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： 长期目标是开发先进的多功能神经接口，用于与生物环境进行局部交互，通过预防、检测和控制生物组织来维持皮质内微电极阵列的长期可靠性。 为了实现这一目标，基于可无缝集成在神经组织内的材料的微型皮质内神经接口将与微流体药物输送功能和用于神经尖峰记录的神经化学传感器集成，但会因神经元缺失而受到阻碍。植入后数周和数月内的神经炎症组织反应导致植入物周围的神经胶质包裹，这被广泛认为是神经尖峰记录质量逐渐丧失的原因，而提高记录可靠性的努力已经取得了进展。虽然已经通过使用新材料来减少探针-组织机械失配或通过递送抗炎剂来实现，但缺乏消除神经炎症反应的多方面方法，目前还没有跟踪组织反应活动的实用技术。在 在封装发生之前，植入物-组织界面处于原位，此时对生物-非生物界面的损害可能是不可逆的。在缺乏神经炎症活性的原位测量的情况下，通过药物输送来缓和组织反应的治疗干预较少。该项目将使用新型聚合物纳米复合材料作为植入物结构材料来防止组织反应，使用谷氨酸传感器来检测组织反应，并使用微流体药物输送能力来控制组织反应。基于微加工的方法可用于将机械自适应聚合物纳米复合材料与闭环控制系统所需的功能集成在一起，以预防和治疗神经植入物的生物反应。目标将使用电化学 集成到皮质内微电极装置中，以评估谷氨酸是组织反应活动指标的假设，将研究三组​​具有集成神经记录电极和谷氨酸电化学传感器的多模式神经探针：刚性硅控制，高度顺应性。聚合物纳米复合材料和适度顺应性的聚合物纳米复合材料探针将被植入 Sprague-Dawley 大鼠的桶状皮质中 3 天、2 周或16 周后，将在整个植入期间定期进行电化学阻抗、神经记录和谷氨酸测量，然后对固定组织进行免疫组织化学 (IHC) 分析，以评估组织反应的程度。将数据与 IHC 数据进行比较，以寻找体内测量值与累积组织反应之间的相关性。通过确认假设，将鉴定出可用于跟踪组织反应和累积反应的简单分析物。作为闭环组织响应控制系统的控制信号，在第二个目标中，将通过设计将微流体药物输送能力集成到聚合物纳米复合材料中。可渗透壁微流体通道可补充纳米复合材料内药物的储存，这将能够控制、持续释放高度局部化的少量抗炎剂。然后，这些功能可以与微电子系统相结合和集成，以感知和控制局部神经炎症反应。