Gas Chromatography-Molecular Rotational Resonance Spectrometer NIH SBIR Direct to Phase II BrightSpec, Inc. Project Summary This project proposes the development of the first commercial gas chromatography-molecular rotational resonance (GC-MRR) spectrometer for analytical characterization of complex mixtures such as biological fluids and tissues, natural products, or environmental water sources. MRR is a spectroscopic technique for unambiguous structure determination and quantitation of small molecules, which has been used for decades in academic research laboratories but only recently commercialized by BrightSpec, driven by recent groundbreaking innovations. The key advantages of MRR motivating its incorporation into a gas chromatography hyphenated system are its selectivity to isomeric compounds, absolute quantitation capabilities, and identification of unknowns without reference standards. GC-MRR not only complements existing techniques (such as mass spectrometry and NMR), but also adds new insights to enhance discovery in numerous fields of research. A proof-of-concept prototype GC-MRR instrument has been used to demonstrate its capabilities to resolve complex mixtures, including co-eluting isotopologues and isotopomers. This preliminary work has de-risked this proposed Phase II project, where this prototype will be refined to develop a product with the sensitivity, speed, and ease-of-use necessary to facilitate its commercial adoption. This includes both the instrument hardware to quickly and precisely measure MRR spectra of analytes as they elute from the chromatographic column, and the software interface to allow users to easily set up measurements, visualize data, and interpret the results. The product will then be tested thoroughly on relevant samples in the market areas where GC-MRR is expected to have the greatest impact. Finally, following this extensive evaluation, the product design will be refined for commercial launch at or before the end of the grant period. The completed GC-MRR product holds the promise to enable breakthrough research in a number of high-impact health-related fields, including metabolomics, natural products drug discovery, and monitoring of environmental pollutants, among others.