The primary goal of this work is to develop compact, bio-compatible, high sensitivity and high resolution neural interfaces utilizing a new family of electro-fluidic capacitive probes. These probes will sense, stimulate and inhibit action potentials, as well as provide the capacity to deliver drugs in a highly targeted manner as well as monitor the physiological response to the drug with unprecedented temporal and spatial resolution. The proposed research entails semiconductor device processing, electrical modeling and simulations, and both in-vitro and in-vivo physiological measurements. Anticipated results will enable deeper understanding of neural functionality in a large population of neurons, determine the scaling limits for neural probes, and be integrated with educational, mentoring and outreach activities.
Intellectual Merit: The proposed program is motivated by the need to overcome technological challenges to understanding the neurological processes by which humans perceive, act, learn and remember, and in doing so make headway toward controlling some of these processes such as limb movements. This requires development of electro-neural interfaces with resolution that can probe at the single cell or sub-cellular level in a network of a large population of neurons. The neural probes need also to be biocompatible, stable, and possess reliable interfaces for durable operation. This task can be best achieved with programmable and targeted microfluidic drug delivery to mitigate the response of the immune system and enhance the probes biocompatibility. Such functionality and resolution is not met with any existing technologies. A new family of neural probes, electro-fluidic capacitive probes, that can meet these requirements will be developed in this program. These probes will utilize a new fabrication process for the purpose of addressing individual 3D neural probes in a dense configuration. This process adds, for the first time in the field of neural probe electrode arrays, multiplexed and highly targeted drug delivery channels through each individual neural probe site, thus enabling a novel and robust neurophysiology platform. Such a platform will lead to new research directions in neurophysiology and new technologies to improve patient care because: (1) The platform is scalable to very dense arrays. (2) The probes are biocompatible because the sensing mechanism relies on capacitive coupling and eliminates electrochemistry at the electrode sites. (3) The multiplexed microfluidic drug delivery ports will help reduce the response of the immune system to implanted electrodes, in contrast to current approaches where biocompatible coatings are temporary and deplete with time. (4) The microfluidic delivery channels will enable targeted drug delivery, and potentially ion sensing, at dimensions that are comparable to neurite size and synaptic distances for the first time. (5) The process is compatible with silicon, allowing ease of integration with signal processing and conditioning silicon circuits.
Broader Impact: The proposed project will enhance the research infrastructure through development of tools that will have far reaching applicability in the areas of biosensing and neuroprosthetic device development. The proposed platform will deliver new insights into neuroscience and has direct relevance to the Brain Research though Advancing Innovative Neurotechnologies (BRAIN Initiative) recently unveiled by President Obama. The resulting devices will enable for the first time highly localized electrical intervention and simultaneous targeted drug delivery that are critical for realizing high fidelity neuroprosthetic devices. Also proposed are plans to enhance graduate and undergraduate curricula in the multidisciplinary area of medical devices by developing and teaching a new core course, Medical Devices and Interfaces, that will include laboratory training not currently available to UCSD graduate students. Through participation in outreach programs coordinated by UCSD's Qualcomm Institute, the PI will mentor and provide research experiences for high school students from underrepresented groups. Active participation in ongoing diversity-promoting initiatives of UCSD's Jacobs School of Engineering will enable the PI to provide research experiences for undergraduate students during the academic year as well as the summer throughout the award period.
