Miniaturized Calorimetric Instruments for Probing Biomolecular Energetics

该奖项旨在开发具有以下改进的小型化量热仪器：（1）数量级更好的灵敏度;（2）数量级减少样品消耗;（3）批量制造，从而降低成本;以及（4）通过使用小型化仪器阵列更快的吞吐量。 微机电系统（MEMS）和微流体将与能够检测~0.1 nW功率的热传感集成。 该项目的目标是：（1）热传递、混合和反应的建模和模拟，以理解小型化量热计原理;（2）独立式微流体系统以及集成热电堆的开发，用于生物分子热的最大灵敏度测量;（3）使用Au-Ni和Bi 2 Te 3热电堆的量热仪器的设计、制造、表征和验证;（4）通过蛋白质稳定性的差示扫描量热法（DSC）研究和小分子-蛋白质相互作用的等温滴定量热法（ITC）研究来测试小型化量热计。 生物量热法（biocalorimetry）是测量生物过程中的热量，是一种重要的生物物理技术。 量热法与许多检测分子相互作用的方法相比具有优势，因为它不需要分子具有放射性或荧光标记或与表面结合。 除了这个仪器开发项目的科学效益外，还有学生和社区的好处。 研究成果将用于加强研究生和本科生课程。研究人员将让本科生，包括那些来自代表性不足的群体的学生参与研究，使他们能够将在课堂上学到的工程技能应用于现实世界的问题。此外，调查人员还将参与对大都会纽约市地区高中学生和教师的外联活动。

This is an award to develop miniaturized calorimetric instruments with the following improvements: (1) order-of-magnitude better sensitivity; (2) orders of magnitude decrease in sample consumption; (3) batch fabrication, leading to lower cost; and (4) faster throughput, through the use of arrays of miniaturized instruments. Microelectromechanical systems (MEMS) and microfluidics will be integrated with thermal sensing capable of detecting ~0.1 nW of power. Objectives of the project are: (1) modeling and simulations of heat transfer, mixing and reaction to understand miniaturized calorimeter principles; (2) development of a freestanding microfluidic system as well as integrated thermopiles for maximally sensitive measurement of biomolecular heat; (3) design, fabrication, characterization and validation of calorimetric instruments using Au-Ni and Bi2Te3 thermopiles; (4) testing the miniaturized calorimeters by Differential Scanning Calorimetry (DSC) studies of protein stability, and Isothermal Titration Calorimetry (ITC) studies of small molecule-protein interactions. Biological calorimetry, or biocalorimetry, measures the heat in biological processes and is an important biophysical technique. Calorimetry has an advantage over many methods for detecting molecular interactions, because it does not require the molecules to have radioactive or fluorescent labels or to be bound to a surface. In addition to the scientific benefits of this instrument-development project, there are benefits to students and the community. Research results will be used to enhance graduate and undergraduate courses. The investigators will involve undergraduate students, including those from underrepresented groups, in research to allow them to apply engineering skills they learned in the classroom to real-world problems. In addition, the investigators will be involved in outreach activities to high school students and teachers in the metropolitan New York City area.