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.

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.

Facile SERS screening of melamine in bovine milk with 2D printed AgNPs/glass fabric filter paper as the flexible substrate

Melamine is one of the most frequently detected adulterants in dairy products.The current study proposes a surface-enhanced Raman spectroscopy(SERS)-based analytical tool for fast and reliable screening of melamine in bovine milk.A hand-held Raman spectrometer was used in conjunction with a substrate composed of silver nanoparticles(AgNPs)that was 2D printed onto glass fiber(GF)filter paper.Under optimized conditions,a sensitive and fingerprint-like signal at 674 cm^(-1) was obtained.The AgNPs/GF substrate exhibited high sensitivity to melamine in milk down to 1.9498×10^(-5)mg/mL,which is well below the USA and EU safety limits(2.5×10^(-3)mg/mL).Remarkably,the proposed technology was also highly reproducible,showing spot-to-spot and block-to-block variations below 3.3%and 4.9%at 674 cm^(-1) in Raman intensity,respectively.The characteristic peak intensity and concentration of melamine showed an acceptable linear relationship(R^(2)=0.9909)within the range of 0.0001-1 mg/mL.Overall,the method established in this study can provide an efficient and effective method for the quantitative target screening and detection of melamine in dairy products.

不同介质中甲醛在Aucore@Ptshell／Pt电极上氧化的原位SERS研究

应用化学还原法合成了Aucore@Ptshell纳米粒子,并用扫描电子显微镜(SEM)和能量色散光谱(EDS)对其进行了表征;采用电化学原位表面增强拉曼散射(SERS)光谱技术研究了不同介质中甲醛在Aucore@Ptshell/Pt电极上的电催化氧化行为,获得了不同介质中甲醛在Aucore@Ptshell/Pt电极上电催化氧化行为的原位SERS谱.研究结果表明,不论在酸性、中性还是碱性介质中,甲醛均能在Aucore@Ptshell/Pt电极上自发氧化解离出强吸附中间体CO,只是在碱性介质中桥式吸附CO的比例明显增大,且桥式吸附比线形吸附CO更易被氧化,使CO在碱性介质中基本氧化完毕的电位比在中性及酸性介质中提前了约950 mV.分子水平的研究结果表明,CO和甲醛在碱性介质中比在中性和酸性介质中更易被氧化.

TiO_2电极表面氰基吡啶吸附的电化学SERS光谱

采用基于核壳纳米粒子的壳层隔绝纳米粒子增强拉曼(SHINERS)以及Au纳米粒子增强技术,对比研究了4-氰基吡啶(4-CNPy)在TiO2表面的吸附行为.结果表明,采用2种技术所获得的光谱存在明显的差别.利用前者得到了4-CNPy在TiO2电极上随电极电位变化的吸附方式.在电位为0时,分子以吡啶环上的N垂直吸附;随电位负移,部分分子变为倾斜吸附,且在电位为-1.0 V时倾斜角度变大.在正电位区间,分子始终以吡啶环上的N垂直吸附.而采用Au纳米粒子滴加在TiO2电极上的方式,则得到吸附在TiO2,Au及TiO2/Au复合结构上的总光谱信息.

Synthesis and characterization of reporter molecules embedded core-shell nanoparticles as SERS nanotags

Surface-enhanced Raman scattering(SERS)spectroscopy is presented as a sensitive and spe-cific molecular tool for clinical diagnosis and prognosis monitoring of various diseases including cancer.In order for clinical application of SERS technique,an ideal method of bulk synthesis of SERS nanoparticles is necessary to obtain sensitive,stable and highly reproducible Raman signals.In this contribution,we determined the ideal conditions for bulk synthesis of Raman reporter(Ra)molecules embedded silver-gold core-shell nanoparticles(Au@Ra@AgNPs)using hydroquinone as reducing agent of silver nitrate.By using UV-Vis spectroscopy,Raman spectroscopy and transmission electron microscopy(TEM),we found that a 2∶1 ratio of silver nitrate to hydroquinone is ideal for a uniform silver coating with a strong and stable Raman signal.Through stability testing of the optimized Au@Ra@AgNPs over a two-week period,these SERS nanotags were found to be stable with minimal signal change occurred.The sta-bility of antibody linked SERS nanotags is also crucial for cancer and disease diagnosis,thus,we further conjugated the as-prepared SERS nanotags with anti-EpCAM antibody,in which the stability of bioconjugated SERS nanotags was tested over eight days.Both UV-Vis and SERS spectroscopy showed stable absorption and Raman signals on the anti-EpCAM conju-gated SERS nanotags,indicating the great potential of the synthesized SERS nanotags for future applications which require large,reproducible and uniform quantities in order for cancer biomarker diagnosis and monitoring.

Ultrasensitive Detection of Polycyclic Aromatic Hydrocarbons(PAHs) in Water Using Three-Dimensional SERS Substrate Based on Porous Material and pH 13 Gold Nanoparticles

Sensitivity is crucially important for surface-enhanced Raman spectroscopy(SERS)application to detect trace-level polycyclic aromatic hydrocarbons(PAHs)in the seawater.In this study,a high sensitivity three-dimensional(3-D)SERS substrate composed with syringe filter,glycidyl methacrylate-ethylene dimethacrylate(GMA-EDMA)porous material and optimal parameters(57 nm,pH 13)gold nanoparticles(Au NPs)was developed for the detection of PAHs in water.The enhancement effect and repeatability of this 3-D substrate were also explored.The Raman intensity of pyrene using 3-D SERS substrate is about 8 times higher than that of substrate only using p H 13 gold colloid solution and about 12 times higher than that of substrate using natural Au NPs and GMA-EDMA porous material,which means both the pH 13 AuN Ps and the GMA-EDMA porous material are important factors for the sensitivity of this 3-D SERS substrate.Good repeatability of this optimal 3-D substrate was obtained.The relative standard deviation(RSD)is less than 8.66% on the same substrate and less than 3.69% on other different substrates.Four kinds of PAHs,i.e.,phenanthrene,pyrene,benzo(a)pyrene,benzo(k)fluoranthene and their mixture,were detected at the different concentrations.Their limits of detection(LODs)are 8.3×10^-10(phenanthrene),2.1×10^-10(pyrene),3.8×10^-10(benzo(a)pyrene)and 1.7×10^-10 mol L^-1(benzo(k)fluoranthene),respectively.In addition,these four PAHs were also detected by fluorescence spectroscopy to evaluate the sensitivity of SERS technology using this optimal 3-D SERS substrate.The results showed that the sensitivity of SERS based on the 3-D SERS substrate even using the portable Raman system was closed to that of fluorescence spectroscopy.Therefore,the SERS technology using this optimal 3-D substrate is expected to be an in-situ method for the detection of environmental PAHs.

SERS activity of carbon nanotubes modified by silver nanoparticles with different particle sizes

A two-dimensional(2D)surface-enhanced Raman scattering(SERS)substrate is fabricated by decorating carbon nanotube(CNT)films with Ag nanoparticles(Ag NPs)in different sizes,via simple and low-cost chemical reduction method and self-assembling method.The change of Raman and SERS activity of carbon nanotubes/Ag nanoparticles(CNTs/Ag NPs)composites with varying size of Ag NPs are investigated by using rhodamine 6G(R6G)as a probe molecule.Meanwhile,the scattering cross section of Ag NPs and the distribution of electric field of CNTs/Ag NPs composite are simulated through finite difference time domain(FDTD)method.Surface plasmon resonance(SPR)wavelength is redshifted as the size of Ag NPs increases,and the intensity of SERS and electric field increase with Ag NPs size increasing.The experiment and simulation results show a Raman scattering enhancement factor(EF)of 108for the hybrid substrate.

Elucidating the Chemisorption Phenomena in SERS Studies via Computational Modeling

Colloidal gold solutions with nanostars and nanospheres as well as KlariteTM gold and gold-copper bimetallic substrates were used for SERS analysis of aniline and nitroaniline isomers to investigate their chemisorption phenomena. Computational modeling based on Density Functional Theory (DFT) was used in conjunction with the SERS analysis to study the adsorption behaviors of the analytes on metal surfaces. Gold nanospheres and KlariteTM samples produced about a 10-fold increase in signal enhancement compared to gold nanostars for the SERS analysis of aniline, nitroaniline isomers, and nitrobenzene. Signal enhancement is significantly greater for aniline compared to nitrobenzene and it is dependent on the proximity of the NH2 to the NO2 group for the nitroaniline isomers. Charge-transfer in chemisorbed analytes is an important contributing factor for SERS signal. The relative strengths of enhancement can be predicted by the DFT calculation of the HOMO-LUMO energy gaps of the analyte-metal cluster. Aniline and the three nitroaniline isomers showed stronger preference for the copper substrates if both the gold and copper substrates are present. The NO2 group in 2-nitroaniline has a very strong preference and affinity for the copper in the Au-Cu bimetallic cluster.

Determination of primary aromatic amines using immobilized nanoparticles based surface-enhanced Raman spectroscopy

Primary aromatic amines （PAAs） are substances with toxicity and suspected human carcinogenicity. A facile method for highly sensitive detection of PAAs using surface-enhanced Raman spectroscopy （SERS） is reported. The immobilization of Au nanoparticles （AuNPs） on the glycidyl methacrylate-ethylene dimethacrylate （GMA-EDMA） materials makes the suhstrate a closely packed but not aggregated Au NP arrays which provides a prominent SERS enhancement. Four PAAs with different substituent groups, namely, p-toluidine, p-nitroaniline, benzidine and 4,4-methylene-bis-（2-chloroaniline） have been successfully identified and quantified. High sensitivity and good linear relationship between SERS signals and concentrations of PAAs are obtained for all four PAAs.

Study on gastric cancer blood plasma based on surface-enhanced Raman spectroscopy combined with multivariate analysis

A surface-enhanced Raman spectroscopy (SERS) method combined with multivariate analysis was developed for non-invasive gastric cancer detection. SERS measurements were performed on two groups of blood plasma samples: one group from 32 gastric patients and the other group from 33 healthy volunteers. Tentative assignments of the Raman bands in the measured SERS spectra suggest interesting cancer-specific biomolecular changes, including an increase in the relative amounts of nucleic acid, collagen, phospholipids and phenylalanine and a decrease in the percentage of amino acids and saccharide in the blood plasma of gastric cancer patients as compared with those of healthy subjects. Principal components analysis (PCA) and linear discriminant analysis (LDA) were employed to develop effective diagnostic algorithms for classification of SERS spectra between normal and cancer plasma with high sensitivity (79.5%) and specificity (91%). A receiver operating characteristic (ROC) curve was employed to assess the accuracy of diagnostic algorithms based on PCA-LDA. The results from this exploratory study demonstrate that SERS plasma analysis combined with PCA-LDA has tremendous potential for the non-invasive detection of gastric cancers.

One-pot synthesis of silver colloid with body-heat for surface-enhanced Raman spectroscopy detections

In this study,a convenient method of preparing the substrate is proposed with one-pot synthesis of silver colloid under body heat,and the SERS detection uses the fresh substrate to avoid the drawback of substrates’short life of use.The synthesis of silver colloid is carried out in a 10 mL vial by using ascorbic acid as a reductant and trisodium citrate as a stabilizer.The vial is grasped with the palm of the experimenter for several minutes without shaking.The proposed method is simple,rapid,green energy and cost-effective.By adjusting the concentration of trisodium citrate,not only the particle size can be controlled from about 110 nm to 50 nm but also the homogeneity of nanoparticles can be improved.As a SERS substrate,the silver colloid has high batch reproducibility and showed good SERS activity.The relative standard deviation between different manufacturers is 5.51%when the substrate of silver colloid is used for the detection of rhodamine 6 G.Using the substrate,the lowest detection concentrations of rhodamine 6 G,crystal violet,enrofloxacin,melamine and leucomalachite green are 1.0×10-8,6.1×10-8,1.4×10-6,7.1×10-5 and 5.1×10-8 mol/L,respectively.Results demonstrate that the developed method has the advantage of convenience and high efficiency in the field preparation of reliable SERS substrate.

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.

Stable and unique graphitic Raman internal standard nanocapsules for surface-enhanced Raman spectroscopy quantitative analysis

Graphitic nanomaterials have unique, strong, and stable Raman vibrations that have been widely applied in chemistry and biomedicine. However, utilizing them as internal standards （ISs） to improve the accuracy of surface-enhanced Raman spectroscopy （SERS） analysis has not been attempted. Herein, we report the design of a unique IS nanostructure consisting of a large number of gold nanoparticles （AuNPs） decorated on multilayered graphitic magnetic nanocapsules （AGNs） to quantify the analyte and eliminate the problems associated with traditional ISs. The AGNs demonstrated a unique Raman band from the graphitic component, which was localized in the Raman silent region of the biomolecules, making them an ideal IS for quantitative Raman analysis without any background interference. The IS signal from the AGNs also indicated superior stability, even under harsh conditions. With the enhancement of the decorated AuNPs, the AGN nanostructures greatly improved the quantitative accuracy of SERS, in particular the exclusion of quantitative errors resulting from collection loss and non-uniform distribution of the analytes. The AGNs were further utilized for cell staining and Raman imaging, and they showed great promise for applications in biomedicine.

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.

Diagnosis of breast cancer by analysis of sialic acid concentrations in human saliva by surface-enhanced Raman spectroscopy of silver nanoparticles

Breast cancer is the most common type of malignant tumor among women and their second leading cause of cancer-related deaths.The most common method for screening and diagnosis is mammography.Nonetheless,two main problems have been identified.First,the dose of radiation received during the test prevents the method from the use on women who are 〈 40 years old.Second,there can be mammogram failure owing to the lack of tumor contrast with the fibrous tissue.Therefore,there is a need for screening methods that will help to identify high-risk cases.We developed a biological marker test that can help to identify them.Increased levels of sialic acid （SA） in saliva are known to correlated with breast cancer.In this study,we evaluated the feasibility of Raman spectroscopy as a method for quantification of SA in saliva,using citrate-reduced silver nanoparticles （cit-Ag-NPs） as a surface-enhanced Raman spectroscopy （SERS） substrate.Quantification of SA was accomplished by measuring its intensity in saliva and comparing it with a calibration curve of SA standards.The mean SA concentration in saliva was found to be significantly higher among 100 breast cancer patients （18.3 ＆#177; 9.4 mg＆#183;dL-1;mean ＆#177; SD） than among 106 healthy controls （3.5 ＆#177; 1.0 mg＆#183;dL-1）.The SERS test showed sensitivity of 94% and specificity 98% for detection of patients with breast cancer,assuming that SA concentration 〉 7 mg＆#183;dL-1 is a cutoff for positive test results.Our findings prove the usefulness of this SERS technique as a simple,convenient,and highly sensitive method of quantitative analysis of SA in saliva.The simplicity of this nanotechnological test may help to substantially reduce the mortality among patients with breast cancer by providing women with a simple,noninvasive screening test that can be applied regardless of age or density of breast tissue.

Reproducibility in Surface-Enhanced Raman Spectroscopy

Surface-enhanced Raman spectroscopy（SERS） is an intense ongoing hot topic because it is an attractive tool for sensing or detecting molecules in trace amounts. Despite its high specificity and sensitivity, the SERS technique has not been established as a routine analytic method most likely due to the low reproducibility of the SERS signal. This review considers the influence factors to produce the poor reproducibility during the SERS measurement. This review starts with the discussion of calculation of surface-enhanced Raman intensity in order to explain the reason why it is so difficult to achieve a high reproducibility of SERS measurement from the origin of enhancement mechanism. Then we focus on the fabrication of SERS substrates generally including two types：① single particles and ② arrays on substrate that are directly used to detect molecules or other components.In addition, we discuss the molecule factors and optical system for the reproducibility for sample-to-sample or spot-to-spot on a substrate. In the final part of this review, some effects resulting in the irreproducibility of Raman bands＇ position from recent literatures are discussed.

Oxygen electrochemistry in Li-O2 batteries probed by in situ surface-enhanced Raman spectroscopy

Surface-enhanced Raman spectroscopy(SERS),as a nondestructive and ultrasensitive single molecular level characterization technique,is a powerful tool to deeply understand the interfacial electrochemistry reaction mechanism involved in energy conversion and storage,especially for oxygen electrochemistry in Li-O2 batteries with unrivaled theoretical energy density.SERS can provide precise spectroscopic identification of the reactants,intermediates and products at the electrode|electrolyte interfaces,independent of their physical states(solid and/or liquid)and crystallinity level.Furthermore,SERS’s power to resolve different isotopes can be exploited to identify the mass transport limitation and reactive sites of the passivated interface.In this review,the application of in situ SERS in studying the oxygen electrochemistry,specifically in aprotic Li-O2 batteries,is summarized.The ideas and concepts covered in this review are also extended to the perspectives of the spectroelectrochemistry in general aprotic metal-gas batteries.

Identification and Analysis of the Intermediates from Photodegradation of 3,3′-diamino-4,4′-azoxyfurazan(DAAF)by SERS and HPLC–MS/MS

Understanding the structural changes and degradation mechanisms of organic pollutants is critical in environmental research.In this work,a xenon lamp was used as an analog light source to simulate the effect of sunlight on 3,3′-diamino-4,4′-azoxyfurazan(DAAF)in aqueous solution.Combining high-performance liquid chromatography coupled with tandem mass spectrometry(HPLC–MS/MS),surface-enhanced Raman spectroscopy(SERS)with density functional theory(DFT),the degradation intermediates and mechanisms of DAAF were investigated.The sequential breakdown of the–NH2 and–O–N=bonds,followed by the removal of atomic O from–N=N(O)–,was emphasized and investigated using two-dimensional correlation spectroscopy(2D-COS)and SERS spectra.Three intermediates with mass-to-charge ratios(m/z)181,251 and 180 were identified and characterized by integrating experimental SERS data with DFT-calculated Raman spectra based on structures hypothesized from MS spectra.The findings from HPLC–MS and SERS not only corroborate each other but also provide a foundation for a detailed examination of the DAAF degradation process.

Electrooxidation Mechanism of Methanol at Pt-Ru Catalyst Modified GC Electrode in Electrolytes with Different pH Using Electrochemical and SERS Techniques

The electrochemical and in-situ surface-enhanced Raman spectroscopy （SERS） techniques were used to investigate the electrooxidation behavior of methanol in acidic, neutral and alkaline media at a Pt-Ru nanoparticle modified glassy carbon （Pt-Ru/GC） electrode. The results showed that methanol could be dissociated spontaneously at the Pt-Ru/GC electrode to produce a strongly adsorbed intermediate, CO. It was found that CO could be oxidized more easily in the alkaline medium than in the acidic and neutral media. The peak potential of methanol oxidation was shifted from 0.663 and 0.708 V in the acidic and neutral media to -0.030 V in the alkaline medium, which is due to that the adsorption strength of CO on the Pt surface in the alkaline medium is weaker than that in the acidic and neutral media. The final product of the methanol oxidation is CO2. However, in the alkaline medium, CO2 produced would form CO3^2- and HCO3^- resulting in the decrease in the alkaline concentration and then in the decrease in the performance of DMFC. Therefore, the performance of the alkaline DMFC is not Stable.