NER: Nanoliter Biocalorimetry on a Chip for Ultrafast Combinatorial Analysis of Proteins

芯片纳升生物量热法用于蛋白质的超快速组合分析。这个项目的目标是开发一种新的蛋白质量热技术(MEMS)，从而为纳米级的生物系统研究产生新的基础设施。该项目的独特之处包括(1)超小(纳升)样品体积和(2)超快扫描速度。极小的样本量比传统的量热DSC系统小一千倍，这是表征通常有限数量合成的新蛋白质所需的。扫描速度的提高比传统的DSC系统快一千倍，这不仅仅是一种快速扭转结果的方式。这些高速率将使我们能够捕捉发生在毫秒级时间尺度上的蛋白质折叠的中间步骤--这是传统DSC所不具备的能力。样品的小尺寸和与传统IC系统的兼容性将使这项技术可以扩展到芯片上的热量计阵列。这使得我们可以进行组合研究，从而只使用少量的蛋白质来同时测量与数百个分子的相互作用。该项目将对加强该国的热特性仪器基础设施产生广泛影响。研究生和本科生对我们研究成果的传播将远远超出通常的材料会议，扩展到核心的热分析和化学热力学学会。我们的结果将作为在研究中使用多学科方法的好处的一个例子：MEMS(电子材料)、蛋白质(化学和生物学)和折叠/结晶动力学(热力学)。该项目为我们的研究生和本科生提供了广泛的设备实践加工教育经验，包括电子和MEMS设备的设计和建造，以及蛋白质的材料分析。

ABSTRACTNanoliter Biocalorimetry on a Chip for Ultrafast Combinatorial Analysis of ProteinsL. H. Allen The goal of this project is to develop a new protein calorimetry technology (MEMS), and thus generating new infrastructure for investigations of Biosystems at the Nanoscale. The unique aspects of this project include (1) an ultra-small (nanoliters) sample volume and (2) an ultrafast scan rate. The extremely small sample size, which is a thousand times smaller than conventional calorimetric DSC systems, is needed for characterization of new proteins that are typically synthesized in limited quantities. The increased scan rate, which is a thousand times faster than conventional DSC systems, is more than just a way to provide a quick turn-around of results. These high rates will allow us to capture the intermediate steps of protein folding that occur on the time scale of milliseconds - a capability not available with conventional DSC. The small sample size and compatibility with conventional IC systems will allow the technology to be extended to an array of calorimeters on a chip. This allows for combinatorial studies allowing us to use only a small amount of protein to measure interactions with hundreds of molecules simultaneously. This project will have a broad impact in boosting the infrastructure of thermal characterization instrumentation for the country. The dissemination of our research results by graduate and undergraduate students will extend well beyond the usual materials conferences to the core Thermal Analysis and Chemical Thermodynamics societies. Our results will serve as an example of the benefits of using multidisciplinary approach in investigations: MEMS (electronic materials), proteins (chemistry and biology), and folding/crystallization dynamics (thermodynamics). This project provides a broad educational experience for our students, both graduate and undergraduate, for hands-on processing of the devices and includes design and construction to of electronic and MEMS devices, and material analysis of proteins.