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Biotechnol Adv. 2014 Mar-Apr;32(2):514-25. doi: 10.1016/j.biotechadv.2014.01.004. Epub 2014 Jan 21.

Multi-stage continuous high cell density culture systems: a review.

Author information

1
Department of Chemical and Biomolecular Engineering, KAIST, 291 Daehak-ro, Daejeon 305-701, Republic of Korea. Electronic address: hnchang@kaist.edu.
2
Department of Chemical and Biomolecular Engineering, KAIST, 291 Daehak-ro, Daejeon 305-701, Republic of Korea.
3
KITECH, 143 Hanggaul-ro, Ansan-si, Gyeonggi-do 426-910, Republic of Korea.
4
Department of Chemical Engineering, Pukyong National University, 365 Sinseon-ro, Busan 608-739, Republic of Korea.

Abstract

A multi-stage continuous high cell density culture (MSC-HCDC) system makes it possible to achieve high productivity together with high product titer of many bioproducts. For long-term continuous operation of MSC-HCDC systems, the cell retention time and hydraulic retention time must be decoupled and strains (bacteria, yeast, plant, and animal cells) must be stable. MSC-HCDC systems are suitable for low-value high-volume extracellular products such as fuel ethanol, lactic acid or volatile fatty acids, and high-value products such as monoclonal antibodies as well as intracellular products such as polyhydroxybutyric acid (PHB), microbial lipids or a number of therapeutics. Better understanding of the fermentation kinetics of a specific product and reliable high-density culture methods for the product-generating microorganisms will facilitate timely industrialization of MSC-HCDC systems for products that are currently obtained in fed-batch bioreactors.

KEYWORDS:

High cell density culture; Multi-stage continuous bioreactors; Product titer improvement; Productivity improvement

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