Improve Cell Culture Processes

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White Paper

Improve Cell Culture Processes

White Paper

White Paper on In-Line Control of CO₂ Accumulation

CO₂ measurements in cell culture processes
CO₂ measurements in cell culture processes

The importance of preventing dissolved CO₂ accumulation
Controlling dissolved CO₂ measurement in mammalian cell culture processes is growing in acceptance.

dCO₂ concentration in the human body is 5% and when growing animal cells ex-vivo it is necessary to maintain this level as a minimum concentration. In an ex-vivo culture model, for example in a bioreactor, measuring and monitoring dCO2 is considered critical for several reasons. dCO2 accumulation can have a substantial negative effect on cell growth as well as on productivity and the glycosylation of the targeted protein of interest.

Blood gas analyzers do not provide sufficient information
Controlling dissolved carbon dioxide accumulation in cell culture by sparging with air or oxygen is common, particularly on production-scale bioreactors. To monitor dCO₂, samples are normally taken for measurement in an off-line blood gas analyzer (BGA). This method is not without its issues: infrequent sampling does not provide continuous insight, and temperature changes and time delay between samples being taken and measured can affect dCO₂ level. These issues are not just confined to BGAs. Any off-line or at-line method can be subject to influences that prevent a true picture of dCO₂ levels being established.

Continuous, in-line measurements lead to higher process yield
As discussed in this white paper, use of in-line dCO₂ sensors in bioreactors provides accurate, real-time measurement without any of the problems of off-line or at-line analysis. Data from in-line sensors can be used to define CO₂ removal (or addition) regardless of bioreactor size, type of gas used for stripping, etc. It has been reported that dCO₂ control can increase cell growth rate by as much as 30%, and specific production rate above 30% with mammalian and insect cells.

The most important further advantage of continuous in-line monitoring, is the possibility to control dCO₂ concentration within defined limit values and to generate alarms when those values are exceeded.

This white paper shows how the METTLER TOLEDO InPro 5000i sensor, the only available in-line dCO₂ sensor for benchtop to production use, provides the real-time, continuous data necessary for allowing an efficient control strategy in mammalian cell culture processes, leading to improved process yield and final-product quality.

Highlights of the white paper:

  • Problems of high and low dCO₂ levels
  • How dCO₂ is controlled
  • Advantages of in-line measurement