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

脑间质液微创生化取样用于研究神经病理学

• 批准号: 9885472
• 负责人: Michael J Cima
• 金额: $ 62.86万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9885472
• 关键词: Acetylcholine; Address; Agonist; Alloys; Analytical Chemistry; Animal Model; Animals; Anxiety; Behavior; Biochemical; Biological Markers; Biomedical Engineering; Blood capillaries; Brain; Brain region; Caliber; Characteristics; Chemicals; Chronic; Clinical; Cocaine; Collection; Coupled; Detection; Devices; Diffusion; Disease; Dynorphins; Family; Functional disorder; Future; Glutamates; Goals; Health; Human; Implant; In Vitro; Intercellular Fluid; Knowledge; Lead; Legal; Link; Liquid Chromatography; Liquid substance; Longitudinal Studies; Measurable; Measurement; Measures; Membrane; Memory; Methods; Microdialysis; Microfabrication; Microinvasive; Molecular; Monitor; Neuropeptides; Neurosciences; Neurotransmitters; Nucleus Accumbens; Opioid; Pathologic; Pathology; Pharmaceutical Preparations; Physiological; Pump; Rattus; Relapse; Resolution; Rodent; Rodent Model; Role; Sampling; Scientist; Self Administration; Shapes; Stress; Substance Use Disorder; Substance abuse problem; System; Techniques; Technology; Testing; Time; Translations; Wireless Technology; Withdrawal; accurate diagnosis; acute stress; addiction; analytical tool; biomaterial compatibility; design; flexibility; fluid flow; gamma-Aminobutyric Acid; human disease; human model; implantable device; in vivo; insight; kappa opioid receptors; materials science; mechanical properties; minimally invasive; monitoring device; nanofluidic; negative emotional state; neural circuit; neurochemistry; nitinol; relating to nervous system; response; sample collection; social; spatiotemporal; subcutaneous; tandem mass spectrometry; temporal measurement; tool

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.

项目总结