Label-free imaging pinpoints molecular markers for disease diagnosis and mechanism investigation

Hyeon Jeong Lee^1*

¹Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, Zhejiang, China

* Presenter:Hyeon Jeong Lee, email:hjlee@zju.edu.cn

Accurate disease classification is crucial for clinical decision-making. Traditional histopathological evaluation often relies on morphology, extensive labeling, and labor-intensive analysis. While molecular information enhances our understanding of cellular physiology, ensemble-averaged measurements from complex tissues can exhibit high variability, complicating disease classification. To address these challenges, spectroscopic imaging modalities have been developed to directly measure molecular concentrations and physical properties via chemical bond vibrations. In this talk, the development of submicron-resolution molecular imaging techniques based on Raman and infrared spectroscopic modalities, along with their application in tissue imaging and in tracking subcellular lipid dynamics in embryos, will be discussed. Vibrational spectroscopic imaging techniques, such as stimulated Raman scattering (SRS) and mid-infrared photothermal microscopy (MIP), offer unique insights into biomolecules within their natural microenvironments. By employing a pump-probe detection scheme, they achieve enhanced sensitivity and spatial resolution, enabling high-speed chemical imaging for disease diagnosis and classification. Our recent work has developed a novel multimodality spectroscopic imaging method that allows comprehensive chemical analysis in cells and tissues at submicron resolution. Furthermore, the photothermal relaxation localization (PEARL) mechanism has led to a super-resolution imaging of non-fluorescent molecules. These improvements in spatial and spectral resolution facilitate the direct localization of chemical bonds, enabling quantitative mapping of chemical dynamics within single cells. Together these technological advancements decode the molecular machinery of living systems, providing unique insights into subcellular biomolecular dynamics and enhancing the identification of spatio-spectral signatures for disease classification.

Keywords: Vibrational spectroscopy, Chemical imaging, Raman scattering, Metabolism , Lipid droplets