Sensitive Surface-enhanced Raman Scattering Signals Research Articles

Face-to-face Assembly Strategy of Au Nanocubes: Induced Generation of Broad Hotspot Regions for SERS-Fluorescence Dual-Signal Detection of Intracellular miRNAs.

While designing anisotropic noble metal nanoparticles (NPs) can enhance the signal intensity of Raman dyes, more sensitive surface-enhanced Raman scattering (SERS) probes can be designed by oriented self-assembly of noble metal nanomaterials into dimers or higher-order nanoclusters. In this study, we engineered a self-assembly strategy in living cells for real-time fluorescence and SERS dual-channel detection of intracellular microRNAs (miRNAs), using Mg2+-dependent 8-17E DNAzyme sequences as the driving motors, gold nanocubes (AuNCs) as the driver components, and three-branched double-stranded DNA as the linking tool. The assembly selects adenine in DNA as a reporter molecule, simplifying the labeling process of Raman reporter molecules and reducing the synthesis process. In addition, adenine is stably distributed between the faces of AuNCs and the wide hotspot region gives good reproducibility of the adenine SERS signal. In this strategy, the SERS channel was consistently stable and more sensitive compared to the fluorescence channel. Among them, the detection limit of the SERS channel was 2.1 pM and the coefficient of variation was 1.26% in the in vitro liquid phase and 1.49% in MCF-7 cells. The strategy successfully achieved accurate tracking and quantification of miRNA-21 in cancer cells, showing good reproducibility in complex samples as well as cells. The reported strategy provides ideas for exploring intracellular specific triggering of nanoparticles for precise control of self-assembly.

Core-shell metallic nanotube arrays for highly sensitive surface-enhanced Raman scattering (SERS) detection

Here, we demonstrate the application of highly ordered, periodic Ag/Au core-shell triangle nanotube arrays as an ultrasensitive and low-cost surface-enhanced Raman scattering (SERS) substrate for the first time. The arrays of core-shell nanotube, with an outer diameter of 1.5 μm, were fabricated using top-down wafer-scale lithography followed by sequential sputter deposition of Ag and Au. The SERS activity of various combinations of core-shell structures was evaluated. It was found that Ag-core nanotubes overlaid with the Au-shell resulted in the highest Raman intensity, where the enhancement factor for R6G as a probe molecule is determined to be 1.38 × 107. Meanwhile, the limit of detections for R6G and ketoprofen analytes was evaluated to be 10−10 and 10−6 M, respectively. Linear correlations between the SERS signal intensities and logarithmical scale of both analytes in different concentrations were also established, ranging 10−4–10−10 and 10−2–10−6 M for R6G and ketoprofen, respectively. The Raman R6G peak intensity mapping suggests our metal nanotube arrays act as effective plasmonic hotspots and, thus, are useful for SERS sensing applications.

Simple and rapid co-freezing construction of SERS signal probes for the sensitive detection of pathogens

In this study, we proposed a rapid and sensitive surface-enhanced Raman scattering (SERS)-based biosensor for pathogen detection. The biosensor utilized wheat germ agglutinin (WGA)-modified raspberry-like Fe3O4@Au magnetic nanoparticles (RAuMNPs) as capture elements to enrich the target pathogen and used co-freezing aptamer/5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB)/gold nanoparticles (AuNps) tags as the signal source. Compared to conventional AuNps tags, aptamer/DTNB tags manufactured by co-freezing were easy to prepare, highly stable and had a high affinity for the target bacteria. WGA-coated RAuMNPs captured Escherichia coli (E. coli) O157:H7 from real samples, such as human urine, serum, and skimmed milk, within 20 min under optimized conditions. The combined use of the co-freezing SERS tags and RAuMNPs-WGA significantly improved the analytical sensitivity of the proposed SERS platform, enabling detection as low as 8 cells/mL of target bacteria with a linear range of 10 to 106 cells/mL. Furthermore, the platform successfully detected DNA from difficult-to-culture or slow-growing pathogens, such as Mycobacterium tuberculosis. Overall, this sensitive and fast SERS platform has promising potential for accurate and efficient identification of pathogenic bacteria from cultures and various samples.

Semi-wrapped gold nanoparticles for surface-enhanced Raman scattering detection

Researchers have struggled to develop highly reliable and sensitive surface-enhanced Raman scattering (SERS) substrates for detecting compounds in complicated systems. In this work, a strategy by constructing Au cores with incompletely wrapped Prussian blue (PB) for highly reliable and sensitive SERS substrate is proposed. The wrapped PB layers can provide the internal standard (IS) to calibrate the SERS signal floatation, whereas the exposed surface of Au cores offers the enhancement effect. The balance between the signal self-calibration and enhancement (hence the trade-off between SERS reliability and sensitivity) is obtained by the approximate semi-wrapping configuration of PB layers on Au cores (i.e., SW-Au@PB). The proposed SW-Au@PB nanoparticles (NPs) exhibit the similar enhancement factor as the pristine Au NPs and contribute to the ultralow RSD (8.55%) of calibrated SERS signals using R6G as probe molecules. The simultaneously realized reliability and sensitivity of SW-Au@PB NPs also enables the detection of hazardous pesticide residues such as paraquat and thiram in herbal plants, with the average detection accuracy up to 92%. Overall, this work mainly provides a controllable synthetic strategy for incompletely wrapped NPs, and most importantly, explores the potential with a proof-of-concept practical application in accurate and sensitive Raman detection of hazardous substances with varying solubility.

Highly sensitive surface-enhanced Raman scattering (SERS) imaging for phenotypic diagnosis and therapeutic evaluation of breast cancer

The invasion and metastasis of breast cancer are closely related to various biomarkers expressed on the surface of tumor cells and the tumor microenvironment. The deficiency of sensitive phenotypic diagnosis and therapeutic evaluation toward breast cancers represents a significant challenge in cancer diagnosis and therapy. Herein, we report a crucial example of surface-enhanced Raman scattering (SERS)-based imaging utilizing highly sensitive SERS probes to serve as a robust platform for the detection of breast cancer phenotypic biomarkers expressed on the cell surfaces and therapeutic evaluation after chemical therapy and surgery. The SERS probes feature gold-silver (Au@Ag) core–shell nanoparticles with double-layer Raman reporters embedding on the surfaces of the gold core and silver shell, respectively, which further conjugate with specific antibodies. The highly enhanced SERS signals permit the sensitive detection of specific phenotypic biomarkers expressed on the cell surface. In the present work, the epidermal growth factor receptors (EGFR and ErbB2) and insulin-like growth factor 1 (IGF1) were selected as the target biomarkers and assessed the expression in MCF-10A human normal breast cell line and MDA-MB-468, SK-BR-3, KPL-4 human breast cancer cell lines through the SERS-based imaging technique. In the xenotransplanted breast tumor model, systematic delivery of SERS probes enabled precise therapeutic evaluation after anticancer drug tamoxifen therapy and surgery treatment through SERS imaging. Consequently, SERS imaging was consistent with H&E and Masson staining. These results suggest the proposed SERS-based imaging technique has a strong potential to be a powerful tool for precise diagnosis and therapeutic efficacy of breast cancers.

Multilayer thin-film flake dispersion gel for surface-enhanced Raman spectroscopy

Ag nanorod arrays/dielectrics/mirror-structured multilayer thin-film are well known, highly sensitive surface-enhanced Raman scattering (SERS) substrates that enhance the Raman scattering cross-section by the interference of light. However, extracting biomarkers directly from human skin using these solid substrates is difficult. To overcome this problem, we propose a multilayer thin-film flake dispersion gel by centrifugal mixing of the multilayer thin-film and hydroxyethyl cellulose (HEC) gel. The multilayer thin-film was prepared by serial bideposition using the dynamic oblique angle deposition technique. The mixing process was optimized to obtain flakes of ~10 {\mu}m so that the optical properties of the multilayer film can be preserved, and there is no risk of adverse effects on humans. The SERS features of the flakes dispersion gel were tested using 4, 4'-bipyridine (BPY). The BPY molecules diffused through the highly porous gel within a few seconds, generating significant SERS signals. The multilayer film flakes dispersion gel showed a SERS signal about 20 times better than the gel-dispersed Ag nanorod arrays without a multilayer film structure. These SERS active flakes dispersion gel can be used directly on the skin surface to collect body fluids from sweat, for biomarker sensing.

Highly-sensitive SERS-based immunoassay platform prepared on silver nanoparticle-decorated electrospun polymeric fibers

A new, highly sensitive surface enhanced Raman scattering (SERS)-based immunoassay platform was prepared using silver nanoparticle (AgNP)-decorated electrospun fibers as the capture substrate. We used electrospinning and silver mirror reaction to generate AgNP-decorated polycaprolactone (PCL) fiber matrix (Ag-PCL). The resultant capture substrates obtained were bi-directionally porous, free-standing, and flexible. AgNP formation on the PCL fibers was confirmed via SEM, AFM, XPS, and TGA analysis. In addition, gold nanoparticles immobilized with a Raman reporter, 4-mercaptobenzoic acid (4-MBA), were prepared as the SERS tag. This tag could significantly enhance the SERS signal via generation of additional hot spots between AgNPs on fibers and AuNPs. For a model immunoassay to detect prostate specific antigen (PSA), PSA antibodies were immobilized on both Ag-PCL and AuNP SERS tags. The large surface area of fiber substrates allowed the immobilization of large amounts of antibodies and their porous structures facilitated the assessment of the target antigen to immobilized antibodies. Binding of PSA between antibodies on AgNPs and AuNPs led to formation of a sandwich structure by the two metal nanostructures, and consequently, highly sensitive detection of PSA was possible up to a detection limit of 1pg/mL within 1h of reaction time. The developed SERS-based immunoassay platform produced uniform and reproducible SERS signals over the entire substrate area and from different samples.

Sensitive surface-enhanced Raman scattering detection of atrazine based on aggregation of silver nanoparticles modified carbon dots

The development of precise detection methods with simply operation for pesticides in various environmental samples is a particular challenge. Here a highly sensitive surface-enhanced Raman scattering (SERS) approach for the selective detection of trace atrazine was proposed with R6G as a Raman reporter, which was adsorbed on silver nanoparticles modified carbon dots. The latter were prepared by the reduction of Ag+ by carbon dots. In the presence of atrazine, the aggregation of the modified carbon dots due to the interaction between silver nanoparticles and atrazine led to great enhancement of the SERS signal of R6G. Under optimal assay conditions, the limit of quantification was estimated to be 10 nM, which matched with the standard for drinking water quality of China and WHO defined limit. A good linear response to atrazine was found in the concentration range of 10–1000 nM with the relative standard deviations between 1.8% and 5.6%. The determination of atrazine in real water samples was also carried out to confirm the practicability of the proposed method, which showed the recoveries from 95% to 117.5%. The target induced aggregation for enhancing the signal offered great potential for sensitive on-site detection of atrazine in environments.

Monodisperse Au@Ag core-shell nanoprobes with ultrasensitive SERS-activity for rapid identification and Raman imaging of living cancer cells

The rapid identification of living cancer cells is highly crucial for cancer diagnosis, prognosis, and treatment monitoring. However, it is a great challenge to develop an effective way for rapid identification and imaging of cancer cells in a living state. Moreover, synthesis of monodisperse nanoparticles (NPs) with high sensitive surface-enhanced Raman scattering (SERS) activity is also a tough work. Herein, we creatively reported a convenient method to synthesize the novel NPs as the substrate of SERS sensors, which possessed a gold nanobipyramid core and silver nanorod shell. These gold nanobipyramid core and silver nanorod shell NPs (Au NBP@Ag NRs) were further modified with 4-mercaptobenzoicacid (4-MBA, Raman reporter molecule) and then conjugated with reduced bovine serum albumin (rBSA) and folic acid (FA) on their surfaces, to finally acquire Au NBP@Ag NR-MBA-rBSA-FA nanoprobes. In this system, With the enhancement factor (EF) of Au NBP@Ag NRs was about 4 × 107, it could significantly enhance Raman signal for Raman reporter molecules, and 4-MBA molecules performed high SERS signals based on their structures; the nanoprobes have favorable specificity and biocompatibility owing to the modification of rBSA which effectively avoided the nonspecific attachment of non-targeted cells. Moreover, the obtained SERS nanoprobes have excellent sensitivity for gastric cancer cells (MGC-803 cells) due to the conjugation of folic acid. Thus, the finally obtained Au NBP@Ag NR-MBA-rBSA-FA nanoprobes possess excellent detection efficiency for living MGC-803 cells. Therefore, our synthesized nanoprobes exhibit ultrasensitive SERS-activity, excellent specificity and superior cancer cells targeting ability, which could be applied for rapid identification and Raman imaging of living cancer cells via the SERS signal detection of the nanoprobes.

Bilayer composites consisting of gold nanorods and titanium dioxide as highly sensitive and self-cleaning SERS substrates

The authors describe a novel recyclable substrate for highly sensitive surface-enhanced Raman scattering (SERS) studies. It consists of gold nanorods (AuNRs) self-assembled on a TiO2 film and combines the high SERS enhancement of assembled AuNRs with the self-cleaning property of the TiO2 film. It overcomes limitations of conventional SERS substrates such as limited sensitivity, high costs, and poor recyclability. The packing density of the AuNRs on the TiO2 film can be well adjusted, and therefore the SERS enhancement factor of the substrates can be tuned. For the optimized substrate, the SERS enhancement factor is as high as 5.4 × 1010 (Raman laser at 782 nm with 10% of 1.15 mW). This indicates extremely high sensitivity and is promising in terms of single molecule detection. Raman mapping experiments showed the SERS signal to be homogeneously distributed over the whole surface, with a maximal deviation of 3.5%. The SERS activity of this substrate can be restored by degradation of the probe molecules through TiO2 photocatalysis under UV irradiation. In our perception, these findings open a new venue for developing ultra-sensitive and recyclable SERS substrates.

Highly sensitive surface-enhanced Raman scattering detection of hexavalent chromium based on hollow sea urchin-like TiO2@Ag nanoparticle substrate

As one of the most toxic heavy metals, hexavalent chromium (Cr(VI)) has long been a concern due to its threats to human health and the environment. In this work, we develop a sensitive surface-enhanced Raman scattering (SERS) sensor for highly specific detection of Cr(VI) using hollow sea urchin-like TiO2@Ag nanoparticles (NPs). The TiO2@Ag NPs are functionalized with glutathione (GSH) and used as substrates with 2-mercaptopyridine (2-MPy) as a Raman reporter for a recyclable SERS-active sensor, enabling ultrasensitive detection of Cr(VI). Excellent SERS signals of 2-MPy reporters are detected when GSH complexation with Cr(VI) causes aggregation of the TiO2@Ag NPs. The developed sensor exhibits good linearity in the range from 10nM to 2μM for Cr(VI) with a detection limit of ca. 1.45nM. It features excellent selectivity to Cr(VI) over other interfering metal ions, and good application for quantitative analysis of Cr(VI) in water samples. Moreover, the proposed SERS sensor can be fully regenerated when exposed to UV light as a result of the self-cleaning ability of the substrates. In contrast to the traditional SERS detection, the present work shed new light on the design and synthesis of hierarchically self-assembled 3D substrate for SERS, catalysis and biosensor development.

Nanoshell-Enhanced Raman Spectroscopy on a Microplate for Staphylococcal Enterotoxin B Sensing.

A sensitive surface-enhanced Raman scattering (SERS) immunosensor based on the Au nanoparticle (Au NP) shell structure was developed to detect staphylococcal enterotoxin B (SEB) on a microplate. Au NPs modified with 4-nitrothiophenol (4-NTP) and coated with Ag shell of controlled thickness at 6.6 nm exhibited excellent SERS intensity and were used as signal reporters in the detection of SEB. The engaged 4-NTP allowed the significant electromagnetic enhancement between Au NPs and the Ag shell and prevented the dissociation of the Raman reporter. More importantly, 4-NTP-differentiated SERS signals between the sample and microplate. The SERS-based immunosensor had a limit of detection of 1.3 pg/mL SEB. Analysis of SEB-spiked milk samples revealed that the developed method had high accuracy. Therefore, the SERS-encoded Au@Ag core-shell structure-based immunosensor is promising for the detection of biotoxins, pathogens, and environmental pollutants.

Sensitive Glycoprotein Sandwich Assays by the Synergistic Effect of In Situ Generation of Raman Probes and Plasmonic Coupling of Ag Core-Au Satellite Nanostructures.

Sensitive surface-enhanced Raman scattering (SERS) assays of glycoproteins have been proposed using p-aminothiophenol (PATP)-embedded Ag core-Au satellite nanostructures modified with p-mercaptophenylboronic acid (PMBA) and the self-assembled monolayer of PMBA on a smooth gold-coated wafer. The apparent Raman probe PATP on the surfaces of the Ag cores underwent a photodimerization to generate 4,4'-dimercaptoazobenzene (DMAB) in situ upon excitation of laser, and the in situ generated DMAB acted as the actual Raman probe with considerably strong SERS signals, which was further enhanced by the plasmonic coupling of the Ag core-Au satellite nanostructures due to the synergistic effect. The sandwich assays of glycoproteins showed high sensitivity and excellent selectivity against nonglycoproteins. The Ag core-Au satellite SERS nanostructures can be used for highly sensitive SERS assays of other analytes.

Building SERS-active heteroassemblies for ultrasensitive Bisphenol A detection

Bisphenol A (BPA) usually exists in daily plastic products, as one of the most important endocrine disrupting chemicals. A sensitive surface-enhanced Raman scattering (SERS)-encoded aptasensor for the detection of BPA was developed, for the first time, based on gold nanoparticle-nanorod heteroassemblies. The high electromagnetic enhancement in narrow gaps between metal nanoparticles of these heteroassemblies led to marked Raman signals. It was found that the assembly degree and the corresponding SERS signals were in inverse correlation to the BPA concentrations over a wide linear range of 0.001–1ng/mL and the limit of detection was as low as 3.9pg/mL. Excellent recovery ranging from 91% to 95.3% was obtained to assess the feasibility of this method for real sample detection, indicating promising application for the detection of BPA.

Double Detection of Mycotoxins Based on SERS Labels Embedded Ag@Au Core-Shell Nanoparticles.

A sensitive surface-enhanced Raman scattering (SERS) signal dependent double detection of mycotoxins is achieved for the first time, without the aid of nucleic acid amplification strategies. SERS labels embedded Ag@Au core-shell (CS) nanoparticles (NPs) as novel SERS tags are successfully prepared through a galvanic replacement-free deposition. SERS tags produce stable and quantitative SERS signal, emerging from the plasmonic coupling at the junction of Ag core and Au shell. SERS tags engineered Raman aptasensors are developed for the double detection of ochratoxin A (OTA) and aflatoxin B1 (AFB1) in maize meal. The limits of detection (LODs) are as low as 0.006 ng/mL for OTA and 0.03 ng/mL for AFB1. The developed protocol can be extended to a large set of different SERS tags for the sensitive detection of multiple targets that possess different lengths of aptamers.

Improved SERS sensitivity on plasmon-free TiO₂ photonic microarray by enhancing light-matter coupling.

Highly sensitive surface-enhanced Raman scattering (SERS) detection was achieved on plasmon-free TiO2 photonic artificial microarray, which can be quickly recovered under simulated solar light irradiation and repeatedly used. The sensitive detection performance is attributed to the enhanced matter-light interaction through repeated and multiple light scattering in photonic microarray. Moreover, the SERS sensitivity is unprecedentedly found to be dependent on the different light-coupling performance of microarray with various photonic band gaps, where microarray with band gap center near to laser wavelength shows a lower SERS signal due to depressed light propagation, while those with band gap edges near to laser wavelength show higher sensitivity due to slow light effect.

Design and fabrication of random silver films as substrate for SERS based nano-stress sensing of proteins

We report a simple and easy to fabricate random silver film (RSF) as a highly sensitive Surface Enhanced Raman Scattering (SERS) substrate which can be fabricated directly onto a dielectric substrate such as glass. An electron beam evaporation system was used for substrate fabrication. The SERS activity is attributed to the formation of electromagnetic ‘hot-spots’ on the film. Substrate performance is analyzed by studying the reproducibility and signal enhancement from the Raman active molecule, 2-naphthalene thiol (NT), which is covalently anchored to the substrate. The metal thickness is optimized to achieve the highest SERS enhancement. Based on this study we found that a 7 nm RSF substrate gave the best SERS activity. The SERS signal intensity exhibited by 7 nm RSF is found to be at least 3 orders of magnitude higher than that of a commercial substrate. The SERS enhancement factor is estimated to be ∼1 × 107 with a point-to-point intensity variation of about 12% and it reaches a maximum of 15% for batch-to-batch comparison. The efficacy of this substrate for biosensing is demonstrated by detecting H1 influenza protein, and the detection limit is found to be ∼10 pM when it is used along with a recently established nano-stress SERS sensor, 4-ATP (4-amino-thiophenol), as linker molecule. This detection limit shows a performance superior to conventional ELISA (which has a nM detection limit). These results show promise for the development of a biosensing platform based on the marriage of RSF with nano-stress sensors.

Au@SiO2 core/shell nanoparticle assemblage used for highly sensitive SERS‐based determination of glucose and uric acid

The use of Au@SiO2 core/shell nanoparticle (NP) assemblage with highly sensitive surface‐enhanced Raman scattering (SERS) was investigated for the determination of glucose and uric acid in this study. Rhodamine 6G dye molecules were used to evaluate the SERS enhancement factor for the synthesized Au@SiO2 core/shell NPs with various silica shell thicknesses. The enhancement of SERS signal from Rhodamine 6G was found to increase with a decrease in the shell thickness. The core/shell assemblage with silica layer of 1–2 nm over a Au NP of ~36 nm showed the highest SERS signal. Our results show that the SERS technique is able to detect glucose and uric acid within wide concentration ranges, i.e. 20 ng/dL to 20 mg/dL (10−12–10−3 M) and 16.8 ng/dL to 2.9 mg/dL (10−11–1.72 × 10−4 M), respectively, with associated lower detection limits of ~20 ng/dL (~1.0 × 10−12 M) and ~16.8 ng/dL (~1.0 × 10−11 M). Our work offers a low‐cost route to the fabrication of agile sensing devices applicable to the monitoring of disease progression. Copyright © 2013 John Wiley & Sons, Ltd.

A fast and low‐cost spray method for prototyping and depositing surface‐enhanced Raman scattering arrays on microfluidic paper based device

In this study, a fast, low-cost, and facile spray method was proposed. This method deposits highly sensitive surface-enhanced Raman scattering (SERS) silver nanoparticles (AgNPs) on the paper-microfluidic scheme. The procedures for substrate preparation were studied including different strategies to synthesize AgNPs and the optimization of spray cycles. In addition, the morphologies of the different kinds of paper substrates were characterized by SEM and investigated by their SERS signals. The established method was found to be favorable for obtaining good sensitivity and reproducible results. The RSDs of Raman intensity of randomly analyzing 20 spots on the same paper or different filter papers depositing AgNPs are both below 15%. The SERS enhancement factor is approximately 2 × 10(7) . The whole fabrication is very rapid, robust, and does not require specific instruments. Furthermore, the total cost for 1000 pieces of chip is less than $20. These advantages demonstrated the potential for growing SERS applications in the area of environmental monitoring, food safety, and bioanalysis in the future.

Enzymatic Control of Plasmonic Coupling and Surface Enhanced Raman Scattering Transduction for Sensitive Detection of DNA Demethylation

We have developed a novel concept for enzymatic control of plasmonic coupling as a surface enhanced Raman scattering (SERS) nanosensor for DNA demethylation. This nanosensor is constructed by decorating gold nanoparticles (AuNPs) with Raman reporters and hemimethylated DNA probes. Demethylation of DNA probes initiates a degradation reaction of the probes by methylation-sensitive endonuclease Bsh 1236I and single-strand selective exonuclease I. This destabilizes AuNPs and mediates the aggregation of AuNPs, generating a strong plasmonic coupling SERS signal in response to DNA demethylation. This nanosensor has the advantages in its high signal-to-noise ratio, superb specificity, and rapid, convenient, and reproducible detection with homogeneous, single-step operation. Thus, it provides a useful platform for detecting DNA demethylation and related molecular diagnostics and drug screening. This work is the first time that enzymatic degradation of DNA substrate probes has been utilized to induce aggregation of AuNPs such that reproducible, sensitive SERS signals can be achieved from biological recognition events. This enzymatic control mechanism for plasmonic coupling may create a new paradigm for the development of SERS nanosensors.