Simultaneous measurements of global vibrational spectra and dephasing times of molecular vibrational modes by broadband time-resolved coherent anti-Stokes Raman scattering spectrography

In broadband coherent anti-Stokes Raman scattering （CARS） spectroscopy with supercontinuum （SC）, the simultaneously detectable spectral coverage is limited by the spectral continuity and the simultaneity of various spectral components of SC in an enough bandwidth. By numerical simulations, the optimal experimental conditions for improving the SC are obtained. The broadband time-resolved CARS spectrography based on the SC with required temporal and spectral distributions is realised. The global molecular vibrational spectrum with well suppressed nonresonant background noise can be obtained in a single measurement. At the same time, the measurements of dephasing times of various molecular vibrational modes can be conveniently achieved from intensities of a sequence of time-resolved CARS signals. It will be more helpful to provide a complete picture of molecular vibrations, and to exhibit a potential to understand not only both the solvent dynamics and the solute-solvent interactions, but also the mechanisms of chemical reactions in the fields of biology, chemistry and material science.

Selective excitation of molecular mode in a mixture by femtosecond resonance-enhanced coherent anti-Stokes Raman scattering spectroscopy

Femtosecond time-resolved coherent anti-Stokes Raman scattering （CARS） spectroscopy is used to investigate gaseous molecular dynamics. Due to the spectrally broad laser pulses, usually poorly resolved spectra result from this broad spectroscopy. However, it can be demonstrated that by the electronic resonance enhancement optimization control a selective excitation of specific vibrational mode is possible. Using an electronically resonance-enhanced effect, iodine molecule specific CARS spectroscopy can be obtained from a mixture of iodine-air at room temperature and a pressure of 1 atm （corresponding to a saturation iodine vapour as low as about 35 Pa）. The dynamics on either the electronically excited state or the ground state of iodine molecules obtained is consistent with previous studies （vacuum, heated and pure iodine） in the femtoseeond time resolved CARS spectroscopy, showing that an effective method of suppressing the non-resonant CARS background and other interferences is demonstrated.

Selective excitation and suppression of coherent anti-Stokes Raman scattering by shaping femtosecond pulses

Femtosecond coherent anti-Stokes Raman scattering （CARS） suffers from poor selectivity between neighbouring Raman levels due to the large bandwidth of the femtosecond pulses. This paper provides a new method to realize the selective excitation and suppression of femtosecond CARS by manipulating both the probe and pump （or Stokes） spectra. These theoretical results indicate that the CARS signals between neighbouring Raman levels are differentiated from their indistinguishable femtosecond CARS spectra by tailoring the probe spectrum, and then their selective excitation and suppression can be realized by supplementally manipulating the pump （or Stokes） spectrum with the π spectral phase step.

Coherent coupling between vibrational modes of C-H bonds at different positions studied by femtosecond time-resolved coherent anti-Stokes Raman scattering

We performed femtosecond time-resolved coherent anti-Stokes Raman scattering （fs-CARS） measurements on liquid toluene and PVK film. For both samples, we selectively excited the CH stretching vibrational modes and observed the expected quantum beat signals. The frequency of the well-defined beats is in good agreement with the energy difference between the two simultaneously excited modes, which demonstrates that a coherent coupling between the vibrational modes of the C H chemical bonds exists at the different positions of the molecules. The dephasing times of the excited modes are obtained simultaneously.

High-resolution imaging of graphene by tip-enhanced coherent anti-Stokes Raman scattering

Coherent anti-Stokes Raman scattering(CARS)is able to enhance molecular signals by vibrational coherence compared to weak Raman signal.The surface or tip enhancement are successful technologies,which make it possible for Raman to detect single molecule with nanometer resolution.However,due to technical diffculties,tip-enhanced CARS(TECARS)is not as successful as expected.For single molecular detection,high sensitivity and resolution are two main challenges.Here,we reported the first single atom layer TECARS imaging on Graphene with the highest resolution about 20 nm,which has ever been reported.The highest EF_(TECARS/CARS) is about 10^(4),the similar order of magnitude with SECARS(EF of tip is usually smaller than that of substrates).Such resolution and sensitivity is promising for medical,biology and chemical applications in the future.

COHERENT ANTI-STOKES RAMAN SCATTERING MICROSCOPY TO MONITOR DRUG DISSOLUTION IN DIFFERENT ORAL PHARMACEUTICAL TABLETS

Coherent anti-Stokes Raman scattering(CARS)microscopy is used to visualize the release of a model drug(theophylline)from a lipid(tripalmitin)based tablet during dissolution.The effects of transformation and dissolution of the drug are imaged in real time.This study reveals that the manufacturing process causes significant differences in the release process:tablets prepared from powder show formation of theophylline monohydrate on the surface which prevents a controlled drug release,whereas solid lipid extrudates did not show formation of monohydrate.This visualization technique can aid future tablet design.

Wide-Field Vibrational Phase Contrast Imaging Based on Coherent Anti-Stokes Raman Scattering Holography

We propose and implement a wide-field vibrational phase contrast detection to obtain imaging of imaginary components of third-order nonlinear susceptibility in a coherent anti-Stokes Raman scattering （CARS） microscope with full suppression of the non-resonant background. This technique is based on the unique ability of recovering the phase of the generated CARS signal based on holographic recording. By capturing the phase distributions of the generated CARS field from the sample and from the environment under resonant illumination, we demonstrate the retrieval of imaginary components in the CARS microscope and achieve background free coherent Raman imaging.

Theoretical and experimental investigations of coherent phonon dynamics in sapphire crystal using femto-second time-resolved coherent anti-Stokes Raman scattering

We report on the theoretical and the experimental investigations of the coherent phonon dynamics in sapphire crystal using the femtosecond time-resolved coherent anti-Stokes Raman scattering （fs-CARS） technique. The temporal chirped white-light continuum （WLC） is used for the Stokes pulse, therefore we can perform the selective excitation of the phonon modes without using a complicated laser system. The expected quantum beat phenomenon is clearly observed. The theoretical formulas consist very well with the experimental results. The dephasing times of the excited phonon modes, the wavenumber difference, and the phase shift between the simultaneously excited modes are obtained and discussed. This work opens up a way to study directly high-frequency coherent phonon dynamics in bulk crystals on a femtosecond time scale and is especially helpful for understanding the nature of coherent phonons.

Analysis of detection limit to time-resolved coherent anti-Stokes Raman scattering nanoscopy

In the implementation of CARS nanoscopy, signal strength decreases with focal volume size decreasing. A crucial problem that remains to be solved is whether the reduced signal generated in the suppressed focal volume can be detected. Here reported is a theoretical analysis of detection limit （DL） to time-resolved CARS （T-CARS） nanoscopy based on our proposed additional probe-beam-induced phonon depletion （APIPD） method for the low concentration samples. In order to acquire a detailed shot-noise limited signal-to-noise （SNR） and the involved parameters to evaluate DL, the T-CARS process is described with full quantum theory to estimate the extreme power density levels of the pump and Stokes beams determined by saturation behavior of coherent phonons, which are both actually on the order of ~ 109 W/cm2. When the pump and Stokes intensities reach such values and the total intensity of the excitation beams arrives at a maximum tolerable by most biological samples in a certain suppressed focal volume （40-nm suppressed focal scale in APIPD method）, the DL correspondingly varies with exposure time, for example, DL values are 103 and 102 when exposure times are 20 ms and 200 ms respectively.

Supercontinuum fiber laser-based coherent anti-Stokes Raman scattering microscopy for label-free chemical imaging

Coherent anti-Stokes Raman scattering(CA RS)microscopy can resolve the chemical compo-nents and distribution of living biological systems in a label-firee manner and is favored in several disciplines.Current CA RS microscopes typically use bulky,high-performance solid-state lasers,which are expensive and sensitive to environmental changes.With their relatively low cost and environmental sensitivity,supercontinum fiber(SF)lasers with a small footprint have found increasing use in biomedical applications.Upon these features,in this paper,we homebuilt a low-cost CARS microscope based on a SF laser module(scCA RS microscope).This SF laser module is specially customized by adding a time synchronized seed source channel to the SF laser to form a dual-channel output laser.The performance of the scCARS microscope is evaluated with dimethyl sulfoxide,whose results confirm a spatial resolution of better than 500nm and a detection sensitivity of millimolar concentrations.The dual-color imaging capability is further demonstrated by imaging different species of mixed microspheres.We finally explore the potential of our scCARS microscope by mapping lipid droplets in different cancer cells and corneal stromal lenses.

Selective Excitation of Two-pulse Femtosecond Coherent Anti-Stokes Raman Scattering in a Mixture

In this paper, we experimentally study the selective excitation of two-pulse femtosecond coherent anti-Stokes Raman scattering (CARS) in a mixture of dibromomethane (CH2Br2) and chloroform (CHCl3) by adaptive pulse shaping based on genetic algorithm. Second harmonic generation frequency-resolved optical gating (SHG-FROG) traces indicate that the spectral amplitude and phase of the optimal pulse are both modulated. Finally, we discuss the physical mechanism for the selective excitation of femtosecond CARS based on the retrieved information from SHG-FROG traces.

Suppression of stimulated Brillouin and Raman scatterings using an alternating frequency laser and transverse magnetic fields

A novel scheme to suppress both stimulated Brillouin scattering(SBS) and stimulated Raman scattering(SRS) by combining an alternating frequency(AF) laser and a transverse magnetic field is proposed. The AF laser allows the laser frequency to change discretely and alternately over time. The suppression of SBS is significant as long as the AF difference is greater than the linear growth rate of SBS or the alternating time of the laser frequency is shorter than the linear growth time of SBS. However, the AF laser proves ineffective in suppressing SRS, which usually has a much higher linear growth rate than SBS. To remedy that, a transverse magnetic field is included to suppress the SRS instability. The electrons trapped in the electron plasma waves(EPWs) of SRS can be accelerated by the surfatron mechanism in a transverse magnetic field and eventually detrapped. While continuously extracting energy from EPWs, the EPWs are dissipated and the kinetic inflation of SRS is suppressed. The one-dimensional particle-in-cell simulation results show that both SBS and SRS can be effectively suppressed by combining the AF laser with a transverse magnetic field with tens of Tesla. The total reflectivity can be dramatically reduced by more than one order of magnitude. These results provide a potential reference for controlling SBS and SRS under the related parameters of inertial confinement fusion.

High enhancement factor of Au nano triangular prism structure for surface enhanced coherent anti-Stokes Raman scattering

Coherent anti-Stokes Raman scattering spectroscopy（CARS） is a well-known detecting tool in biosensing and nonlinear spectroscopy. It can provide a non-invasive alternative without the need for exogenous labels,while the enhancement factor for surface plasmon resonances（SPR） are extensively used to increase the local field close to the oscillators and which can obtain high enhancement. In this work, we investigate the enhancement factor of our structure for surface-enhanced coherent anti-Stokes Raman scattering. The absorption spectrum of the structure has been studied, a wide range of absorption has been realized. The enhancement can be as high as 10^（16） over standard CARS. Our design is very useful for improving the enhancement factor of surface-enhanced coherent anti-Stokes Raman scattering.

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.

A New Method for In-Situ Measurement of Internal Solitary Waves Based on the Stimulated Raman Scattering in Optical Fibers

In-situ measurement of internal solitary waves(ISWs)is complicated in the ocean due to their randomness.At present,the ISWs are mainly detected by the chain structure of conductivity-temperature-depth systems(CTDs)or temperature sensors.The high cost limits the spatial resolution,which ultimately affects the measuring accuracy of the ISW amplitude.In this paper,we developed an experimental measurement system for detecting ISWs based on the stimulated Raman scattering in distributed optical fibers.This system has the advantages of high precision,low cost,and easy operation.The experimental results show that the system is consistent with CTDs in the measurement of vertical ocean temperature variation.The spatial resolution of the system can reach 1.0 m and the measuring accuracy of temperature is 0.2℃.We successfully detected 3 ISWs by the system in the South China Sea and two optical remote sensing images collected on May 18,2021,the same day of two detected ISWs,verify the occurrence of the measured ISWs.We used the image pairs method to calculate the phase velocity of ISW and the result is 1.71 ms^(-1).By extracting the distances between wave packets,it can be found that the semi-diurnal tide generates the detected ISWs.The impact of the tidal current velocity on the ISW in amplitude is undeniable.Undoubtedly,the system has a great application prospect for detecting ISWs and other dynamic phenomena in the ocean.

Coherent Raman scattering imaging of lipid metabolism in cancer

Cancer cells dysregulate lipid metabolism to accelerate energy production and biomolecule synthesis for rapid growth.Lipid metabolism is highly dynamic and intrinsically heterogeneous at the single cell level.Although°uorescence microscopy has been commonly used for cancer research,bulky°uorescent probes can hardly label small lipid molecules without perturbing their biological activities.Such a challenge can be overcome by coherent Raman scattering(CRS)microscopy,which is capable of chemically selective,highly sensitive,submicron resolution and high-speed imaging of lipid molecules in single live cells without any labeling.Recently developed hyperspectral and multiplex CRS microscopy enables quantitative mapping of various lipid metabolites in situ.Further incorporation of CRS microscopy with Raman tags greatly increases molecular selectivity based on the distinct Raman peaks well separated from the endogenous cellular background.Owing to these unique advantages,CRS microscopy sheds new insights into the role of lipid metabolism in cancer development and progression.This review focuses on the latest applications of CRS microscopy in the study of lipid metabolism in cancer.

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.

Stimulated Raman scattering microscopy on biological cellular machinery

Beneting from the developments of advanced optical microscopy techniques,the mysteries of biological functions at the cellular and subcellular levels have been continuously revealed.Stimulated Raman scattering(SRS)microscopy is a rapidly growing technique that has attracted broad attentions and become a powerful tool for biology and biomedicine,largely thanks to its chemical specicity,high sensitivity and fast image speed.This review paper introduces the principles of SRS,discusses the technical developments and implementations of SRS microscopy,then highlights and summarizes its applications on biological cellular machinery andnally shares our visions of potential breakthroughs in the future.

A mini review and hypothesis for coronavirus detection using photonics: surface enhanced Raman scattering and fluorescence resonance energy transfer

COVID-19 has devastated numerous nations around the world and has overburdened numerous healthcare systems,which has also caused the loss of livelihoods due to prolonged shutdowns and further led to a cascading effect on the global economy.COVID-19 infections have an incubation period of 2–7 days,but 40 to 45%of cases are asymptomatic or show mild to moderate respiratory symptoms after the period due to subclinical lung abnormalities,making it more likely to spread the pandemic disease.To restrict the spread of the virus,on-site diagnosis methods that are quicker,more precise,and easily accessible are required.Rapid Antigen Detection Tests and Polymerase Chain Reaction tests are currently the primary methods used to determine the presence of COVID-19 viruses.These tests are typically time-consuming,not accurate,and,more importantly,not available to everyone.Hence,in this review and hypothesis,we proposed equipment that employs the properties of photonics to improve the detection of COVID-19 viruses by taking the advantage of typical binding of coronavirus with angiotensin-converting enzyme 2(ACE2)receptors.This hypothetical model would combine Surface-Enhanced Raman Scattering(SERS)and Fluorescence Resonance Energy Transfer(FRET)to provide great flexibility,high sensitivities,and enhanced accessibility.

基于anti-Stokes Raman散射温度效应的温度解调理论研究

激光脉冲进入光纤中,与光纤分子相互作用,产生Raman散射和Raylei曲散射。由于Raman散射具有温度效应,其散射光强度受温度调制,可作为温度信息的载体,用于温度解调及测温系统设计。本文提出了可行的温度解调方法及理论推导,并推导出单通道和双通道条件下的测温关系,设计出两种条件下的传感器系统。