Project Summary / Abstract The purpose of this project is to optimize circuit and system architectures of active electrode arrays which will provide low-noise, multiplexed acquisition of neural signals from thousands of electrodes. We will reduce noise by exploiting a novel current-sensing circuit approach and new multiplexing strategies, such as Code-Division Multiple Access (CDMA). We will also apply novel system level de-noising approaches using kriging. Finally, we will demonstrate our low noise, active arrays using a unique, ultra-flexible 3D neural interface paradigm: Neuro-CROWN: CMOS-based, ROlling-enabled, loW-noise Neuroelectronics. These electrode arrays include thousands of electrodes that can be used for both recording and stimulation, enabling studies that require recordings from multiple, large cortical regions in rodents and non-human primates (NHP) at cellular scale. The electrode arrays are extremely thin (<25 µm) and flexible, and are made in both non-penetrating and 3D penetrating configurations, of which the latter will be formed from a simple and unique rolling of 2D soft electrode array (ROSE) method. Amplifiers and multiplexers integrated directly into the electrode array, using commercially fabricated silicon transistors, intelligently combine signals inside the array so that recording from up to 4,096 electrodes is possible with fewer than 20 multiplexed external wire connections. The small number of interface wires facilitates long-term experiments in chronically-implanted, freely-behaving animals and eases future wireless integration. The electrode arrays will be manufactured in large quantities (3800 devices / run) using full wafers at X-fab. By leveraging a cost-effective manufacturing process, the raw materials cost of each electrode array will be ~$10, excluding post processing labor which will be supplied by this program. Our dissemination program will make device broadly available to a large cohort of end users. We have previously disseminated early-stage technology to ~10 labs are now scaling up to disseminate that technology to ~100 labs. Based on feedback we received during this dissemination effort, neural interfaces with high SNR and 3-dimensional measurement are critically important to neuroscience research, motivating this project. We will disseminate this new technology to at least 10 labs in this effort, solicited from the neuroscience community at large. We will solicit end user feedback through a workshop at the Society for Neuroscience (SfN) meeting and use this feedback to shape our device designs. This project seeks to enable BRAIN Initiative investigators and the broader neuroscience community to perform very large-scale recordings in animal models. Further, the research enabled by this technology will be able to be rapidly translated to humans in the future, through parallel, separately-funded efforts by our team to bring actively-multiplexed electrode arrays to human use.