Use Of Surface-enhanced Raman Scattering Research Articles

Multiplex Determination of Glycan Profiles on Urinary Prostate-Specific Antigen by Quartz-Crystal Microbalance Combined with Surface-Enhanced Raman Scattering.

Prostate cancer remains a major health concern, with prostate-specific antigen (PSA) being a key biomarker for its detection and monitoring. However, PSA levels often fall into a "gray zone", where PSA levels are not clearly indicative of cancer, thus complicating early diagnosis and treatment decisions. Glycosylation profiles, which often differ between healthy and diseased cells, have emerged as potential biomarkers to enhance the specificity and sensitivity of cancer diagnosis in these ambiguous cases. We propose the integration of two complementary techniques, namely quartz-crystal microbalance with dissipation (QCM-D) and surface-enhanced Raman scattering (SERS) to study PSA glycan profiles. QCM-D offers real-time operation, PSA mass quantification, and label-free detection with high sensitivity, as well as enhanced specificity and reduced cross-reactivity when using nucleic acid aptamers as capture ligands. Complementary SERS sensing enables the determination of the glycosylation pattern on PSA, at low concentrations and without the drawbacks of photobleaching, thereby facilitating multiplexed glycosylation pattern analysis. This integrated setup could retrieve a data set comprising analyte concentrations and associated glycan profiles in relevant biological samples, which may eventually improve early disease detection and monitoring. Prostate-specific antigen (PSA), a glycoprotein secreted by prostate epithelial cells, serves as our proof-of-concept analyte. Our platform allows multiplex targeting of PSA multiplex glycosylation profiles of PSA at "gray zone" concentrations for prostate cancer diagnosis. We additionally show the use of SERS for glycan analysis in PSA secreted from prostate cancer cell lines after androgen-based treatment. Differences in PSA glycan profiles from resistant cell lines after androgen-based treatment may eventually improve cancer treatment.

Designing SERS nanotags for profiling overexpressed surface markers on single cancer cells: A review

This review focuses on the chemical design and the use of Surface-Enhanced Raman Scattering (SERS)-active nanotags for measuring surface markers that can be overexpressed at the surface of single cancer cells. Indeed, providing analytical tools with true single-cell measurements capabilities is capital, especially since cancer research is increasingly leaning toward single-cell analysis, either to guide treatment decisions or to understand complex tumor behaviour including the single-cell heterogeneity and the appearance of treatment resistance. Over the past two decades, SERS nanotags have triggered significant interest in the scientific community owing their advantages over fluorescent tags, mainly because SERS nanotags resist photobleaching and exhibit sharper signal bands, which reduces possible spectral overlap and enables the discrimination between the SERS signals and the autofluorescence background from the sample itself. The extensive efforts invested in harnessing SERS nanotags for biomedical purposes, particularly in cancer research, highlight their potential as the next generation of optical labels for single-cell studies. The review unfolds in two main parts. The first part focuses on the structure of SERS nanotags, detailing their chemical composition and the role of each building block of the tags. The second part explores applications in measuring overexpressed surface markers on single-cells. The latter encompasses studies using single nanotags, multiplexed measurements, quantitative information extraction, monitoring treatment responses, and integrating phenotype measurements with SERS nanotags on single cells isolated from complex biological matrices. This comprehensive review anticipates SERS nanotags to persist as a pivotal technology in advancing single-cell analytical methods, particularly in the context of cancer research and personalized medicine.

Research Status in the Use of Surface-Enhanced Raman Scattering (SERS) to Detect Pesticide Residues in Foods and Plant-Derived Chinese Herbal Medicines.

Surface-enhanced Raman scattering (SERS) technology has unique advantages in the rapid detection of pesticides in plant-derived foods, leading to reduced detection limits and increased accuracy. Plant-derived Chinese herbal medicines have similar sources to plant-derived foods; however, due to the rough surfaces and complex compositions of herbal medicines, the detection of pesticide residues in this context continues to rely heavily on traditional methods, which are time consuming and laborious and are unable to meet market demands for portability. The application of flexible nanomaterials and SERS technology in this realm would allow rapid and accurate detection in a portable format. Therefore, in this review, we summarize the underlying principles and characteristics of SERS technology, with particular focus on applications of SERS for the analysis of pesticide residues in agricultural products. This paper summarizes recent research progress in the field from three main directions: sample pretreatment, SERS substrates, and data processing. The prospects and limitations of SERS technology are also discussed, in order to provide theoretical support for rapid detection of pesticide residues in Chinese herbal medicines.

Surface-enhanced Raman spectroscopy in women with benign and malignant endometrial diseases

Background. This study aimed to enhance early detection of endometrial cancer in women and distinguish benign conditions from endometrial cancer using surface-enhanced Raman scattering (SERS) analysis of blood plasma, thus increasing diagnostic efficacy.
 Materials and methods. The study of blood plasma from 95 female patients aged 22–79 years was performed. The patients were divided into four groups: group 1 included 29 women with endometrial adenocarcinoma, group 2 included 31 patients with endometrial polyp, group 3 included 10 women with endometrial hyperplasia, and the comparison group consisted of 25 healthy women. Blood plasma was analyzed via SERS, with three Raman spectra recorded per sample. Spectral measurements of the SERS substrate were assessed using dried samples on an experimental bench equipped with the spectrometric system RL785 (LLC “Foton-Bio”, Russia), incorporating a CCD detector, laser radiation source with a wavelength of 785 nm, and ADF U300 microscope (ADF, China). A silver substrate composed of dried silver colloid was used to demonstrate the enhancement effect on the Raman signal from the surface of the blood plasma.
 Results. Spectral and specific features that distinguish adenocarcinoma, polyps, and endometrial hyperplasia were identified and evaluated. Spectral and quantitative differences specific to each condition, which are crucial for the differential diagnosis of pathologic tissues, were also identified. The accuracy rates of the optical diagnostics in distinguishing endometrial adenocarcinoma from the control group and endometrial hyperplasia were 87% and 85%, respectively, for the calibration and verification spectral sets (where the sensitivity and specificity were 66% and 92% for the spectral verification set, respectively). The accuracy rates of distinguishing control from endometrial hyperplasia and endometrial adenocarcinoma were 86% and 85%, respectively, and the accuracy of distinguishing endometrial hyperplasia from control and endometrial adenocarcinoma was 81% for the calibration and verification sets of spectra. In addition, the study demonstrated improved accuracy in differentiating adenocarcinoma from hyperplasia, including polyps. The accuracy rate was 93% in the calibration set of spectra, with sensitivity and specificity of 96% and 90%, whereas in the validation set, it was 91%, with sensitivity and specificity of 93% and 88%, respectively.
 Conclusions. The study demonstrated the potential use of SERS for differentiating expression patterns in endometrial cancer from those in benign conditions.

Food Safety Issues in the Oltrepò Pavese Area: A SERS Sensing Perspective.

Handly and easy-to-use optical instrumentation is very important for food safety monitoring, as it provides the possibility to assess law and health compliances at every stage of the food chain. In particular, the Surface-enhanced Raman Scattering (SERS) method appears highly promising because the intrinsic drawback of Raman spectroscopy, i.e., the natural weakness of the effect and, in turn, of the signal, is overcome thanks to the peculiar interaction between laser light and plasmonic excitations at the SERS substrate. This fact paved the way for the widespread use of SERS sensing not only for food safety but also for biomedicine, pharmaceutical process analysis, forensic science, cultural heritage and more. However, the current technological maturity of the SERS technique does not find a counterpart in the recognition of SERS as a routine method in compliance protocols. This is mainly due to the very scattered landscape of SERS substrates designed and tailored specifically for the targeted analyte. In fact, a very large variety of SERS substrates were proposed for molecular sensing in different environments and matrices. This review presents the advantages and perspectives of SERS sensing in food safety. The focus of the survey is limited to specific analytes of interest for producers, consumers and stakeholders in Oltrepò Pavese, a definite regional area that is located within the district of Pavia in the northern part of Italy. Our attention has been addressed to (i) glyphosate in rice fields, (ii) histamine in a world-famous local product (wine), (iii) tetracycline, an antibiotic often detected in waste sludges that can be dangerous, for instance in maize crops and (iv) Sudan dyes-used as adulterants-in the production of saffron and other spices, which represent niche crops for Oltrepò. The review aims to highlight the SERS performance for each analyte, with a discussion of the different methods used to prepare SERS substrates and the different reported limits of detection.

SERS Detection of the Anti-Epileptic Drug Perampanel in Human Saliva.

Surface-Enhanced Raman Scattering (SERS) can obtain the spectroscopic response of specific analytes. In controlled conditions, it is a powerful quantitative technique. However, often the sample and its SERS spectrum are complex. Pharmaceutical compounds in human biofluids with strong interfering signals from proteins and other biomolecules are a typical example. Among the techniques for drug dosage, SERS was reported to detect low drug concentrations, with analytical capability comparable to that of the assessed High-Performance Liquid Chromatography. Here, for the first time, we report the use of SERS for Therapeutic Drug Monitoring of the Anti-Epileptic Drug Perampanel (PER) in human saliva. We used inert substrates decorated with gold NPs deposited via Pulsed Laser Deposition as SERS sensors. We show that it is possible to detect PER in saliva via SERS after an optimized treatment of the saliva sample. Using a phase separation process, it is possible to extract all the diluted PER in saliva from the saliva phase to a chloroform phase. This allows us to detect PER in the saliva at initial concentrations of the order of 10-7 M, thus approaching those of clinical interest.

Surface enhanced Raman scattering active substrate based on hydrogel microspheres for pretreatment-free detection of glucose in biological samples

Determining glucose in biological samples is tedious and time-consuming due to sample pretreatment. The sample is usually pretreated to remove lipids, proteins, hemocytes and other sugars that interfere with glucose detection. A surface-enhanced Raman scattering (SERS) active substrate based on hydrogel microspheres has been developed to detect glucose in biological samples. Due to the specific catalytic action of glucose oxidase (GOX), the high selectivity of detection is guaranteed. The hydrogel substrate prepared by microfluidic droplets technology protects the silver nanoparticles from the surrounding environment and improves the stability and reproducibility of the assay. In addition, the hydrogel microspheres have size-adjustable pores that selectively allow small molecules to pass through. The pores block the entry of large molecules, such as impurities, enabling glucose detection through glucose oxidase etching without sample pretreatment. This hydrogel microsphere-SERS platform is highly sensitive and enables reproducible detection of different glucose concentrations in biological samples. The use of SERS to detect glucose provides clinicians with new diagnostic methods for diabetes and a new application opportunity for SERS-based molecular detection techniques.

Surface-enhanced Raman scattering for biosensing platforms: a review

ABSTRACT The past few decades have seen rapid advances in surface-enhanced Raman scattering (SERS) techniques which have enabled increasingly efficient detection of infinitesimal molecular traces down to the single molecule. This occurrence paved the way for promising applications, among which the use of SERS in highly efficient label-free optical sensors, thus attaining a large interest, especially in the biomedical field. SERS sensors are realized following different strategies, usually involving the control of size and shape of nanoantennas and the design of nanostructures arrays to precisely set the Localized Surface Plasmon resonances (LSP) and the hot spots positions. However, this may entail the use of lithographic techniques with high fabrication costs. Other approaches are based on disordered arrays of plasmonic nanostructures, much cheaper and easier to fabricate, although the control of the hot spots position and performances is lost. Here we review the more recent SERS strategies approached in order to obtain the desired detection of analytes and specific biomolecular species, ranging from the realization of particularly efficient SERS substrates suitable for hydrated molecules to the creation of hot spots in a liquid environment enabling highly sensitive spectroscopic sensors in the natural habitat of the biomolecules.

Recent Advances in the Use of Surface-Enhanced Raman Scattering for Illicit Drug Detection.

The rapid increase in illicit drug use and its adverse health effects and socio-economic consequences have reached alarming proportions in recent years. Surface-enhanced Raman scattering (SERS) has emerged as a highly sensitive analytical tool for the detection of low dosages of drugs in liquid and solid samples. In the present article, we review the state-of-the-art use of SERS for chemical analysis of illicit drugs in aqueous and complex biological samples, including saliva, urine, and blood. We also include a review of the types of SERS substrates used for this purpose, pointing out recent advancements in substrate fabrication towards quantitative and qualitative detection of illicit drugs. Finally, we conclude by providing our perspective on the field of SERS-based drug detection, including presently faced challenges. Overall, our review provides evidence of the strong potential of SERS to establish itself as both a laboratory and in situ analytical method for fast and sensitive drug detection and identification.

Hierarchically ordered microcrater array with plasmonic nanoparticle clusters for highly sensitive surface-enhanced Raman scattering

Surface-enhanced Raman scattering (SERS) with unique molecular vibrational fingerprints for identifying analytes provides an effective spectroscopic approach for the detection of trace molecules in biomedical/analytical fields. Although a great amount of efforts has been devoted to developing various SERS substrates with hierarchical micro/nanostructures, challenges remain in completely concentrating the target molecules within a sensitive area and thereby enhancing detection sensitivity. Here, we report trace molecular detection using superhydrophobic microcrater array as surface-enhanced Raman substrate (SMA-SERS). The hierarchically ordered microcrater array with plasmonic nanoparticle clusters is quickly obtained by the two-step process of femtosecond laser texturing and magnetron sputtering. The resultant substrates with hierarchical micro-/nanostructures show excellent superhydrophobicity with a contact angle above 150° and satisfactory plasmonic nanostructures with the easily attainable Raman signal enhancement factor of ~4.82 × 108. The signals on the SMA-SERS maintain uniformity with a relative standard deviation of <15%. These findings manifest that the SMA-SERS is an extraordinary strong candidate for obtaining high-quality and reliable SERS, facilitating a widespread use of SERS for practical applications.

Single‐Particle Analysis on Plasmonic Nanogap Systems for Quantitative SERS

AbstractWith advances in the design, synthesis and analysis of various metallic nanoparticles and substrates, surface‐enhanced Raman scattering (SERS) with plasmonic nanostructures has been extensively studied, and numerous SERS applications have been demonstrated in various applications including biomedical applications; however, the mechanism of SERS is not completely understood yet, and many challenges, including structural and spectral reproducibility, exist to achieve quantitative SERS analysis for practical and reliable use of SERS. Since SERS signal reproducibility mainly stems from structural reproducibility of targeted nanostructures, single‐particle SERS analysis is highly beneficial in understanding SERS signals generated from different plasmonic nanostructures and provides analytical insights that cannot be obtained with ensemble‐average spectrum‐based analysis. Single‐particle analysis is typically composed of single‐particle images and spectra, and the statistical results show the single‐particle SERS enhancement factor distribution of SERS signals and precise structure‐spectrum relationship. In particular, studying and evaluating single‐molecule SERS results require single‐particle analysis to fully understand how single‐particle images and spectra are correlated with how the position, orientation and resonance of a Raman dye affect single‐molecule SERS signals from individual nanoparticles, and this is often correlated with computational simulation results. In this mini‐review, we introduce key issues for quantitative SERS and present the fundamental SERS features obtained by single‐particle analysis, focused on plasmonic nanogap structures since these structures offer the very strong electromagnetic field‐based SERS signals with high controllability in structure and signal. We categorized the nanogap particle‐based SERS platforms into two different classes – plasmonic nanogap strctures with an intergap (the gap between two structures; intergap nanoparticles) and plasmonic nanogap structures with an intragap (the gap formed inside a single particle; intragap nanoparticles). Finally, we discuss the challenges and perspectives in designing and synthesizing nanogap structures that deliver strong, reproducible, and reliable SERS signals for the quantitative SERS analysis.

Trace level detection of select opioids (fentanyl, hydrocodone, oxycodone, and tramadol) in suspect pharmaceutical tablets using surface-enhanced Raman scattering (SERS) with handheld devices.

The opioid crisis in the USA has resulted in over 702,000 overdose fatalities between 1999 and 2017 and can be attributed to over-prescription of opioids and abuse of synthetic opioids in combination with other illicit drugs. A rapid and sensitive SERS method has been developed for trace detection of opioids including fentanyl, hydrocodone, oxycodone, and tramadol in low-dosage suspect tablets using two different handheld Raman spectrometers equipped with 785 and 1064nm lasers. The method involves a micro-extraction procedure using 10% methanol in deionized water, followed by filtration and addition of colloidal silver and aqueous KBr, resulting in a mixture that can be measured directly via a glass vial. The lowest concentration (Cmin ) of fentanyl, tramadol, oxycodone, and hydrocodone standards that yielded a positive match was 250ng/ml, 5, 10, and 10μg/ml using the 1064nm laser device and 100ng/ml, 1μg/ml, 500ng/ml, and 750ng/ml using the 785nm laser device, respectively. For the analysis of suspect tablets containing these opioids, the Cmin ranges between 5 and 75µg/ml for 1064nm laser device and 1 and 50µg/ml for 785nm laser device. The overall positive identification rate for all the opioids studied in the suspect counterfeit tablets analyzed ranged from 80% to 100%. The use of SERS for rapid chemical identification at remote sampling sites, such as international mail facilities (IMFs) and express courier hubs (ECHs), provides a rugged, simple, and practical method applicable for point-of-entry sampling and analysis.

Recent advances in nanoporous AAO based substrates for surface-enhanced raman scattering

Abstract Nanoporous anodic aluminium oxide (AAO) has become one of the most attractive engineered template for sensing, drug delivery, catalysis, photonics, electronics, energy generation, and storage applications. The formation of AAO is based on the low-cost self-ordering anodization of pure aluminium, which provides perpendicularly aligned, well-organized nanoporous structures with hexagonal symmetry. Due to its distinctive physical and chemical characteristics, it has been widely examined for the development of advanced, cheap, reproducible, and portable sensing devices. On the other hand, from the last few decades, surface-enhanced Raman scattering (SERS) spectroscopy has drawn a wide range of attention because of its label-free detection capability and extreme sensitivity towards the detection of a lower limit of analytes. The key barrier to the extensive use of SERS for regular recognition is the lack of reproducibility of the substrate (periodicity, surface roughness, thickness) as well as the signal (wavelength position and intensity) which are significant for SERS applications. This paper provides a review of AAO templates for the fabrication of reproducible SERS active substrate for sensing various kind of molecules.

Cyclodextrin-Based Synthesis and Host-Guest Chemistry of Plasmonic Nanogap Particles with Strong, Quantitative, and Highly Multiplexable Surface-Enhanced Raman Scattering Signals.

We developed a synthetic strategy to form cyclodextrin-based intrananogap particles (CIPs) with a well-defined ∼1 nm interior gap in a high yield (∼97%), and were able to incorporate 10 different Raman dyes inside the gap using the cyclodextrin-based host-guest chemistry, leading to strong, reproducible, and highly multiplexable surface-enhanced Raman scattering (SERS) signals. The average SERS enhancement factor (EF) for CIPs was 3.0 × 109 with a very narrow distribution of the EFs that range from 9.5 × 108 to 9.5 × 109 for ∼95% of the measured particles. Remarkably, 10 different Raman dyes can be loaded within the nanogap of CIPs, and 6 different Raman dye-loaded CIPs with little spectral overlaps were distinctly detected for cancer cell imaging applications with a single excitation source. Our synthetic strategy provides new platforms in precisely forming plasmonic nanogap structures with all key features for widespread use of SERS including strong signal intensity, reliability in quantification of signal and multiplexing capability.

Improvement of Surface-Enhanced Raman Scattering Method for Single Bacterial Cell Analysis.

Surface-enhanced Raman scattering (SERS) is a useful tool for label-free analysis of bacteria at the single cell level. However, low reproducibility limits the use of SERS. In this study, for the sake of sensitive and reproducible Raman spectra, we optimized the methods for preparing silver nanoparticles (AgNPs) and depositing AgNPs onto a cell surface. We found that fast dropwise addition of AgNO3 into the reductant produced smaller and more stable AgNPs, with an average diameter of 45 ± 4 nm. Compared with that observed after simply mixing the bacterial cells with AgNPs, the SERS signal was significantly improved after centrifugation. To optimize the SERS enhancement method, the centrifugal force, method for preparing AgNPs, concentration of AgNPs, ionic strength of the solution used to suspend the cells, and density of the cells were chosen as impact factors and optimized through orthogonal experiments. Finally, the improved method could generate sensitive and reproducible SERS spectra from single Escherichia coli cells, and the SERS signals primarily arose from the cell envelope. We further verified that this optimal method was feasible for the detection of low to 25% incorporation of 13C isotopes by the cells and the discrimination of different bacterial species. Our work provides an improved method for generating sensitive and reproducible SERS spectra.

Gold and silver nanoparticles used for SERS detection of S. aureus and E. coli

Surface enhanced Raman scattering (SERS) is emerging as a robust analytical method used in sensing applications in chemical as well as biological systems. SERS has been reported to be used in fast detection of micro-organisms up to the specificity of strain identification. However, use of SERS is tricky because of difficulties involved in selection of SERS active substrate so as to give uniform, sensitive as well as reproducible results. We have synthesized silver and gold nanoparticles using chemical, electrochemical and microwave-assisted methods followed by their characterization. Uses of these nanoparticles in association with micro-organisms such as S. aureus and E. coli have been analyzed using SERS to generate signature spectra. This demonstrates use of so synthesized gold and silver nanoparticles as SERS active substrates for rapid detection of micro-organisms which pave way to find applications in disease diagnostics.

Direct SERDS sensing of molecular biomarkers in plants under field conditions.

Molecular biomarkers such as microRNAs (miRNAs) play important roles in regulating various developmental processes in plants. Understanding these pathways will help bioengineer designing organisms for efficient biomass accumulation. Current methods for RNA analysis require sample extraction and multi-step sample analysis, hindering work in field studies. Recent work in the incorporation of nanomaterials for plant bioengineering research is leading the way of an agri-tech revolution. As an example, surface-enhanced Raman scattering (SERS)-based sensors can be used to monitor RNA in vivo. However, the use of SERS in the field has been limited due to issues with observing Raman signal over complex background. To this end, shifted-excitation Raman difference spectroscopy (SERDS) offers an effective solution to extract the SERS signal from high background based on a physical approach. In this manuscript, we report the first application of SERDS on SERS sensors. We investigated this technique on SERS sensor developed for the detection of a microRNA biomarker, miR858. We tested the technique on in vitro samples and validated the technique by detecting the presence of exogenous miR858 in plants directly under ambient light in a growth chamber. The possibility of moving the detection of nucleic acid targets outside the constraints of laboratory setting enables numerous important bioengineering applications. Such applications can revolutionize biofuel production and agri-tech through the use of nanotechnology-based monitoring of plant growth, plant health, and exposure to pollution and pathogens.

Facile Fabrication of Micro/Nano Hierarchical SERS Sensor via Anisotropic Etching and Electrochemical Treatment for Malachite Green Detection

We propose a facile method to produce micro/nano hierarchical surface-enhanced Raman scattering (SERS) active substrates using simple steps and inexpensive costs. The proposed SERS substrate is a silicon pyramid array covered by a nanostructured gold film (AuNS @ SiPA). Through finite element method (FEM) simulation, we showed that many strong local electric field enhancements (hot spots) were formed between the nano-gap of gold nanostructures. In addition, the micron-scale pyramid structure not only increases the sensing surface area of the sensor, but also helps trap light. By combining these micro and nano structures, the proposed micro/nano hierarchical SERS sensor exhibited high sensitivity. Experimental results confirmed that the AuNS @ SiPA substrate has high sensitivity. The SERS signal enhancement factor obtained from the Rhodamine 6G (R6G) probe molecules was as high as 1 × 107 and the SERS substrates were found to be able to detect a very low concentration of 0.01 nM malachite green (MG) solution. Therefore, this study provides a novel and practical method for fabricating SERS substrates that can facilitate the use of SERS in medicine, food safety, and biotechnology.

Hierarchic Interfacial Nanocube Assembly for Sensitive, Selective, and Quantitative DNA Detection with Surface-Enhanced Raman Scattering.

Surface-enhanced Raman scattering (SERS)-based sensing is promising in that it has potential to allow for highly sensitive, selective, and multiplexed detection and imaging. However, the controlled assembly and gap formation between plasmonic particles for generating strong SERS signals in a quantitative manner is highly challenging, especially on biodetection platforms, and particle-to-particle variation in the signal enhancement can vary by several orders of magnitude in a single batch, largely limiting the reliable use of SERS for practical sensing applications. Here, a hierarchic-nanocube-assembly based SERS (H-Cube-SERS) bioassay to controllably amplify the electromagnetic field between gold nanocubes (AuNCs) is developed. Based on this strategy, H-Cube-SERS assay allows for detecting target DNA with a wide dynamic range from 100 aM to 10 pM concentrations in a stable and reproducible manner. It is also found that the uniformly formed AuNCs with flat surfaces are much more suitable for highly sensitive, reliable, and quantitative biodetection assays due to faster DNA binding kinetics, sharper DNA melting transition, wider hot spot regions, and less dependence on light polarization direction than spherical Au nanoparticles with curved interfaces. This work paves the pathways to the quantitative and sensitive biodetection on a SERS platform and can be extended to other particle assembly systems.

Use of Surface-Enhanced Raman Scattering (SERS) Probes to Detect Fatty Acid Receptor Activity in a Microfluidic Device.

In this study, 4-mercaptobenzoic acid (MBA)-Au nanorods conjugated with a GPR120 antibody were developed as a highly sensitive surface-enhanced Raman spectroscopy (SERS) probe, and were applied to detect the interaction of fatty acids (FA) and their cognate receptor, GPR120, on the surface of human embryonic kidney cells (HEK293-GPRR120) cultured in a polydimethylsiloxane (PDMS) microfluidic device. Importantly, the two dominant characteristic SERS peaks of the Raman reporter molecule MBA, 1078 cm−1 and 1581 cm−1, do not overlap with the main Raman peaks from the PDMS substrate when the appropriate spectral scanning range is selected, which effectively avoided the interference from the PDMS background signals. The proposed microfluidic device consisted of two parts, that is, the concentration gradient generator (CGG) and the cell culture well array. The CGG part was fabricated to deliver five concentrations of FA simultaneously. A high aspect ratio well structure was designed to address the problem of HEK cells vulnerable to shear flow. The results showed a positive correlation between the SERS peak intensity and the FA concentrations. This work, for the first time, achieved the simultaneous monitoring of the Raman spectra of cells and the responses of the receptor in the cells upon the addition of fatty acid. The development of this method also provides a platform for the monitoring of cell membrane receptors on single-cell analysis using SERS in a PDMS-based microfluidic device.