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.

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.

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.

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.

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.

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.

A distinction of gliomas at cellular and tissue level by surface-enhanced Raman scattering spectroscopy

Glioblastoma multiforme(GBM)is the most common malignant primary brain tumor in adults.The precise identification and distinction of GBM heterogeneity from surrounding brain parenchyma at the cellular level and even at the tissue level are important for GBM therapy.In this study,GBM cells are distinguished from normal astrocytes and non-central nervous system(CNS)tumor cells by surface-enhanced Raman scattering(SERS)based on gold nanoshell(SiO_(2)@Au)particles and support vector machine(SVM)algorithm.In addition,the gold nanoisland(AuNI)SERS substrates are further developed and explored for accurate detection of GBM at the tissue level.The distinction between glioma and trauma tissues,identification of different tumor grades,and IDH mutation are realized with the assistance of orthogonal partial least squares discriminant analysis(OPLS-DA)in a rapid,non-invasive,and convenient method.The results show that the developed SERS-based analytical method has the potential for practical application for the detection of GBM at the single-cell and tissue levels and even for real-time intraoperative diagnosis.

Au@Ag Core-shell Nanorods Self-assembled on Polyelectrolyte Multilayers for Ultra-High Sensitivity SERS Fiber Probes

We demonstrated a chemical process in the fabrication of a SERS fiber probe with an ultrahigh sensitivity.The synthesis was carried out by preparing Au@Ag core-shell nanorods (Au@Ag-NRs) selfassembled on polyelectrolyte (PE) multilayers,for which Au@Ag-NRs were controlled by adjusting the silver layer thickness.The effect of silver layer thickness of Au@Ag-NRs on the SERS performance of the fiber probe was investigated.The SERS fiber probe shows the best performance when the silver layer thickness is controlled at 8.57 nm.Under the condition of optimizing silver layer thickness,the fiber probe exhibits ultra-high sensitivity (i e,10^(-10) M crystalline violet,CV),good reproducibility (i e,RSD of 3.5%) and stability.Besides,electromagnetic field distribution of the SERS fiber probe was also investigated.The strongest enhancement is found within the core of fiber,whereas a weakened electromagnetic field exists in the fiber cladding layer.The SERS fiber probe can be a good candidate in ultra-trace detection for biomedical and environmental areas.

Ferroelectrically modulate the Fermi level of graphene oxide to enhance SERS response

Surface-enhanced Raman scattering(SERS)substrates based on chemical mechanism(CM)have received widespread attentions for the stable and repeatable signal output due to their excellent chemical stability,uniform molecular adsorption and controllable molecular orientation.However,it remains huge challenges to achieve the optimal SERS signal for diverse molecules with different band structures on the same substrate.Herein,we demonstrate a graphene oxide(GO)energy band regulation strategy through ferroelectric polarization to facilitate the charge transfer process for improving SERS activity.The Fermi level(Ef)of GO can be flexibly manipulated by adjusting the ferroelectric polarization direction or the temperature of the ferroelectric substrate.Experimentally,kelvin probe force microscopy(KPFM)is employed to quantitatively analyze the Ef of GO.Theoretically,the density functional theory calculations are also performed to verify the proposed modulation mechanism.Consequently,the SERS response of probe molecules with different band structures(R6G,CV,MB,PNTP)can be improved through polarization direction or temperature changes without the necessity to redesign the SERS substrate.This work provides a novel insight into the SERS substrate design based on CM and is expected to be applied to other two-dimensional materials.

Applications of magnetic nanoparticles in surface-enhanced Raman scattering(SERS)detection of environmental pollutants

Environmental pollution, a major problem worldwide, poses considerable threat to human health and ecological environment. Efficient and reliable detection technologies, which focus on the appearance of emerging environmental and trace pollutants, are urgently needed. Surface-enhanced Raman scattering(SERS) has become an attractive analytical tool for sensing trace targets in environmental field because of its inherent molecular fingerprint specificity and high sensitivity. In this review, we focused on the recent developments in the integration of magnetic nanoparticles(MNPs) with SERS for facilitating sensitive detection of environmental pollutants. An overview and classification of different types of MNPs for SERS detection were initially provided, enabling us to categorize the huge amount of literature that was available in the interdisciplinary research field of MNPs based SERS technology. Then, the basic working principles and applications of MNPs in SERS detection were presented. Subsequently, the detection technologies integrating MNPs with SERS that eventually were used for the detection of various environmental pollutions were reviewed. Finally, the advantages of MNP-basedSERS detection technology for environmental pollutants were concluded, and the current challenges and future outlook of this technology in practical applications were highlighted. The application of the MNPsbasedSERS techniques for environmental analysis will be significantly advanced with the great progresses of the nanotechnologies, optics, and materials.

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.

食品中苏丹红Ⅰ和辣椒红的表面增强拉曼散射(SERS)光谱与激发-发射矩阵荧光光谱鉴别

利用表面增强拉曼散射(SERS)光谱及激发-发射矩阵(EEM)荧光光谱对食品中非法添加剂苏丹红Ⅰ和合法食品添加剂辣椒红进行了定性分析和检测.SERS光谱结果表明,苏丹红Ⅰ在低波数区域分子的扭转振动信号增强比较明显;而辣椒红在1521和1158 cm-1处拉曼信号增强效果比较明显;EEM荧光光谱结果表明,苏丹红Ⅰ的乙醇溶液在P1(λex=285 nm,λem=345 nm)和P2(λex=335 nm,λem=548 nm)处有2个明显的荧光特征峰;而辣椒红的乙醇溶液有3个特征荧光峰,分别为P1(λex=545 nm,λem=580 nm),P2(λex=560 nm,λem=665 nm)和P3(λex=608 nm,λem=672 nm).

Laser irradiation induced spectral evolution of the surface-enhanced Raman scattering(SERS) of 4-tert-butylbenzylmercaptan on gold nanoparticles assembly

The spectral evolution of the surface-enhanced Raman scattering (SERS) of 4-tert-butylbenzylmer-captan (4-tBBM) on gold nanoparticles assembly under laser irradiation is reported. The relative intensities of typical peaks in the spectrum of 4-tBBM gradually change with irradiation time. Comparison of the rate of spectral changes under several experimental conditions indicates that the surface plasmon resonance (SPR) induced heat in the gold nanoparticles assembly is the origin of the spectral evolution. During the process of self-assembly, 4-tBBM molecules do not form a compact ordered monolayer because of the spatial hindrance of the 4-tert-butyl end group. The heat induced by laser irradiation drives the 4-tBBM molecules to rearrange to a more stable orientation.

Rapid synthesis of MoS_(2)-Ag nanocomposites via photoreduction for optical tuning and surface-enhanced Raman scattering applications

Semiconductoremetal nanocomposites have been widely investigated to modify the intrinsic properties of materials used for optoelectronic devices and sensing applications.In this study,a method for rapid synthesis of MoS_(2)-Ag nanocomposites via laser-assisted photoreduction was proposed.For the photoreduction process,we used AgNO_(3)solution as a metal source.Under laser irradiation,Ag ions were easily reduced on MoS_(2)by photo-generated electrons from MoS_(2).The optical properties of MoS_(2)-Ag nanocomposites were easily controlled by simple adjustment of the photoreduction time.To investigate the surface-enhanced Raman scattering(SERS)effect of the MoS_(2)-Ag nanocomposites,the SERS spectra of methylene blue(MB)on MoS_(2)-Ag nanocomposites were measured,and the nanocomposites were found to enhance the Raman scattering intensity of MB up to~106.Therefore,the laser-assisted photoreduction method has great potential for rapid synthesis and optical tuning of semiconductoremetal nanocomposites.

A microfluidic surface-enhanced Raman scattering(SERS) sensor for microRNA in extracellular vesicles with nucleic acid-tyramine cascade amplification

Exosomal micro RNA(mi RNA) is an ideal candidate of noninvasive biomarker for the early diagnosis of cancer. Sensitive and accurate sensing of abnormal exosomal mi RNA plays essential role for clinical promotion due to its close correlation with tumor proliferation and progression. Herein, a microfluidic surface-enhanced Raman scattering(SERS) sensor was proposed for an on-line detection of exosomal mi RNA based on rolling circle amplification(RCA) and tyramine signal amplification(TSA) strategy. The microfluidic chip consists of a magnetic enrichment chamber, a serpentine fluidic mixer and a plasmonic SERS substrate functionalized with capture probes. The released mi RNA activates the capture probe, triggers RCA reaction, and generates a large number of single-stranded DNA products to drive the catalysis of nanotags deposition via TSA, producing numerous “hot spots” to enhance the SERS signals. In merit of the microfluidics chip and nucleic acid-tyramine cascade amplification, the developed SERS sensor significantly improves the sensitivity for the exosomal mi RNA assay, resulting in a limit of detection(LOD) as low as 1 pmol/L and can be successfully applied in the analysis of exosomes secreted from breast tumor cells, which demonstrates the potential utility in practical applications.

Surface-enhanced Raman scattering(SERS)based on surface plasmon resonance coupling techniques

Surface plasmon resonance(SPR)can provide a remarkably enhanced electromagetic field around metal surface.It is one of the enhancement models for explaining surface-enhanced Raman scattering(SERS)phonomenon.With the development of SERS theories and techniques,more and more studies referred to the configurations of the optical devices for coupling the excitation and radiation of SERS,including the prism-coupling,waveguide-coupling,and grating-coupling modes.In this review,we will summarize the recent experimental improvements on the surface plasmoncoupled SERS.

适配体调控高SERS活性金纳米检测多菌灵

利用柠檬酸三钠还原氯金酸(HAuCl_4)制备具有较高表面增强拉曼散射(surface-enhanced Raman scattering,SERS)活性的金纳米(gold nanoparticles,AuNPs)溶胶作为基底,结合适配体与靶向物质特异性结合的性质,建立一个稳定性和重现性好的检测靶物质多菌灵(carbendazim,CBZ)的SERS定量检测方法。结果表明,在AuNPs浓度为6 mmol/L、NaCl浓度为15 mmol/L、维多利亚蓝B(Victoria blue B,VBB)浓度为0.25 mmol/L以及适配体溶液浓度为27 nmol/L的条件下,该法检出限为4.13 nmol/L,线性范围6.5 nmol/L~520 nmol/L,相关系数为0.998 8。