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

生物基础设施部的生物研究仪器开发（IDBR）计划和化学部的化学测量和成像（CMI）计划授予哈佛大学开发新仪器的奖项，该仪器可以测量在不同化学和生物化学环境中发现的挥发性分子的复杂混合物。该仪器将能够完全分析微生物组和快速变化的化学环境中分子的复杂混合物。生活在脊椎动物上和脊椎动物内的微生物在新陈代谢中起着关键作用，但其影响的分子机制尚未得到很好的理解。该仪器将允许同时监测这些微生物产生的许多分子。同样的仪器也将用于探测重要的、寿命短的化学物质。 这些高活性物质在许多化学反应中起着核心作用-例如，在火焰和大气中-但许多从未被直接观察到。开发这种仪器也将提供一个理想的竞技场的跨学科合作，其中本科生和研究生在物理，化学和化学生物学将了解对方的科学领域的挑战和能力。 总的来说，这项技术的发展将为微生物学和化学界目前可用的化学分析工具套件增加一种强大的技术。检测、识别和量化微生物组和许多其他化学环境中发现的挥发性、反应性分子的复杂混合物是一个具有挑战性和重要性的问题。目前存在许多灵敏的混合物分析技术，但没有一种技术可以确定地分析具有数百种组分的气相混合物，并且许多方法需要对待分析的每个新物种进行费力的调整。短寿命的活性物质的分析是一个特别困难的问题，因为大多数分离技术操作太慢，无法观察到这样的分子。傅里叶变换微波光谱（FTMW）非常适合这一具有挑战性的分析问题。FTMW的工作原理是激发并检测气相分子中窄的、高度特异性的旋转（微波）共振。不同物种的指纹可以通过电子方式分离，不需要对样品进行物理分离或纯化，即使是含有数百种成分的混合物。新仪器利用微波光谱技术、低温学和快速电子学的最新进展，大幅提高FTMW的灵敏度。 这里使用的低温技术进一步提供了有史以来最惰性的化学环境之一，允许稳定和检测高活性化合物。这些反应性化合物在许多化学环境中起着关键作用，尽管在典型条件下持续时间很短。该仪器将适用于研究微生物组中产生的复杂混合物和快速变化的化学环境中产生的反应混合物。这种仪器将使科学家能够解开以前无法管理的复杂化学环境，为研究广泛的重要化学和生物化学系统提供重要的新工具。该奖项由两个项目联合颁发-（1）生物基础设施部（生物科学理事会）的生物研究仪器开发，以及（2）化学部的化学测量和成像

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