Microfabricated Neural Probe for the Rapid Detection of Multiple Neurochemicals I

用于快速检测多种神经化学物质的微型神经探针 I

• 批准号: 8739598
• 负责人: Brian Glenn Jamieson
• 金额: $ 19.02万
• 依托单位: DIAGNOSTIC BIOCHIPS, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-25 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8739598
• 关键词: Accounting; Achievement; Acute; Adenosine; Alcohol consumption; Animals; Area; Behavior; Behavioral; Biomedical Research; Biosensor; Brain; Cell Separation; Chemicals; Collection; DNA; Data; Data Collection; Decision Making; Detection; Disease; Dopamine; Electrodes; Engineering; Enzymes; Ethanol; Event; Feasibility Studies; Glutamates; Hour; Immobilization; Implant; Lead; Legal patent; Length; Letters; Life; Longevity; Measurement; Measures; Methods; Microdialysis; Microelectrodes; Modification; Mus; Neurons; Neurosciences; Neurosciences Research; Neurotransmitters; Parkinson Disease; Pattern; Pharmaceutical Preparations; Pharmacodynamics; Phase; Process; Rattus; Reaction Time; Recovery; Research Personnel; Resolution; Role; Scanning; Seizures; Services; Signal Transduction; Site; Stimulus; Surface; System; Techniques; Technology; Telemetry; Testing; Therapeutic; Time; Tissues; Transplantation; Work; aptamer; ascorbate; base; carbon fiber; clinical application; commercialization; cost; design; experience; gamma-Aminobutyric Acid; improved; in vivo; microsystems; neurochemistry; optogenetics; prototype; public health relevance; rapid detection; relating to nervous system; research study; response; sensor; success; technology development; tool

DESCRIPTION (provided by applicant): The specific aim of this application is to test the feasibility of developing a long-lasting, implantable probe for rapid measurement of multiple neurochemicals in the brain. Currently, neuroscience research is limited to three techniques for measuring the concentrations of neurochemicals in vivo; microdialysis to obtain average concentrations over a relatively long time period (5-20 minutes), enzyme-based biosensors to detect a single neurochemical every second over a relatively large spatial area (500¿m length electrode), and carbon-fiber microelectrodes to detect dopamine with fast scan cyclic voltammetry (FSCV). A new tool is required for rapid detection of concentrations of multiple neurochemicals with spatial resolution on the cellular level. Such a tool would allow neuroscience researchers to ask new questions about the mechanisms behind disease states and behaviors, such as alcohol drinking. The proposed neural probe fulfills this need by detecting two neurochemicals every 4 seconds with 50 ¿m spatial resolution. SB Microsystems has already developed a proprietary MEMS process for fabricating implantable, multi-site neural probes for studying the rat brain. Our existing probes have the feature size necessary for a 10-fold spatial resolution improvement over the available enzyme-based electrodes. The proposed probe will build on our existing platform by functionalizing the probe site surfaces with molecules for the detection of specific neurochemicals. Detection of multiple neurochemicals will be achieved by patterning different neurochemical- specific detection molecules onto adjacent probe sites. Our Phase I application will determine feasibility for commercialization of these probes by; 1) improving functionalized probe fabrication by adjusting aptamer molecule modifications, immobilization technique, and electrical signal detection to achieve the best possible sensitivity and time response, 2) developing a potentiostat circuit based for detection, 3) developing two aptamer molecules; one that is specific, sensitive, and long-lasting for ethanol, and another for GABA. Next, we will 4) functionalize the probe to detect multiple analytes with the newly develop aptamers and 5) implant probes into mice for in vivo data collection. Success in this Phase I feasibility study will be determined by the accurate detection of physiologically relevant concentrations of ethanol and GABA by probes that are stable in vivo for 2 days. In Phase II, we plan to develop more aptamers that can be applied to our probes for the detection of more than 2 neurotransmitters. We will use principles of robust design to turn our prototype into a commercial product. The attached letters of support indicate that we may be able to sell a successful prototype from Phase I to neuroscience researchers. !

描述（由应用程序提供）：本应用的具体目的是测试开发持久的可植入探针以快速测量大脑中多种神经化学物质的可行性。目前，神经科学研究仅限于测量体内神经化学物质浓度的三种技术。在相对长时间（5-20​​分钟）内获得平均浓度的微透析，基于酶的生物传感器每秒在相对较大的空间区域（500€Menthend Electrode）和碳纤维微电极在相对较大的空间区域内每秒检测到单个神经化学，以检测具有快速扫描式环状电触电（FSCL）的多巴胺（FSCV）。需要一种新的工具来快速检测具有细胞水平空间分辨率的多种神经化学物质的浓度。这样的工具将使神经科学研究人员能够向疾病状态和行为（例如饮酒）的机制提出新问题。提出的神经探针通过每4秒检测两种神经化学物质，以50？m的空间分辨率来满足这一需求。 SB微型系统已经开发了一个专有的MEMS过程，用于制造可植入的多站点神经问题来研究大鼠脑。我们现有的问题具有比可用的基于酶的电极进行10倍空间分辨率改进所需的特征大小。所提出的探针将通过用分子功能功能化探针位点表面来构建我们的现有平台 通过将不同神经化学特异性检测分子模式化到相邻的探针位点，可以实现多种神经化学物质的检测。我们的I阶段应用将确定这些问题商业化的可行性； 1）通过调整APATMER分子的修饰，固定技术和电信号检测来改善功能化探针的制造以达到最佳的敏感性和时间响应，2）开发基于检测的潜在静态电路，3）开发两个APATMER分子；一种是特定，敏感且对乙醇的持久，另一个是GABA。接下来，我们将4）功能化探针以检测新开发的apatamers和5）在体内数据收集中植入小鼠中的多个分析物。在这一阶段，I可行性研究将取决于通过体内稳定2天稳定的问题准确检测物理相关乙醇和GABA的浓度。在第二阶段，我们计划开发更多的适体，这些适体可以应用于我们的探针以检测2个以上的神经递质。我们将使用强大的设计原理将原型变成商业产品。附带的支持信，表明我们可能能够将成功的原型从I期出售给神经科学研究人员。呢