KAUST Research Workshop on Innovative Technologies to Study Brain Energy Metabolism
University of Pennsylvania, USA
Sergei Vinogradov is Professor of Biochemistry and Biophysics at the Perelman Schol of Medicine, University of Pennsylvania. Dr. Vinogradov's research is focused on the development of advanced probes for microscopy and imaging applications. On the fundamental level our interests encompass chemistry of porphyrins and other pyrrolic dyes, energy and electron transfer in multichromophoric systems, spectroscopy and imaging. Over the past years the main focus of the lab has been optical imaging of oxygen in biological systems, including chemistry of imaging probes, phosphorescence lifetime imaging instrumentation, image reconstruction methods and a variety of applications of phosphorescence. Other bio-analytes of interests have been pH and metal ions. Currently the laboratory also pursues interests in optical energy upconversion and magnetic field effects on luminescence in view of their applications in imaging. Dr. Vinogradov collaborates broadly with laboratories across the world whose interests include basic studies of cellular metabolism and applications in neuroscience, stem cell biology, cancer therapy, tissue engineering and ophthalmology.
Molecular oxygen plays a unique role in energy metabolism. Consumption of oxygen is tightly coupled to production of cellular energy, while oxygen levels vary considerably depending on the tissue type and metabolic load. Low oxygen ultimately causes decrease in the cellular energy state, affecting multiple pathways and in many cases indicating onset of pathology. Our laboratory has been developing the phosphorescence quenching method for biological oximetry - an optical technique possessing intrinsic microscopic capability. In the past we have designed the dendritically protected oxygen probes for quantitative imaging of oxygen in tissues, and more recently developed probes for two-photon phosphorescence lifetime microscopy (2PLM) of oxygen, which has proven to be a useful tool in neuroscience and stem cell biology. Here we present new probes for 2PLM, whose much higher performance enables new applications of the method in neuroimaging and beyond. In addition, some of these new molecules make it possible to image oxygen simultaneously with temperature. For quantitative oxygen imaging independent non-invasive highly localized measurements of temperature are required, since calibrations of all oxygen probes are intrinsically temperature-dependent. Furthermore, optical imaging of temperature would be highly useful in other areas, such as thermotherapy of cancer, diagnostics of local inflammation as well as in optimization of hypothermic treatment of brain injury and stroke.