SBIR Phase I: A Programmable Residual Solvent Analyzer based on Fourier Transform Molecular Rotational Resonance (FT-MRR) Spectroscopy

这个小企业创新研究第一阶段项目将开发一种新的分析化学技术，用于快速定量复杂混合物中的化学物质。 生命科学和化学仪器市场每年为450亿美元。 质量源于设计制造工艺的引入增加了对准确、高速、免维护化学分析技术的需求。 该项目的目标应用是检测药品生产中的残留化学溶剂和遗传毒性杂质。 即将开发的新技术使用分子旋转共振（MRR）光谱法根据分子的三维几何形状识别分子，从而产生具有高度化学特异性的方法。 MRR是一种高分辨率的光谱技术，可以直接分析含有大量化学品的气体混合物，而不需要使用色谱法进行事先的化学分离-这是当前分析方法中耗时的步骤，需要大量的技术监督。 因此，基于MRR的化学分析仪器可以提供化学品痕量水平的快速测量，其方式与需要持续测量以保证质量的实时制造过程兼容。 使用MRR光谱的化学分析仪器通过更高的测量通量、更低的耗材成本和免维护操作来降低拥有成本。 该项目的智力价值是引入了一种新的化学分析技术，解决了该领域现有工具中的主要问题。 MRR光谱具有任何光谱技术中最高的化学选择性，并且可以轻松区分分子异构体-这对于依赖质量来确定化学身份的技术来说是一个挑战。 与其他光谱技术相比，该方法具有更高的光谱分辨率，可以准确分析许多化合物的混合物样品（具有痕量水平的几种组分）。 与质谱法不同，气体混合物可以直接分析，而不需要使用气相色谱法（GC）进行事先的化学分离。 作为一种光谱学方法，可以进行定量化学分析，而无需运行测量标准的劳动密集型和耗时的过程。 该仪器结合了高功率固态毫米波（mm波）光源、低成本微波合成器集成电路和高速数字电子器件的最新进展，实现了时域傅里叶变换（FT）测量方法。与现有的旋转光谱技术相比，FT-MRR光谱仪将测量时间减少了1000倍或更多，使该技术与其他高灵敏度化学分析工具竞争。

This Small Business Innovation Research Phase I project will develop a new analytical chemistry technique for rapid quantitation of chemicals in complex mixtures. The life science and chemical instrumentation market is $45 billion annually. The introduction of Quality by Design manufacturing processes has increased the need for accurate, high-speed, maintenance-free techniques for chemical analysis. The target application for this project is the detection of residual chemical solvents and genotoxic impurities in pharmaceutical manufacturing. The new technique to be developed uses molecular rotational resonance (MRR) spectroscopy to identify molecules based on their three dimensional geometry, resulting in a method with high chemical specificity. MRR is a high-resolution spectroscopy technique that makes it possible to directly analyze gas mixtures containing a large number of chemicals without the need for prior chemical separation using chromatography - a time-consuming step of current analysis methods that requires significant technical supervision. As a result, MRR-based chemical analysis instruments can provide rapid measurements of trace levels of chemicals in a manner that is compatible with real-time manufacturing processes requiring constant measurement for quality assurance. Chemical analysis instruments using MRR spectroscopy offer lower cost of ownership through higher measurement throughput, reduced consumables cost, and maintenance-free operation. The intellectual merit of this project is the introduction of a new technique for chemical analysis that solves major problems in the current set of tools available to the field. MRR spectroscopy has the highest chemical selectivity of any spectroscopy technique and can easily distinguish molecular isomers - a challenge for techniques that rely on mass to establish the chemical identity. Compared to other spectroscopy techniques, the method has higher spectral resolution that makes it possible to accurately analyze samples that are mixtures of many compounds (with several components at trace levels). Unlike mass spectrometry methods, the gas mixtures can be directly analyzed without the need for prior chemical separation using gas chromatography (GC). As a spectroscopy method, quantitative chemical analysis can be performed without the labor intensive and time-consuming process of running measurement standards. The instrument combines recent advances in high-power, solid-state millimeter wave (mm-wave) light sources, low-cost microwave synthesizer integrated circuits, and high-speed digital electronics to implement a time-domain, Fourier transform (FT) measurement approach. FT-MRR spectrometers reduce the measurement time by a factor of 1000 or more over existing rotational spectroscopy techniques, making the technique competitive with other high-sensitivity chemical analysis tools.