Surface-enhanced Raman Scattering Research Articles

Label-Free Surface-Enhanced Raman Spectroscopy Detection of Amyloid Beta on Silver Nanostructured Substrates for Alzheimer's Diagnosis.

Alzheimer's disease (AD) is a public health concern, for which an early diagnosis is essential. Biomass-derived carbon fibres with surface-decorated silver nanoparticles (Ag@CFs) have been utilized as surface enhanced raman spectroscopy (SERS) sensor platformfor the detection of the amyloid beta Aβ (25-35) for the pre-diagnosis of Alzheimer's disease. Structural and morphological characterizations confirmed the distribution of plasmonic silver nanoparticles over the surface of carbon fibres. The SERS sensor performance of Ag@CFs was evaluated using rhodamine 6G, which showed an enhancement of the order of 106 which proved the effectiveness of the developed SERS sensor towards trace level detection of analyte. A range of amyloid beta concentrations, from 100uM to 10pM, have been analyzed as a proof-of concept for this study, showcasing the efficacy of the Ag@CFs based SERS sensor to detect trace level concentrations of amyloid beta, even as low as 10 pM. This investigation is a promising development in the field of AD diagnostics since it may turn out to be a non-invasive, economical and early diagnostic tool.

Identifying the Molecular Fingerprint of Beta-Lactams via Raman/SERS Spectroscopy Using Unconventional Nanoparticles for Antimicrobial Stewardship

Background/Objectives: Beta-lactam antibiotics, derived from penicillin, are the most used class of antimicrobials used for treating bacterial infections. Over the years, microorganisms have developed resistance mechanisms capable of preventing the effect of these drugs. This condition has been a significant public health concern for the 21st century, especially after predictions that antimicrobial resistance could lead to 10 million deaths annually by 2050. The challenge of developing new antimicrobials brings with it the need to ensure the efficacy of existing ones, hence the importance of developing fast and low-cost monitoring techniques. Methods: In this study, we present an alternative based on nanophotonics using Surface-Enhanced Raman Spectroscopy (SERS) mediated by nanoparticles for the detection of antimicrobials, with emphasis on some beta-lactam antibiotics commonly prescribed in cases of critically ill patients. It is a sensitive and accurate technique for drug monitoring, allowing for rapid and specific detection of its molecular signatures. This approach is crucial to address the challenge of antimicrobial resistance and ensure the therapeutic efficacy of existing treatments. Results: Our experiments demonstrate the possibility of identifying spectra with characteristic vibrations (fingerprints) of these antimicrobials via SERS. Conclusions: Our results point to new strategies for molecular monitoring of drugs by optical techniques using unconventional nanoparticles.

Competitive Binding Strategy for Reliable Signal-off Surface Enhanced Raman Scattering Sensing in Protecting Apples from Patulin without External Interference

Patulin is a toxin that can be found in damaged or moldy fruits, especially apples. Very high detection sensitivity can be achieved using the SERS (Surface Enhanced Raman Scattering) technique, which provides information about molecular vibrations. However, unexpected desorption of target toxins from the surface of the SERS substrate and interference from other substances pose a major challenge. Here we investigate a competitive binding strategy for reliable SERS analysis of PAT. Core-Raman molecule-shell (CMS) structures and programmable, specific DNA interactions are utilized to regulate Raman signal intensity without affecting the embedded Raman molecules. Specfically, aptamer-functionalized CMS structures are combined with metal-organic scaffold nanoparticles that possess complementary DNA sequences. In the presence of PAT, binding of the aptamer to the toxin leads to degradation of the hybrid nano assembly, which can be measured by a change in the SERS signal. This SERS strategy enables turn-off sensing in apple juice over a wide range (10pg/mL to 1μg/mL), with a detection limit as low as 0.02ng/mL. Analysis of real samples gives results consistent with high-performance liquid chromatography (HPLC) test. The excellent selectivity and sensitivity of the SERS sensor demonstrate its potential for a wide range of SERS sensor applications.

Surface double defects-dominated TiO2 with high liquid phase stability for smart SERS sensing of dye additives in foods

Surface defect engineering is an effective strategy to regulate the physical and chemical properties of semiconductors for a wide range of applications. Herein, a surface-highly-reduced anatase TiO2 (R-TiO2) with double defects (surface oxygen vacancy defect and Ti3+ energy level defect) was developed as a plasmon-free surface-enhanced Raman scattering (SERS) substrate for ultrasensitive detection of food additives. Abundant surface oxygen vacancies enable R-TiO2 to exist stably in liquid phase, which realizes a smart SERS detection for dye target molecules due to evading fluorescent interference from analytes, while SERS enhancement of analytes cannot be observed on the solid phase substrate at all. Due to the joint contribution of surface double defects, a multi-channel charge transfer mode and a stronger Herzberg-Teller coupling between substrate and analyte are formed, which greatly enhance SERS effect of the substrate for sensitive detection of dye additives in foods with an enhancement factor of 1.6 × 106.

Uniformly aligned Ag NPs/graphene paper for enhanced SERS detection of pesticide residue

The surface-enhanced Raman scattering (SERS) technique provides a quick and reliable method for detecting pesticide residues. In this study, flexible substrates, composed of orderly arranged silver nanospheres (Ag NPs) films on graphene paper, were fabricated through a simple, low-cost Ag NP self-assembly process at a liquid–liquid interface, followed by transfer of the films onto the graphene paper. The SERS performance of the fabricated substrates was evaluated using a portable Raman spectrometer, with rhodamine 6G (R6G) serving as the probe molecule. The results indicate that the bilayer Ag NP films-covered graphene paper exhibits optimal overall performance, characterized by high sensitivity and high uniformity. The limit of detection (LOD) for the R6G molecule is as low as 8.73 × 10−9 M, demonstrating the strong signal amplification capability of the SERS substrate. Moreover, the relative standard deviation (RSD) of the Raman intensity at 1508 cm−1 for different selected points on the substrate is 5.018 %, indicating high uniformity of the SERS substrate. Finally, the performance of the SERS substrate was further evaluated by detecting thiram in fresh orange juice, demonstrating the capability to detect concentrations as low as 10−6 M. This result highlights the significant potential of the developed SERS substrate for practical applications in food safety and quality control.

Antibody screening-assisted multichannel nanoplasmonic sensing chip based on SERS for viral screening and variants identification

The Omicron variants of SARS-CoV-2 have been spreading globally and has never disappeared from our sight, indicating that its coexistence with humans has become a fact, and monitoring its evolution and spread remains a current task. Although polymerase chain reaction (PCR) is the most commonly used virus detection method, it requires labor-intensive and time-consuming procedures in a laboratory setting. Herein, a multichannel nanoplasmonic sensing chip based on surface enhanced Raman spectroscopy (SERS) was developed for detecting N and S proteins, as well as IgG and IgM, related to SARS-CoV-2 Omicron variants. Through a self-screening process, specific antibodies for on-site and rapid identification of important variants of concerns (VoCs) were obtained, and their binding was confirmed by protein structure analysis. The use of these S protein specific antibodies can accurately identify Omicron VoCs (BA. 5, BF.7，XBB.1.5) with the detection limit (LoD) at 0.16 pg/mL. Then, the proposed SERS array chip was integrated with a hand-held Raman spectrometer to successfully detect the Omicron subvariants in real saliva samples within only 20 minutes, greatly reducing the detection time of PCR. This sensing technology will provide a powerful and rapid point-of-care testing (POCT) method for virus diagnosis, subtype identification, and post infection antibody level monitoring.

Surface-enhanced raman scattering detection of persistent organic pollutants using Graphene/Ag-Nanocube hybrid nanostructure substrate

Persistent organic pollutants (POPs) constitute a group of very hazardous chemicals that pose a severe worldwide danger to ecosystems due to their persistence and toxicity to human health and environment. Surface-enhanced Raman scattering (SERS) is an important analytical technique for ultrasensitive chemical and biochemical analysis, providing valuable trace-level spectral information that can be used for POPs detection. The development of ultra-sensitiveSERS substrates for trace-leveldetection of POPsis very desirable. This study presents a straightforward approach to synthesize a highly sensitive SERS substrate as hybrid nanostructure consisting of graphene and Ag nanocubes (graphene/Ag-NCs). The graphene/Ag-NC substrate was successfully employed in the SERS detection of rhodamine-6G (R6G) at concentrations as low as 10−12 M, displaying a remarkable analytical enhancement factor (AEF) of ∼ 1.5 × 109. The estimated limit of detectable (LOD) concentrations of three POPs were found as low as ∼4.13 × 10−9 M for dichlorodiphenyltrichloroethane (DDT), ∼4.47 × 10−9 M for fluorene, and ∼1.7 × 10−8 M for naphthalene. The observed high AEF value and extremely low LODs were attributed to strong adsorption ability of graphene, high electromagnetic enhancement of Ag NCs, revealing the high sensitivity and suitability of the graphene/Ag-NC hybrid substrate for different sensing applications and trace analyte detection.

Investigating SERS performance of controllable fabricated Ag periodic nanostructures with morphologies of nanoclaws and nanocones in detecting SARS-CoV-2 S protein

Surface-enhanced Raman scattering (SERS) spectroscopy plays an important role in enabling high-precision detection and non-invasive diagnostics. Periodic metallic nanostructures with strong electromagnetic fields and tunable localized surface plasmon resonance can achieve high SERS sensitivity, but fabricating such nanostructures remains a challenge. In this work, the anodic aluminum oxide (AAO) nanocavity template-assisted process of fabricating periodic nanostructures with modulating morphologies from Ag nanoclaws (AgNCWs) to Ag nanocones (AgNCEs) is proposed. The morphologies-related SERS performances of nanostructures are analyzed by using rhodamine 6 g (R6G) as a probe molecule and the optimized AgNCEs possess a limit of detection (LOD) of 1 × 10−9 M. A sandwich strategy is applied to detect SARS-CoV-2 S protein in phosphate-buffered saline (PBS) and pharyngeal swab solution (PSS). The ACE2-modified AgNCEs (ACE2/AgNCEs) structure is applied to bind to the SARS-CoV-2 S protein. The 4-MBA and SARS-CoV-2 S antibody functionalized Au nanoparticles (AuNPs) are used as nanotags. By forming the ACE2/AgNCEs-SARS-CoV-2 S protein-nanotags sandwich structure, characteristic peak intensities of 1580 cm−1 are used as the report signal, and the LOD for SARS-CoV-2 S protein in PBS and PSS solution are 10 fg/mL.

Rapid dual-modal detection of two types of pesticides in fruits using SERS-based immunoassay

Pesticide residue is a harmful chemical residue produced in agricultural production, posing a threat to human health. To detect mixed pesticide residues in food rapidly and simultaneously, we present a dual-channel dual-modal test strip immunoassay. According to the standard colorimetric bar, the naked-eye test can achieve semi-quantitative detection. By collecting the Raman spectra of the signal probes, surface-enhanced Raman scattering (SERS) detection can achieve accurate quantification of pesticide residues. Specifically, a double-layer 4-mercaptobenzoic acid (4-MBA) molecule-labeled bimetallic core-shell material (AuMBA@AgMBA) was conjugated with target antibodies to obtain signal probes. Here, antibody bonding was achieved by the dehydrated condensation of its amino group with the carboxyl group of the outer 4-MBA. In addition, the Au nanoparticles were connected to rabbit IgG by electrostatic adsorption as indicating probes to ensure the normal operation of the test strips. Under the optimal parameters, the detection ranges of acetamiprid and carbendazim were 0.3 - 2μg/kg and 3 - 30μg/kg, respectively. Furthermore, the recovery experiments showed that the results of the SERS method matched well with the high-performance liquid chromatography method. The SERS immunoassay is characterized by high sensitivity, rapidity and reliability, which has potential to simultaneously detect mixed pesticides in the field.

Practical SERS Substrates by Spray Coating of Silver Solutions for Deep Learning-Assisted Sensitive Antigen Identification

Surface-enhanced Raman spectroscopy (SERS) has long been recognized for its rapid and sensitive detection capabilities; however, challenges persist in practical fabrication of the substrates and interpreting complex data. Herein, we propose a deep learning (DL) assisted SERS approach to enable rapid and sensitive detection of analytes on a practical yet highly effective substrates prepared by direct spray-coating of a nanoparticle-free true solution of a reactive Ag ink and on-site thermal annealing mediated generation of nanostructures. This design ensured homogeneous distribution of Ag nanostructures throughout the entire substrate, significantly increasing the number of hotspots and enhancing the Raman signals, thereby achieving an impressive analytical enhancement factor of ~1010 in a reproducible and consistent manner. The diagnostic utility of this platform was demonstrated by detecting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein in both buffer and saliva, with detection limits of 74.3pg/mL and 7.43ng/mL, respectively. The DL-assisted SERS not only accurately identified the presence or absence of viral antigen, but also automatically quantified the viral load. This automatic identification achieved an outstanding accuracy of ~99.9%, highlighting the exceptional performance of the proposed platform. This simple, cost-effective, scalable, and ultra-sensitive DL-assisted SERS platform offers significant opportunities for early and precise detection in a range of analytical scenarios.

Surface plasmon-coupled Ag nanosphere-internalized nanocavity arrays for ultrasensitive SERS sensing

Surface-enhanced Raman spectroscopy (SERS) is strongly dependent on the metallic plasmonic nanostructures that can generate plasmon resonance coupling effects. Plasmonic nanostructures with sub-nanometer interparticle gaps or cavities have shown great potential in generating high local electromagnetic fields. Unfortunately, achieving precise control over the geometrical morphology of these nanostructures at the sub-nanometer scale presents significant challenges, particularly in applications where high consistency and homogeneity are required. Here, a reliable approach is proposed to construct plasmon-coupled Ag nanosphere-internalized nanocavity (SIC) arrays to enhance sensitivity and reproducibility in SERS sensing. This novel SIC nanostructure consists of a precise arrangement of Ag nanospheres located at the bottom of Au nanocavities, separated by a precisely controlled nano-Al2O3 dielectric layer. The Al2O3 dielectric layer plays a crucial role in inhibiting quantum tunneling effects at the nanogaps, thereby suppressing charge recombination and leading to strong plasmon resonance coupling. The SERS enhancement tends to significantly diminishes as the nanogap size increases from 4 to 10nm, a spatially averaged SERS enhancement factor of 3.5*108 was obtained when the gap size is 4nm, aligning well with the FDTD simulation results. As a representative application, an indirect detection strategy is utilized to selectively detect TNT with a high level of homogeneity and reproducibility, achieving a relative standard deviation of less than 7.8%. Together with the capability to be fabricated on a flexible polyimide substrate, the SIC substrate shows significant potential for practical applications.

Development and evaluation of a nontargeted electrochemical surface-enhanced Raman spectroscopy (EC-SERS) screening method applied to forensic seized drug casework samples

Screening tests in forensic laboratories are a critical step in ensuring an efficient and effective analytical scheme for presumptive identification. Electrochemical surface-enhanced Raman spectroscopy (EC-SERS) represents a novel workflow that can be applied both in the laboratory and on-site as a fast, inexpensive, and selective approach to seized drug screening. Using cyclic voltammetry and a 785 nm Raman spectrometer, a nontargeted screen was developed using silver screen-printed electrodes and tested on a panel of common drugs of abuse and adulterants. Following characterization of the analyte panel, in-house binary and tertiary mixtures were assessed and the effectiveness of the developed EC-SERS method was tested using common score-based algorithms including correlation, hit-quality-index, spectral angle mapper, and correlation of the 1st derivative. For in-house blind samples, this approach allowed for positive identification of at least one compound in 100 % of samples. Identification of all compounds was lower at 52 %. Seized drug samples from adjudicated casework were tested on-site at the Maryland State Police laboratory as a fit-for-purpose study. EC-SERS provided an accurate screening result of 86 % using the 1st derivative correlation. Applying knowledge of both the local drug landscape and the prevalence of specific adulterants, this value improved to a positive screening of 93 % for the authentic samples. EC-SERS represents a novel approach to drug screening that could impact forensic laboratories, customs and border patrol, public health, and scene investigations. Future work should focus on improved data processing and chemometric tools for data generated in EC-SERS methods.

Elucidating Interplay of Chemical and Metal Interface Damping in Single Gold Nanorods Coated with an Ultrathin Palladium Shell.

Understanding plasmon damping pathways in gold nanoparticles is crucial for its efficient utilization in photochemical processes and biosensing experiments. However, elucidating the competition and interplay between chemical and metal interface damping pathways remains a significant challenge. Herein, we investigate the plasmon decay pathways of thiolated ultrathin palladium (Pd)-coated gold nanorods (AuNRs@Pd) by using dark-field (DF) spectroscopy and surface-enhanced Raman spectroscopy (SERS). AuNRs@Pd were synthesized via bottom-up epitaxial Pd growth at five Pd precursor concentrations. The resulting AuNRs@Pd exhibited a redshift and line width broadening in the DF scattering spectra as the Pd loading on the nanoparticles increased. The attachment of thiol adsorbates (thiophenol) to the nanoparticle surface induced further redshift and narrowed the line width, which was particularly pronounced with increased Pd loading. Electron-withdrawing adsorbates (p-nitrothiophenol) on the nanoparticle surface led to line width narrowing and redshift, attributed to reduced electron density on the AuNR core lattices. This electron density reduction was confirmed through SERS, with AuNRs@Pd53 demonstrating the highest enhancement factor at four Raman peak points. Therefore, we elucidate plausible plasmon decay pathways under the coexistence of chemical interface damping and metal interface damping in single AuNRs@Pd.

Chip-Scale Aptamer Sandwich Assay Using Optical Waveguide-Assisted Surface-Enhanced Raman Spectroscopy

Chip-scale optical waveguide-assisted surface-enhanced Raman spectroscopy (SERS) that used nanoparticles (NPs) was demonstrated. The Raman signals from Raman reporter (RR) molecules on NPs can be efficiently excited by the waveguide evanescent field when the molecules are in proximity to the waveguide surface. The Raman signal was enhanced by plasmon resonance due to the NPs close to the waveguide surface. The optical waveguide mode and the NP-induced field enhancement were calculated using a finite difference method (FDM). The sensing performance of the waveguide-assisted SERS device was experimentally characterized by measuring the Raman scattering from various RRs, including 4-mercaptobenzoic acid (4-MBA), 5,5′-dithio-bis-(2-nitrobenzoic acid) (DTNB), and malachite green isothiocyanate (MGITC). The observed Raman spectral features were identified and assigned to the complex vibrational modes associated with different reporters. A low detection limit of 1 nM was achieved. In addition, the device sensing method was applied to the detection of the biomarker cardiac troponin I (cTnI) using an aptamer sandwich assay immobilized on the device surface. Overall, the optical waveguides integrated with SERS show a miniaturized sensing platform for the detection of small molecules and large proteins, potentially enabling multiplexed detection for clinically relevant applications.

A simple, rapid, and low-cost approach for colloidal nanoparticle-based surface enhanced Raman Scattering detection of endosulfan pesticide at trace levels

Abstract Surface Enhanced Raman Spectroscopy (SERS) is a highly specific, sensitive, and portable technique with great potential for on-site pesticide detection and monitoring. Endosulfan, an organochlorine pesticide known for its high toxicity, slow degradation, and bioaccumulation, has poor affinity for metallic SERS substrates. This study presents a label-free SERS detection method for endosulfan, using aggregating agents like potassium chloride (KCl), potassium hydroxide (KOH), potassium bromide (KBr), and sodium hydroxide (NaOH) to modify the behavior of Ag colloidal nanoparticles (NPs) and enhance the SERS signal of endosulfan molecules trapped within formed hot-spots. We analyzed the UV–Vis spectra, the hydrodynamic diameter, and zeta-potential of Ag NPs with the addition of these agents and endosulfan. Successful detection of both α- and ß- endosulfan isomers at μM concentrations in both ethanol and methanol was achieved with KOH-treated Ag NPs. The method was also applied to detect endosulfan in real water samples, along with simultaneous detection of λ-cyhalothrin, showcasing its capability to identify multiple analytes. The selectivity and specificity were confirmed using a mixture of endosulfan and thiabendazole, highlighting the crucial role of selecting the appropriate aggregating agent for each analyte. Overall, the findings emphasize the potential of aggregating agents to mediate the SERS enhancement of endosulfan, facilitating simple and rapid protocols for environmental pollutant detection, while shedding light on the intricate interplay between NP behavior, surface chemistry, and analyte interaction.

Ultrasensitive NIR-II Surface-Enhanced Resonance Raman Scattering Nanoprobes with Nonlinear Photothermal Effect for Optimized Phototheranostics.

Surface-enhanced resonance Raman scattering (SERRS) in the second near-infrared (NIR-II) window has great potential for improved phototheranostics, but lacks nonfluorescent, resonant and high-affinity Raman dyes. Herein, it is designed and synthesize a multi-sulfur Raman reporter, NF1064, whose maximum absorption of 1064nm rigidly resonates with NIR-II excitation laser while possessing absolutely nonfluorescent backgrounds. Ultrafast spectroscopy suggests that the fluorescence quenching mechanism of NF1064 originates from twisted intramolecular charge transfer (TICT) in the excited state. Gold nanorods (AuNRs) decorated with such nonfluorescent NF1064 (AuNR@NF1064) show remarkable SERRS performances, including zero-fluorescence background, femtomolar-level sensitivity as well as superb photostability without fluorescence photobleaching. More importantly, AuNR@NF1064 exhibits a nonlinear photothermal effect upon plasmonic fields of AuNRs by amplifying the non-radiative decay of nonfluorescent NF1064, thus achieving a high photothermal conversion of 68.5% in NIR-II window with potential for further augmentation. With remarkable SERRS and photothermal properties, the NIR-II nanoprobes allow for high-precision intraoperative guided tumor resection within 8min, and high-efficient hyperthermia combating of drug-resistant bacterial infection within living mouse body. This work not only unlocks the potential of nonfluorescent resonant dyes for NIR-II Raman imaging, but also opens up a new method for boosting photothermal conversion efficiency of nanomaterials.

Innovative Applications and Perspectives of Surface-Enhanced Raman Spectroscopy Technology in Biomedicine.

Surface-enhanced Raman spectroscopy (SERS) has become a revolutionary technique in the biomedical field, providing unparalleled sensitivity for the detection and characterization of biological samples. In this review, recent SERS innovations are comprehensively discussed, including advanced substrate materials, different SERS detection strategies, and multimodal approaches that combine SERS with other biotechnologies. Among them, the role of SERS in the accurate diagnosis of tumors is highlighted, which has promoted accurate molecular analysis and real-time monitoring of treatment effects. In addition, the growing potential of SERS in the treatment of chronic diseases such as cardiovascular disease, diabetes, and neurodegenerative diseases is discussed. Moreover, the integration with microfluidic chip systems for precise single-cell analysis is presented. To give a forward-looking view, the key challenges faced by SERS technology are also proposed, and possible solutions to overcome these obstacles are provided.

Dual SERS enhancement based on Ag@Au Nanopizza combined with superhydrophobic silicon substrate for the detection of early bladder cancer marker-APOA1

Currently, clinical detection of early bladder cancer (BC) biomarkers suffers from insufficient specificity and sensitivity. In this study, a novel triangular nanostructure with protrusions on the surface shaped like a pizza was prepared. It combined with a superhydrophobic Si substrate to achieve trace and ultra-sensitive Surface-enhanced Raman spectroscopy (SERS) detection of APOA1, a urinary biomarker for early BC. Firstly, we precisely controlled the number and spacing of gold protrusions on the surface of Ag@Au Nanopizza to achieve an enhancement factor (EF) of 3.86 × 107 for Ag@Au Nanopizza. In addition, we prepared substrates with superhydrophobic properties by functionalized modification using PS microsphere films as substrate. The enrichment of nanoparticles on the superhydrophobic Si substrate achieves a secondary enhancement of its SERS performance (EF = 5.73 × 107), while also attenuating the coffee-ring effect and improving the homogeneity of the substrate performance. The double SERS enhanced strategy was successfully applied to detect early BC biomarker APOA1. In a wide range (100 fg/mL-100 ng/mL), we achieved quantitative detection of APOA1 with a limit of detection (LOD) of 52 fg/mL. This provides an ultrasensitive, specific, and non-invasive diagnostic strategy for the early diagnosis of BC.

SERS-Based Aptamer Sensing Strategy for Diabetes Biomarker Detection.

Accurate detection of glucose and insulin is crucial for early diagnosis, classification, and timely prevention of diabetes. In this study, we present a novel surface-enhanced Raman scattering (SERS) aptasensor for glucose and insulin detection. The SERS aptasensor is composed of gold bipyramidal nanoparticles (Au BPs), SH-aptamer-methylene blue (MB), and thiolated polyethylene glycol (SH-PEG). As a SERS substrate, the Au BPs provide abundant "hot spots" for the aptasensor to detect target molecules with reasonable sensitivity. One end of the aptamer is modified with a thiol group to facilitate chemical immobilization of SH-aptamer-MB via the Au-S bond, while the other end is functionalized with MB as a probe molecule. SH-PEG is used to block nonspecific adsorption. Glucose and insulin are specifically trapped by SH-aptamer-MB and cause conformational changes in SH-aptamer-MB, which in turn induce changes in the SERS signal of the modified MB, allowing detection of glucose and insulin. Finally, we validated the usefulness of this method on saliva samples and obtained satisfactory results. The proposed aptasensor exhibits strong selectivity and reliable sensitivity and provides an effective strategy for using SERS in disease biomarkers detection.

Reaction-Based SERS Probes for the Detection of Raman-Inactive Species.

Surface-enhanced Raman spectroscopy (SERS) has the advantages of high sensitivity, low water interference, narrow spectral peaks for multicomponent analysis, and rich molecular fingerprint information, presenting great potential to be a robust analytical technology. However, a key issue is the unavailability in directly detecting Raman-inactive species with a small Raman scattering cross-section. Current research has addressed this issue by using specific chemical reactions to induce significant characteristic changes in SERS signals, enabling the sensitive and selective detection of Raman-inactive species. This reaction-activated SERS sensing strategy provides a clever approach to the precise determination of Raman-inactive species. In this review, we have first summarized the design principles and types of reaction-based SERS probes. Furthermore, we have examined the enormous potential of reaction-based SERS probes in the detection of bioactive species, environmental pollutants, and food contaminants. Finally, we have discussed in depth the challenges and prospects of reaction-based SERS probes on stability, reliability, and intelligence. The review is aimed to inspire a more advanced design of reaction-based SERS probes, thus further facilitating their extensive applications in SERS analysis.