Labeling method for high-resolution imaging of hundreds of tissue antigens

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 DESCRIPTION (provided by applicant): Neurodegenerative diseases are among the most expensive, disruptive, and least well treated of human maladies, arguably because they are not well understood. Array tomography (AT) is a new method for tissue imaging with resolution in all three dimensions sufficient to resolve individual synapses and provide quantitative characterization of multple molecular constituents. AT imaging data enable description of neural networks in the ontext of the three-­-dimensional tissue architecture. We believe such data will enable researchers to begin o comprehend the proper function of neural circuits and, importantly, to begin to undestand how it is that the various neurodegenerative processes present and progress. AT is, however, complex and expensive, and has been used in relatively few studies following the first publication in 2007 by Micheva and Smith. Aratome is currently providing AT services to the research community. The present application proposes proof-­-of-­-concept studies of a novel direct labeling method that could be the basis of a fully automated AT system, analogous to a NextGen Sequencer. The sample would be loaded into a microfluidic chamber, placed on the imaging instrument and imaging data for tens-­-tohundreds of antigens would be acquired, automatically. We would develop such an instrument, as well as the catalog of directly-­-labeled antibody and detection reagents, under Phase 2 funding.