Miniaturized Calorimetric Instruments for Probing Biomolecular Energetics

这是一个开发小型化量热仪器的奖项，具有以下改进：(1)灵敏度提高了数量级；(2)样品消耗减少了数量级；(3)批量制造，导致成本更低；(4)通过使用小型化仪器阵列，产量更快。微电子机械系统(MEMS)和微流体将与能够检测~0.1 NW功率的热传感集成在一起。该项目的目标是：(1)对热传递、混合和反应进行建模和模拟，以了解小型量热计的原理；(2)开发独立的微流体系统以及集成的热电堆，用于最灵敏地测量生物分子热；(3)使用Au-Ni和Bi2Te3热电堆设计、制造、表征和验证热计仪器；(4)通过差示扫描量热仪(DSC)研究蛋白质稳定性和等温滴定量热法研究小分子与蛋白质的相互作用，测试小型量热仪。生物量热法，或称生物量热法，测量生物过程中的热量，是一种重要的生物物理技术。与许多检测分子相互作用的方法相比，量热法具有优势，因为它不需要分子具有放射性或荧光标记，也不需要结合到表面。除了这个仪器开发项目的科学益处外，对学生和社区也有好处。研究成果将用于加强研究生和本科课程。调查人员将让本科生，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，调查人员将参与纽约大都会地区高中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.