Project Summary The brain’s functions are determined by its neural circuits, which consist of approximately 85 billion neuronal cells. Current brain recording technology is not sufficient to accomplish the goal of a high resolution mapping of brain activity due to the lack of a large-scale recording technology. Another vital challenge for current brain recording technology is obtaining longer lifetime for the implanted electrodes to prevent repeated surgeries. As over time, the harsh physiological environment (wet, ionic, reactive oxidizing species, immune response, etc.) in the neural tissue breaks down and/or encapsulates the electrode implants. To overcome these obstacles, we propose to develop and validate an implantable Transition Micro- Electrode Array (tMEA) for large-scale brain recording and modulation. This approach has the potential to eventually achieve an interface density of 106 “electrodes” per cm2, which is several orders of magnitude beyond established neural recording solutions. Except for the ultra-high recording capability, radically different from existing neural technologies, the tMEA uses living neurons as means of electrical recording and its axon guiding probes will be fabricated from degradable biopolymer via 3D printing. We expect the biocompatibility of the tMEA’s unique design will greatly decrease tissue damage and may suppress inflammatory immune response in the brain. The tMEA technology will use biopolymers that degrade safely after implantation, exposing living neural stem cells that will project their axons into local brain regions to form synaptic connections with the patient’s own neurons. In this way, the biological neuronal axons grow into a stable “electrode array” and replace a failure-prone abiotic interface with natural biotic connections act as a high- performance brain-machine interface. All these distinctive features endow the tMEA with unique potential for neuroscientists and clinicians to explore human brain functions and treat neurological disease, enabling an advancement of neuroscience, medical practice, and a variety of other future technologies.

Project Narrative This project aims to demonstrate a proof-of-concept of an innovative technology for brain-machine interfaces, “transition Micro-Electrode Array” (tMEA). The device is designed to integrate living neurons for accurate large-scale recording of neural activity. If successful, this tMEA technology could revolutionize microelectrode methodology and has a great potential to advance neuroscience as well as support medical treatment in the future.