Scale-up and optimization of an acoustic filter for 200 L/day perfusion of a CHO cell culture
Article first published online: 24 SEP 2002
Copyright © 2002 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 80, Issue 4, pages 438–444, 20 November 2002
How to Cite
Gorenflo, V. M., Smith, L., Dedinsky, B., Persson, B. and Piret, J. M. (2002), Scale-up and optimization of an acoustic filter for 200 L/day perfusion of a CHO cell culture. Biotechnol. Bioeng., 80: 438–444. doi: 10.1002/bit.10386
- Issue published online: 24 SEP 2002
- Article first published online: 24 SEP 2002
- Manuscript Accepted: 23 APR 2002
- Manuscript Received: 4 JAN 2001
- Natural Sciences and Engineering Research Council of Canada
- mammalian cell culture;
- Chinese hamster ovary cells (CHO cells);
- cell retention;
Acoustic cell retention devices have provided a practical alternative for up to 50 L/day perfusion cultures but further scale-up has been limited. A novel temperature-controlled and larger-scale acoustic separator was evaluated at up to 400 L/day for a 107 CHO cell/mL perfusion culture using a 100-L bioreactor that produced up to 34 g/day recombinant protein. The increased active volume of this scaled-up separator was divided into four parallel compartments for improved fluid dynamics. Operational settings of the acoustic separator were optimized and the limits of robust operations explored. The performance was not influenced over wide ranges of duty cycle stop and run times. The maximum performance of 96% separation efficiency at 200 L/day was obtained by setting the separator temperature to 35.1°C, the recirculation rate to three times the harvest rate, and the power to 90 W. While there was no detectable effect on culture viability, viable cells were selectively retained, especially at 50 L/day, where there was a 5-fold higher nonviable washout efficiency. Overall, the new temperature-controlled and scaled-up separator design performed reliably in a way similar to smaller-scale acoustic separators. These results provide strong support for the feasibility of much greater scale-up of acoustic separations. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 438–444, 2002.