Functionalized Multi-Modal Tetrode Arrays for Real-Time, Site-Specific Neurochemical Monitoring

摘要 这项提议的目标是开发一种多模式、多分析的传感器系统，包括有线和无线 电子产品和软件。这套新工具将使安培传感器能够同时记录 (谷氨酸、葡萄糖、乳酸、胆碱和/或氧气)、电生理学和快速扫描循环伏安法 (生物胺)在清醒的、自由活动的啮齿动物中。拟议的阵列和测量系统将使 对啮齿类动物大脑中化学和电学条件的同步测量。这间套房将包括 用于同步、同步数据收集的新仪器和软件以及新的功能化 四极管阵列，可以在大脑中的一个位置记录多个模式和分析物。 理想的多模式传感器应该在最小的体积内支持各种测量，没有 化学或电气串扰，而不改变传感器的局部环境，同时允许长时间- 术语，可量化，高空间和时间分辨率，仅对分析物/现象进行测量 利息。在实践中，所有测量模式都是有限的，但是通过将多个模式组合成单个， 可配置的探头，研究人员可以利用各种技术的优势来最适合 实验近在咫尺。《大脑-2025年报告》(https://braininitiative.nih.gov/strategic-planning/brain-2025-report) 州/州： 我们的任务是了解神经活动的回路和模式，这些回路和模式产生精神体验和 行为。要实现任何电路的这一目标，都需要其组件单元类型、其本地 和长距离突触连接，它们随时间的电和化学活动，以及功能 这种活动在电路、大脑和行为层面上的后果。将这些元素组合在 即使对于一个电路来说也是非常困难的，但我们还必须将许多联锁电路编织在一起 在一个单独的大脑里。正如总统在白宫记者会上所说，这确实是一项“巨大的挑战 为21世纪服务。“ 拟议的功能化四极管阵列、仪器和支持软件将为研究人员提供 在确保实验一致性的同时实现这些目标所需的实验灵活性(机械 设计)、数据质量(电子设计)、实验灵活性(软件设计)、最大化总体 可重复性，同时最大限度地减少啮齿动物的使用。

ABSTRACT The goal of this proposal is to develop a multimodal, multianalyte sensor system including wired and wireless electronics and software. This new suite of tools will enable simultaneous recording of amperometric sensors (glutamate, glucose, lactate, choline, and/or oxygen), electrophysiology, and fast-scan cyclic voltammetry (biogenic amines) in conscious, freely moving rodents. The proposed array and measurement system will enable the synchronous measurement of chemical and electrical conditions in the rodent brain. This suite will include new instrumentation and software for simultaneous, synchronized data collection and a novel functionalized tetrode array that will enable the recording of multiple modalities and analytes at a single location in the brain. An ideal multi-modal sensor would support a wide variety of measurements in a minimal volume, with no chemical or electrical crosstalk and without altering the local environment of the sensor, while allowing long- term, quantifiable, high spatial and temporal resolution, measurements of only the analytes/phenomena of interest. In practice, all measurement modalities are limited, but by combining multiple modalities in a single, configurable probe, researchers can leverage the strengths of the individual techniques to best suit the experiment at hand. The Brain-2025 Report (https://braininitiative.nih.gov/strategic-planning/brain-2025-report) states: “Our charge is to understand the circuits and patterns of neural activity that give rise to mental experience and behavior. To achieve this goal for any circuit requires an integrated view of its component cell types, their local and long‐range synaptic connections, their electrical and chemical activity over time, and the functional consequences of that activity at the levels of circuits, the brain, and behavior. Combining these elements is at present immensely difficult even for one circuit, yet we must also weave together the many interlocking circuits in a single brain. As the President said in his White House press conference, this is indeed a “grand challenge for the 21st century.” The proposed functionalized tetrode array, instrumentation, and support software will give researchers the experimental flexibility required to pursue these goals while ensuring experimental consistency (mechanical design), data quality (electronics design), experimental flexibility (software design), maximizing overall reproducibility while minimizing rodent use.