Miltenyi UltraMicroscope Blaze with Lightspeed mode for the University of North Carolina at Chapel Hill - Project Summary/Abstract The University of North Carolina at Chapel (UNC-CH) is requesting a Miltenyi UltraMicroscope Blaze with Lightspeed mode (Blaze). This is a light-sheet microscope that can take images of large, cleared tissue samples, with cellular resolution. It is ideal for imaging whole mouse organs, mouse tumors and human biopsies with high quality at high speed. This instrument will catalyze the research programs of twenty-four laboratories with funding from the National Institutes of Health, engaged in research in neuroscience, immunology, cancer biology and therapeutics, lung disease, kidney development, and vascular biology. Many of these projects cannot move forward without this new microscope. The Blaze light-sheet microscope will replace an obsolete system, a LaVision UltraMicroscope II (UM-II), that has significant limitations in terms of speed and optical quality, and which will no longer be eligible for a service contract from December of 2025. In detailed comparisons we measured the speed of the Blaze to be at least an order of magnitude faster than the UM-II in many relevant workflows, with equivalent or improved imaging quality. This makes feasible experiments that are currently out of reach because of prohibitively long imaging times. We are requesting a configuration of the system with the Lightspeed mode upgrade, that allows these fast imaging speeds, a full complement of lenses, and a custom configuration with five lasers (488, 561, 640, 685, 785 nm) that are well suited for imaging multiple fluorophores compatible with large, cleared tissue samples. The University is requesting $426,104.25 in Federal Funds, which it will supplement with $35,000 from internal sources to add software that will accelerate workflows. This microscope will be placed in the Microscopy Services Laboratory, a recharge core facility with a 30+ year history supporting the microscopy needs of the UNC-CH community. This core is strongly supported by the University, has deep expertise in the type of instrument being requested, and a strong track record training and assisting researchers. Many members of our User Group have experience with this form of microscopy, in the form of currently trained personnel and/or publications using our current microscope. The strong foundation of expertise in the core and User Group with this technology, as well as our experience during an extended demo with the Blaze give us great confidence that the new system will have a fast and very positive impact on many research projects. Ultimately, we expect this instrument will lead to important discoveries in multiple areas relevant to human health, and possibly to the development of new treatments.