NER: Nanoliter Biocalorimetry on a Chip for Ultrafast Combinatorial Analysis of Proteins

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ABSTRACTNanoliter Biocalorimetry on a Chip for Ultrafast Combinatorial Analysis of ProteinsL. H. Allen The goal of this project is to develop a new protein calorimetry technology (MEMS), and thus generating new infrastructure for investigations of Biosystems at the Nanoscale. The unique aspects of this project include (1) an ultra-small (nanoliters) sample volume and (2) an ultrafast scan rate. The extremely small sample size, which is a thousand times smaller than conventional calorimetric DSC systems, is needed for characterization of new proteins that are typically synthesized in limited quantities. The increased scan rate, which is a thousand times faster than conventional DSC systems, is more than just a way to provide a quick turn-around of results. These high rates will allow us to capture the intermediate steps of protein folding that occur on the time scale of milliseconds - a capability not available with conventional DSC. The small sample size and compatibility with conventional IC systems will allow the technology to be extended to an array of calorimeters on a chip. This allows for combinatorial studies allowing us to use only a small amount of protein to measure interactions with hundreds of molecules simultaneously. This project will have a broad impact in boosting the infrastructure of thermal characterization instrumentation for the country. The dissemination of our research results by graduate and undergraduate students will extend well beyond the usual materials conferences to the core Thermal Analysis and Chemical Thermodynamics societies. Our results will serve as an example of the benefits of using multidisciplinary approach in investigations: MEMS (electronic materials), proteins (chemistry and biology), and folding/crystallization dynamics (thermodynamics). This project provides a broad educational experience for our students, both graduate and undergraduate, for hands-on processing of the devices and includes design and construction to of electronic and MEMS devices, and material analysis of proteins.