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

项目概要（宋、吉） 拥有可靠的工具，可选择性地同时在体内实时测定多种神经递质 将允许前所未有的信息获取关键了解潜在的机制， 许多脑相关精神障碍和疾病的神经通路，如帕金森氏症和 老年痴呆症在这些例子中，有一个故障或退化的神经信号， 这些通路涉及释放和吸收各种神经递质，如果完全暴露出来， 更好地了解这种神经疾病的原因，并可能有助于治疗的发展， 疗方因此，非常需要建立一种可植入传感器技术，以量化多种生物传感器。 神经递质的平行，快速，并选择性地延长一段时间在一个活着的大脑， 引起神经炎症我们的长期目标是开发一种集成的植入式和生物相容性 提供多种神经递质的准确和快速测定并减少 植入区域的炎症，以保持器械性能的寿命。我们的目标将是 通过追求以下两个具体目标来实现：（1）实现用于 多物种神经递质检测，和（2）开发一种灵活的和生物相容性的设备， 微流控抗炎药物递送系统。目标#1将通过利用分子印迹 聚合物选择性地识别目标分析物，用于鉴定和定量主要的 哺乳动物的神经递质多分析物传感器阵列将通过形成每个单独的 传感元件，其具有在微制造电极上图案化的独特分子印迹聚合物。的 多分析物传感器阵列的功能将通过在腹侧植入装置来证明。 以大鼠活体脑被盖区（VTA）为模型，观察VTA内神经递质的动态变化。六 选择目标神经递质作为分析物：多巴胺、血清素、去甲肾上腺素、组胺、γ- 氨基丁酸和乙酰胆碱。一旦传感器被牢固地定位在腹侧被盖区， 给药以观察腹侧被盖区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，结合微流体抗- 炎症药物递送系统可最大限度地减少异物免疫反应，从而实现长期 体内监测能力。组胺H4受体拮抗剂药物和前体药物的有效性 将通过微流体注射给药来研究炎性细胞因子抑制剂药物 系统直接植入植入部位并观察免疫应答的表达。

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.