Surface-enhanced Raman spectroscopy (SERS) substrates have undergone extensive development over the years, yet the challenge of significantly enhancing their sensitivity persists. Most existing substrates face considerable difficulties in obtaining the strongest electromagnetic coupling to maximize SERS signal intensity, i.e., it is hard to achieve optimal structural parameters such as the gap width and particle size, and to fabricate surfaces that are free from contamination such as surfactants. Therefore, there is a pressing need for a substrate optimization approach that allows for in-situ monitoring and real-time dynamic adjustments to precisely achieve the ideal substrate characteristics for superior performance.

In this study, a highly sensitive porous copper-gold (Cu-Au) SERS substrate was fabricated using the galvanic replacement reaction (GRR), coupled with in-situ SERS monitoring to optimize substrate preparation. The Cu-Au nanoparticles formed and grew on sacrificial templates while noble metal ions were reduced by the sacrificial metal during GRR. The substrate preparation process revealed that the optimal preparation time was 200 ± 20 s. The SERS performance with crystal violet (CV) as a probe molecule demonstrated the substrate's remarkable sensitivity with detecting concentrations as low as 10-16 M, which surpasses most literature reports. The optimized SERS substrate was further tested for detecting malachite green (MG), yielding an ultra-high enhancement factor (EF) of 8.96 × 1014. The entire optimization process did not involve the addition of aggregation or surfactant agents, ensuring a clean substrate surface.

This study is a further proof of the significance of the in-situ optimization of SERS substrates via GRR which allows real-time adjustment of nanoparticle size and gap width to enhance sensitivity. This approach has enabled us to develop substrates with exceptional sensitivity and reproducibility. These significant contributions may open up new avenues for the facile fabrication of ultrasensitive SERS substrates.

As a highly sensitive analytical technology, surface enhanced Raman spectroscopy (SERS) based on localized surface plasmon resonance has been widely explored in the field of environment monitoring, food safety, material identification and biomedicine. In the field of biosensing, the design of sensing models, the regulation of enhancement factors (EFs), and the stability of detection results have always been crucial research keys. Progress in these areas has continuously expanded the application scope of SERS technology and improved the feasibility of its application. Among them, the regulation of EFs through physical enhancement and chemical enhancement is a crucial point in improving the performance of SERS. Starting from the physicochemical mechanism, this review discusses the relevant influencing parameters and then summarizes the latest regulation strategies based on the above theory, as well as special regulation methods such as E-SERS. A diverse array of regulation strategies underpinned by the SERS enhancement mechanism have been effectively harnessed to amplify the EF of the SERS system. These include a wide spectrum of metal nanostructures based on the electromagnetic mechanism (EM), as well as regulation approaches predicated on the chemical mechanism (CM), such as energy-level manipulation, defect engineering, and material coupling. In addition, it encompasses specialized regulation methods such as analyte pre-concentration. This article focuses on summarizing the principal regulation approaches that have significantly impacted SERS enhancement in recent years, complemented by specialized regulation methods, with the hope of facilitating smoother progress in future work related to SERS.

Recent advancements in Surface-enhanced Raman Scattering (SERS) bioprobes have substantially enhanced their bioimaging capabilities for disease theranostics. This review systematically analyzes three categories of engineered SERS probes: noble metal nanostructures, metal oxide hybrids, and multifunctional composite materials, emphasizing their optimized designs for targeted tumor detection and image-guided surgery. Key developments include improved in vitro biosensing platforms for rapid tumor screening and advanced in vivo probes enabling real-time intraoperative imaging with molecular specificity. The integration of SERS with complementary modalities (fluorescence, photoacoustic, MRI) is critically examined as a strategy to overcome individual technical limitations and achieve multiscale tissue characterization. Technical progress in spatial resolution enhancement, multiplex biomarker detection, and biocompatibility optimization is quantitatively highlighted. Current challenges in signal consistency across biological systems and scalable probe manufacturing are discussed, proposing standardized evaluation frameworks as essential for clinical translation. This work establishes SERS as a multimodal imaging cornerstone for precision oncology, particularly in tumor margin delineation and metastatic lesion identification.

Surface-enhanced Raman scattering (SERS) has become an advanced spectroscopic analysis method in the fields of chemistry, biomedical sensing, and imaging, owing to its excellent vibrational signal recognition and sensitivity for single-molecule detection. The effectiveness of SERS technology relies on the development of high-performance substrates, which must possess high sensitivity, uniformity, and repeatability. In this study, the enhanced substrates with high Raman activity were successfully prepared by adopting the three-phase self-assembly method to assemble gold nanorods (AuNRs) into nanopores of ultrathin porous alumina (AAO) films. By precisely controlling the pore size of AAO and the dimensions of AuNRs, the ability of the substrates and the Raman detection limits are enhanced significantly. Probe molecules, including Rhodamine 6G (R6G), Crystal Violet (CV), and Aspartame (APM), were selected to test the substrates sensitivity and uniformity, with detection limits of 10-13, 10-12 M, and 7.8 mg/L, respectively. Random sampling was conducted on the substrate surface to analyze the spectral characteristics of the characteristic peaks of R6G and CV molecules, and the relative standard deviations (RSD) were 4.3 and 3.18% at characteristic peaks 612 and 1619 cm-1, respectively, demonstrating the enhanced uniformity of the prepared substrates. This research indicates that assembling AuNRs onto AAO substrates results in significant Raman activity, providing a more reliable platform for the application of SERS technology.

Early diagnosis of brain tumors is challenging due to their complexity and delicate structure. Conventional imaging techniques like MRI, CT, and PET are unable to provide detailed visualization of early-stage brain tumors. Early-stage detection of brain tumors is vital for enhancing patient outcomes and survival rates. So far, several scientists have dedicated their efforts to innovating advanced diagnostic probes to efficiently cross the BBB and selectively target brain tumors for optimal imaging. The integration of these techniques presents a viable pathway for non-invasive, accurate, and early-stage tumor identification. Herein, we provide a timely update on the various imaging probes and potential challenges for the diagnosis of early-stage brain tumors. Furthermore, this review highlights the significance of integrating advanced imaging probes for improving the early detection of brain tumors, ultimately enhancing treatment outcomes. Hopefully, this review will stimulate the interest of researchers to accelerate the development of new imaging probes and even their clinical translation for improving the early diagnosis of brain tumors.

With the discovery and in-depth research of 2D carbide/nitride MXene, MXene-based nanocomposites have attracted widespread attention due to their unique enhancement and synergistic effects, demonstrating tremendous application potential in the biomedical field. Hence, this review provides a comprehensive discussion of the synthesis methods, optical properties, and biomedical applications of MXene-based nanocomposites. Firstly, it discusses and compares various synthesis methods for MXenes and MXene-based nanocomposites, and categorizes the combination types based on surface engineering strategies and distinct properties. Subsequently, the optical properties of MXene-based nanocomposites are summarized, including localized surface plasmon resonance (LSPR), surface-enhanced Raman scattering (SERS), and photothermal conversion efficiency (PCE). Furthermore, this review provides an in-depth discussion of the applications of MXene-based nanocomposites in biosensors, optical therapeutics, and bioimaging. Finally, we thoroughly explore the challenges and opportunities for the future development of MXene-based nanocomposites, aiming to offer a feasible approach for the development of high-performance materials for biomedical applications.

With the advancement of research on life systems and disease mechanisms, the precision of analysis tends to be at a single molecule or single gene level. The surface-enhanced Raman scattering (SERS) method is highly anticipated because of its sensitive detection ability down to a single molecule level. The SERS-based microfluidic platforms retain both advantages of SERS and microfluidics, working in a complementary way. The combination of microfluidics and SERS can provide rapid, non-destructive, high-sensitive, and high-throughput analysis for biological samples, which is of great significance to developing potential biomedical applications, thus occupying an outstanding position among the current research hot topics. This review briefly summarized the recent developments and applications of SERS-based microfluidic platforms in biological analysis. This paper first introduced the SERS-based microfluidic platforms and gave a classification of this method including continuous flow-based method, microarrays-based method, droplet-based method, lateral flow assay (LFA)-based method, and digital-based method. In particular, the bioanalytical applications of SERS-based microfluidic platforms in recent years, including biomolecule detection, cell analysis, and disease diagnosis, have been reviewed. It illustrated that SERS-based microfluidic platforms have great potential in bioanalysis.

Over the last 2 decades, research has increasingly focused on cancer stem cells (CSCs), considered responsible for tumor formation, resistance to therapies, and relapse. The traditional "static" CSC model used to describe tumor heterogeneity has been challenged by the evidence of CSC dynamic nature and plasticity. A comprehensive understanding of the mechanisms underlying this plasticity, and the capacity to unambiguously identify cancer markers to precisely target CSCs are crucial aspects for advancing cancer research and introducing more effective treatment strategies. In this context, Raman spectroscopy (RS) and specific Raman schemes, including CARS, SRS, SERS, have emerged as innovative tools for molecular analyses both in vitro and in vivo. In fact, these techniques have demonstrated considerable potential in the field of cancer detection, as well as in intraoperative settings, thanks to their label-free nature and minimal invasiveness. However, the RS integration in pre-clinical and clinical applications, particularly in the CSC field, remains limited. This review provides a concise overview of the historical development of RS and its advantages. Then, after introducing the CSC features and the challenges in targeting them with traditional methods, we review and discuss the current literature about the application of RS for revealing and characterizing CSCs and their inherent plasticity, including a brief paragraph about the integration of artificial intelligence with RS. By providing the possibility to better characterize the cellular diversity in their microenvironment, RS could revolutionize current diagnostic and therapeutic approaches, enabling early identification of CSCs and facilitating the development of personalized treatment strategies.

Raman spectroscopy is a widely used technique in several contexts, including chemical analysis, materials characterization, and catalysis. However, to exploit the high capacities of this technique, signal enhancement is needed. For this purpose, several methodologies can be used, and those known as surface enhanced Raman scattering (SERS), or resonance Raman (RR) have been widely used. However, there are some new strategies, such as electrochemical surface oxidation enhanced Raman scattering (EC-SOERS), that require further understanding for optimum exploitation in diverse analytical contexts. In EC-SOERS, the enhancement of the Raman signal is observed during the electrochemical oxidation of silver in the presence of a precipitating agent, but only for specific concentrations of this agent. In this work, we use electrochemical dark-field microscopy (DFM) to explore and reveal the origin of this concentration dependency by monitoring the oxidative formation of EC-SOERS substrates in solutions of different chloride concentrations. These operando studies provide a complete picture of the processes taking place on the electrode surface and at the solution adjacent to it with a high time resolution, showing that the formation of the EC-SOERS substrate requires sufficient Cl- to generate AgCl nanocrystals without blocking the surface and allowing the release of Ag+ cations. Thanks to the gained mechanistic insights, the selection of a suitable precipitation agent concentration can move from a trial and error selection process to a knowledge-based selection, allowing the rational design of different SOERS substrates that will facilitate the efficient application of SOERS in different research contexts.

This paper presents a multivariate calibration model based on Near Infrared Spectroscopy (NIR) and Surface Enhanced Raman Spectroscopy (SERS) techniques, aiming to achieve efficient and accurate detection of pesticide residues in food by integrating the spectral information from both techniques. The study utilizes the Hilbert-Schmidt Independence Criterion-based Variable Space Iterative Optimization algorithm (HSIC-VSIO) for feature variable selection, and combines it with Partial Least Squares Regression (PLSR) to build a spectral fusion quantitative model. Experimental results show that the calibration set Root Mean Square Error (RMSE1) of the NIR and SERS feature-layer fusion model is 0.160, the prediction set RMSE (RMSE2) is 0.185, the prediction set coefficient of determination (R²) is 0.988, and the Relative Percent Deviation (RPD) is 8.290. Compared to single spectral techniques, the NIR and SERS spectral feature-layer fusion method demonstrates significant superiority in detecting pesticide residues in complex matrix samples. The findings further validate the high sensitivity of SERS technology in detecting low concentrations of pesticides and show that the feature-layer fusion method effectively suppresses matrix interference, enhancing the model's generalization ability. This study provides a reliable tool for the rapid and accurate detection of pesticide residues in food and offers new insights into the application of spectral analysis technologies in the food safety field.

Since 1997, driven by advancements in nanoscience, single-molecule plasmon-enhanced Raman spectroscopy (SM-PERS) has developed into a powerful technique for ultrasensitive trace analysis through fingerprint vibrational chemical information. The nanocavity between the coupled plasmonic nanostructures, offering an exceptionally high Raman signal enhancement factor (i.e., plasmonic field hotspot), is crucial for the achievement of SM-PERS. Herein, we first briefly review the development of SM-PERS, followed by an introduction of the features and methodologies of SM-PERS, as well as the applications of SM-PERS in biological analysis, high-resolution chemical imaging, and the investigations of single-molecule reactions. Finally, a perspective highlighting the advancement of new methods and applications of nano-driven SM-PERS is presented.

Cell analysis is crucial to contemporary biomedical research, as it plays a pivotal role in elucidating life processes and advancing disease diagnosis and treatment. Raman spectroscopy, harnessing distinctive molecular vibrational data, provides a non-destructive method for cell analysis. This review surveys the progress of Raman spectroscopy in cellular analysis, emphasizing its utility in identifying individual cells, monitoring biomolecules, and assessing intracellular environments. A significant focus is placed on the novel application of triple-bond molecules as Raman tags, which enhance imaging capabilities by creating a distinctive signature with minimal background noise. The summary of Raman spectroscopy studies provides a forward-looking perspective on its applications.

Surface-enhanced Raman spectroscopy (SERS) is a highly sensitive analytical technique that captures vibrational spectra of analytes adsorbed to rough coin metal surfaces with remarkable signal intensities. However, its wider application is limited by challenges in substrate range, quantification, and the disposable nature of SERS substrates partly due to irreversible analyte adsorption-commonly referred to as the 'memory effect'. Overcoming these limitations and achieving real-time analysis in flow-through systems remains a key challenge for the advancement of SERS. This study presents a SERS flow cell incorporating an Ag-based SERS substrate and a Pt counter-electrode, enabling the investigation of how electrochemical methods can address existing challenges. Our approach demonstrates that signal intensities can be both enhanced and spectroelectrochemically modified. Additionally, the combination of constant solvent flow and electrochemical potentials enhances the longevity of the SERS substrate, facilitating multianalyte measurements while mitigating the memory effect. Key parameters have been systematically studied, including SERS substrate materials (silver and copper), solvents, buffers, supporting electrolytes, and electrochemical protocols. We achieved consistent and reproducible electrochemical tuning of SERS signals by using halogen-free electrolytes in polar solvents commonly used in techniques like HPLC. The versatility of the system was validated through the analysis of several model compounds and the sequential detection of multiple analytes. We also successfully applied the system to detect and characterise contaminants and pharmaceuticals, highlighting its potential for a wide range of analytical applications.

Functional nucleic acids constitute a distinct category of nucleic acids that diverge from conventional nucleic acid amplification methodologies. They are capable of forming intricate hybrid structures through Hoogsteen and reverse Hoogsteen hydrogen bonding interactions between double-stranded and single-stranded DNA, thereby broadening the spectrum of DNA interactions. In recent years, functional DNA/RNA-based surface-enhanced Raman spectroscopy (SERS) has emerged as a potent platform capable of ultrasensitive and multiplexed detection of a variety of analytes of interest. This review aims to elucidate the operational principles of several functional nucleic acids in SERS detection, including DNAzymes, G-quadruplexes, aptamers, CRISPR, origami etc., alongside the design methodologies and practical applications of functional DNA/RNA-based SERS sensing. Initially, an overview is summarized encompassing the structural attributes and SERS sensing mechanisms inherent to diverse functional DNA/RNA. Following this, various innovative strategies for constructing functional nucleic acid-based SERS sensors are illustrated in detail, aimed at improving the present detection capabilities. A comprehensive summing up is then conducted on the applications of these sensors in crucial fields, such as disease diagnosis, environmental monitoring, and food safety detection, with a particular focus on SERS sensitivity, specificity, and analytical versatility. Finally, conclusive remarks are offered along with an exploration of the existing challenges and prospective avenues for future research in this developed field.

Veterinary drug residues in poultry and livestock products present persistent challenges to food safety, necessitating precise and efficient detection methods. Surface-enhanced Raman scattering (SERS) has been identified as a powerful tool for veterinary drug residue analysis due to its high sensitivity and specificity. However, the development of reliable SERS substrates and the interpretation of complex spectral data remain significant obstacles. This review summarizes the development process of SERS substrates, categorizing them into metal-based, rigid, and flexible substrates, and highlighting the emerging trend of multifunctional substrates. The diverse application scenarios and detection requirements for these substrates are also discussed, with a focus on their use in veterinary drug detection. Furthermore, the integration of deep learning techniques into SERS-based detection is explored, including substrate structure design optimization, optical property prediction, spectral preprocessing, and both qualitative and quantitative spectral analyses. Finally, key limitations are briefly outlined, such as challenges in selecting reporter molecules, data imbalance, and computational demands. Future trends and directions for improving SERS-based veterinary drug detection are proposed.

Surface-enhanced Raman scattering (SERS) has emerged as a powerful tool for trace substances detection due to its exceptional sensitivity, high anti-interference capability, and ease of operation, enabling detection at the single-molecule level. This makes SERS particularly promising for applications such as environmental monitoring, biomedical diagnostics, and food safety. Despite these advantages, SERS faces limitations due to the difficulty of enriching trace substances and the small Raman scattering cross sections of certain molecules. Metal-organic frameworks (MOFs), characterized by their high surface areas and porosity, tunable structures, and diverse functionalities, offer a promising solution to these challenges. By integrating MOFs with SERS technology, we explore how MOF-based SERS probes can enhance the sensitivity, selectivity, and efficiency of trace substance detection through mechanisms such as analyte enrichment, selective molecular capture, and electromagnetic field manipulation. In this paper, a comprehensive review of the structure and synthesis of MOF-SERS composites is presented, with an emphasis on their application in the detection of trace substances. The paper also discusses key challenges in the design and optimization of MOF-based SERS probes, particularly in terms of stability, reproducibility, and integration with existing detection platforms, aiming to broaden their practical applications and improve their detection efficiency.

Molybdenum nitride is a promising candidate for surface-enhanced Raman scattering (SERS) substrates due to its high conductivity, surface plasmon resonance, and chemical stability. Core-shell structures possess unique physical and chemical properties, such as high-volume ratio, low density, short diffusion length, and high load-bearing capacity, making them favorable for SERS applications. In this research, core-shell MoO3 is first synthesized as a precursor oxide using a sacrificial template method, and core-shell MoN microspheres are successfully prepared via subsequent nitriding. As a representative transition metal nitride, the obtained core-shell MoN nanospheres show strong localized surface plasmon resonance and SERS effects. Using these MoN microspheres as Raman substrates allows a range of highly targeted compounds to be accurately detected, and the detection limits for this non-precious-metal substrate morphology are exceptionally high, reaching 10-10 M. In addition, MoN nanospheres exhibit excellent resistance to acid-base corrosion, oxidation, and radiation, thus rendering them suitable for use as substrates in harsh environments.

Nanoparticles have been widely used in cancer diagnostics and treatment research due to their unique properties. Magnetic nanoparticles are popular in imaging techniques due to their ability to alter the magnetization field around them. Plasmonic nanoparticles are mainly applied in cancer treatments like photothermal therapy due to their ability to convert light into heat. While these nanoparticles are popular among their respective fields, magnetic-plasmonic core-shell nanoparticles (MPNPs) have gained popularity in recent years due to the combined magnetic and optical properties from the core and shell. MPNPs have stood out in cancer theranostics as a multimodal platform capable of serving as a contrast agent for imaging, a guidable drug carrier, and causing cellular ablation through photothermal energy conversion. In this review, we summarize the different properties of MPNPs and the most common synthesis approaches. We particularly discuss applications of MPNPs in cancer diagnosis and treatment based on different mechanisms using the magnetic and optical properties of the particles. Lastly, we look into current challenges they face for clinical applications and future perspectives using MPNPs for cancer detection and therapy.

Plasmonic structures using noble metal nano-assemblies are created and printed or stamped with a seal for use as information tags that carry both authenticity and information. We created an ink that contains stealth nanobeacons and evaluated its printing characteristics. Stealth nanobeacons are composed of noble metal nano-assemblies, which are fabricated via a self-assembly process and have indefinite shapes. This plasmonic structure was made into simple ink by mixing it with pure water or existing inkjet printer inks. We discharged this adjusted ink on an inkjet printer to evaluate its surface-enhanced Raman scattering activity and other properties, and confirmed that the ink containing stealth nanobeacons can be printed successfully. The printable ink is expected to be developed into a "Nanotag" information tag and an authenticity tag.

Surface-enhanced Raman spectroscopy (SERS) has evolved significantly over fifty years into a powerful analytical technique. This review aims to achieve five main goals. (1) Providing a comprehensive history of SERS's discovery, its experimental and theoretical foundations, its connections to advances in nanoscience and plasmonics, and highlighting collective contributions of key pioneers. (2) Classifying four pivotal phases from the view of innovative methodologies in the fifty-year progression: initial development (mid-1970s to mid-1980s), downturn (mid-1980s to mid-1990s), nano-driven transformation (mid-1990s to mid-2010s), and recent boom (mid-2010s onwards). (3) Illuminating the entire journey and framework of SERS and its family members such as tip-enhanced Raman spectroscopy (TERS) and shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) and highlighting the trajectory. (4) Emphasizing the importance of innovative methods to overcome developmental bottlenecks, thereby expanding the material, morphology, and molecule generalities to leverage SERS as a versatile technique for broad applications. (5) Extracting the invaluable spirit of groundbreaking discovery and perseverant innovations from the pioneers and trailblazers. These key inspirations include proactively embracing and leveraging emerging scientific technologies, fostering interdisciplinary cooperation to transform the impossible into reality, and persistently searching to break bottlenecks even during low-tide periods, as luck is what happens when preparation meets opportunity.

Monitoring the kinetic changes of drugs and metabolites plays a crucial role in fundamental research, preclinical and clinical application. Raman spectroscopy (RS) is regarded as a fingerprinting technique that can reflect molecular structures but limited in applications due to poor sensitivity. Surface-enhanced Raman spectroscopy (SERS) significantly amplifies the detection sensitivity by plasmonic substrates, facilitating the identification and quantification of small molecules in biological samples, such as serum, urine, and living cells. This review will focus on advances in how SERS has been utilized to monitor the dynamic processes of small molecule drugs and metabolites in recent years. We first provide readers with a comprehensive overview of the mechanism and practical considerations of SERS, including enhancement theory, substrate design, sample pretreatment, molecule-substrate interactions and spectral analysis. Then we describe the latest advances in SERS for the detection and analysis of metabolites and drugs in cells, dynamic monitoring of drug in various biological matrices, and metabolic profiling for health assessment in biological fluids. We believe that high-performance SERS substrates, standardized technical regulations, and artificial intelligence spectral analysis will boost sensitive, accurate, reproducible, and universal molecular detection in the future. We hoped this review could inspire researchers working in related fields to better understand and utilize SERS for the analytical detection of drugs and metabolites.

Plasmonics and superhydrophobicity have garnered broad interest from academics and industry alike, spanning fundamental scientific inquiry and practical technological applications. Plasmonic activity and superhydrophobicity rely heavily on nanostructured surfaces, providing opportunities for their mutually beneficial integration. Engineering surfaces at microscopic and nanoscopic length scales is necessary to achieve superhydrophobicity and plasmonic activity. However, the dissimilar surface energies of materials commonly used in fabricating plasmonic and superhydrophobic surfaces and different length scales pose various challenges to harnessing their properties in synergy. In this review, an overview of various techniques and materials that researchers have developed over the years to overcome this challenge is provided. The underlying mechanisms of both plasmonics and superhydrophobicity are first overviewed. Next, a general classification scheme is introduced for strategies to achieve plasmonic and superhydrophobic properties. Following that, applications of multifunctional plasmonic and superhydrophobic surfaces are presented. Lastly, a future perspective is presented, highlighting shortcomings, and opportunities for new directions.

Raman spectroscopy (RS) is increasingly applied in medical fields to distinguish neoplastic from normal tissues, with recent advancements enabling its use in neurosurgery. This review explores RS as a diagnostic and surgical aid for brain gliomas, detailing its various modalities and applications. Through a comprehensive search in databases including PubMed, Google Scholar, and eLibrary, over 300 references were screened, resulting in 74 articles that met inclusion criteria. Key findings reveal RS's potential in neuro-oncology for examining native biopsy specimens, frozen and paraffin-embedded tissues, and body fluids, as well as performing intraoperative assessments. RS offers promise for identifying gliomas, differentiating them from healthy brain tissue, and establishing precise tumor boundaries during resection.

A multiscale quantum mechanical (QM)/classical approach is presented that is able to model the optical properties of complex nanostructures composed of a molecular system adsorbed on metal nanoparticles. The latter is described by a combined atomistic-continuum model, where the core is described using the implicit boundary element method (BEM) and the surface retains a fully atomistic picture and is treated employing the frequency-dependent fluctuating charge and fluctuating dipole (ωFQFμ) approach. The integrated QM/ωFQFμ-BEM model is numerically compared with state-of-the-art fully atomistic approaches, and the quality of the continuum/core partition is evaluated. The method is then extended to compute surface-enhanced Raman scattering within a time-dependent density functional theory framework.

Detection of biomolecules, Glutathione (GSH) in particular, is important because it helps assess antioxidant capacity, cellular protection, detoxification processes, and potential disease associations. Monitoring glutathione levels can provide valuable information about overall health and well-being. Many medical disorders have been connected to glutathione levels. Higher glutathione levels have been seen in several cancer cell types, which may increase their resistance to radiation and chemotherapy. Glutathione levels can be measured through various methods, such as colorimetric assays and fluorescent probes. However, surface-enhanced Raman scattering (SERS) has been known as an efficient and selective technique for biomolecule detection. Here in this perspective review, we have reported two distinctive methods based on SERS technique in detection of GSH; heat-induced method and reversed reporting agent method. Several variables that can impact the detection scheme were elaborated in the "heat-induced method," including pretreatment, nanoparticle reduction time, the process temperature, the pH of the colloidal solution, the concentration of citrate buffer, and the concentration of participating nanoparticles. To choose the best reporting agent for a reverse reporting scheme using SERS approaches, several reporting agents were examined in the second method. In order to grasp the situation at hand, biomolecule detection-specifically, GSH detection schemes-was briefly discussed. SERS spectroscopy and its associated terminology were then covered followed by the perspective and outlook of GSH detection at the end. To meet the demands of real-time applications in everyday life and to enhance SERS methods for biomolecule detection-in particular, GSH detection-such a thorough investigation is unavoidable.

High-sensitivity and repeatable detection of hydrophobic molecules through the surface-enhanced Raman scattering (SERS) technique is a tough challenge because of their weak adsorption and non-uniform distribution on SERS substrates. In this research, we present a simple self-assembly protocol for monolayer SERS mediated by 6-deoxy-6-thio-β-cyclodextrin (β-CD-SH). This protocol allows for the rapid assembly of a compact silver nanoparticle (Ag NP) monolayer at the oil/water interface within 40 s, while entrapping analyte molecules within hotspots. The proposed method shows general applicability for detecting hydrophobic molecules, exemplified as Nile blue, Nile red, fluconazole, carbendazim, benz[a]anthracene, and bisphenol A. The detection limits range from 10-6to 10-9 M, and the relative standard deviations (RSDs) of signal intensity are less than 10%. Moreover, this method was used to investigate the release behaviors of a hydrophobic pollutant (Nile blue) adsorbed on the nanoplastic surface in the water environment. The results suggest that elevated temperatures, increased salinities, and the coexistence of fulvic acid promote the release of Nile blue. This simple and fast protocol overcomes the difficulties related to hotspot accessibility and detection repeatability for hydrophobic analytes, holding out extensive application prospects in environmental monitoring and chemical analysis.

Confocal Raman microscopy is a powerful technique for identifying materials and molecular species; however, the signal from Raman scattering is extremely weak. Typically, handheld Raman instruments are cost-effective but less sensitive, while high-end scientific-grade Raman instruments are highly sensitive but extremely expensive. This limits the widespread use of Raman technique in our daily life. To bridge this gap, we explored and developed a cost-effective yet highly sensitive confocal Raman microscopy system. The key components of the system include an excitation laser based on readily available laser diode, a lens-grating-lens type spectrometer with high throughput and image quality, and a sensitive detector based on a linear charge-coupled device (CCD) that can be cooled down to -30 °C. The developed compact Raman instrument can provide high-quality Raman spectra with good spectral resolution. The 3rd order 1450 cm-1 peak of Si (111) wafer shows a signal-to-noise ratio (SNR) better than 10:1, demonstrating high sensitivity comparable to high-end scientific-grade Raman instruments. We also tested a wide range of different samples (organic molecules, minerals and polymers) to demonstrate its universal application capability.

Cow's milk allergy (CMA) is considered one of the most prevalent food allergies and a public health concern. Modern medical research shows that the effective way to prevent allergic reactions is to prevent allergic patients from consuming allergenic substances. Therefore, the development of rapid and accurate detection technology for milk allergens detection and early warning is critical to safeguarding those with a cow milk allergy. As the oligonucleotide sequences with high specificity and selectivity, aptamers frequently assemble with transduction elements forming multifarious aptasensors for quantitative detection owing to their high-affinity binding to the target. Current aptasensors in the field of cow's milk allergen detection in recent years are explored in this review. This review takes a look back at a few common assays, including ELISA and PCR, before presenting a clear overview of the aptamer and threshold doses. It delves into a detailed discussion of the current aptamer-based detection techniques and related theories for milk allergen identification. Last but not least, we conclude with a discussion and outlook of the advancements made in allergen detection with aptamers. We sincerely hope that there will be more extensive applications for aptasensors in the future contributing to reducing the possibility of patients suffering from adverse reactions.

Microtaggant technologies for on-dose authentication have garnered significant interest for use in the anti-counterfeit activities and traceability of pharmaceutical dosage forms. Previously, we proposed a stealth nanobeacon (NB) comprising self-assembled colloidal gold nanoparticles with reporter molecules that demonstrated characteristic surface-enhanced Raman scattering (SERS) activity. However, the integration of such microtaggants into standard production lines remains underexplored. In this study, we demonstrate the incorporation of NB into tablet coatings using a simple mixing method with conventional coating solutions. Rapid and discernible SERS responses from the NB-coated tablets were observed in response to laser excitation at 785 nm for 0.1s, implying that it is an advanced and efficient method for counterfeit detection. In addition, the SERS intensity of NB increased with coating time, suggesting that NB can be used as a tracer for the real-time monitoring of coating thickness. Furthermore, NB-coated tablets were indistinguishable from NB-free tablets, even during colorimetric analysis. These results suggest that the NB possesses stealth properties and can be easily incorporated into counterfeit detection products.

Plasmonic nanogaps in strongly coupled metal nanostructures can confine light to nanoscale regions, leading to huge electric field enhancement. This unique capability makes plasmonic nanogaps powerful platforms for boosting light-matter interactions, thereby enabling the rapid development of novel phenomena and applications. This review traces the progress of nanogap systems characterized by well-defined morphologies, controllable optical responses, and a focus on achieving extreme performance. The properties of plasmonic gap modes in far-field resonance and near-field enhancement are explored and a detailed comparative analysis of nanogap fabrication techniques down to sub-nanometer scales is provided, including bottom-up, top-down, and their combined approaches. Additionally, recent advancements and applications across various frontier research areas are highlighted, including surface-enhanced spectroscopy, plasmon-exciton strong coupling, nonlinear optics, optoelectronic devices, and other applications beyond photonics. Finally, the challenges and promising emerging directions in the field are discussed, such as light-driven atomic effects, molecular optomechanics, and alternative new materials.

Surface-enhanced Raman scattering (SERS) sensors typically employ nanophotonic structures that support high-field confinement and enhancement in hotspots to increase the Raman scattering from target molecules by orders of magnitude. In general, high field and SERS enhancement can be achieved by reducing the critical dimensions and mode volumes of the hotspots to nanoscale. To this end, a multitude of SERS sensors employing photonic structures with nanometric hotspots have been demonstrated. However, delivering analyte molecules into nanometric hotspots is challenging, and the trade-off between field confinement/enhancement and analyte delivery efficiency is a critical limiting factor for the performance of many nanophotonic SERS sensors. Here, a new type of SERS sensor employing solid-metal nanoparticles and bulk liquid metal is demonstrated to form nanophotonic resonators with a nanoparticle-on-liquid-mirror (NPoLM) architecture, which effectively resolves this trade-off. In particular, this unconventional sensor architecture allows for the convenient formation of nanometric hotspots by introducing liquid metal after analyte molecules are efficiently delivered to the surface of gold nanoparticles. In addition, a cost-effective and reliable process is developed to produce gold nanoparticles on a substrate suitable for forming NPoLM structures. These NPoLM structures achieve two orders of magnitude higher SERS signals than the gold nanoparticles alone.

Proton-coupled electron transfer (PCET) has been significant in understanding the reactions in solution. In a solid-gas interface, it remains a challenge to identify electron transfer or proton transfer intermediates. Here, in a Au/N2 interface, we regulated and characterized the PCET from p-aminothiophenol (PATP) to p-nitrothiophenol (PNTP) in the plasmon-mediated conversion to p,p'-dimercaptoazobenzene by variable-temperature surface-enhanced Raman spectroscopy. The Raman bands of PATP and PNTP characteristically blue shifted and red shifted as the laser wavelength- and power density-regulated PCET from PATP to PNTP, respectively. These characteristic Raman band shifts were well reproduced by the density functional theoretical simulations of positively charged PATP and negatively charged PNTP, which explicitly evidenced the electron transfer intermediates of PATP or PNTP on the Au surface. PCET did not occur in the temperature cycle between 100 and 370 K without laser illumination. These results demonstrated a characteristic local PCET loop composed of electron transfer between PATP/PNTP and Au followed by intermolecular proton transfer between PATP and PNTP and the significance of conducting electron transfer on Au.

As a nondestructive and ultrasensitive technique, surface-enhanced Raman spectroscopy (SERS) has captivated the attention of the global scientific community for over 50 years. Among the various spectroscopic techniques derived from SERS, shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) stands as a cutting-edge advancement. The innovative and versatile core-shell nanoparticle structures used in SHINERS have emerged as an ideal platform for interfacial research, offering high sensitivity and broad applicability across diverse materials and single-crystal surfaces. Consequently, SHINERS has seen widespread adoption in pivotal fields, such as interface chemistry, electrocatalysis, biomedicine, materials, and food safety. In this Perspective, we outline the evolutionary journey of SHINERS, delve deep into its applications in fundamental research for interface characterization and catalysis, and explore its practical utility in critical areas of food safety and biomedicine analysis. Additionally, we map out the prospective trajectory and future milestones that await SHINERS as it continues to revolutionize the landscape of scientific exploration.

Vibrational Raman scattering-a process where light exchanges energy with a molecular vibration through inelastic scattering-is most fundamentally described in a quantum framework where both light and vibration are quantized. When the Raman scatterer is embedded inside a plasmonic nanocavity, as in some sufficiently controlled implementations of surface-enhanced Raman scattering (SERS), the coupled system realizes an optomechanical cavity where coherent and parametrically amplified light-vibration interaction becomes a resource for vibrational state engineering and nanoscale nonlinear optics. The purpose of this Perspective is to clarify the connection between the languages and parameters used in the fields of molecular cavity optomechanics (McOM) versus its conventional, "macroscopic" counterpart and to summarize the main results achieved so far in McOM and the most pressing experimental and theoretical challenges. We aim to make the theoretical framework of molecular cavity optomechanics practically usable for the SERS and nanoplasmonics community at large. While quality factors (Q) and mode volumes (V) essentially describe the performance of a nanocavity in enhancing light-matter interaction, we point to the light-cavity coupling efficiencies (η) and optomechanical cooperativities () as the key parameters for molecular optomechanics. As an illustration of the significance of these quantities, we investigate the feasibility of observing optomechanically induced transparency with a molecular vibration-a measurement that would allow for a direct estimate of the optomechanical cooperativity.

Plasmonic nanoparticles (NPs) have played a significant role in the evolution of modern nanoscience and nanotechnology in terms of colloidal synthesis, general understanding of nanocrystal growth mechanisms, and their impact in a wide range of applications. They exhibit strong visible colors due to localized surface plasmon resonance (LSPR) that depends on their size, shape, composition, and the surrounding dielectric environment. Under resonant excitation, the LSPR of plasmonic NPs leads to a strong field enhancement near their surfaces and thus enhances various light-matter interactions. These unique optical properties of plasmonic NPs have been used to design chemical and biological sensors. Over the last few decades, colloidal plasmonic NPs have been greatly exploited in sensing applications through LSPR shifts (colorimetry), surface-enhanced Raman scattering, surface-enhanced fluorescence, and chiroptical activity. Although colloidal plasmonic NPs have emerged at the forefront of nanobiosensors, there are still several important challenges to be addressed for the realization of plasmonic NP-based sensor kits for routine use in daily life. In this comprehensive review, researchers of different disciplines (colloidal and analytical chemistry, biology, physics, and medicine) have joined together to summarize the past, present, and future of plasmonic NP-based sensors in terms of different sensing platforms, understanding of the sensing mechanisms, different chemical and biological analytes, and the expected future technologies. This review is expected to guide the researchers currently working in this field and inspire future generations of scientists to join this compelling research field and its branches.

Surface-enhanced Raman scattering (SERS) is an innovative spectroscopic technique that amplifies the Raman signals of molecules adsorbed on rough metal surfaces, making it pivotal for single-molecule detection in complex biological and environmental matrices. This review aims to elucidate the design strategies and recent advancements in the application of standalone SERS nanoprobes, with a special focus on quantifiable SERS tags. We conducted a comprehensive analysis of the recent literature, focusing on the development of SERS nanoprobes that employ novel nanostructuring techniques to enhance signal reliability and quantification. Standalone SERS nanoprobes exhibit significant enhancements in sensitivity and specificity due to optimized hot spot generation and improved reporter molecule interactions. Recent innovations include the development of nanogap and core-satellite structures that enhance electromagnetic fields, which are crucial for SERS applications. Standalone SERS nanoprobes, particularly those utilizing indirect detection mechanisms, represent a significant advancement in the field. They hold potential for wide-ranging applications, from disease diagnostics to environmental monitoring, owing to their enhanced sensitivity and ability to operate under complex sample conditions.

Surface-enhanced Raman spectroscopy (SERS), with molecular fingerprint information and single-molecule sensitivity, has been widely used for qualitative and quantitative analysis in various fields. Plenty of nanostructured plasmonic materials have been fabricated to achieve high SERS activity. Currently, great difficulty lies in evaluating the SERS performance among substrates, making it difficult to standardize. Addressing this problem, this work proposed the SERS performance factor (S P F = Δ I S E R S Δ C S E R S / Δ I R a m a n Δ C R a m a n ) as a practically operational parameter to evaluate the sensitivity of SERS substrates. Experimentally, SPF can be obtained by taking the ratio of the slopes (i.e., the sensitivity) for concentration-dependent SERS and normal Raman measurements in the linear range of the intensity response under identical experimental conditions. Theoretically, SPF quantitatively describes the overall contribution to the SERS performance, (i.e., the electromagnetic (EM) enhancement of the SERS substrate and the interfacial interaction between the probe and substrate). The use of SPF as the criterion for evaluating the SERS performance was validated on Au nanoparticles in colloidal and solid states, where the tendency of SPF is consistent with that of the sensitivity of the probe molecules. Derived from the typically used surface enhancement factor EF in which accurate parameters are hardly achievable and different from concentration-dependent analytical enhancement factor AEF, SPF distinguishes itself with a simpler calculation and thereby offers a convenient and reliable protocol for the evaluation of the performance of different SERS substrates, which is very important to the practical application of SERS.

In light of the intensifying global energy crisis and the mounting demand for environmental protection, it is of vital importance to develop advanced hydrogen energy conversion systems. Electrolysis cells for hydrogen production and fuel cell devices for hydrogen utilization are indispensable in hydrogen energy conversion. As one of the electrolysis cells, water splitting involves two electrochemical reactions, hydrogen evolution reaction and oxygen evolution reaction. And oxygen reduction reaction coupled with hydrogen oxidation reaction, represent the core electrocatalytic reactions in fuel cell devices. However, the inherent complexity and the lack of a clear understanding of the structure-performance relationship of these electrocatalytic reactions, have posed significant challenges to the advancement of research in this field. In this work, the recent development in revealing the mechanism of electrocatalytic reactions in hydrogen energy conversion systems is reviewed, including in situ characterization and theoretical calculation. First, the working principles and applications of operando measurements in unveiling the reaction mechanism are systematically introduced. Then the application of theoretical calculations in the design of catalysts and the investigation of the reaction mechanism are discussed. Furthermore, the challenges and opportunities are also summarized and discussed for paving the development of hydrogen energy conversion systems.

The enhancement of the molecular Raman signal in plasmon-assisted surface-enhanced Raman scattering (SERS) results from electromagnetic and chemical mechanisms, the latter determined to a large extent by the chemical interaction between the molecules and the hosting plasmonic nanoparticles. A precise quantification of the chemical mechanism in SERS based on quantum chemistry calculations is often challenging due to the interplay between the chemical and electromagnetic effects. Based on an atomistic description of the SERS signal, which includes the effect of strong field inhomogeneities, we introduce a comprehensive approach to evaluate the chemical enhancement in SERS, which conveniently removes the electromagnetic contribution inherent to any quantum calculation of the Raman polarization. Our approach uses density functional theory (DFT) and time-dependent DFT to compute the total SERS signal, together with the electromagnetic and chemical enhancement factors. We apply this framework to study the chemical enhancement of biphenyl-4,4'-dithiol embedded between two gold clusters. Although we find that for small clusters the total SERS enhancement is mainly determined by the chemical mechanism, our procedure enables removal of the electromagnetic contribution and isolation of the contribution of the bare chemical effect. This approach can be applied to reproduce and understand Raman line activation and strength in practical and challenging SERS configurations such as in plasmonic nano- and pico-cavities.

Catalysis stands as an indispensable cornerstone of modern society, underpinning the production of over 80% of manufactured goods and driving over 90% of industrial chemical processes. As the demand for more efficient and sustainable processes grows, better catalysts are needed. Understanding the working principles of catalysts is key, and over the last 50 years, surface-enhanced Raman Spectroscopy (SERS) has become essential. Discovered in 1974, SERS has evolved into a mature and powerful analytical tool, transforming the way in which we detect molecules across disciplines. In catalysis, SERS has enabled insights into dynamic surface phenomena, facilitating the monitoring of the catalyst structure, adsorbate interactions, and reaction kinetics at very high spatial and temporal resolutions. This review explores the achievements as well as the future potential of SERS in the field of catalysis and energy conversion, thereby highlighting its role in advancing these critical areas of research.