CAREER: Multifunctional Nanostructured Electrodes for Closed-Loop Control of Neural Activity

University Of California-Davis, Davis CA

Investigators

Abstract

PI: Seker, Erkin Proposal Number: 1454426 A complex network of chemical and electrical signals is the basis of how the brain works. Medical devices that can be implanted into the brain, commonly referred to as neural interfaces, are emerging as powerful tools for treating neurological disorders as well as understanding the complex network underlying the brain's operation. These devices need to be engineered with attributes to minimize adverse tissue response, enhance fidelity in recording electrical signals, and controlling brain activity by precise delivery of electrical and chemical signals. Miniaturization technology used by the microelectronics industry has shrunk the dimensions of neural interfaces down to a few hair-widths. However, the demand for integrating multiple functions on these devices requires innovations in even smaller dimensions, where novel device coatings have shown promise. The overarching goal of this project is to engineer multifunctional devices that can monitor electrical signals that precede an epileptic seizure and in response deliver anti-epileptic drugs to prevent a full-blown seizure. To that end, the investigator will develop advanced device coatings that enhance the sensitivity in monitoring electrical signals and can deliver pharmaceuticals. The engineered materials and devices will be tested on brain slices from rats, which mimic tissue response to implanted devices and epileptic activity. The scientific knowledge and technology around the novel multifunctional materials will benefit a wide-range of fields, including vascular stent and orthopedic implant coatings, catalytic fuel cells, and biosensors for pathogens. In order to train a continuum of engineers and scientist conversant across engineering and life sciences, the investigator will engage undergraduate students in a "write and execute your own research proposal" style learning experience, deliver workshops for high school teachers on lesson plan development, and prototype an online course that merges miniaturization technology and life sciences for a diverse audience. This proposal is co-funded by the Biomedical Engineering Program in the Chemical, Bioengineering, Environmental and Transport Systems Division, and by the Metals and Metallic Nanostructures Program in the Division of Materials Research. An essential component of a neural interface is the electrode, which couples the neural tissue and the electronics. A critical step in engineering materials that interface with neural tissue is to understand the relationship between material properties, electrode performance, and biological responses. Nanoporous metals, with their highly-tunable properties, are promising candidates for systematically studying these fundamental relationships. One such material is nanoporous gold (np-Au), a nanostructured metal that is synthesized by self-assembly. Np-Au offers a tunable nanostructure, a large surface area-to-volume ratio, ease of integration with miniature devices, electrical conductivity, and drug-delivery capabilities. The central goal of the project is to employ a novel material screening platform to investigate material-tissue interactions simultaneously on both histological and electrophysiological levels. This in turn will reveal the relationship between tissue response and recording fidelity as a function of systematically-tuned topographical and soluble cues. Specifically, the investigator will develop an essential framework around selective promotion of specific cell types via soluble and topographical cues, as well as on demand delivery of neuromodulator pharmaceuticals. The project will finally employ organotypic brain slices as an epilepsy model to assess the capability of the multifunctional electrode coating in monitoring and pharmaceutically modulating neural electrophysiology in a closed-loop fashion. This will establish a unique, monolithically-manufacturable technology that can be easily scaled up and integrated into implantable neural interfaces for fundamental studies of neural circuitry.