High-density microelectrode array - PI: Kiehl, Thomas R. , Regenerative Research Foundation, High-Density Microelectrode Array SUMMARY/ABSTRACT With this application, we request funding to procure the HyperCAM Alpha platform from 3Brain AG (Zürich Switzerland). The HyperCAM Alpha is a multi-well, high-density microelectrode array system for observing and stimulating in vitro electrophysiological activity in electro-active cell cultures, cell constructs, organoids, and primary tissue samples. This instrument provides several key features: 1) high-resolution recording capability; 2) dynamic stimulation functionality, 3) a multi-well format; 4) 3D sensor options, and 5) sophisticated analysis software. These features ensure its utility across a range of biological investigations to meet the high-throughput and high-fidelity demands of our users and collaborators. This submission addresses a significant unmet need in our institute and region, namely the ability to test the functional impact of cellular interactions, genetic changes or of perturbagens on neural systems at scale. The researchers identified in this submission (spanning five institutions) are engaged in the study of a wide range of neurological disfunction from disease, aging, injury and developmental disorders. Placement of this instrument will directly advance work in frontotemporal dementia, Alzheimer’s, vascular contributions to dementia, sex- specific aging impact on cognitive function, tissue regeneration, spinal cord injury, brain development, and disease impact on neurological development. This instrument will help to quantify model systems, such as brain organoids, that have fast become the workhorses of the field. Projects described here also advance the development of new, more capable, model systems and even of next generation MEA-related devices. The primary, concrete, long-range benefit of this instrument to the biomedical research goals of RRF/NSCI/NeuraCell is to provide routine, clear, high-resolution, easily captured, characterization and quantification of the behavior and function of the numerous neurological systems under study at our institution. The use of this instrument will be integrated into nearly every research program within our walls. Beyond our organization, this instrument will: amplify the existing programs of our major users; help our minor users establish and grow their related research programs; and endow a foundation for future technology development.