DESCRIPTION (provided by applicant): The technological advancements in neural engineering have provided an increasingly more powerful toolset of designs, materials, components and integrated devices for establishing high-fidelity chronic neural interfaces. A primary requirement of these neural interfaces for majority of the neuroscience studies is the ability to simultaneously record and/or stimulate from a large neuronal aggregates for specific periods of time. The future progress in neuroscience to a large extent relies on the ability of these neural interfaces to allow simultaneous observation and experimental access of complex neural networks and properties of cooperating neurons. Two critical solutions for achieving this goal are placing a large number of electrode sites in a small amount of tissue at the sub-millimeter range without significant tissue damage and efficient isolation of action potentials emanating from individual neurons. These solutions have remained largely unexploited mainly because of technological challenges, inherent limitations in design tolerances, and non-standard manufacturing techniques used in existing neural devices. Today, most of the success achieved in understating the physiological function of the brain is based on the sequential analysis of single-site recordings. And one neural interface, which has been successful in achieving this is the Utah electrode array (UEA), the only FDA approved commercialized device that has been extensively used in human clinical trials. Although the reasons are debatable as to its prevalence, the UEA records a rich feature set of neuronal information by distributing its electrodes at regular spacing over a large region across the cortical surface. However, this also implies that the data on any given electrode may be the only source of such information and, hence, it is not a robust source of information. As a result there has been a long-desire in the neuroscience community for having the ability to have multiple active sites distributed along each UEA electrode shanks, which could give it the robustness in feature extraction but not at the expense of losing its ability to record across the a wide region of cortical surface. We have developed a novel focused ion beam (FIB) technology that allows fabricating multiple sites on the shafts of the UEA. The FIB technology allows one to literally "write" with platinum on the shaft of the UEA with precise control and <1 um resolution. As the underlying structure of the proposed Utah Multisite electrode array (UMEA) is a UEA, our proposed innovation does not lose the value of the standard UEA but does gain the advantage of robustness in detection of neuronal sources. Furthermore, the flexibility in patterning multiple sites on each shank readily allows the creation of tetrode and laminar configurations of multisites on the shaft of the UEA so that the device can be tailored to the task. Also the electrode sites can be realized from a variety of materials, can have a range of surface areas, and can be placed anywhere along the shanks at any spacing. The objective of this research is to design, investigate and validate different configurations of high density (56 electrodes/mm2) UMEA (specific aim-I). We will perform in-vitro testing (specific aim-II) and in-vivo validation and comparison of recording performance of different configuration of the UMEA (specific aim-III). The presented innovation and objectives in this proposal will open a whole spectrum of new possibilities for the neuroscience researcher. It is envisioned that the UMEA will be a better tool for understanding neuronal activity by providing recordings sites in a three dimensional region of cortex. The ease and flexibility of incorporating any multisite design of on the UEA shanks makes the presented approach simple and yet efficient. As a result, the proposed study will be a shortest path towards product validation (device and animal) and the clinical implementation of a new electrode technology (UMEA).

PUBLIC HEALTH RELEVANCE: The ability to record and/or stimulate, for example, through multiple electrode sites simultaneously has the potential to greatly improve the speed and accuracy of the mapping procedure. The proposed research for the first time enables a large high precision design space (example electrode site area, spacing, shape, location) for fabricating multisites on a commercial device: Utah electrode array. It allows the end users for the first time to map neurons in three dimensional space. The presented innovation and objectives in this proposal will open a whole spectrum of new possibilities for the neuroscience researchers.