PROJECT SUMMARY/ABSTRACT: The Stanford Cardiovascular Institute (CVI) proposes the acquisition of a Vala Sciences’ IC200 Kinetic Imaging Cytometer (KIC) to be placed in a shared setting in the new Biomedical Innovations (BMI) Building that is centrally located on campus. The IC200 KIC is a cutting edge instrument that combines aspects of high content screening systems with high speed video imaging and cell-by-cell analysis features of physiological recording instrumentation such as patch clamp electrophysiology setups. No other type of instrument combines these features, and no comparable instrument is available on Stanford campus or in the vicinity. The instrument will be used for in-depth studies that probe disease mechanisms of excitable cells such as cardiomyocytes on an unprecedented whole genome and whole proteome level. The focus on mechanism-based understanding of disease, and ultimately the development of mechanism- based therapeutics, aligns with the long-term strategic plan of the Stanford CVI and School of Medicine, and is consistent with recent faculty recruitment. The capability of high throughput assessment of physiological function of heart cells plays a central role in this plan. The instrument will be managed by an experienced group with expertise in high content screening and disease modelling using induced pluripotent stem cell (iPSC)-based models. The CVI comprises more than 400 investigators and more than 125 faculty-led research groups and spans diverse departments including Medicine, Pediatrics, Ophthalmology and Biomedical Engineering. The Major and Minor Users highlighted in this proposal range from junior faculty who are just starting their own laboratories to established full professors with over 20 years of research experience. All the major users have NIH funding, and the collective benefit to NIH grants comprises over 80% of the anticipated user time of the instrument. The institution is committing considerable financial resources and dedicated space to ensure the maintenance and continued operation of the instrument, including its integration into a robotics facility. We expect that the IC200 will positively impact a broad cross section of cardiovascular and other diseases, notably heart failure and cardiovascular complications of diabetes and cancer treatments. In addition, the high throughput and physiology recording aspects of the IC200 will propel research towards our drug development and our translational goal of improving care of patients with cardiovascular disease.