Miniaturized Calorimetric Instruments for Probing Biomolecular Energetics

用于探测生物分子能量学的小型量热仪器

• 批准号: 0650020
• 负责人: Qiao Lin
• 金额: $ 58.64万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0650020&HistoricalAwards=false
• 关键词: Miniaturized; Calorimetric; Instruments; Probing; Biomolecular

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.

该奖项旨在开发具有以下改进的小型化量热仪器：(1)提高数量级的灵敏度；(2)样品消耗量下降了几个数量级；(3)批量制造，降低成本；(4)通过小型化仪器阵列的使用，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功率的热传感相结合。该项目的目标是：(1)传热、混合和反应的建模和模拟，以了解小型化热量计的原理；(2)开发独立式微流控系统和集成热电堆，用于最灵敏的生物分子热测量；(3)利用Au-Ni和Bi2Te3热电堆设计、制造、表征和验证量热仪器；(4)通过差示扫描量热法（DSC）对小型化量热计进行蛋白质稳定性研究，等温滴定量热法（ITC）对小分子-蛋白质相互作用进行研究。生物量热法测量生物过程中的热量，是一项重要的生物物理技术。量热法比许多检测分子相互作用的方法有优势，因为它不需要分子有放射性或荧光标记，也不需要分子与表面结合。除了这个仪器开发项目的科学效益外，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。研究人员将让本科生参与研究，包括那些来自代表性不足群体的学生，让他们将在课堂上学到的工程技能应用到现实世界的问题中。此外，调查人员还将参与向纽约大都市地区的高中学生和教师进行宣传活动。