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ECE PhD Thesis Defense: Xiaowei Ge

Title: High Sensitivity Stimulated Raman Microscopy for Metabolism Mapping

Presenter: Xiaowei Ge

Advisor: Professor Ji-Xin Cheng

Chair: TBA

Committee: Professor Anna K Swan, Professor Jerome C Mertz, Professor Lei Tian.

Google Scholar Link: https://scholar.google.com/citations?user=Mr_9AhcAAAAJ&hl=en

Abstract: Vibrational spectroscopic imaging, leveraging the intrinsic vibrational contrast of chemical bonds, has proven to be a powerful analytical tool for characterizing biological samples. Among these, Raman scattering uniquely encodes chemical bond information through wavelength and molecular concentration through intensity. Stimulated Raman scattering (SRS), by amplifying spontaneous Raman processes by several orders of magnitude, enables hyperspectral visualization of subcellular features in biosamples. Despite its potential, SRS has been underutilized in complex biological systems due to two key limitations: the lack of multimodal information integration and the sensitivity constraints that limit detection to millimolar concentrations. My work addresses these challenges with two major innovations.

To enable multimodal understanding of complex biological systems, we developed the Stimulated Raman Scattering–Fluorescence In Situ Hybridization (SRS-FISH) platform. This technique bridges microbial identity with metabolic activity at single-cell resolution, enhancing throughput by 1-2 orders of magnitude compared to state-of-the-art approaches. The platform analyzed 30,000 cells from the human gut microbiome, combining multimodal imaging processing with statistical analysis to provide unprecedented insights into microbial dynamics in response to nutritional and pharmacological stimuli.

To overcome the sensitivity limits of conventional SRS, we developed Stimulated Raman Photothermal (SRP) microscopy. This novel technique exploits photothermal effects of SRS to achieve over 500-fold improved contrast, enabling precise and quantitative metabolic imaging. We explored and optimized the influencing factors of the newly invented microscopy scheme in both hardware setup by tuning laser property and optical alignment and software part including single pulse digitization, baseline correction and matched filtering. Additionally, the implementation of a fiber-laser-based SRP system advances the translational applications of Raman microscopy, offering superior sensitivity and user-friendly design.

These advancements represent a significant leap forward in the capability of stimulated Raman microscopy, establishing it as a versatile and powerful tool for investigating complex biological systems. By addressing key limitations, the innovations presented here provide critical methodologies for exploring vibrational chemical imaging and contribute to the broader field of optical microscopy.