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

由生物基础设施部的生物研究仪器开发（IDBR）项目和化学部的化学测量和成像（CMI）项目授予哈佛大学一项奖项，用于开发能够测量在不同化学和生化环境中发现的挥发性分子复杂混合物的新仪器。该仪器将能够在微生物组和快速变化的化学环境中完全分析复杂的分子混合物。生活在脊椎动物身上和体内的微生物在新陈代谢中起着至关重要的作用，但其影响的分子机制尚不清楚。这种仪器可以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。这些高度活跃的物质在许多化学反应中发挥着核心作用，例如在火焰和大气中，但许多物质从未被直接观察到。开发这种仪器还将为跨学科合作提供一个理想的舞台，在这个舞台上，物理学、化学和化学生物学的本科生和研究生将了解彼此科学领域的挑战和能力。总的来说，推进这项技术将为微生物学和化学社区目前可用的化学分析工具套件增加一项强大的技术。检测、鉴定和量化在微生物组和许多其他化学环境中发现的挥发性、活性分子的复杂混合物是一个具有挑战性和重要的问题。目前存在大量灵敏的混合物分析技术，但没有一种技术可以明确地分析含有数百种成分的气相混合物，而且许多方法需要为分析的每个新物种进行艰苦的调整。分析寿命短的活性物质是一个特别困难的问题，因为大多数分离技术操作太慢，无法观察到这类分子。傅里叶变换微波光谱（FTMW）非常适合于这个具有挑战性的分析问题。FTMW的工作原理是激发并探测气相分子中狭窄的、高度特异的旋转（微波）共振。不同物种的指纹可以通过电子方式分离，即使是含有数百种成分的混合物，也不需要对样品进行物理分离或纯化。新的仪器利用了微波光谱技术、低温学和快速电子学的最新进展，极大地提高了FTMW的灵敏度。这里使用的低温技术进一步提供了迄今为止最惰性的化学环境之一，允许稳定和检测高活性化合物。这些活性化合物在许多化学环境中发挥着关键作用，尽管在典型条件下只能持续不到一秒的时间。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性混合物。该仪器将使科学家能够解开以前难以管理的复杂化学环境，为研究广泛的重要化学和生化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和(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