Micro-invasive biochemical sampling of brain interstitial fluid for investigating neural pathology

项目摘要 这项研究的目的是为材料科学家，生物医学工程师，分析化学家， 麻省理工学院的神经科学家开发了一种微创植入式设备，用于监测生物化学成分 不同的大脑区域。这种用于对脑间质液（ISF）中的神经化学物质进行采样的分析工具承诺 为生理和病理状态下神经回路的动力学提供有价值的见解。我们将 应用此工具研究神经肽在物质使用障碍（SUD）中的作用。强啡肽家族 长期以来，神经肽一直与成瘾有关，但目前还没有分析工具能够调查 这些神经化学物质在体内的长期时空动力学。我们的目标是证明 我们的采样平台在测量SUD啮齿动物模型中的神经肽表达动态。这将 更深入地了解成瘾和戒断的生化基础，但也许更重要的是， 建立我们的技术作为一种有效的技术，了解神经系统疾病的发病和发展， 疾病我们的具体目标概括如下：1）设计一种微创的植入式装置 用于在体内长期采样ISF。该装置将由纳米流体泵（纳米泵）耦合到微流体泵（微流体泵）组成。 刻度探针（微探针），在转换为独立探针之前在体外优化了流体流动特性 体内装置。2)优化小体积ISF样品的储存和处理，通过 纳米泵，用于通过液相色谱-串联质谱法（LC-MS/MS）分析。3)确定 在体外ISF中强啡肽神经肽家族的检测限， 在生理和病理浓度下的体内样品中。4)对强啡肽进行短期监测 在基线和急性应激中，以证明该工具在跟踪这些大神经肽中的功效， 实时的5)在可卡因SUD的啮齿动物模型中追踪神经肽的强啡肽家族， 深入了解物质戒断和复发的生化基础。我们的目标是证明 该采样平台在体内的功能，并建立其精确监测神经肽动力学的能力， 时空控制我们的目标是为神经科学家提供一种新的工具， 在成熟的动物模型中进行神经病理学的研究，使神经病理学的诊断和治疗更加准确。 在未来的人类疾病。

Project Summary The purpose of this study is for a team of materials scientists, biomedical engineers, analytical chemists, and neuroscientists at MIT to develop a micro-invasive implantable device for monitoring the biochemical composition of distinct brain regions. This analytical tool for sampling neurochemicals in brain interstitial fluid (ISF) promises to provide valuable insight into the dynamics of neural circuits in physiological and pathological states. We will apply this tool to study the role of neuropeptides in substance use disorder (SUD). The dynorphin family of neuropeptides has long been implicated in addiction, but no current analysis tool has been able to investigate the long-term spatiotemporal dynamics of these neurochemicals in vivo. Our goal is to demonstrate the efficacy of our sampling platform in measuring neuropeptide expression dynamically in a rodent model of SUD. This will lend greater insight into the biochemical basis of addiction and withdrawal, but perhaps more importantly establish our technology as an effective technique for understanding the onset and progression of neural diseases. Our specific goals are summarized as follows: 1) Design a minimally invasive and implantable device for sampling ISF chronically in vivo. The device will consist of a nanofluidic pump (nanopump) coupled to micro- scale probes (microprobes), with fluid flow characteristics optimized in vitro prior to translation to a stand-alone in vivo device. 2) Optimize the storage and processing of small volumes of sampled ISF, withdrawn via nanopump, for analysis via liquid chromatography-tandem mass spectrometry (LC-MS/MS). 3) Determine the detection limits for the dynorphin neuropeptide family in ISF in vitro prior to detection of these neurochemicals in in vivo samples at physiological and pathological concentrations. 4) Perform short-term monitoring of dynorphin at baseline and in acute stress to demonstrate the efficacy of this tool in tracking these large neuropeptides in real-time. 5) Track the dynorphin family of neuropeptides in a rodent model of cocaine SUD, lending greater insight into the biochemical basis of substance withdrawal and relapse. Our aim is to demonstrate the failsafe function of this sampling platform in vivo and establish its ability to monitor neuropeptide dynamics with precise spatiotemporal control. We aim to provide neuroscientists with a new tool for investigating the biochemical basis of neural pathology in well-established animal models, enabling more accurate diagnosis and treatment of neural disorders in humans in the future.