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

神经技术具有激发和感知体内电活动细胞的能力，具有解决癫痫等疾病的潜力，并有助于保持因脊髓疾病引起的身体功能，还可以通过周期性兴奋神经来创造治疗疾病的新方法。神经接口技术在电子电路和电极感知和激发神经和神经元方面取得了重大进展。尽管神经接口技术的前景和进步，有两个方面的缺陷阻碍了神经和神经元的长期稳定接口。这些包括神经的非特异性兴奋和长期稳定的兴奋和动作电位的感觉。在深部脑植入和迷走神经刺激的情况下，激发是通过大电极暴露神经元组织，电流同时刺激许多神经元和轴突来实现的。非细胞特异性兴奋可导致身体许多部位的电刺激效应产生意想不到的下游效应。轴突特异性或轴突束特异性兴奋将有利于针对特定身体功能的神经，这是该计划的目标。探针中与神经元和组织的导电或电容界面持续时间不会超过几周到几个月，因为电极上的神经胶质细胞反应将电子流隔离，并通过电容读出减弱信号。这种寿命限制阻碍了神经探针的广泛使用，甚至在需要重复手术替代绝缘探针的应用中。这一提议将开发超声神经接口来感知病人一生的动作电位，为基于神经探针的疾病诊断和控制铺平道路。这项研究的目标是开发一种神经探针技术，这种技术可以依靠超高频超声波来影响神经元的激活，并感知细胞产生的动作电位。CMOS集成GHz超声换能器将刺激神经元并检测动作电位。该技术将首先在神经元的体外操作中进行优化，然后在小鼠大脑中进行探针测试。将设计和制造工作频率为400 MHz至2 ghz的超声波换能器阵列。超声波换能器将采用微流控芯片组件。微流控芯片将允许超声波刺激和传感机制的隔离和控制。微流控室通过控制体积和声边界条件来调节声流和声辐射压力，同时为超声脉冲检测动作电位相关离子通量提供途径。超声细胞刺激将通过光学全内反射荧光显微镜（TIRFm）和电探针的电测量来验证，此外还有超声询问。所创造的新知识将通过培训研究生和开设超声微系统课程来传播。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.