Monitoring Chinese hamster ovary cell culture by the analysis of glucose and lactate metabolism

摘要

Monitoring cell growth is crucial to the success of an animal cell culture process that can be accomplished by a variety of direct or indirect methodologies. Glucose is a major carbon and energy source for cultured mammalian cells in most cases, but glycolytic metabolism often results in the accumulation of lactate. Glucose and lactate levels are therefore routinely measured to determine metabolic activities of a culture. Typically, neither glucose consumption rate nor lactate accumulation rate has a direct correlation with cell density due to the changes in culture environment and cell physiology. We discovered that although the metabolic rate of glucose or lactate varies depending on the stages of a culture, the cumulative consumption of glucose and lactate combined (Q(GL)) exhibits a linear relationship relative to the integral of viable cells (IVC), with the slope indicating the specific consumption rate of glucose and lactate combined (q(GL)). Additional studies also showed that the q(GL) remains relatively constant under different culture conditions. The insensitivity of the q(GL) to process variations allows a potentially easy and accurate determination of viable cell density by the measurement of glucose and lactate. In addition, the more predictable nature of a linear relationship will aid the design of better forward control strategies to improve cell culture processes.