Metabolomics as molecular analysis tool in cell culture engineering

So far, cell culture engineering has used the high-throughput transcriptional and more recently protein profiling techniques attempting to further understand and resolve significant issues regarding the cell culture performance and its optimization. At the metabolic level, flux analysis has been used to monitor changes in the metabolic state that could affect the successful outcome of cell cultures. Metabolomics, referring to the simultaneous quantification of the (relative) concentration of the free small metabolites, is the most recently introduced high-throughput method for the measurement of the metabolic fingerprint of a biological system. Considering the role of metabolism in the context of the overall cellular function, it is easily understandable why quantifying a complete and accurate metabolomic profile is foreseen to have a major positive impact in cell culture engineering research. We will present application of Gas Chromatorgaphy-Mass Spectrometry metabolomics to monitor and analyze mammalian cell culture systems. Specifically, two bioreactor processes will be discussed in which baby hamster kidney cells were cultivated in high-cell density perfusion reactors at both laboratory and manufacturing scales and samples were analyzed over the course of the cultivation. Metabolomics enabled the differentiation between cell cultures based on bioreactor type, and stage of cell growth. Multivariate statistical analysis enabled the identification of the metabolites whose change in concentration was characteristic of the modification in any of these macroscopic parameters. The acquired results support the usefulness of metabolomics as a molecular analysis tool in cell culture engineering.