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Fe(III)-oxalate complexes are ubiquitous in atmospheric environments, which can release reactive oxygen species (ROS) such as H

Aerosol microdroplets as microreactors for many important atmospheric reactions are ubiquitous in the atmosphere. pH largely regulates the chemical processes within them; however, how pH and chemical species spatially distribute within an atmospheric microdroplet is still under intense debate. The challenge is to measure pH distribution within a tiny volume without affecting the chemical species distribution. We demonstrate a method based on stimulated Raman scattering microscopy to visualize the three-dimensional pH distribution inside single microdroplets of varying sizes. We find that the surface of all microdroplets is more acidic, and a monotonic trend of pH decreasing is observed in the 2.9-μm aerosol microdroplet from center to edge, which is well supported by molecular dynamics simulation. However, bigger cloud microdroplet differs from small aerosol for pH distribution. This size-dependent pH distribution in microdroplets can be related to the surface-to-volume ratio. This work presents noncontact measurement and chemical imaging of pH distribution in microdroplets, filling the gap in our understanding of spatial pH in atmospheric aerosol.

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Focal therapy (FT) has been proposed as an approach to eradicate clinically significant prostate cancer while preserving the normal surrounding tissues to minimize treatment-related toxicity. Rapid histology of core needle biopsies is essential to ensure the precise FT for localized lesions and to determine tumor grades. However, it is difficult to achieve both high accuracy and speed with currently available histopathology methods. Here, we demonstrated that stimulated Raman scattering (SRS) microscopy could reveal the largely heterogeneous histologic features of fresh prostatic biopsy tissues in a label-free and near real-time manner. A diagnostic convolutional neural network (CNN) built based on images from 61 patients could classify Gleason patterns of prostate cancer with an accuracy of 85.7%. An additional 22 independent cases introduced as external test dataset validated the CNN performance with 84.4% accuracy. Gleason scores of core needle biopsies from 21 cases were calculated using the deep learning SRS system and showed a 71% diagnostic consistency with grading from three pathologists. This study demonstrates the potential of a deep learning–assisted SRS platform in evaluating the tumor grade of prostate cancer, which could help simplify the diagnostic workflow and provide timely histopathology compatible with FT treatment.Significance:A platform combining stimulated Raman scattering microscopy and a convolutional neural network provides rapid histopathology and automated Gleason scoring on fresh prostate core needle biopsies without complex tissue processing.

Focal therapy (FT) has been proposed as an approach to eradicate clinically significant prostate cancer while preserving the normal surrounding tissues to minimize treatment-related toxicity. Rapid histology of core needle biopsies is essential to ensure the precise FT for localized lesions and to determine tumor grades. However, it is difficult to achieve both high accuracy and speed with currently available histopathology methods. Here, we demonstrated that stimulated Raman scattering (SRS) microscopy could reveal the largely heterogeneous histologic features of fresh prostatic biopsy tissues in a label-free and near real-time manner. A diagnostic convolutional neural network (CNN) built based on images from 61 patients could classify Gleason patterns of prostate cancer with an accuracy of 85.7%. An additional 22 independent cases introduced as external test dataset validated the CNN performance with 84.4% accuracy. Gleason scores of core needle biopsies from 21 cases were calculated using the deep learning SRS system and showed a 71% diagnostic consistency with grading from three pathologists. This study demonstrates the potential of a deep learning–assisted SRS platform in evaluating the tumor grade of prostate cancer, which could help simplify the diagnostic workflow and provide timely histopathology compatible with FT treatment.Significance:A platform combining stimulated Raman scattering microscopy and a convolutional neural network provides rapid histopathology and automated Gleason scoring on fresh prostate core needle biopsies without complex tissue processing.

People of all ages consume salt every day, but is it really just salt? Plastic nanoparticles (nanoplastics) polluting the oceans and the atmosphere are posing an increasing environmental threat and have begun to contaminate everyday salt in consumer goods. Herein, we developed a combined Surface Enhanced Raman Scattering (SERS) and Stimulated Raman Scattering (SRS) approach that can simultaneously realize the filtration, enrichment, and detection of nanoplastics in commercial salt. SERS was used to explore the potential types of nanoplastic contaminants in salts. SRS was used to conduct imaging and to quantify the presence of nanoplastics. Nanoplastics in sea salts produced from different sources were studied, with the following nanoplastics detected: polystyrene (PS), polyethylene (PE), polypropylene (PP). We estimate that, depending on location, an average person could be ingesting as many as 63,100 nanoplastics per year through the consumption of sea salt alone. Nanoplastics can readily adsorb organic matter and heavy metal particles, so the potential harm to human health should not be underestimated.

We report the generation of parabolic pulses with broadband spectrum from a core-pumped Yb-doped fiber amplifier seeded by a dispersion managed fiber oscillator. The net cavity dispersion of Yb-doped oscillator was continuously changed from 0.074 to -0.170 ps2, which enabled us to achieve dissipative soliton, stretched pulse and soliton mode-locking operations. Spectral evolution processes in the core-pumped nonlinear fiber amplifier seeded by various input solitons were investigated experimentally and theoretically. Our finding indicates that cavity dispersion of oscillator can be used to engineer the input pulse parameter for amplifier, thus forming a pre-chirper free fiber amplification structure. In the experiment, we obtained 410-mW parabolic pulses with spectral bandwidth up to 56 nm. In combination with a passively synchronized frequency-doubled Er-doped fiber laser, we have demonstrated coherent anti-Stokes Raman imaging. The compact dual-color fiber laser source may facilitate practical applications of nonlinear biomedical imaging beyond the laboratory environment.

Gastroscopic biopsy provides the only effective way for gastric cancer diagnosis, but the gold standard histopathology is time-consuming and incompatible with gastroscopy. Conventional stimulated Raman scattering (SRS) microscopy has shown promise in label-free diagnosis on human tissues, yet it requires the tuning of picosecond lasers to achieve chemical specificity at the cost of time and complexity. Here, we demonstrated single-shot femtosecond SRS (femto-SRS) could reach the maximum speed and sensitivity with preserved chemical resolution by integrating with U-Net. Fresh gastroscopic biopsy was imaged in < 60 seconds, revealing essential histoarchitectural hallmarks perfectly agreed with standard histopathology. Moreover, a diagnostic neural network (CNN) was constructed based on images from 279 patients that predicts gastric cancer with accuracy > 96%. We further demonstrated semantic segmentation of intratumor heterogeneity and evaluation of resection margins of endoscopic submucosal dissection (ESD) tissues to simulate rapid and automated intraoperative diagnosis. Our method holds potential for synchronizing gastroscopy and histopathological diagnosis.

Coherent anti-Stokes Raman scattering (CARS) can be used to excite vibrational bonds with chemical selectivity, high spatial and spectral resolution, and high sensitivity, which has many applications in biomedical research. The common way to realize CARS imaging is illuminating sample with two synchronized ultra-short pulses. Recent development of various fiber laser schemes based on nonlinear optical effect provides compact laser source for CARS imaging. However, the nonlinear conversion in optical fiber may inevitably introduce temporal or spectral noise to the newly generated pulses. In this paper, we have proposed a polarization-maintaining (PM) passive-synchronized picosecond fiber laser system that generates dual-color picosecond pulses for CARS. An Er-doped fiber laser and a Yb-doped fiber laser were passively synchronized by cross phase modulation based on master-slave injection scheme. In the experiment, the wavelength of one branch was fixed at 791 nm, which was generated by second harmonic generation of Er-doped fiber laser. The wavelength of the other branch can be continuously tuned from 1017-1047 nm, which was obtained by adding an active spectral broadening module and an optical bandpass filter after Yb-doped fiber laser. As a result, the laser source allows to probe vibrational bonds with frequencies difference between 2809 cm-1 and 3091 cm-1 . Finally, the achieved tunable synchronized pulses enabled us to microscopically image mouse ear samples. The compact optical fiber laser proposed with PM fiber design, stable synchronization and large wavelength tunability would become a promising laser source for CARS imaging in clinical use.

Photochromic probes with reversible fluorescence have revolutionized the fields of single molecule spectroscopy and super-resolution microscopy, but lack sufficient chemical specificity. In contrast, Raman probes with stimulated Raman scattering (SRS) microscopy provides superb chemical resolution for super-multiplexed imaging, but are relatively inert. Here we report vibrational photochromism by engineering alkyne tagged diarylethene to realize photo-switchable SRS imaging. The narrow Raman peak of the alkyne group shifts reversibly upon photoisomerization of the conjugated diarylethene when irradiated by ultraviolet (UV) or visible light, yielding “on” or “off” SRS images taken at the photoactive Raman frequency. We demonstrated photo-rewritable patterning and encryption on thin films, painting/erasing of cells with labelled alkyne-diarylethene, as well as pulse-chase experiments of mitochondria diffusion in living cells. The design principle provides potentials for super-resolution microscopy, optical memories and switches with vibrational specificity., Probes with reversible fluorescence are useful in super-resolution microscopy, but lack sufficient chemical specificity. Here, the authors engineer alkyne tagged diarylethene to realize photo-switchable stimulated Raman scattering probes with high chemical resolution, for applications in living cells.

Gout is a common metabolic disease with growing burden, caused by monosodium urate (MSU) microcrystal deposition. In situ and chemical-specific histological identification of MSU is crucial in the diagnosis and management of gout, yet it remains inaccessible for current histological methods. Methods: Stimulated Raman scattering (SRS) microscopy was utilized to image MSU based on its fingerprint Raman spectra. We first tested SRS for the diagnosis capability of gout and the differentiation power from pseudogout with rat models of acute gout arthritis, calcium pyrophosphate deposition disease (CPDD) and comorbidity. Then, human synovial fluid and surgical specimens (n=120) were were imaged with SRS to obtain the histopathology of MSU and collagen fibers. Finally, quantitative SRS analysis was performed in gout tissue of different physiological phases (n=120) to correlate with traditional histopathology including H&E and immunohistochemistry staining. Results: We demonstrated that SRS is capable of early diagnosis of gout, rapid detection of MSU in synovial fluid and fresh unprocessed surgical tissues, and accurate differentiation of gout from pseudogout in various pathophysiological conditions. Furthermore, quantitative SRS analysis revealed the optical characteristics of MSU deposition at different pathophysiological stages, which were found to matched well with corresponding immunofluorescence histochemistry features. Conclusion: Our work demonstrated the potential of SRS microscopy for rapid intraoperative diagnosis of gout and may facilitate future fundamental researches of MSU-based diseases.

We have proposed and implemented a polarization-maintaining passively synchronized fiber laser system, which could deliver tunable dual-color picosecond pulses by including a frequency-doubling module and a spectral broadening module. Specifically, the output from the involved Er-doped fiber laser were used to generate second-harmonic pulses at 790 nm with a quadratic nonlinear crystal. In parallel, the amplified pulses from the synchronized Yb-doped fiber laser were launched into a 150-m single mode fiber, which resulted in not only substantial spectral bandwidth broadening from 0.1 to 20.1 nm, but also a significant Raman-induced signal around 1080 nm. Consequently, narrow spectra from 1018-1051 nm and 1070-1095 nm could be continuously tuned via a tunable bandpass filter, corresponding to Raman bonds from 2835-3143 cm−1 and 3312-3525 cm−1. Finally, the achieved tunable synchronized pulses enabled us to microscopically examine mouse ear samples based on coherent anti-Stokes Raman and second harmonic generation imaging. Therefore, our tunable passively-synchronized fiber laser system would be promising to provide a simple and compact laser source for subsequent coherent Raman microscopy.

Polarization-maintaining passively synchronized ytterbium and erbium fiber lasers were demonstrated to deliver tunable pulses of 1016-1048 nm and frequency doubled pulses at 790 nm, which were used in coherent anti-Stokes Raman imaging.

We have demonstrated a compact fiber laser with broad and fast wavelength tunability for coherent anti-Stokes Raman scattering (CARS) microscopy. Originated from an Er-doped fiber laser, the Stokes pulses can be tuned from 1015 to 1060 nm within 300 μs from supercontinuum of a tapered high nonlinear fiber, while pump pulses at 790 nm were obtained by second harmonic generation. The two beams were then sent to microscopes for CARS detection of oil, ethanol and mouse ear samples. This fast and broadly tunable fiber laser in the all-polarization-maintaining architecture would be promising to implement rapid label-free histology in clinical translation.