BioInVision, Inc. and Case Western Reserve University researchers will develop a cryo-imaging system for 3D imaging of mice. It will serve very many applications in biological research and the biotechnology industry, including mouse anatomical phenotyping, drug delivery, imaging agents, metastastic cancer, pathogen/immune system response, and stem cells/regenerative medicine, as well as many other studies of disease and therapeutic processes. By alternately sectioning and imaging, the system will acquire 3D, high-resolution anatomical color and cellular and molecular fluorescence images. The cryo-imaging system will consist of a mouse-sized, motorized cryostat with special features for imaging, a modified, bright-field/fluorescence microscope, and a robotic xyz imaging system positioner, all of which will be fully automated by a control system. The system will image fluorescent-reporter-gene labeled cells. By imaging with high resolution and sensitivity, we will establish a method for identifying single cells or cell clusters within a mouse. Once cells are identified, cell locations can be mapped relative to the tissue anatomy in the high contrast, 3D cryo-image color volumes. Cryo-imaging is unique among all in vivo and microscopic techniques in that it allows micron resolution and information-rich contrast mechanisms over very large 3D fields of view. It will fill the gap between whole animal in vivo imaging and histology, allowing one to image a mouse along the continuum from the mouse ->organ ->tissue structure ->cell ->sub-cellular domains.