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Development of a single‐pass ceramic matrix bioreactor for large‐scale mammalian cell culture
Author(s) -
Applegate Mark A.,
Stephanopoulos Gregory
Publication year - 1992
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.260400909
Subject(s) - bioreactor , residence time (fluid dynamics) , residence time distribution , continuous stirred tank reactor , scale up , chromatography , materials science , chemical engineering , chemistry , process engineering , pulp and paper industry , mineralogy , engineering , physics , inclusion (mineral) , geotechnical engineering , organic chemistry , classical mechanics
A single‐pass, plug‐flow bioreactor has been developed in which oxygen is supplied to entrapped hybridoma cells via sllicone tubes threaded through the square channels of a macroporous ceramic monolith. Oxygen diffuses from the gas phase, through the silicone tubing, across the open square channel, and into the pores of the ceramic wall where it is consumed by entrapped cells. Advantages of such a reactor include higher product yields, protection of cells from detrimental hydrodynamic effects, no internal moving parts to compromise asepsis, and simplicity of operation. A prototype bioreactor was constructed and operated over a range of residence times. A side‐by‐side experimental comparison with a conventional recycle bioreactor was performed by inoculating both bioreactors with cells from the same stock culture and feeding medium from the same reservoir. Final antibody titers were 80% higher in the single‐pass bioreactor at a residence time of 200 minutes compared with those of the recycle bioreactor at a residence time of 800 minutes. A theoretical analysis of oxygen transport in this bioreactor is developed to highlight important design criteria and operating strategies for scale‐up. © 1992 John Wiley & Sons, Inc.