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

摘要 本提案的目标是开发一种多模态、多分析物传感器系统，包括有线和无线传感器。 电子和软件。这套新的工具将能够同时记录电流传感器 （谷氨酸、葡萄糖、乳酸、胆碱和/或氧）、电生理学和快速扫描循环伏安法 （生物胺）在有意识的，自由移动的啮齿动物。拟议的阵列和测量系统将使 同步测量啮齿类动物大脑中的化学和电状态。该套房将包括 新的仪器和软件，用于同时、同步的数据收集和新的功能化的 四极阵列，这将使记录的多种形式和分析物在一个单一的位置在大脑中。 理想的多模态传感器将在最小的体积内支持各种各样的测量， 化学或电串扰，并且不改变传感器的局部环境，同时允许长时间的 术语，可量化，高空间和时间分辨率，仅测量分析物/现象， 兴趣在实践中，所有测量模式都是有限的，但通过将多种模式组合在一个单一的， 可配置的探针，研究人员可以利用个别技术的优势，以最好地适应 实验在手大脑-2025报告（https：//brainitiative.nih.gov/strategic-planning/brain-2025-report） 国家： “我们的任务是了解引起心理体验的神经活动的回路和模式， 行为为了实现这一目标，任何电路都需要对其组件单元类型、其局部 和长距离突触连接，它们随时间的电和化学活性，以及功能性突触连接。 这种活动在电路、大脑和行为层面上的后果。结合这些元素， 即使对一个电路来说也非常困难，但我们也必须将许多联锁电路编织在一起 在一个大脑里。正如总统在白宫的记者招待会上所说，这确实是一个“巨大的挑战 为21世纪而战。” 拟议的功能化四极阵列，仪器和支持软件将为研究人员提供 实验的灵活性需要追求这些目标，同时确保实验的一致性（机械 设计），数据质量（电子设计），实验灵活性（软件设计），最大限度地提高整体 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.