Miniaturized Calorimetric Instruments for Probing Biomolecular Energetics

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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.