BIOLOGICAL RESPONSES OF HYBRIDOMA CELLS TO HYDRODYNAMIC SHEAR IN AN AGITATED BIOREACTOR

被引:37
作者
ABUREESH, I [1 ]
KARGI, F [1 ]
机构
[1] WASHINGTON UNIV,DEPT CHEM ENGN,BIOTECHNOL ENGN LAB,ST LOUIS,MO 63130
关键词
HYDRODYNAMIC SHEAR; HYBRIDOMA; AGITATED BIOREACTOR; MONOCLONAL ANTIBODIES;
D O I
10.1016/0141-0229(91)90108-M
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Effects of long-term hydrodynamic shear on hybridoma cells were investigated in a 250-ml continuous stirred-tank reactor (CSTR). Cells grown at steady state were subjected to step changes in agitation rates. Cell viability, glucose consumption, and monoclonal antibody (MAb) production were determined at high agitation rates and compared with the control (100 rev min-1). Impeller tip speeds higher than 40 cm s-1 caused a significant drop in cell concentration and respiration activity, and increased lactate dehydrogenase (LDH) release to the culture medium. Also, high agitation speeds caused a decrease in MAb concentration and an increase in specific glucose consumption rate. The effects of dilution rate and serum concentration on the sensitivity of hybridoma cells to hydrodynamic shear were determined. Serum was found to protect the cells against shear damage and had a significant positive effect on hybridoma growth and MAb production. Shear damage on cells in CSTR was approximated to first-order kinetics. The death rate constant increased sharply at impeller tip speeds above 40 cm s-1.
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页码:913 / 919
页数:7
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