Imaging Method development
Chemical imaging plays an essential role in studying heterogeneous biological systems. We focus on the method development of nonlinear optical spectroscopy-based label-free chemical imaging tools, particularly stimulated Raman scattering microscopy and transient absorption microscopy. The former directly measures chemical composition through vibrational Raman signatures and the latter detects absorptive species (e.g. hemoglobin) through nonlinear optical absorption. Resolution, sensitivity, and specificity are key metrics in terms of imaging capability. A major innovation in the lab is the development of quantitative imaging methods to enable absolute concentration mapping of molecules or relative quantification of molecular properties.
Hardware development
The core instruments we use in the lab are multimodal optical microscopes. Our home-built laser scanning microscopes (in both upright and inverted configurations) incorporate stimulated Raman scattering, transient absorption, and two-photon fluorescence detection, allowing imaging of a wide variety of biological samples from cell cultures to living animals. To push the resolution, sensitivity, and specificity limit, we also build ultrafast lasers (both solid-state lasers and fiber lasers) to extend the capability of our microscope.
Data science tool development
Chemical imaging generates an enormous amount of 3D/4D/5D hyperspectral data (3D spatial, 1D spectral, and 1D temporal). Advanced computational algorithms are required to process these data and extract meaningful and interpretable information about the sample. We apply machine learning and deep learning to imaging data to perform image segmentation, classification, and prediction. In particular, we are interested in using convolutional neural networks to transfer one type of chemical information to another (e.g. prediction of fluorescence from Raman) to augment the capability of chemical imaging.
Cancer diagnosis
Diagnosing cancerous tissue quickly and accurately in an intraoperative setting is critical to ensure the successful surgical removal of malignant tumors. Current pathology tools rely on century-old techniques of tissue staining (e.g. H&E staining) that highlight cell nuclei and cytoplasm. However, such staining requires extensive tissue processing, including tissue sectioning, fixation, and staining. Such processing is not only lengthy but also artifact-prone. Real-time imaging of fresh, unprocessed surgical tissue with stimulated Raman scattering (SRS) can generate equivalent histopathology images. Moreover, it has the potential to provide chemically specific information that may further improve diagnostic accuracy. We collaborate with UW pathologists and investigate the potential application of SRS in a number of cancer diagnosis applications.
Brain structure and function
Mammalian brains are enormously complex with numerous cell types, a dense microvasculature, and a hierarchical neural network. Understanding brain function at the cellular level has mostly relied on fluorescent labeling of specific cell types or structures. We leverage the capabilities of our label-free imaging technology to investigate brain structure and function. In particular, we are interested in exploring the role of capillaries in oxygen delivery and the contribution of dysfunctional capillaries to neurodegenerative diseases. We are also interested in in vivo label-free brain mapping.
Drug transport and drug response
Binding of drug molecules to their intracellular target requires efficient transport of drugs from the bloodstream to the cells of interest. Commonly used cancer drugs, including both chemotherapeutic drugs and kinase inhibitors, often suffer from drug resistance. Understanding how drugs transports through complex tissue environments and enter the cell cytoplasm will help illuminate the underlying mechanisms of drug resistance. We develop quantitative chemical imaging tools to quantify single-cell drug uptake and single-cell drug response, with the goal of understanding transport-related drug resistance mechanisms and developing better drug screening methods.
Non-biological applications
Stimulated Raman scattering microscopy can be applied to many different non-biological systems to quantify chemical heterogeneity and chemical changes under various environmental conditions. We collaborate with pharmaceutical companies to investigate the physical and chemical stability of pharmaceutical products, including solid dosage formulations and protein therapeutics.