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: 8453739
• 负责人: Brian Glenn Jamieson
• 金额: $ 18.99万
• 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/8453739
• 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（由申请人提供）：本申请的具体目的是测试开发用于快速测量大脑中多种神经化学物质的持久、可植入探针的可行性。目前，神经科学研究仅限于三种测量体内神经化学物质浓度的技术：微透析，以获得相对较长时间内的平均浓度（5-20分钟），酶基生物传感器在相对较大的空间区域内每秒检测一种神经化学物质（500 μ m长的电极）和碳纤维微电极以用快速扫描循环伏安法（FSCV）检测多巴胺。需要一种新的工具来快速检测细胞水平上具有空间分辨率的多种神经化学物质的浓度。这样的工具将允许神经科学研究人员提出关于疾病状态和行为背后机制的新问题，例如饮酒。所提出的神经探针通过以50 μ m的空间分辨率每4秒检测两种神经化学物质来满足这一需求。SB微系统公司已经开发出一种专有的MEMS工艺，用于制造可植入的多部位神经探针，用于研究大鼠大脑。我们现有的探针具有比现有的基于酶的电极提高10倍空间分辨率所需的特征尺寸。所提出的探针将建立在我们现有的平台上，通过用分子功能化探针位点表面 用于检测特定的神经化学物质。多种神经化学物质的检测将通过将不同的神经化学特异性检测分子图案化到相邻的探针位点上来实现。我们的I期申请将通过以下方式确定这些探针商业化的可行性：1）通过调整适体分子修饰、固定技术和电信号检测来改进功能化探针制造，以实现最佳可能的灵敏度和时间响应，2）开发基于检测的恒电位电路，3）开发两种适体分子;一种对乙醇具有特异性、敏感性和持久性，另一种对GABA具有特异性、敏感性和持久性。接下来，我们将4）用新开发的适体使探针功能化以检测多种分析物，5）将探针植入小鼠体内用于体内数据收集。本I期可行性研究的成功将通过使用在体内稳定2天的探针准确检测乙醇和GABA的生理相关浓度来确定。在第二阶段，我们计划开发更多适体，可应用于我们的探针，用于检测2种以上的神经递质。我们将使用稳健设计的原则，将我们的原型变成商业产品。所附的支持信表明，我们可能能够出售一个成功的原型，从第一阶段的神经科学研究人员。!