Project Summary/Abstract The Optical Biology Core (OBC) at the University of California, Irvine (UC Irvine) requests a Shared Instrumentation Grant to purchase a Zeiss LSM 980 Non-Linear Optics (NLO) confocal with Airyscan 2 FLIM ready. The LSM 980 will bring new capabilities such as higher resolution, more rapid data acquisition and AI- based sample finding that are not currently available to users. Importantly, the LSM 980 will replace a current microscope that is very heavily used and is over 10 years old and thus no longer eligible for service contract coverage after October 2022. The existing LSM 780 NLO confocal microscope has been used on average over 270 hours per month for the past 12 months, excluding the 3-month pandemic shutdown, with current usage close to 80 hours per week. This flagship instrument has been a critical component for researchers in over 34 labs across campus, and replacing it is essential to maintaining the highest level of instrument functionality, dependability, and availability across this wide disciplinary range. The LSM 980 will be located in dedicated space within the OBC. The OBC will provide administrative and technical support to maintain the microscope as well as advice on experimental set up, training and imaging, and data analysis expertise to enable users to take full advantage of its capabilities. The OBC has operated at UC Irvine since 1987 demonstrating its stability, capability and a long-standing institutional commitment to microscopy and imaging resources. The OBC receives robust financial commitments towards instrument service contracts, staff salaries and microscope accessories from a broad array of institutional sectors including the Office of Research, the NCI-funded Chao Family Comprehensive Cancer Center and four individual Schools: Biological Sciences, Engineering, Medicine, and Physical Sciences. Replacement of the existing LSM 780 will bring significantly improved imaging capabilities. The LSM 980 incorporates the Airyscan detector (first introduced in 2014), which samples high spatial frequencies with an end result of a two-fold improvement in resolution (120 nm and axial resolution of 350 nm) and up to an eight-fold improvement in signal to noise. Additional design and engineering improvements in the LSM 980 permit a larger field of view and much faster scanning than is possible with the LSM 780 while continuing to support two-photon and Fluorescence Lifetime Imaging (FLIM). These improved capabilities will enhance research currently using the LSM 780 by providing higher-resolution images in less time. Specific benefits to human health from projects of the major users include gaining a better understanding of: (1) how new drug therapies for cancer and other diseases can be enhanced; (2) delivery of synthetic vectors to cells; (3) how macrophages behave in response to natural and synthetic biopolymers; (4) antibiotic development; (5) tissue and nerve regeneration; (6) wound repair; and (...