Surface-enhanced Raman Scattering Substrates Research Articles

Surface Enhanced Raman Scattering in thin films: The importance of Raman Analyte-Plasmonic Particle inverse geometry

Abstract Most of the successful applications of surface enhanced Raman scattering (SERS) involves placing the Raman analyte molecule over the SERS substrate. This conventional geometry of SERS does not work when the Raman analyte is in the form of a thin film. In this report, we experimentally demonstrate the importance of the rarely explored inverse geometry wherein a plasmonic particle is placed over an analyte thin film for SERS study. Initially, as a case study, the effect of size, concentration, and distribution of gold nanoparticles (AuNPs) on the SERS of Si wafer was performed. The AuNPs, prepared by optimized annealing of direct current sputtered Au, were characterized by scanning electron microscopy, atomic force microscopy, and UV-Visible spectrophotometry. Finally, as an application, SERS in inverse geometry was successfully performed with an electron-beam evaporated Si thin film. For the first time, a working formula has been proposed to determine the experimental enhancement factor (EEF) for the inverse geometry of SERS. The values of EEF were estimated to be 1526 and 3274 respectively for Si wafer and Si thin film for the similar distribution of AuNPs of average size 52 nm. This study provides an insight into the characterization of thin films.

Ag nanopines over Al nanoneedle arrays enable high SERS sensitivity and reproducibility for molecular sensing

In this study, highly uniform 3D Al nanoneedle arrays (AlNNAs) decorated with Ag nanopines are synthesized by anodization of Al foil with prior nanoimprinting and subsequent electrodeposition method, demonstrating remarkable surface-enhanced Raman scattering (SERS) property. The AlNNAs possess a highly ordered periodicity of 1 μm and nanoneedle height of 800 nm, making it an optimal supporting matrix to host Ag-NPs as SERS substrate. Such well-ordered Ag@AlNNAs SERS substrate with precisely electrodeposited Ag nanopines generate high density SERS host spots and abundant sites to adsorb target molecules. As a result, Ag@AlNNAs exhibit high sensitivity for rhodamine 6 G down to 10–13 M and good signal reproducibility with a relative standard deviation of 7.2 %, as well as an average enhancement factor of 4.23 × 109. For practical detection of pollutants, 10–8 M adenine, 10–12 M bisphenol in water, and melamine (10–7 M) in opaque milk are clearly identified by using the Ag@AlNNAs sensor. This study opens a bright way to fabricate SERS substrate with a good balance of sensitivity, reproducibility and cost, indicating promising potential for environmental monitoring and food safety.

Metal-Organic Frameworks/Heterojunction Structures for Surface-Enhanced Raman Scattering with Enhanced Sensitivity and Tailorability.

Metal-organic frameworks (MOFs), which are composed of crystalline microporous materials with metal ions, have gained considerable interest as promising substrate materials for surface-enhanced Raman scattering (SERS) detection via charge transfer. Research on MOF-based SERS substrates has advanced rapidly because of the MOFs' excellent structural tunability, functionalizable pore interiors, and ultrahigh surface-to-volume ratios. Compared with traditional noble metal SERS plasmons, MOFs exhibit better biocompatibility, ease of operation, and tailorability. However, MOFs cannot produce a sufficient limit of detection (LOD) for ultrasensitive detection, and therefore, developing an ultrasensitive MOF-based SERS substrate is imperative. To the best of our knowledge, this is the first study to develop an MOFs/heterojunction structure as an SERS enhancing material. We report an in situ ZIF-67/Co(OH)2 heterojunction-based nanocellulose paper (nanopaper) plate (in situ ZIF-67 nanoplate) as a device with an LOD of 0.98 nmol/L for Rhodamine 6G and a Raman enhancement of 1.43 × 107, which is 100 times better than that of the pure ZIF-67-based SERS substrate. Further, we extend this structure to other types of MOFs and develop an in situ HKUST-1 nanoplate (with HKUST-1/Cu(OH)2). In addition, we demonstrate that the formation of heterojunctions facilitates efficient photoinduced charge transfer for SERS detection by applying the Mx(OH)y-assisted (where M = Co, Cu, or other metals) MOFs/heterojunction structure. Finally, we successfully demonstrate the application of medicine screening on our nanoplates, specifically for omeprazole. The nanoplates we developed still maintain the tailorability of MOFs and perform high anti-interference ability. Our approach provides customizing options for MOF-based SERS detection, catering to diverse possibilities in future research and applications.

Nanoplastics Detected in Commercial Sea Salt.

People of all ages consume salt every day, but is it really just salt? Plastic nanoparticles [nanoplastics (NPs)] pose an increasing environmental threat and have begun to contaminate everyday salt in consumer goods. Herein, we developed a combined surface enhanced Raman scattering (SERS) and stimulated Raman scattering (SRS) approach that can realize the filtration, enrichment, and detection of NPs in commercial salt. The Au-loaded (50 nm) anodic alumina oxide substrate was used as the SERS substrate to explore the potential types of NP contaminants in salts. SRS was used to conduct imaging and quantify the presence of the NPs. SRS detection was successfully established through standard plastics, and NPs were identified through the match of the hydrocarbon group of the nanoparticles. Simultaneously, the NPs were quantified based on the high spatial resolution and rapid imaging of the SRS imaging platform. NPs in sea salts produced in Asia, Australasia, Europe, and the Atlantic were studied. We estimate that, depending on the location, an average person could be ingesting as many as 6 million NPs per year through the consumption of sea salt alone. The potential health hazards associated with NP ingestion should not be underestimated.

Fullerene nanosheets for surface-enhanced Raman spectroscopy

Most surface-enhanced Raman scattering (SERS) substrates are based on noble metals or transition metal semiconductors. Developing nonmetallic SERS substrates is of great significance for expanding the application scope of SERS substrate materials. In this study, ultrathin C60 nanosheets with two-dimensional structures were synthesized using CVD and used as SERS substrates. Owing to the combined effects of favorable factors such as the expanded specific surface area and matched interfacial charge transport paths, the substrate has a minimum detection limit of 10−11 for Rhodamine 6G and a Raman enhancement factor of 107. In addition, the C60 nanosheets exhibited good stability and uniformity as SERS substrates.

Snowflake Cu2S@ZIF-67: A Novel Heterostructure Substrate for Enhanced Adsorption and Sensitive Detection in SERS

Snowflake Cu2S@ZIF-67: A Novel Heterostructure Substrate for Enhanced Adsorption and Sensitive Detection in SERS

Nano-Architected Titania/Gold@GO Nanosheets for Sonocatalytic Degradation of Azo Dyes in Textile Wastewater

Environmental pollution, a huge issue on a global scale, poses serious risks to both human health and the natural environment. There is an urgent need for effective and reliable detection and degradation methods that focus on the evolution of environmental and trace contaminants. Photochemical methods such as surface-enhanced Raman scattering (SERS) and sono-catalytic degradation can be used to accelerate the detection and degradation of toxic dyes. In the present work, a titania/gold/graphene oxide nanocomposite (ATG) was investigated as a potential dual substrate for SERS sensing and sono-catalytic degradation of pollutants. The nanosize distribution (6-12nm) of ATG was determined by a solvothermal route. X-ray diffraction pattern illustrates the anatase phase of the titanium dioxide. Sonocatalytic degradation was envisaged using Raman spectroscopy. The effectiveness of ATG as a sono-catalytic substrate and SERS sensor was first evaluated using commercial dyes, such as malachite green and bismarck brown. Furthermore, research has been conducted on the harmful elements in actual textile effluents (TE). The N=N and C-N bands found in the SERS spectra of TE are useful indicators of the presence of carcinogenic azo-dye impurities. The enhancement factor was achieved to be 5.77×1012with the limit of detection (LOD) as 6.0×10−12M. Additionally, the sono-catalysis of ATG was evaluated for the elimination of these dye pollutants in TE. Following sono-catalysis by ATG, a high degradation rate constant of approximately 8.44 ×10-3/min was noted in TE with 89% of degradation efficiency. The enhanced SERS detection and sono-catalytic degradation of synthetic dyes and actual effluent stem from the combined action of’ plasmonic characteristics of Au NPs, anatase TiO2, and GO's via π-π stacking nature of GO.

Generalized ratiometric surface-enhanced Raman scattering biosensor for okadaic acid in food based on Au-triggered signal amplification

BackgroundReliability and robustness have been recognized as key challenges for Surface-enhanced Raman scattering (SERS) analytical techniques. Quantifying the concentration of an analyte using a single characteristic peak from SERS has been a controversial topic because the Raman signal is susceptible to highly concentrated electromagnetic hotspots, inhomogeneity of SERS substrate, or non-standardization of measurement conditions. Ratiometric SERS strategies have been demonstrated as a promising solution to effectively balance and compensate for signal fluctuations caused by matrix heterogeneity. However, it is not easy to construct ratiometric SERS sensors with monitoring the ratio of two different signal intensities for target analysis. ResultsAn attempt has been made to develop a novel ratiometric biosensor that can be applied to detect okadaic acid (OA). Aptamer-anchored magnetic particles were first combined with gold-tagged short complementary DNA (Au-cDNA) to create heterogeneous nanostructures. When the target was present, the Au-cDNA was dissociated from nanostructures, and 4-nitrothiophenol (4-NTP) was initiated to reduce to 4-aminothiophenol (4-ATP) in the presence of hydrogen sources. The SERS ratio change of 4-NTP and 4-ATP was finally detected by AuNPs-coated film. OA was successfully quantified, and the detection limit was as low as 2.4524 ng/mL. The constructed biosensor had good stability and reproducibility with a relative standard deviation of less than 4.47%. The proposed method used gold nanoparticles as an intermediate to achieve catalytic signal amplification and subsequently increased the sensitivity of the biosensor. Significance and NoveltyCatalytic reaction-based ratiometric SERS biosensors combine the multiple advantages of catalytic signal amplification and signal self-calibration and provide new insights into the development of stable, reproducible, and reliable SERS detection techniques. This ratiometric SERS technique offered a universal method that is anticipated to be applicable for the detection of other targets by substituting the aptamer.

Superlattice assembly strategy of small noble metal nanoparticles for surface-enhanced Raman scattering

The self-assembly of noble metal nanoparticles into periodic structures has been a theme of great interest for surface-enhanced Raman scattering (SERS) and use in functional devices. However, small nanoparticle self-assembly faces numerous challenges in tunability, referring to controlling their structural properties like structure, gaps, and arrangement. These issues highlight the need for further research and development to enhance the tunability and stability of self-assembled small nanoparticles. Here, we report a general centimeter-scale superlattice assembly strategy for noble metal nanoparticles less than 15 nm in size. Not only is this monolayer superlattice assembly generally applicable to different kinds and sizes of noble metal nanoparticles, but also, the crystal plane spacing can also be quickly and conveniently controlled by changing the ethanol concentration. SERS results reveal that optimized superlattice membranes of noble metal nanoparticles possess high detection sensitivity and ordered hot spots. Therefore, our strategy offers prospects for high-performance SERS substrates based on small noble metal nanoparticle superlattices.

Hierarchically porous coralloid ZnO@Ag microspheres as SERS substrate for highly sensitive malachite green detection

The improper management and unreasonable use of malachite green (MG) in aquatic transportation and large-scale aquaculture pose a significant threat to human health. It is crucial to develop a rapid and reliable approach for detecting MG. In this study, hierarchically porous coralloid ZnO@Ag (C–ZnO@Ag) microspheres were developed as a surface-enhanced Raman scattering (SERS) substrate to detect MG content in water. The hierarchical and porous structure supporting plenty of Ag nanoparticles provides numerous “hot spots” to excite the strong enhanced local electromagnetic field for enlarging the Raman signals of analytes. Moreover, C–ZnO@Ag generates an additional pathway to improve the charge transfer between the substrate and analytes. The manifold mechanisms resulted in the Raman enhancement factor as high as 1.61 × 107 when R6G was selected as the probe. The MG solution at an ultralow concentration of 10−9 M can be successfully identified using the C–ZnO@Ag substrate, which is much lower than the maximum MG residual concentration in water set by the European Union. Therefore, the C–ZnO@Ag substrate has promising opportunities to be applied in rapid SERS-based detection of toxic organic residues.

Silver Dendrite‐Coated Silicon Pyramid Substrate as Surface‐Enhanced Raman Scattering Probe for Detecting Glucose

Raman spectroscopy offers a rapid and nondestructive method for qualitatively and quantitatively analyzing the molecular structure of substances. Herein, a facile and cost‐effective approach for the preparation of three‐dimensional (3D) surface‐enhanced Raman scattering (SERS) substrates is proposed, in which pyramid structures are fabricated using silicon anisotropic wet etching and silver dendrites are decorated on these silicon pyramid (PSi) substrates by immersing them in a mixture of hydrofluoric acid and silver nitrate for several minutes. The 3D SERS substrates, based on PSi coated with Ag dendrites, reveal high‐performance SERS enhancement (with an analytical enhancement factor reaching 3.54 × 1010) and can detect rhodamine 6G (R6G) in the presence of chemical enhancer (lithium chloride) at low concentrations down to 10−11 m. For glucose detection, 2‐thienylboronic acid is employed to faciliate glucose attachment to the substrate surface, achieving a detection limit as low as 10−6 m. The substrate exhibits good repeatability with a relative standard deviation of 11.223%, as well as reusability and long‐term stability for detection. The results also highlight the excellent sensitivity of the PSi‐based SERS substrate, which is expected to be instrumental in biochemical analysis and holds significant potential for developing noninvasive glucose sensor for diabetic patients using saliva samples.

Construction of an Au/g-C3N4/GO/Au substrate by a layer-by-layer assembly approach for surface-enhanced Raman spectroscopy

In this work, an Au/g-C3N4/GO/Au hybrid nanofilm for surface-enhanced Raman scattering (SERS) substrate application was prepared by a facile layer-by-layer assembly technique using nanosheet-structured graphitic carbon nitride (g-C3N4), graphene oxide (GO) and 40 nm-gold nanoparticles (Au NPs). The effects of composition, assembly sequence and assembly cycles on the SERS performance were optimized to achieve the SERS-active substrate. The detection limit of Au/g-C3N4/GO/Au substrate for crystal violet and rhodamine 6 G probe molecules reached as high as 10−8 M, with good stability and uniformity. Its further application in food colorants detection (erythrosine, carmine and temptation red) had successfully met the national food safety standards and the quantitative detection for erythrosine and temptation red had also been established. Based on finite-difference time-domain element simulation and density functional theory quantum chemical calculation, the mechanism of the SERS effect of the substrate was unveiled, which is attributed to the combination of electromagnetic enhancement effect of Au nanoparticle aggregates and chemical enhancement effect of GO and g-C3N4. Notably, water droplet evaporation induced Raman enhancement was observed on the Au/g-C3N4/GO/Au substrate. This can be ascribed to the inhomogeneous evaporation of the droplet that promotes the enrichment of the probe molecules into the center of the droplet. This novel enhancement strategy provides a new idea for further improving detection sensitivity of SERS substrate materials.

Charge-transfer-driven ultrasensitive SERS sensing in a two-dimensional titanium carbonitride MXene.

Two-dimensional (2D) MXenes stand out as promising platforms for surface-enhanced Raman scattering (SERS) sensing owing to their metallic feature, various compositions, high surface area, compatibility with functionalization, and ease of fabrication. In this work, we report a high-performance 2D titanium carbonitride (Ti3CN) MXene SERS substrate. We reveal that the abundant electronic density of states near the Fermi level of Ti3CN MXene boosts the efficiency of photo-induced charge transfer at the interface of Ti3CN/molecule, resulting in significant Raman enhancement. The SERS sensitivity of Ti3CN MXene is further promoted through a 2D morphology regulation and molecular enrichment strategies. Moreover, prohibited drugs are detectable on this substrate, presenting the potential of trace-amount analysis on Ti3CN MXene. This work provides a deep insight of the SERS mechanisms of Ti3CN MXene and broadens the practical application of transition metal carbonitride MXene SERS substrates.

Cellulose Nanofiber Films with Gold Nanoparticles Electrostatically Adsorbed for Facile Surface-Enhanced Raman Scattering Detection.

Cellulose nanofiber (CNF) holds great promise in applications such as surface-enhanced Raman scattering (SERS), catalysis, esthesia, and detection. This study aimed to build novel CNF-based SERS substrates through a facile synthetic method. Citrate-reduced gold nanoparticles (AuNPs) were adsorbed on the cationized CNF surface due to electrostatic interactions, and uniform AuNPs@(2,3-epoxypropyl trimethylammonium chloride)EPTMAC@CNF flexible SERS substrates were prepared by a simple vacuum-assisted filtration method. The probe molecule methylene blue was chosen to assess the performance of the CNF-based SERS substrate with a sensitivity up to 10-9 M, superior signal reproducibility (relative standard deviation (RSD) = 4.67%), and storage stability (more than 30 days). Tensile strength tests indicated that the CNF-based films had good mechanical properties. In addition, CNF-based substrates can easily capture and visually identify microplastics in water. These results demonstrate the potential application of the flexible, self-assembled AuNPs@EPTMAC@CNF flexible SERS substrate for prompt and sensitive detection of trace substances.

TiO2 multi-leg nanotubes for surface-enhanced Raman scattering

Abstract In the recent past, significant research efforts have been put forth to fabricate cost-effective substrates for surface-enhanced Raman scattering (SERS) applications. Here we propose semiconducting TiO2 multi-leg nanotubes and Au nanoparticle-coated TiO2 multi-leg nanotubes (TiO2 MLNTs and Au/TiO2 MLNTs) as SERS substrates. The unique multi-leg architecture of TiO2 nanotubes demonstrated enhanced light-harvesting properties facilitated by an induced photonic absorption edge. Remarkable high SERS sensitivity is observed towards the detection of Methylene blue (MB), up to nM concentration (E.F. ~104) using TiO2 MLNTs. The same is attributed to the resonantly matched photonic absorption edge of TiO2 MLNTs with the wavelength of incident laser probe light. On the other hand, the Au nanoparticle coating further leveraged the light absorption ability of TiO 2 MLNTs with the aid of localized surface plasmon resonance mode (LSPRs). As such, Au/TiO2 MLNTs showed excellent enhancement in SERS sensitivity (E.F. ~105, for nM of MB) facilitated by the synergy between the plasmonic modes of Au and the photonic absorption mode of TiO2 MLNTs. UV-Vis diffuse reflectance and Raman spectroscopy measurements are highlighted to elucidate the light absorption and SERS sensitivity of the TiO2 and Au/TiO2 MLNTs.

Single-cell SERS imaging of dual cell membrane receptors expression influenced by extracellular matrix stiffness

Membrane receptors perform a diverse range of cellular functions, accounting for more than half of all drug targets. The mechanical microenvironment regulates cell behaviors and phenotype. However, conventional analysis methods of membrane receptors often ignore the effects of the extracellular matrix stiffness, failing to reveal the heterogeneity of cell membrane receptors expression. Herein, we developed an in-situ surface-enhanced Raman scattering (SERS) imaging method to visualize single-cell membrane receptors on substrates with different stiffness. Two SERS substrates, Au@4-mercaptobenzonitrile@Ag@Sgc8c and Au@4-pethynylaniline@Ag@SYL3c, were employed to specifically target protein tyrosine kinase-7 (PTK7) and epithelial cell adhesion molecule (EpCAM), respectively. The polyacrylamide (PA) gels with tunable stiffness (2.5–25 kPa) were constructed to mimic extracellular matrix. The simultaneous SERS imaging of dual membrane receptors on single cancer cells on substrates with different stiffness was achieved. Our findings reveal decreased expression of PTK7 and EpCAM on cells cultured on stiffer substrates and higher migration ability of the cells. The results elucidate the heterogeneity of membrane receptors expression of cells cultured on the substrates with different stiffness. This single-cell analysis method offers an in-situ platform for investigating the impacts of extracellular matrix stiffness on the expression of membrane receptors, providing insights into the role of cell membrane receptors in cancer metastasis.

Detection and Identification of Pesticides in Fruits Coupling to an Au-Au Nanorod Array SERS Substrate and RF-1D-CNN Model Analysis.

In this research, a method was developed for fabricating Au-Au nanorod array substrates through the deposition of large-area Au nanostructures on an Au nanorod array using a galvanic cell reaction. The incorporation of a granular structure enhanced both the number and intensity of surface-enhanced Raman scattering (SERS) hot spots on the substrate, thereby elevating the SERS performance beyond that of substrates composed solely of an Au nanorod. Calculations using the finite difference time domain method confirmed the generation of a strong electromagnetic field around the nanoparticles. Motivated by the electromotive force, Au ions in the chloroauric acid solution were reduced to form nanostructures on the nanorod array. The size and distribution density of these granular nanostructures could be modulated by varying the reaction time and the concentration of chloroauric acid. The resulting Au-Au nanorod array substrate exhibited an active, uniform, and reproducible SERS effect. With 1,2-bis(4-pyridyl)ethylene as the probe molecule, the detection sensitivity of the Au-Au nanorod array substrate was enhanced to 10-11 M, improving by five orders of magnitude over the substrate consisting only of an Au nanorod array. For a practical application, this substrate was utilized for the detection of pesticides, including thiram, thiabendazole, carbendazim, and phosmet, within the concentration range of 10-4 to 5 × 10-7 M. An analytical model combining a random forest and a one-dimensional convolutional neural network, referring to the important variable-one-dimensional convolutional neural network model, was developed for the precise identification of thiram. This approach demonstrated significant potential for biochemical sensing and rapid on-site identification.

Metal-Organic Framework-Enabled Trapping of Volatile Organic Compounds into Plasmonic Nanogaps for Surface-Enhanced Raman Scattering Detection.

Utilizing electromagnetic hotspots within plasmonic nanogaps is a promising approach to create ultrasensitive surface-enhanced Raman scattering (SERS) substrates. However, it is difficult for many molecules to get positioned in such nanogaps. Metal-organic frameworks (MOFs) are commonly used to absorb and concentrate diverse molecules. Herein, we combine these two strategies by introducing MOFs into plasmon-coupled nanogaps, which has so far remained experimentally challenging. Ultrasensitive SERS substrates are fabricated through the construction of nanoparticle-on-mirror structures, where Au nanocrystals are encapsulated with a zeolitic imidazolate framework-8 (ZIF-8) shell and then coupled to a gold film. The ZIF-8 shell, as a spacer that separates the Au nanocrystal and the Au film, can be adjusted in thickness over a wide range, which allows the electric field enhancement and plasmon resonance wavelength to be varied. By trapping Raman-active molecules within the ZIF-8 shell, we show that our plasmon-coupled structures exhibit a superior SERS detection performance. A range of volatile organic compounds at the concentrations of 10-2 mg m-3 can be detected sensitively and reliably. Our study therefore offers an attractive route for synergistically combining plasmonic electric field enhancement and MOF-enabled molecular enrichment to design and create SERS substrates for ultrasensitive detection.

Differentiating Plasmon-Enhanced Chemical Reactions on AgPd Hollow Nanoplates through Surface-Enhanced Raman Spectroscopy.

Plasmonic photocatalysis demonstrates great potential for efficiently harnessing light energy. However, the underlying mechanisms remain enigmatic due to the transient nature of the reaction processes. Typically, plasmonic photocatalysis relies on the excitation of surface plasmon resonance (SPR) in plasmonic materials, such as metal nanoparticles, leading to the generation of high-energy or "hot electrons", albeit accompanied by photothermal heating or Joule effect. The ability of hot electrons to participate in chemical reactions is one of the key mechanisms, underlying the enhanced photocatalytic activity observed in plasmonic photocatalysis. Interestingly, surface-enhanced Raman scattering (SERS) spectroscopy allows the analysis of chemical reactions driven by hot electrons, as both SERS and hot electrons stem from the decay of SPR and occur at the hot spots. Herein, we propose a highly efficient SERS substrate based on cellulose paper loaded with either Ag nanoplates (Ag NPs) or AgPd hollow nanoplates (AgPd HNPs) for the in situ monitoring of C-C homocoupling reactions. The data analysis allowed us to disentangle the impact of hot electrons and the Joule effect on plasmon-enhanced photocatalysis. Computational simulations revealed an increase in the rate of excitation of hot carriers from single/isolated AgPd HNPs to an in-plane with a vertical stacking assembly, suggesting its promise as a photocatalyst under broadband light. In addition, the results suggest that the incorporation of Pd into an alloy with plasmonic properties may enhance its catalytic performance under light irradiation due to the collection of plasmon-excitation-induced hot electrons. This work has demonstrated the performance-oriented synthesis of hybrid nanostructures, providing a unique route to uncover the mechanism of plasmon-enhanced photocatalysis.

Potential of a deep eutectic solvent in silver nanoparticle fabrication for antibiotic residue detection.

Deep eutectic solvents (DESs) have recently emerged as an alternative solvent for nanoparticle synthesis. There have been numerous advancements in the fabrication of silver nanoparticles (Ag NPs), but the potential of DESs in Ag NP synthesis was neither considered nor studied carefully. In this study, we present a novel strategy to fabricate Ag NPs in a DES (Ag NPs-DES). The DES composed of ᴅ-glucose, urea, and glycerol does not contain any anions to precipitate with Ag+ cations. Our Ag NPs-DES sample is used in a surface-enhanced Raman scattering (SERS) sensor. The two analytes for SERS quantitation are nitrofurantoin (NFT) and sulfadiazine (SDZ) whose residues can be traced down to 10-8 M. The highest enhancement factors (EFs) are competitive at 6.29 × 107 and 1.69 × 107 for NFT and SDZ, respectively. Besides, the linearity coefficients are extremely close to 1 in the range of 10-8 to 10-3 M of concentration, and the SERS substrate shows remarkable uniformity along with great selectivity. This powerful SERS performance indicates that DESs have tremendous potential in the synthesis of nanomaterials for biosensor substrate construction.