Implantable sensor array for in vivo, real-time monitoring of multiple neurotransmitters

用于体内多种神经递质实时监测的植入式传感器阵列

• 批准号: 9211725
• 负责人: Edward Song
• 金额: $ 22.5万
• 依托单位: UNIVERSITY OF NEW HAMPSHIRE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9211725
• 关键词: Acetylcholine; Acetylcholinesterase Inhibitors; Address; Affinity; Alzheimer' s Disease; Animal Experiments; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Area; Autoimmune Responses; Behavior; Biocompatible Materials; Biomedical Engineering; Brain; Chemicals; Clinical; Complex; Detection; Development; Devices; Disease; Dopamine; Drug Delivery Systems; Effectiveness; Electrodes; Elements; Environment; Equipment Malfunction; Foreign Bodies; Future; Goals; Hand; Histamine; Immune response; Implant; In Vitro; Individual; Inflammation; Inflammatory; Injection of therapeutic agent; Location; Longevity; Measurement; Mental disorders; Microdialysis; Microfluidics; Modeling; Molecular; Monitor; Neurologic; Neurotransmitters; Norepinephrine; Organism; Parkinson Disease; Pathway interactions; Pattern; Performance; Pharmaceutical Preparations; Polymers; Positioning Attribute; Principal Component Analysis; Psyche structure; Rattus; Reading; Research; Resolution; Route; Secure; Serotonin; Signal Pathway; Site; Specific qualifier value; Stimulus; System; Techniques; Technology; Time; Tissues; Ventral Tegmental Area; Work; base; biomaterial compatibility; cytokine; flexibility; gamma-Aminobutyric Acid; implantable device; implanted sensor; imprint; in vivo; inhibitor/antagonist; miniaturize; molecular recognition; neuroinflammation; neurotransmission; prevent; receptor; relating to nervous system; sensor; temporal measurement; therapy development; tool

PROJECT SUMMARY (SONG, JI) Having reliable tools for selective, simultaneous in vivo determination of multiple neurotransmitters in real-time will allow for unprecedented acquisition of information key to understanding the underlying mechanisms and neurological pathways of numerous brain-associated mental disorders and diseases, such as Parkinson’s and Alzheimer’s diseases. In these examples, there is a malfunction or a degeneration in the neural signaling pathways that involve releasing and absorbing of various neurotransmitters which, if fully uncovered, can help better understand the cause of such neural disorders and potentially help the development of treatments and cure. As such, there is a great need for establishing an implantable sensor technique to quantify numerous neurotransmitters in parallel, rapidly, and selectively for extended periods of time in a living brain, without causing neuro-inflammation. Our long-term goal is to develop an integrated implantable and biocompatible device that provides accurate and fast determination of multiple neurotransmitters and that reduces inflammation at the implanted area to preserve the longevity of the device performance. Our goal will be achieved by pursuing the following two Specific Aims: (1) Implementation of a microscale sensor array for multi-species neurotransmitter detection, and (2) Development of a flexible and biocompatible device with microfluidic anti-inflammatory drug delivery system. Aim #1 will be achieved by utilizing molecularly imprinted polymers to selectively recognize the target analyte for the identification and quantification of the major mammalian neurotransmitters. A multi-analyte sensor array will be constructed by forming each individual sensing element with a unique molecularly imprinted polymer patterned on a microfabricated electrode. The functionality of the multi-analyte sensor array will be demonstrated by implanting the device at the ventral tegmental area (VTA) of a live rat brain as a model to observe the dynamics of neurotransmitters in VTA. Six target neurotransmitters are selected as analyte: dopamine, serotonin, norepinephrine, histamine, gamma- aminobutyric acid and acetylcholine. Once the sensor is securely positioned in the VTA, a neural stimulant is administered to observe the changes in the level of neurotransmitters that occurs in the VTA. Aim #2 will be achieved through the use of flexible and biocompatible materials, in conjunction with a microfluidic anti- inflammatory drug delivery system to minimize the foreign-body immune response and thus enabling long-term in vivo monitoring capability. The effectiveness of the histamine H4 receptor antagonist drug and the pro- inflammatory cytokine inhibitor drug will be studied by administering them through the microfluidic injection system directly into the implanted site and observing the expression of immune responses.

项目摘要（Song，JI） 具有可靠的工具，可实时选择性，简单的体内确定多个神经递质 将允许对信息的空前获取关键，以了解基本机制和 许多与脑相关的精神障碍和疾病的神经途径，例如帕金森氏症和疾病 阿尔茨海默氏症的疾病。在这些示例中，神经信号传导发生故障或变性 涉及释放和吸收各种神经递质的途径，如果完全发现，可以帮助 更好地了解这种神经疾病的原因，并有可能帮助发展治疗和 治愈。因此，非常需要建立一种可植入的传感器技术来量化众多 神经递质并联，快速和有选择性地在活大脑中长时间，没有 引起神经炎症。我们的长期目标是开发综合植入和生物相容性 提供准确，快速确定多个神经递质并减少的设备 植入区域的炎症以保持设备性能的寿命。我们的目标将是 通过追求以下两个具体目标来实现：（1）实施微观传感器阵列 多种物种神经递质检测，（2）开发具有柔性和生物相容性的设备 微流体抗炎药输送系统。 AIM＃1将通过使用分子图表来实现 聚合物可以选择性地识别目标分析物以识别和数量 哺乳动物神经递质。通过形成每个个体，将构建多分析器传感器阵列 具有独特的分子印迹聚合物在微生物电极上的传感元件。这 多分析物传感器阵列的功能将通过将设备植入腹侧来证明 活大鼠大脑的细分区域（VTA）是观察VTA中神经递质动力学的模型。六 选择靶神经递质作为分析物：多巴胺，5-羟色胺，去甲肾上腺素，组胺，γ- 氨基丁酸和乙酰胆碱。一旦将传感器牢固地位于VTA中，中性刺激剂为 用于观察VTA中发生的神经递质水平的变化。目标＃2将是 通过使用柔性和生物相容性材料与微流体抗 - 炎症药物输送系统以最大程度地减少外国体内免疫反应，从而可以长期 体内监测功能。组胺H4受体拮抗剂药物的有效性和前 炎性细胞因子抑制剂将通过微流体注射来进行研究 系统直接进入植入部位并观察免疫复杂的表达。