High density culture of mammalian cells with dynamic perfusion based on on-line oxygen uptake rate measurements.
In a continuous culture with cell retention the perfusion rate must be adjusted dynamically to meet the cellular demand. An automated mechanism of adjusting the perfusion rate based on real-time measurement of the metabolic load of the bioreactor is important in achieving a high cell concentration and maintaining high viability. We employed oxygen uptake rate (OUR) measurement as an on-line metabolic indicator of the physiological state of the cells in the bioreactor and adjusted the perfusion rate accordingly. Using an internal hollow fiber microfiltration system for total cell retention, a cell concentration of almost 10(8) cells/mL was achieved. Although some aggregates were formed during the cultivation, the viability remained high as examined with confocal microscopy after fluorescent vital staining. The results demonstrate that on-line OUR measurement facilitates automated dynamic perfusion and allows a high cell concentration to be achieved.
Kyung
Y S
YS
Department of Chemical Engineering & Materials Science, University of Minnesota, Minneapolis.
Peshwa
M V
MV
Gryte
D M
DM
Hu
W S
WS
D002460:Cell Line / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D009862:Online Systems; D010100:Oxygen / Q000378:metabolism*; D010477:Perfusion
D010100:Oxygen