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Boosting Bioreactor Performance by Enhancing Mass Flow Controller Accuracy


Today’s biopharmaceuticals are revolutionizing healthcare. Drugs used to treat complex cancers or chronic conditions such as rheumatoid arthritis are offering new hope for decades-old problems.

Bioreactor using Mass Flow Controllers

The biotechnologies associated with new drugs and gene-based therapies have become increasingly complex, requiring correspondingly complex manufacturing processes. Biopharmaceuticals, also known as biologics, are drugs that are derived from biological sources such as organs, tissues, mammalian cell lines, or genetically modified cells & organisms. Researching and producing these cutting-edge biologics requires the newest generation of bioreactors capable of providing a stable, precisely controlled growth environment for highly sensitive botanical and mammalian cell cultures. To create those environments, bioreactors require accurate, stable gas control to maintain critical process parameters, combined with maximum uptime to reach target yields.

Mass Flow Controllers (MFCs) in Bioreactors: Controlling Critical Flows of Dissolved Oxygen and pH Levels

Maintaining a controlled environment within the bioreactor is an essential step toward achieving optimal cell growth. Two critical factors that govern cell culture yield are the levels of dissolved oxygen (DO) in the bioreactor and the pH of the fermentation broth. The cells within the bioreactor survive only if certain process parameters, such as DO and pH, stay within specified operating conditions. To maintain these optimal process conditions, bioreactors rely on mass flow controllers to deliver accurate and stable flow of critical gases that stabilize key functions within the bioreactor.

Tight control of dissolved oxygen is achieved by enriching the airflow with oxygen, or by depleting it with nitrogen. Maintaining the proper levels of DO in turn regulates cell growth and reduces the production of toxic cell by-products. Together, these conditions increase reactor yields – enriching air flow with O2 or depleting it with N2 better regulates overall cell growth rates.

Tight control of pH with carbon dioxide flow is also critical for creating the proper growth environment within the bioreactor. Some bioreactor processes introduce acids and bases to achieve the desired pH level, but this approach is often too harsh for the delicate mammalian cells involved in bioprocessing. Using CO2 to tightly control pH levels has been found to be a more effective approach to maintain a stable fermentation broth for those delicate cell cultures. 

The gas flow meter is a key element to overall bioreactor performance and uptime. The gas flow meters control the delivery of the critical gasses that maintain the proper levels of both dissolved oxygen and the pH of the fermentation broth – and because typical bioreactor process runs can last up to 15 days, precise accuracy and continuous stable performance of the flow meter are vital. That’s why it’s important to be certain the gas flow meter is actually delivering the flow rate stated in its technical documentation.

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About The Author

Steve Kannengieszer
Director of Marketing

Steve is director of marketing, mass flow products at Brooks Instrument with responsibility for Coriolis, thermal mass flow and pressure products.

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