Nanoflow Capillary Liquid Chromatographic-Mass Spectrometry for High Throughput Quantitative Metabolomic Analyses

Metabolomics is a holistic approach to the study of a biological system's metabolite complement (often generalized to include essentially all small molecules), and its practice is anticipated to greatly impact biomedical research, drug discovery, nutrition science, and clinical practices. The ability to broadly measure metabolites is, in conjunction with gene expression and proteomics data, essential for the delineation of complex cellular networks and pathways. Metabolomics also has great potential utility in clinical settings for rapidly diagnosing disease or characterizing drug toxicity by identifying biomarkers of those cellular pathways altered in the disease state or targeted by therapeutic treatment. Research at PNNL is focusing on the development of ultra-sensitive, quantitative, and high throughput metabolomics measurements based upon the use of high performance liquid chromatography with high accuracy mass spectrometry. We will describe the benefits provided by high quality separations and the use of nano-LC to minimize ion suppression and increase sensitivity. Our initial progress will be illustrated by applications to microbial and mammalian systems.