title: Fermentanomics: monitoring mammalian cell cultures with NMR spectroscopy.
abstract: As the number of therapeutic proteins produced by mammalian cell cultures in the pharmaceutical industry continues to increase, the need to improve productivity and ensure consistent product quality during process development activities becomes more significant. Rational medium design is known to improve cell culture performance, but an understanding of nutrient consumption and metabolite accumulation within the medium is required. To this end, we have developed a technique for using 1D (1)H NMR to quantitate nonprotein feed components and metabolites in mammalian cell cultures. We refer to the methodology as "Fermentanomics" to differentiate it from standard metabolomics. The method was found to generate spectra with excellent water suppression, signal-to-noise, and resolution. More importantly, nutrient consumption and metabolite accumulation was readily observed. In total, 50 media components have been identified and quantitated. The application of Fermentanomics to the optimization of a proprietary CHO basal medium yielded valuable insight regarding the nutrient levels needed to maintain productivity. While the focus here is on the extracellular milieu of CHO cell cultures, this methodology is generally applicable to quantitating intracellular concentrations and can be extended to other mammalian cell lines, as well as platforms such as yeasts, fungi, and Escherichia coli.
authors.affiliation: Analytical Science Research and Development, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Bradley
authors.forename: Anli
authors.initials: A
authors.lastname: Ouyang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Purdie
authors.forename: Tim A
authors.initials: TA
authors.lastname: Smitka
authors.forename: Tongtong
authors.initials: T
authors.lastname: Wang
authors.forename: Andreas
authors.initials: A
authors.lastname: Kaerner
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*
chemical_list: D003470:Culture Media