Microfluidic/controlled systems on brain microprobes

脑微探针上的微流体/控制系统

• 批准号: 6849265
• 负责人: W. Mark Saltzman
• 金额: $ 26.11万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6849265
• 关键词: antiinflammatory agents; blood brain barrier; brain derived neurotrophic factor; brain disorder chemotherapy; confocal scanning microscopy; dexamethasone; drug delivery systems; fluid flow; fluorescence microscopy; growth factor; laboratory rat; neurotransmitters; plasmids; serotonin; technology /technique development

DESCRIPTION (provided by applicant): Many neurological diseases are potentially treatable through pharmacologic approaches, but current clinical therapies are limited by our inability to deliver agents at a controlled rate over a prolonged period to a specified target location in the brain. This problem is magnified in the brain, in comparison with other organs, because of the blood-brain barrier, which renders brain cells inaccessible to agents in the bloodstream unless very high (often toxic) levels are applied. We propose to develop general technology for releasing controlled quantities of agents into the brain in association with microfabricated materials that are commonly used for brain recording and stimulation. These new technologies would permit the coupling of precisely controlled pharmacologic interventions to electrical recording and/or stimulation Once developed, this controlled delivery technology will be useful in a variety of settings including 1) real-time study of the influence of pharmacologic agents on the response of the brain during recording or stimulation and 2) when coupled with signal recording capability, will provide the opportunity to adjust the controlled delivery mechanism in response to a biological effect in the tissue. In the present application, we propose to examine two different, but potentially complementary, delivery techniques: controlled release and microfluidics. We will design and build delivery systems for four different neuroactive agents, which represent the spectrum of agents that are of interest in treating disease in the brain (neurotransmitter, dopamine; anti-inflammatory agent, dexamethasone; protein growth factor, BDNF; and gene therapy vector, plasmid DNA). To develop a complete,quantitative, and predictive understanding of these two delivery technologies, we propose a series of inter-related specific aims, including 1) development and characterization of delivery systems; 2) studies of agent delivery to the brain using both systems; 3) dynamic studies of agent transport in tissue using live brain slice and two-photon laser scanning microscopy.

描述（由申请人提供）：许多神经系统疾病可能通过药物方法来治疗，但是当前的临床疗法受到我们无法在长时间内以受控速率传递给大脑指定目标位置的药物的限制。与其他器官相比，由于血脑屏障的障碍，该问题在大脑中被放大，这使血液中的脑细胞无法接近血液中的脑细胞，除非应用很高（通常有毒）水平。我们建议开发一般技术，以将受控量的代理释放到大脑中，并与通常用于大脑记录和刺激的微生物材料相关。这些新技术将允许将精确控制的药理学干预措施与电气记录和/或刺激耦合，一旦开发出来，该受控的输送技术将在各种环境中有用，包括1）实时研究药理药物在记录或刺激过程中与信号记录能力的响应机构的响应机构的响应的实时研究，并在信号能力上与一定的机会进行调整时，将其与信号的效果相结合，并将其与信号耦合，并将其构成一定的机会，并将其耦合到一定的机会上，并将其耦合到一定的效果上，则在某种程度上将其耦合到一定的效果，并将其构成。 组织。在本应用中，我们建议检查两种不同但潜在的互补交付技术：受控释放和微流体学。我们将为四种不同的神经活性剂设计和建造输送系统，这些神经活性剂代表了对治疗脑部疾病感兴趣的药物（神经递质，多巴胺；抗炎剂，去氨甲米松；蛋白质生长因子，BDNF；以及基因治疗载体，基因载体，质粒DNA）。为了对这两种交付技术产生完整，定量和预测性的理解，我们提出了一系列相互关联的特定目的，包括1）传递系统的发展和表征； 2）使用这两个系统研究代理向大脑传递的研究； 3）使用活脑切片和两光子激光扫描显微镜在组织中转运的动态研究。