Flexible Multi-Sensory Mode Neural Devices for Neurochemical Control

用于神经化学控制的灵活多感官模式神经设备

• 批准号: 9313654
• 负责人: Allison Hess Dunning
• 金额: --
• 依托单位: LOUIS STOKES CLEVELAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9313654
• 关键词: Adverse effects; Affect; Anti-Inflammatory Agents; Attenuated; Biological; Biosensor; Brain; Cells; Characteristics; Chronic Disease; Clinical; Computers; Data; Deep Brain Stimulation; Detection; Devices; Diffusion; Disease; Dose; Drug Delivery Systems; Electrodes; Engineering; Environment; Equipment Malfunction; Failure; Film; Glutamates; Goals; Implant; In Situ; Individual; Inflammatory Response; Infusion procedures; Intervention; Lead; Limb structure; Measurement; Measures; Mechanics; Medical; Microelectrodes; Microfabrication; Microfluidics; Modality; Motor; Permeability; Pharmaceutical Preparations; Pharmacology; Physiological; Polymers; Prevention; Process; Quadriplegia; Rattus; Reaction; Research; Research Project Grants; Resolution; Risk; Robotics; Safety; Sensory; Signal Transduction; Silicon; Spinal cord injury; Sprague-Dawley Rats; Structure; System; Techniques; Technology; Therapeutic Intervention; Thinking; Tissues; Traumatic injury; Treatment Efficacy; Veterans; Work; aqueous; arm; barrel cortex; base; biological systems; brain machine interface; clinical translation; design; electric impedance; extracellular; flexibility; fluid flow; implantable device; implantation; improved; in vivo; innovation; microdevice; microsystems; motor disorder; motor impairment; multisensory; nanocomposite; nanoscale; neurochemistry; neuroinflammation; novel; particle; prevent; programs; public health relevance; relating to nervous system; response; response biomarker; restoration; seal; sensor; temporal measurement; tissue phantom

 DESCRIPTION: The long-term goal is to develop advanced, multi-functional neural interfaces for localized interaction with the biological environment. Long-term, intracortical microelectrode array reliability will be maintained through preventing, detecting, and controlling the biological tissue response to the implanted device. To accomplish this goal, microscale intracortical neural interfaces based on materials that seamlessly integrate within the neural tissue will be integrated with microfluidic drug delivery capabilities and neurochemical sensors. Intracortical implants for neural spike recording are hampered by a loss of neural recording quality in the weeks and months after implantation. The neuroinflammatory tissue response leading to glial encapsulation around the implants is widely hypothesized as the cause of the gradual loss of neural spike recording quality. While efforts to extend recording reliability have been made through the use of novel materials to reduce probe-tissue mechanical-mismatch or by delivery of anti-inflammatory agents, a multi-faceted approach to eliminating the neuroinflammatory response is lacking. There is currently no practical technique to track tissue response activity at the implant-tissue interface in situ before encapsulation has occurred, at which point damage to the biotic-abiotic interface may be irreversible. In the absence of an in situ measure of neuroinflammatory activity, therapeutic intervention to temper the tissue response via drug delivery is less effective. This project will use a novel polymer nanocomposite as the implant structural material to prevent the tissue response, a glutamate sensor to detect the tissue response, and microfluidic drug delivery capabilities to control the tissue response. The primary hypothesis of this proposal is that a microfabrication-based approach can be used to integrate a mechanically-adaptive polymer nanocomposite with the functions required for a closed-loop control system for preventing and treating the biological response to neural implants. This research project is divided into two distinct specific aims. The first aim will use electrochemical sensors integrated into intracortical microelectrode devices to evaluate the hypothesis that glutamate is an indicator of tissue response activity. Three sets of multi-modal neural probes with both integrated neural recording electrodes and glutamate electrochemical sensors will be studied: a rigid silicon control, a highly-compliant polymer nanocomposite, and a moderately- compliant polymer nanocomposite. Probes will be implanted in the barrel cortex of Sprague-Dawley rats for either 3 days, 2 weeks, or 16 weeks. Electrochemical impedance, neural recordings, and glutamate measurements will be made regularly throughout the implant duration. Afterward, immunohistochemical (IHC) analysis will be performed on fixed tissue to assess the extent of the tissue response. Impedance, neural spike, and glutamate data will be compared to the IHC data to look for correlations between in vivo measures and the cumulative tissue response. By confirming the hypothesis, a simple analyte will have been identified that can be used to track tissue response and serve as a control signal for a closed-loop tissue response control system. In the second aim, microfluidic drug-delivery capabilities will be integrated into the polymer nanocomposite. The moisture permeability of the mechanically-adaptable polymer nanocomposite will be exploited with the design of permeable-walled microfluidic channels to replenish the storage of pharmacologic agents within the nanocomposite. This will enable for controlled, sustained release of a small amount of anti- inflammatory agents highly localized to the region surrounding the implant. These capabilities can then be combined and integrated with microelectronic systems to sense and control the local neuroinflammatory response.

 描述： 长期目标是开发与生物环境局部相互作用的高级多功能神经接口。长期的，物质内微电极阵列可靠性将通过预防，检测和控制生物组织来维持 对植入设备的响应。为了实现这一目标，基于在神经元组织中无缝集成的材料的皮质内神经元界面将与微流体药物递送能力和神经化学传感器集成在一起。植入后的几周和几个月，神经科学质量的丧失会阻碍神经冲突记录的皮质内意义。广泛认为导致植入物周围神经胶质包裹的神经炎性组织反应被广泛认为是神经传球记录质量的年级丧失的原因。尽管已经通过使用新型材料来减少探针组织机械不匹配或通过抗炎剂进行了延长记录可靠性的努力，但缺乏一种多方面的方法来消除神经炎症反应。目前没有跟踪组织反应活动的实用技术 在发生封装之前，原位植入物 - 组织界面对生物育种界面的损害可能是不可逆的。在没有现场测量神经炎性活性的情况下，通过药物递送来调节组织反应的热干预效果较低。该项目将使用新型的聚合物纳米复合材料作为植入物结构材料，以防止组织反应，谷氨酸传感器检测组织反应以及微流体药物输送能力，以控制组织反应。该提议的主要假设是，基于微生物的方法可用于将机械适应性的聚合物纳米复合材料与闭环控制系统所需的功能相结合，以防止和治疗对神经植物的生物学反应。该研究项目分为两个不同的特定目标。第一个目标将使用电化学 传感器集成到皮质内微电极设备中，以评估谷氨酸是组织反应活性的指标的假设。与整合神经元记录电极和谷氨酸电化学传感器的三组多模式神经元问题将是研究二：一种刚性硅的控制，高度融合的聚合物纳米复合材料和现代综合的聚合物纳米复合材料。探针将植入Sprague-Dawley大鼠的桶皮层3天，2周或16周。在整个植入物期间，将定期进行电化学阻抗，神经元记录和谷氨酸测量。之后，将在固定组织上进行免疫组织化学（IHC）分析，以评估组织反应的程度。阻抗，神经元尖峰和谷氨酸数据将与IHC数据进行比较，以寻找体内测量与累积组织反应之间的相关性。通过确认该假设，将确定一个简单的分析物，可用于跟踪组织反应并作为闭环组织响应控制系统的控制信号。在第二个目的中，微流体降低功能将集成到聚合物纳米复合材料中。机械适应的聚合物纳米复合材料的水分渗透性将通过设计可渗透的壁微流体通道的设计来利用，以复制在纳米复合材料中的药理学剂的储存。这将实现可控制的，持续释放少量抗炎药，高度位于植入物周围区域。然后可以将这些功能与微电体系统组合并集成，以感知和控制局部神经炎症反应。