Development of a Microfluidic Thermal Regulator for Studies of Cortical Function

开发用于皮层功能研究的微流体温度调节器

• 批准号: 8240838
• 负责人: LEAH ANN KRUBITZER
• 金额: $ 17.92万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8240838
• 关键词: Address; Affect; Animal Experiments; Animal Model; Animals; Area; Attention; Behavior; Behavioral; Behavioral Paradigm; Biomechanics; Biomedical Engineering; Brain; California; Cognitive; Collaborations; Communities; Complex; Computer software; Data; Development; Devices; Dimensions; Discipline; Disease; Drops; Electrodes; Engineering; Epilepsy; Feedback; Ferrets; Generations; Goals; Heating; Hippocampus (Brain); Implant; Laboratories; Longevity; Manuals; Maps; Measures; Methods; Microelectrodes; Microfluidics; Modeling; Monitor; Monkeys; Motivation; Motor; Neocortex; Neurons; Neurophysiology - biologic function; Neurosciences; Operative Surgical Procedures; Parietal Lobe; Perception; Performance; Prefrontal Cortex; Property; Pump; Rattus; Regulation; Rest; Rodent Model; Running; Series; Shapes; Short-Term Memory; Structure; System; Techniques; Technology; Temperature; Testing; Therapeutic; Time; Tissues; Training; Universities; base; biomaterial compatibility; brain tissue; cognitive system; design; elastomeric; flexibility; functional disability; implantation; innovation; lithography; long term memory; miniaturize; novel; novel therapeutics; prototype; relating to nervous system; research study; response; sensorimotor system; software systems; somatosensory; tool; user-friendly; vascular bed

DESCRIPTION (provided by applicant): The goal of this project is to develop a miniaturized microfluidic thermal regulator to reversibly deactivate one or multiple areas of the neocortex through thermal regulation. This device, or "cooling chip", includes indwelling microthermocouples and recording microelectrodes to monitor temperature and neural response and make online adjustments of cooling parameters to reach a desired cortical temperature. The cooling chip is being designed, assembled and tested as a multi-disciplinary collaboration between four different laboratories at the University of California Davis spanning three different departments. Although previous cooling devices have been used to reduce brain activity, the significance of our new design lies in its smaller size and the presence of indwelling electrodes/thermocouple ensemble, which will greatly expand the range of animals and experiments in which it can be used. Design criteria for the cooling chip include biocompatibility with brain tissue and a structure that accommodates the geometry of the cortical area where it is placed. Innovative soft lithography fabrication of elastomeric material (i.e., polydimethylsilane, or PDMS) offers excellent biomechanical flexibility and compliance; compact device dimensions (< 9 mm3) as well as desired heat transfer properties, which have been characterized at the tissue interface. The current prototype absorbs ~ 2 kCal/min, and produces a highly localized temperature drop from 370C to 200C within a minute. This device is highly innovative because its flexibility in size and shape allow it to be used in different animal models from rats to monkeys. A primary application for the cooling chip will be to probe cortical macrocircuitry and the specific behaviors that cortical areas generate. Further, this device can be generalized easily across a number of neuroscience disciplines for studies of sensory and motor systems as well as cognitive systems such as long-term memory (e.g., hippocampus), working memory (e.g., prefrontal cortex), and attention (e.g., parietal lobe). Its user-friendly interface with commercially available hardware and software running on a laboratory PC will make it adaptable for use in any number of laboratories. Finally, questions regarding the neural basis of complex behaviors that are currently conducted almost exclusively in non-primates can now be addressed in the more ubiquitous rodent model. PUBLIC HEALTH RELEVANCE: The goal of this project is to produce the first microfluidic based cooling chip with indwelling electrodes to provide ongoing feedback on the status of neural activity in cortex as cortical tissue is cooled. In addition to the ability to address questions about the neural basis of behavior, this technology will be ground breaking for the next generation of therapeutic devices that can auto regulate neuronal activity in dysfunctional areas of cortex. The technology developed in this proposal will be critical for moving implantable therapeutics forward to thermally regulate neural activity in debilitating diseases such as epilepsy in which chaotic neuronal activity results in severe functional impairments.

描述（由申请人提供）：该项目的目标是开发一种小型化的微流体热调节器，通过热调节可逆地使新皮层的一个或多个区域失活。该装置，或“冷却芯片”，包括留置微热电偶和记录微电极，以监测温度和神经反应，并在线调整冷却参数以达到所需的皮质温度。该冷却芯片的设计、组装和测试是由加州大学戴维斯分校（University of California Davis）四个不同实验室跨三个不同部门的多学科合作完成的。虽然以前的冷却装置已被用于减少大脑活动，但我们新设计的意义在于其更小的尺寸和留置电极/热电偶集成的存在，这将大大扩大其可用于动物和实验的范围。冷却芯片的设计标准包括与脑组织的生物相容性，以及与放置芯片的皮质区域的几何形状相适应的结构。弹性体材料（即聚二甲基硅烷或PDMS）的创新软光刻制造提供了出色的生物力学灵活性和顺应性；紧凑的设备尺寸（< 9 mm3）以及所需的传热性能，已在组织界面表征。目前的原型吸收~ 2 kCal/min，并在一分钟内产生从370℃到200℃的高度局部温度下降。这种装置具有高度创新性，因为它的大小和形状具有灵活性，可以用于从老鼠到猴子的不同动物模型。该冷却芯片的主要应用将是探测皮层宏观电路和皮层区域产生的特定行为。此外，这种装置可以很容易地推广到许多神经科学学科中，用于研究感觉和运动系统以及认知系统，如长期记忆（如海马体）、工作记忆（如前额叶皮层）和注意力（如顶叶）。其用户友好的界面与商用硬件和软件运行在实验室PC上，将使其适应在任何数量的实验室使用。最后，关于复杂行为的神经基础的问题，目前几乎只在非灵长类动物中进行，现在可以在更普遍的啮齿动物模型中解决。