Sensitive Surface-enhanced Raman Scattering Substrates Research Articles

Self-growth of dense Ag nanoislands on Ag-59.3at%V alloy films as sensitive SERS substrates

High-performance and high-stability surface enhanced Raman scattering (SERS) substrates are urgently needed in the detection field, chemical engineering, etc. Ag nanoislands/Ag-V alloy films on polyimide (PI) have been designed and fabricated as high-sensitivity SERS substrates. The dependence of surface morphology, roughness, water contact angle, and contents of islands and films on SERS performance are systematically discussed. In addition, covering the surface of the annealed alloy films with a 12 nm Ag layer could improve the SERS performance of the alloy films by coupling enhancement of the electric field. The Ag layer/Ag nanoisland/Ag-V alloy films SERS substrates are capable of detecting rhodamine 6 G (R6G) solution at a consistency of 5 × 10−13 mol/L. The low-cost, mass-producible Ag nanoisland/film prepared in this paper can be used as stable and sensitive SERS substrates.

Formation of Armored Silicon Nanowires Array via High-Repetition-Rate Femtosecond Laser Oxidation for Robust Surface-Enhanced Raman Scattering Detection.

Superhydrophobic nanostructures with dense hotspots and high concentration efficiency are of paramount importance for highly sensitive surface-enhanced Raman scattering (SERS) detection. However, their low mechanical strength makes them susceptible to damage from external interferences, leading to hotspot loss and superhydrophobicity failure. In this study, robust SERS detection is achieved using an armored superhydrophobic silicon nanowires array. A micro/nanocross-scale oxide mask is created through high-repetition-rate femtosecond laser oxidation to fabricate the armored nanowires array. The underlying mechanisms of the nanoparticle layer serving as a mask in deep reactive ion etching (DRIE) are analyzed to elucidate the formation of the silicon nanowires. The armored nanowires array SERS substrate exhibits a high contact angle of 158°, demonstrating exceptional analyte enrichment capability. Combined with the dense hotspots provided by the high aspect ratio nanostructures, the detection limit for Rhodamine 6G is 10-13 M, and the enhancement factor (EF) is 4.35 × 109. After undergoing various mechanical tests, the substrate maintains its superhydrophobicity along with a stable Raman signal enhancement, demonstrating its resistance to potential external interference in SERS detection. The sensitive detection of various analytes highlights the promising applications of the armored nanowires substrate in diverse SERS scenarios.

Facile fabrication of Au-Ag alloy nanoparticles/Ag nanowires SERS substrates with bimetallic synergistic effect for ultra-sensitive detection of crystal violet and alkali blue 6B

The bimetallic nanostructure of Au and Ag can integrate two distinct properties into a novel substrate compared to single metal nanostructures. This work presents a rapid and sensitive surface-enhanced Raman scattering (SERS) substrate for detecting illegal food additives and dyes of crystal violet (CV) and alkali blue 6B (AB 6B). Au-Ag alloy nanoparticles/Ag nanowires (Au-Ag ANPs/Ag NWs) were prepared by solid-state ionics method and vacuum thermal evaporation method at 5μA direct current electric field (DCEF), the molar ratio of Au to Ag was 1:18.34. Many 40 nm-140 nm nanoparticles regularly existed on the surface of Ag NWs with the diameters from 80 nm to 150 nm. The fractal dimension of Au-Ag ANPs/Ag NWs is 1.69 due to macroscopic dendritic structures. Compared with single Ag NWs, the prepared Au-Ag ANPs/Ag NWs substrates show superior SERS performance because of higher surface roughness, the SERS active of Ag NWs and bimetallic synergistic effect caused by Au-Ag ANPs, so the limit of detections (LOD) of Au-Ag ANPs/Ag NWs SERS substrates toward detection of CV and AB 6B were as low as 10-16mol/L and 10-9mol/L, respectively. These results indicate that Au-Ag ANPs/Ag NWs substrates can be used for rapid and sensitive detection of CV and AB 6B and have great development potential for detection of illegal food additives and hazardous substances in the fields of environmental monitoring and food safety.

SERS-active core-satellite nanostructures in a membrane filter-integrated microfluidic device for sensitive and continuous detection of trace molecules

We developed a surface-enhanced Raman scattering (SERS)-active plasmonic core-satellite nanostructure and incorporated it into a membrane filter-integrated microfluidic device for continuous monitoring of molecules in solution. The core-satellite nanostructures were fabricated by immobilizing a high number density of gold nanoparticles (AuNPs) on silica beads.to create many nanogaps among the AuNPs. The sizes of the nanogaps were fine-tuned by adding a silver (Ag) shell to optimize the SERS activity. In addition, citrate molecule, the capping agent of the nanoparticles, was displaced by alkali halides. The displacement not only reduced the SERS signals of citrate but also enhanced the adsorption of target molecules. The alkali halide-treated core-satellite nanostructures were accumulated onto a membrane filter integrated into a microfluidic device, serving as a uniform and sensitive SERS substrate. By increasing the volume of the sample solution flowing through the membrane filter, we increased the number of molecules adsorbed to the nanostructures, amplifying the intensities of their characteristic Raman peaks. Our microfluidic SERS device demonstrated continuous SERS detection of malachite green at a concentration as low as 500 fM. In summary, while various core-satellite nanostructures and microfluidic SERS devices have been reported, the integration of the membrane filter-containing microfluidic device with the core-satellite nanostructures facilitated sensitive and continuous molecule detection in our study.

Flexible SERS substrates with gradient porous Cu structure dealloying from the thermal diffusion couples of Al/Cu stacking foils

Accurate and sensitive surface-enhanced Raman scattering (SERS) substrates are urgently demanded for the various analytic techniques. The SERS substrates with multimodal and gradient porous structure, utilized for the Rhodamine 6G (R6G) detection, have been designed and successfully fabricated from the thermal diffusion couples of Al and Cu foils via chemical dealloying. The structural inheritance of the initial microstructure of thermal diffusion couple precursors governs the formation of the final layer-by-layer gradient porous Cu with different characteristic pore sizes and morphology. An outmost surface layer of disordered lipstick-like porous structure on the SERS substrates enhances SERS effects as has been expected. The SERS activity of R6G Raman probes on gradient porous Cu is evaluated as a SERS enhancement factor of 6.63 × 1012 and limit of detection of 2.10 × 10−17 mol/L, higher than other porous SERS substrates. Meanwhile, the present SERS substrates are flexible and exhibit good bending properties due to the unreacted Cu layer as a supporting skeleton and other gradient porous Cu layers. The superior SERS performances are considered to result from the synergetic effects of the surface scattering of porous Cu rods and enhancements of the high electromagnetic fields between the small gaps between the nanopores.

Fabrication of Superhydrophobic–Hydrophilic Patterned Cu@Ag Composite SERS Substrate via Femtosecond Laser

Ultralow concentration molecular detection is critical in various fields, e.g., food safety, environmental monitoring, and disease diagnosis. Highly sensitive surface-enhanced Raman scattering (SERS) based on ultra-wettable surfaces has attracted attention due to its unique ability to detect trace molecules. However, the complexity and cost associated with the preparation of traditional SERS substrates restrict their practical application. Thus, an efficient SERS substrate preparation with high sensitivity, a simplified process, and controllable cost is required. In this study, a superhydrophobic–hydrophilic patterned Cu@Ag composite SERS substrate was fabricated using femtosecond laser processing technology combined with silver plating and surface modification treatment. By inducing periodic stripe structures through femtosecond laser processing, the developed substrate achieves uniform distribution hotspots. Using the surface wettability difference, the object to be measured can be confined in the hydrophilic region and the edge of the hydrophilic region, where the analyte is enriched by the coffee ring effect, can be quickly located by surface morphology difference of micro-nanostructures; thus, greatly improving detection efficiency. The fabricated SERS substrate can detect Rhodamine 6G (R6G) at an extraordinarily low concentration of 10−15 mol/L, corresponding to an enhancement factor of 1.53 × 108. This substrate has an ultralow detection limit, incurs low processing costs and is simple to prepare; thus, the substrate has significant application potential in the trace analysis field.

Structure-regulated enhanced Raman scattering on a semiconductor to study temperature-influenced enantioselective identification.

Surface-enhanced Raman scattering (SERS) spectroscopy is an effective technique that can reveal molecular structure and molecular interaction details. Semiconductor-based SERS platforms exhibit multifaceted tunability and unique selectivity to target molecules as well as high spectral reproducibility. However, the detection sensitivity of semiconductors is impeded by inferior SERS enhancement. Herein, a surface and interference co-enhanced Raman scattering (SICERS) platform based on corrugated TiO2 nanotube arrays (c-TiO2 NTs) was developed, and the coupling of structural regulation and photo-induced charge transfer (PICT) effectively optimized the SERS performance of the semiconductor substrate. Due to the regularly oscillating optical properties of the c-TiO2 NTs, well-defined interference patterns were generated and the local electric field was significantly increased, which greatly promoted both the electromagnetic mechanism and PICT processes. The c-TiO2 NTs were subsequently applied as a highly sensitive SICERS substrate to investigate the mechanism of temperature influence on enantioselective identification. This identification process is related to the existence of temperature-sensitive hydrogen bonds and π-π interaction. This work demonstrates a simply prepared, low-cost, and sensitive SERS substrate that enables better investigation into molecular identification.

Ultrasensitive Determination of Thiabendazole in Fruit Juice by Surface-Enhanced Raman Scattering (SERS) Using a Covalent Organic Framework (COF) Gold Nanoparticle (Au NP) Substrate

An effective and sensitive SERS substrate (TPDH-COF/Au NPs) on a covalent organic framework (TPDH-COF) decorated with gold nanoparticles (Au NPs) was fabricated via electrostatic self-assembly and successfully applied for the determination of thiabendazole (TBZ) in fruit juice. The “raspberry-like” structure SERS substrate combined the properties of the abundant “hot spots” between the Au NPs and the adsorption performance of TPDH-COFs for trace analytes. Excellent SERS performance was observed, which achieved a high enhancement factor value of 2.01 × 108 for rhodamine 6 G, with considerable reproducibility and excellent long-term stability of at least 28 d. The limit of detection was estimated to be 5 ppb for TBZ in fruit juice. The result demonstrated that the TPDH-COF/Au NPs have great potential for SERS analyses and determination of pesticide residues in foods.

2D TiS2-Nanosheet-Coated Concave Gold Arrays with Triple-Coupled Resonances as Sensitive SERS Substrates.

Herein, a hybrid substrate for surface-enhanced Raman scattering (SERS) is fabricated, which couples localized surface plasmon resonance (LSPR), charge transfer (CT) resonance, and molecular resonance. Exfoliated 2D TiS2 nanosheets with semimetallic properties accelerate the CT with the tested analytes, inducing a remarkable chemical mechanism enhancement. In addition, the LSPR effect is coupled with a concave gold array located underneath the thin TiS2 nanosheet, providing a strong electromagnetic enhancement. The concave gold array is prepared by etching silicone nanospheres assembled on larger polystyrene nanospheres, followed by depositing a gold layer. The LSPR intensity near the gold layer can be adjusted by changing the layer thickness to couple the molecular and CT resonances, in order to maximize the SERS enhancement. The best SERS performance is recorded on TiS2-nanosheet-coated plasmonic substrates, with a detectable methylene blue concentration down to 10-13m and an enhancement factor of 2.1 × 109 and this concentration is several orders of magnitude lower than that of the TiS2 nanosheet (10-11m) and plasmonic substrates (10-9m). The present hybrid substrate with triple-coupled resonance further shows significant advantages in the label-free monitoring of curcumin (a widely applied drug for treating multiple cancers and inflammations) in serum and urine.

Highly Uniform Self-Assembly of Gold Nanoparticles by Butanol-Induced Dehydration and Its SERS Applications in SARS-CoV-2 Detection.

We report the development of a reproducible and highly sensitive surface-enhanced Raman scattering (SERS) substrate using a butanol-induced self-assembly of gold nanoparticles (AuNPs) and its application as a rapid diagnostic platform for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The butanol-induced self-assembly process was used to generate a uniform assembly of AuNPs, with multiple hotspots, to achieve high reproducibility. When an aqueous droplet containing AuNPs and target DNAs was dropped onto a butanol droplet, butanol-induced dehydration occurred, enriching the target DNAs around the AuNPs and increasing the loading density of the DNAs on the AuNP surface. The SERS substrate was evaluated by using Raman spectroscopy, which showed strong electromagnetic enhancement of the Raman signals. The substrate was then tested for the detection of SARS-CoV-2 using SERS, and a very low limit of detection (LoD) of 3.1 × 10-15 M was obtained. This provides sufficient sensitivity for the SARS-CoV-2 screening assay, and the diagnostic time is significantly reduced as no thermocycling steps are required. This study demonstrates a method for the butanol-induced self-assembly of AuNPs and its application as a highly sensitive and reproducible SERS substrate for the rapid detection of SARS-CoV-2. The results suggest the potential of this approach for developing rapid diagnostic platforms for other biomolecules and infectious diseases.

Thermally generated Au–Ag nanostructures with tunable localized surface plasmon resonance as SERS activity substrates

Various Au–Ag bimetallic alloy nanostructures were obtained as sensitive surface-enhanced Raman scattering (SERS) substrates by changing the thermal annealing sequence. The atomic force microscopy (AFM) and scanning electron microscopy (SEM) results confirm that Au/Ag bimetallic clusters and Ag–Au core-shell like structures can be designed by thermal annealing. The absorption spectra showed that the localized surface plasmon resonance (LSPR) frequency of the annealed Au/Ag bimetallic alloy structure could effectively shift from the near ultraviolet to the visible region. At the same time, the Au/Ag bimetallic alloy films modified by thermal annealing have shown satisfactory performance as SERS substrates. Raman enhancement mechanism of Au–Ag bimetallic alloy films is verified by finite-difference time-domain (FDTD) simulation results.

Detection and analysis of rotavirus in clinical stool samples using silver nanoparticle functionalized paper as SERS substrate

Among the different analytical techniques, surface-enhanced Raman scattering (SERS) approach is a widely used technique for the detection and analysis of various chemicals and biological samples. Present study reports a low-cost, sensitive SERS substrate that has an ability to detect rotavirus in clinical stool samples. The proposed SERS substrate has been fabricated through drop-casting of silver nanoparticles (AgNPs) on a printing-grade paper. Rotavirus particles were extracted from clinical stool samples. The presence of rotavirus antigen in stool samples was confirmed using enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and sequencing. The characteristic Raman peaks of rotavirus (RV) particles in solution were found to be significantly enhanced when Raman signals were recorded from the paper-based SERS substrates. Using the proposed SERS substrate, rotavirus samples with concentration as low as 1% could be reliably recorded by the Raman spectrometer. The paper SERS substrate reported herein is an extremely cost-efficient platform and may find applications in other research and clinical laboratories as well.

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.

A dense SERS substrate of the AgNPs@GO compound film for detecting homocysteine molecules.

This study focuses on the development of a highly sensitive surface-enhanced Raman scattering (SERS) sensor for detecting homocysteine (Hcy) molecules. The Hcy sensor was created by depositing silver nanoparticles (AgNPs) onto the surface of graphene oxide (GO) film to form a dense AgNPs@GO composite film. The AgNPs on the composite film interacted with sulfur atoms (S) of Hcy molecules to form Ag-S bonds, which boosted the chemisorption of Hcy molecules and enabled them to be specifically recognized. The SERS sensor exhibited a maximum enhancement factor of up to 1.1 × 104, with a reliable linear response range from 1 to 60 ng mL-1. The limit of detection (LOD) for Hcy molecules was as low as 1.1 × 10-9 M. Moreover, Hcy molecules were successfully distinguished in a mixed solution of γ-aminobutyric acid and Hcy molecules. In this study, a simple preparation process of SERS substrate and a novel detection method for Hcy molecules provided a new pathway for the rapid and effective detection of Hcy molecules in the food and biomedicine fields.

Nanoporous Ag-Decorated Ag7O8NO3 Micro-Pyramids for Sensitive Surface-Enhanced Raman Scattering Detection

Porous noble metal nanomaterials can be employed to construct sensitive surface-enhanced Raman scattering (SERS) substrates, because the plasmonic nanopores and nanogaps of the porous materials can provide a larger number of hotspots, and can also serve as containers of analyte molecules. However, the fabrication processes of nanoporous noble metal are generally complicated. Here, a facile method is presented to prepare nanoporous Ag nanoparticles-decorated Ag7O8NO3 micro-pyramids, which are fabricated through the chemical reduction of the electrodeposited Ag7O8NO3 micro-pyramids using NaBH4. The Ag7O8NO3 micro-pyramids are fabricated by electrodeposition by using a simple aqueous solution of AgNO3 as electrolyte. Then, porous Ag-decorated Ag7O8NO3 micro-pyramids are achieved by the chemical reduction of the surface of the electrodeposited Ag7O8NO3 micro-pyramids with NaBH4. The high-density nanopores and nanogaps of the fabricated nanoporous Ag can provide plenty of hot spots for Raman enhancement. Additionally, the nanopores have an effective capacity to trap and enrich analytes. Using rhodamine 6G (R6G) as a probe molecule, the SERS performance of the fabricated SERS substrate has been investigated. It is found that a limit of detection (LOD) ~1.0 × 10−15 M can be achieved for R6G. Then, the SERS substrates are employed to detect dye molecule (crystal violet) and pesticide (thiram), and their LODs are calculated down to 9.6 × 10−13 M and 1.3 × 10−15 M, respectively. The enhancement factor of the fabricated SERS substrate is estimated to be as high as 5.6 × 108. Therefore, the nanoporous Ag-decorated Ag7O8NO3 micro-pyramids have shown promising application in the sensitive SERS detection of organic molecules.

Ultrasensitive determination of lipid soluble antioxidants in food products using silver nano-tripod SERS substrates

Lipid soluble antioxidants can effectively prevent the oxidative deterioration of oils and fat-containing foods. However, long-term consumption of foods containing antioxidants may damage human health. Herein, a highly sensitive surface-enhanced Raman scattering (SERS) method was explored for the detection of antioxidants by constructing multi-hot silver nano-tripod (AgNT) substrates. Finite difference time domain (FDTD) calculation demonstrated that the “hot spots” of AgNT structures are widely spread, which endows the substrate with excellent detection ability. The enhancement factors (EFs) for trans-1,2-bis(4-pyridyl)ethylene (BPE) and rhodamine 6G (R6G) were 1.08 × 109 and 4.46 × 108, respectively. Combined with density functional theory, AgNT substrates achieved rapid detection of four common antioxidants such as butylated hydroxyanisole (BHA), tertiary butylhydroquinone (TBHQ), butylated hydroxytoluene (BHT) and propyl gallate (PG). The limit of detection (LOD) of BHA, TBHQ and PG was 1 mg/L, and the LOD of BHT was 2 mg/L. Moreover, the substrate combined with principal component analysis can effectively identify antioxidants in fried potato chips. This substrate-based SERS method does not require complex sample pretreatments, and can identify and analyze types and contents of antioxidants added in food in a short time (2 min), providing a portable means for food safety control.

Interfacial layer-by-layer self-assembly of PS nanospheres and Au@Ag nanorods for fabrication of broadband and sensitive SERS substrates

Broadband surface-enhanced Raman scattering (SERS) substrates can achieve strong SERS enhancement at multiple excitation wavelengths, which is highly desirable in diverse fields. Here, a facile and reliable interfacial layer-by-layer self-assembly technique was proposed to construct broadband and sensitive Au@Ag nanorod (NR) monolayer film over nanosphere (MFON) substrate. The Au@Ag NR MFON substrate with ultra-broad spectrum from visible to near-infrared region was achieved by varying the shape of plasmonic nanoparticles, which exhibits excellent SERS activity at different excitation wavelengths. Besides, the size of Au@Ag NRs and polystyrene spheres, and the layer numbers of Au@Ag NR film were altered to optimize the sensitivity of SERS substrates. Notably, the SERS intensity of the optimally designed Au@Ag NR MFON substrate is 25-fold larger than that of Au@Ag NR monolayer film deposition on the plane Si wafer. Furthermore, the optimal Au@Ag NR MFON substrate presents excellent reproducibility and a much wider quantitative detection range, which enables a wide-linear-range analysis of thiram in grape juice by a portable Raman spectrometer. Therefore, we envision that this study opens a new avenue toward the design of ultra-sensitive and broadband SERS platforms with widespread applications.

Investigation of a Highly Sensitive Surface-Enhanced Raman Scattering Substrate Formed by a Three-Dimensional/Two-Dimensional Graphene/Germanium Heterostructure.

Three-dimensional graphene (3D-graphene) is used in surface-enhanced Raman spectroscopy (SERS) because of its plasmonic nanoresonator structure and good ability to interact with light. However, a thin (3-5 nm) layer of amorphous carbon (AC) inevitably appears as a template layer between the 3D-graphene and object substrate when the 3D-graphene layer is synthesized, weakening the enhancement factor. Herein, two-dimensional graphene (2D-graphene) is employed as a template layer to directly synthesize 3D-graphene on a germanium (Ge) substrate via plasma-assisted chemical vapor deposition, bypassing the formation of an AC layer. The interaction and photoinduced charge transfer ability of the 3D-graphene/Ge heterojunction with incident light are improved. Moreover, the high density of electronic states close to the Fermi level of the heterojunction induces the adsorbed probe molecules to efficiently couple to the 3D-graphene-based SERS substrate. Our experimental results imply that the lowest concentrations of rhodamine 6G and rhodamine B that can be detected on the 3D/2D-graphene/Ge SERS substrate correspond to 10-10 M; for methylene blue, it is 10-8 M. The detection limits of the 3D/2D-graphene/Ge SERS substrate with respect to 3-hydroxytyramine hydrochloride and melamine (in milk) are both less than 1 ppm. This work may provide a viable and convenient alternative method for preparing 3D-graphene SERS substrates. It also constitutes a new approach to developing SERS substrates with remarkable performance levels.

A Multilayer Interlaced Ag Nanosheet Film Prepared by an Electrodeposition Method on a PPy@PEDOT:PSS Film: A Strategy to Prepare Sensitive Surface-Enhanced Raman Scattering Substrates.

A highly sensitive multilayer interlaced silver (Ag) nanosheet (MISN) film was prepared on a PPy@PEDOT:PSS film via an electrodeposition method for surface-enhanced Raman scattering (SERS) applications. After the PPy@PEDOT:PSS film was pretreated with ascorbic acid solution, many sparse Ag nanoparticles (NPs) could be directly reduced on the surface of the PPy@PEDOT:PSS film in AgNO3 solution. Then, the MISN film was directionally grown along the surface of sparse Ag NPs by using an electrochemical galvanostatic method to form a Ag/PPy@PEDOT:PSS film for a SERS substrate. The results indicated that with the increase in electrodeposition time, the density of Ag nanosheets was also increased for boosting the SERS effect. Accordingly, owing to the directional growth of Ag NPs, the increase in the length–width ratio of single Ag nanosheets would further promote the SERS signal of the substrate. Moreover, the maximum enhancement factor of the SERS substrate could reach to 12,478, and the minimum limit of detection of melamine solution was down to 5.42 ng/mL. The SERS sensitivity of the Ag nanosheet film reached 100.65. This method of preparing the SERS substrate provides a novel and robust strategy for the low-cost and high-sensitivity detection in biomedicine, drugs, and food.

Highly sensitive characteristic of surface enhanced Raman scattering for CuO/Au core/shell nanowires substrate

In this paper, we report a facile process to fabricate CuO/Au core/shell nanowires, where CuO core and Au shell were prepared by thermal oxidation and sputtering, respectively. The as-prepared CuO/Au nanowires are highly sensitive surface-enhanced-Raman-scattering (SERS) substrates, which can detect methylene blue down to a very low concentration of 10 −13 M. The major advantages of SERS substrates based on CuO/Au core/shell nanowires compared with others SERS substrates are the high sensitivity, uniformity, and purity due to the absence of any organic surfactants in the synthesis process.