Fundamental studies on enhancement and blinking mechanism of surface-enhanced Raman scattering （SERS） and basic applications of SERS biological sensing

We review recent our results in the fundamental study of surface-enhanced Raman scattering （SERS） with emphasis on experiments that attempted to identify the enhancement and blinking mechanism using single Ag nanoparticle dimers attached to dye molecules. These results are quantitatively discussed in the framework of electromagnetic mechanism. We also review recent our results in basic SERS applications for biological sensing regarding detections of cell surface molecules and distinction of disease marker molecules under single cell and single molecule level.

Label-free breast cancer detection and classification by convolutional neural network-based on exosomes surface-enhanced raman scattering

Because the breast cancer is an important factor that threatens women's lives and health,early diagnosis is helpful for disease screening and a good prognosis.Exosomes are nanovesicles,secreted from cells and other body fluids,which can reflect the genetic and phenotypic status of parental cells.Compared with other methods for early diagnosis of cancer(such as circulating tumor cells(CTCs)and circulating tumor DNA),exosomes have a richer number and stronger biological stability,and have great potential in early diagnosis.Thus,it has been proposed as promising biomarkers for diagnosis of early-stage cancer.However,distinguishing different exosomes remain is a major biomedical challenge.In this paper,we used predictive Convolutional Neural model to detect and analyze exosomes of normal and cancer cells with surface-enhanced Raman scattering(SERS).As a result,it can be seen from the SERS spectra that the exosomes of MCF-7,MDA-MB-231 and MCF-10A cells have similar peaks(939,1145 and 1380 cm^(-1)).Based on this dataset,the predictive model can achieve 95%accuracy.Compared with principal component analysis(PCA),the trained CNN can classify exosomes from different breast cancer cells with a superior performance.The results indicate that using the sensitivity of Raman detection and exosomes stable presence in the incubation period of cancer cells,SERS detection combined with CNN screening may be used for the early diagnosis of breast cancer in the future.

Application of microfluidic technology based on surface-enhanced Raman scattering in cancer biomarker detection:A review

With the continuous discovery and research of predictive cancer-related biomarkers,liquid biopsy shows great potential in cancer diagnosis.Surface-enhanced Raman scattering(SERS)and microfluidic technology have received much attention among the various cancer biomarker detection methods.The former has ultrahigh detection sensitivity and can provide a unique fingerprint.In contrast,the latter has the characteristics of miniaturization and integration,which can realize accurate control of the detection samples and high-throughput detection through design.Both have the potential for point-of-care testing(POCT),and their combination(lab-on-a-chip SERS(LoC-SERS))shows good compatibility.In this paper,the basic situation of circulating proteins,circulating tumor cells,exosomes,circulating tumor DNA(ctDNA),and microRNA(miRNA)in the diagnosis of various cancers is reviewed,and the detection research of these biomarkers by the LoC-SERS platform in recent years is described in detail.At the same time,the challenges and future development of the platform are discussed at the end of the review.Summarizing the current technology is expected to provide a reference for scholars engaged in related work and interested in this field.

Surface-enhanced Raman Scattering of Aflatoxin B1 on Silver by DFT Method

The structure, electrostatic properties, and Raman spectra of aflatoxin B1 （AFB1） and AFB1-Ag complex are studied by density functional theory with B3LYP/6- 311G（d,p）/Lan12dz basis set. The results show that the surface-enhanced Raman scattering （SERS） and pre-resonance Raman spectra of AFB1-Ag complex strongly depend on the adsorption site and the excitation wavelength found to enhance 102-103 order compared to of the incident light. The SERS factors are normal Raman spectrum of AFB1 molecule due to the larger static polarizabilities of the AFB1-Ag complex, which directly results in the stronger chemical enhancement in SERS spectra. The pre-resonance Raman spectra of AFB1-Ag complex are explored at 266, 482, 785, and 1064 nm incident light wavelength, in which the enhancement factors are about 10^2-10^4, mainly caused by the charge-transfer excitation resonance. The vibrational modes are analyzed to explain the relationship between the vibrational direction and the enhanced Raman intensities.

Surface-enhanced Raman scattering sensor based on fused biconical taper zone of optical fiber

In this paper, a novel surface-enhanced Raman scattering （SERS） sensor combined with fused biconical taper fiber （FBTF） and film coated with silver sols is proposed. This structure is designed to significantly increase the SERS active surface when the length of the taper is increased and the radius is reduced, since the penetration depth is inversely proportional to the taper radius and proportional to the taper length according to the fiber-optic evanescent-wave theory. Based on the SERS sensing principle, the feasibility of FBTF sensor is analyzed in this paper. As a result, the Raman spectrum of R6G is obtained from the fused biconical taper zone surface coating with the silver sols in our experiments. The detected concentration is up to 10-7mol/L.

柠檬汁还原法制备AgNPs用于果蔬农药残留的SERS快速检测

[目的/意义]为满足目前市场上对农产品农药残留的快速灵敏检测需求,报道一种基于柠檬汁还原制备银纳米粒子(AgNPs)的方法。[方法]首先将新鲜柠檬汁经滤纸过滤,稀释成2%的柠檬汁水溶液,再配制一定浓度的AgNO3溶液、50 mM的NaOH溶液,放置室温保存。然后在室温下,将10 mL的ddH2O、2mL的NaOH、2mL的2%柠檬汁和5 mL的AgNO3溶液混合,待溶液颜色变为澄清的黄色时,溶液离心即可获得AgNPs。[结果和讨论]该方法制备的AgNPs,其颗粒形貌大小基本均一,约为20 nm,具有很好的表面增强拉曼散射(Surface Enhancement of Raman Scattering,SERS)增强效应,即良好的SERS信号稳定性,较强的SERS增强性能。该胶体中AgNPs分散较均匀,并且具有较长时间储存的稳定性,因此可用于微量农残检测。柠檬汁中主要还原成分抗坏血酸、葡萄糖和果糖,其含量分别为395.76μg/mL、5.95 mg/mL和5.90 mg/mL。将柠檬汁还原法制备的AgNPs用于果蔬表面农残检测,对于百草枯、多菌灵的检出限分别最低至3.90 ng/kg及0.22μg/kg。[结论]这项工作为果蔬农残快检提供了一种绿色、便捷的SERS材料制备方法,为实现农产品农药残留的快速、灵敏检测提供一种新的途径。

Chemical Enhancement on Surface-Enhanced Resonance Raman Scattering of Au3-1,4-BenzenedithioI-Au3 Junction

Surface-enhanced Raman scattering （SERS） and surface-enhanced resonance Raman scattering （SERRS） spectra of the 1,4-benzenedithiol molecule in the junction of two Au3 clusters have been calculated using density functional theory （DFT） and time-dependent DFT method. In order to investigate the contribution of charge transfer （CT） enhancement, the wavelengths of incident light are chosen to be at resonance with four representative excited states, which correspond to CT in four different forms. Compared with SERS spectrum, SERRS spectra are enhanced enormously with distinct enhancement factors, which can be attributed to CT resonance in different forms.

Controllable Silver Plating on Silica for Surface-enhanced Raman Scattering

We proposed a facile and rapid method for preparing silica-silver core-shell（SSCS） substrates to use Ag electroless plating on SiO2@Au-seed particles.UV-Vis-NIR absorption spectrometer and SEM were employed to monitor the reaction process of the formation of Ag on the surfaces of silica beads,and the optical resonance of the substrate could shift from visible to NIR region.It has been found that surface-enhanced Raman scattering（SERS） enhancement changes with the electroless plating time and the SSCS substrate with the plating time of 90 s（90SSCS） shows the strongest SERS response under the laser excitation at 514.5 nm.Signals collected over multiple spots and substrate of rhodamine 6G（R6G） resulted in a relative standard deviation（RSD） of 9.75%.The calculated enhancement factor（EF） was approximately 105 ＂106.SSCS substrate exhibits high SERS performance,which is due to electromagnetic SERS enhancement with additional localization field within closely packed Ag nanoparticles decorated on the SiO2 nanoparticles.And this substrate presents tunable and broad localized surface plasmon resonance（LSPR）,so this method may open a new way for SERS studies with other laser excitation.

Raman and Surface-enhanced Raman Scattering of Chlorophenols

Raman spectrum is a powerful analytical tool for determining the chemical information of compounds. In this study, we obtained analytical results of chlorophenols（CPs） molecules including 4-chlorophenol（4-CP）, 2,6-dich- lorophenol（2,6-DCP） and 2,4,6-trichlorophenol（2,4,6-TCP） on the surface of Ag dendrites by surface-enhanced Raman scattering（SERS） spectra. SEM images indicate that the SERS substrate of Ag dendrites is composed of a large number of polygonal nanocrystallites, which self-assembled into a 3D hierarchical structure. It was found that there were distinct differences for those three molecules from Raman and SERS spectra. This indicates that SERS could be a new tool of detection technique regarding trace amounts of CPs.

Molybdenum Nanoscrews:A Novel Non-coinage-Metal Substrate for Surface-Enhanced Raman Scattering

For the first time, Mo nanoscrew was cultivated as a novel non-coinage-metal substrate for surface-enhanced Raman scattering(SERS). It was found that the nanoscrew is composed of many small screw threads stacking along its length direction with small separations. Under external light excitation, strong electromagnetic coupling was initiated within the gaps, and many hot-spots formed on the surface of the nanoscrew, which was confirmed by high-resolution scanning near-field optical microscope measurements and numerical simulations using finite element method. These hotspots are responsible for the observed SERS activity of the nanoscrews. Raman mapping characterizations further revealed the excellent reproducibility of the SERS activity. Our findings may pave the way for design of low-cost and stable SERS substrates.

Quantitative and sensitive detection of prohibited fish drugs by surface-enhanced Raman scattering

Rapid and simple detections of two kinds of prohibited fish drugs, crystal violet （CV） and malachite green （MG）, were accomplished by surface-enhanced Raman scattering （SERS）. Based on the optimized Au/cicada wing, the detectable concentration of CV/MG can reach 10-7 M, and the linear logarithmic quantitative relationship curves between log/and logC allows for the determination of the unknown concentration of CV/MG solution. The detection of these two analytes in real environment was also achieved, demonstrating the application potential of SERS in the fast screening of the prohibited fish drugs, which is of great benefit for food safety and environmental monitoring.

Surface-enhanced resonance Raman scattering spectroscopy of single R6G molecules

Surface-enhanced resonance Raman scattering （SERRS） of Rhodamine 6G （R6G） adsorbed on colloidal silver clusters has been studied. Based on the great enhancement of the Raman signal and the quench of the fluorescence, the SERRS spectra of R6G were recorded for the samples of dye colloidal solution with different concentrations. Spectral inhomogeneity behaviours from single molecules in the dried sample films were observed with complementary evidences, such as spectral polarization, spectral diffusion, intensity fluctuation of vibrational lines and even ＂breathing＂ of the molecules. Sequential spectra observed from a liquid sample with an average of 0.3 dye molecules in the probed volume exhibited the expected Poisson distribution for actually measuring 0, 1 or 2 molecules. Difference between the SERRS spectra of R6G excited by linearly and circularly polarized light were experimentally measured.

Surface-enhanced Raman scattering on nanodiamond-derived carbon onions

Annealing nanodiamonds(ND) at high temperatures up to 1700 ℃ is a common method to synthesize carbon onions. The transformation from NDs to carbon onions is particularly interesting because of carbon onions' potential in the field of tribology and their application in ultra-charge/discharge devices. In this paper, a novel surface-enhanced Raman scattering technique that involves coating the sample with nanoscopic gold particles is proposed to characterize the NDs after different annealing treatments. Conventional Raman and surfaceenhanced Raman spectra were obtained, and the changes of peak parameters as the function of annealing temperature were evaluated. It was found that the widths of the D and the G peaks decreased with increasing annealing temperature, reflecting an improved order in the sp^2-hybridized carbon during the transformation from NDs to carbon onions. After annealing at 1700 ℃, the sp^2?carbon was highly ordered, indicating desirable electrical conductivity and lubricity. With increasing annealing temperature, the D peak showed a blue shift of almost30 cm^(-1), while the G peak merely shifted by 5 cm^(-1). For annealing temperatures above 1100 ℃, an increase of intensity ratio ID/IGwas observed. Compared to the uncoated area, red shifts of 0.5-2 cm^(-1) and of 5-9 cm^(-1) for the G and D peaks, respectively, were detected for the gold-coated area, which was due to the coupling of the plasmons and the phonons of the samples.

Preparation of nano-structured Ag solid materials and application to surface-enhanced Raman scattering

Silver nano-particles with average diameter of about 60 nm were compacted in a high-strength mold under different pressures at 523 K to produce nano-structured Ag solid materials. The structure and characteristic of the nano-structured Ag solid materials (NSS-Ag) were studied using X-ray diffraction (XRD), scanning electron microscope (SEM) and Raman spectrometer. The NSS-Ag could be used as highly efficient surface-enhanced Raman scattering (SERS) active substrates. The common probe molecules Rhodamine 6G (R6G, 1×10-10 mol/L) were used to test the SERS activity on these substrates at very low concentrations. It is found that the SERS enhancement ability is dependent on the density of NSS-Ag. When the relative density of NSS-Ag is 83.87%, the materials reveal great SERS signal.

SURFACE-ENHANCED RAMAN SCATTERING:PRINCIPLES,NANOSTRUCTURES,FABRICATIONS,AND BIOMEDICAL APPLICATIONS

This article gives an overview of the development and applications of the surfaceenhanced Raman scattering(SERS)techniques in biomedicine.We first introduce the fundamental principles of the SERS mechanisms.We also present the different fabrication techniques of SERS nanostructures and substrates.Finally,the importance and potential roles of the SERS nanostructures and substrates in biomedical applications are summarized.

Comparison of Surface-enhanced Raman Scattering Spectra of Two Kinds of Silver Nanoplate Films

Surface-enhanced Raman scattering（SERS） spectra of different silver nanoplate selt-assembled tllmS at different excitation wavelengths were fairly compared. Shape conversion from silver nanoprisms to nanodisks on slides was in situ carried out. The SERS spectra of 4-mercaptopyridine（4-MPY） on these anisotropic silver nanopar- ticle self-assembled films present that strong enhancement appeared when the excitation line and the surface plasmon resonance（SPR） band of silver substrate overlapped. In this model, the influence of the crystal planes of silver na- noplates on SERS enhancement could be ignored because the basal planes were nearly unchanged in two kinds of silver nanoplate self-assembled films.

SERS光谱技术在结直肠癌诊断中的应用效果

选取扬州大学附属江都人民医院收集的50例结直肠癌组血清和50例健康组血清。以金纳米星(AuNS)为基底,利用Renishaw inVia Reflex激光共焦Raman光谱仪,对血清样本的表面增强Raman散射(SERS)光谱进行测定。借助Origin 2021对Min-Max归一化后平均光谱的特征峰分析,并用主成分分析(PCA)-K最邻近(KNN)模型对关键特征提取、分类。结果表明AuNS基底具有良好的均匀性、灵敏度和洁净性。结直肠癌患者在572、633、873、1065、1314、1417和1655 cm^(-1)特征峰处强度明显高于健康组,在1000和1536 cm^(-1)特征峰处强度低于健康组。PCA-KNN模型的准确率达到95%,灵敏度、特异性和曲线下的面积(AUC)分别达到90.0%、96.7%和0.933。结合PCA-KNN模型和SERS光谱技术可实现对结直肠癌快速、准确的识别,为诊断结肠癌提供了一种探索性的新方法。

Selective synthesis of three-dimensional ZnO@Ag/SiO2@Ag nanorod arrays as surface-enhanced Raman scattering substrates with tunable interior dielectric layer

We describe the synthesis of three-dimensional(3D) multilayer ZnO@Ag/SiO2@Ag nanorod arrays by the physico–chemical method. The surface-enhanced Raman scattering(SERS) performance of the 3D multilayer Zn O@Ag/SiO2@Ag nanorod arrays is studied by varying the thickness of dielectric layer SiO2 and outer-layer noble Ag. The 3D Zn O@Ag/SiO2@Ag nanorod arrays create a huge number of SERS "hot spots" that mainly contribute to the high SERS sensitivity. The great enhancement of SERS results from the electron transfer between ZnO and Ag and different electromagnetic enhancements of Ag nanoparticles(NPs) with different thicknesses. Through the finite-difference time-domain(FDTD) theoretical simulation, the enhancement of SERS signal can be ascribed to a strong electric field enhancement produced in the 3D framework. The simplicity and generality of our method offer great advantages for further understanding the SERS mechanism induced by the surface plasmon resonance(SPR) effect.

STUDY ON PHOTO-INDUCED ORIENTATION OF A NOVEL PHOTO-ALIGNMENT FILM WITH SURFACE ENHANCED RAMAN SCATTERING (SERS) SPECTROSCOPY

Surface enhanced Raman scattering (SERS) spectroscopy was first utilized to study the photo-orientation behaviour of the photoreactive groups on a novel photo-alignment film surface and elucidate the generation mechanism of pretilt angle. The novel photo-alignment film was prepared by spin-coating a solution of ladderlike polysiloxane (LPS) bearing dual photoreactive group on an ITO surface and by irradiation with linear-polarized ultraviolet (LPUV) light A Si—H terminal compound (M) containing an identical photosensitive part has been used to fabricate a model film for SERS investigation.

基于Ni纳米颗粒的SERS基底制备及其性能

以Ni纳米材料为研究对象,提出了一种新的基于超声辅助的表面增强Raman散射(SERS)基底的制备方法,以实现对生物分子罗丹明6G(R6G)的高灵敏检测。首先,通过超声辅助法制备Ni纳米溶液,然后,采用旋涂法制备SERS基底,以R6G为探针分子,研究了基底的SERS活性、重复性以及在基底制备过程中加入表面活性剂甲基丙烯酸甲酯(MMA)对基底SERS活性的影响。结果表明,在加入MMA的实验条件下,基底表面的纳米颗粒分散更加均匀,能提供的SERS热点更多,有助于增强基底的SERS强度。该SERS基底对R6G的最低检测限(LOD)为1×10^(-6)mol/L,增强因子约为2.56×10^(4),重复性测试的相对标准偏差为10.19%(R6G浓度为1×10^(4)mol/L)。该方法经济、简单、快速、有效,可以作为未来生物传感应用的候选方法。