Surface-enhanced Raman spectroscopy of serum predicts sensitivity to docetaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer

Docetaxel-based chemotherapy,as the first-line treatment for metastatic castration-resistant prostate cancer(mCRPC),has succeeded in helping quite a number of patients to improve quality of life and prolong survival time.However,almost half of mCRPC patients are not sensitive to docetaxel chemotherapy initially.This study aimed to establish models to predict sensitivity to docetaxel chemotherapy in patients with mCRPC by using serum surface-enhanced Raman spectroscopy(SERS).A total of 32 mCPRC patients who underwent docetaxel chemo-therapy at our center from July 2016 to March 2018 were included in this study.Patients were dichotomized in prostate-specific antigen(PSA)response group(n=17)versus PSA failure group(n=15)according to the response to docetaxel.In total 64 matched spectra from 32 mCRPC patients were obtained by using SERS of serum at baseline(q0)and after 1 cycle of docetaxel chemotherapy(ql).Comparing Raman peaks of serum samples at baseline(q0)be-tween two groups,significant differences revealed at the peaks of 638,810,890(p<0.05)and 1136cm^(-1)(p<0.01).The prediction models of peak 1363 cm^(-1)and principal component anal-ysis and linear discriminant analysis(PCA-LDA)based on Raman data were established,re-spectively.The sensitivity and specificity of the prediction models were 71%,80%and 69%,78%through the way of leave-one-out cross-validation.According to the results of five-cross-valida-tion,the PCA-LDA model revealed an accuracy of 0.73 and AUC of 0.83.

A new semi-quantitative Surface-Enhanced Raman Spectroscopy (SERS) method for detection of maleimide (2,5-pyrroledione) with potential application to astrobiology

Nitrogen-containing heterocyclic compounds are fundamental biochemical components of all life on Earth and,presumably,life elsewhere in our solar system.Detection and characterization of these compounds by traditional solvent extraction,chromatographic separation,and GC-MS analysis require more sample mass than will be available from samples returned to Earth from Mars.With its small sample mass requirement,Surface Enhanced Raman Spectroscopy could be an appropriate technique for analysis of returned samples.We have developed a SERS method for the detection of maleimide(2,5-pyrroledione),an N-containing heterocycle with a structure that is widespread in biochemicals.This semi-quantitative methodology accurately determines maleimide concentration in the range from 60 mg/mL to 120 mg/mL.We present a maleimide SERS standard spectrum which will be useful as a reference for future works.The present work demonstrates an easy,accurate,and effective method for the non-destructive qualitative and semi-quantitative study of maleimide as a first step toward developing a method for analysis of related compounds.

Rapid Identification of Legionella Pathogenicity by Surface-Enhanced Raman Spectroscopy

Objective To establish Surface-enhanced Raman Spectroscopy（SERS） can be used as a rapid and reliable method to distinguish virulent strain and mild strain of L. pneumophila. Methods We isolated and characterized of bacterial strains from ATCC and water samples strains, while we analyzed data from SERS technology using gold nanoparticles as a base and cell infections were employed to rapidly detect L. pneumophila strains. Origin 8.0 was used to collect Raman spectra, smooth and homogenize data, and to contrast spectra. Principal component analysis（PCA） was conducted to discriminate differences between groups using the multivariate analysis package Py Chem 3.0.5. Results Our results indicated that the peaks of high virulence strains reached ≥4000. This criterion was verified by subsequent cell experiments. In addition, we also conducted SERS rapid identification on the virulence of several collected clinical strains and obtained accurate results. Conclusion The present study indicates that the established SERS protocol can be used as a rapid and reliable method to distinguish virulent and mildly virulent strains of L. pneumophila, which can be further used in clinical samples.

Self-assembly 2D plasmonic nanorice film for surface-enhanced Raman spectroscopy

As an ultrasensitive sensing technology,the application of surface enhanced Raman spectroscopy(SERS)is one interesting topic of nano-optics,which has huge application prospectives in plenty of research fields.In recent years,the bottleneck in SERS application could be the fabrication of SERS substrate with excellent enhancement.In this work,a two-dimensional(2D)Ag nanorice film is fabricated by self-assembly method as a SERS substrate.The collected SERS spectra of various molecules on this 2D plasmonic film demonstrate quantitative detection could be performed on this SERS substrate.The experiment data also demonstrate this 2D plasmonic film consisted of anisotropic nanostructures has no obvious SERS polarization dependence.The simulated electric field distribution points out the SERS enhancement comes from the surface plasmon coupling between nanorices.And the SERS signals is dominated by molecules adsorbed at different regions of nanorice surface at various wavelengths,which could be a good near IR SERS substrate for bioanalysis.Our work not only enlarges the surface plasmon properties of metal nanostructure,but also exhibits the good application prospect in SERS related fields.

Identification and analysis of serum samples by surface-enhanced Raman spectroscopy combined with characteristic ratio method and PCA for gastric cancer detection

This study aimed to explore the application of surface-enhanced Raman scattering(SERS)in the rapid diagnosis of gastric cancer.The SERS spectra of 68 serum samples from gastric cancer patients and healthy volunteers were acquired.The characteristic ratio method(CRM)and principal component analysis(PCA)were used to differentiate gastric cancer serum from normal serum.Compared with healthy volunteers,the serum SERS intensity of gastric cancer patients was relatively high at 722 cm^(-1),while it was relatively low at 588,644,861,1008,1235,1397,1445 and 1586 cm^(-1).These results indicated that the relative content of nucleic acids in the serum of gastric cancer patients rises while the relative content of amino acids and carbohydrates decreases.In PCA,the sensitivity and specificity of discriminating gastric cancer were 94.1%and 94.1%,respectively,with the accuracy of 94.1%.Based on the intensity ratios of four characteristic peaks at 722,861,1008 and 1397 cm^(-1),CRM presented the diagnostic sensitivity and specificity of 100%and 97.4%,respectively,and the accuracy of 98.5%.Therefore,the three peak intensity ratios of I_(722)/I_(861),I_(722)/I_(1008)and I_(722)/I_(1397)can be considered as biologicalfingerprint information for gastric cancer diagnosis and can rapidly and directly reflect the physiological and pathological changes associated with gastric cancer development.This study provides an important basis and standards for the early diagnosis of gastric cancer.

Multivariate analysis of serum surface-enhanced Raman spectroscopy of liver cancer patients

Early diagnosis of liver cancer plays a significant role in reducing its high mortality.In this preliminary study,the feasibility of using serum surface-enhanced Raman spectroscopy(SERS)to identify liver cancer was studied.Serum samples were obtained from liver cancer patients and healthy controls.The differences between the SERS spectra of pre-operation and postoperation of liver cancer patients were also analyzed.The general shape and trend of SERS spectra of health control and liver cancer patients were similar.Multivariate analysis,e.g.,PLSSVM,might be useful for the discrimination of serum SERS spectra of pre-operation and post-operation.

Surface-enhanced Raman spectroscopy chips based on two-dimensional materials beyond graphene

Surface-enhanced Raman spectroscopy(SERS) based on two-dimensional(2 D) materials has attracted great attention over the past decade. Compared with metallic materials, which enhance Raman signals via the surface plasmon effect, 2 D materials integrated on silicon substrates are ideal for use in the fabrication of plasmon-free SERS chips, with the advantages of outstanding fluorescence quenching capability, excellent biomolecular compatibility, tunable Fermi levels, and potentially lowcost material preparation. Moreover, recent studies have shown that the limits of detection of 2 D-material-based SERS may be comparable with those of metallic substrates, which has aroused significant research interest. In this review, we comprehensively summarize the advances in SERS chips based on 2 D materials. As several excellent reviews of graphene-enhanced Raman spectroscopy have been published in the past decade, here, we focus only on 2 D materials beyond graphene, i.e., transition metal dichalcogenides, black phosphorus, hexagonal boron nitride, 2 D titanium carbide or nitride, and their heterostructures. We hope that this paper can serve as a useful reference for researchers specializing in 2 D materials, spectroscopy, and diverse applications related to chemical and biological sensing.

Diagnosis of knee osteoarthritis by OCT and surface-enhanced Raman spectroscopy

In this paper,optical coherence tomography(OCT)and surface-enhanced Raman spectroscopy(SERS)were used to characterize normal knee joint(NKJ)tissue and knee osteoarthritis(KOA)tissue ex vivo.OCT images show that there is a clear hierarchical structure in NKJ tissue,including surface layer,transitional layer,radiation layer and cartilage matrix calcification layer tissue structure,while the hierarchical structure of KOA tissue is not clear and unevenly distributed,and the pathological tissues at different stages also show significant di®erences.SERS shows that NKJ tissue and mild osteoarthritic knee cartilage(MiKOA)tissue have strong characteristic Raman peaks at 964,1073(1086),1271,1305,1442,1660 and 1763 cm^(-1).Compared with the Raman spectrum of NKJ tissue,the Raman characteristic peaks of MiKOA tissue have some shifts,moving from 1073 cm^(-1)to 1086 cm^(-1)and from 1542 cm^(-1)to 1442 cm^(-1).There is a characteristic Raman peak of 1271 cm^(-1)in MiKOA tissue,but not in NKJ tissue.Compared with NKJ tissue,severely degenerated cartilage(SdKOA)tissues show some new SERS peaks at 1008,1245,1285,1311 and 1321 cm^(-1),which are not seen in SERS spectra of NKJ tissue.Principal component analysis(PCA)was used to analyze the Raman spectra of 1245–1345 cm^(-1)region.The results show that PCA can distinguish NKJ,MiKOA and SdKOA tissues and the accuracy is about 90%.These results indicate that OCT can clearly distinguish NKJ,MiKOA,moderate osteoarthritic knee cartilage(MoKOA)and SdKOA tissue,while SERS can provide further judgment basis.The results also prove that the contents of protein and polysaccharide in knee tissue are changed during the pathological process of knee tissue,which is the cause of pain caused by poor friction in knee joint during movement.

Sensitive and Label-Free Detection of Protein Secondary Structure by Amide Ⅲ Spectral Signals using Surface-Enhanced Raman Spectroscopy

Proteins and peptides perform a vital role in living systems, however it remains a challenge for accurate description of proteins at the molecular level. Despite that surface-enhanced Raman spectroscopy (SERS) can provide the intrinsic fingerprint information of samples with ultrahigh sensitivity, it suffers from the poor reproducibility and reliability. Herein, we demonstrate that the silver nanorod array fabricated by an oblique angle deposition method is a powerful substrate for SERS to probe the protein secondary structures without exogenous labels. With this method, the SERS signals of two typical proteins (lysozyme and cytochrome c) are successfully obtained. Additionally, by analyzing the spectral signals of the amide Ⅲ of protein backbone, the influence of concentration on the folding status of proteins has been elucidated. With the concentration increasing, the components of α-helix and β-sheet structures of lysozyme increase while the secondary structures of cytochrome c almost keep constant. The SERS method in this work offers an effective optical marker to characterize the structures of proteins.

Azimuthal vector beam illuminating plasmonic tips circular cluster for surface-enhanced Raman spectroscopy

Noble metallic nanostructures with strong electric near-field enhancement can significantly improve nanoscale light-matter interactions and are critical for high-sensitivity surface-enhanced Raman spectroscopy[SERS].Here,we use an azimuthal vector beam[AVB]to illuminate the plasmonic tips circular cluster[PTCC]array to enhance the electric near-field intensity of the PTCC array,and then use it to improve SERS sensitivity.The PTCC array was prepared based on the self-assembled and inductive coupled plasmon[ICP]etching methods.The calculation results show that,compared with the linearly polarized beam[LPB]and radial vector beam excitations,the AVB excitation can obtain stronger electric near-field enhancement due to the strong resonant responses formed in the nanogap between adjacent plasmonic tips.Subsequently,our experimental results proved that AVB excitation increased SERS sensitivity to 10-13mol/L,which is two orders of magnitude higher than that of LPB excitation.Meanwhile,the PTCC array had excellent uniformity with the Raman enhancement factor calculated to be~2.4×10^[8].This kind of vector light field enhancing Raman spectroscopy may be applied in the field of sensing technologies,such as the trace amount detection.

Combining urine surface-enhanced Raman spectroscopy with PCA-SVM algorithm for improving the identification of colorectal cancer at different stages

Cancer staging detection is important for clinician to assess the patients' status and make optimal therapy decision. In this study, the machine learning algorithm based on principal component analysis(PCA) and support vector machine(SVM) was combined with urine surface-enhanced Raman scattering(SERS) spectroscopy for improving the identification of colorectal cancer(CRC) at early and advanced stages. Two discriminant methods, linear discriminant analysis(LDA) and SVM were compared, and the results indicated that the diagnostic accuracy of SVM(93.65%) was superior to that of LDA(80.95%). This exploratory study demonstrated the great promise of urine SERS spectra along with PCA-SVM for facilitating more accurate detection of CRC at different stages.

In situ speciation analysis and kinetic study of arsenic adsorption on ferrihydrite with surface-enhanced Raman spectroscopy

Arsenic pollution poses a serious threat to human health,and is one of the most concerning environmental problems worldwide.The adsorption,fixation,and dissolution behaviors of arsenic on the surface of iron-(hydr-)oxides influence the environmental routes of arsenic cycle geochemistry.Both inner-sphere and outer-sphere adsorption configurations of arsenic on iron oxides have been proposed based on X-ray adsorption spectra.However,there is no systematic study on the in situ speciation analysis and adsorption kinetics of these species at such interfaces,because of the lack of an efficient monitoring strategy.The correlation of surface speciation and environmental stability is still unknown.Here,a shell-isolated SiO_(2)@Ag@Au-based surface-enhanced Raman spectroscopy(SERS)platform was developed for speciation analysis of the adsorbed arsenic species by eliminating the chemical interaction between arsenic and silver.Using ferrihydrite as a typical iron oxide,the intrinsic Raman spectra of the inner-sphere(~830 cm^(−1))and outer-sphere(~660 cm^(−1))complexes at the adsorption interface were identified.For the first time,the in situ kinetic monitoring of the formation and transformation of these species was realized.By correlating the speciation to the sequential extraction results,the environmental stability of arsenic on ferrihydrite was shown to be closely related to the adsorption configuration.It was shown that stability can be significantly promoted by transforming loosely bonded species(outer-sphere complexes)into inner-sphere structures.Our work demonstrated the applicability of SERS with shell-isolated plasmonic particles for arsenic geochemical cycle monitoring and mechanism studies.It also provided a convenient tool for developing effective strategies for arsenic pollutant control and abatement.

Surface-enhanced Raman spectroscopy for emerging contaminant analysis in drinking water

Emerging contaminants(ECs)in drinking water pose threats to public health due to their environmental prevalence and potential toxicity.The occurrence of ECs in our drinking water supplies depends on their physicochemical properties,discharging rate,and susceptibility to removal by water treatment processes.Uncertain health effects of long-term exposure to ECs justify their regular monitoring in drinking water supplies.In this review article,we will summarize the current status and future opportunities of surface-enhanced Raman spectroscopy(SERS)for EC analysis in drinking water.Working principles of SERS are first introduced and a comparison of SERS and liquid chromatography-tandem mass spectrometry in terms of cost,time,sensitivity,and availability is made.Subsequently,we discuss the strategies for designing effective SERS sensors for EC analysis based on five categories—per-and polyfluoroalkyl substances,novel pesticides,pharmaceuticals,endocrine-disrupting chemicals,and microplastics.In addition to maximizing the intrinsic enhancement factors of SERS substrates,strategies to improve hot spot accessibilities to the targeting ECs are equally important.This is a review article focusing on SERS analysis of ECs in drinking water.The discussions are not only guided by numerous endeavors to advance SERS technology but also by the drinking water regulatory policy.

Rapid fabrication of large-area and uniform surface-enhanced Raman spectroscopy substrate of Au nano-hemisphere array and its application in the detection of Malachite Green in tilapia

Although surface-enhanced Raman spectroscopy(SERS)substrates have achieved high sensitivity,it is still difficult to apply these SERS protocols to the on-site detection of real samples due to the SERS substrate being fabrication-complexed,unstable,reproducible,or unable to be applied in batch production.Here,a large-scale ordered two-dimensional array of Au nano-hemispheres was developed through electron beam vaporization of Au onto the easy-available commercialized anodic aluminum oxide(AAO)template with two-layer nanostructures of different diameters.The uniform Au nano-hemisphere is reliable for SERS detection of malachite green(MG)due to the relative standard deviation(RSD)of the SERS intensities at different locations less than 10%.With the optimized excitation wavelength,solvent effect and pH environment,the linear range of MG detection spans from 10^(-10) to 10^(-6) mol/L with a limit of detection(LOD)of 4×10^(-10) mol/L.The enhancement factor can reach 1.2×10^(6).After extraction with acetonitrile and dichloromethane,MG in the spiked tilapia was detected with satisfactory recovery.The results indicate that the Au nano-hemisphere array can be expected to greatly facilitate SERS practical applications in detecting harmful food additives and chemicals due to the advantages of chemical inertness,physical robustness,simple fabrication,controllability,large-area uniformity,and large-batch production.

Metal-organic frameworks based surface-enhanced Raman spectroscopy technique for ultra-sensitive biomedical trace detection

Metal-organic frameworks(MOFs)have attracted widespread interest due to their unique and unprecedented advantages in microstructures and properties.Besides,surface-enhanced Raman scattering(SERS)technology has also rapidly developed into a powerful fingerprint spectroscopic technique that can provide rapid,non-invasive,non-destructive,and ultra-sensitive detection,even down to single molecular level.Consequently,a considerable amount of researchers combined MOFs with the SERS technique to further improve the sensing performance and broaden the applications of SERS substrates.Herein,representative synthesis strategies of MOFs to fabricate SERS-active substrates are summarized and their applications in ultra-sensitive biomedical trace detection are also reviewed.Besides,relative barriers,advantages,disadvantages,future trends,and prospects are particularly discussed to give guidance to relevant researchers.

Surface-Enhanced Raman Spectroscopy:Principles,Methods,and Applications in Energy Systems

Surface-enhanced Raman spectroscopy(SERS)has advanced significantly since its inception.Numerous experimental and theoretical efforts have been made to understand the SERS effect and demonstrate its potential.Due to its extremely high sensitivity and selectivity and ability to provide molecular fingerprint information,SERS has a wide range of applications in surface and interfacial chemistry,energy,materials,biomedicine,environmental analysis,etc.This review aims to provide readers with an understanding of the principles,methodologies,and applications of SERS.We briefly introduce the fundamental theory of the SERS enhancement mechanism and summarize the details of the preparation of SERS-active substrates.Recent applications of SERS in energy systems are then highlighted,including probing surface reactions and interfacial charge transfer of batteries and electrocatalysts.Finally,the challenges and prospects of SERS research are discussed.

Optical penetration of surface-enhanced micro-scale spatial offset Raman spectroscopy in turbid gel and biological tissue

The limited penetration of photons in biological tissue restricts the deep-tissue detection and imaging application.The micro-scale spatially offset Raman spectroscopy(micro-SORS)with an optical fiber probe,colleting photons from deeper regions by offsetting the position of laser excitation from the collection optics in a range of hundreds of microns,shows great potential to be integrated with endoscopy for inside-body noninvasive detection by circumventing this restric-tion,particularly with the combination of surface-enhanced Raman spectroscopy(SERS).However,a detailed tissue penetration study of micro-SORS in combination with SERS is still lacking.Herein,we compared the signal decay of enhanced Raman nanotags through the tissue phantom of agarose gel and the biological tissue of porcine muscle in the near-infrared(NIR)region using a portable Raman spectrometer with a micro-SORS probe(2.1 mm in diameter)and a conventional hand-held probe(9.7mm in diameter).Two kinds of Raman nanotags were prepared from gold nanorods decorated with the nonresonant(4-nitrobenzenethiol)or resonant Raman reporter molecules(IR-780 iodide).The SERS measurements show that the penetration depths of two Raman nanotags are both over 2 cm in agarose gel and 3 mm in porcine muscle.The depth could be improved to over 4 cm in agarose gel and 5 mm in porcine tissue when using the micro-SORS system.This demonstrates the superiority of optical-fiber micro-SORS system over the conventional Raman detection for the detection of nanotags in deeper layers in the turbid medium and biological tissue,offering the possibility of combining the micro-SORS technique with SERS for noninvasive in vivo endoscopy-integrated clinical application.

Roadmap for single-molecule surface-enhanced Raman spectroscopy

In the near future,single-molecule surface-enhanced Raman spectroscopy(SERS)is expected to expand the family of popular analytical tools for single-molecule characterization.We provide a roadmap for achieving single molecule SERS through different enhancement strategies for diverse applications.We introduce some characteristic features related to single-molecule SERS,such as Raman enhancement factor,intensity fluctuation,and data analysis.We then review recent strategies for enhancing the Raman signal intensities of single molecules,including electromagnetic enhancement,chemical enhancement,and resonance enhancement strategies.To demonstrate the utility of single-molecule SERS in practical applications,we present several examples of its use in various fields,including catalysis,imaging,and nanoelectronics.Finally,we specify current challenges in the development of single-molecule SERS and propose corresponding solutions.

Rapid determination of histamine concentration in fish(Miichthys Miiuy)by surface-enhanced Raman spectroscopy and density functional theory

Histamine is a type of biogenic amine,which plays a major role in the health problems associated with seafood consumption.Legislative limits of histamine level in seafood have been set in many countries.This study focuses on investigating the feasibility and potentiality of determining histamine concentration in fish(Miichthys miiuy)by surface-enhanced Raman spectroscopy(SERS)combined with density functional theory(DFT).Both a gold colloid and a silver colloid were used to determine the enhancement effect for SERS detection of histamine standard solution,and the gold colloid exhibited more effective as compared to the silver colloid.The protocol on extraction of histamine with 12%trichloroacetic acid and adjustment of pH with NaOH solution(5 mol/L)could significantly shorten sample preparation(20 min)and provide clear SERS spectra of histamine.The peaks of histamine molecules were classified using the DFT and five spectra(953 cm^(-1),992 cm^(-1),1106 cm^(-1),1262 cm^(-1)and 1317 cm^(-1))were selected as the characteristic bands of histamine discrimination.Moreover,the intensity of the peak at 1262 cm^(-1)had a good linear relationship with histamine concentration at 5-400 mg/kg with R^(2)=0.9755.It is concluded that the SERS-DFT approach will be a potential method for rapidly and reliably detecting histamine at levels from 5 mg/kg to 400 mg/kg in fresh fish.

Preparation of Large-area Controllable Patterned Silver Nanocrystals for High Sensitive and Stable Surface-enhanced Raman Spectroscopy

A novel and facile method for fabricating large-area pattemed silver nanocrystals was introduced and the investigation on the high sensitive and stable surface-enhanced Raman spectroscopy（SERS） of the nanocrystals was carried out. Nanostructured silicon substrate was processed by laser interference and used as a template for growing silver nanocrystals via galvanic battery reaction method. The substrate with large area for violent chemical reaction was tailored into a nanocell array. The limited reaction area hindered the growth of silver nanocrystals and made their size uniform and controllable. The size and gaps of the nanocrystals could be controlled by template period and ratio, which were easily reproduced by laser interference. Taking 10^-8 to 10^-11 mol/L RhoG for example, the optimized silver arrays exhibited great potential for ultrasensitive molecular sensing in terms of its high SERS enhancement ability, favorable stability, and excellent reproducibility.