Abstract:
:Increasing the throughput and efficiency of cell culture process development has become increasingly important to rapidly screen and optimize cell culture media and process parameters. This study describes the application of a miniaturized bioreactor system as a scaled-down model for cell culture process development using a CHO cell line expressing a recombinant protein. The microbioreactor system (M24) provides non-invasive online monitoring and control capability for process parameters such as pH, dissolved oxygen (DO), and temperature at the individual well level. A systematic evaluation of the M24 for cell culture process applications was successfully completed. Several challenges were initially identified. These included uneven gas distribution in the wells due to system design and lot to lot variability, foaming issues caused by sparging required for active DO control, and pH control limitation under conditions of minimal dissolved CO2. A high degree of variability was found which was addressed by changes in the system design. The foaming issue was resolved by addition of anti-foam, reduction of sparge rate, and elimination of DO control. The pH control limitation was overcome by a single manual liquid base addition. Intra-well reproducibility, as indicated by measurements of process parameters, cell growth, metabolite profiles, protein titer, protein quality, and scale-equivalency between the M24 and 2 L bioreactor cultures were very good. This evaluation has shown feasibility of utilizing the M24 as a scale-down tool for cell culture application development under industrially relevant process conditions.
journal_name
Biotechnol Bioengjournal_title
Biotechnology and bioengineeringauthors
Chen A,Chitta R,Chang D,Amanullah Adoi
10.1002/bit.22031subject
Has Abstractpub_date
2009-01-01 00:00:00pages
148-60issue
1eissn
0006-3592issn
1097-0290journal_volume
102pub_type
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