Biotechnology and Bioengineering · 1986 · 346 citations · 19 references
Life SciencesBiotechnologyCell BiologyBioenergeticsCellular MetabolismMetabolismAnimal Cell CultureCell Growth KineticsCellular Energy MetabolismMammalian Cell CultureNutrient MetabolismNutrient UtilizationAtp Production RateCell Culture KineticsConcentrationLactic Acid ProductionOxygen Uptake RateOxygen Uptake Rate EstimationProduct Yield EnhancementProduction Costs
Mammalian cell cultures excrete lactic acid and ammonium, limiting growth and product synthesis, and frequent medium replenishment—necessary to prevent waste accumulation—raises serum usage and production costs. The study demonstrates strategies to reduce lactic acid and ammonium production in mammalian cultures by controlling glucose and glutamine addition. The authors model ammonium–glutamine kinetics, develop an online cell‑concentration estimator based on ATP production from oxygen uptake and lactic‑acid rates, and highlight its importance for precise nutrient control.
Mammalian cells grown in culture excrete lactic acid and ammonium ions in quantities that may limit growth and reduce product synthesis. Frequent replenishment of the culture medium is often necessary to prevent waste product accumulation which could inhibit cell growth. Since increased medium replenishment results in increased usage of animal serum, the most expensive raw material, excessive production of waste products lowers the cell and product yield on serum, and hence increases production costs. Strategies for reducing the production of lactic acid and ammonium bymammalian cells via controlled addition of glucose and glutamine will be demonstrated. Mathematical relations coupling ammonium and glutamine kinetics will be described. Additionally, a method for automatic on-line estimation of the cell concentration was developed. This method involves calculating the ATP production rate from the oxygen uptake rate and the lactic acid production rate. Automatic online estimation of the cell concentration is critical if nutrient levels in large-scale mammaliancell cultures are to be accurately maintained via process control.
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The serial cultivation of human diploid cell strains
Leonard Hayflick, Paul S. Moorhead · Experimental Cell Research · 1961 · 8.4K citations
Food and Cosmetics Toxicology · 1966 · 4.3K citations