IDBR: Development of Ultrasensitive, Superfast, and Microliter-Volume Differential Scanning Nanocalorimeter for Direct Characterization of Biomolecular Interactions

获奖摘要：超灵敏、超快、微容积差示扫描纳米量热仪的研制所有生物现象都依赖于分子间的相互作用，如配体与蛋白质的结合，或分子内的相互作用，如蛋白质的折叠。作为一种无标记和无固定化的方法，现代量热仪器是直接表征分子相互作用的热力学特征的金标准，包括吉布斯自由能，焓，熵，比热和化学计量，为研究生物分子机制和药物设计提供有价值的信息，这些信息不能单独从结构或计算方法中获得。然而，目前最先进的量热仪需要大体积、高浓度的蛋白质，并且需要非常长的测量时间，这限制了它们在生物学研究中的实用性。 该奖项的目标是开发一种创新的基于MEMS的差示扫描纳米热量计和阵列，将生物大分子的消耗从毫升减少到微升，并将测量时间从数小时减少到数分钟，从而能够直接，精确和快速地检测生物分子相互作用。 为了实现这一目标，计划了四个具体任务，包括1）设计和制造超灵敏的低噪声传感器，2）最小化纳米热量计的寄生热损失，3）设计和集成低噪声电子器件和反馈控制器，和4）的方法测试并将该技术应用于膜蛋白研究和药物筛选。拟议的差示扫描纳米量热仪将显着减少样品体积和缩短测量时间，并提供了一个强大的工具，全面的高内容的热力学研究，在早期的药物发现阶段，并在膜蛋白的研究。这项多学科研究将为年轻科学家和工程师，特别是妇女和代表性不足的少数民族提供极好的机会。在应用范围的不同方面与国家实验室和工业界的互动将有助于加速实施所开发的知识。

Award Abstract: Development of Ultrasensitive, Superfast, and Microliter-Volume Differential Scanning Nanocalorimeter for Direct Characterization of Biomolecular InteractionsAll biological phenomena depend on molecular interactions, which is either intermolecular, as with ligand binding to a protein, or intramolecular, as with protein folding. As a label-free and immobilization-free method, modern calorimetry instrumentation is the gold standard for directly characterizing the thermodynamic profiles of molecular interactions, including Gibbs free energy, enthalpy, entropy, specific heat, and stoichiometry, providing valuable information for investigating biolomolecular mechanisms and drug design, information that cannot be obtained from structural or computational methods alone. However, the current state-of-the-art calorimeters require large-volume, high-concentration proteins and need very long measurement times, which limits their utility for biological studies. The objective of this award is to develop an innovative MEMS-based differential scanning nanocalorimeter and array to reduce the consumption of biological macromolecules from milliliters to micro liters, and to decrease the measurement time from hours to minutes, and thus enable direct, precise, and rapid detection of biomolecular interactions. To achieve this goal, four specific tasks are planned, including 1) designing and fabricating ultrasensitive low-noise sensors, 2) minimizing the parasitic heat loss of the nanocalorimeter, 3) designing and integrating low-noise electronics and feedback controller, and 4) testing and applying this technology to membrane protein study and pharmaceutical screening.The proposed differential scanning nanocalorimeter will significantly reduce the sample volume and shorten the measurement time, and provide a powerful tool for comprehensive high-content thermodynamics studies, in the early stage of drug discovery, and in the study of membrane proteins. This multidisciplinary research will provide excellent opportunities to young scientists and engineers, especially women and underrepresented minorities. Interaction with national laboratories and industry at different ends of the application spectrum will enable accelerated implementation of the developed knowledge.