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Fermentanomics: Monitoring Mammalian Cell Cultures with NMR Spectroscopy
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Analytical Science Research and Development.
, ‡Bioprocess Research and Development.
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 1H 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.
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This article has been cited by 2 ACS Journal articles (2 most recent appear below).
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Metabolomics Profiling of Cell Culture Media Leading to the Identification of Riboflavin Photosensitized Degradation of Tryptophan Causing Slow Growth in Cell Culture
Li Zang, Ruth Frenkel, Jeffrey Simeone, Maureen Lanan, Mark Byers, and Yelena LyubarskayaAnalytical Chemistry2011 Article ASAPMetabolomics Profiling of Cell Culture Media Leading to the Identification of Riboflavin Photosensitized Degradation of Tryptophan Causing Slow Growth in Cell Culture
Li Zang, Ruth Frenkel, Jeffrey Simeone, Maureen Lanan, Mark Byers, and Yelena LyubarskayaAnalytical Chemistry2011 Article ASAPAs more protein biopharmaceuticals are produced using mammalian cell culture techniques, it becomes increasingly important for the biopharmaceutical industry to have tools to characterize the cell culture media and evaluate its impact on the cell culture ...
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History
- Published In Issue July 21, 2010
- Article ASAPJune 25, 2010
- Received: March 08, 2010
Received: March 08, 2010
ACS
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