Project Summary The ability to monitor activity of ensembles of neurons at single-cell resolution, chronically, over long time periods is greatly desired by neuroscientists. A variety of multi-electrode arrays (MEAs) have been developed for in vivo studies. These arrays are capable of revealing the activity of neuronal ensembles. Unfortunately, none of the devices on the market is fully capable of obtaining recordings that are simultaneously high-yield and high-quality, as well as stable and useful over months to years. This well-known challenge has greatly limited our ability to track the activity of populations of single neurons over a sufficient period of time to fully investigate circuit change during learning and memory, development and aging, or disease progression and wound healing. Additionally, the clinical use of brain machine interface (BMI), which utilize recorded neural activities to decode movement intent for controlling machine, has been hindered by the unstable and unreliable recording. We have developed a biomimetic coating composed of a brain-derived L1-cell adhesion molecule that mitigate the inflammatory host tissue reaction. In rodents, L1 coated NeuroNexas probes maintained high quality neural recording over the period of 16 weeks with significant higher single unit yield and signal to noise ratio than the uncoated control probes. Meanwhile, recordings in non-human primates (NHPs) with L1-coated Blackrock MEAs also demonstrated high quality performance in single unit yield and signal amplitude for at least 6 months. MEA manufacturers and users expressed strong interest in utilizing this technology. However, the coating made of biological protein is fragile and may lose bioactivity during the harsh environment of shipping, storage and sterilization. In order to make the L1 coating a technology that can be widely adopted by the neuroscience community, we propose to optimize the coating stability and develop practical protocols for coating preservation, storage, packaging, delivery and sterilization. The bioactivity of the coating prepared with different protocols will first be tested with cell cultures. Promising procedures will then be tested with implantation and recording in rodents at the University of Pittsburgh. Once optimum coating and procedures are determined, coated arrays will be delivered to users to evaluate the coating performance. Dr. Buzsaki (NYU) will test the L1 coated NeuroNexas arrays in freely moving rats. Dr. Schwartz (U. Pitt) and Dr. Chestek (U. Michigan) will test the L1 coated Blackrock arrays in NHPs for BMI studies. Users will work closely with us to define specific performance criteria in their recording applications, compare performance of coated and uncoated arrays, and provide user input for us to improve the packaging and delivery. Throughout the project, representatives from two MEA manufacturers, Blackrock Microsystems and NeuroNexus Technology, will serve as consultants to ensure compatibility of our procedures with their devices and guide us on the path to dissemination. The project will produce a coating technology that is both easy to adopt and generalizable to all types of state- of-art and emerging MEAs. Solving the practical issues of sterilization, packaging and delivery is a critical step toward commercial and clinical translation of the technology. High quality and stable of neural recording will greatly improve our ability to map brain activity in long-term experiments, and benefit brain-computer interfaces and other types of neural prostheses. In a broader sense, the protocols developed here for preserving immobilized protein during storage, delivery and sterilization should be applicable to other medical implants containing bioactive proteins, immunoassays, protein arrays, enzyme-based biosensors or any micro/nano devices that incorporate biological components.