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

神经技术具有刺激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，有助于保护因脊髓疾病而导致的身体功能，还通过周期性兴奋神经来创造治疗疾病的新方法。在神经接口技术方面已经取得了重大进展，其中电子电路和电极感知并兴奋神经和神经元。尽管神经接口技术有希望和进步，但仍有两个领域的不足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以及动作电位的兴奋和感觉的长期稳定性。在脑深部植入和迷走神经刺激的情况下，兴奋是由大电极进行的，暴露于神经元组织的电流同时刺激许多神经元和轴突。这种非细胞特异性的兴奋可能会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靶向特定身体功能的神经，这也是本项目的目标之一。探针中与神经元和组织的导电或电容界面不会超过几周到几个月，因为神经胶质细胞在电极上的反应隔离了电子流，并通过电容读数削弱了信号。这一寿命限制阻碍了神经探头的广泛使用，即使在需要的应用中，重复手术也会取代绝缘探头。这项提议将开发超声波神经接口来感知患者一生中的动作电位，这将为基于神经探头的疾病诊断和控制铺平道路。拟议的努力是开发一种神经探针技术，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型集成GHz超声换能器将刺激神经元并检测动作电位。这项技术将首先在神经元上进行体外操作，然后在小鼠大脑中测试探针。将设计和制造工作频率从400 MHz到2 GHz的超声换能器阵列。将应用微流控芯片组件并将其连接到超声波换能器上。微流控芯片将允许分离和控制超声波刺激和传感的机制。微流体室将控制体积和声边界条件，以调制声流和声辐射压力，同时为超声波脉冲检测与动作电位相关的离子通量提供路径。除了超声波检查外，还将使用光学全内反射荧光显微镜(TIRFM)和使用电探针的电测量来验证超声波对细胞的刺激。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NSF的法定使命，并通过使用基金会的智力优势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.