Metabolomics for high-resolution monitoring of the cellular physiological state in cell culture engineering

Cell culture engineering has to-date used transcriptomic, proteomic, and metabolic flux analyses, attempting to resolve significant questions regarding cell culture performance. Despite the foreseen positive impact, the metabolomic analytical platform has not yet been vastly deployed. Presently, there is no published application of metabolomics to industrial-scale mammalian cell culture. We applied gas chromatography–mass spectrometry metabolomics to analyze baby hamster kidney (BHK) cells of various cell ages cultivated in high-cell density perfusion reactors at both laboratory and manufacturing scales. Cell growth, metabolic activity and protein productivity measurements, which are currently used to monitor the cellular physiological state, suggested consistency across bioreactors and over the course of the cultivation. Nevertheless, metabolomic profiling enabled the differentiation of cell cultures based on cell age, bioreactor scale and cell source. These results support the usefulness of metabolomics as a high resolution molecular analysis tool in cell culture engineering.