Plasmon-Induced Charge Transfer-Enhanced Raman Scattering on a Semiconductor: Toward Amplification-Free Quantification of SARS-CoV-2

Semiconductors demonstrate great potentials as chemical mechanism-based surface-enhanced Raman scattering (SERS) substrates in determination of biological species in complex living systems with high selectivity. However, low sensitivity is the bottleneck for their practical applications, compared with that of noble metal-based Raman enhancement ascribed to electromagnetic mechanism. Herein, a novel Cu₂O nanoarray with free carrier density of 1.78×10²¹ cm⁻³ comparable to that of noble metals was self-assembled, creating a record in enhancement factor (EF) of 3.19×10¹⁰ among semiconductor substrates. The significant EF was mainly attributed to plasmon-induced hot electron transfer (PIHET) in semiconductor which was never reported before. This Cu₂O nanoarray was subsequently developed as a highly sensitive and selective SERS chip for non-enzyme and amplification-free SARS-CoV-2 RNA quantification with a detection limit down to 60 copies/mL within 5 min. This unique Cu₂O nanoarray demonstrated the significant Raman enhancement through PIHET process, enabling rapid and sensitive point-of-care testing of emerging virus variants.     

Dealloying Ag–Al Alloy to Prepare Nanoporous Silver as a Substrate for Surface‐Enhanced Raman Scattering: Effects of Structural Evolution and Surface Modification

Sensitive detection of molecules by using the surface‐enhanced Raman scattering (SERS) technique depends on the nanostructured metallic substrate and many efforts have been devoted to the preparation of SERS substrates with high sensitivity, stability, and reproducibility. Herein, we report on the fabrication of stable monolithic nanoporous silver (NPS) by chemical dealloying of Ag–Al precursor alloys with an emphasis on the effect of structural evolution on SERS signals. It was found that the dealloying conditions had great influence on the morphology (the ligament/pore size) and the crystallization status, which determined the SERS signal of rhodamine 6G on the NPS. NPS with small pores, low residual Al, and perfect crystallization gave high SERS signals. A high enhancement factor of 7.5×10⁵ was observed on bare NPS obtained by dealloying Ag₃₀Al₇₀ in 2.5 wt % HCl at room temperature followed by 15 min aging at around 85 °C. After coating Ag nanoparticles on the NPS surface, the enhancement factor increased to 1.6×10⁸ owing to strong near‐field coupling between the ligaments and nanoparticles.     

ZnGa2O4 Nanorod Arrays Decorated with Ag Nanoparticles as Surface‐Enhanced Raman‐Scattering Substrates for Melamine Detection

The availability of sensitive, reproducible, and stable substrates is critically important for surface‐enhanced Raman spectroscopy (SERS)‐based applications, but it presently remains a challenge. In this work, well‐aligned zinc gallate (ZnGa₂O₄) nanorod arrays grown on a Si substrate by chemical vapor deposition were used as templates to fabricate SERS substrates by deposition of Ag nanoparticles onto the ZnGa₂O₄ nanorod surfaces. The coverage of the Ag nanoparticles on the ZnGa₂O₄ nanorod surfaces was easily controlled by varying the amount of AgNO₃. SERS measurements showed that the number density of Ag nanoparticles on the ZnGa₂O₄ nanorod surfaces had a great effect on SERS activity. The SERS signals collected by point‐to‐point and SERS mapping images showed that as‐prepared SERS substrates exhibited good spatial uniformity and reproducibility. Detection of melamine molecules at low concentrations (1.0×10^?7 M ) was used as an example to show the possible application of such a substrate. In addition, the effect of benzoic acid on the detection of melamine was also investigated. It was found that the SERS signal intensity of melamine decreased greatly as the concentration of benzoic acid was increased.     

Determination of 2,6-Dichlorophenol by Surface-Enhanced Raman Scattering with Molecular Imprinting

A novel method has been reported for 2,6-dichlorophenol using surface-enhanced Raman scattering (SERS). SiO₂/gold composites were selected as the SERS substrates to provide the response of gold nanoparticles. Molecular imprinting was subsequently used for the development of a specific detector to 2,6-dichlorophenol with precipitation polymerization. The molecularly imprinted polymer provided sensitive and selective SERS detection for the determination of 2,6-dichlorophenol. The intensity and concentration obeyed a linear relationship from 1?×?10^?5 to 1?×?10^?9?mol?L^?1 2,6-dichlorophenol. The sensitivity of SERS with the molecularly imprinted polymers provides a promising approach for practical analysis.     

Microspectrometric investigation of active substrates for surface enhanced Raman scattering

The results of investigations of several new active silver substrates and some previously reported active silver substrates for surface enhanced Raman spectrometry (SERS) using a Raman microprobe are given. Filter-papers of different composition and porosity, silver membranes and glass slides are evaluated as supports for SERS active substrates. Methods of silver preparation include evaporation and chemical reduction. The Raman microprobe facilitates the acquisition of SER spectra of the adsorbate over the metal microstructure being observed on a TV monitor. This capability allows the establishment of practical relationships between the surface morphology and SERS activity which can be used as guidelines for SERS experiments with the microprobe. For the most monodisperse substrates, it is possible to establish a linear relationship between SERS intensity and adsorbate concentration. In the lower extreme of the calibration graph, the amount of adsorbate being observed under the microscope objective is only 0.3 amol or 1.9 × 10⁵ molecules.     

A new semiconductor-based SERS substrate with enhanced charge collection and improved carrier separation: CuO/TiO2 p-n heterojunction

In this paper, CuO/TiO₂ p-n heterojunction was developed as a new surface enhanced Raman scattering (SERS) substrate to magnify Raman signal of 4-mercaptobenzoic acid (4-MBA) molecule. In the heterojunction-molecule system, CuO as an “electron capsule” can not only offer more electrons to inject into the surface state energy level of TiO₂ and consequently bring additional charge transfer, but also improve photogenerated carrier separation efficiency itself due to strong interfacial coupling in the interface of heterojunction, which together boost SERS performance of the heterojunction substrate. As expected, owing to the enhanced charge collection capacity and the improvement of photogenerated carrier separation efficiency derived from internal electric field and strong interface coupling provided in the interface of heterojunction, this substrate exhibits excellent SERS detection sensitivity towards 4-MBA, with a detection limit as low as 1 × 10⁻¹⁰ mol/L and an enhancement factor of 8.87 × 10⁶.     

Coating of silver nanoparticles (AgNPs) on glass fibers by a chemical method as plasmonic surface-enhanced Raman spectroscopy (SERS) sensors to detect molecular vibrations of Doxorubicin (DOX) drug in blood plasma

In the present study, Doxorubicin (DOX) drug in healthy blood plasma was the focus of the investigation by surface-enhanced Raman scattering (SERS). In recent years, chemotherapy has been the most popular treatment for various types of cancer; however, its adverse side effects on the patient's health have made a negative aspect regarding the use of this technique. DOX is the most common chemotherapy drug and is used for the treatment of an extensive range of human malignancies. The surface-enhanced Raman scattering (SERS) is a precise technique for the detection of chemicals and biomaterials with significantly low concentrations. The glass fiber substrates coated with silver nanoparticles (AgNPs) have been used to detect DOX. First, the Tollens' method was applied to prepare the AgNPs, and the characteristics of fabricated AgNPs were evaluated using ultraviolet–visible spectroscopy (UV–Vis) and X-ray diffraction (XRD). Then, AgNPs were coated on the glass fiber substrate by a chemical method. Finally, the enhancement of the Raman signal resulted from the molecular vibrations of DOX was evaluated using these SERS-active substrates as plasmonic and Raman spectroscopy sensors. Afterward, for making the sensors practical, the DOX in blood plasma were deposited on the fabricated sensors, and the Raman vibrations were evaluated. The SERS-active substrates, AgNPs deposited on glass fiber substrates, were fabricated for the detection of DOX in and out of the blood plasma; the limit of detection (LOD) for both was 10^?10 M, and the mean relative standard deviation at concentrations of 10^?10 M of DOX out of blood plasma, and 10^?10 M of DOX in blood plasma were obtained to be 3.76% and 3.61%, respectively for ten repeated measurements in which the AgNPs were SERS-active substrates of the biosensors for detecting the DOX. In addition, the enhancement factor was calculated both experimentally and via finite-difference time-domain (FDTD) simulation, which was 29.76 × 10³ and 24.95 × 10³, respectively. Therefore, these SERS-active substrates can be used to develop microsensors and show positive results for SERS-based investigations.     

SERS and FDTD simulation of gold nanoparticles grafted on germanium wafer via galvanic displacement

Uniform and dense Au nanoparticles grown on Ge (Au/Ge) were fabricated by a facile galvanic displacement method and employed as surface‐enhanced Raman scattering (SERS) substrates. The substrates exhibited excellent reproducibility in the detection of rhodamine 6G aqueous solution with a relative standard deviation of <20%. The substrate showed a high Raman enhancement factor of 3.44 × 10⁶. This superior SERS sensitivity was numerical confirmed by the three‐dimensional finite‐difference time‐domain method, which demonstrated a stronger electric field intensity (|E/E₀|²) distribution around the Au nanoparticles grown on Ge. This facile and low‐cost prepared Au/Ge substrate with high SERS sensitivity and reproducibility might have potential applications in monitoring in situ reaction in aqueous solution. Copyright © 2014 John Wiley & Sons, Ltd.     

Determination of mercury(II) by surface-enhanced Raman scattering spectroscopy based on thiol-functionalized silver nanoparticles

Silver nanoparticles (Ag NPs) modified with sodium 2-mercaptoethanesulfonate (mesna) exhibit strong surface-enhanced Raman scattering (SERS). Their specific and strong interaction with heavy metal ions led to a label-free assay for Hg(II). The covalent bond formed between mercury and sulfur is stronger than the one between silver and sulfur and thus prevents the adsorption of mesna on the surface of Ag NPs. This results in a decrease of the intensity of SERS in the presence of Hg(II) ions. The Raman peak at 795?cm^?1 can be used for quantification. The effect of the concentration of mesna, the concentration of sodium chloride, incubation time and pH value on SERS were optimized. Under the optimal conditions, the intensity of SERS decreases with increasing concentration of Hg(II). The decrease is linear in the 0.01 and 2?μmol L^?1 concentration range, with a correlation coefficient (R²) of 0.996 and detection limit (S/N?=?3) is 0.0024?μmol L^?1. The method was successfully applied to the determination of the Hg(II) in spiked water samples.

A SERS-based immunoassay for porcine circovirus type 2 using multi-branched gold nanoparticles

We report on a facile immunoassay for porcine circovirus type 2 (PCV2) based on surface enhanced Raman scattering (SERS) using multi-branched gold nanoparticles (mb-AuNPs) as substrates. The mb-AuNPs in the immunosensor act as Raman reporters and were prepared via Tris base-induced reduction and subsequent reaction with p-mercaptobenzoic acid (pMBA). They possess good stability and high SERS activity. Subsequently, the modified mb-AuNPs were covalently conjugated to the monoclonal antibody (McAb) against the PCV2 cap protein to form SERS immuno nanoprobes. These were captured in a microtiterplate via a immunoreaction in the presence of target antigens. The effects of antibody concentration, reaction time and temperature on the sensitivity of the immunoassay were investigated. Under optimized assay conditions, the Raman signal intensity at 1,076 cm^?1 increases logarithmically with the concentrations of PCV2 in the concentration ranging from 8?×?10² to 8?×?10⁶ copies per mL. The limit of detection is 8?×?10² copies per mL. Compared to conventional detecting methods such as those based on PCR, the method presented here is rapid, facile and very sensitive.

Multifunctional Fe3O4@mTiO2@noble metal composite NPs as ultrasensitive SERS substrates for trace detection

Multifunctional materials have become the development trend of current material preparation. We reported a typical layer-by-layer method for the fabrication of multifunctional Fe₃O₄@mTiO₂@noble metal triplex core-shell composite nanoparticle (NP), which is composed of a magnetic Fe₃O₄ particle as the core, a mesoporous TiO₂ interlayer and a layer of Ag nanoparticles or Au nanorods as the shell. The obtained Fe₃O₄@mTiO₂@noble metal composite NPs have shown excellent surface enhanced Raman scattering (SERS) sensitivity. Raman results present that the limit of detection (LOD) for crystal violet (CV), p-aminothiophnol (p-ATP) and p-mercaptobenzoic acid (p-MBA) of the Fe₃O₄@mTiO₂@noble metal composite NPs substrates are as low as 1.0 × 10⁻⁹ M, 1.0 × 10⁻¹² M and 1.0 × 10⁻⁹ M, respectively. In addition, the composite NPs also show high reproducibility and stability across the entire area with relative standard deviations (RSD) less than 15.00%. These highly sensitivity with good reproducibility can be attributed to the presence of plentiful “hot spots” produced by magnetic aggregation and target molecules enrichment by mesoporous TiO₂ adsorption for practical application. Fe₃O₄@mTiO₂@Ag composite NPs were used for thiram detection and the detection limit can reach to 5.0 × 10⁻⁸ M (about 0.012 ppm), which is lower than the maximal residue limit of 7 ppm in fruit prescribed by the U.S. Environmental Protection Agency. These multifunctional composite NPs provide easy separation, enrichment and trace detection of the analyte, exhibiting a great prospect as a potential SERS sensor in complex environments.     

Rolling‐Circle Amplification Detection of Thrombin Using Surface‐Enhanced Raman Spectroscopy with Core‐Shell Nanoparticle Probe

An ultrasensitive surface‐enhanced Raman spectroscopy (SERS) sensor based on rolling‐circle amplification (RCA)‐increased “hot‐spot” was developed for the detection of thrombin. The sensor contains a SERS gold nanoparticle@Raman label@SiO₂ core‐shell nanoparticle probe in which the Raman reporter molecules are sandwiched between a gold nanoparticle core and a thin silica shell by a layer‐by‐layer method. Thrombin aptamer sequences were immobilized onto the magnetic beads (MBs) through hybridization with their complementary strand. In the presence of thrombin, the aptamer sequence was released; this allowed the remaining single‐stranded DNA (ssDNA) to act as primer and initiate in situ RCA reaction to produce long ssDNAs. Then, a large number of SERS probes were attached on the long ssDNA templates, causing thousands of SERS probes to be involved in each biomolecular recognition event. This SERS method achieved the detection of thrombin in the range from 1.0×10^?12 to 1.0×10^?8 M and a detection limit of 4.2×10^?13 M , and showed good performance in real serum samples.     

基于Co3O4纳米粒子的“串联酶”活性检测葡萄糖的表面增强拉曼光谱策略

采用一种简单的湿化学法合成Co₃O₄纳米粒子(NPs),并将其作为一种"串联酶"(同时具有类过氧化物酶和类葡萄糖氧化酶活性)用于过氧化氢(H₂O₂)和葡萄糖的表面增强拉曼散射(SERS)光谱检测。作为一种灵敏的SERS底物,在pH=4.0的NaAc缓冲液条件下,Co₃O₄NPs可以催化葡萄糖和O₂生成葡萄糖酸和H₂O₂。然后H₂O₂可以氧化3,3′,5,5′-四甲基联苯胺(TMB),形成蓝色氧化产物氧化TMB(oxTMB),其在1188、1330、1610 cm^-1处表现出强烈的SERS信号。因此,我们开发了一种新的SERS策略来分析葡萄糖,检测限为1×10^-10mol·L^-1,表明Co₃O₄NPs具有生物传感器、免疫分析和医学研究的潜力。     

Surface enhanced Raman scattering of ammonia

A surface enhanced Raman scattering (SERS) spectrum of 0.5 M NH₃ in 4.0 M KCl has been observed on a silver electrode. An approximate enhancement factor of 3 × 10⁵ is calculated, and additional evidence for the enhanced nature of the spectrum is provided by the observation that totally symmetric vibrations are depolarized and by the strong potential dependence of the intensity of surface lines. Assignments have been given to the SERS lines with the low-frequency lines assigned to a AgCl and AgN stretch. The positive shift of the maximum of the intensity versus voltage curve with a lower laser excitation frequency is taken as evidence for the occurrence of a charge transfer process from ammonia to the silver electrode. The fact that the SERS spectrum of NH₃ on Ag can only be observed at large electrolyte concentrations is attributed to the breaking of hydrogen bonding at the electrode-solution interface.     

Local and Remote Charge‐Transfer‐Enhanced Raman Scattering on One‐Dimensional Transition‐Metal Oxides

The one‐dimensional (1D) transition‐metal oxide MoO₃ belt is synthesized and characterized with X‐ray diffraction, scanning electron microscopy, and Raman spectroscopy. Charge‐transfer‐(CT) enhanced Raman scattering of 4‐mercaptobenzoic acid (4‐MBA) on a 1D MoO₃ belt was investigated experimentally and theoretically. The chemical enhancement of surface‐enhanced Raman scattering (SERS) of 4‐MBA on the MoO₃ belt by CT is in the order of 10³. The SERS of 4‐MBA was investigated theoretically by using a quantum chemical method. The remote SERS of 4‐MBA along the 1D MoO₃ belt (the light excitation to one side of the MoO₃ belt, and the SERS spectrum is collected on the other side of the MoO₃ belt) is also shown experimentally, which provides potential applications of SERS. The incident polarization dependence of remote SERS spectra has also been investigated experimentally.     

Design of Silica@Au Hybrid Nanostars for Enhanced SERS and Photothermal Effect

Core-shell nanostructures of silicon oxide@noble metal have drawn a lot of interest due to their distinctive characteristics and minimal toxicity with remarkable biocompatibility. Due to the unique property of localized surface plasmon resonance (LSPR), plasmonic nanoparticles are being used as surface-enhanced Raman scattering (SERS) based detection of pollutants and photothermal (PT) agents in cancer therapy. Herein, we demonstrate the synthesis of multifunctional silica core – Au nanostars shell (SiO₂@Au NSs) nanostructures using surfactant free aqueous phase method. The SERS performance of the as-synthesized anisotropic core-shell NSs was examined using Rhodamine B (RhB) dye as a Raman probe and resulted in strong enhancement factor of 1.37×10⁶. Furthermore, SiO₂@Au NSs were also employed for PT killing of breast cancer cells and they exhibited a concentration-dependent increase in the photothermal effect. The SiO₂@Au NSs show remarkable photothermal conversion efficiency of up to 72 % which is unprecedented. As an outcome, our synthesized NIR active SiO₂@Au NSs are of pivotal importance to have their dual applications in SERS enhancement and PT effect.     

Synthesis of p-aminothiophenol-embedded gold/silver core-shell nanostructures as novel SERS tags for biosensing applications

We describe a novel surface-enhanced Raman scattering (SERS) tag that is based on Au/Ag core-shell nanostructures embedded with p-aminothiophenol. The Au/Ag core-shell sandwich nanostructures demonstrate bright and dark stripe structure and possess very strong SERS activity. Under optimum conditions, the maximum SERS signal was obtained with a 10?nm thick Ag nanoshell, and the enhancement factor is 3.4?×?10⁴ at 1077?cm^?1. After conjugation to the antibody of muramidase releasing protein (MRP), the Au/Ag core-shell nanostructures were successfully applied to an SERS-based detection scheme for MRP based on a sandwich type of immunoassay.

Surface-enhanced Raman scattering for quantitative detection of ethyl carbamate in alcoholic beverages

Ethyl carbamate, a by-product of fermentation and storage with widespread occurrence in fermented food and alcoholic beverages, is a compound potentially toxic to humans. In this work, a new approach for quantitative detection of ethyl carbamate in alcoholic beverages, based on surface-enhanced Raman scattering (SERS), is reported. Individual silver-coated gold nanoparticle colloids are used as SERS amplifiers, yielding high Raman enhancement of ethyl carbamate in three kinds of alcoholic beverages (vodka, Obstler, and white rum). The characteristic band at 1,003 cm^-1, which is the strongest and best reproducible peak in the SERS spectra, was used for quantitative evaluation of ethyl carbamate. The limit of detection, which corresponds to a signal-to-noise ratio of 3, was 9.0?×?10^-9 M (0.8 μg?·?L^-1), 1.3?×?10^-7 M (11.6 μg?·?L^-1), and 7.8?×?10^-8 M (6.9 μg?·?L^-1), respectively. Surface-enhanced Raman spectroscopy offers great practical potential for the in situ assessment and identification of ethyl carbamate in the alcoholic beverage industry.     

Long‐Term Stable Silver Subsurface Ion‐Exchanged Glasses for SERS Applications

We report on the formation of silver subsurface ion‐exchanged metal oxide (silver SIMO) glasses and their surface‐enhanced Raman scattering (SERS) activity. The samples were prepared by a combined thermal and chemical three‐step methodology and characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), environmental electron scanning microscopy (ESEM), and UV/Vis spectroscopy. This unique method provides SERS substrates with protection against contamination and strong, reliable and reproducible SERS enhancement. The Raman enhancement factors of the long‐term stable SIMO glasses were estimated to approximately 10⁷.     

First Principles Calculations Toward Understanding SERS of 2,2′-Bipyridyl Adsorbed on Au,Ag, and Au–Ag Nanoalloy

First principles electrodyanmics and quantum chemical simulations are performed to gain insights into the underlying mechanisms of the surface enhanced Raman spectra of 22BPY adsorbed on pure Au and Ag as well as on Au–Ag alloy nanodiscs. Experimental SERS spectra from Au and Ag nanodiscs show similar peaks, whereas those from Au–Ag alloy reveal new spectral features. The physical enhancement factors due to surface nano-texture were considered by numerical FDTD simulations of light intensity distribution for the nano-textured Au, Ag, and Au–Ag alloy and compared with experimental results. For the chemical insights of the enhancement, the DFT calculations with the dispersion interaction were performed using Au₂₀, Ag₂₀, and Au₁₀Ag₁₀ clusters of a pyramidal structure for SERS modeling. Binding of 22BPY to the clusters was simulated by considering possible arrangements of vertex and planar physical as well as chemical adsorption models. The DFT results indicate that 22BPY prefers a coplanar adsorption on a (111) face with trans-conformation having close energy difference to cis-conformation. Binding to pure Au cluster is stronger than to pure Ag or Au–Ag alloy clusters and adsorption onto the alloy surface can deform the surface. The computed Raman spectra are compared with experimental data and assignments for pure Au and Ag models are well matching, indicating the need of dispersion interaction to reproduce strong Raman signal at around 800 cm^–1. This work provides insight into 3D character of SERS on nanorough surfaces due to different binding energies and bond length of nanoalloys. © 2018 Wiley Periodicals, Inc.