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.

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.

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.

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。

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.

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.

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.

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.

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.

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.

Ultraviolet-visible and Surface-enhanced Raman Scattering Spectroscopy Studies on Ruthenium Phthalocyanine Monolayer Films Formed on Terephthalonitrile-modified Silver Substrates

A self\|assembled monolayer film(SAM) of ruthenium phthalocyanine(RuPc) fabricated on a silver substrate premodified with an SAM of terephthalonitrile(TPN) was studied by means of surface\|enhanced Raman scattering(SERS) and ultraviolet\|visible(UV\|Vis) spectroscopies. TPN was used as a ligand to link RuPc since it can not only modify the silver substrate but also deliver the nitrile groups protruding from the silver surface. Therefore,we can explore the relationship between the structure and the orientation of RuPc and the TPN\|modified substrate. The UV\|Vis spectra indicate a strong interaction between RuPc and TPN in the composite film. The result is further confirmed by the SERS spectra of RuPc\|TPN SAM,in which the vibrational bands arising from both the RuPc and TPN moieties appear clearly,indicating that the RuPc is successfully assembled on the TPN film.

An effective surface-enhanced Raman scattering template based on gold nanoparticle/silicon nanowire arrays

A large-scale Si nanowire array （SiNWA） is fabricated with gold （Au） nanoparticles by simple metal-assisted chemical etching and metal reduction processes. The three-dimensional nanostructured Au/SiNWA is evaluated as an active substrate for surface-enhanced Raman scattering （SERS）. The results show that the detection limit for rhodamine 6G is as low as 10-7 M, and the Raman enhancement factor is as large as 105 with a relative standard deviation of less than 25%. After the calibration of the Raman peak intensifies of rhodamine 6G and thiram, organic molecules could be quantitatively detected. These results indicate that Au/SiNWA is a promising SERS-active substrate for the detection of biomolecules present in low concentrations. Our findings are an important advance in SERS substrates to allow fast and quantitative detection of trace organic contaminants.

A novel AgNPs/MOF substrate-based SERS sensor for high-sensitive on-site detection of wheat gluten

Gluten,known as the major allergen in wheat,has gained increasing concerns in industrialized countries,resulting in an urgent need for accurate,high-sensitive,and on-site detection of wheat gluten in complex food systems.Herein,we proposed a silver nanoparticles(AgNPs)/metal-organic framework(MOF)substrate-based surface-enhanced Raman scattering(SERS)sensor for the high-sensitive on-site detection of wheat gluten.The detection occurred on the newly in-situ synthesized AgNPs/MOF-modified SERS substrate,providing an enhancement factor(EF)of 1.89×10^(5).Benefitting from the signal amplification function of AgNPs/MOF and the superiority of SERS,this sensor represented high sensitivity performance and a wide detection range from 1×10^(-15)mol/L to 2×10^(-6)mol/L with a detection limit of 1.16×10^(-16)mol/L,which allowed monitoring the trace of wheat gluten in complex food system without matrix interference.This reliable sandwich SERS sensor may provide a promising platform for high-sensitive,accurate,and on-site detection of allergens in the field of food safety.

Controllable Synthesis of Au NRs and Its Flexible SERS Optical Fiber Probe with High Sensitivity

The surface-enhanced Raman scattering(SERS) optical fiber probes were successfully prepared by self-assembling on polyelectrolyte multilayers. Gold nanorods(Au NRs) were used as SERS enhancement material to give excellent biological affinity and stability to the SERS optical fiber probes. Au NRs were synthesized by seed growth method. The synergistic effect between AgNO_(3) and surfactant was investigated, and the highest yield was found when AgNO_(3) was 500 uL. Meanwhile, different SERS optical fiber probes were obtained by selecting silane coupling agent, polyelectrolyte multilayer and graphene oxide(GO) to treat quartz fiber. It was found that the SERS optical fiber probes obtained by the self-assembled on polyelectrolyte multilayers method performed better than those by other methods. In addition, Mapping was combined with finite element simulation to analyze the electromagnetic field distribution at the fiber end face.The electromagnetic field distribution of Au NRs was investigated, the difference of electromagnetic field intensity around the Au NRs with different arrangements was compared, the strongest signal was obtained when the Au NRs were head-to-head. Finally, sensitivity of the optimized SERS optical fiber probes could reach 10^(-9)mol/L, with excellent stability and repeatability.

Efficient concentration of trace analyte with ordered hotspot construction for a robust and sensitive SERS platform

Surface-enhanced Raman scattering(SERS)platform,which enables trace analyte detection,has important application prospects.By structuring/modifying the surface of the SERSsubstrate,analyte in highly diluted solutions can be concentrated into localized active areas for highly sensitive detection.However,subject to the difficulty of the fabrication process,itremains challenging to balance hot-spot construction and the concentration capacity of analyte simultaneously.Therefore,preparing SERS substrates with densely ordered hot spots andefficient concentration capacity is of great significance for highly sensitive detection.Herein,we propose an Ag and fluoroalkyl-modified hierarchical armour substrate(Ag/F-HA),which has a double-layer stacking design to combine analyte concentration with hotspot construction.The microarmour structure is fabricated by femtosecond-laser processing to serve as asuperhydrophobic and low-adhesive surface to concentrate analyte,while the anodic aluminium oxide(AAO)template creates a nanopillar array serving as dense and ordered hot spots.Under the synergistic action of hot spots and analyte concentration,Ag/F-HA achieves a detectionlimit down to 10^(-7)M doxorubicin(DOX)molecules with a RSD of 7.69%.Additionally,Ag/F-HA exhibits excellent robustness to resist external disturbances such as liquid splash or abrasion.Based on our strategy,SERS substrates with directional analyte concentrations are further explored by patterning microcone arrays with defects.This work opens a way to the realistic implementation of SERS in diverse scenarios.