IDBR TYPE A: Definitive Chemical Analysis of Microbial Volatile Mixtures and Chemical Intermediates via Microwave Spectroscopy

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An award is made by the Instrument Development for Biological Research (IDBR) program in the Division of Biological Infrastructure and the Chemical Measurement and Imaging (CMI) program in the division of Chemistry to Harvard University to develop new instrumentation which can measure the complex mixtures of volatile molecules found in diverse chemical and biochemical environments. The instrument will be able to completely analyze complex mixtures of molecules in microbiomes and in rapidly changing chemical environments. The microbes that live on and within vertebrates play a critical role in metabolism, but the molecular mechanisms underlying their influence are not well understood. This instrument will allow simultaneous monitoring of many molecules produced by these microbes. The same instrumentation will also be adapted to detect important, short-lived chemical species. These highly reactive species play central roles in many chemical reactions - for example, in flames and in the atmosphere - but many have never been directly observed. Developing this instrumentation will also provide an ideal arena for an interdisciplinary collaboration in which undergraduate and graduate students in physics, chemistry, and chemical biology will learn about the challenges and capabilities of each other's areas of science. Overall, advancing this technology will add a powerful technique to the suite of chemical analysis tools currently available to the microbiology and chemistry communities.Detecting, identifying, and quantifying the complex mixtures of volatile, reactive molecules found in microbiomes and many other chemical environments is a challenging and important problem. A host of sensitive mixture analysis techniques exist today, but no technique can definitively analyze gas phase mixtures with hundreds of components, and many methods require laborious adjustment for each new species to be analyzed. The analysis of short lived, reactive species is a particularly difficult problem, as most separation techniques operate too slowly to observe such molecules. Fourier Transform Microwave Spectroscopy (FTMW) is exceptionally well suited to this challenging analysis problem. FTMW works by exciting and then detecting narrow, highly specific rotational (microwave) resonances in gas phase molecules. Fingerprints of distinct species can be separated electronically, and physical separation or purification of samples is not required, even for mixtures with hundreds of components. The new instrumentation leverages recent advances in microwave spectroscopy techniques, cryogenics, and fast electronics to dramatically increase the sensitivity of FTMW. The cryogenic techniques used here further provide one of the most inert chemical environments ever achieved, allowing for the stabilization and detection of highly reactive compounds. These reactive compounds play critical roles in many chemical environments, despite lasting for a small fraction of a second under typical conditions. The instrumentation will be adapted to study both complex mixtures produced in microbiomes and reactive mixtures produced in rapidly changing chemical environments. This instrumentation will allow scientists to unravel chemical environments of previously unmanageable complexity, providing an important new tool for studying a wide range of important chemical and biochemical systems. This award is being made jointly by two Programs- (1) Instrument Development for Biological Research, in the Division of Biological Infrastructure (Biological Sciences Directorate), and (2) Chemical Measurement and Imaging, in the Division of Chemistry