deposition time which directly influences the plasmonic coupling between neghibouring NPs. This broad tunability supports strong SERS activity from visible to near infrared (NIR) excitation wavelengths. We performed SERS and electrical measurements of a non-resonant molecule 4-mercaptobenzonitrile (4-MBN) as a sample Raman reporter molecule to determine the SERS enhancement factor of our SERS substrate. We measured an average SERS enhancement factor of 10(7) from our close-packed plasmonic nanoparticle monolayer thin-film sensor. Films which were grown below or above one nanoparticle monolayer both exhibited significantly lower SERS performance in one or more of SERS enhancement factor (EF), uniformity or repeatability. Our close-packed plasmonic nanoparticle monolayer thin-film sensors are highly uniform from point-to-point across the entire substrate and showed good reproducibility from batch-to-batch. These qualities are highly desirable for quantifiable detection of chemical and biological molecules. As an example application, this type of substrates provides an affordable and reliable sensing and identification capability for combatting new and emerging chemical and biological threats in support of security applications.

Preparation of urea-modified graphene oxide-gold composite for detection of nitrite

Surface enhanced Raman scattering (SERS) is a widely used analytical technique for detecting trace-level molecules based on an indispensable SERS substrate. SERS substrates with high tailorability are assumed to be attractive and desirable for SERS detection, because the substrates match the need for the selective detection of different species. Nevertheless, the rational design of such SERS substrates is rather challenging for both noble-metal and semiconductor substrates. Herein, expanding beyond conventional SERS substrates, we demonstrate that metal-organic framework (MOF) materials can serve as a type of SERS substrate with molecular selectivity, which are rarely realized for SERS detection without any special pretreatment. A salient structural characteristic of MOF-based SERS substrates benefiting the SERS selectivity is their high tailorability. By controlling the metal centers, organic ligands, and framework topologies of our MOF-based SERS substrates, we show that the electronic band structures of MOF-based SERS substrate can be purposively manipulated to match those of the target analytes, thus resulting in different detectable species. Going further, the SERS enhancement factors (EFs) of the MOF-based SERS substrates can be greatly enhanced to as high as 106 with a low detection limit of 10-8 M by pore-structure optimization and surface modification, which is comparable to the EFs of noble metals without "hot spots" and recently reported semiconductors. This selective enhancement is interpreted as being due to the controllable combination of several resonances, such as the charge-transfer, interband and molecule resonances, together with the ground-state charge-transfer interactions. Our study opens a new venue for the development of SERS substrates with high-design flexibility, which is especially important for selective SERS detection toward specific analytes.

In this paper, we present bridged-bowtie nanohole arrays and cross bridged-bowtie nanohole arrays in a gold thin film as surface enhanced Raman scattering (SERS) substrates. These SERS substrates not only exhibit large electromagnetic enhancement of SERS but also have the SERS enhancement spread over a much larger area than what could be present in SERS substrates consisting of nanopillar arrays or nanopillar plasmonic nanoantennas. Numerical simulations based on the finite difference time domain (FDTD) method are employed to determine electric field enhancement factors (EFs) and therefore the electromagnetic SERS enhancement factor for these SERS substrates. It was observed that bridged-bowtie nanohole arrays and cross bridge-bowtie nanohole arrays exhibit a highest electromagnetic SERS enhancement factor (EF) of ~109, which is orders of magnitude higher than what has been previously reported for nanohole arrays as SERS substrates. This electromagnetic SERS EF (of ~109) is spread over a hotspot region of ~100 nm2 (in each periodic unit of the array), which is larger than the case of nanopillar arrays. In addition, it was observed that an electromagnetic SERS enhancement factor of at least 108 is spread over a large area (500 nm2 in each periodic unit of the array), thus increasing the average enhancement factor. It was observed that the bridged-bowtie nanohole arrays and the cross bridged-bowtie nanohole arrays can be employed as effective SERS substrates in both the transmission mode and the reflection mode. The resonance wavelength of these arrays of nanoholes can be tuned by altering the size of the nanoholes. The effects of varying the gold film thickness and the diameter of the bridged-bowtie nanoholes forming the arrays were also analyzed. The bridged-bowtie nanohole arrays and cross bridged-bowtie nanohole arrays exhibit very high electric field enhancement factors (EFs) at more than one wavelength, and can therefore be used to obtain a multi-wavelength SERS response. Moreover, the cross bridged-bowtie nanohole array allows the tunability of the position of the hotspot with the rotation of the direction of the polarization of incident field.

In this paper, a comprehensive theoretical framework for understanding surface-enhanced Raman scattering (SERS) measurements in both solution and thin-film setups, focusing on electromagnetic enhancement principles, was presented. Two prevalent types of SERS substrates found in the literature were investigated: plasmonic colloidal particles, including spherical and spheroid nanoparticles, nanoparticle diameters, and thin-film-based SERS substrates, like ultra-thin substrates, bundled nanorods, plasmonic thin films, and porous thin films. The investigation explored the impact of analyte adsorption, orientation, and the polarization of the excitation laser on effective SERS enhancement factors. Notably, it considered the impact of analyte size on the SERS spectrum by examining scenarios where the analyte was significantly smaller or larger than the hot spot dimensions. The analysis also incorporated optical attenuations arising from the optical properties of the analyte and the SERS substrates. The findings provide possible explanations for many observations made in SERS measurements, such as variations in relative peak intensities during SERS assessments, reductions in SERS intensity at high analyte concentrations, and the occurrence of significant baseline fluctuations. This study offers valuable guidance for optimizing SERS substrate design, enhancing SERS measurements, and improving the quantification of SERS detection.

We report herein a method for the ultra-trace detection of TNT on p-aminothiophenol-functionalized silver nanoparticles coated on silver molybdate nanowires based on surface-enhanced Raman scattering (SERS). The method relies on π-donor-acceptor interactions between the π-acceptor TNT and the π-donor p,p'-dimercaptoazobenzene (DMAB), with the latter serving to cross-link the silver nanoparticles deposited on the silver molybdate nanowires. This system presents optimal imprint molecule contours, with the DMAB forming imprint molecule sites that constitute SERS "hot spots". Anchoring of the TNT analyte at these sites leads to a pronounced intensification of its Raman emission. We demonstrate that TNT concentrations as low as 10(-12) M can be accurately detected using the described SERS assay. Most impressively, acting as a new type of SERS substrate, the silver/silver molybdate nanowires complex can yield new silver nanoparticles during the detection process, which makes the Raman signals very stable. A detailed mechanism for the observed SERS intensity change is discussed. Our experiments show that TNT can be detected quickly and accurately with ultra-high sensitivity, selectivity, reusability, and stability. The results reported herein may not only lead to many applications in SERS techniques, but might also form the basis of a new concept for a molecular imprinting strategy.

Applications of magnetic nanoparticles in surface-enhanced Raman scattering (SERS) detection of environmental pollutants

Surface Enhanced Raman Scattering (SERS) technique merges an excellent sensitivity and a highly specific label free detection which can be exploited in miniaturized devices with a multiplexed approach. The development of plasmonic nanostructures, aimed to SERS analysis, satisfies therefore the need for point-of-care multianalyte sensing and biosensing platforms, both in the framework of diagnostics and therapy monitoring. In this thesis, SERS active metal-dielectric nanostructures based on silver-coated porous silicon (Ag-pSi) are carefully optimized for biodetection purposes. The thesis is organized in two parts. Basic concepts, necessary to the understanding of the experimental work are provided in the Background section, dealing with fundamentals of SERS spectroscopy (Chapter 1), SERS substrates fabrication aimed to biosensing applications (Chapter 2) and the main techniques devoted to the substrates characterization (Chapter 3). On the other side, the Experimental part includes the applied materials and methods (Chapter 4) and the presentation and discussion of the experimental results. (Chapters 5-8). In detail, a reliable SERS sensing requires a deep characterization of the optical and SERS response of the substrate providing the Raman enhancement. Theoretical and experimental techniques (FEM simulations and multi-wavelength Raman mapping) are systematically applied to get new insight into the fundamental and applicative SERS properties of Ag-pSi (Chapter 5). Two different approaches for the fabrication of Ag-pSi multianalyte platforms are then presented and discussed. Chapter 6 deals with the in situ synthesis of silver nanoparticles (NPs) patterns synthesized by ink-jet printing. The correlation between the growth parameters, morphology and SERS response is studied in order to optimize the SERS signal efficiency and uniformity of the Ag-pSi printed nanostructures. On the other hand, Chapter 7 concerns with the fabrication of multichamber Ag-pSi-PDMS microfluidic chips, which can be applied as portable SERS multiplexing devices. An all-microfluidic in-flow synthesis of silver NPs is performed, integrating the preparation of the SERS active substrate and the detection step on the same chip. Finally, a biofunctionalization protocol developed for the detection of miRNA222 (a recognized tumor marker) is optimized for the application to the Ag-pSi SERS substrates, assessing their compatibility to bioassays and suggesting the Ag-pSi nanostructures integrated in elastomeric chips as advantageous platforms for miRNA profiling, as well as for several other bioanalytical applications (Chapter 8)

Aliquid-phase interfacial surface-enhanced Raman scattering (SERS) ratiometric sensor is proposed through integrating with catalytic hairpin assembly (CHA)-engineered biobarcoded nanoparticle probes for sensitive and accurate kanamycin (Kana) detection. In the SERS ratiometric sensors, the Au-MBA@Ag nanoparticles (Au-MBA@Ag NPs) array generated by self-assembly on the hexane-water interface functionalized with Cy5-labeled Cu2+-specific DNAzyme (Cu-Enz), serving as SERS platform. Kana-driven aptamer specificity recognition followed by CHA-engineered biobarcoded-like copper oxide nanoparticles (CuO NPs) probe, generating a cascade Cu2+ dual-signal amplification. The products of Cu2+ activate DNAzyme, which cleaves the substrate strand on the SERS substrate, bringing the Raman label Cy5 closer to the SERS substrate and generating a strong SERS signal ("on" status). Quantitative detection of Kana is achieved by using the SERS intensity ratio between Cy5 and 4-MBA, which serves as corrective internal standard (IS). Benefiting from the synergistic amplification of CHA and CuO NPs chemical signal amplification, the ratiometric amplifier specifically measures Kana with a sensitivity of 0.003ng/mL. Compared with solid-phase SERS substrates, ratio-dependent liquid-phase interfacial SERS platforms can effectively enhance the reproducibility and reducethe instability of the signal analysis, enabling todistinguish Kana evenfrom excess coexisting interferences. Significantly, the SERS ratiometric sensors can achieve reliable and accurate detection of Kana in honey, indicating that this method has great potential for practical applications in food analysis.

Surface-enhanced Raman scattering (SERS) is a powerful tool for intracellular analyses due its minimally invasive nature and molecular specificity. This research focuses on optimizing the sensitivity of SERS in order to widely apply it to the detection of ultra-trace biomolecules within individual living cells. Recent results have shown that large SERS enhancement factors (EF) can be achieved with multi-layer SERS substrates. To fabricate multi-layer SERS substrates, alternating layers of metal films and dielectric spacers are cast over a non-confluent monolayer of nanostructures. Individual particles of these substrates are then immobilized with antibodies to develop SERS-based immuno-nanosensors. The multi-layer SERS EFs can be increased by the use of appropriate dielectric spacer to fabricate the substrates. To further understand the effect of dielectric spacers on the multi-layer SERS EFs, this talk discusses the characterization of the SERS enhancements of multi-layer metal film on nanostructure SERS substrates fabricated with self-assembled monolayer (SAM) spacers. Monolayers with different chain lengths have been systematically capped with varying amount of metal films. It was found that the SERS EFs depend on the nature of the monolayer formed and the amount of metal film deposited on the monolayer. Using optimal SAMs and the appropriate amount of metal film overlayers, SAM multi-layer SERS substrate with optimized SERS intensity can be fabricated. This talk will also explore the functionalization of the SERS substrates with appropriate bio-recognition elements to develop SERS-based immuno-nanosensors.

Surface-enhanced Raman spectroscopy of arsenate and arsenite using Ag nanofilm prepared by modified mirror reaction