Advanced vibrational microscopy for clinical translation
OA Version
Citation
Abstract
The label-free chemical imaging capability of vibrational microscopy overcomes the limitations of fluorescence microscopy, which arise from the use of exogenous fluorescent dyes. Advanced vibrational microscopy techniques, including mid-infrared photothermal and coherent Raman scattering, have found broad applications in life sciences and demonstrated great potential for clinical applications. However, clinical translation of vibrational microscopy faces two remaining challenges: the lack of a universally-available, clinical-compatible imaging systems and the challenge of limited imaging depth. My dissertation made three advances in instrumentation to address these challenges. In the first advance, we developed a clinically-compatible stimulated Raman microscope with a rapid widely-tunable fiber laser. By implementing auto-balanced detection, we improved the imaging signal-to-noise ratio by 23 times and achieved high-quality multi-window chemical imaging. The second advance provided biomarker information in stimulated Raman histology. Utilizing the rich chemical information in the hyperspectral stimulated Raman imaging, we demonstrated high-content mapping of tissue components in human breast cancer sections. With a spectral selective-sampling method, we improved the data acquisition speed by 9 times. The last advance is to overcome the challenge of limited imaging depth. We invented the short-wave infrared photothermal microscopy (SWIP) to push vibrational imaging depth to millimeter scale for in-vivo measurements. By pumping the overtone transition of carbon–hydrogen bonds and probing the subsequent photothermal lens with shortwave infrared light, SWIP obtained chemical contrast from 1 μm polymer particles located at 800 μm depth in a highly scattering phantom. We further demonstrated that SWIP resolves intracellular lipids across an intact tumor spheroid and the layered structure in thick liver, skin, brain and breast tissues.
Together, my dissertation advances the clinical translation of vibrational microscopy by developing a clinical-compatible system, providing biomarker information, and pushing vibrational imaging depth to millimeter scale. We expect these advances to open new possibilities for a broad range of biomedical applications.
Description
2025
License
Attribution-NonCommercial-NoDerivatives 4.0 International