Abstract
There are many commercially and scientifically relevant products that must be produced in mammalian cell systems. Growth and maintenance systems (bioreactors) for mammalian cells are not well characterized, however, since these cells are more fastidious and sensitive than are microorganisms. Optimization of mammalian cell bioreactors can be facilitated by nondestructive monitoring of cellular physiology and metabolism in situ. Nuclear Magnetic Resonance (NMR) spectroscopy is ideal for this application. NMR can monitor a variety of parameters of intra and extracellular metabolites that contain nuclei with net magnetic moments. Such analyses can be used to determine energization, levels of 31P and 1Hcontaining metabolites, selected enzyme kinetics, compartmentalized ion activities, metabolic fates of 3H, 2H, 13C, 15N or 19Flabeled tracers, O2 tension, compartmentalized redox potential, membrane potential, cell number and cell volume. These can all be monitored with reasonable time resolution with minimum perturbation of the sample.
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Both Microgon (Laguna Hills, CA—ph ♯ 800.654.0111) and SETEC (Livermore, CA—ph ♯ 415.449.1727) are in the process of developing NMR-compatible hollow fiber bioreactors for commercial use.
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Gillies, R., MacKenzie, N. & Dale, B. Analyses of Bioreactor Performance by Nuclear Magnetic Resonance Spectroscopy. Nat Biotechnol 7, 50–54 (1989). https://doi.org/10.1038/nbt0189-50
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DOI: https://doi.org/10.1038/nbt0189-50