Collaborative Research: An implantable intracranial ultrasound stimulation for treating neurodiseases

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Ultrasound stimulation has been demonstrated to be an effective therapeutic tool for treating several brain related disorders in humans. Reducing the symptoms of chronic disorders such as migraine, epilepsy, neuropathic pain due to spinal cord damage, essential tremors and Parkinson’s disease can be accomplished through neuromodulation and targeted delivery of drugs to specific regions of the brain via temporary disruption of the blood- brain-barrier (BBB). However, current ultrasound neuromodulation technology uses a bulky arrangement of several single element ultrasonic transducers inside a helmet shaped device that require high voltage for operation. This limits its use to only clinical settings in hospitals. In contrast, minimally invasive, implantable intracranial ultrasonic stimulation microchips can help treat neurodiseases that require intermittent and chronic stimulation over prolonged periods. Towards this goal, this project will design, fabricate, and validate a low power and biocompatible intracranial micromachined ultrasound chip for temporary opening of the BBB. Such a chip will consume minimal power, operate at safe low voltage, and has the potential to treat chronic neural diseases requiring intermittent on-demand stimulation over periods of months to years. Beyond the application proposed here, successful demonstration of miniaturized ultrasonic chips could also find applications for non-invasive wearable imaging of arterial blood flow for diagnosing vascular diseases and inspection of critical fractures and material failures in aircraft and infrastructural constructions like bridges and pipelines. The multidisciplinary research will enable integration of new pedagogical materials on ultrasound neuromodulation and piezoelectric micromachined ultrasound transduces (PMUTs) design and development, into both undergraduate and graduate engineering curriculum and Senior Capstone Design projects. Outreach activities will target diverse middle and high school students, underrepresented in engineering, with the goal of raising interest and curiosity in ultrasound transduction and imaging methods.This project addresses the current need for implantable focused ultrasound (fUS) technology by leveraging a microelectromechanical systems (MEMS) approach to fabricate miniaturized curved 3D transducers in single and array formats and demonstrate their use for trans-BBB drug delivery. To suit implantable and wearable applications, low-voltage, scandium-doped aluminum nitride (Sc-AlN) MEMS approach will be used to realize the PMUTs. To achieve ultra-high electromechanical coupling coefficient, unique curved PMUT membrane shapes will be developed using chip-scale glass-blowing fabrication. The proposed curved PMUT arrays will use optimized Sc-AlN thin films for piezoelectric material, thus ensuring lead-free and biocompatible implants. Inherently curved 3D PMUTs are expected to reduce beam width in elevational direction and thus deliver ultrasound energy more efficiently to the neural target of interest. Overall, by using a set of innovations at material, structure, and system level, 8 x 8 PMUT arrays will be demonstrated to generate steerable focused ultrasound output at up to 2 cm depth in the brain tissue with 1 MPa pressure at the focal spot and 0.5 mm resolution. This approach will offer unique flexibility to cover a large region of interest in brain with high resolution for ultrasound stimulation applications. Further, the pressure output of the fabricated curved PMUT array device will be validated using experiments on brain tissue. BBB-opening capabilities will be tested using in vitro cell culture experiments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.