Long term shear effects on a hybridoma cell line by dynamic perfusion devices |
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Authors: | T L LaPorte J Shevitz Y Kim S S Wang |
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Institution: | (1) Present address: Bristol-Myers Squibb Company, 08903 New Brunswick, NJ, USA;(2) Present address: Incell Corporation, 07039 Livingston, NJ, USA;(3) Department of Chemical and Biochemical Engineering, Rutgers, The State University of NJ, 08855 Piscataway, NJ, USA;(4) New Brunswick Scientific, 08818 Edison, NJ, USA |
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Abstract: | The long term shear effects on a hybridoma cell line were studied by the simulation of a hollow fiber perfusion system. Various mechanical/environmental stress conditions were applied and steady state concentrations of live, dead and lysed cells were measured or calculated in a continuous culture. From mathematical modeling, it is shown that inclusion of a lysed cell index (LCI) renders a better fit to the material balance equation at steady state. The specific cell death rate increased with increasing shear force as expected only when the LCI was included. Without the inclusion of the LCI, the calculated specific cell growth rates are about 25–60% of the value when included. The results reported may lend some insight to design improvements since most perfusion devices add shear stresses to the cells in the reactor.List of Symbols
b ml/hr
continuous culture flow rate
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D hr–1
dilution rate (b/V)
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m g glucose/109 cells/hr
specific maintenance coefficient
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S
0
g/l
feed substrate concentration
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S g/l
reactor substrate concentration
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t hr
time
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V ml
reactor volume
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X
+ cells/ml
live cell concentration
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X
– cells/ml
dead cell concentration
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X
0 cells/ml
lysed cell concentration
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Y
x/s
109 cells/g glucose
cell/substrate yield coefficient
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hr–1
specific growth rate
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hr–1
specific death rate
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hr–1
specific lysis rate
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hr–1
specific lysis rate for simultaneous death and lysis |
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Keywords: | |
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