Development of a Microfluidic Thermal Regulator for Studies of Cortical Function

描述（由申请人提供）：本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。这种装置，或称“冷却芯片”，包括留置微型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，以达到所需的皮层温度。冷却芯片的设计、组装和测试是加州戴维斯大学三个不同系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/热电偶组合的存在，这将大大扩展其可用于的动物和实验范围。冷却芯片的设计标准包括与脑组织的生物相容性以及适应其放置的皮质区域的几何形状的结构。弹性体材料的创新软光刻制造（即，聚二甲基硅烷或PDMS）提供了优异的生物力学灵活性和顺应性;紧凑的装置尺寸（<9mm 3）以及所需的热传递特性，其已在组织界面处表征。目前的原型吸收约2 kCal/min，并在一分钟内产生从370 C到200 C的高度局部温度下降。该设备具有高度创新性，因为其尺寸和形状的灵活性使其能够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皮层宏电路和皮层区域产生的特定行为。此外，该装置可以容易地在许多神经科学学科中推广，用于研究感觉和运动系统以及认知系统，例如长期记忆（例如，海马体），工作记忆（例如，前额叶皮层），和注意力（例如，顶叶）。其用户友好的界面与商业上可用的硬件和软件在实验室PC上运行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。

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.