High-resolution laser scanning microscopes are widely used in ceIIular biology for the study of fluorescently tagged molecules in vitro. Sub-micron resolution and fluorescence markers permits the in vitro study of cells, subcellular organelles, cellular dynamics, cellular molecules, and proteins derived from the genome. For instance, the GFP (green fluorescent protein) gene, and other mutant forms of GFP, can be transfected with viral vectors into the genome, and are activated when a protein is produced from those genes to which it is specifically fused. The study of that protein is thus made possible by it being fluorescently tagged with GFP. The microscopic study of subcellular organelles and cellular processes has heretofore not been possible in vivo except by gross observation via fluorescence spectroscopy or by imaging through biological windows embedded in model mammalian animals. We will develop a novel miniature high-resolution fluorescence microscope for minimally invasive in vivo microscopy of animal models. The microscope can be used to image fluorescently tagged molecular markers in vivo. It will allow the observation of cells, cellular organelles, and proteins from specifically tagged genes and permit their study in vivo. Sub-micron resolution is possible from the miniature microscope that has a millimeter form factor allowing minimally invasive insertion into mammals to study gene expression. In addition, a large field of view is obtained while achieving good imaging depths. Molecular markers and gene expression have the potential to detect early stage cancer. PROPOSED COMMERCIAL APPLICATION: Potential applications exist in developmental biology, tumor cell detection, and to accurately direct pharmacological and mechanical interventions in such diverse fields as cardiology, pulmonolgy, oncology, and transplantation.
