Miniaturized silicon neurochemical probe to monitor brain chemistry

用于监测大脑化学物质的微型硅神经化学探针

• 批准号: 10401696
• 负责人: Yurii Vlasov
• 金额: $ 321.91万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-03 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10401696
• 关键词: Abeta clearance; Address; Adopted; Adoption; Amyloid beta-Protein; Animals; Area; Behavior; Brain; Brain Chemistry; Chemicals; Collection; Communities; Development; Dialysis procedure; Drug Delivery Systems; Electrochemistry; Electrophysiology (science); Elements; Extracellular Fluid; Generations; Gonadotropins; Grant; Hippocampus (Brain); Hormones; Hypothalamic structure; Industry; Intervention; Kinetics; Label; Libraries; Location; Mass Spectrum Analysis; Measures; Membrane; Methods; Microfluidics; Monitor; Neurobiology; Neuromodulator; Neurons; Neurosciences; Neurosecretory Systems; Neurotransmitters; Optics; Pharmaceutical Preparations; Pharmacology; Proteins; Readiness; Research; Resolution; Sampling; Seizures; Series; Signal Transduction; Silicon; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stress; Stress Tests; System; Technology; Thinness; Time; Tissues; Trust; Validation; awake; design; detection limit; experimental study; flexibility; gamma-Aminobutyric Acid; glymphatic system; in vivo; information processing; innovation; local drug delivery; microelectronics; miniaturize; nano-electrospray; nanodialysis; nervous system disorder; neural circuit; neural correlate; neurochemistry; neuroregulation; optogenetics; relating to nervous system; small molecule; spatiotemporal; temporal measurement; translational applications

PROJECT SUMMARY/ABSTRACT Miniaturized silicon neurochemical probe to monitor brain chemistry. Monitoring local concentrations of neurochemicals in specific parts of the brain in vivo is critical for correlating neural circuit functionality to behavior as long-range neuromodulation can significantly alter information processing. Current methods for detecting neuromodulators have limited temporal and/or spatial resolution, limited sensitivity, and/or are prohibitively invasive. The objective of this grant is to develop a versatile silicon technology platform for the design and fabrication of implantable nanodialysis probes that enable fast (1sec) and sensitive (100nM) sampling of multiple neurochemicals from the alive and behaving mammalian brain. The Application-Specific Integrated Nano-Dialysis (ASIND) technology allows collection in a time-sequential manner a series of isolated pL-volume analytes from the brain extracellular fluid (ECF) with high chemical information content. Once collected and stored on-chip, these analytes are delivered for subsequent ultra-sensitive mass spectrometry (MS) analysis to monitor temporal profiles of several important neurochemicals (from 100Da up to 5KDa). To extend the applicability of the ASIND technology to a large number of diverse neurobiology experiments, we develop, validate and integrate advanced microfluidic components with add-on functionalities (multiplexed chemical sampling, local drug delivery, electrophysiology, electrochemistry, optogenetics, and nano-electrospray) into a system-on-chip on a silicon implantable neural probe with a significantly reduced cross-section (<1000 µm2) equivalent to just a few neuron bodies across. To stress-test the technology and demonstrate its advanced capabilities to study the chemical brain, we adapt the platform to three different neurobiological experiments to address important open questions that are difficult or impossible to explore with traditional approaches. Such development extends the technology readiness level from a demonstration of basic capabilities to proof-of-concept validation for both scientific and translational applications in various areas of neuroscience This contribution is significant since the instrumental platform will allow monitoring concentration gradients of various neuromodulators and drugs from precise brain locations time-synchronized with recordings of neural activity and behavior that should enable advances in fundamental systems neuroscience as well as accelerate the development of new treatments for neurological diseases. The proposed research is innovative because we will develop highly sensitive nanodialysis probes on a silicon platform that allows us to attain unprecedented temporal and spatial resolution. The developed and verified ASIND silicon platform will significantly facilitate the broad dissemination of this manufacturable technology.

项目总结/摘要 微型硅神经化学探针监测脑化学。 监测体内大脑特定部位的神经化学物质的局部浓度对于将神经回路功能与行为相关联至关重要，因为远程神经调节可以显著改变信息处理。用于检测神经调质的当前方法具有有限的时间和/或空间分辨率、有限的灵敏度和/或具有禁止性侵入性。这项资助的目的是开发一种多功能的硅技术平台，用于设计和制造可植入的纳米透析探针，使其能够快速（1秒）和灵敏（100 nM）地从活的和行为的哺乳动物大脑中采集多种神经化学物质。特定应用集成纳米透析（ASIND）技术允许以时间顺序的方式从脑细胞外液（ECF）中收集一系列具有高化学信息含量的分离的pL体积分析物。一旦收集并存储在芯片上，这些分析物将用于随后的超灵敏质谱（MS）分析，以监测几种重要神经化学物质（从100 Da到5 KDa）的时间分布。为了将ASIND技术的适用性扩展到大量不同的神经生物学实验，我们开发，验证和集成了具有附加功能的先进微流体组件（多重化学取样，局部药物递送，电生理学，电化学，光遗传学，和纳米电喷雾）到具有显著减小的横截面的硅可植入神经探针上的片上系统中（<1000 µm2）相当于几个神经元体。为了对该技术进行压力测试并展示其研究化学大脑的先进能力，我们将该平台应用于三种不同的神经生物学实验，以解决传统方法难以或不可能探索的重要开放问题。这种发展将技术准备水平从基本能力的演示扩展到神经科学各个领域的科学和转化应用的概念验证。这一贡献是重要的，因为仪器平台将允许从精确的大脑位置监测各种神经调质和药物的浓度梯度。与神经活动和行为的记录同步，这应该能够促进基础系统神经科学的进步，并加速神经系统疾病新疗法的开发。这项研究是创新的，因为我们将在硅平台上开发高灵敏度的纳米透析探针，使我们能够获得前所未有的时间和空间分辨率。开发和验证的ASIND硅平台将大大促进这种可制造技术的广泛传播。