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

基于芯片的纳米升生物热分析法用于蛋白质的超快速组合分析。该项目的目标是开发一种新的蛋白质量热技术（MEMS），从而为纳米尺度的生物系统研究提供新的基础设施。这个项目的独特之处在于(1)超小（纳升）的样品体积和(2)超快的扫描速度。极小的样本量，比传统的量热DSC系统小一千倍，需要用于表征通常合成数量有限的新蛋白质。增加的扫描速度，比传统的DSC系统快一千倍，不仅仅是一种提供快速周转结果的方法。这些高速率将使我们能够捕捉到发生在毫秒时间尺度上的蛋白质折叠的中间步骤，这是传统DSC无法提供的能力。小样本量和与传统IC系统的兼容性将允许该技术扩展到芯片上的热量计阵列。这使得组合研究允许我们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。该项目将对促进该国热表征仪器的基础设施产生广泛影响。研究生和本科生对我们的研究成果的传播将远远超出通常的材料会议，延伸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教育经验，用于动手处理设备，包括电子和MEMS设备的设计和构建，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.