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Both spontaneous Raman scattering and stimulated Raman scattering (SRS) are cornerstones of modern photonics, spectroscopy, and imaging. However, a unified understanding of the ultimate detectability of Raman scattering is lacking, due to both historical and technical reasons. Starting from quantum electrodynamics, we formulate the fundamental detectability for both spontaneous Raman scattering and SRS. The key concept is recognizing spontaneous Raman scattering as stimulated Raman process driven by vacuum field fluctuation. A simple and unified expression, Eq. (17), is derived, which can be depicted on a two-dimensional phase-diagram-like graph with inherent symmetry. It turns out that the particle nature of light dictates the ultimate detectability of spontaneous Raman scattering, which can be represented by a line on this detectability diagram. Importantly, if provided with a reasonably strong Stokes photon flux, SRS can breach this fundamental limit and open uncharted territory of drastically accelerated measurement speed and much lower detection concentration relevant to biological imaging. Such new territory in the detectability diagram is otherwise forbidden by the spontaneous counterpart. Diagrammatical analysis explains the empirical observations, provides quantitative insights, and makes new predictions. Notably, recent experimental applications of SRS microscopy can almost entirely be captured by this diagram, further supporting the explanatory power of the theory. Thus, this unified diagrammatic approach outlines a framework to understand all Raman-based measurement and provides a theoretical explanation for the remarkable utility of the emerging SRS microscopy. [ABSTRACT FROM AUTHOR]

Raman microscopy is a vibrational imaging technology that can detect molecular chemical bond vibrational signals. Since this signal is originated from almost every vibrational mode of molecules with different vibrational energy levels, it provides spatiotemporal distribution of various molecules in living organisms without the need for any labeling. The limitations of low signal strength in Raman microscopy have been effectively addressed by incorporating a stimulated emission process, leading to the development of stimulated Raman scattering (SRS) microscopy. Furthermore, the issue of low spatial resolution has been resolved through the application of computational techniques, specifically image deconvolution. In this article, we present a comprehensive guide to super-resolution SRS microscopy using an Adam-based pointillism deconvolution (A-PoD) algorithm, complemented by a user-friendly graphical user interface (GUI). We delve into the crucial parameters and conditions necessary for achieving super-resolved images through SRS imaging. Additionally, we provide a step-by-step walkthrough of the preprocessing steps and the use of GUI-supported A-PoD. This complete package offers a user-friendly platform for super-resolution SRS microscopy, enhancing the versatility and applicability of this advanced microscopy technique to reveal nanoscopic multimolecular nature. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Super-resolution stimulated Raman scattering microscopy with graphical user interface-supported A-PoD Support Protocol: Deuterium labeling on cells with heavy water for metabolic imaging.

Tracking drug disposition in the skin in a non-destructive and at least semi-quantitative fashion is a relevant objective for the assessment of local (cutaneous) bioavailability. Confocal Raman spectroscopy has been shown potentially useful in this regard and, importantly, recent advances have enabled the presence of applied chemicals in the viable epidermis below the stratum corneum (SC) to be determined without ambiguity and having addressed the challenges of (a) background signals from endogenous species and noise and (b) signal attenuation due to absorption and scattering. This study aimed to confirm these observations using a different vibrational spectroscopy approach - specifically, stimulated Raman scattering (SRS) microscopy – and the more conventional in vitro skin penetration test (IVPT). SRS is a nonlinear optical imaging technique which enables more precise location of the skin surface and enhanced skin depth resolution relative to confocal Raman microscopy. The method can also probe larger areas of the sample under investigation and identify the localization of the permeating chemical in specific structural components of the skin. Here, SRS was shown capable of tracking the uptake and distribution of 4-cyanophenol (CP), the same model compound used in the recent confocal Raman investigation, at depths beyond the SC following skin treatment with different vehicles and for different times. The SRS results correlated well with those from the confocal Raman experiments, and both were consistent with independent IVPT measurements. Acquired images clearly delineated CP preference for the intercellular lipid layers of the SC relative to the corneocytes. The stage is now set to apply these and other correlative techniques to examine commercial drug products. [Display omitted] [ABSTRACT FROM AUTHOR]

Intraoperative histology is essential for surgical guidance and decision-making. However, frozen-sectioned hematoxylin and eosin (H&E) staining suffers from degraded accuracy, whereas the gold-standard formalin-fixed and paraffin-embedded (FFPE) H&E is too lengthy for intraoperative use. Stimulated Raman scattering (SRS) microscopy has shown rapid histology of brain tissue with lipid/protein contrast but is challenging to yield images identical to nucleic acid-/protein-based FFPE stains interpretable to pathologists. Here, we report the development of a semi-supervised stimulated Raman CycleGAN model to convert fresh-tissue SRS images to H&E stains using unpaired training data. Within 3 minutes, stimulated Raman virtual histology (SRVH) results that matched perfectly with true H&E could be generated. A blind validation indicated that board-certified neuropathologists are able to differentiate histologic subtypes of human glioma on SRVH but hardly on conventional SRS images. SRVH may provide intraoperative diagnosis superior to frozen H&E in both speed and accuracy, extendable to other types of solid tumors. [ABSTRACT FROM AUTHOR]

For this study, we employed intense 400 nm, 100 fs pulses linearly propagated through a 50 cm water medium, initially self-stretching the excitation pulses to 2.50 ps. Subsequently, the self-stretched 2.50 ps pulses were focused into deionized water, and we conducted transient absorption experiments to measure and investigate the dynamics of hydrated electrons in water. The excess electrons generated were injected into the hydrogen bond network of the water cluster, leading to the observation of saturated hydrated electrons. Additionally, we observed the emergence of the forward stimulated Raman scattering (SRS) of water molecules. We report the experimental observation of a weak forward SRS emission at 463 nm (corresponding to 3400 cm−1), indicative of the ordinary OH stretching vibration in the liquid phase. Moreover, we observed an intense forward SRS emission at 460 nm in water, corresponding to two anomalous Raman shifts at 3260 cm−1 and 3355 cm−1. These anomalous Raman shifts resulted from changes in the hydrogen bond network structure. We determine that the formation of not fully hydrated and saturated hydrated electrons plays a crucial role in producing this phenomenon. [ABSTRACT FROM AUTHOR]

We investigate a new phenomenon, where a reciprocal fiber ring laser switches from bidirectional to unidirectional operation above a certain pump power threshold. Significant simplifications regarding earlier experiments are presented, which for the first time allow the identification of individual nonlinear effects. We highlight the unique role of stimulated Raman scattering in triggering unidirectional operation, and that additional conditions apply. The threshold is reduced from 30 to 3.8 W, which eases potential applications. [ABSTRACT FROM AUTHOR]

In this study, we conducted a detailed exploration of stimulated Raman scattering (SRS) in heavy water (D2O), focusing specifically on its behavior at the air–D2O interface. The analysis revealed discernible SRS characteristic peaks corresponding to different vibrational modes, showing a 3.31-fold reduction in the SRS threshold at the air–D2O interface. Notably, we achieved a remarkable 6.83% energy conversion efficiency, approximately 3.36 times higher than the 2.03% efficiency observed in bulk D2O. Through cascaded Raman scattering and Raman-enhanced four-wave mixing (FWM) processes, up to third-order Stokes and corresponding anti-Stokes SRS were obtained in an unprecedented manner at a low pump energy of 8.26 mJ. Additionally, distinctive conical spatial structures of Stokes and anti-Stokes generated at air–D2O interface were attributed to Raman-enhanced FWM processes. Our investigation into the temporal behavior of SRS pulses revealed a unique mechanism: the initial decline of pump pulse was due to SRS-induced pump energy loss and heat dissipation, while the behavior of latter half resulted from non-uniform refractive index, causing self-defocusing and inhibiting the sustained generation of SRS. Our study sheds light on the development of multi-wavelength and significant frequency shift Raman lasers, offering valuable perspectives for future research endeavors. [ABSTRACT FROM AUTHOR]

Generic drugs are essential for affordable medicine and improving accessibility to treatments. Bioequivalence (BE) is typically demonstrated by assessing a generic product's pharmacokinetics (PK) relative to a reference-listed drug (RLD). Accurately estimating cutaneous PK (cPK) at or near the site of action can be challenging for locally acting topical products. Certain cPK approaches are available for assessing local bioavailability (BA) in the skin. Stimulated Raman scattering (SRS) microscopy has unique capabilities enabling continuous, high spatial and temporal resolution and quantitative imaging of drugs within the skin. In this paper, we developed an approach based on SRS and a polymer-based standard reference for the evaluation of topical product BA and BE in human skin ex vivo. BE assessment of tazarotene-containing formulations was achieved using cPK parameters obtained within different skin microstructures. The establishment of BE between the RLD and an approved generic product was successfully demonstrated. Interestingly, within the constraints of the current study design the results suggest similar BA between the tested gel formulation and the reference cream formulation, despite the differences in the formulation/dosage form. Another formulation containing polyethylene glycol as the vehicle was demonstrated to be not bioequivalent to the RLD. Compared to using the SRS approach without a standard reference, the developed approach enabled more consistent and reproducible results, which is crucial in BE assessment. The abundant information from the developed approach can help to systematically identify key areas of study design that will enable a better comparison of topical products and support an assessment of BE. Stimulated Raman scattering (SRS) microscopy enables bioequivalence (BE) assessment of pharmacokinetics parameters obtained within different skin microstructures. The developed polymer standard reference normalizes the SRS intensity and enables more consistent results. [Display omitted] • Develop a method based on a stimulated Raman microscope to monitor drug in ex vivo human skin. • Develop a stable standard reference to remove the effects of signal fluctuations for monitoring drugs with high specificity. • Quantify the drug and assess the cutaneous bioequivalence of topical formulations using the developed method. • Demonstrate bioequivalence of an approved generic drug and corresponding RLD within different microstructures in the skin. • Demonstrate that the lab-made formulation with PEG, a distinct vehicle from the RLD cream, is not bioequivalent to the RLD. [ABSTRACT FROM AUTHOR]

Raman microlasers form on-chip versatile light sources by optical pumping, enabling numerical applications ranging from telecommunications to biological detection. Stimulated Raman scattering (SRS) lasing has been demonstrated in optical microresonators, leveraging high Q factors and small mode volume to generate downconverted photons based on the interaction of light with the Stokes vibrational mode. Unlike redshifted SRS, stimulated anti-Stokes Raman scattering (SARS) further involves the interplay between the pump photon and the SRS photon to generate an upconverted photon, depending on a highly efficient SRS signal as an essential prerequisite. Therefore, achieving SARS in microresonators is challenging due to the low lasing efficiencies of integrated Raman lasers caused by intrinsically low Raman gain. In this work, high-Q whispering gallery microresonators were fabricated by femtosecond laser photolithography assisted chemo-mechanical etching on thin-film lithium niobate (TFLN), which is a strong Raman-gain photonic platform. The high Q factor reached 4.42 × 106, which dramatically increased the circulating light intensity within a small volume. And a strong Stokes vibrational frequency of 264 cm−1 of lithium niobate was selectively excited, leading to a highly efficient SRS lasing signal with a conversion efficiency of 40.6%. And the threshold for SRS was only 0.33 mW, which is about half the best record previously reported on a TFLN platform. The combination of high Q factors, a small cavity size of 120 μm, and the excitation of a strong Raman mode allowed the formation of SARS lasing with only a 0.46 mW pump threshold. [ABSTRACT FROM AUTHOR]

Supercontinuum radiation has found numerous applications in diverse fields encompassing spectroscopy, pulse compression, and tunable laser sources. Anomalous enhanced stimulated Raman scattering (SRS) of cyclohexane–benzene mixtures was obtained in this study. SRS of the pure solvent, the multi-order Stokes of the strongest fundamental vibration modes, and energy transfer in intra-molecular modes were observed. SRS of the mixture revealed that the cross-pumping effect was generated between the C–H stretching (v2) mode of cyclohexane and the C=C ring skeleton (v1) mode of benzene, thereby producing the intermolecular secondary stimulated Raman emission and the appearance of two super-broadband radiations at 664.36–673.9 nm and 704.62–729.22 nm. The results suggest that the energy transfer of intermolecular vibrational modes, where the strongest vibrational mode excites other vibrational modes, is a simple approach for generating supercontinuum coherent radiation. [ABSTRACT FROM AUTHOR]

Abstract This paper presents a numerical study and the optimization of very short discrete multi-pump Raman amplifiers using Tellurite-based optical fibers. While most studies about discrete Raman amplifiers usually focus on cases where hundreds of meters of fiber are used, here we consider a multi-pumped Raman amplifier setup with extremely short dimensions, in which the length of the gain media was varied from 2.5 to 30 meters. The optimization process was developed over an broad amplification band from 1520 to 1600 nm, considering a maximum acceptable ripple of 3 dB, and using 2, 3 and 4 pumps with individual powers always below 2.5 W. The results show that it is possible to achieve net gains as high as 10 dB for gain media around 20 meters, and close to 15 dB for 30 meters. These high gains highlight the fact that Tellurite-based optical fibers can be used for the construction of very short and compact broadband amplifiers using just a few pump lasers with modest optical powers.

As one of the popular coherent Raman scattering techniques, stimulated Raman scattering (SRS) has made significant progress in recent years, especially in label-free biological imaging. Polarization provides an additional degree of freedom to manipulate the SRS process. In previous studies, only linearly polarized SRS was fully investigated, in which both pump and Stokes laser fields are linearly polarized. Here, we theoretically analyzed the SRS process excited by two circularly polarized laser fields and then experimentally demonstrated it by taking a spherical symmetric CH4 molecule as a model system. The experimental results are in good agreement with the theoretical ones. It is shown that circularly polarized SRS (CP-SRS) has unique characteristics different from linear polarization. When the handedness of circular polarization states of two laser fields is the same, CP-SRS further suppresses the depolarized vibrational band while keeping the polarized band almost unaffected. On the other hand, when the handedness is opposite, CP-SRS enhances the depolarized band while suppressing the polarized band. Therefore, the CP-SRS not only allows us to resolve the symmetry of vibrational modes but also can enhance vibrational contrast based on symmetry selectivity by suppressing or enhancing the signal from a specific vibrational mode. These results will have potential applications in improving chemical selectivity and imaging contrast as well as spectral resolution SRS microscopy. In addition, the CP-SRS has the ability to determine the depolarization ratio ρ and identify the overlapping Raman bands. [ABSTRACT FROM AUTHOR]

Stimulated Raman scattering of second harmonic picosecond pulses (60 ps, 532 nm) of an Nd3+:YAG laser in water when focusing a Bessel beam behind a conical concentrator with the displacement of the beam caustic through the free surface is studied. The generation of two Stokes (650 and 836 nm) and two anti-Stokes (390 and 450 nm) components of stimulated Raman scattering with an axisymmetric ring beam structure in the cross section is achieved. A significant decrease in the spectral bandwidth of stretching OH vibrations of water molecules in the first circular Stokes component of forward stimulated Raman scattering has been detected (to ~70 cm–1 compared to ~400 cm–1 for spontaneous Raman scattering). For the first time, a fourfold increase in the efficiency of converting the pump pulse energy into the first Stokes component of forward stimulated Raman scattering has been achieved using Bessel beams for excitation instead of Gaussian beams. [ABSTRACT FROM AUTHOR]

The Sasa-Satsuma equation is a widely used mathematical model in the fields of nonlinear optics, ultra-short optical pulse propagation, pulse compression, telecommunications, spectroscopy, optical coherence tomography, nonlinear dynamics of optical pulses, self-steeping, self-frequency shifting resulting from stimulated Raman scattering, and higher-order dispersion of light pulses. Balancing the higher order dispersion and self-steeping, we obtain closed-form optical soliton solutions, including kink, periodic soliton, compacton, bell-shaped soliton, and others using the straightforward ( G ′ / G , 1 / G )-expansion approach. This study carries out a thorough investigation of analytical soliton solutions to the time-fractional higher-order Sasa-Satsuma equation, aiming to widely understand these related phenomena, and explain their significance in mathematical context. The presence of fractional derivative, which introduce memory effects and long-range interactions, finding analytical solutions for this equation is particularly challenging. The novelty of the results is supported by comparing them with previous analytical results. Moreover, we study the impact of fractional-order derivative on soliton dynamics through two-dimensional graphs and provide an explanation. [ABSTRACT FROM AUTHOR]

Nanomedicine has emerged as a revolutionary strategy of drug delivery. However, fundamentals of the nano-neuro interaction are elusive. In particular, whether nanocarriers can cross the blood-brain barrier (BBB) and release the drug cargo inside the brain, a basic process depicted in numerous books and reviews, remains controversial. Here, we develop an optical method, based on stimulated Raman scattering, for imaging nanocarriers in tissues. Our method achieves a suite of capabilities--single-particle sensitivity, chemical specificity, and particle counting capability. With this method, we visualize individual intact nanocarriers crossing the BBB of mouse brains and quantify the absolute number by particle counting. The fate of nanocarriers after crossing the BBB shows remarkable heterogeneity across multiple scales. With a mouse model of aging, we find that blood-brain transport of nanocarriers decreases with age substantially. This technology would facilitate development of effective therapeutics for brain diseases and clinical translation of nanocarrier-based treatment in general. [ABSTRACT FROM AUTHOR]

Plastics are now omnipresent in our daily lives. The existence of microplastics (1 μm to 5 mm in length) and possibly even nanoplastics (<1 μm) has recently raised health concerns. In particular, nanoplastics are believed to be more toxic since their smaller size renders them much more amenable, compared to microplastics, to enter the human body. However, detecting nanoplastics imposes tremendous analytical challenges on both the nano-level sensitivity and the plastic-identifying specificity, leading to a knowledge gap in this mysterious nanoworld surrounding us. To address these challenges, we developed a hyperspectral stimulated Raman scattering (SRS) imaging platform with an automated plastic identification algorithm that allows micro-nano plastic analysis at the single-particle level with high chemical specificity and throughput. We first validated the sensitivity enhancement of the narrow band of SRS to enable high-speed single nanoplastic detection below 100 nm. We then devised a data-driven spectral matching algorithm to address spectral identification challenges imposed by sensitive narrow-band hyperspectral imaging and achieve robust determination of common plastic polymers. With the established technique, we studied the micro-nano plastics from bottled water as a model system. We successfully detected and identified nanoplastics from major plastic types. Micro-nano plastics concentrations were estimated to be about 2.4 ± 1.3 × 105 particles per liter of bottled water, about 90% of which are nanoplastics. This is orders of magnitude more than the microplastic abundance reported previously in bottled water. High-throughput single-particle counting revealed extraordinary particle heterogeneity and nonorthogonality between plastic composition and morphologies; the resulting multidimensional profiling sheds light on the science of nanoplastics. [ABSTRACT FROM AUTHOR]

Significance: The molecular mechanisms driving the progression from nonalcoholic fatty liver (NAFL) to fibrosing steatohepatitis (NASH) are insufficiently understood. Techniques enabling the characterization of different lipid species with both chemical and spatial information can provide valuable insights into their contributions to the disease progression. Aim: We extend the utility of stimulated Raman scattering (SRS) microscopy to characterize and quantify lipid species in liver tissue sections from patients with NAFL and NASH. Approach: We applied a dual-band hyperspectral SRS microscopy system for imaging tissue sections in both the C-H stretching and fingerprint regions. The same sections were imaged with polarization microscopy for detecting birefringent liquid crystals in the tissues. Results: Our imaging and analysis pipeline provides accurate classification and quantification of free cholesterol, saturated cholesteryl esters (CEs), unsaturated CE, and triglycerides in liver tissue sections. The subcellular resolution enables investigations of the heterogeneous distribution of saturated CE, which has been under-examined in previous studies. We also discovered that the birefringent crystals, previously found to be associated with NASH development, are predominantly composed of saturated CE. Conclusions: Our method allows for a detailed characterization of lipid composition in human liver tissues and enables further investigation into the potential mechanism of NASH progression. [ABSTRACT FROM AUTHOR]

Numerical model for calculating convective gains and absolute thresholds of stimulated Raman scattering (SRS) in inhomogeneous plasmas is constructed based on the Fourier-space method. The model is valid for arbitrary density profiles and scattering geometries, including both backscattering and side scattering. It is shown that 90 deg side scatter has a lower absolute threshold than other scattering geometries. Backscatter, on the other hand, has a relatively large absolute threshold under conventional direct-drive ignition conditions. For a parabolic density profile, the absolute threshold of backscatter decreases dramatically at the peak of parabola, but is still much larger than that of side scatter. We also discuss the absolute thresholds of side scatter under different density profiles, showing not big differences with the linear density profile as well as the analytic formulas. Convective gains, however, are sensitive to the density profiles and collisional damping. The k-space numerical model is verified via analytic formulas and real-space envelope model, and it offers us new perspective on the scattering angles compared with previous models for SRS. [ABSTRACT FROM AUTHOR]

Due to its particular geometry, stimulated Raman side-scattering (SRSS) drives scattered light emission in non-usually diagnosed directions, leading to scarce and complex experimental observations. Direct-irradiation campaigns at the SG-II Upgrade facility have measured the scattered light driven by SRSS over a wide range of angles. Typical interaction conditions were as follows: an overlapped laser intensity of 1.2 × 10 15 W cm−2 propagated into a plasma with a density scale length L n c / 4 ≈ 250 μm and an electron temperature T e ≈ 2.2 keV. It indicated an emission at large polar angles over a broad azimuthal range, sensitive to the plasma profile, resulting in a loss of about 5% of the total laser energy. Direct comparison with back-scattering measurement, both in the full-aperture back-scattered direction and sampled at smaller polar angles in the same azimuthal plane, has evidenced SRSS as the dominant Raman scattering process. The predominance of SRSS was confirmed by two-dimensional particle-in-cell simulations, and its angular spread has been corroborated by ray-tracing simulations. The main implication is that a complete characterization of the SRS instability and an accurate measurement of the energy losses require the collection of the scattered light in a broad range of directions. Otherwise, spatially limited measurement could lead to an underestimation of the energetic importance of stimulated Raman scattering. [ABSTRACT FROM AUTHOR]

Coherent Raman scattering (CRS) microscopy is an attractive label‐free imaging method providing high chemical sensitivity, sub‐micron spatial resolution, and video‐rate imaging speed. When extended to hyperspectral CRS (HS‐CRS), it is capable of distinguishing molecules even in complex heterogeneous systems by probing multiple Raman resonances. Solid‐state lasers, associated with their high cost, large footprint, and slow tuning speed, currently limit the widespread application of HS‐CRS. Fiber lasers with comparable properties usually suffer from poor noise performance or instabilities during wavelength tuning. A tunable two‐color fiber laser is demonstrated that can be electronically tuned at rates of up to 1 kHz. The use of polarization‐maintaining fibers and an all‐optical synchronization mechanism guarantees its mode‐locking stability. The superior noise performance of this system is evaluated by the side‐by‐side comparison with data obtained by a commercial optical parametric oscillator (OPO)‐based laser. Large‐area multimodal imaging of liver tissue sections surgically resected from a patient suffering from a non‐neoplastic liver parenchyma with micronodular cirrhosis in combination with a multilocular hepatocellular carcinoma is demonstrated. By exploiting the fast‐hyperspectral scanning capability of the laser and multivariate statistical analysis, virtual staining of tissue sections and a comparison of the diagnostic properties of HS‐CRS to the classical histopathological approach are achieved. [ABSTRACT FROM AUTHOR]

Stimulated Raman scattering is an attractive way to extend the operation spectral range of optical sources. However, the spectral extension range of a tunable Raman laser is limited by the Raman frequency shift and pump tuning bandwidth. This makes it challenging to realize chip-scale, widely tunable Raman lasers, as on-chip lasers only provide limited pump power and tuning bandwidth. Here, we tackle this by dispersion engineering of a thin-film lithium niobate microring resonator, where its high-quality factor (~ 2.5 million) ensures a sub-milli-watt (0.8 mW) threshold for Raman lasing while its strong normal dispersion with suppressed avoided mode crossing restrains the competing Kerr comb generation process. Combining the multi-wavelength Raman gain response of lithium niobate and cascaded Raman lasing, we demonstrate a widely tunable Raman laser covering 1592–1955 nm, showing a 335-nm spectral extension range from a 94-nm-tuning-bandwidth pump laser. Our demonstration paves the way to realize chip-scale, widely-tunable Raman lasers. Extending the spectral range of on-chip tunable Raman laser is challenging due to the limited Raman frequency shifts and pump tuning bandwidth. The authors combine the dispersion engineering of thin film lithium niobate with cascaded Raman lasing to realize a widely tunable laser with 335-nm spectral extension and sub-milliwatt threshold. [ABSTRACT FROM AUTHOR]

We demonstrate the generation of multiple lasing wavelength in the L- and U-band from a Brillouin-Raman fiber laser. It was designed in a full-open cavity with a dispersion compensating fiber section as the nonlinear and Raman gain medium. A broadband source originated from the amplified spontaneous emission of an erbium-ytterbium-doped fiber amplifier was employed as the primary Raman pump. The proposed fiber laser system required a threshold power of 400 mW to initiate its first Brillouin Stokes line with 0.165 nm wavelength spacing. A total of 397 Stokes lines within 3-dB flatness of peak power extended from 1609.7 to 1675.0 nm corresponding to 65.3 nm wavelength range were obtained at the pump power of 850 mW. The utilization of broadband Raman pump source has enhanced the spectral bandwidth of multiwavelength generation. This approach is simple and can be employed to other wavelength ranges subject to the availability of the broadband pump source. [ABSTRACT FROM AUTHOR]

The influence of the interference between coherent processes in third-order nonlinear Raman scattering on the spectral shapes of Raman-scattered light waves is numerically modeled and discussed in the cases of commonly used coherent Raman spectroscopy techniques. The effects on the lineshapes depending on the laser intensity are analyzed for the coherent Raman spectroscopy performed via the excitation of molecular systems with focused laser pulses at high intensities. In this case, the interplay between the coherent processes in nonlinear Raman scattering, as well as laser power-induced resonance effects, may be significant and should be taken into account in the spectral lineshape analysis in coherent Raman spectroscopy and its related applications, since the coherent Raman spectra may be considerably modified. [ABSTRACT FROM AUTHOR]

This paper presents a theoretical investigation on stimulated Raman scattering (SRS) of intense Laguerre–Gaussian (LG) laser beams propagating through plasma with axial density ramp. The optical nonlinearity of the plasma has been considered to be originating due the ponderomotive force acting on the plasma electrons due to intensity gradient over the cross section of laser beam. An intense laser beam with frequency ω 0 propagating through plasma gets coupled with a preexisting electron plasma wave (EPW) at frequency ωep and produces a back scattered wave at frequency ω s = ω 0 - ω ep . Using variational theory semi-analytical solution of the set of coupled wave equations for the pump, EPW and scattered wave has been obtained under W.K.B approximation. It has been observed that power of the scattered wave is significantly affected by the self-focusing effect of pump beam. [ABSTRACT FROM AUTHOR]

Optical imaging with photo-controllable probes has greatly advanced biological research. With superb chemical specificity of vibrational spectroscopy, stimulated Raman scattering (SRS) microscopy is particularly promising for super-multiplexed optical imaging with rich chemical information. Functional SRS imaging in response to light has been recently demonstrated, but multiplexed SRS imaging with reversible photocontrol remains unaccomplished. Here, we create a multiplexing palette of photoswitchable polyynes with 16 Raman frequencies by coupling asymmetric diarylethene with super-multiplexed Carbow (Carbow-switch). Through optimization of both electronic and vibrational spectroscopy, Carbow-switch displays excellent photoswitching properties under visible light control and SRS response with large frequency change and signal enhancement. Reversible and spatial-selective multiplexed SRS imaging of different organelles are demonstrated in living cells. We further achieve photo-selective time-lapse imaging of organelle dynamics during oxidative stress and protein phase separation. The development of Carbow-switch for photoswitchable SRS microscopy will open up new avenues to study complex interactions and dynamics in living cells with high spatiotemporal precision and multiplexing capability. Bioimaging with photocontrol and multiplexing capability is vital for studying cellular interactions and dynamics, but multiplexed stimulated Raman scattering (SRS) imaging with reversible photocontrol is elusive. Here, the authors report SRS microscopy with Carbow-switch enabling multiplexed SRS imaging and tracking in live cells with reversible photocontrol and high spatiotemporal selectivity. [ABSTRACT FROM AUTHOR]

In this paper, the influence of pump radiation parameters and laser resonator configurations on the characteristics of high-energy 589 nm KGW Raman lasers is investigated and explained. The best energy efficiency is obtained in lasers with a flat resonator, while the best angular characteristics are obtained in lasers with an unstable resonator. The use of stable spherical resonators results in the worst energy and angular characteristics. The angular divergence in lasers with flat cavities increases with pump intensity because of wing growth, whereas the core width remains unchanged. The structure of the wings is recorded and analyzed. [ABSTRACT FROM AUTHOR]

This paper presents a numerical study and the optimization of very short discrete multi-pump Raman amplifiers using Tellurite-based optical fibers. While most studies about discrete Raman amplifiers usually focus on cases where hundreds of meters of fiber are used, here we consider a multi-pumped Raman amplifier setup with extremely short dimensions, in which the length of the gain media was varied from 2.5 to 30 meters. The optimization process was developed over an broad amplification band from 1520 to 1600 nm, considering a maximum acceptable ripple of 3 dB, and using 2, 3 and 4 pumps with individual powers always below 2.5 W. The results show that it is possible to achieve net gains as high as 10 dB for gain media around 20 meters, and close to 15 dB for 30 meters. These high gains highlight the fact that Tellurite-based optical fibers can be used for the construction of very short and compact broadband amplifiers using just a few pump lasers with modest optical powers. [ABSTRACT FROM AUTHOR]

This study describes the relativistic q-Gaussian laser beam's stimulated Raman scattering (SRS) in an unmagnetized plasma. Moreover, the influence of the pump laser's relativistic self-focusing on the SRS process has been investigated. Using variational theory, we derived analytical solutions to the coupled nonlinear wave equations describing the pump, EPW, and scattered waves. The resulting equations were numerically solved to see the impacts of laser and plasma characteristics on the dynamics of the pump beam and its influence on the power of scattered waves. The power of the scattered wave was observed to be significantly altered via the self-focusing action of the pump beam, where when the effect of self-focus increases, it leads to an increase in the effect of stimulated Raman scattering. The stimulated Raman scattering yield is investigated based on the laser beam's and plasma's intensity. The main finding is that as q increases, the SRS yield increases, and as the intensity of the laser beam and plasma density increase, the SRS yield also increases. The scattering of the self-focused beam takes place at a greater distance than the beam of the pump, due to the relatively diminished level of scattered power. The value of the integrated reflection increases with the increase of q and the growth rate.

ABSTRACTStimulated Raman scattering (SRS) microscopy has gained popularity in recent years due to its linearity to molecule concentration and laser intensity, and to the lack of the nonresonant background that affects its analogous technique, coherent anti-Stokes Raman scattering. However, SRS is not a background-free technique. In fact, there are other optical processes – nonlinear transient scattering and nonlinear transient absorption – that can be detrimental to the contrast and sensitivity of SRS microscopy. In this review, we provide a description of these competing optical processes and present an up-to-date description of current solutions to minimize their effect on SRS measurements.

The photodissociation dynamics of alkyl iodides along the C–I bond are captured by attosecond extreme-ultraviolet (XUV) transient absorption spectroscopy employing resonant ∼20 fs UV pump pulses. The methodology of previous experiments on CH3I [Chang et al., J. Chem. Phys. 154, 234301 (2021)] is extended to the investigation of a C–I bond-breaking reaction in the dissociative A-band of C2H5I, i-C3H7I, and t-C4H9I. Probing iodine 4d core-to-valence transitions in the XUV enables one to map wave packet bifurcation at a conical intersection in the A-band as well as coherent vibrations in the ground state of the parent molecules. Analysis of spectroscopic bifurcation signatures yields conical intersection crossing times of 15 ± 4 fs for CH3I, 14 ± 5 fs for C2H5I, and 24 ± 4 fs for i-C3H7I and t-C4H9I, respectively. Observations of coherent vibrations, resulting from a projection of A-band structural dynamics onto the ground state by resonant impulsive stimulated Raman scattering, indirectly reveal multimode C–I stretch and CCI bend vibrations in the A-bands of C2H5I, i-C3H7I, and t-C4H9I. [ABSTRACT FROM AUTHOR]

Lipid metabolism plays crucial roles during aging processes, but how it is regulated by diets and how it interplays with aging still remain unclear. We proposed a new optical imaging platform by integrating heavy water (D2 O) probing with stimulated Raman scattering (DO-SRS) microscopy, for the first time, to directly visualize and quantify lipid metabolism regulated by different diets and insulin signaling pathway in Drosophila fat body during aging. We found that calorie restriction, low protein diet, and (moderately) high protein and high sucrose diets enhanced lipid turnover in flies at all ages, while (moderately) high fructose and glucose diets only promoted lipid turnover in aged flies. The measured lipid turnover enhancements under diverse diets were due to different mechanisms. High protein diet shortened the lifespan while all other diets extended the lifespan. Downregulating the insulin signaling pathway enhanced lipid turnover, which is likely related to lifespan increase, while upregulating insulin signaling pathway decreased lipid turnover that would shorten the lifespan. Our study offers the first approach to directly visualize spatiotemporal alterations of lipid turnover in aging Drosophila in situ, for a better understanding of the interconnections between lipid metabolism, diets, and aging.

The influence of the interference between coherent processes in third-order nonlinear Raman scattering on the spectral shapes of Raman-scattered light waves is numerically modeled and discussed in the cases of commonly used coherent Raman spectroscopy techniques. The effects on the lineshapes depending on the laser intensity are analyzed for the coherent Raman spectroscopy performed via the excitation of molecular systems with focused laser pulses at high intensities. In this case, the interplay between the coherent processes in nonlinear Raman scattering, as well as laser power-induced resonance effects, may be significant and should be taken into account in the spectral lineshape analysis in coherent Raman spectroscopy and its related applications, since the coherent Raman spectra may be considerably modified.

In this paper, the influence of pump radiation parameters and laser resonator configurations on the characteristics of high-energy 589 nm KGW Raman lasers is investigated and explained. The best energy efficiency is obtained in lasers with a flat resonator, while the best angular characteristics are obtained in lasers with an unstable resonator. The use of stable spherical resonators results in the worst energy and angular characteristics. The angular divergence in lasers with flat cavities increases with pump intensity because of wing growth, whereas the core width remains unchanged. The structure of the wings is recorded and analyzed.

For this study, we employed intense 400 nm, 100 fs pulses linearly propagated through a 50 cm water medium, initially self-stretching the excitation pulses to 2.50 ps. Subsequently, the self-stretched 2.50 ps pulses were focused into deionized water, and we conducted transient absorption experiments to measure and investigate the dynamics of hydrated electrons in water. The excess electrons generated were injected into the hydrogen bond network of the water cluster, leading to the observation of saturated hydrated electrons. Additionally, we observed the emergence of the forward stimulated Raman scattering (SRS) of water molecules. We report the experimental observation of a weak forward SRS emission at 463 nm (corresponding to 3400 cm−1), indicative of the ordinary OH stretching vibration in the liquid phase. Moreover, we observed an intense forward SRS emission at 460 nm in water, corresponding to two anomalous Raman shifts at 3260 cm−1 and 3355 cm−1. These anomalous Raman shifts resulted from changes in the hydrogen bond network structure. We determine that the formation of not fully hydrated and saturated hydrated electrons plays a crucial role in producing this phenomenon.

The symmetric and anti-symmetric stretching vibrations of C–H extensively exist in organic molecules, which constantly arise together in Raman spectroscopy. In this study, a method was presented to switch stimulated Raman scattering peak from symmetric vibrations (2870 cm−1) to anti-symmetric vibrations (2924 cm−1) of –CH2 by regulating the hydrogen bonding (HB) associated through intermolecular and intramolecular in diethylene glycol (DEG) molecules. Such dominant association structure can be converted from DEG-DEG to DEG-H2O in the aqueous DEG solutions. The interaction between H2O and DEG was investigated through the density functional theory calculation. The changes in intermolecular HB have effects on the intramolecular vibrational modes by the intermolecular forces and symmetry of the DEG molecule. This study has exciting potential prospect and can be extended to other mixing solutions. [ABSTRACT FROM AUTHOR]

Multiplex optical detection in live cells is challenging due to overlapping signals and poor signal‐to‐noise associated with some chemical reporters. To address this, the application of spectral phasor analysis to stimulated Raman scattering (SRS) microscopy for unmixing three bioorthogonal Raman probes within cells is reported. Triplex detection of a metallacarborane using the B−H stretch at 2480–2650 cm−1, together with a bis‐alkyne and deuterated fatty acid can be achieved within the cell‐silent region of the Raman spectrum. When coupled to imaging in the high‐wavenumber region of the cellular Raman spectrum, nine discrete regions of interest can be spectrally unmixed from the hyperspectral SRS dataset, demonstrating a new capability in the toolkit of multiplexed Raman imaging of live cells. [ABSTRACT FROM AUTHOR]

In the present study, we propose a scheme for generating multi-mode resonance-enhanced stimulated Raman scattering (SRS) of H2O in a low concentration (6.5 mol/L) sulfuric acid aqueous solution. The SRS of H2O exhibits a prominent vibrational feature peak at 3371 cm−1 and a secondary peak at 3325 cm−1. The closeness of the vibrational frequencies for the H–O stretching modes in different water structures allows for resonance interaction. The enhanced vibrational mode can serve as a "new starting point" for a cascaded resonance process, resulting in the generation of eight SRS Stokes signals with a normal distribution centered on the characteristic Raman peak at 3371 cm−1. This research holds potential implications for the development of multi-wavelength and significant frequency shift Raman lasers. [ABSTRACT FROM AUTHOR]

LD end-pumped passively Q-switched Nd:YLF/SrWO4/Cr4+:YAG Raman laser for multi-Raman-modes is investigated for the first time. Based on the main Raman mode (923 cm−1), the maximum average output power of 0.462 W is achieved for 1st Stokes laser at 1159 nm. When the pumping power is 2 W, the maximum optical conversion efficiency of 17.4% is obtained with the pulse repetition frequency of 6.6 kHz and pulse width of 21 ns. By selecting an appropriate cavity mirror to suppress stimulated Raman scattering process of main Raman mode, SRS conversion of the minor mode (334.5 cm−1) of SrWO4 crystal is realized separately for the first time in intracavity Raman laser. The maximum output power at 1085 nm obtained is 0.111 W. In experiments, multi-pulse phenomena of Stokes laser output with the main Raman mode (923 cm−1) are observed, which are more obvious for smaller initial transmittance of saturable absorber and higher reflectivity of output coupler. [ABSTRACT FROM AUTHOR]

We report an experimental scheme for stimulated Raman scattering (SRS) microscopy with excitation in the visible spectral region. This allows electronically preresonant (epr) SRS microscopy of a broad range of chromophores with sensitivities as low as 1 μM. Our experiment is based on two synchronously near-infrared pumped optical parametric oscillators (OPO). One of the outputs is modulated at a fourth of the repetition rate with a novel broadband electro-optical modulator. Using a combination of spectral focusing and tuning of the OPO, we show the recording of epr-SRS spectra over the whole range of molecular vibrations at a speed up to 20 times faster than classical wavelength tuning. The imaging capabilities of this setup are demonstrated with material scientific and cellular samples. [ABSTRACT FROM AUTHOR]

We examine the impact of the hot drifting electron on stimulated Raman backscattering, which is coupled to decay instability, in a magnetized plasma. Through parametric coupling, this produces a plasma wave that moves forward and an electromagnetic wave that shifts downward. The plasma wave produced by stimulated Raman scattering (SRS) in this process decays into an ion-acoustic wave and a secondary, longer-wavelength Langmuir wave traveling opposite to the ion-acoustic wave. This energy diversion and attenuation of the primary Langmuir wave by drifting electrons limit the amplitude of SRS. In the presence of drifting electrons, the SRS is suppressed significantly and the plasma wave is attenuated resonantly at a higher rate. [ABSTRACT FROM AUTHOR]

Stimulated Raman scattering offers an alternative strategy to explore continuous‐wave (c.w.) organic lasers, which, however, still suffers from the limitation of inadequate Raman gain in organic material systems. Here we propose a metal‐linking approach to enhance the Raman gain of organic molecules. Self‐assembled microcrystals of the metal linked organic dimers exhibit large Raman gain, therefore allowing for c.w. Raman lasing. Furthermore, broadband tunable Raman lasing is achieved in the organic dimer microcrystals by adjusting excitation wavelengths. This work advances the understanding of Raman gain in organic molecules, paving a way for the design of c.w. organic lasers. [ABSTRACT FROM AUTHOR]

We previously developed a hollow-core photonic crystal fiber (HCPCF) based Raman scattering enhancement technique for gas/human breath analysis. It enhances photon–gas molecule interactions significantly but is still based on CW laser excitation spontaneous Raman scattering, which is a low-probability phenomenon. In this work, we explored nanosecond/sub-nanosecond pulsed laser excitation in HCPCF based fiber enhanced Raman spectroscopy (FERS) and successfully induced stimulated Raman scattering (SRS) enhancement. Raman measurements of simple and complex gases were performed using the new system to assess its feasibility for gas analysis. We studied the gas Raman scattering characteristics, the relationship between Raman intensities and pump energies, and the energy threshold for the transition from spontaneous Raman scattering to SRS. H2, CO2, and propene (C3H6) were used as test gases. Our results demonstrated that a single-beam pulsed pump combined with FERS provides an effective Raman enhancement technique for gas analysis. Furthermore, an energy threshold for SRS initiation was experimentally observed. The SRS-capable FERS system, utilizing a single-beam pulsed pump, shows great potential for analyzing complex gases such as propene, which is a volatile organic compound (VOC) gas, serving as a biomarker in human breath for lung cancer and other human diseases. This work contributes to the advancement of gas analysis and opens alternative avenues for exploring novel Raman enhancement techniques. [ABSTRACT FROM AUTHOR]

We address the role of the delayed Kerr nonlinearity associated with stimulated rotational Raman scattering on the propagation of intense ultrashort two-color filaments with elliptical polarization in gases and examine its impact on the generation of optical frequencies as well as terahertz frequencies. We find that in air the nonlinearity associated with stimulated Raman scattering strongly impacts the dynamics of the laser filaments and modifies the overall pulse spectral content. In particular, it alters the THz spectra upon propagation in the filamentation regime. Differences between linearly and circularly polarized two-color pump pulses are discussed. [ABSTRACT FROM AUTHOR]

Ultrafast laser pulses interacting with plasmas can give rise to a rich spectrum of physical phenomena, which have been extensively studied both theoretically and experimentally. Less work has been devoted to the study of polarized plasmas, where the electron spin may play an important role. In this short review, we illustrate the use of phase-space methods to model and simulate spin-polarized plasmas. This approach is based on the Wigner representation of quantum mechanics, and its classical counterpart, the Vlasov equation, which are generalized to include the spin degrees of freedom. Our approach is illustrated through the study of the stimulated Raman scattering of a circularly polarized electromagnetic wave interacting with a dense electron plasma. [ABSTRACT FROM AUTHOR]

The article focuses on photon upconversion (UC) in a quasi-2D perovskite material, (PEA)2PbI4, demonstrating an exceptional anti-Stokes shift of up to 220 meV, the highest reported for phonon-assisted UC. The study reveals that this significant energy gain results from strong lattice fluctuations in the soft organic-inorganic hybrid lattice, which leads to subgap photon absorption and radiative recombination of electron-hole pairs, shedding light on the UC mechanisms in perovskite materials.

A series of 2D in-plane plane wave particle-in-cell simulations find distinctive paths of laser-plasma instability evolution in OMEGA-scale implosions, depending on the initial electron temperature. At low temperatures, two-plasmon decay (TPD) dominates in both initial growth and the steady state. At high temperatures, the initial dominant modes switch to stimulated Raman scattering, but TPD still dominates a steady state characterized by cavitation and Langmuir turbulence. A hot electron scaling is also obtained from the simulations that, when combined with laser/plasma conditions from hydro simulations, can predict hot electron generation in implosions that do not employ smoothing-by-spectral-dispersion (SSD). It also shows that under the same laser/plasma conditions, SSD can reduce hot electron generation. [ABSTRACT FROM AUTHOR]

Information on the penetration depth, pathways, metabolization, storage of vehicles, active pharmaceutical ingredients (APIs), and functional cosmetic ingredients (FCIs) of topically applied formulations or contaminants (substances) in skin is of great importance for understanding their interaction with skin targets, treatment efficacy, and risk assessment—a challenging task in dermatology, cosmetology, and pharmacy. Non-invasive methods for the qualitative and quantitative visualization of substances in skin in vivo are favored and limited to optical imaging and spectroscopic methods such as fluorescence/reflectance confocal laser scanning microscopy (CLSM); two-photon tomography (2PT) combined with autofluorescence (2PT-AF), fluorescence lifetime imaging (2PT-FLIM), second-harmonic generation (SHG), coherent anti-Stokes Raman scattering (CARS), and reflectance confocal microscopy (2PT-RCM); three-photon tomography (3PT); confocal Raman micro-spectroscopy (CRM); surface-enhanced Raman scattering (SERS) micro-spectroscopy; stimulated Raman scattering (SRS) microscopy; and optical coherence tomography (OCT). This review summarizes the state of the art in the use of the CLSM, 2PT, 3PT, CRM, SERS, SRS, and OCT optical methods to study skin penetration in vivo non-invasively (302 references). The advantages, limitations, possibilities, and prospects of the reviewed optical methods are comprehensively discussed. The ex vivo studies discussed are potentially translatable into in vivo measurements. The requirements for the optical properties of substances to determine their penetration into skin by certain methods are highlighted. [ABSTRACT FROM AUTHOR]