Multi-stage continuous high cell density culture systems: a review.
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.
Department of Chemical and Biomolecular Engineering, KAIST, 291 Daehak-ro, Daejeon 305-701, Republic of Korea. Electronic address: hnchang@kaist.edu.
Ho Nam
HN
Chang
Department of Chemical and Biomolecular Engineering, KAIST, 291 Daehak-ro, Daejeon 305-701, Republic of Korea.
Kwonsu
K
Jung
Department of Chemical and Biomolecular Engineering, KAIST, 291 Daehak-ro, Daejeon 305-701, Republic of Korea.
Jin-Dal-Rae
JD
Choi
KITECH, 143 Hanggaul-ro, Ansan-si, Gyeonggi-do 426-910, Republic of Korea.
Joon Chul
JC
Lee
Department of Chemical Engineering, Pukyong National University, 365 Sinseon-ro, Busan 608-739, Republic of Korea.
Hee-Chul
HC
Woo
D001419:Bacteria; D056804:Biofuels; D019149:Bioreactors; D002452:Cell Count; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D003470:Culture Media; D005285:Fermentation; D011994:Recombinant Proteins / Q000378:metabolism
D056804:Biofuels; D003470:Culture Media; D011994:Recombinant Proteins
High cell density culture; Multi-stage continuous bioreactors; Product titer improvement; Productivity improvement