Development of a Microfluidic Thermal Regulator for Studies of Cortical Function

描述(申请人提供)：该项目的目标是开发一种微型微流控热调节器，通过热调节可逆地使新皮质的一个或多个区域失活。这种装置，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。冷却芯片的设计、组装和测试是加州大学戴维斯分校三个不同部门的四个不同实验室之间的多学科合作。虽然以前的冷却装置已经被用来减少大脑活动，但我们新设计的意义在于它的尺寸更小，并且存在留置电极/热电偶组合，这将极大地扩大它可以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兼容性，以及适应放置芯片的皮质区域几何形状的结构。创新的软光刻制造弹性体材料(即聚二甲基硅烷，或PDMS)提供了出色的生物力学灵活性和顺应性；紧凑的设备尺寸(&lt；9mm3)以及所需的热传输特性，这些都已在组织界面处得到表征。目前的样机吸收~2千卡/分钟，并在一分钟内产生从370摄氏度到200摄氏度的高度局域温降。这种设备具有很高的创新性，因为它在大小和形状上的灵活性使它可以用于从大鼠到猴子的不同动物模型。冷却芯片的主要应用将是探测大脑皮层大回路和大脑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，用于研究感觉和运动系统以及认知系统，如长期记忆(例如，海马体)、工作记忆(例如，前额叶)和注意力(例如，顶叶)。它与实验室PC上运行的商用硬件和软件的用户友好界面将使其适用于任何数量的实验室。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。 公共卫生相关性：该项目的目标是生产第一个带有留置电极的基于微流控的冷却芯片，以便在皮质组织冷却时提供关于皮质神经活动状态的持续反馈。除了能够解决有关行为的神经基础的问题外，这项技术还将是下一代治疗设备的开创性进展，这种设备可以自动调节皮质功能障碍区域的神经元活动。这项提案中开发的技术将是推动植入式疗法向前发展的关键，以便对癫痫等衰弱疾病的神经活动进行热调节，在癫痫等疾病中，混乱的神经元活动会导致严重的功能障碍。

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.