WincsNanotrode development for DBS

描述（由申请人提供）：脑深部刺激（DBS）是一种有效的神经外科方法，用于治疗各种神经和精神疾病，包括帕金森病，特发性震颤，癫痫和抑郁症等。本研究计划旨在通过使用基于纳米碳纤维（CNF）的电极设计，开发一种基于脑电极界面电化学监测的新型术中监测方法，以推进DBS技术的发展。这种方法利用了梅奥诊所开发的无线瞬时神经递质浓度传感器（WINCS），这是一种仪器系统，结合了数字遥测、快速扫描循环伏安法（FSCV）和电流测定法，以及美国国家航空航天局（NASA）开发的基于CNF的电极技术，称为WINCSnanotrode。根据Mayo IRB批准的协议，WINCS的安全性和可行性已经在接受DBS神经外科手术的人类患者中成功进行了测试。近年来，CNF纳米电极已被证明是电化学检测的优良衬底，具有超高灵敏度、高信噪比和快速采样的特点，同时为更有效的刺激提供了改进的脑电极接口，从而节省了电池寿命。凭借其亚秒级的化学分辨率记录，FSCV被认为是测量实验动物神经递质（包括多巴胺、血清素、去甲肾上腺素和腺苷）的最先进技术。通过实时关联神经递质释放和治疗性刺激，梅奥诊所的WINCS与NASA的WINCSnanotrode相结合，将提供一个强大的新工具来评估DBS的机制，指导电极放置，测试刺激的准确性和效率。三个具体目标是(1)完成WINCS和WINCSnanotrode的开发，以产生一种能够用于人体电化学传感的装置，(2)建立WINCSnanotrode方法用于DBS神经外科大动物（猪）模型的术中神经化学监测，(3)建立WINCS和WINCSnanotrode方法用于DBS神经外科手术中人类术中神经化学监测。我们认为，WINCS和WINCSnanotrode技术在确定DBS的特定靶点、简化已经漫长而困难的植入过程、评估刺激参数的效率以及提高刺激电极的准确性和效率方面具有巨大的潜力。

DESCRIPTION (provided by applicant): Deep brain stimulation (DBS) is an effective neurosurgical approach for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, epilepsy, and depression, among others. This research proposal is intended to advance DBS technology by developing a novel intraoperative monitoring approach based on electrochemical monitoring at the brain-electrode interface by use of carbon nanofiber (CNF) based electrode design. This approach utilizes technology developed at the Mayo Clinic, the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS), an instrumentation system that combines digital telemetry with fast-scan cyclic voltammetry (FSCV) and amperometry, coupled to CNF based electrode technology developed at National Aeronautic and Space Administration (NASA) called WINCSnanotrode. Under Mayo IRB approved protocol, WINCS safety and feasibility has already been tested successfully in human patients undergoing DBS neurosurgery. Recently, CNF nanoelectrodes have been shown to be an excellent substrate for electrochemical detection demonstrating ultra high sensitivity, high signal to noise ratio, and rapid sampling, while at the same time providing an improved brain-electrode interface for more efficient stimulation, thereby conserving battery life. By virtue of its sub-second, chemically resolved recording, FSCV is recognized as state-of-the-art for measuring neurotransmitters, including dopamine, serotonin, norepinephrine, and adenosine, in laboratory animals. By correlating the release of neurotransmitter and therapeutic stimulation in real time, Mayo Clinic's WINCS coupled to NASA's WINCSnanotrode will provide a powerful new tool to assess the mechanism of DBS, guiding electrode placement, and testing accuracy and efficiency of stimulation. The three Specific Aims are (1) complete WINCS and WINCSnanotrode development to generate a device that is capable of use in humans for electrochemical sensing, (2) establish WINCSnanotrode approach for intraoperative neurochemical monitoring in a large-animal (pig) model of DBS neurosurgery, and (3) establish WINCS and WINCSnanotrode approach for intraoperative neurochemical monitoring in humans during DBS neurosurgery. We believe that WINCS and WINCSnanotrode technology engenders great potential to identify specific targets for DBS, to streamline the already long and difficult implantation procedure, to assess efficiency of stimulation parameter, and to improve the accuracy and efficiency of stimulating electrode.