Analysis of oxygen transport to hepatocytes in a flat-plate microchannel bioreactor.
Oxygen transfer to cultured hepatocytes in microchannel parallel-plate bioreactors with and without an internal membrane oxygenator was investigated with a mathematical model and the results were corroborated with fluorescence imaging experiments. The consumption of oxygen by hepatocytes was assumed to follow Michaelis-Menten kinetics. Our simulations indicate that under conditions of low Péclet (Pe) number (<80) and fixed Damlkohler number (= 0.14, corresponding to rat hepatocytes) the cells are hypoxic in the bioreactor without an internal membrane oxygenator. Under the same conditions, the bioreactor with an internal membrane oxygenator can avoid cell hypoxia by appropriate selection of membrane Sherwood number and/or the gas phase oxygen partial pressure, thus providing greater control of cell oxygenation. At high Pe, both bioreactors are well oxygenated. Experimentally determined oxygen concentrations within the bioreactors were in good qualitative agreement with model predictions. At low Pe, cell surface oxygen depletion was predicted from analytically derived criteria. Hepatocytes with oxygen dependent functional heterogeneity may exhibit optimal function in the bioreactor with the internal membrane oxygenator.
Roy
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P
Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, Boston, USA.
Baskaran
H
H
Tilles
A W
AW
Yarmush
M L
ML
Toner
M
M
D000818:Animals; D019149:Bioreactors; D003198:Computer Simulation; D005260:Female; D005470:Fluorometry; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008954:Models, Biological; D010100:Oxygen / Q000097:blood / Q000378:metabolism*; D010107:Oxygenators, Membrane; D010477:Perfusion / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D015203:Reproducibility of Results; D012212:Rheology
D010100:Oxygen