A Wireless, Closed-Loop Neural Probe for Optogenetics, Pharmacology and Neurochemical Monitoring

用于光遗传学、药理学和神经化学监测的无线闭环神经探针

• 批准号: 10320710
• 负责人: Yi Zhang
• 金额: $ 327.7万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320710
• 关键词: Wireless; Closed; Loop; Neural; Probe

PROJECT SUMMARY/ABSTRACT Emerging tools and technologies, including optogenetics and pharmacology, have provided important avenues for neuroscience research. However, despite intensive work, it is still challenging to achieve closed-loop neuromodulation in a way that allows the free movement of animals, multimodal operation, and multiplexed monitoring of neurochemicals with high sensitivity, selectivity, spatiotemporal resolution, and cellular specificity, simultaneously. Our long-term goal is to develop advanced tools and approaches that support these capabilities for large-scale modulation and monitoring of the nervous system. Our immediate goal is to develop wireless, closed-loop neural probe systems for optogenetics, pharmacology, and neurochemical monitoring in freely moving mice and rats. We will achieve this goal by pursuing the following three specific aims: (1) to develop soft neural probes for the selective and sensitive monitoring of neurochemicals with high spatiotemporal resolution and cellular specificity; (2) to develop wireless, closed-loop neural probes for optogenetics, pharmacology, and neurochemical monitoring; and (3) to evaluate and characterize the efficiency and functionality of the wireless, closed-loop neural probes in vivo in freely moving mice and rats. The proposed research is innovative for five key reasons: First, the aptamer-enhanced graphene-field effect transistors (AeG- FETs) combine the high selectivity of the aptamer with the high sensitivity of G-FETs, thereby enabling sensitive (femtomolar) and selective (> 19-fold) detection of neurochemicals. Second, the nearly cellular-scale dimensions (50 μm x 50 μm), fast response time (~1 s), and site selective functionalization of AeG-FETs make it possible to monitor multiple neurochemicals, including dopamine, serotonin, norepinephrine, and neuropeptide Y, with high spatiotemporal resolution, sensitivity, and selectivity. Third, coupling state-of-the-art genetically encoded fluorescent sensors with a wireless multicolor photometer makes it possible to detect multiple neurochemicals in genetically defined neurons of freely moving animals. Fourth, multimodal operation and a customized graphical user interface (GUI) provide a robust, easy-to-use automated data analysis and control interface for closed-loop optogenetic and/or pharmacological manipulation, thereby enabling adjustable and on-demand neuromodulation. Finally, magnetic resonance coupling and wireless data communication allow fully wireless, battery-free operation, thereby enabling lightweight construction and eliminating concerns about battery life, charging status, and other issues that often arise during extended behavioral tests, while at the same time allowing animals to move freely. The successful completion of the proposed research will yield wireless, “all- in-one” closed-loop neural probes with several innovative features for neurochemical monitoring and optogenetic and/or pharmacological stimulation during freely moving behaviors. We believe these neural probes will be of great interest to the neuroscience community for basic studies in neuroscience as well as for studies of disease-related processes in various contexts relevant to the BRAIN initiative.

项目摘要/摘要 新兴工具和技术（包括光遗传学和药理学）提供了重要的途径 用于神经科学研究。但是，Dospite密集型工作仍然挑战要实现闭环 神经调节以允许动物自由运动，多模式手术和多重运动的方式进行神经调节 对具有高灵敏度，选择性，时空分辨率和细胞特异性的神经化学物质的监测， 相似地。我们的长期目标是开发支持这些功能的高级工具和方法 用于大规模调制和对神经系统的监测。我们的直接目标是开发无线， 用于光遗传学，药理学和神经化学监测的闭环神经元探针系统自由 移动老鼠和老鼠。我们将通过追求以下三个特定目标来实现这一目标：（1）发展 软神经探针，用于对具有高时空的神经化学物质的选择性和敏感监测 分辨率和细胞特异性； （2）为光遗传学发展无线的闭环神经元问题， 药理学和神经化学监测； （3）评估和表征效率和 自由移动的小鼠和大鼠体内无线闭环神经问题的功能。提议 研究具有创新性，原因有五个关键原因：首先，适体增强的石墨烯场效应晶体管（AEG- FETS）将座垫的高选择性与G-FET的高灵敏度结合起来，从而使敏感 （femtomalol）和选择性（> 19倍）神经化学物质的检测。其次，几乎细胞尺度的尺寸 （50μmx50μm），快速响应时间（〜1 s）和位点选择性功能化AEG-FETS使得 监测多种神经化学物质，包括多巴胺，5-羟色胺，去甲肾上腺素和神经肽Y，高 时空分辨率，灵敏度和选择性。第三，耦合最先进的基因编码 带有无线多色光度计的荧光传感器使得可以检测多个神经化学物质 在普遍定义的自由动物的神经元中。第四，多模式操作和定制的图形 用户界面（GUI）提供了一个易于使用的自动数据分析和闭环的控制界面 光遗传学和/或药理操作，从而实现可调节和按需的 神经调节。最后，磁共振耦合和无线数据通信允许完全无线， 无电池操作，从而实现了轻质的构造并消除了对电池寿命的担忧 充电状态以及在行为测试期间经常出现的其他问题，同时 允许动物自由移动。拟议研究的成功完成将产生无线的“ 一对一的”闭环神经探针具有几种创新特征，用于神经化学监测和 自由移动行为期间的光遗传学和/或药理刺激。我们相信这些神经问题 神经科学界的神经科学基础研究以及研究将引起人们的极大兴趣 与大脑倡议有关的各种情况下与疾病相关的过程的。

项目成果

Multiplexed Monitoring of Neurochemicals via Electrografting-Enabled Site-Selective Functionalization of Aptamers on Field-Effect Transistors.

• DOI: 10.1021/acs.analchem.1c05531
• 发表时间: 2022-06-21
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Gao, Zan;Wu, Guangfu;Song, Yang;Li, Huijie;Zhang, Yuxuan;Schneider, Michael J.;Qiang, Yingqi;Kaszas, Jackson;Weng, Zhengyan;Sun, He;Huey, Bryan D.;Lai, Rebecca Y.;Zhang, Yi
• 通讯作者: Zhang, Yi

Covalently Attached Slippery Surface Coatings to Reduce Protein Adsorptions on Poly(dimethylsiloxane) Planar Surfaces and 3D Microfluidic Channels

• DOI: 10.1021/acsami.2c20834
• 发表时间: 2023-02-10
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Cao, Yue;Chen, Xingchi;Zhang, Yi
• 通讯作者: Zhang, Yi