Neural Probe for high spatial and temporal resolution detection of cocaine and su

描述(申请人提供)：这项提议的具体目的是测试开发一种长期的、可植入的探头的可行性，用于快速测量大脑中的多种神经化学物质。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；微透析法获得相对较长时间(5-20分钟)的平均浓度，酶生物传感器在相对较大的空间区域(500米长的电极)上每秒检测一种神经化学物质，以及碳纤维微电极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多种神经化学物质的浓度，并在细胞水平上具有空间分辨率。这样的工具将允许神经科学研究人员就疾病状态和行为背后的机制提出新的问题，例如药物消费。所提出的神经探测器满足了这一需求，它以50？m的空间分辨率每4秒检测两种神经化学物质。拟议的调查将检测可卡因和P物质，P物质是一种暗示可卡因成瘾的神经肽(Kampman，2010)。2008年，报告指出，140万美国人符合滥用或依赖可卡因的标准，这与暴力和监禁有关(NIDA，2010年；Nyamathi等人，2012年)。SB MicroSystems已经开发了一种专有的MEMS工艺，用于制造可植入的多点神经探针，用于研究大鼠的大脑。我们现有的探针具有所需的特征尺寸，空间分辨率比现有的基于酶的电极提高了10倍。拟议中的探测器将建立在我们现有平台的基础上，通过使用用于检测特定神经化学物质的分子来使探测器部位表面功能化。多种神经化学物质的检测将通过将不同的神经化学特定检测分子构图到相邻的探针点上来实现。我们的第一阶段计划将通过以下方式确定这些探针商业化的可行性：1)通过调整适配子分子修饰、固定技术和电信号检测来改进功能化探针制造，以获得最佳的灵敏度和时间响应；2)开发基于检测的恒电位电路。接下来，我们将3)使探头功能化，以使用可卡因和P物质适配子检测多种分析物；4)将探头植入大鼠体内收集数据。这项第一阶段可行性研究的成功将取决于通过在体内稳定2天的探针准确检测生理上相关的可卡因和P物质浓度。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，以检测两种以上的神经递质。我们将使用稳健设计的原则将我们的原型转化为商业产品。所附的支持信表明，我们可能能够将第一阶段的成功原型出售给神经科学研究人员。

DESCRIPTION (provided by applicant): The specific aim of this proposal 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 drug consumption. The proposed neural probe fulfills this need by detecting two neurochemicals every 4 seconds with 50 ¿m spatial resolution. The proposed probe will detect cocaine and substance P, a neuropeptide implied in cocaine addiction (Kampman, 2010). In 2008, reports stated that 1.4 million Americans meet the criteria for abuse or dependence on cocaine, which is associated with violence and incarceration (NIDA 2010; Nyamathi et al., 2012). 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 proposal 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 and 2) developing a Potentiostat circuit based for detection. Next, we will 3) functionalize the probe to detect multiple analytes with the cocaine and substance P aptamers and 4) implant probes into rats for in vivo data collection. Success in this Phase I feasibility study will be determined by te accurate detection of physiologically relevant concentrations of cocaine and substance P 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.