BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the b...BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the bench side to routine clinical practice.In this study,we present a method that uses Raman spectroscopy(RS)to detect cancer in unstained formalin-fixed,resected specimens of the esophagus and stomach.Our method can record a clear Raman-scattered light spectrum in these specimens,confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue.AIM To evaluate the use of Raman-scattered light spectrum for detecting endoscopically resected specimens of esophageal squamous cell carcinoma(SCC)and gastric adenocarcinoma(AC).METHODS We created a Raman device that is suitable for observing living tissues,and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues.We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility,ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions.Furthermore,a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed.RESULTS We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens.After data capture,the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations.Based on data analysis of molecular-level substrates,we established cut-off values for the diagnosis of esophageal SCC and gastric AC.By analyzing specific Raman shifts,we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses.CONCLUSION Our technique provides qualitative information for real-time morphological diagnosis.However,further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.展开更多
Due to its ubiquitous occurrence in igneous,metamorphic,and sedimentary rocks and its wide application in geochronology and geochemistry,zircon has become the most widely used accessory mineral in the geological commu...Due to its ubiquitous occurrence in igneous,metamorphic,and sedimentary rocks and its wide application in geochronology and geochemistry,zircon has become the most widely used accessory mineral in the geological community.Nevertheless,the decay of U and Th causes radiation damage to the zircon structure,resulting in various degrees of metamictization,which can affect the accuracy of U–Pb dates and Hf and O isotope results.If the degree of zircon radiation damage can be quantified,the influence on geochemical analyses can be evaluated,and the results can be corrected more precisely.In this paper,synthetic and natural zircon crystals with different crystallization ages were selected for Raman spectroscopy analysis,cathodoluminescence imaging,and determination of the U and Th concentrations.The results show that Raman FWHM(full width at half bandmaximum)and Raman shift correlate with alpha dose(Da)ofzirconsfollowingtheseequations,FWHM=44.36(±2.32)×[1-exp(-2.74×Da)]-+1.7(±0.19),Raman Shift=-6.53×Da+1007.69.Analysis of synthetic zircon crystals shows that doped REEs(rare earth elements and P)can also lead to an increase in the FWHM.However,this effect can be ignored for natural zircon samples with REE contents at a normal level of hundreds to a few thousand ppm.The FWHM and Raman shift can be used as proxies to measure the degree of zircon radiation damage.Using the updated equations to calculate the latest age when zircon began to accumulate radiation damage,a more accurate and more meaningful“radiation damage age”can be obtained.展开更多
Bronze phase titanium dioxide(TiO_(2)(B))could be a promising high-power anode for lithium ion battery.However,TiO_(2)(B)is a metastable material,so the as-synthesized samples are inevitably accompanied by the existen...Bronze phase titanium dioxide(TiO_(2)(B))could be a promising high-power anode for lithium ion battery.However,TiO_(2)(B)is a metastable material,so the as-synthesized samples are inevitably accompanied by the existence of anatase phases.It has been found that the TiO_(2)(B)'s purity is positively correlated with its electrochemical performance.Herein,we have established an accurate quantification of the TiO_(2)(B)/anatase ratio,by figuring out the function between the purity of TiO_(2)(B)phase in the high purity range and its Raman spectra features in combination of the calibration by the synchrotron radiation X-ray diffraction(XRD).Compared with the time-consuming electrochemical method,the rapid,sensitive and non-destructive features of Raman spectroscopy have made it a promising candidate for determining the purity of TiO_(2)(B).Further,the correlations developed in this work should be instructive in synthesizing pure TiO_(2)(B)and furthermore optimizing its electrochemical charge storage properties.展开更多
The skin is the largest organ in humans.It comprises about 16%of our body.Many diseases originate from the skin,including acne vulgaris,skin cancer,fungal skin disease,etc.As a common skin cancer in China,melanoma alo...The skin is the largest organ in humans.It comprises about 16%of our body.Many diseases originate from the skin,including acne vulgaris,skin cancer,fungal skin disease,etc.As a common skin cancer in China,melanoma alone grows at year rate of nearly 4%.Therefore,it is crucial to develop an objective,reliable,accurate,non-invasive,and easy-to-use diagnostic method for skin diseases to support clinical decision-making.Raman spectroscopy is a highly specic imaging technique,which is sensitive,even to the single-cell level in skin diagnosis.Raman spectroscopy provides a pattern of signals with narrow bandwidths,making it a common and essential tool for researching individual characteristics of skin cells.Raman spectroscopy already has a number of clinical applications,including in thyroid,cervical and colorectal cancer.This review will introduce the advantages and recent developments in Raman spectroscopy,before focusing on the advances in skin diagnosis,including the advantages,methods,results,analysis,and notications.Finally,we discuss the current limitations and future progress of Raman spectroscopy in the context of skin diagnosis.展开更多
Electronic properties of two-dimensional(2D) materials can be strongly modulated by localized strain. The typical spatial resolution of conventional Kelvin probe force microscopy(KPFM) is usually limited in a few hund...Electronic properties of two-dimensional(2D) materials can be strongly modulated by localized strain. The typical spatial resolution of conventional Kelvin probe force microscopy(KPFM) is usually limited in a few hundreds of nanometers, and it is difficult to characterize localized electronic properties of 2D materials at nanoscales. Herein, tip-enhanced Raman spectroscopy(TERS) is proposed to combine with KPFM to break this restriction. TERS scan is conducted on ReS2bubbles deposited on a rough Au thin film to obtain strain distribution by using the Raman peak shift. The localized contact potential difference(CPD) is inversely calculated with a higher spatial resolution by using strain measured by TERS and CPD-strain working curve obtained using conventional KPFM and atomic force microscopy. This method enhances the spatial resolution of CPD measurements and can be potentially used to characterize localized electronic properties of 2D materials.展开更多
As one type of spatially offset Raman spectroscopy(SORS), inverse SORS is particularly suited to in vivo biomedical measurements due to its ring-shaped illumination scheme. To explain inhomogeneous Raman scattering du...As one type of spatially offset Raman spectroscopy(SORS), inverse SORS is particularly suited to in vivo biomedical measurements due to its ring-shaped illumination scheme. To explain inhomogeneous Raman scattering during in vivo inverse SORS measurements, the light–tissue interactions when excitation and regenerated Raman photons propagate in skin tissue were studied using Monte Carlo simulation. An eight-layered skin model was first built based on the latest transmission parameters. Then, an open-source platform, Monte Carlo e Xtreme(MCX), was adapted to study the distribution of 785 nm excitation photons inside the model with an inverse spatially shifted annular beam. The excitation photons were converted to emission photons by an inverse distribution method based on excitation flux with spatial offsets Δs of 1 mm, 2 mm, 3 mm and 5 mm. The intrinsic Raman spectra from separated skin layers were measured by continuous linear scanning to improve the simulation accuracy. The obtained results explain why the spectral detection depth gradually increases with increasing spatial offset, and address how the intrinsic Raman spectrum from deep skin layers is distorted by the reabsorption and scattering of the superficial tissue constituents. Meanwhile, it is demonstrated that the spectral contribution from subcutaneous fat will be improved when the offset increases to 5 mm, and the highest detection efficiency for dermal layer spectral detection could be achieved when Δs = 2 mm. Reasonably good matching between the calculated spectrum and the measured in vivo inverse SORS was achieved, thus demonstrating great utility of our modeling method and an approach to help understand the clinical measurements.展开更多
The limited penetration of photons in biological tissue restricts the deep-tissue detection and imaging application.The micro-scale spatially offset Raman spectroscopy(micro-SORS)with an optical fiber probe,colleting ...The limited penetration of photons in biological tissue restricts the deep-tissue detection and imaging application.The micro-scale spatially offset Raman spectroscopy(micro-SORS)with an optical fiber probe,colleting photons from deeper regions by offsetting the position of laser excitation from the collection optics in a range of hundreds of microns,shows great potential to be integrated with endoscopy for inside-body noninvasive detection by circumventing this restric-tion,particularly with the combination of surface-enhanced Raman spectroscopy(SERS).However,a detailed tissue penetration study of micro-SORS in combination with SERS is still lacking.Herein,we compared the signal decay of enhanced Raman nanotags through the tissue phantom of agarose gel and the biological tissue of porcine muscle in the near-infrared(NIR)region using a portable Raman spectrometer with a micro-SORS probe(2.1 mm in diameter)and a conventional hand-held probe(9.7mm in diameter).Two kinds of Raman nanotags were prepared from gold nanorods decorated with the nonresonant(4-nitrobenzenethiol)or resonant Raman reporter molecules(IR-780 iodide).The SERS measurements show that the penetration depths of two Raman nanotags are both over 2 cm in agarose gel and 3 mm in porcine muscle.The depth could be improved to over 4 cm in agarose gel and 5 mm in porcine tissue when using the micro-SORS system.This demonstrates the superiority of optical-fiber micro-SORS system over the conventional Raman detection for the detection of nanotags in deeper layers in the turbid medium and biological tissue,offering the possibility of combining the micro-SORS technique with SERS for noninvasive in vivo endoscopy-integrated clinical application.展开更多
Surface-enhanced Raman spectroscopy(SERS) based on two-dimensional(2 D) materials has attracted great attention over the past decade. Compared with metallic materials, which enhance Raman signals via the surface plasm...Surface-enhanced Raman spectroscopy(SERS) based on two-dimensional(2 D) materials has attracted great attention over the past decade. Compared with metallic materials, which enhance Raman signals via the surface plasmon effect, 2 D materials integrated on silicon substrates are ideal for use in the fabrication of plasmon-free SERS chips, with the advantages of outstanding fluorescence quenching capability, excellent biomolecular compatibility, tunable Fermi levels, and potentially lowcost material preparation. Moreover, recent studies have shown that the limits of detection of 2 D-material-based SERS may be comparable with those of metallic substrates, which has aroused significant research interest. In this review, we comprehensively summarize the advances in SERS chips based on 2 D materials. As several excellent reviews of graphene-enhanced Raman spectroscopy have been published in the past decade, here, we focus only on 2 D materials beyond graphene, i.e., transition metal dichalcogenides, black phosphorus, hexagonal boron nitride, 2 D titanium carbide or nitride, and their heterostructures. We hope that this paper can serve as a useful reference for researchers specializing in 2 D materials, spectroscopy, and diverse applications related to chemical and biological sensing.展开更多
Angle-resolved polarized Raman(ARPR) spectroscopy can be utilized to assign the Raman modes based on crystal symmetry and Raman selection rules and also to characterize the crystallographic orientation of anisotropi...Angle-resolved polarized Raman(ARPR) spectroscopy can be utilized to assign the Raman modes based on crystal symmetry and Raman selection rules and also to characterize the crystallographic orientation of anisotropic materials.However, polarized Raman measurements can be implemented by several different configurations and thus lead to different results. In this work, we systematically analyze three typical polarization configurations: 1) to change the polarization of the incident laser, 2) to rotate the sample, and 3) to set a half-wave plate in the common optical path of incident laser and scattered Raman signal to simultaneously vary their polarization directions. We provide a general approach of polarization analysis on the Raman intensity under the three polarization configurations and demonstrate that the latter two cases are equivalent to each other. Because the basal plane of highly ordered pyrolytic graphite(HOPG) exhibits isotropic feature and its edge plane is highly anisotropic, HOPG can be treated as a modelling system to study ARPR spectroscopy of twodimensional materials on their basal and edge planes. Therefore, we verify the ARPR behaviors of HOPG on its basal and edge planes at three different polarization configurations. The orientation direction of HOPG edge plane can be accurately determined by the angle-resolved polarization-dependent G mode intensity without rotating sample, which shows potential application for orientation determination of other anisotropic and vertically standing two-dimensional materials and other materials.展开更多
Marine sediment is the primary sink of microplastics and is an indicator of pollution levels.However,although there are well-developed detection methods,detection is rarely focused on lowmicrometer-sized particles,mai...Marine sediment is the primary sink of microplastics and is an indicator of pollution levels.However,although there are well-developed detection methods,detection is rarely focused on lowmicrometer-sized particles,mainly due to technique limitations.In this study,a simplifi ed process omitting digestion procedures was developed to pretreat microplastics obtained from marine sediment and was coupled with micro-Raman spectroscopy to identify microplastics.Based on the overall analysis of the characteristic peak assignments,a Raman spectral reference library was constructed for 18 types of plastic.In addition,the eff ects of the measurement parameters were systematically described.Field research was then conducted to validate the developed process and investigate microplastic contamination in Huiquan Bay,Qingdao,China.This simplifi ed process could retain the original appearance of microparticles and accomplish the detection of<500μm-sized microplastics in environmental samples.Microplastics in the size range of 10-150μm accounted for 76%of all microplastics,and 56%of the total particles was particles smaller than 50μm.Polypropylene(42%)and polyethylene(20%)were predominant components of the particles.In particular,polypropylene particles smaller than 10μm were identifi ed in marine sediment.This work demonstrates that Raman spectroscopy is not only an eff ective tool for detecting environmental particles but also highly applicable for identifying particles extracted from marine sediment.展开更多
Nitrogen-doped single-walled carbon nanotubes (CNx-SWNTs) with tunable dopant concentrations were synthesized by chemical vapor deposition (CVD), and their structure and elemental composition were characterized by...Nitrogen-doped single-walled carbon nanotubes (CNx-SWNTs) with tunable dopant concentrations were synthesized by chemical vapor deposition (CVD), and their structure and elemental composition were characterized by using transmission electron microscopy (TEM) in combination with electron energy loss spectroscopy (EELS). By comparing the Raman spectra of pristine and doped nanotubes, we observed the doping-induced Raman G band phonon stiffening and 2D band phonon softening, both of which reflect doping-induced renormalization of the electron and phonon energies in the nan- otubes and behave as expected in accord with the n-type doping effect. On the basis of first principles calculations of the distribution of delocalized carrier density in both the pristine and doped nanotubes, we show how the n-type doping occurs when nitrogen heteroatoms are substitutionally incorporated into the honeycomb tube-shell carbon lattice.展开更多
Downstream processing or product recovery plays a vital role in the development of bioprocesses.To improve the bioprocess efficiency,some unconventional methods are much required.The continuous manufacturing in downst...Downstream processing or product recovery plays a vital role in the development of bioprocesses.To improve the bioprocess efficiency,some unconventional methods are much required.The continuous manufacturing in downstream processing makes the Process Analytical Technologies(PATs)as an important tool.Monitoring and controlling bioprocess are an essential factor for the principles of PAT and quality by design.Spectroscopic methods can apply to monitor multiple analytes in real-time with less sample processing with significant advancements.Raman spectroscopy is an extensively used technique as an analytical and research tool owing to its modest process form,non-destructive,non-invasive optical molecular spectroscopic imaging with computer-based analysis.Generally,its application is essential for the analysis and characterization of biological samples,and it is easy to operate with minimal sample.The innovation on various types of enhanced Raman spectroscopy was designed to enhance the Raman analytical technique.Raman spectroscopy could couple with chemometrics to provide reliable alternative analysis method of downstream process analysis.Thus,this review aims to provide useful insight on the application of Raman spectroscopy for PAT in downstream processing of biotechnology and Raman data analysis in biological fields.展开更多
BACKGROUND Colorectal cancer(CRC) is an important disease worldwide, accounting for the second highest number of cancer-related deaths and the third highest number of new cancer cases. The blood test is a simple and m...BACKGROUND Colorectal cancer(CRC) is an important disease worldwide, accounting for the second highest number of cancer-related deaths and the third highest number of new cancer cases. The blood test is a simple and minimally invasive diagnostic test. However, there is currently no blood test that can accurately diagnose CRC.AIM To develop a comprehensive, spontaneous, minimally invasive, label-free, bloodbased CRC screening technique based on Raman spectroscopy.METHODS We used Raman spectra recorded using 184 serum samples obtained from patients undergoing colonoscopies. Patients with malignant tumor histories as well as those with cancers in organs other than the large intestine were excluded. Consequently, the specific diseases of 184 patients were CRC(12), rectal neuroendocrine tumor(2), colorectal adenoma(68), colorectal hyperplastic polyp(18), and others(84). We used the 1064-nm wavelength laser for excitation. The power of the laser was set to 200 mW.RESULTS Use of the recorded Raman spectra as training data allowed the construction of a boosted tree CRC prediction model based on machine learning. Therefore, the generalized R^2 values for CRC, adenomas, hyperplastic polyps, and neuroendocrine tumors were 0.9982, 0.9630, 0.9962, and 0.9986, respectively.CONCLUSION For machine learning using Raman spectral data, a highly accurate CRC prediction model with a high R^2 value was constructed. We are currently planning studies to demonstrate the accuracy of this model with a large amount of additional data.展开更多
As an important wide-bandgap semiconductor,gallium nitride(GaN)has attracted considerable attention.This paper describes the use of confocal Raman spectroscopy to characterize undoped GaN,n-type GaN,and p-type GaN thr...As an important wide-bandgap semiconductor,gallium nitride(GaN)has attracted considerable attention.This paper describes the use of confocal Raman spectroscopy to characterize undoped GaN,n-type GaN,and p-type GaN through depth profiling using 405-,532-,and 638-nm wavelength lasers.The Raman signal intensity of the sapphire substrate at different focal depths is studied to analyze the depth resolution.Based on the shift of the E2 H mode of the GaN epitaxial layer,the interfacial stress for different types of GaN is characterized and calculated.The results show that the maximum interfacial stress appears approximately at the junction of the GaN and the sapphire substrate.Local interfacial stress analysis between the GaN epitaxial layer and the substrate will be very helpful in furthering the applications of GaN devices.展开更多
A preliminary study was conducted to outline the laser Raman spectroscopy technique for determination of salinity in the aqueous phase in fluid inclusions. The skewing parameters of the Raman profiles of the calibrat...A preliminary study was conducted to outline the laser Raman spectroscopy technique for determination of salinity in the aqueous phase in fluid inclusions. The skewing parameters of the Raman profiles of the calibration solutions determined were used to derive a calibration curve for the estimation of the equivalent mass fraction NaCl in aqueous solutions. This technique was also verified in the analysis of the natural fluid inclusions from Tongshankou porphyry Cu (Mo) deposit, Hubei Province, China. Although the analyses on the natural fluid inclusions are limited, an acceptable agreement has been reached on the salinities, for most fluid inclusions, determined by the Raman spectroscopy and microthermometry techniques, indicating the reliability of the Raman technique for determination of salinity in fluid inclusion studies.展开更多
This study aimed to use Raman spectroscopy to identify the producing areas of peanut oil and build a robust discriminant model to further screen out the characteristic spectra closely related to the origin. Raman spec...This study aimed to use Raman spectroscopy to identify the producing areas of peanut oil and build a robust discriminant model to further screen out the characteristic spectra closely related to the origin. Raman spectra of 159 peanut oil samples from different provinces and different cities of the same province were collected. The obtained data were analyzed by stepwise linear discriminant analysis(SLDA), k-nearest neighbor analysis(k-NN),support vector machine(SVM) and multi-way analysis of variance. The results showed that the overall recognition rate of samples based on full spectra was higher than 90%. The producing origin, variety and their interaction influenced Raman spectra of peanut oil significantly, and 1 400–1 500 cmand 1 600– 1 700 cmwere selected as the characteristic spectra of origin and less affected by variety. The best classification model established by SLDA combined with characteristic spectra could rapidly and accurately identify peanut oil’s origin.展开更多
Layered P2–Na_(2/3)Ni_(1/3)Mn_(2/3)O_2 is a promising cathode material. It exhibits a high capacity and suitable operating voltage and undergoes a phase transition from P2 to O2 during charge/discharge.Researchers ha...Layered P2–Na_(2/3)Ni_(1/3)Mn_(2/3)O_2 is a promising cathode material. It exhibits a high capacity and suitable operating voltage and undergoes a phase transition from P2 to O2 during charge/discharge.Researchers have used Ti substitution to improve the cathode, yet the chemical principles that underpin elemental substitution and functional improvement remain unclear. To clarify these principles, we used in situ Raman spectroscopy to monitor chemical changes in P2–Na2/3 Ni1/3 Mn1/3 Ti1/3 O2 and P2–Na_(2/3)Ni_(1/3)Mn_(2/3)O_2 during charge/discharge. Based on the change in the A_(1g) and E_g peaks during charge/discharge, we concluded that Ti substitution compressed the transition metal layer and expanded the planar oxygen layer in the unit cell. Titanium stabilized the P2 phase structure, which improved the cycling stability of P2–NaNMT. Our results provide clear theoretical support for future research on modifying electrodes by elemental substitution.展开更多
Nitrogen-containing heterocyclic compounds are fundamental biochemical components of all life on Earth and,presumably,life elsewhere in our solar system.Detection and characterization of these compounds by traditional...Nitrogen-containing heterocyclic compounds are fundamental biochemical components of all life on Earth and,presumably,life elsewhere in our solar system.Detection and characterization of these compounds by traditional solvent extraction,chromatographic separation,and GC-MS analysis require more sample mass than will be available from samples returned to Earth from Mars.With its small sample mass requirement,Surface Enhanced Raman Spectroscopy could be an appropriate technique for analysis of returned samples.We have developed a SERS method for the detection of maleimide(2,5-pyrroledione),an N-containing heterocycle with a structure that is widespread in biochemicals.This semi-quantitative methodology accurately determines maleimide concentration in the range from 60 mg/mL to 120 mg/mL.We present a maleimide SERS standard spectrum which will be useful as a reference for future works.The present work demonstrates an easy,accurate,and effective method for the non-destructive qualitative and semi-quantitative study of maleimide as a first step toward developing a method for analysis of related compounds.展开更多
Multivariate calibration is an important tool for spectroscopic measurermnent of analyte con-centrations.We present a detailed study of a hybrid multivariate calibration technique,con-strained regularization(CR),and d...Multivariate calibration is an important tool for spectroscopic measurermnent of analyte con-centrations.We present a detailed study of a hybrid multivariate calibration technique,con-strained regularization(CR),and demonstrate its utility in noninvasive glucose sensing uasing Raman spectroscopy.Similar to partial least squares(PIS)and principal component regression(PCR),CR builds an implicit model and requires knowledge only of the concentrations of the analyte of interest.Calibration is treated as an inverse problem in which an optimal balance between model complexity and noise rejection is achieved.Prior information is included in the form of a spectroscopic constraint that can be obtained conveniently.When used with an appropriate constraint,CR provides a better calibration model compared to PLS in both numerical and experimental studies.展开更多
Objective To establish Surface-enhanced Raman Spectroscopy(SERS) can be used as a rapid and reliable method to distinguish virulent strain and mild strain of L. pneumophila. Methods We isolated and characterized of ...Objective To establish Surface-enhanced Raman Spectroscopy(SERS) can be used as a rapid and reliable method to distinguish virulent strain and mild strain of L. pneumophila. Methods We isolated and characterized of bacterial strains from ATCC and water samples strains, while we analyzed data from SERS technology using gold nanoparticles as a base and cell infections were employed to rapidly detect L. pneumophila strains. Origin 8.0 was used to collect Raman spectra, smooth and homogenize data, and to contrast spectra. Principal component analysis(PCA) was conducted to discriminate differences between groups using the multivariate analysis package Py Chem 3.0.5. Results Our results indicated that the peaks of high virulence strains reached ≥4000. This criterion was verified by subsequent cell experiments. In addition, we also conducted SERS rapid identification on the virulence of several collected clinical strains and obtained accurate results. Conclusion The present study indicates that the established SERS protocol can be used as a rapid and reliable method to distinguish virulent and mildly virulent strains of L. pneumophila, which can be further used in clinical samples.展开更多
基金Supported by MEXT KAKENHI,JP17K09022 and JP20K07643.
文摘BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the bench side to routine clinical practice.In this study,we present a method that uses Raman spectroscopy(RS)to detect cancer in unstained formalin-fixed,resected specimens of the esophagus and stomach.Our method can record a clear Raman-scattered light spectrum in these specimens,confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue.AIM To evaluate the use of Raman-scattered light spectrum for detecting endoscopically resected specimens of esophageal squamous cell carcinoma(SCC)and gastric adenocarcinoma(AC).METHODS We created a Raman device that is suitable for observing living tissues,and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues.We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility,ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions.Furthermore,a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed.RESULTS We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens.After data capture,the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations.Based on data analysis of molecular-level substrates,we established cut-off values for the diagnosis of esophageal SCC and gastric AC.By analyzing specific Raman shifts,we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses.CONCLUSION Our technique provides qualitative information for real-time morphological diagnosis.However,further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.
基金supported by funds from the Strategic Priority Research Program(B)of the Chinese Academy of Sciences(XDB 41000000)the National Natural Science Foundation of China(41973002,41772187)+1 种基金the Fundamental Research Funds for the Central UniversitiesNatural Sciences and Engineering Research Council of Canada(NSERC)Discovery Grant to J.M Hanchar(RGPIN/004649-2015)。
文摘Due to its ubiquitous occurrence in igneous,metamorphic,and sedimentary rocks and its wide application in geochronology and geochemistry,zircon has become the most widely used accessory mineral in the geological community.Nevertheless,the decay of U and Th causes radiation damage to the zircon structure,resulting in various degrees of metamictization,which can affect the accuracy of U–Pb dates and Hf and O isotope results.If the degree of zircon radiation damage can be quantified,the influence on geochemical analyses can be evaluated,and the results can be corrected more precisely.In this paper,synthetic and natural zircon crystals with different crystallization ages were selected for Raman spectroscopy analysis,cathodoluminescence imaging,and determination of the U and Th concentrations.The results show that Raman FWHM(full width at half bandmaximum)and Raman shift correlate with alpha dose(Da)ofzirconsfollowingtheseequations,FWHM=44.36(±2.32)×[1-exp(-2.74×Da)]-+1.7(±0.19),Raman Shift=-6.53×Da+1007.69.Analysis of synthetic zircon crystals shows that doped REEs(rare earth elements and P)can also lead to an increase in the FWHM.However,this effect can be ignored for natural zircon samples with REE contents at a normal level of hundreds to a few thousand ppm.The FWHM and Raman shift can be used as proxies to measure the degree of zircon radiation damage.Using the updated equations to calculate the latest age when zircon began to accumulate radiation damage,a more accurate and more meaningful“radiation damage age”can be obtained.
基金This work was financially supported by the National Natural Science Foundation of China(22075074)Outstanding Young Scientists Research Funds from Hunan Province(2020JJ2004)+3 种基金Major Science and Technology Program of Hunan Province(2020WK2013)Natural Science Foundation of Hunan Province(2020JJ5035)National Natural Science Foundation of China(Grant No.11704185)the Opening Project of State Key Laboratory of High Performance Ceramics and Superfine Microstructure(SKL201802SIC).
文摘Bronze phase titanium dioxide(TiO_(2)(B))could be a promising high-power anode for lithium ion battery.However,TiO_(2)(B)is a metastable material,so the as-synthesized samples are inevitably accompanied by the existence of anatase phases.It has been found that the TiO_(2)(B)'s purity is positively correlated with its electrochemical performance.Herein,we have established an accurate quantification of the TiO_(2)(B)/anatase ratio,by figuring out the function between the purity of TiO_(2)(B)phase in the high purity range and its Raman spectra features in combination of the calibration by the synchrotron radiation X-ray diffraction(XRD).Compared with the time-consuming electrochemical method,the rapid,sensitive and non-destructive features of Raman spectroscopy have made it a promising candidate for determining the purity of TiO_(2)(B).Further,the correlations developed in this work should be instructive in synthesizing pure TiO_(2)(B)and furthermore optimizing its electrochemical charge storage properties.
基金support received from the Medicine and Engineering Cross Research Foundation of Shanghai Jiao Tong University(Project No.YG2022QN047)as well as the National Nature Science Foundation of China(Grant No.62027824)the National Key Research and Development Program of China(2019YFC1604604).
文摘The skin is the largest organ in humans.It comprises about 16%of our body.Many diseases originate from the skin,including acne vulgaris,skin cancer,fungal skin disease,etc.As a common skin cancer in China,melanoma alone grows at year rate of nearly 4%.Therefore,it is crucial to develop an objective,reliable,accurate,non-invasive,and easy-to-use diagnostic method for skin diseases to support clinical decision-making.Raman spectroscopy is a highly specic imaging technique,which is sensitive,even to the single-cell level in skin diagnosis.Raman spectroscopy provides a pattern of signals with narrow bandwidths,making it a common and essential tool for researching individual characteristics of skin cells.Raman spectroscopy already has a number of clinical applications,including in thyroid,cervical and colorectal cancer.This review will introduce the advantages and recent developments in Raman spectroscopy,before focusing on the advances in skin diagnosis,including the advantages,methods,results,analysis,and notications.Finally,we discuss the current limitations and future progress of Raman spectroscopy in the context of skin diagnosis.
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China (Grant No. LZ22A040003)the National Natural Science Foundation of China (Grant No. 52027809)。
文摘Electronic properties of two-dimensional(2D) materials can be strongly modulated by localized strain. The typical spatial resolution of conventional Kelvin probe force microscopy(KPFM) is usually limited in a few hundreds of nanometers, and it is difficult to characterize localized electronic properties of 2D materials at nanoscales. Herein, tip-enhanced Raman spectroscopy(TERS) is proposed to combine with KPFM to break this restriction. TERS scan is conducted on ReS2bubbles deposited on a rough Au thin film to obtain strain distribution by using the Raman peak shift. The localized contact potential difference(CPD) is inversely calculated with a higher spatial resolution by using strain measured by TERS and CPD-strain working curve obtained using conventional KPFM and atomic force microscopy. This method enhances the spatial resolution of CPD measurements and can be potentially used to characterize localized electronic properties of 2D materials.
基金Project supported by the National Natural Science Foundation of China (Grant No. 61911530695)the Key Research and Development Project of Shaanxi Province, China (Grant No. 2023-YBSF-671)。
文摘As one type of spatially offset Raman spectroscopy(SORS), inverse SORS is particularly suited to in vivo biomedical measurements due to its ring-shaped illumination scheme. To explain inhomogeneous Raman scattering during in vivo inverse SORS measurements, the light–tissue interactions when excitation and regenerated Raman photons propagate in skin tissue were studied using Monte Carlo simulation. An eight-layered skin model was first built based on the latest transmission parameters. Then, an open-source platform, Monte Carlo e Xtreme(MCX), was adapted to study the distribution of 785 nm excitation photons inside the model with an inverse spatially shifted annular beam. The excitation photons were converted to emission photons by an inverse distribution method based on excitation flux with spatial offsets Δs of 1 mm, 2 mm, 3 mm and 5 mm. The intrinsic Raman spectra from separated skin layers were measured by continuous linear scanning to improve the simulation accuracy. The obtained results explain why the spectral detection depth gradually increases with increasing spatial offset, and address how the intrinsic Raman spectrum from deep skin layers is distorted by the reabsorption and scattering of the superficial tissue constituents. Meanwhile, it is demonstrated that the spectral contribution from subcutaneous fat will be improved when the offset increases to 5 mm, and the highest detection efficiency for dermal layer spectral detection could be achieved when Δs = 2 mm. Reasonably good matching between the calculated spectrum and the measured in vivo inverse SORS was achieved, thus demonstrating great utility of our modeling method and an approach to help understand the clinical measurements.
基金This work was financially supported by National Natural Science Foundation of China(Nos.81871401 and 81901786)China Postdoctoral Science Foundation(Nos.2018M640395 and 2019T120343)+3 种基金the Science and Technology Commission of Shanghai Municipality(No.19441905300)Innovation Research Plan supported by Shanghai Municipal Education Commission(No.ZXWF082101)Shanghai Jiao Tong University(Nos.YG2017MS54 and YG2019QNA28)the Shanghai Key Laboratory of Gynecologic Oncology.
文摘The limited penetration of photons in biological tissue restricts the deep-tissue detection and imaging application.The micro-scale spatially offset Raman spectroscopy(micro-SORS)with an optical fiber probe,colleting photons from deeper regions by offsetting the position of laser excitation from the collection optics in a range of hundreds of microns,shows great potential to be integrated with endoscopy for inside-body noninvasive detection by circumventing this restric-tion,particularly with the combination of surface-enhanced Raman spectroscopy(SERS).However,a detailed tissue penetration study of micro-SORS in combination with SERS is still lacking.Herein,we compared the signal decay of enhanced Raman nanotags through the tissue phantom of agarose gel and the biological tissue of porcine muscle in the near-infrared(NIR)region using a portable Raman spectrometer with a micro-SORS probe(2.1 mm in diameter)and a conventional hand-held probe(9.7mm in diameter).Two kinds of Raman nanotags were prepared from gold nanorods decorated with the nonresonant(4-nitrobenzenethiol)or resonant Raman reporter molecules(IR-780 iodide).The SERS measurements show that the penetration depths of two Raman nanotags are both over 2 cm in agarose gel and 3 mm in porcine muscle.The depth could be improved to over 4 cm in agarose gel and 5 mm in porcine tissue when using the micro-SORS system.This demonstrates the superiority of optical-fiber micro-SORS system over the conventional Raman detection for the detection of nanotags in deeper layers in the turbid medium and biological tissue,offering the possibility of combining the micro-SORS technique with SERS for noninvasive in vivo endoscopy-integrated clinical application.
基金supported by the National Natural Science Foundation of China (61805175)the Promotion of Science (JP18K13798)China Postdoctoral Sci-ence Foundation (2020M670641)。
文摘Surface-enhanced Raman spectroscopy(SERS) based on two-dimensional(2 D) materials has attracted great attention over the past decade. Compared with metallic materials, which enhance Raman signals via the surface plasmon effect, 2 D materials integrated on silicon substrates are ideal for use in the fabrication of plasmon-free SERS chips, with the advantages of outstanding fluorescence quenching capability, excellent biomolecular compatibility, tunable Fermi levels, and potentially lowcost material preparation. Moreover, recent studies have shown that the limits of detection of 2 D-material-based SERS may be comparable with those of metallic substrates, which has aroused significant research interest. In this review, we comprehensively summarize the advances in SERS chips based on 2 D materials. As several excellent reviews of graphene-enhanced Raman spectroscopy have been published in the past decade, here, we focus only on 2 D materials beyond graphene, i.e., transition metal dichalcogenides, black phosphorus, hexagonal boron nitride, 2 D titanium carbide or nitride, and their heterostructures. We hope that this paper can serve as a useful reference for researchers specializing in 2 D materials, spectroscopy, and diverse applications related to chemical and biological sensing.
基金supported by the National Key Research and Development Program of China(Grant No.2016YFA0301204)the National Natural Science Foundation of China(Grant Nos.11604326,11434010,11474277,and 11225421)
文摘Angle-resolved polarized Raman(ARPR) spectroscopy can be utilized to assign the Raman modes based on crystal symmetry and Raman selection rules and also to characterize the crystallographic orientation of anisotropic materials.However, polarized Raman measurements can be implemented by several different configurations and thus lead to different results. In this work, we systematically analyze three typical polarization configurations: 1) to change the polarization of the incident laser, 2) to rotate the sample, and 3) to set a half-wave plate in the common optical path of incident laser and scattered Raman signal to simultaneously vary their polarization directions. We provide a general approach of polarization analysis on the Raman intensity under the three polarization configurations and demonstrate that the latter two cases are equivalent to each other. Because the basal plane of highly ordered pyrolytic graphite(HOPG) exhibits isotropic feature and its edge plane is highly anisotropic, HOPG can be treated as a modelling system to study ARPR spectroscopy of twodimensional materials on their basal and edge planes. Therefore, we verify the ARPR behaviors of HOPG on its basal and edge planes at three different polarization configurations. The orientation direction of HOPG edge plane can be accurately determined by the angle-resolved polarization-dependent G mode intensity without rotating sample, which shows potential application for orientation determination of other anisotropic and vertically standing two-dimensional materials and other materials.
基金Supported by the Laboratory for Marine Geology,Qingdao Pilot National Laboratory for Marine Science and Technology(No.MGQNLMTD201904)the NSFC-Shandong Joint Fund for Marine Science Research Centers(No.U1606401)+1 种基金the Key Research Program of Frontier Sciences,CAS(No.QYZDB-SSW-DQC004)the Young Taishan Scholars Program(No.tsqn201909158)。
文摘Marine sediment is the primary sink of microplastics and is an indicator of pollution levels.However,although there are well-developed detection methods,detection is rarely focused on lowmicrometer-sized particles,mainly due to technique limitations.In this study,a simplifi ed process omitting digestion procedures was developed to pretreat microplastics obtained from marine sediment and was coupled with micro-Raman spectroscopy to identify microplastics.Based on the overall analysis of the characteristic peak assignments,a Raman spectral reference library was constructed for 18 types of plastic.In addition,the eff ects of the measurement parameters were systematically described.Field research was then conducted to validate the developed process and investigate microplastic contamination in Huiquan Bay,Qingdao,China.This simplifi ed process could retain the original appearance of microparticles and accomplish the detection of<500μm-sized microplastics in environmental samples.Microplastics in the size range of 10-150μm accounted for 76%of all microplastics,and 56%of the total particles was particles smaller than 50μm.Polypropylene(42%)and polyethylene(20%)were predominant components of the particles.In particular,polypropylene particles smaller than 10μm were identifi ed in marine sediment.This work demonstrates that Raman spectroscopy is not only an eff ective tool for detecting environmental particles but also highly applicable for identifying particles extracted from marine sediment.
基金supported by the National Natural Science Foundation of China(Grant Nos.11004230,51172273,11290161,and 11027402)the National Key Basic Research Program of China(Grant Nos.2012CB933003 and 2013CB932603)the Innovative Project of the Chinese Academy of Sciences(GrantNo.KJCX2-YW-W35)
文摘Nitrogen-doped single-walled carbon nanotubes (CNx-SWNTs) with tunable dopant concentrations were synthesized by chemical vapor deposition (CVD), and their structure and elemental composition were characterized by using transmission electron microscopy (TEM) in combination with electron energy loss spectroscopy (EELS). By comparing the Raman spectra of pristine and doped nanotubes, we observed the doping-induced Raman G band phonon stiffening and 2D band phonon softening, both of which reflect doping-induced renormalization of the electron and phonon energies in the nan- otubes and behave as expected in accord with the n-type doping effect. On the basis of first principles calculations of the distribution of delocalized carrier density in both the pristine and doped nanotubes, we show how the n-type doping occurs when nitrogen heteroatoms are substitutionally incorporated into the honeycomb tube-shell carbon lattice.
基金This work was supported by the National Natural Science Foundation of China(No.21878263,22078286)。
文摘Downstream processing or product recovery plays a vital role in the development of bioprocesses.To improve the bioprocess efficiency,some unconventional methods are much required.The continuous manufacturing in downstream processing makes the Process Analytical Technologies(PATs)as an important tool.Monitoring and controlling bioprocess are an essential factor for the principles of PAT and quality by design.Spectroscopic methods can apply to monitor multiple analytes in real-time with less sample processing with significant advancements.Raman spectroscopy is an extensively used technique as an analytical and research tool owing to its modest process form,non-destructive,non-invasive optical molecular spectroscopic imaging with computer-based analysis.Generally,its application is essential for the analysis and characterization of biological samples,and it is easy to operate with minimal sample.The innovation on various types of enhanced Raman spectroscopy was designed to enhance the Raman analytical technique.Raman spectroscopy could couple with chemometrics to provide reliable alternative analysis method of downstream process analysis.Thus,this review aims to provide useful insight on the application of Raman spectroscopy for PAT in downstream processing of biotechnology and Raman data analysis in biological fields.
基金the Japanese Society for the Promotion of Science (JSPS),based on the JSPS KAKENHI Grants-in-Aid for Scientific Research (C),No. JP17K09022。
文摘BACKGROUND Colorectal cancer(CRC) is an important disease worldwide, accounting for the second highest number of cancer-related deaths and the third highest number of new cancer cases. The blood test is a simple and minimally invasive diagnostic test. However, there is currently no blood test that can accurately diagnose CRC.AIM To develop a comprehensive, spontaneous, minimally invasive, label-free, bloodbased CRC screening technique based on Raman spectroscopy.METHODS We used Raman spectra recorded using 184 serum samples obtained from patients undergoing colonoscopies. Patients with malignant tumor histories as well as those with cancers in organs other than the large intestine were excluded. Consequently, the specific diseases of 184 patients were CRC(12), rectal neuroendocrine tumor(2), colorectal adenoma(68), colorectal hyperplastic polyp(18), and others(84). We used the 1064-nm wavelength laser for excitation. The power of the laser was set to 200 mW.RESULTS Use of the recorded Raman spectra as training data allowed the construction of a boosted tree CRC prediction model based on machine learning. Therefore, the generalized R^2 values for CRC, adenomas, hyperplastic polyps, and neuroendocrine tumors were 0.9982, 0.9630, 0.9962, and 0.9986, respectively.CONCLUSION For machine learning using Raman spectral data, a highly accurate CRC prediction model with a high R^2 value was constructed. We are currently planning studies to demonstrate the accuracy of this model with a large amount of additional data.
基金the National Natural Science Foundation of China(Grant Nos.51575389 and 51761135106)the National Key Research and Development Program of China(Grant No.2016YFB1102203)+1 种基金the State Key Laboratory of Precision Measuring Technology and Instruments(Pilt1705)the‘111’Project of the State Administration of Foreign Experts Affairs and the Ministry of Education of China(Grant No.B07014).
文摘As an important wide-bandgap semiconductor,gallium nitride(GaN)has attracted considerable attention.This paper describes the use of confocal Raman spectroscopy to characterize undoped GaN,n-type GaN,and p-type GaN through depth profiling using 405-,532-,and 638-nm wavelength lasers.The Raman signal intensity of the sapphire substrate at different focal depths is studied to analyze the depth resolution.Based on the shift of the E2 H mode of the GaN epitaxial layer,the interfacial stress for different types of GaN is characterized and calculated.The results show that the maximum interfacial stress appears approximately at the junction of the GaN and the sapphire substrate.Local interfacial stress analysis between the GaN epitaxial layer and the substrate will be very helpful in furthering the applications of GaN devices.
文摘A preliminary study was conducted to outline the laser Raman spectroscopy technique for determination of salinity in the aqueous phase in fluid inclusions. The skewing parameters of the Raman profiles of the calibration solutions determined were used to derive a calibration curve for the estimation of the equivalent mass fraction NaCl in aqueous solutions. This technique was also verified in the analysis of the natural fluid inclusions from Tongshankou porphyry Cu (Mo) deposit, Hubei Province, China. Although the analyses on the natural fluid inclusions are limited, an acceptable agreement has been reached on the salinities, for most fluid inclusions, determined by the Raman spectroscopy and microthermometry techniques, indicating the reliability of the Raman technique for determination of salinity in fluid inclusion studies.
基金supported by the Natural Science Foundation of Shandong Province,China(ZR2019BC033)。
文摘This study aimed to use Raman spectroscopy to identify the producing areas of peanut oil and build a robust discriminant model to further screen out the characteristic spectra closely related to the origin. Raman spectra of 159 peanut oil samples from different provinces and different cities of the same province were collected. The obtained data were analyzed by stepwise linear discriminant analysis(SLDA), k-nearest neighbor analysis(k-NN),support vector machine(SVM) and multi-way analysis of variance. The results showed that the overall recognition rate of samples based on full spectra was higher than 90%. The producing origin, variety and their interaction influenced Raman spectra of peanut oil significantly, and 1 400–1 500 cmand 1 600– 1 700 cmwere selected as the characteristic spectra of origin and less affected by variety. The best classification model established by SLDA combined with characteristic spectra could rapidly and accurately identify peanut oil’s origin.
基金supported by the NSFC (21905239, 21925404, and 21775127)the Natural Science Foundation of Shanxi Province of China (201901D211265)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (2019L0609)。
文摘Layered P2–Na_(2/3)Ni_(1/3)Mn_(2/3)O_2 is a promising cathode material. It exhibits a high capacity and suitable operating voltage and undergoes a phase transition from P2 to O2 during charge/discharge.Researchers have used Ti substitution to improve the cathode, yet the chemical principles that underpin elemental substitution and functional improvement remain unclear. To clarify these principles, we used in situ Raman spectroscopy to monitor chemical changes in P2–Na2/3 Ni1/3 Mn1/3 Ti1/3 O2 and P2–Na_(2/3)Ni_(1/3)Mn_(2/3)O_2 during charge/discharge. Based on the change in the A_(1g) and E_g peaks during charge/discharge, we concluded that Ti substitution compressed the transition metal layer and expanded the planar oxygen layer in the unit cell. Titanium stabilized the P2 phase structure, which improved the cycling stability of P2–NaNMT. Our results provide clear theoretical support for future research on modifying electrodes by elemental substitution.
基金supported through the“Terrestrial and Planetary Alteration Processes”strategic project(ref.PES 18/57)funded by the University of the Basque Country(UPV/EHU).
文摘Nitrogen-containing heterocyclic compounds are fundamental biochemical components of all life on Earth and,presumably,life elsewhere in our solar system.Detection and characterization of these compounds by traditional solvent extraction,chromatographic separation,and GC-MS analysis require more sample mass than will be available from samples returned to Earth from Mars.With its small sample mass requirement,Surface Enhanced Raman Spectroscopy could be an appropriate technique for analysis of returned samples.We have developed a SERS method for the detection of maleimide(2,5-pyrroledione),an N-containing heterocycle with a structure that is widespread in biochemicals.This semi-quantitative methodology accurately determines maleimide concentration in the range from 60 mg/mL to 120 mg/mL.We present a maleimide SERS standard spectrum which will be useful as a reference for future works.The present work demonstrates an easy,accurate,and effective method for the non-destructive qualitative and semi-quantitative study of maleimide as a first step toward developing a method for analysis of related compounds.
基金funding from the National Science Foundation (NSF) CAREER Award (CBET1151154)the National Aeronautics and Space Administration (NASA)Early Career Faculty Grant (NNX12AQ44G)+2 种基金Gulf of Mexico Research Initiative (GoMRI-030)Cullen College of Engineering at the University of Houstonthe MIT Laser Biomedical Research Center supported by the NIH National Center for Research Resources,Grant No.P41-RR02594.
文摘Multivariate calibration is an important tool for spectroscopic measurermnent of analyte con-centrations.We present a detailed study of a hybrid multivariate calibration technique,con-strained regularization(CR),and demonstrate its utility in noninvasive glucose sensing uasing Raman spectroscopy.Similar to partial least squares(PIS)and principal component regression(PCR),CR builds an implicit model and requires knowledge only of the concentrations of the analyte of interest.Calibration is treated as an inverse problem in which an optimal balance between model complexity and noise rejection is achieved.Prior information is included in the form of a spectroscopic constraint that can be obtained conveniently.When used with an appropriate constraint,CR provides a better calibration model compared to PLS in both numerical and experimental studies.
基金supported by National Key Technologies Research and Development Program of China(2013ZX10004-610)China Ministry of Science and Technology(MOST)Project 973(2012CB955501)WL is a principal investigator of the NSFC Innovative Research Group(Grant No.81321063)
文摘Objective To establish Surface-enhanced Raman Spectroscopy(SERS) can be used as a rapid and reliable method to distinguish virulent strain and mild strain of L. pneumophila. Methods We isolated and characterized of bacterial strains from ATCC and water samples strains, while we analyzed data from SERS technology using gold nanoparticles as a base and cell infections were employed to rapidly detect L. pneumophila strains. Origin 8.0 was used to collect Raman spectra, smooth and homogenize data, and to contrast spectra. Principal component analysis(PCA) was conducted to discriminate differences between groups using the multivariate analysis package Py Chem 3.0.5. Results Our results indicated that the peaks of high virulence strains reached ≥4000. This criterion was verified by subsequent cell experiments. In addition, we also conducted SERS rapid identification on the virulence of several collected clinical strains and obtained accurate results. Conclusion The present study indicates that the established SERS protocol can be used as a rapid and reliable method to distinguish virulent and mildly virulent strains of L. pneumophila, which can be further used in clinical samples.