Multiplexed chemical sensing on ultra-narrow electrophysiological neural probes

超窄电生理神经探针的多重化学传感

基本信息

批准号：
8684951
负责人：
MICHAEL L ROUKES
金额：
$ 23.95万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-15 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8684951
关键词：
Acetylcholine Adoption Animals Architecture Biochemical Brain Brain region Chemicals Choline Collaborations Commit Communities Data Analyses Detection Development Dopamine Electrodes Electrophysiology (science)Engineering Evaluation Evolution Figs - dietary Foundations Generations Goals Heterogeneity Hippocampus (Brain)In Vitro Individual Institutes Laboratories Lead Length Letters Maps Measurement Medicine Mus Nanotechnology Neuromodulator Neurosciences Neurotransmitters Parkinson Disease Phase Play Rattus Reaction Time Research Resolution Role Sampling Schizophrenia Silicon Site Specificity Structure Technology Thick Time Triad Acrylic Resin Validation Variant Vertebrates Work awake base brain research brain tissue college density design direct application improved in vivo insight interest nanopattern nanoprobe nanoscale nervous system disorder neurochemistry neuroregulation novel programs prototype public health relevance relating to nervous system research study response sensor spatiotemporal time use tool

项目摘要

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.

描述（由适用提供）：在体内绘制空间时间电化学反应，尤其是在清醒脊椎动物的大脑中，可以阐明神经调节在脑活动中的作用。但是，神经科学中的当前工具不足以完成任务。在过去的十年中，电生理学的多重神经探针技术的进步提高了简单电记录的复杂性和空间分辨率，这些记录现在已经在脑组织内实现了。最新的艺术品由我们正在开发的基于硅的神经元纳米探针来表示，以实现1000个位点的简单体内电气记录。相比之下，可以在体内实现局部电化学传感器的探针并没有与电生理学方面的这些进步保持敏捷。尽管如此，对电化学传感器的改进，用于在体内检测感兴趣的个体神经调节剂，例如多巴胺和乙酰胆碱 - 现在可以分别通过〜400？m和〜1秒钟的空间和临时分辨率在物理相关水平上进行局部敏感性。我们建议利用我们在工程高度多路复用的纳米探针中获得的专业知识来进行电生理学，并基于体内电化学感应的最新改进，以开发新一代的高度多重，多位多的神经纳米诺杆菌，以简单的神经元素的简单电化学感应多神经化学感应。这些问题将在狭窄（〜50？m）硅柄的狭窄（〜5mm）中进行制造，这对于大脑记录而言是最佳的；在这些上将集成一系列化学敏感性“三合会”。每个三合会将完成三个不同的位点，以实现神经化学靶标的安培敏感性（例如多巴胺，乙酰胆碱和胆碱），这些三合会的线性阵列将沿着探头柄组装，这些三合会的线性阵列将组装为小于100滴。这些传感器阵列将可以简单地检测大脑扩展区域的多个不同神经调节剂靶标的空间时间变化。一个重要的应用是对大鼠，小鼠和其他小动物的大脑的多层皮质和海马层进行采样神经调节剂的变化，在这些大鼠，小鼠和其他小动物中，单个层厚度可以为〜100？m。我们将在这项工作中开发的先进的，基于探测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化打开新窗口。