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.

项目概要/摘要 包括光遗传学和药理学在内的新兴工具和技术提供了重要途径 然而，尽管进行了大量工作，实现闭环仍然具有挑战性。 以允许动物自由运动、多模式操作和多路复用的方式进行神经调节 以高灵敏度、选择性、时空分辨率和细胞特异性监测神经化学物质， 同时，我们的长期目标是开发支持这些功能的先进工具和方法。 我们的近期目标是开发无线、 用于自由光遗传学、药理学和神经化学监测的闭环神经探针系统 我们将通过追求以下三个具体目标来实现这一目标：（1）发展。 用于高时空选择性和灵敏监测神经化学物质的软神经探针 分辨率和细胞特异性；（2）开发用于光遗传学的无线闭环神经探针， 药理学和神经化学监测；（3）评估和表征效率和 无线闭环神经探针在自由移动的小鼠和大鼠体内的功能。 研究具有创新性有五个关键原因：首先，适配体增强石墨烯场效应晶体管（AeG- FET）将适配体的高选择性与 G-FET 的高灵敏度相结合，从而实现灵敏 （飞摩尔）和选择性（> 19 倍）神经化学物质的检测 其次，近细胞尺度的尺寸。 (50 μm x 50 μm)、快速响应时间 (~1 s) 和 AeG-FET 的位点选择性功能化使得 监测多种神经化学物质，包括多巴胺、血清素、去甲肾上腺素和神经肽 Y， 第三，结合最先进的基因编码。 带有无线多色光度计的荧光传感器可以检测多种神经化学物质 第四，多模式操作和定制图形。 用户界面 (GUI) 为闭环提供强大、易于使用的自动化数据分析和控制界面 光遗传学和/或药理学操作，从而实现可调节和按需 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，从而实现轻量化结构并消除对电池寿命的担忧， 充电状态以及在扩展行为测试中经常出现的其他问题，同时 允许动物自由移动。所提议的研究的成功完成将产生无线的、“全- In-one”闭环神经探针具有多项创新功能，可用于神经化学监测和 我们相信这些神经探针在自由移动行为过程中受到光遗传学和/或药理学刺激。 神经科学界将对神经科学的基础研究以及研究产生极大的兴趣 与 BRAIN 计划相关的各种背景下的疾病相关过程。

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