Multianalyte Nanoprobe for Neurochemicals

用于神经化学物质的多分析物纳米探针

• 批准号: 8738715
• 负责人: Jesus Delgado Alonso
• 金额: $ 29.47万
• 依托单位: INTELLIGENT OPTICAL SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-13 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8738715
• 关键词: Address; Area; Binding; Biochemical; Biological Neural Networks; Brain; Calcium; Calcium ion; Caliber; California; Cells; Chemicals; Concentration measurement; Consult; Detection; Disease; Dopamine; Effectiveness; Electrodes; Elements; Endorphins; Epilepsy; Evaluation; Event; Fiber; Geometry; Glass; Glutamine; Government; Hand; Histamine; Hydrogen Sulfide; Immobilization; In Vitro; Individual; Kinetics; Lead; Left; Legal patent; Light; Los Angeles; Maps; Measures; Microelectrodes; Monitor; Neurobiology; Neurologic; Neurons; Neurosciences; Neurotransmitters; Noise; Norepinephrine; Optics; Oxygen; Persons; Phase; Physiological; Polymers; Preparation; Reaction Time; Reporting; Resolution; Serotonin; Signal Transduction; Slice; Solutions; Stroke; Structure; Surface; System; Techniques; Technology; Testing; Time; Toxin; Tryptophan; Universities; Work; base; brain cell; crosslink; extracellular; in vivo; interest; millisecond; nanoprobe; neurochemistry; optical fiber; optical sensor; public health relevance; sensor; small molecule; submicron; tool

DESCRIPTION (provided by applicant): In cellular and extracellular studies of individual neurons and neural networks, it is imperative to monitor both electrophysiological and neurochemical activity. Electrochemical probes have now been fabricated at a size scale appropriate for such studies, but many neurotransmitters cannot be detected electrochemically. Furthermore, chemically-sensitive electrodes often consume their target analytes; at the sub-micron size scales of interest, this can lead to significant perturbation of the system being studied. Intelligent Optical Systems (IOS), working with the University of California Los Angeles (UCLA), proposes to create a new tool for cell-level studies of neurochemistry - a probe that can measure the concentrations of multiple analytes in sub- micron volumes. In this proposed sensor a multi-channel optical waveguide structure, tapered to a size smaller than the wavelengths of light it uses, will be functionalized with fluorescent indicators that react reversily with target substances. This unique probe will enable continuous monitoring of localized neurochemical concentrations on a time scale of milliseconds. During Phase I of the proposed project, IOS will construct 3- and 4-channel "nanoprobes" and, consulting with UCLA, will activate them with chemical- and biochemical-based recognition systems for analytes of interest. Optically-activated crosslinking will immobilize organic indicators embedded in permeable polymer "dots" directly in the near field of optical channels for detection of ionic species (e.g., Ca++) and small molecules. For other species of interest, photoactivated binding will be used to form a layer of patented biochemical "reversible chemical recognition units" in the optical field. After fabrication, these probes will be calibrated in stock solutions containing their target molecules, and then used to study extracellular analyte levels in ex vivo (cultured) neurons and brain slices to demonstrate their effectiveness in studying critically important neurobiological phenomena. In Phase II, in vivo applications will be investigated. Ultimately, the IOS-UCLA team plans to combine these optical neuro-nanoprobes with microelectrode-based sensors of similar size to create arrays with large numbers (>100) of multifunction probes for simultaneous electrical and chemical mapping of neurological activity at a scale out of reach, and a level of chemical detail currently out of reach with state-of-the-art technology.

描述（由申请人提供）：在单个神经元和神经网络的细胞和细胞外研究中，必须监测电生理和神经化学活性。电化学探针现在已经被制造成适合于这种研究的尺寸尺度，但是许多神经递质不能被电化学检测。此外，化学敏感电极通常消耗其目标分析物;在感兴趣的亚微米尺寸尺度下，这可能导致正在研究的系统的显著扰动。智能光学系统（IOS）与加州大学洛杉矶分校（UCLA）合作，提出创建一种用于神经化学细胞水平研究的新工具-一种可以测量亚微米体积中多种分析物浓度的探针。在这个提出的传感器中，多通道光波导结构，锥形到小于它使用的光的波长的尺寸，将与荧光指示剂功能化，与目标物质发生可逆反应。这种独特的探针将能够在毫秒的时间尺度上连续监测局部神经化学物质的浓度。在拟议项目的第一阶段，内部监督办公室将建造3通道和4通道的“纳米探针”，并与加州大学洛杉矶分校协商，将用化学和生物化学识别系统激活它们，以识别感兴趣的分析物。光活化交联将使嵌入可渗透聚合物“点”中的有机指示剂直接在光通道的近场中用于检测离子物质（例如，Ca++）和小分子。对于其他感兴趣的物种，光活化结合将用于形成一层专利的生物化学“可逆化学识别单元”在光学领域。制造后，这些探针将在储备溶液中进行校准， 它们的靶分子，然后用于研究离体（培养的）神经元和脑切片中的细胞外分析物水平，以证明它们在研究至关重要的神经生物学现象中的有效性。在第二阶段，将研究体内应用。最终，IOS-UCLA团队计划将这些光学神经纳米探针与类似尺寸的基于微电极的传感器结合联合收割机，以创建具有大量（>100）多功能探针的阵列，用于同时进行神经活动的电学和化学映射，其规模超出了目前最先进的技术水平。