WincsNanotrode development for DBS

描述(申请人提供)：脑深部刺激(DBS)是一种有效的神经外科方法，治疗各种神经和精神疾病，包括帕金森氏病、特发性震颤、癫痫和抑郁症等。本研究旨在通过基于碳纳米纤维(CNF)的电极设计，开发一种新的基于脑-电极界面电化学监测的术中监测方法，以推动DBS技术的发展。这种方法利用了梅奥诊所开发的技术-无线瞬时神经递质浓度传感器(WINCS)，这是一种将数字遥测与快速扫描循环伏安法(FSCV)和安培测量相结合的仪器系统，与美国国家航空航天局(NASA)开发的基于CNF的电极技术WINCS纳米电极相结合。根据Mayo IRB批准的方案，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测试。最近，CNF纳米电极被证明是一种极好的电化学检测基底，表现出超高的灵敏度、高信噪比和快速采样，同时提供了改进的脑-电极接口，以实现更有效的刺激，从而延长电池寿命。由于其亚秒级的化学分辨记录，FSCV被公认为测量实验动物的神经递质，包括多巴胺、5-羟色胺、去甲肾上腺素和腺苷的最先进水平。通过实时关联神经递质的释放和治疗刺激，Mayo Clinic的WINCS与NASA的WINCS纳米电极相结合，将提供一个强大的新工具来评估DBS的机制，指导电极放置，以及测试刺激的准确性和效率。这三个具体目标是(1)完成WINCS和WINCS纳米电极的开发，以产生能够用于人类的电化学传感设备；(2)在DBS神经外科的大动物(猪)模型中建立用于术中神经化学监测的WINCS纳米电极方法；以及(3)建立用于DBS神经外科手术中人类神经化学监测的WINCS和WINCS纳米电极方法。我们相信，WINCS和WINCS纳米电极技术在识别DBS的特定靶点、简化本已漫长而困难的植入程序、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.