ENG: CCSS: Long Term Reliable Neural Recordings and Neuro Modulation Using GHz Ultrasonics

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Neural technology with the ability to excite and sense electrically active cells in the body has the potential of solving diseases such as epilepsy, and help preserve body function due to spinal cord disorders, and also create new approaches to treat diseases by periodic excitation of nerves. There have been significant advances in the neural interface technology in which electronic circuits and electrodes sense and excite nerve and neurons. Despite the promise and the advancements in neural interfaces technology, there are two areas of deficiency that have prevented long-term stable interfaces to nerves and neurons. These include non-specific excitation of nerves and long-term stability of excitation and sensing of action potentials. In the case of deep brain implants and vagus nerve stimulation, the excitation is conducted by large electrodes that expose the neuronal tissue with current exciting many neurons and axons concurrently. The non-cell-specific excitation can lead to unintended downstream effects in electrically stimulating effects in many parts of the body. Axon specific or axon-bundle specific excitation would be beneficial for targeting nerves intended for particular body function and is a goal of this program. The conductive or capacitive interfaces to neurons and tissue in probes do not last beyond a few weeks to a few months, as glial cell response on electrodes insulates the electron flow, and weakens signals with capacitive readout. This lifetime limitation prevents the wide-spread use of neural probes, and even in applications where that are required, repeated surgeries replace insulated probes. This proposal will develop ultrasonic neural interfaces to sense action potentials over a patient's lifetime would pave the way for neural probe-based diagnosis and control of diseases. The proposed effort is to develop a neural probe technology that can rely on ultra-high frequency ultrasonic waves to affect neuron activation and to sense the action potentials generated by the cells. CMOS integrated GHz ultrasonic transducers will stimulate neurons and detect action potentials. The technology will be optimized first in vitro operation on neurons, and then test probes in mice brains. Ultrasonic transducer arrays with operating frequencies from 400 MHz to 2-GHz will be designed and fabricated. A microfluidic chip assembly will be applied and attached to the ultrasonic transducers. The microfluidic chip will allow for the isolation and control of the mechanisms of ultrasonic stimulation and sensing. The microfluidic chamber will control the volume and acoustic boundary conditions to modulate acoustic streaming and acoustic radiation pressure while providing pathways for the action potential related ion fluxes to be detected by ultrasonic pulses. The cell stimulation with ultrasound will be verified using optical Total Internal Reflection Fluorescence microscopy (TIRFm) and electrical measurements using electrical probes, in addition to ultrasonic interrogations. The new knowledge created will be disseminated by training graduate students, and developing a class on ultrasonic microsystems.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.