Arizona State University

This four-year project aims to build a novel, live-cell imaging instrument for basic and clinical science application. The 3D microscope called the “cell CT scanner” will provide functional images, revealing the molecular mechanisms underlying important metabolic and disease processes. Cell CT is analogous to diagnostic radiology CT in that it will reconstruct 3D images with isotropic, submicron resolution from hundreds of projections acquired from many angles as the cell is rotated. A key component of the research is to determine the best method for rotating cells, which must be done extremely precisely without harming the cell. The team will investigate several cell rotation methods including one that rotates an optically trapped cell in a microfluidic vortex and another that uses an infrared light beam having asymmetrical intensity distribution. They will use fluorescent antibody probes and fusion-protein constructs specific to the proteins of interest to label cells for emission CT scanning. The technology will be validated by studying cells from immortalized cell lines representative of various stages of epithelial cancers, and cells disaggregated from human biopsies spanning the same disease spectrum. Cell CT may enable for the first time rapid spatial localization of proteins, and assessment of their concentrations in subcellular compartments and microdomains, providing insights concerning relationships between cell structure, function and disease.