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The field of semiconductor surface‐enhanced Raman scattering (SERS) substrates has experienced significant advancements, leading to a wide range of applications in several fields. However, the quest for new ultra‐sensitive semiconductor SERS materials is still of utmost importance. In this regard, an efficient and novel substrate, F4TCNQ/MoS2 heterostructure is introduced, assisted by V‐shaped aluminum anodic oxide (AAO) nanocavities with different depths. Utilizing the efficient charge transfer of organic/inorganic semiconducting heterostructure and the photoconfinement capability of the nanocavity structure of the AAO nanotemplate, excellent stability, fast sensing, enhanced Raman, and photodegradation activities are achieved. Due to its unique 3D structure, the optimized F4TCNQ/MoS2/AAO with 1500 nm depth achieves ultra‐high sensitivity detection of 9.0×10−16 M for conventional probe molecules. Furthermore, precise detection of water contaminants is observed for the first time with a V‐shaped heterostructure due to combined organic/inorganic features that differ significantly from conventional MoS2 structures or other metal/inorganic or inorganic/inorganic semiconductors. This research presents a novel and versatile strategy for SERS and demonstrates its diverse potential performance in practical applications. [ABSTRACT FROM AUTHOR]

Au@Pt core-satellite nanoparticles (CSNPs) with dual-functionality as both catalyst and surface-enhanced Raman scattering (SERS) substrate are successfully synthesized by decorating Pt nanocrystals on plasmonic Au colloids. The coupling "hotspot" structures at the Au-Pt interface significantly promotes the catalytic decarboxylation reaction, and provides spectroscopic insights into the molecule-plasmon interface in universal plasmon-promoted catalytic reactions. [Display omitted] Plasmon-induced hot carriers are a promising "active" energy source, attracting increasing attention for their potential applications in photocatalysis and photodetection. Here, we hybridize plasmonic Au spherical nanoparticles (SNPs) with catalytically active Pt nanocrystals to form Au@Pt core-satellite nanoparticles (CSNPs), which act as both an efficient catalyst for plasmon-promoted decarboxylation reaction and a robust surface-enhanced Raman scattering (SERS) substrate for plasmon-enhanced molecular spectroscopic detection. By regulating the coverage of Pt nanocrystals on the Au SNPs, we modulated the "hotspot" structures of the Au@Pt CSNPs to optimize the SERS detecting capability and catalytic decarboxylation performance. The coupling functionalities enable us with unique opportunities to in-situ SERS monitor universal reactions catalyzed by active catalysts (e.g. Pt, Pd) in the chemical industry in real-time. The decarboxylation rate of 4-mercaptophenylacetic acid was dynamically controlled by the surface catalytic decarboxylation step, following first-order overall reaction kinetics. Moreover, the reaction rate exhibited a strong correlation with the local field enhancement |E/E 0 |4 of the hotspot structure. This work provides spectroscopic insights into the molecule-plasmon interface under the plasmon-promoted catalytic reactions, guiding the rational design of the plasmonic interface of nanocatalysts to achieve desired functionalities. [ABSTRACT FROM AUTHOR]

Nucleic acids (deoxyribonucleic acid – DNA and ribonucleic acid – RNA) are essential components of all living organisms, with DNA encoding genetic information and RNA facilitating vital biological processes. The detection of nucleic acids having a specific sequence is crucial for identifying organisms and diagnosing genetic diseases. Because surface-enhanced Raman spectroscopy (SERS) is considered as one of the most promising analytical methods that offers important benefits such as short analysis time and exceptional sensitivity compared to other techniques, many groups are trying to apply SERS for nucleic acid detection. This review discusses how SERS spectroscopy can be used for DNA/RNA detection. Beginning with an overview of SERS theory, we delve into various SERS DNA/RNA sensors, including those based on a direct analysis of the SERS spectra of nucleic acids, and many types of sensors based on a selective hybridisation of probe and target nucleic acids. We describe how various types of sensors with increased sensitivity and reliability have evolved (from the first SERS DNA/RNA sensors described in the literature to recently developed ones). Challenges and future directions in SERS sensor development for nucleic acid detection and determination are also discussed. This comprehensive review aims to help researchers understand the field's nuances, and to foster advancements in the use of SERS spectroscopy in the medical sector. [ABSTRACT FROM AUTHOR]

A metasurface composed of silver nanoflower arrays, which exhibit asymmetrical absorption and surface‐enhanced Raman scattering (SERS) due to hybrid plasmonic effects, is reported. The silver nanoflowers are fabricated by oblique deposition of silver on a polymer nanohole array on a glass substrate, forming petal‐like semicontinuous thin films on the inner walls of the holes. Depending on the deposition angle, three‐ or five‐petal nanoflowers are obtained. The nanoflower arrays show strong reflection from the air side and broadband and wide‐angle absorption from the glass side, as a result of transmission surface plasmon resonance and localized surface plasmon resonance, respectively. The three‐petal structure, which absorbs most of the incident light from the glass side, induces a localized enhancement of electric field in the center of each nanohole, providing a high‐sensitivity SERS substrate. The SERS performance of the metasurface by direct measurement and near‐field simulation is demonstrated. [ABSTRACT FROM AUTHOR]

Tuberculosis is a highly infectious disease caused by the bacterium Mycobacterium tuberculosis, and the spread of this agent has caused serious health problems worldwide. The rapid and accurate detection of M. tuberculosis is essential for controlling the spread of infection and for preventing the emergence of multidrug-resistant strains. In this study, the powerful trans-cleavage ability of CRISPR-Cas12a for ssDNA was combined with a surface-enhanced Raman spectroscopy (SERS)–based strategy to establish a CRISPR-SERS sensor for the hypersensitive detection of M. tuberculosis DNA. We observed a linear relationship between the concentration of M. tuberculosis DNA and the output signal over the range of 5 to 100 pM. The equation describing the standard curve was y = 24.10x + 1594, with R2 = 0.9914. The limit of detection was as low as 4.42 pM for genomic DNA, and a plasmid containing an M. tuberculosis–specific sequence was detected at 5 copy/μL. A detection accuracy of 100% was achieved in the analysis of DNA isolated from the sputum of hospitalized patients with tuberculosis. The entire detection process is simple to deploy and only takes 50 min and results in the sensitive and specific detection of M. tuberculosis DNA. This study provides a new method for the detection of tuberculosis. The tool is stable and can be utilized on-site, and it thus broadens the diagnostic application of CRISPR-Cas12a-based sensor technology. [ABSTRACT FROM AUTHOR]

Surface-enhanced Raman scattering (SERS) is widely used for trace detection of substances, and the key to this technology lies in the preparation of the substrate material. In this study, a composite SERS material of Au NRs/4-MBA/PAM was constructed and characterized to better immobilize the reference molecule 4-mercaptobenzoic acid (4-MBA). Electron transmission microscopy results demonstrated that the PAM film helps Au NRs to pack closely, enhancing the stability of the material structure and reducing the interference of external environmental factors on the response of 4-MBA, thus improving the accuracy of quantitative determination. Comparative experimental results with the Au NRs/4-MBA substrate showed that the relative standard deviations (RSDs) of the detection results for MG on different batches of Au NRs/4-MBA/PAM were less than 8.0%, and the RSDs of different points on the same material were less than 10.0%, indicating that the Au NRs/4-MBA/PAM has higher uniformity, better reproducibility, and higher sensitivity in detecting malachite green (MG). Applying this material in the recovery determination of fish extract showed that the recovery rates of MG were between 75.60% and 83.24%. Therefore, the Au NRs/4-MBA/PAM substrate can accurately detect and quantify veterinary drug residue in complex matrices such as food tissue. [ABSTRACT FROM AUTHOR]

The surface of hydroxyapatite (HA) was functionalized with silver nanoparticles by reducing silver nitrate in the presence of glucose or hydrazine hydrochloride. Two types of (HA)Ag nanocomposite were obtained presumably possessing excess negative charge ((HA)Ag-I) or positive charge ((HA)Ag-II). Plasmonic coatings of (HA)Ag-I and (HA)Ag-II nanoparticles were formed on the surface of glass substrates using the droplet deposition method and their structural and spectral properties were studied. A comparative study of the intensity of surface-enhanced Raman scattering (SERS) spectra of cationic and anionic porphyrins CuTMpyP4 and CuTPPS4 as well as rhodamine 6G adsorbed on the surface of both types of nanocomposites was carried out. Plasmonic structures (HA)Ag-I provide the greatest enhancement of the SERS signal for the cationic porphyrin CuTMpyP4, while high spectral intensity is observed for the anionic porphyrin CuTPPS4 adsorbed on films of the (HA)Ag-II composite, which is almost forty times higher than for (HA)Ag-I. For Rh6G molecules with charge +1, the efficiency of the SERS signal amplification by (HA)Ag-II nanostructures is several times higher than by plasmonic films of (HA)Ag-I. Hence, feasibility was demonstrated for obtaining various SERS-active substrates with highly-efficient SERS enhancement for both anionic and cationic analyte molecules by changing the synthesis conditions. [ABSTRACT FROM AUTHOR]

A novel technique was developed for the preparation of bilayer sandwich-type structures containing monolayers or laterally-oriented silver nanoplates electrostatically deposited onto thin polymer films. The surface-enhanced Raman scattering (SERS) signal of 4-mercaptobenzoic acid in the ligand layer of the silver nanoplates was found to depend on the surface concentration of the deposited silver nanoplates in the monolayer. A two-fold enhancement was found for the surface-enhanced Raman scattering signal of the analyte located in the gaps between the silver nanoplate monolayers compared to the signal from a single silver nanoplate monolayer with identical surface concentration of the analyte molecules. [ABSTRACT FROM AUTHOR]

Schiff base reactions are widely used in pharmacy, catalysis, and volatile aldehyde detection. However, common biomarker sensing methods struggle to monitor this reaction process precisely due to their sensitivity, their time-consuming nature, and complex substrates. Here, we introduce the Nanoparticle-on-Mirror structure for in situ monitoring this reaction process through the application of a Au nanoparticle-p-Aminothiophenol-Au thin-film platform by surface-enhanced Raman scattering (SERS). Owing to the exposure of -NH2 groups and the local ultra-strong electromagnetic field in the nanocavity, the Schiff base reactions process can be rapidly monitored within two minutes. Meanwhile, the monitoring platform can detect benzaldehyde molecules as low as 10−6 M, showing excellent SERS performance. Notably, the Au-nanoparticle-p-Aminothiophenol-Au thin-film platform exhibited anti-interference and specificity, being able to identify BA in the presence of interference. The use of the Au-nanoparticle-p-Aminothiophenol-Au thin-film platform provides a sensing method for Schiff base reactions with accuracy and simplicity of operation, achieving a balanced approach for low-cost and high-performance real-time monitoring, which is expected to be applied in various catalytic reaction process monitoring and catalyst design processes. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a serious complication that poses risks to both mothers and their children. This condition is typically asymptomatic until the second or even third trimester, which can lead to poor outcomes and can be costly. Detection is particularly challenging in low- and middle-income countries, where a lack of centralized testing facilities coincides with high rates of PE-related maternal mortality. Variations in the levels of hsa-miR-17-5p have been identified as constituting a potential early indicator for distinguishing between individuals with PE and those without PE during the first trimester. Thus, developing a screening test to measure hsa-miR-17-5p levels would not only facilitate rapid detection in the early stages of pregnancy but also help democratize testing globally. Here, we present a proof-of-principle lateral-flow assay (LFA) designed to measure hsa-miR-17-5p levels using DNA-hairpin recognition elements for enhanced specificity and nanoprobes for sensitive surface-enhanced resonance Raman scattering (SERS) signal transduction. The theoretical limit of detection for hsa-miR-17-5p was 3.84 × 10−4 pg/µL using SERS. [ABSTRACT FROM AUTHOR]

Abstract Nanometal-based composite fibers have been widely explored in flexible sensors due to their outstanding optical and electrical properties. However, the weak binding force between metallic nanomaterial and fiber greatly limits the real application. In this work, nano silver (Ag) are strongly bonded with poly(3,4-ethylenedioxythiophene)-poly (styrene sulfonate) (PEDOT: PSS) fiber by the wet-spun process. Ag-S chemical bonds are formed by the interaction of Ag and PEDOT. The Ag/PEDOT: PSS composite fiber shows excellent surface-enhanced Raman scattering (SERS) sensitivity on Rhodamine 6G (R6G) molecules. The detection limit can reach 10–11 M and Raman enhancement factor (EF) is of 1.3 × 107. The high-sensitive SERS activity of Ag/PEDOT: PSS composite fiber mainly results from PEDOT: PSS, and the enhancement factor is 3 orders of magnitude better than that of other PEDOT: PSS based SERS substrates. Moreover, the composite fiber has metal-level conductivity of 1019 S/cm. This is 5 times higher than the conductivity of PEDOT: PSS fiber and a two-fold improvement over the reported values for nanometal/PEDOT: PSS based fabrics. The composite fiber has electric stability under bending test with bending speeds of 2 Hz indicating the composite fiber has good structural stability. In addition, the temperature of the composite fiber with 7 cm length can reach 76.5 °C at a voltage of 18 V. Additionally, the composite fiber shows anti-bacterial property and melting drop resistance, which pave the way for the integration of fiber-based optical and electrical sensors in the future multifunctional flexible devices.

Abstract Osteoporosis (OP) is a chronic disease characterized by diminished bone mass and structural deterioration, ultimately leading to compromised bone strength and an increased risk of fractures. Diagnosis primarily relies on medical imaging findings and clinical symptoms. This study aims to explore an adjunctive diagnostic technique for OP based on surface-enhanced Raman scattering (SERS). Serum SERS spectra from the normal, low bone density, and osteoporosis groups were analyzed to discern OP-related expression profiles. This study utilized partial least squares (PLS) and support vector machine (SVM) algorithms to establish an OP diagnostic model. The combination of Raman peak assignments and spectral difference analysis reflected biochemical changes associated with OP, including amino acids, carbohydrates, and collagen. Using the PLS-SVM approach, sensitivity, specificity, and accuracy for screening OP were determined to be 77.78%, 100%, and 88.24%, respectively. This study demonstrates the substantial potential of SERS as an adjunctive diagnostic technology for OP.

Fengsong Chen,1 Yanhua Huang,1 Yayun Qian,2 Ya Zhao,2 Chiwen Bu,3 Dong Zhang3 1Department of Gastroenterology, Haimen People’s Hospital, Nantong, 226000, People’s Republic of China; 2Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China; 3Institute of Surgery, Guanyun People’s Hospital, Guanyun, 222200, People’s Republic of ChinaCorrespondence: Dong Zhang; Chiwen Bu, Email gyxrmyykjk@163.com; gyxrmyybcw@163.comBackground: Gastric lesions pose significant clinical challenges due to their varying degrees of malignancy and difficulty in early diagnosis. Early and accurate detection of these lesions is crucial for effective treatment and improved patient outcomes.Methods: This paper proposed a label-free and highly sensitive classification method for serum of patients with different degrees of gastric lesions by combining surface-enhanced Raman scattering (SERS) and machine learning analysis. Specifically, we prepared Au lotus-shaped (AuLS) nanoarrays substrates using seed-mediated and liquid–liquid interface self-assembly method for measuring SERS spectra of serum, and then the collected spectra were processed by principal component analysis (PCA) - multi-local means based nearest neighbor (MLMNN) model to achieve differentiation.Results: By employing this pattern analysis, AuLS nanoarray substrates can achieve fast, sensitive, and label-free serum spectral detection. The classification accuracy can reach 97.5%, the sensitivity is higher than 96.7%, and the specificity is higher than 95.0%. Moreover, by analyzing the PCs loading plots, the most critical spectral features distinguishing different degrees of gastric lesions were successfully captured.Conclusion: This discovery lays the foundation for combining SERS with machine learning for real-time diagnosis and recognition of gastric lesions.Keywords: surface-enhanced Raman scattering, gastric lesions, Au lotus-shaped nanoarrays, principal component analysis, multi-local means based nearest neighbor

Surface-enhanced Raman scattering (SERS) is vital in many fields because of its high sensitivity, fast response, and fingerprint effect. The surface-enhanced Raman mechanisms are generally electromagnetic enhancement (EM), which is mainly based on noble metals (Au, Ag, etc.), and chemical enhancement (CM). With more and more studies on CM mechanism in recent years, non-noble metal nanomaterial SERS substrates gradually became widely researched and applied due to their superior economy, stability, selectivity, and biocompatibility compared to noble metal. In addition, non-noble metal substrates also provide an ideal new platform for SERS technology to probe the mechanism of biomolecules. In this paper, we review the applications of non-noble metal nanomaterials in SERS detection for biomedical engineering in recent years. Firstly, we introduce the development of some more common non-noble metal SERS substrates and discuss their properties and enhancement mechanisms. Subsequently, we focus on the progress of the application of SERS detection of non-noble metal nanomaterials, such as analysis of biomarkers and the detection of some contaminants. Finally, we look forward to the future research process of non-noble metal substrate nanomaterials for biomedicine, which may draw more attention to the biosensor applications of non-noble metal nanomaterial-based SERS substrates. [ABSTRACT FROM AUTHOR]

Adenosine phosphates (adenosine 5′-monophosphate (AMP), adenosine 5′-diphosphate (ADP), and adenosine 5′-triphosphate (ATP)) play important roles in energy storage and signal transduction in the human body. Thus, a measurement method that simultaneously recognizes and detects adenosine phosphates is necessary to gain insight into complex energy-relevant biological processes. Surface-enhanced Raman scattering (SERS) is a powerful technique for this purpose. However, the similarities in size, charge, and structure of adenosine phosphates (APs) make their simultaneous recognition and detection difficult. Although approaches that combine SERS and machine learning have been studied, they require massive quantities of training data. In this study, limited AP spectral data were obtained using fabricated gold nanostructures for SERS measurements. The training data were created by feature selection and data augmentation after preprocessing the small amount of acquired spectral data. The performances of several machine learning models trained on these generated training data were compared. Multilayer perceptron model successfully detected the presence of AMP, ADP, and ATP with an accuracy of 0.914. Consequently, this study establishes a new measurement system that enables the highly accurate recognition and detection of adenosine phosphates from limited SERS spectral data. [ABSTRACT FROM AUTHOR]

As an important trace molecular detection technique, surface-enhanced Raman scattering (SERS) has been extensively investigated, while the realization of simple, low-cost, and controllable fabrication of wafer-scale, flexible SERS-active substrates remains challenging. Here, we report a facile, low-cost strategy for fabricating wafer-scale SERS substrates based on Ag-TiO2 nanoparticle–film hybrids by combining dip-coating and UV light array photo-deposition. The results show that a centimeter-scale Ag nanoparticle (AgNP) film (~20 cm × 20 cm) could be uniformly photo-deposited on both non-flexible and flexible TiO2 substrates, with a relative standard deviation in particle size of only 5.63%. The large-scale AgNP/TiO2 hybrids working as SERS substrates show high sensitivity and good uniformity at both the micron and wafer levels, as evidenced by scanning electron microscopy and Raman measurements. In situ bending and tensile experiments demonstrate that the as-prepared flexible AgNP/TiO2 SERS substrate is mechanically robust, exhibiting stable SERS activity even in a large bending state as well as after more than 200 tensile cycles. Moreover, the flexible AgNP/TiO2 SERS substrates show excellent performance in detecting sub-micrometer-sized plastics (≤1 μm) and low-concentration organic pollutants on complex surfaces. Overall, this study provides a simple path toward wafer-scale, flexible SERS substrate fabrication, which is a big step for practical applications of the SERS technique. [ABSTRACT FROM AUTHOR]

The following research paper concerns the analysis and characterisation of commercially available surface-enhanced Raman scattering (SERS) substrates. SERS has long been a potentially very powerful method with a great deal of interest around it; however, there are still many obstacles which do not allow SERS to be easily applied to real-world detection and analysis problems. As such, research around the various types of substrates is ongoing, in the hope of streamlining and improving the Raman enhancement mechanism. Scanning electron microscope images were obtained for each of the three substrates, and their features and scales were described. Enhanced Raman spectra for Rhodamine B were obtained for a range of concentrations using each of the three substrates, and, in addition, surface enhancement maps are presented. Enhancement factors were calculated for the 1358 cm−1 peak of Rhodamine B. Complementing the experimental work, theoretical FEM modelling in COMSOL Multiphysics was performed, with the resulting calculations yielding an enhancement prediction adequately accurate to the real substrates. [ABSTRACT FROM AUTHOR]

Plasmonic materials have been extensively explored for surface-enhanced Raman scattering (SERS) due to their high tunability and excellent localized electric field enhancement. Most research for now has focused on noble metals, with limited investigation into corrosion-resistant materials for SERS effects. In this study, a photolithography process is firstly used to create a patterned dot array on a silicon substrate. Next, magnetron sputtering is employed to deposit molybdenum films, finally resulting in the molybdenum truncated cone array substrates for SERS applications. The fabricated truncated cone array experimentally facilitates the coupling of localized surface plasmon polaritons, consistent with simulation results obtained via the finite-difference time-domain method. The formation of hot spots between the cone unit cell arrays leads to the improved Raman signals and can act as traps for target molecules. This study demonstrates that molybdenum-based micro-nano structures can serve as reliable SERS substrates for sensitive molecular sensing applications in highly corrosive environments. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP) is a chronic disease characterized by diminished bone mass and structural deterioration, ultimately leading to compromised bone strength and an increased risk of fractures. Diagnosis primarily relies on medical imaging findings and clinical symptoms. This study aims to explore an adjunctive diagnostic technique for OP based on surface-enhanced Raman scattering (SERS). Serum SERS spectra from the normal, low bone density, and osteoporosis groups were analyzed to discern OP-related expression profiles. This study utilized partial least squares (PLS) and support vector machine (SVM) algorithms to establish an OP diagnostic model. The combination of Raman peak assignments and spectral difference analysis reflected biochemical changes associated with OP, including amino acids, carbohydrates, and collagen. Using the PLS-SVM approach, sensitivity, specificity, and accuracy for screening OP were determined to be 77.78%, 100%, and 88.24%, respectively. This study demonstrates the substantial potential of SERS as an adjunctive diagnostic technology for OP. [ABSTRACT FROM AUTHOR]

Surface-enhanced Raman scattering (SERS) spectroscopy was used for the structural characterization of 4-aminothiophenol molecules in silver and gold colloids. During the SERS experiment on silver nanoparticles, structural changes occurred in the molecules adsorbed on the metal surface. The observed changes were associated with the dimerization process of 4-aminothiophenol under the influence of laser radiation, leading to the formation of 4,4'-dimercaptoazobenzene. The use of excitation at 532 nm with radiation power that is quite low for traditional SERS measurements proved to be optimal for catalyzing the dimerization process, while using laser excitation at 785 nm less stimulated dimerization of the studied compound. Unlike silver, gold nanospheres proved to be less suitable substrates for catalyzing the dimerization process under the chosen experimental conditions. Unmodified, freshly prepared silver colloid proved to be an adequate substrate for stimulating the dimerization of 4-aminothiophenol during classical SERS measurements, even when an excitation radiation power of less than 5 mW was used. [ABSTRACT FROM AUTHOR]

TiN–Ag@Ag composite substrates were prepared via ammonia reduction nitridation followed by electrochemical deposition. Fabricated TiN–Ag@Ag substrates were characterized using X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy, and ultraviolet-visible spectrophotometry. The surface-enhanced Raman spectroscopy activity of these substrates was evaluated using ibuprofen as the probe molecule. The size of the Ag particles prepared via electrochemical deposition was approximately 1 μm, and Ag nanoparticles with an average particle size of 100 nm were uniformly distributed on the surface of TiN–Ag films. The Raman signal of ibuprofen was significantly enhanced, and the minimum detection concentration of ibuprofen was 10–5 M. The mechanism by which the TiN–Ag@Ag composite substrate enhanced the Raman signals was analyzed using ultraviolet photoelectron spectroscopy and density functional theory implemented in the Gaussian software. Overall, charge transfer and the local electromagnetic field effect enhanced the Raman signals of ibuprofen. [ABSTRACT FROM AUTHOR]

Plasmonic intragap nanostructures (PINs) have garnered intensive attention in Raman-related analysis due to their exceptional ability to enhance light–matter interactions. Although diverse synthetic strategies have been employed to create these nanostructures, the emphasis has largely been on PINs with simple configurations, which often fall short in achieving effective near-field focusing. Three-dimensional (3D) complex PINs, distinguished by their intricate networks of internal gaps and voids, are emerging as superior structures for effective light trapping. These structures facilitate the generation of hot spots and hot zones that are essential for enhanced near-field focusing. Nevertheless, the synthesis techniques for these complex structures and their specific impacts on near-field focusing are not well-documented. This review discusses the recent advancements in the synthesis of 3D complex PINs and their applications in surface-enhanced Raman scattering (SERS). We begin by describing the foundational methods for fabricating simple PINs, followed by a discussion on the rational design strategies aimed at developing 3D complex PINs with superior near-field focusing capabilities. We also evaluate the SERS performance of various 3D complex PINs, emphasizing their advanced sensing capabilities. Lastly, we explore the future perspective of 3D complex PINs in SERS applications. [ABSTRACT FROM AUTHOR]

Optical fiber Raman and surface-enhanced Raman scattering (SERS) probes hold great promise for in vivo biosensing and in situ monitoring of hostile environments. However, the silica Raman scattering background generated within the optical fiber increases in proportion to the length of the fiber, and it can swamp the signal from the target analyte. While filtering can be applied at the distal end of the fiber, the use of bulk optical elements has limited probe miniaturization to a diameter of 600 µm, which in turn limits the potential applications. To overcome this limitation, femtosecond laser micromachining was used to fabricate a prototype micro-optical filter, which was directly integrated on the tip of a 125 µm diameter double-clad fiber (DCF) probe. The outer surface of the microfilter was further modified with a nanostructured, SERS-active, plasmonic film that was used to demonstrate proof-of-concept performance with thiophenol as a test analyte. With further optimization of the associated spectroscopic system, this ultra-compact microprobe shows great promise for Raman and SERS optical fiber sensing. [ABSTRACT FROM AUTHOR]

Colorectal cancer remains a major global health concern. Colonoscopy, the gold-standard colorectal cancer diagnostic, relies on the visual detection of lesions and necessitates invasive biopsies for confirmation. Alternative diagnostic methods, based on nanomedicine, can facilitate early detection of malignancies. Here, we examine the uptake of surface-enhanced Raman scattering nanoparticles (SERS NPs) as a marker for intestinal tumor detection and imaging using an established Drosophila melanogaster model for gut disease. Young and old Oregon-R and w1118 flies were orally administered SERS NPs and scanned without and upon gut lumen clearance to assess nanoparticle retention as a function of aging. Neither young nor old flies showed significant NP retention in their body after gut lumen clearance. Moreover, tumorigenic flies of the esg-Gal4/UAS-RasV12 genotype were tested for SERS NP retention 2, 4 and 6 days after RasV12 oncogene induction in their midgut progenitor cells. Tumorigenic flies showed a statistically significant NP retention signal at 2 days, well before midgut epithelium impairment. The signal was then visualized in scans of dissected guts revealing areas of NP uptake in the posterior midgut region of high stem cell activity. [ABSTRACT FROM AUTHOR]

Rapid identification of microorganisms with a high sensitivity and selectivity is of great interest in many fields, primarily in clinical diagnosis, environmental monitoring, and the food industry. For over the past decades, a surface-enhanced Raman scattering (SERS)-based detection platform has been extensively used for bacterial detection, and the effort has been extended to clinical, environmental, and food samples. In contrast to other approaches, such as enzyme-linked immunosorbent assays and polymerase chain reaction, SERS exhibits outstanding advantages of rapid detection, being culture-free, low cost, high sensitivity, and lack of water interference. This review aims to cover the development of SERS-based methods for bacterial detection with an emphasis on the source of the signal, techniques used to improve the limit of detection and specificity, and the application of SERS in high-throughput settings and complex samples. The challenges and advancements with the implementation of artificial intelligence (AI) are also discussed. [ABSTRACT FROM AUTHOR]

A metasurface composed of silver nanoflower arrays, which exhibit asymmetrical absorption and surface‐enhanced Raman scattering (SERS) due to hybrid plasmonic effects, is reported. The silver nanoflowers are fabricated by oblique deposition of silver on a polymer nanohole array on a glass substrate, forming petal‐like semicontinuous thin films on the inner walls of the holes. Depending on the deposition angle, three‐ or five‐petal nanoflowers are obtained. The nanoflower arrays show strong reflection from the air side and broadband and wide‐angle absorption from the glass side, as a result of transmission surface plasmon resonance and localized surface plasmon resonance, respectively. The three‐petal structure, which absorbs most of the incident light from the glass side, induces a localized enhancement of electric field in the center of each nanohole, providing a high‐sensitivity SERS substrate. The SERS performance of the metasurface by direct measurement and near‐field simulation is demonstrated.

Tong Zhang,1– 3,* Han Wu,1,2,* Chenling Qiu,1,2 Mingxin Wang,1,2 Haiting Wang,1,2 Shunhua Zhu,1,4 Yinhai Xu,2 Qingli Huang,1,4 Shibao Li1,2 1Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 3Chuzhou Center for Disease Control and Prevention, Chuzhou City, Anhui, 239000, People’s Republic of China; 4Public Experimental Research Center of Xuzhou Medical University, Xuzhou City, Jiangsu, 221004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingli Huang; Shibao Li, Email qlhuang@xzhmu.edu.cn; sdjnshlb@xzhmu.edu.cnIntroduction: Insulin and C-peptide played crucial roles as clinical indicators for diabetes and certain liver diseases. However, there has been limited research on the simultaneous detection of insulin and C-peptide in trace serum. It is necessary to develop a novel method with high sensitivity and specificity for detecting insulin and C-peptide simultaneously.Methods: A core-shell-satellites hierarchical structured nanocomposite was fabricated as SERS biosensor using a simple wet-chemical method, employing 4-MBA and DTNB for recognition and antibodies for specific capture. Gold nanorods (Au NRs) were modified with Raman reporter molecules and silver nanoparticles (Ag NPs), creating SERS tags with high sensitivity for detecting insulin and C-peptide. Antibody-modified commercial carboxylated magnetic bead@antibody served as the capture probes. Target materials were captured by probes and combined with SERS tags, forming a “sandwich” composite structure for subsequent detection.Results: Under optimized conditions, the nanocomposite fabricated could be used to detect simultaneously for insulin and C-peptide with the detection limit of 4.29 × 10− 5 pM and 1.76 × 10− 10 nM in serum. The insulin concentration (4.29 × 10− 5– 4.29 pM) showed a strong linear correlation with the SERS intensity at 1075 cm− 1, with high recoveries (96.4– 105.3%) and low RSD (0.8%– 10.0%) in detecting human serum samples. Meanwhile, the C-peptide concentration (1.76 × 10− 10– 1.76 × 10− 3 nM) also showed a specific linear correlation with the SERS intensity at 1333 cm− 1, with recoveries 85.4%– 105.0% and RSD 1.7%– 10.8%.Conclusion: This breakthrough provided a novel, sensitive, convenient and stable approach for clinical diagnosis of diabetes and certain liver diseases. Overall, our findings presented a significant contribution to the field of biomedical research, opening up new possibilities for improved diagnosis and monitoring of diabetes and liver diseases.Keywords: surface-enhanced Raman scattering, SERS, nanocomposites, insulin, C-peptide

A flexible wipe paper for rapid nondestructive detection of ferbam residues on the surface of fruits and vegetables by surface-enhanced Raman scattering (SERS) was prepared using filter paper as the substate by a simple soaking method. The synthesis and storage conditions were optimized to ensure that the SERS method has excellent performance. The results showed that concentration factor of silver nanoparticles (AgNPs), soaking time in AgNP solution and drying method greatly affected the performance of the SERS wipe paper. The performance under the condition of soaking for 8 h in a 5-fold concentrate of AgNP solution was significantly better than that under other conditions. The SERS wipe paper prepared by vacuum drying had better performance that those prepared by other drying methods. After 9 days of storage at −20 ℃, the optimized substrate retained approximately 50% of the original peak value. Besides, it exhibited good sensitivity, uniformity, and repeatability. The limit of detection (LOD) for ferbam on a glass plate was 4.07 × 10-6 mg/mL, and the LOD for ferbam on the surface of spinach and nectarine were 0.043 and 0.062 mg/kg, respectively. This study provides an excellent basis for the development and utilization of SERS wipe paper.

Abstract Hotspots are high-intensity electromagnetic zones that form, for example, at the interstitials of plasmonic nanoaggregates, resulting in a considerable rise in the enhancement factor. However, it is inevitable to achieve specific nanometric geometry as well as a suitable technique to capture the details of hotspots. We report near-field surface-enhanced Raman scattering (SERS) spectroscopy of a well-defined gold nanoaggregate of a few nanoparticles adsorbed with a small number of target analytes. A spectrally and spatially resolved SERS measurement setup using an aperture near-field scanning optical microscope (a-NSOM) facilitated the direct observation of localized electromagnetic (EM) fields at the interstitials through SERS. Correlated optical image and corresponding nanometric geometry were captured through the home-built a-NSOM setup. Near-field SERS spectra were recorded at different sites of interest. It was evident that the interstitial positioned at the center of the tetramer provided the most intense Raman scattering, implying the possibility of a SERS-active hotspot therein. SERS bands of the spectrum of the Raman-active dye Rhodamine 6G recorded at the same hotspot coincided well with those reported so far. It was noteworthy that most of the SERS bands in such scenery got enhanced. Such direct observation with high spatial resolution is indispensable to understanding the origin of localized EM fields at “hotspots” and the EM enhancement factor in the SERS process. A finite-difference time-domain (FDTD) analysis was carried out to validate the results.

We developed an unconventional seed-mediated in situ synthetic method, whereby gold nanostars are formed directly on the internal walls of microfluidic reactors. The dense plasmonic substrate coatings were grown in microfluidic channels with different geometries to elucidate the impacts of flow rate and profile on reagent consumption, product morphology, and density. Nanostar growth was found to occur in the flow-limited regime and our results highlight the possibility of creating shape gradients or incorporating multiple morphologies in the same microreactor, which is challenging to achieve with traditional self-assembly. The plasmonic-microfluidic platforms developed herein have implications for a broad range of applications, including cell culture/sorting, catalysis, sensing, and drug/gene delivery.

Sensitive detection and efficient inactivation of pathogenic bacteria are crucial for halting the spread and reproduction of foodborne pathogenic bacteria. Herein, a novel Apt-modified PDMS-ZnO/Ag multifunctional biosensor has been developed for high-sensitivity surface-enhanced Raman scattering (SERS) detection along with photocatalytic sterilization towards Salmonella typhimurium (S. typhimurium). The distribution of the electric field in PDMS-ZnO/Ag with different Ag sputtering times was analyzed using a finite-difference time-domain (FDTD) algorithm. Due to the combined effect of electromagnetic enhancement and chemical enhancement, PDMS-ZnO/Ag exhibited outstanding SERS sensitivity. The limit of detection (LOD) for 4-MBA on the optimal SERS substrate (PZA-40) could be as little as 10−9 M. After PZA-40 was modified with the aptamer, the LOD of the PZA-40-Apt biosensor for detecting S. typhimurium was only 10 cfu/mL. Additionally, the PZA-40-Apt biosensor could effectively inactivate S. typhimurium under visible light irradiation within 10 min, with a bacterial lethality rate (Lb) of up to 97%. In particular, the PZA-40-Apt biosensor could identify S. typhimurium in food samples in addition to having minimal cytotoxicity and powerful biocompatibility. This work provides a multifunctional nanoplatform with broad prospects for selective SERS detection and photocatalytic sterilization of pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Abrin and ricin, both type II ribosome-inactivating proteins, are toxins of significant concern and are under international restriction by the Chemical Weapons Convention and the Biological and Toxin Weapons Convention. The development of a rapid and sensitive detection method for these toxins is of the utmost importance for the first emergency response. Emerging rapid detection techniques, such as surface-enhanced Raman spectroscopy (SERS) and lateral flow assay (LFA), have garnered attention due to their high sensitivity, good selectivity, ease of operation, low cost, and disposability. In this work, we generated stable and high-affinity nanotags, via an efficient freezing method, to serve as the capture module for SERS-LFA. We then constructed a sandwich-style lateral flow test strip using a pair of glycoproteins, asialofetuin and concanavalin A, as the core affinity recognition molecules, capable of trace measurement for both abrin and ricin. The limit of detection for abrin and ricin was 0.1 and 0.3 ng/mL, respectively. This method was applied to analyze eight spiked white powder samples, one juice sample, and three actual botanic samples, aligning well with cytotoxicity assay outcomes. It demonstrated good inter-batch and intra-batch reproducibility among the test strips, and the detection could be completed within 15 min, indicating the suitability of this SERS-LFA method for the on-site rapid detection of abrin and ricin toxins. [ABSTRACT FROM AUTHOR]

Topological insulators (TIs) exhibit unconventional quantum phases that can be tuned by external quantum confinements. The geometry of the surface of 3D TIs plays a crucial role. For example, the geometrical crossover from 2D surfaces to a 1D cylinder results in a novel state with a Spin‐Berry Phase (SBP). Surface‐Enhanced Raman Scattering (SERS) with a sub‐micron spatial resolution is utilized to study the quantum‐confinement effects of quasi‐relativistic electrons along the perimeter of the circular bismuth selenide (Bi2Se3) nanowires. The presence of diameter‐dependent SERS in nanowires can be attributed to the self‐interference effect of the electronic wave‐function along the circumferential direction of the TI nanowires. Nanoribbons with rectangular cross‐section do not show this effect. Further gold nanoparticles are applied as plasmonic SERS sensors attached to the distinct topological surface states to manipulate quasi‐relativistic surface states of nanoribbons and nanowires. This technique enables to discriminate between different geometries of TI surface states and also opens a novel pathway to probe the quantum properties of topological surface states. [ABSTRACT FROM AUTHOR]

[Display omitted] Developing innovative surface-enhanced Raman scattering (SERS) nanotags continues to attract significant attention due to their unparalleled sensitivity and specificity for in vitro diagnostic and in vivo tumor imaging applications. Here, we report a new class of bright and stable SERS nanotags using alkylmercaptan-PEG (AMP) polymers. Due to its amphiphilic structure and a thiol anchoring group, these polymers strongly absorb onto gold nanoparticles, leading to an inner hydrophobic layer and an outer hydrophilic PEG layer. The inner hydrophobic layer serves to "lock in" the Raman reporter molecules adsorbed on the particle surface via favorable hydrophobic interactions that also allow denser PEG coatings, which "lock out" other molecules from competitive binding or adsorbing to the gold surface, thereby providing superior colloidal and signal stability. The higher grafting densities of AMP polymers compared to conventional thiolated PEG also led to dramatic increases in cellular target selectivity, with specific-to-nonspecific binding ratios reaching beyond an order of magnitude difference. Experimental evaluations and theoretical considerations of dielectric polarization and light scattering indicate that the hydrophobic layer provides a more favorable dielectric environment with less plasmon dampening, greater particle scattering efficiency, and increased Raman reporter polarizability. Accordingly, SERS nanotags with AMP polymer coatings are observed to be considerably brighter (∼10-fold). Furthermore, the AMP-coated SERS nanotag's increased intensity and avidity can boost cellular detection sensitivity by nearly two orders of magnitude. [ABSTRACT FROM AUTHOR]

Lysosome, the digestive organelle in eukaryotic cells, plays an important role in the degradation and recirculation of cellular products as well as in maintaining the stability of cellular metabolic microenvironment. Surface‐enhanced Raman scattering (SERS) is a molecular fingerprint technology with high detection sensitivity and photostability, suited for revealing various intracellular molecular information by inducing endocytosis of SERS‐active nanoparticles. However, it remains challenging to selectively extract the molecular information of specific organelles (e.g., lysosomes) from a high‐dimensional spectral set. Herein, we proposed a novel paradigm by combining label‐free SERS spectroscopy with confocal fluorescence imaging to investigate the digestion behavior of lysosomes in cells. The structural similarity algorithm was innovatively introduced and exhibited its effectiveness in screening out the wavenumbers in the SERS spectral set with high correlation with the metabolic behaviors of lysosomes. With comprehensive experiments on HeLa single cells, we captured the intracellular macromolecular digestion phenomenon and discovered the changing pattern of cellular SERS spectra after starvation‐induced autophagy, and analyzed the molecular information within the lysosomes in three‐dimensional space. [ABSTRACT FROM AUTHOR]

Optical bioassays are challenged by the growing requirements of sensitivity and simplicity. Recent developments in the combination of redox cycling with different optical methods for signal amplification have proven to have tremendous potential for improving analytical performances. In this review, we summarized the advances in optical bioassays based on the signal amplification of redox cycling, including colorimetry, fluorescence, surface-enhanced Raman scattering, chemiluminescence, and electrochemiluminescence. Furthermore, this review highlighted the general principles to effectively couple redox cycling with optical bioassays, and particular attention was focused on current challenges and future opportunities. [ABSTRACT FROM AUTHOR]

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Abstract To develop a field applicable hazardous molecular detection system, highly sensitive and multiplex detection capability is required for practical utilization. Here, a paper‐based 3D spiky needle‐clustered gold grown on silver (Ag@Au) plasmonic nanoarchitecture (3D‐SNCP) is fabricated through whole solution process. The developed substrate is investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X‐ray diffraction (XRD) to find out morphological development mechanism. Also, finite‐domain time difference (FDTD) simulation is conducted for the observation of electromagnetic field (E‐field) distribution. After surface‐enhanced Raman scattering (SERS) characterization, the 3D‐SNCP is utilized for ultra‐sensitive and multiplex hazardous molecular detection, such as bipyridine pesticides including paraquat (PQ), diquat (DQ), and difenzoquat (DIF). Then, each of pesticide molecular Raman signals are trained by a machine learning technique of multinomial logistic regression (MLR), followed by multiplex classificationf of blank, PQ, DQ, DIF, and four mixture types of each pesticide, spiked in real agricultural matrix. The developed 3D‐SNCP substrate combined with the machine learning method successfully verifies the multiple pesticides and it is expected to be applied for various hazardous molecular detection in much complicated matrix environments.

Abstract This review reports diverse microfluidic systems utilizing surface-enhanced Raman scattering (SERS) detection for disease diagnosis. Integrating SERS detection technology, providing high-sensitivity detection, and microfluidic technology for manipulating small liquid samples in microdevices has expanded the analytical capabilities previously confined to larger settings. This study explores the principles and uses of various SERS-based microfluidic devices developed over the last two decades. Specifically, we investigate the operational principles of documented SERS-based microfluidic devices, including continuous-flow channels, microarray-embedded microfluidic channels, droplet microfluidic channels, digital droplet channels, and gradient microfluidic channels. We also examine their applications in biomedical diagnostics. In conclusion, we summarize the areas requiring further development to translate these SERS-based microfluidic technologies into practical applications in clinical diagnostics.

Raman scattering can provide information on molecular fingerprints, which have been widely applied in various fields of material science and nanobiotechnology. Notably, low interference with water molecules in obtaining the Raman spectra between 500 and 2000 cm−1 made it a powerful spectroscopic tool in biology, such as imaging and signaling for a living cell. To be a robust tool for cell biology, the performance of obtaining molecular-specific information with high sensitivity, high resolution in real time, and without inducing cell damage is strongly required. The conventional fluorescence-based method has been suffered from the rapid photobleaching of organic fluorophores and the lack of molecular information. In contrast, Raman scattering is a promising spectroscopic tool to acquire cellular information, and the extremely low signal intensity of Raman scattering could be amplified by incorporating the plasmonic nanomaterials. Along with the fundamental research focus on surface-enhanced Raman scattering (SERS), the practical approaches of SERS for cellular imaging as a new tool for drug screening and monitoring cellular signals have been extensively explored based on new optical setups and new designing strategies for the nanostructures. Diverse nanostructure and surface chemistry for targeting or sensing have been played pivotal roles in acquiring cellular information and high resolution cell imaging. In this regard, this review focused on the recent advances of SERS-based technologies for a live cell imaging investigated such as potential drug screening, signaling for chemicals or biomolecules in cell, in situ sensing, and high spatiotemporal resolution.

Abstract We report an innovative and facile approach to fabricating an ultrasensitive plasmonic paper substrate for surface-enhanced Raman spectroscopy (SERS). The approach exploits the self-assembling capability of poly(styrene-b-2-vinyl pyridine) block copolymers to form a thin film at the air-liquid interface within the single microdroplet scale for the first time and the subsequent in situ growth of silver nanoparticles (AgNPs). The concentration of the block copolymer was found to play an essential role in stabilizing the droplets during the mass transfer phase and formation of silver nanoparticles, thus influencing the SERS signals. SEM analysis of the morphology of the plasmonic paper substrates revealed the formation of spherical AgNPs evenly distributed across the surface of the formed copolymer film with a size distribution of 47.5 nm. The resultant enhancement factor was calculated to be 1.2 × 107, and the detection limit of rhodamine 6G was as low as 48.9 pM. The nanohybridized plasmonic paper was successfully applied to detect two emerging pollutants—sildenafil and flibanserin—with LODs as low as 1.48 nM and 3.45 nM, respectively. Thus, this study offers new prospects for designing an affordable and readily available, yet highly sensitive, paper-based SERS substrate with the potential for development as a lab-on-a-chip device.

Preeclampsia (PE) is a serious complication that poses risks to both mothers and their children. This condition is typically asymptomatic until the second or even third trimester, which can lead to poor outcomes and can be costly. Detection is particularly challenging in low- and middle-income countries, where a lack of centralized testing facilities coincides with high rates of PE-related maternal mortality. Variations in the levels of hsa-miR-17-5p have been identified as constituting a potential early indicator for distinguishing between individuals with PE and those without PE during the first trimester. Thus, developing a screening test to measure hsa-miR-17-5p levels would not only facilitate rapid detection in the early stages of pregnancy but also help democratize testing globally. Here, we present a proof-of-principle lateral-flow assay (LFA) designed to measure hsa-miR-17-5p levels using DNA-hairpin recognition elements for enhanced specificity and nanoprobes for sensitive surface-enhanced resonance Raman scattering (SERS) signal transduction. The theoretical limit of detection for hsa-miR-17-5p was 3.84 × 10−4 pg/µL using SERS.

Surface-enhanced Raman scattering (SERS) is widely used for trace detection of substances, and the key to this technology lies in the preparation of the substrate material. In this study, a composite SERS material of Au NRs/4-MBA/PAM was constructed and characterized to better immobilize the reference molecule 4-mercaptobenzoic acid (4-MBA). Electron transmission microscopy results demonstrated that the PAM film helps Au NRs to pack closely, enhancing the stability of the material structure and reducing the interference of external environmental factors on the response of 4-MBA, thus improving the accuracy of quantitative determination. Comparative experimental results with the Au NRs/4-MBA substrate showed that the relative standard deviations (RSDs) of the detection results for MG on different batches of Au NRs/4-MBA/PAM were less than 8.0%, and the RSDs of different points on the same material were less than 10.0%, indicating that the Au NRs/4-MBA/PAM has higher uniformity, better reproducibility, and higher sensitivity in detecting malachite green (MG). Applying this material in the recovery determination of fish extract showed that the recovery rates of MG were between 75.60% and 83.24%. Therefore, the Au NRs/4-MBA/PAM substrate can accurately detect and quantify veterinary drug residue in complex matrices such as food tissue.