Research
Our research program in Biomedical Optics involves developing and applying methods of optical science and engineering to probe and quantify the living systems found in biology and medicine, with a goal of impacting patient care via the development of non- and minimally-invasive biomedical optical diagnostic technologies. The translational ("bench to bedside") research strategy we employ can be described in terms of three major approaches: (1) Biomolecular Imaging (basic, pre-clinical studies on model systems); (2) Clinical Biosensing (applied, clinical studies on human tissues); (3) Computational Modeling.
Biomolecular Imaging: An important area of research in Biomedical Optics involves the development and application of advanced methods of laser spectroscopy and microscopy to study living biological systems. With support from The Whitaker Foundation, we developed a unique system for fluorescence lifetime imaging microscopy (FLIM) with picosecond resolution that enables us to conduct measurements on model systems under experimental conditions identical to those found in our clinical instrumentation, using endogenous (without stain) or exogenous contrast. Because fluorophore lifetimes are highly sensitive to local, microenvironmental conditions, while being generally independent of artifacts influencing fluorescence intensity, FLIM has enabled us to detect signatures of pre-malignant transformation in epithelial cells, monitor metabolic activity and intracellular oxygen, and detect fluorescence resonance energy transfer (FRET) in living cells. FRET events occur between biomolecules at nanometer length scales, thus offering an exciting opportunity for high spatial-sensitivity sub-cellular localization and binding studies in living cells. The NIH has supported our approach using FRET/FLIM and we demonstrated for the first time the binding of a specific oncogene in living cells.
Clinical Biosensing: In the body, pre-disease manifests itself through both biochemical and morphological changes in tissue. These alterations may be probed in vivo via noninvasive optical biosensing methods for signatures of pre-disease. To investigate the complex physical relationship between disease and tissue optical response in vivo, we conduct applied research to engineer clinically compatible optical instrumentation. Previously, we developed a laser-based technique employing time-resolved fluorescence spectroscopy to detect pre-cancerous tissue in the human gastrointestinal tract, which was the first measurement of its kind performed endoscopically in humans. The National Science Foundation, NIH, the U of M Medical School, and the Wallace H. Coulter Foundation Translational Research Partnership have supported our efforts to further develop this technology and apply it to other organs, as well as tissue engineered constructs.
Computational Modeling: Computational methods provide the necessary quantitative link between the complex optical signals detected clinically and the basic biological optical response identified from pre-clinical studies. We have developed and validated the first computational code capable of simulating photon migration in multi-layered biological tissues, with multiple fluorophores per layer, for arbitrary source-detector fiber geometries and optical fiber specifications, and that records in three dimensions spatially- and temporally-resolved information for both excitation light and fluorescence emission. Recently, we parallelized the code to run on the advanced computing facilities available at U of M. The NIH has supported our work to increase code efficiency, make the code generally available to the research community, and apply this computational approach to quantitative studies in living human tissues and tissue-engineered constructs.