Flexible Surface-enhanced Raman Scattering Research Articles

Preparation of flexible SERS substrate with excellent performance based on the electrospraying technique

Paper-based flexible surface-enhanced Raman scattering (SERS) substrate has significant advantages in the detection of pesticide residues on the surface of fruits and vegetables due to its full contact with the sample surface. However, it is found that the development of new paper-based flexible SERS substrate preparation technology is still necessary through the evaluation of the current preparation technology. In addition, the development of new application scenarios can also promote the further development of SERS technology. Herein, a highly sensitive paper-based flexible SERS substrate is prepared by depositing Cu2O/Ag(4) composite particles on commercial filter paper by electrospraying technique. Compared with other preparation technologies, in addition to the characteristics of simplicity and speed, more importantly, it will not cause waste of nanoparticles. By adjusting the parameters, the optimized substrate shows excellent SERS performance with the minimum detection concentrations are 10−9 M and 10−9 M for R6G and thiram, respectively. It also has good linear correlation of concentration (R2 = 0.952), good reproducibility, and excellent time stability. Furthermore, based on the good filtration characteristics of commercial filter paper, the rapid detection of pesticide residues in soil was successfully realized. This proposed a new scheme for the practical application of SERS technology in the field of food and environmental safety.

Flexible Surface-Enhanced Raman Scattering (SERS) sensor for residue-free pesticide detection based on agriculture 4.0 concepts

Given the health and environmental risks associated with pesticide misuse, achieving zero pesticide residues is pivotal in Agriculture 4.0. Traditional detection methods such as HPLC and GC-MS are both complex and time-consuming. In contrast, surface-enhanced Raman scattering (SERS) offers rapid detection and high sensitivity, aligning with the efficiency and accuracy requirements of Agriculture 4.0. In this study, we developed a high-performance flexible substrate using a simple chemical synthesis method. We used material adsorption, anisotropic charge attraction and electron migration to facilitate the growth of the substrate material, which promoted more 'hot spots' and electron transfer, and continued optimisation of the preparation process, which resulted in a significant increase in spectral intensity. The substrate demonstrated outstanding detection capability, with a detection limit of 10−15 M for thiabendazole (TBZ). In practical fruit testing, TBZ residue concentrations on the surface of American cherries could be detected as low as 10−8 mg/mL, well below China's prescribed limit of 5 mg/kg. Relative to previous work in the field of pesticide detection, our study has lower detection limits and concentrations, as well as lower cost and simpler preparation, which provide more options for the detection of very low concentrations of hazardous substances. At the same time, it was confirmed that SERS is consistent with the zero pesticide residue goal of Agriculture 4.0, demonstrating practical efficacy and accuracy within this framework.

Flexible Multicavity SERS Substrate Based on Ag Nanoparticle-Decorated Aluminum Hydrous Oxide Nanoflake Array for Highly Sensitive In Situ Detection.

Flexible surface-enhanced Raman scattering (SERS) substrates are very promising to meet the needs for real-time and on-field detection in practical applications. However, high-performance flexible SERS substrates often suffer from complexity and high cost in fabrication, limiting their widespread applications. Herein, we developed a facile method to fabricate a flexible multicavity SERS substrate composed of a silver nanoparticle (AgNP)-decorated aluminum hydrous oxide nanoflake array (NFA) grown on a polydimethylsiloxane (PDMS) membrane. Strong plasmon couplings promoted by multiple nanocavities afford high-density hotspots within such a flexible AgNPs@NFA/PDMS film, boosting high SERS sensitivity with an enhancement factor (EF) of ∼1.54 × 109, and a limit of detection (LOD) of ∼7.4 × 10-13 M for rhodamine 6G (R6G) molecules. Furthermore, benefiting from the high sensitivity, high mechanical stability, and transparency of this substrate, in situ SERS detections of trace thiram and crystal violet (CV) molecules on the surface of cherry tomatoes and fish have been realized, with LODs much lower than the maximum allowable limit in food, demonstrating the great potential of such a flexible substrate in food safety monitoring. More importantly, the preparation processes are very simple and environmentally friendly, and the techniques involved are completely compatible with well-established silicon device technologies. Therefore, large-area fabrication with low cost can be readily realized, enabling the extensive applications of SERS sensors in daily life.

Self-Assembly of Strain-Adaptable Surface-Enhanced Raman Scattering Substrate on Polydimethylsiloxane Nanowrinkles.

Flexible surface-enhanced Raman scattering (SERS) substrates adaptable to strains enable effective sampling from irregular surfaces, but the preparation of highly stable and sensitive flexible SERS substrates is still challenging. This paper reports a method to fabricate a high-performance strain-adaptable SERS substrate by self-assembly of Au nanoparticles (AuNPs) on polydimethylsiloxane (PDMS) nanowrinkles. Nanowrinkles are created on prestrained PDMS slabs by plasma-induced oxidation followed by the release of the prestrain, and self-assembled AuNPs are transferred onto the nanowrinkles to construct the high-performance SERS substrate. The results show that the nanowrinkled structure can improve the surface roughness and enhance the SERS signals by ∼4 times compared to that of the SERS substrate prepared on flat PDMS substrates. The proposed SERS substrate also shows good adaptability to dynamic bending up to ∼|0.4| 1/cm with excellent testing reproducibility. Phenolic pollutants, including aniline and catechol, were quantitatively tested by the SERS substrate. The self-assembled flexible SERS substrate proposed here provides a powerful tool for chemical analysis in the fields of environmental monitoring and food safety inspection.

Silver Nanoparticle-Immobilized Cotton Fabric Serves as Flexible Surface-Enhanced Raman Scattering Substrate for Detection of Toxin

We designed composite materials containing silver nanoparticles (AgNPs) and cotton fabric (CF). The cellulose in cotton fabric contains -OH groups. These -OH groups were deprotonated by a pretreatment process, and Ag+ ions were allowed to bind. In the consecutive step, the Ag+ ions were reduced to fiber-bound AgNPs, generating AgNP@CF. Three different AgNP@CF composites were created, varying the concentration of the precursor AgNO3 solution. The composite materials were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDX), powder X-ray diffraction (XRD), and FTIR spectroscopy. The AgNP@CF composites were assessed for the detection of toxins using the surface-enhanced Raman scattering (SERS) technique.

Flexible Surface-Enhanced Raman Scattering Tape Based on Ag Nanostructured Substrate for On-Site Analyte Detection.

Surface-enhanced Raman scattering (SERS) has emerged as a powerful surface analytical technique that amplifies Raman scattering signals of molecules adsorbed onto metal nanostructured surfaces. The droplet reaction method has recently been employed to fabricate large-scale microring patterns of silver (Ag) nanostructures on rigid substrates, which enables sensitive detection within the ring area. However, these rigid substrates present limitations for direct on-site detection of analyte residues on irregular sample surfaces. There is a need to develop soft and flexible SERS substrates that can intimately conform to arbitrary surfaces. In this study, we presented a SERS substrate using flexible and adhesive tape as the supporting material. This SERS tape was fabricated by repeatedly transferring presynthesized Ag nanostructures from a rigid substrate to the tape. For a model compound adenine, our SERS tape exhibited a good linear response from 5 × 10-4 M to 5 × 10-5 M with a low limit of detection (LOD) of 5 × 10-7 M and displayed a SERS enhancement factor (EF) of 3.2 × 105. The relative standard deviation (RSD) of SERS intensity achieved was as low as 1.93%, indicating its outstanding uniformity. The as-prepared SERS tape was used for in situ detection of pesticide residue on an apple surface and dye residue on human hair. Leveraging the large surface area of Ag nanostructure patterns from the droplet reaction, the developed SERS tape demonstrates excellent performance in terms of sensitivity and uniformity. The successful detection of analyte residues on arbitrary surfaces of apple and human hair highlights the potential of this flexible SERS tape for real-world applications across various industries for enhanced diagnostic accuracy.

A simple low-cost flexible plasmonic patch based on spiky gold nanostars for ultra-sensitive SERS sensing.

Recently, transparent and flexible surface-enhanced Raman scattering (SERS) substrates have received great interest for direct point-of-care detection of analytes on irregular nonplanar surfaces. In this study, we proposed a simple cost-effective strategy to develop a flexible SERS patch utilizing multibranched sharp spiked gold nanostars (GNS) decorated on a commercially available adhesive Scotch Tape for achieving ultra-high SERS sensitivity. The experimental SERS measurements were correlated with theoretical finite element modeling (FEM), which indicates that the GNS having a 2.5 nm branch tip diameter (GNS-4) exhibits the strongest SERS enhancement. Using rhodamine 6G (R6G) as a model analyte, the SERS performance of the flexible SERS patch exhibited a minimum detection limit of R6G as low as 1 pM. The enhancement factor of the SERS patch with GNS-4 was calculated as 6.2 × 108, which indicates that our flexible SERS substrate has the potential to achieve ultra-high sensitivity. The reproducibility was tested with 30 different spots showing a relative standard deviation (RSD) of SERS intensity of about 5.4%, indicating good reproducibility of the SERS platform. To illustrate the usefulness of the flexible SERS sensor patch, we investigated the detection of a carcinogenic compound crystal violet (CV) on fish scales, which is often used as an effective antifungal agent in the aquaculture industry. The results realized the trace detection of CV with the minimum detection limit as low as 1 pM. We believe that our transparent, and flexible SERS patch based on GNS-4 has potential as a versatile, low-cost platform for real-world SERS sensing applications on nonplanar surfaces.

Au-coated quartz fabric by plasma treatment as a flexible SERS substrate for rapid detection of harmful substances

Food safety remains a global concern and there is always demanded to advance methods to ensure that toxic substances and contamination do not pose safety concerns. This study discusses the development of a rapid, low-cost, portable, in situ method for the detection of harmful substances on the surface of fruits and vegetables to ensure safety for human consumption. Gold nanoparticles (Au NPs) are deposited onto quartz fabric by using a magnetron sputtering system. The argon flow rate and sputtering time are both controlled to produce Au NPs of different sizes on the quartz fabric with different gap distances. Scanning electron microscope images, X-ray diffraction spectra, and Raman intensity are used to evaluate the produced substrates. With an average grain size of about 32.35 nm, the Au particles with a thickness of 70 nm deposited onto the quartz fabric (i.e., Qt-70) provide the best surface-enhanced Raman scattering (SERS) performance of 65,639 counts towards a 10−3 M methylene blue (MB) solution. The results show that the Qt-70 SERS substrate is highly sensitive, reproducible, and stable, and demonstrates good reusability. Images of “hotspots” that form between two Au nanoparticles based on electric field distribution are simulated by using the finite-difference time-domain (FDTD) method to explain for the signal enhancement. In addition, Qt-70 can be used for the direct collection of pesticides, such as Rhodamine B (RhB), Rhodamine 6G (R6G), and Malachite green (MG), from food surfaces. This novel flexible SERS (FSERS) substrate has good potential for the rapid detection of harmful substances on food.

Fabrication of polydimethylsiloxane (PDMS)-Based Flexible Surface-Enhanced Raman Scattering (SERS) Substrate for Ultrasensitive Detection.

This article presents a fabrication method for a flexible substrate designed for Surface-Enhanced Raman Scattering (SERS). Silver nanoparticles (AgNPs) were synthesized through a complexation reaction involving silver nitrate (AgNO3) and ammonia, followed by reduction using glucose. The resulting AgNPs exhibited a uniform size distribution ranging from 20 nm to 50 nm. Subsequently, 3-aminopropyl triethoxysilane (APTES) was employed to modify a PDMS substrate that had been surface-treated with oxygen plasma. This process facilitated the self-assembly of AgNPs onto the substrate. A systematic evaluation of the impact of various experimental conditions on substrate performance led to the development of a SERS substrate with excellent performance and an Enhanced Factor (EF). Utilizing this substrate, impressive detection limits of 10-10 M for R6G (Rhodamine 6G) and 10-8 M for Thiram were achieved. The substrate was successfully employed for detecting pesticide residues on apples, yielding highly satisfactory results. The flexible SERS substrate demonstrates great potential for real-world applications, including detection in complex scenarios.

Flexible silver ring SERS substrate array fabrication by vortex evaporation method and its application for high sensitive detection of sulfonamides residues in water

Flexible surface-enhanced Raman scattering (SERS) substrates have driven much attention in Raman detection of environmental pollutants due to their unique advantage of sensitivity, low-cost and fast sampling. However, it is still a high challenge for fabricating flexible SERS substrate with high reproducibility and sensitivity. In this study, we developed a novel silver nanoparticle assembly method based on vortex evaporation method to batch assemble multiple silver ring (SR) SERS substrate array on a parafilm. The flexible SR SERS substrates were uniformly covered with active silver nano-islands, which significantly improved the Raman signal intensity of the targets by 126 folds and showed 5 times Raman enhancement compared with the common SERS substrate by direct evaporation method, and also represented the unique bending response properties of flexible substrate. The Raman detection for sulfonamide residues in water with SR SERS substrate represented high sensitivity, which limits of detection for Sulfapyridine and Sulfacloropyridazine were 9.46 and 9.3 × 10−8 mol/L, respectively. The quantitative relationships were obtained in wide linear range of 4 orders with good accuracy and stability. The flexible SR SERS substrate array can be large-scale prepared with good repeatability, stability, and low-cost, which has promising applications for trace contaminants detection in water environment.

Flexible, high-performance and facile PVA/cellulose/Ag SERS chips for in-situ and rapid detection of thiram pesticide in apple juice

Flexible surface-enhanced Raman scattering (SERS) sensors have gained significant attention for their practical applications in detecting chemical and biological molecules. However, the fabrication of flexible SERS chips is often complex and requires advanced techniques. In this study, we present a simple and rapid method to design a flexible SERS chip based on polyvinyl alcohol (PVA), cellulose, and silver nanoparticles (AgNPs) using mechanical stirring and drying methods. Benefiting from the abundant hydroxide groups on cellulose, AgNPs easily adhere and distribute evenly on the cellulose surface. The combination of PVA and cellulose forms a bendable film-like SERS chip. This chip allows convenient immersion in liquid analyte samples. We demonstrate its effectiveness by using it to detect the thiram pesticide in apple juice using the “dip and dry” method, achieving an outstanding detection limit of 1.01 × 10−8 M. The Raman signals on the SERS chips exhibit high repeatability and reproducibility, with relative standard deviation values below 10%. These findings show that the flexible PVA/cellulose/Ag SERS chips is a strong candidate for real-world analysis.

Fabrication of flexible multidimensional CC/MoS2@Ag@PDMS hybrids as stable and self-cleaning SERS substrate for sensitive and quantitative point-of-care testing

Flexible surface-enhanced Raman scattering (SERS) sensors are ideal for point-of-care testing (POCT) of hazardous materials. The key to practical applications lies in their quantitative detection capabilities and high stability for cycle use. In this study, we propose a simple method to develop a recoverable CC/MoS2@Ag@PDMS composite SERS substrate using chemical vapor deposition (CVD) technology. This flexible SERS substrate, utilizing 4-aminothiophenol (4-ATP) as the detection molecule, demonstrated a high enhancement factor (∼ 107) and a low detection limit (10−12 M). The corrected linearity problem achieved good linear correlation (R2 = 0.997) by using the intrinsic Raman signal from the polydimethylsiloxane (PDMS) substrate. The results of theoretical calculations illustrate this excellent SERS performance by a combination of electromagnetic and chemical enhancements. In addition, in the presence of MoS2, the substrate demonstrated excellent self-cleaning cycle detection and maintained high SERS activity through more than 100 mechanical deformations of bending and twisting. In situ detection was performed for tetramethylthiuram disulfide (TMTD), ampicillin (AMP), and ciprofloxacin (CI) with detection limits of 10−9 M. These promising detection results suggest that this highly stable and flexible substrate can be used for POCT and environmental safety by simply wiping objects to obtain contaminant samples.

One-pot platform for the collection and detection of nanoparticles: Flexible surface-enhanced Raman scattering (SERS) substrates with nano-pore structure

The potential of using flexible surface-enhanced Raman scattering (SERS) for single polymer nanoparticle detection has been recognized, however, most studies have used SERS substrates consisting of metal nanoparticles (MNPs) on hard materials, which have limited volume analysis and can easily be damaged. To overcome these issues, researchers have conducted recent studies on flexible or 3D-structured SERS substrates. This study used polydimethylsiloxane (PDMS) membranes for flexible substrates, Ag nanowires (AgNWs) to form nano-pores, and PDMS-polyethylene glycol (PEG) block copolymer (BCP) to improve solvent application. The SERS substrates were able to detect rhodamine 6G (R6G) probes with a limit of detection (LOD) of 7.06 × 10−11 M, and were mechanically stable under various conditions such as bending, stretching, and torsion. The nano-pores of the SERS substrates could separate polystyrene (PS) particles from the solution, and filtered particles were visually distinguishable from AgNWs using a dark field microscope. The flexibility of the SERS substrates also allows for swab sampling of irregular surfaces. We were able to detect up to 10–10 M of crystal violet (CV) in the contaminated scallops and collect and detect PS in stainless-steel structures covered with 200 nm PS particles. Overall, the study shows the potential of using flexible SERS substrates for single polymer nanoparticle detection in various fields.

Flexible surface-enhanced Raman scattering substrate of cotton swab-Ag combination with smartphone app for chemical warfare agent simulants detection

A simple method was developed for the one-step synthesis of silver nanoparticles (AgNPs), co-stabilized by poly[N-(3-trimethoxysilylpropyl)diethylenetriamine] (PATS) and embedded on a flexible cotton swab (CS). PATS served as the capping agent for AgNPs. The flexible CS-PATS-AgNPs substrate was subjected to surface-enhanced Raman scattering (SERS) for the detection of single and multiple chemical warfare agent simulants (CWAS). SERS peak intensity versus concentration changes were rapidly detected and analyzed using a self-developed smartphone-based app system, which performs quantitative detection of the analyte. The results showed that CWAS (dimethyl methylphosphonate, DMMP; 2-chloroethylethylsulfide, 2-CEES; acetonitrile, ACN can be detected with a high sensitivity, with a limit of detection (LOD) of DMMP, 2-CEES and ACN was 1.0, 46.7 and 57.9 g/L, respectively. The flexible SERS substrate, CS-PATS-AgNPs, in conjunction with a Raman spectrometer and a smartphone-based app system, possesses practical applications primarily owing to the low cost and simple sampling technique.

Fabrication of flexible SERS substrate based on Au nanostars and PDMS for sensitive detection of Thiram residue in apple juice

We developed a novel fabrication of flexible surface-enhanced Raman scattering (SERS) substrate to perform selective and sensitive determination of thiram residue in fruits and juices. Au nanostars (Au NSs) with multi-branching structure were self-assembled on aminated Polydimethylsiloxane (PDMS) slides by electrostatic interaction. By measuring the Thiram’s characteristic peak intensity at 1371 cm−1, the SERS method could distinguish Thiram from other pesticide residues. A good linear relationship between the peak intensity at 1371 cm−1 and thiram’s concentration was established at the range from 0.01 ppm to 100 ppm and the Limit of detection is 0.0048 ppm. We directly used this SERS substrate to detect Thiram in apple juice. By standard addition method, recoveries varied in the range of 97.05% to 106.00% and the RSD were from 3.26% to 9.35%. The SERS substrate exhibited a good sensitivity, stability and selectively for the detection of Thiram in food samples, which can be spread as a common method for the detection of pesticides in food samples.

Plasmonic Coupling of Au Nanoclusters on a Flexible MXene/Graphene Oxide Fiber for Ultrasensitive SERS Sensing.

High sensitivity, good signal repeatability, and facile fabrication of flexible surface enhanced Raman scattering (SERS) substrates are common pursuits of researchers for the detection of probe molecules in a complex environment. However, fragile adhesion between the noble-metal nanoparticles and substrate material, low selectivity, and complex fabrication process on a large scale limit SERS technology for wide-ranging applications. Herein, we propose a scalable and cost-effective strategy to a fabricate sensitive and mechanically stable flexible Ti3C2Tx MXene@graphene oxide/Au nanoclusters (MG/AuNCs) fiber SERS substrate from wet spinning and subsequent in situ reduction processes. The use of MG fiber provides good flexibility (114 MPa) and charge transfer enhancement (chemical mechanism, CM) for a SERS sensor and allows further in situ growth of AuNCs on its surface to build highly sensitive hot spots (electromagnetic mechanism, EM), promoting the durability and SERS performance of the substrate in complex environments. Therefore, the formed flexible MG/AuNCs-1 fiber exhibits a low detection limit of 1 × 10-11 M with a 2.01 × 109 enhancement factor (EFexp), signal repeatability (RSD = 9.80%), and time retention (remains 75% after 90 days of storage) for R6G molecules. Furthermore, the l-cysteine-modified MG/AuNCs-1 fiber realized the trace and selective detection of trinitrotoluene (TNT) molecules (0.1 μM) via Meisenheimer complex formation, even by sampling the TNT molecules at a fingerprint or sample bag. These findings fill the gap in the large-scale fabrication of high-performance 2D materials/precious-metal particle composite SERS substrates, with the expectation of pushing flexible SERS sensors toward wider applications.

Application of Cotton Swab–Ag Composite as Flexible Surface-Enhanced Raman Scattering Substrate for DMMP Detection

It is both important and required to quickly and accurately detect chemical warfare agents, such as the highly toxic nerve agent sarin. Surface-enhanced Raman scattering (SERS) has received considerable attention due to its rapid results, high sensitivity, non-destructive data acquisition, and unique spectroscopic fingerprint. In this work, we successfully prepared SERS cotton swabs (CSs) for the detection of the sarin simulant agent dimethyl methyl phosphonate (DMMP) by anchoring N1-(3-trimethoxysilylpropyl) diethylenetriamine (ATS)/silver nanoparticle (AgNP) nanocomposites on CSs using ATS as the stabilizer and coupling agent. Simultaneously, the binding mode and reaction mechanics between the AgNP, ATS, and CS were confirmed by XPS. The modified CSs exhibited good uniformity, stability, and adsorption capability for SERS measurements, enabling the adsorption and detection of DMMP residue from an irregular surface via a simple swabbing process, with a detection limit of 1 g/L. The relative standard deviations (RSDs) of RSD710 = 5.6% had high reproducibility. In this research, the fabrication method could easily be extended to other cellulose compounds, such as natural fibers and paper. Furthermore, the versatile SERS CSs can be used for the on-site detection of DMMP, particularly in civil and defense applications, to guarantee food security and the health of the population.

Flexible PDMS-Based SERS Substrates Replicated from Beetle Wings for Water Pollutant Detection

The flexible surface-enhanced Raman scattering (SERS) sensor, which has the bionic 3D nanoarray structure of a beetle-wing substrate (BWS), was successfully prepared by replicated technology and thermal evaporation. The bionic structure was replicated with polydimethylsiloxane (PDMS) and then silver (Ag) nanoisland thin films were deposited by thermal evaporation. The deposition times and thicknesses (25-40 nm) of the Ag thin films were manipulated to find the optimal SERS detection capability. The Ag nanoisland arrays on the surface of the bionic replicated PDMS were observed by scanning electron microscope (SEM), X-ray diffraction (XRD), and contact angle, which can generate strong and reproducible three-dimensional hotspots (3D hotspots) to enhance Raman signals. The water pollutant, rhodamine 6G (R6G), was used as a model molecule for SERS detection. The results show that 35 nm Ag deposited on a PDMS-BWS SERS substrate displays the strongest SERS intensity, which is 10 times higher than that of the pristine BWS with 35 nm Ag coating, due to the excellent 3D bionic structure. Our results demonstrate that bionic 3D SERS sensors have the potential to be applied in wearable devices and sensors to detect biomolecules and environmental pollutants, such as industrial wastewater, in the future.

Monodisperse Ag Nanoparticle-Decorated Bacterial Nanocellulose as Flexible Surface-Enhanced Raman Scattering Sensors for Trace Detection of Toxic Thiram

Monodisperse Ag Nanoparticle-Decorated Bacterial Nanocellulose as Flexible Surface-Enhanced Raman Scattering Sensors for Trace Detection of Toxic Thiram

Ag Nanoparticles@Agar Gel as a 3D Flexible and Stable SERS Substrate with Ultrahigh Sensitivity.

Flexible surface-enhanced Raman scattering (SERS) substrates have become one of the research hot spots due to the facile sampling by swabbing or wrapping on rough surfaces and the sensitive and nondestructive detection of contaminants. In this work, we proposed a simple and fast in situ reduction method to prepare Ag nanoparticles (Ag NPs) composited agar hydrogel (Ag NPs@Agar) flexible SERS substrate. Owing to the three-dimensional (3D) structure, good hydrophilicity and adsorption of the agar hydrogel, Ag NPs were grown uniformly in the 3D cross-linked structure. The distribution density of Ag NPs was further increased by the volume shrinkage when the hydrogel was dried in air. This high density and uniformly distribution of Ag NPs produced a large number of highly active SERS regions. In addition, the sensitivity of Ag NPs@Agar was further improved with the assistance of hydrophilic agar gel, which can trap the probe molecules into highly active SERS areas. The SERS results showed that the substrate can be used to detect dye molecules (rhodamine 6G), the minimum detectable concentration was 10-15 M, the relative standard deviation tested at 18 different positions was only 7.58%, and the intensity of the characteristic peak at 611 cm-1 decreased only about 10% after 49 days of storage, demonstrating the superior stability. Moreover, the Ag NPs@Agar substrate also could successfully achieve the micro-trace detection of melamine and sodium penicillin G in Xinjiang specialty camel milk powder. The above available results show that the prepared flexible Ag NPs@Agar SERS substrates possess potentials for the illegal additives and antibiotics in food safety analysis.