Monitoring cellular state transitions in a production-scale CHO-cell process using an electronic nose.

Area of Science:

• Biotechnology
• Bioprocess Engineering
• Analytical Chemistry

Background:

• Monitoring bioreactor off-gas composition is crucial for optimizing cell culture processes.
• Chinese Hamster Ovary (CHO) cell lines are widely used for recombinant protein production, including therapeutic proteins like factor VIII.
• Real-time process monitoring aids in maintaining product quality and detecting deviations.

Purpose of the Study:

• To evaluate the applicability of an electronic nose for monitoring bioreactor off-gas composition in CHO-cell cultures.
• To assess the electronic nose's capability for monitoring cellular state transitions and enabling process control.
• To demonstrate the early detection of microbial infections in bioprocesses.

Main Methods:

• Utilized an electronic nose to analyze off-gas from perfused CHO-cell bioreactors producing recombinant human blood coagulation factor VIII.
• Employed Principal Component Analysis (PCA) for visualizing process states and ideal conditions.
• Correlated electronic nose data with key process parameters like product and lactate formation.

Main Results:

• The electronic nose successfully identified characteristic process states linked to factor VIII and lactate production.
• The instrument demonstrated the ability to detect microbial infections at a very early stage.
• Principal Component Analysis (PCA) effectively visualized ideal process conditions, highlighting the on-line applicability of this method.

Conclusions:

• The electronic nose shows significant potential as an on-line sensor for bioprocess monitoring.
• It can ensure product and process quality in production-scale bioprocesses by providing real-time insights.
• Early detection of infections and monitoring of cellular states are key benefits for biopharmaceutical manufacturing.