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.

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.

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.

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.

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.

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.

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.

Surface-enhanced Raman scattering properties of highly ordered self-assemblies of gold nanorods with different aspect ratios

Gold nanorods with aspect ratios of from 1 （particles） to 31.6 were synthesized by the seed-mediated method and packed in a highly ordered structure on a large scale on silicon substrates through capillary force induced self-assembly behaviour during solvent evaporation. The gold nanorod surface exhibits a strong enhancing effect on Raman scattering spectroscopy. The enhancement of Raman scattering for two model molecules （2-naphthalenethiol and rhodamine 6C） is about 5-6 orders of magnitude. By changing the aspect ratio of the Au nanorods, we found that the enhancement factors decreased with the increase of aspect ratios. The observed Raman scattering enhancement is strong and should be ascribed to the surface plasmon coupling between closely packed nanorods, which may result in huge local electromagnetic field enhancements in those confined junctions.

Mechanism of Surface-Enhanced Raman Scattering and Its Application to Highly Sensitive Protein Detection

Surface-enhanced resonance Raman scattering(SERRS)has recently attracted great interest in analytical science due toenormous enhancement factors that have decreased the detec-tionli mits of a wide variety of molecules to the single moleculelevel.The SERRS-electromagnetic(EM)model describessingle-molecule SERRS

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.

Monitoring the penetration and accumulation of gold nanoparticles in rat skin ex vivo using surface-enhanced Raman scattering spectroscopy

Contamination by accidental cutaneous contact with the commercial products and the air pol-hutants raised a considerable health and safety issue.This study aimed to trace the dynamics of the 20 nm gold nanopartide(GNP)penetration and accumulation in rat skin tissues using a surface-enhanced Raman scattering(SERS)techmique.After the topical application of GNPs on rat skin surface,the SERS spectra were recorded for every 15 pum to an overall depth of 75 pum from skin surface for 150 min.The processes of GNP penetration in rat skin were accompanied by aggregation of GNPs,which affected SERS spectra.The results revealed that 20 nm GNPs can penetrate through stratum corneum layer,viable epidermis layer,and then into dermis layer.This study demonstrated for the first time the potential of SERS spectroscopy to monitor the penetration and accumulation of GNPs in rat skin.

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.

Ultrasensitive and point-of-care detection of plasma phosphorylated tau in Alzheimer’s disease using colorimetric and surface-enhanced Raman scattering dual-readout lateral flow assay

Phosphorylation of tau at Ser(396,404)(p-tau^(396,404))is one of the earliest phosphorylation events,plasma p-tau^(396,404) level appears to be a potentially promising biomarker of Alzheimer’s disease(AD).The low abundance and easy degradation of p-tau in the plasma make the lateral flow assay(LFA)a suitable choice for point-of-care detection of plasma p-tau^(396,404) levels.Herein,based on our screening of a pair of p-tau^(396,404)-specific antibodies,we developed a colorimetric and surface-enhanced Raman scattering(SERS)dual-readout LFA for the rapid,highly sensitive,robust detection of plasma p-tau^(396,404) levels.This LFA realized a detection limit of 60 pg/mL by the naked eye or 3.8 pg/mL by SERS without cross-reacting with other tau species.More importantly,LFA rapidly and accurately differentiated AD patients from healthy controls,suggesting that it has the potential for clinical point-of-care application in AD diagnosis.This dual-readout LFA has the advantages of simple operation,rapid,ultra-sensitive detection,providing a new way for early AD diagnosis and intervention,especially in primary and community AD screening.

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.