Multiplexed chemical sensing on ultra-narrow electrophysiological neural probes

描述（由申请人提供）：绘制体内时空电化学响应，特别是在清醒脊椎动物的脑内，可以阐明神经调节在脑活动中的作用。然而，目前神经科学的工具不足以完成这项任务。在过去的十年中，电生理学的多路神经探针技术的进步已经提高了脑组织内同步电记录的复杂性和空间分辨率。最先进的是硅基神经纳米探针，我们正在开发，使同时在体内电记录从1000个网站。相比之下，能够在体内进行局部电化学传感的探针没有跟上电生理学的这些进展。尽管如此，已经取得了改进，以电化学传感器在体内检测个别神经调质的利益，如多巴胺和乙酰胆碱-和局部传感在生理相关的水平，现在是可能的空间和时间分辨率~400？m和~1秒。我们建议利用我们在电生理学工程高度多路复用纳米探针中获得的专业知识，并建立在体内电化学传感的最新改进的基础上，开发新一代高度多路复用的多位点神经纳米探针，用于同时电化学传感体内多个神经调质靶点。探针将被制造为长（~ 5 mm）、窄（~50？m）硅柄，证明是大脑记录的最佳选择;在这些柄上将集成多种化学传感“三元组”。每个三联体将包括三个不同的位点，用于神经化学靶点的电流传感--例如多巴胺、乙酰胆碱和胆碱--这些三联体的线性阵列，以小于100 μ m的间距分开，将沿着探针柄沿着组装。这些传感器阵列将能够同时检测大脑中扩展区域内多个不同神经调节剂靶点的时空变化。一个重要的应用是沿着大鼠、小鼠和其他小动物的大脑的多个皮质和海马层采样神经调质变化，其中单个层厚度可以是~100 μ m。M.我们将在这项工作中开发的先进的基于探针的电化学传感技术将为分布式大脑区域的功能神经化学异质性的时空演变打开一个新的窗口。

DESCRIPTION (provided by applicant): Mapping spatiotemporal electrochemical responses in vivo, especially within the brains of awake vertebrates, can elucidate the role of neuromodulation in brain activity. However, present tools in neuroscience are insufficient for the task. In the past decade, advances in the technology of multiplexed neural probes for electrophysiology has improved both the complexity and the spatial resolution of simultaneous electrical recordings that are now possible within brain tissue. The state-of-the-art is represented by silicon-based neural nanoprobes that we are developing to enable simultaneous in vivo electrical recording from 1000 sites. Probes that enable local electrochemical sensing in vivo, by comparison, have not kept apace with these advances in electrophysiology. Nonetheless, improvements have been made to electrochemical sensors for in vivo detection of individual neuromodulators of interest, such as dopamine and acetylcholine -- and local sensing at physiologically relevant levels is now possible with spatial and temporal resolution of ~400?m and ~1 second, respectively. We propose to leverage the expertise we've gained in engineering highly multiplexed nanoprobes for electrophysiology, and to build upon the recent improvements of in vivo electrochemical sensing, to develop a new generation of highly multiplexed, multi-site neural nanoprobes for simultaneous electrochemical sensing of multiple neuromodulator targets in vivo. The probes will be fabricated as long (~5mm), narrow (~50?m) silicon shanks that prove optimal for brain recording; onto these will be integrated a multiplicity of chemical sensing "triads". Each triad will comprise three distinct sites for amperometric sensing of neurochemical targets -- for example, dopamine, acetylcholine, and choline -- and linear arrays of these triads, separated with less than 100¿m pitch, will be assembled along the probe shanks. These sensor arrays will enable simultaneous detection of the spatiotemporal variation of multiple different neuromodulator targets across extended regions in the brain. An important application is sampling neuromodulator variations along the multiple cortical and hippocampal layers of the brains of rats, mice and other small animals, where individual layer thicknesses can be ~100?m. The advanced, probe-based electrochemical sensing technology we will develop in this effort will open a new window into the spatiotemporal evolution of functional neurochemical heterogeneities across distributed brain regions.