Spatial light-modulated stimulated Raman scattering (SLM-SRS) microscopy for rapid multiplexed vibrational imaging

Bae, Kideog; Zheng, Wei; Huang, Zhiwei

doi:10.7150/thno.38551

Cited by 21 publications

(13 citation statements)

References 24 publications

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“…However, low measurement times can only be reached for small (scanning) areas. Therefore, they are not competitive with established scanning methods, that are suitable to analyse whole tissue sections with a pathological assessment in efficient time 18 – 20 .…”

Section: Introductionmentioning

confidence: 99%

Rapid brain structure and tumour margin detection on whole frozen tissue sections by fast multiphotometric mid-infrared scanning

Kümmel

Marwick

Rittel

et al. 2021

Sci Rep

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Frozen section analysis is a frequently used method for examination of tissue samples, especially for tumour detection. In the majority of cases, the aim is to identify characteristic tissue morphologies or tumour margins. Depending on the type of tissue, a high number of misdiagnoses are associated with this process. In this work, a fast spectroscopic measurement device and workflow was developed that significantly improves the speed of whole frozen tissue section analyses and provides sufficient information to visualize tissue structures and tumour margins, dependent on their lipid and protein molecular vibrations. That optical and non-destructive method is based on selected wavenumbers in the mid-infrared (MIR) range. We present a measuring system that substantially outperforms a commercially available Fourier Transform Infrared (FT-IR) Imaging system, since it enables acquisition of reduced spectral information at a scan field of 1 cm2 in 3 s, with a spatial resolution of 20 µm. This allows fast visualization of segmented structure areas with little computational effort. For the first time, this multiphotometric MIR system is applied to biomedical tissue sections. We are referencing our novel MIR scanner on cryopreserved murine sagittal and coronal brain sections, especially focusing on the hippocampus, and show its usability for rapid identification of primary hepatocellular carcinoma (HCC) in mouse liver.

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Section: Introductionmentioning

confidence: 99%

Rapid brain structure and tumour margin detection on whole frozen tissue sections by fast multiphotometric mid-infrared scanning

Kümmel

Marwick

Rittel

et al. 2021

Sci Rep

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“…Another example was presented using an optimal mask pattern generated by SLM to select the significant wavenumbers in the Raman spectrum with a relatively high peak power and SNR. [ 39 ] Additionally, if the spectral composition is known in advance, focusing on the wavenumbers in the corresponding Raman peaks can be a shortcut. Examples also include real‐time two‐peak imaging achieved by dual‐phase SRS microscopy [ 40 ] and three‐peak imaging achieved by AOTF SRS microscopy.…”

Section: Technique and Methods Developmentmentioning

confidence: 99%

Review of Stimulated Raman Scattering Microscopy Techniques and Applications in the Biosciences

Shen

et al. 2020

Advanced Biology

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elastically scattered photons) featuring time-consuming spectral integration and hence a poor acquisition speed (several seconds per line or minutes per frame). This weakness constitutes a large obstacle for real-time monitoring of dynamic events in organisms. Recently, several variations of Raman spectroscopy have been developed to enhance the sensitivity of Raman spectroscopy and dynamic processes of biological samples, including coherent Raman scattering (CRS) spectroscopy and surfaceenhanced Raman spectroscopy (SERS). SERS involves a plasmonic effect where molecules absorbed on a rough metal surface can result in high Raman scattering intensities by increasing the incident electric field. [5] For SERS technology, a SERS substrate must be introduced to enhance the detection sensitivity, and the properties of the substrate (the composition, size, shape and aggregation degree of nanoparticles) affect the shape of the SERS spectra. In addition, only gold, silver, copper, and a few rare alkali metals (such as lithium and sodium) have strong SERS effects, and it is necessary to effectively solve the biocompatibility and safety issues in the preparation of nanomaterials. With the development of laser and nonlinear optics, CRS microscopy has also been demonstrated to break the speed limit for vibrational imaging. [6] CRS has two major forms: coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS); [7] both techniques can dramatically increase the Raman signal by a few orders of magnitude and hence are able to achieve video-rate molecular imaging in vivo. [8,9] CARS and SRS processes often exist in a sample concurrently because of the same excitation conditions (spatiotemporal overlap of the pump and Stokes beam) with a frequency difference (Raman shift) matching the molecular vibrational frequency. However, CARS is an optical parametric process accompanied by a nonresonant part originating from fourwave mixing processes. This intrinsic nonresonant background results in a deviation or even distortion of the Raman spectrum. SRS is a direct process of photon-vibration energy transfer: in brief, the interaction between the electron cloud of a sample and the photons of two lasers creates an induced dipole moment within the molecule based on its polarizability, resulting in a pump energy loss (stimulated Raman loss, SRL) and a Stokes energy increase (stimulated Raman gain, SRG). The Raman signal can, therefore, be deduced from SRL or SRG, resulting in a high-fidelity Raman spectrum free from the nonresonant background. Moreover, the SRS signal exhibits Stimulated Raman scattering (SRS) microscopy is a nonlinear optical imaging method for visualizing chemical content based on molecular vibrational bonds. Featuring high speed, high resolution, high sensitivity, high accuracy, and 3D sectioning, SRS microscopy has made tremendous progress toward biochemical information acquisition, cellular function investigation, and label-free medical diagnosis in the biosciences. In this review, the principle of ...

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“…Rapid scanning of the delay is possible through various means, for instance with the aid of acousto-optic filters, producing spectral scans in as little as 12.5 μs per pixel. 82 Other approaches use spectral modulation techniques, whereby the spectrum is amplitude modulated by a spatial light modulator, 83 digital micromirror device, 84 or AOTF, 85 and the spectrum is retrieved computationally from a sequence of CRS measurements obtained for different realizations of the spectral content of the input beams. A similar concept can also be applied when a single-broadband beam is employed to drive the CRS process, using amplitude and phase shaping to achieve the desired resolution.…”

Section: Speedmentioning

confidence: 99%

Coherent Raman scattering microscopy: capable solution in search of a larger audience

Prince

Potma

2021

J. Biomed. Opt.

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Significance: Coherent Raman scattering (CRS) microscopy is an optical imaging technique with capabilities that could benefit a broad range of biomedical research studies.Aim: We reflect on the birth, rapid rise, and inescapable growing pains of the technique and look back on nearly four decades of developments to examine where the CRS imaging approach might be headed in the next decade to come.Approach: We provide a brief historical account of CRS microscopy, followed by a discussion of the challenges to disseminate the technique to a larger audience. We then highlight recent progress in expanding the capabilities of the CRS microscope and assess its current appeal as a practical imaging tool.Results: New developments in Raman tagging have improved the specificity and sensitivity of the CRS technique. In addition, technical advances have led to CRS microscopes that can capture hyperspectral data cubes at practical acquisition times. These improvements have broadened the application space of the technique. Conclusion:The technical performance of the CRS microscope has improved dramatically since its inception, but these advances have not yet translated into a substantial user base beyond a strong core of enthusiasts. Nonetheless, new developments are poised to move the unique capabilities of the technique into the hands of more users.

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Spatial light-modulated stimulated Raman scattering (SLM-SRS) microscopy for rapid multiplexed vibrational imaging

Cited by 21 publications

References 24 publications

Rapid brain structure and tumour margin detection on whole frozen tissue sections by fast multiphotometric mid-infrared scanning

Rapid brain structure and tumour margin detection on whole frozen tissue sections by fast multiphotometric mid-infrared scanning

Review of Stimulated Raman Scattering Microscopy Techniques and Applications in the Biosciences

Coherent Raman scattering microscopy: capable solution in search of a larger audience

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