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  • 1
    ISSN: 1573-0778
    Keywords: air lift ; macroporous ; microcarrier ; shear ; sparging ; Vero cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The death rate of Vero cells grown on Cytodex-3 microcarriers was studied as a function of the gas flow rate in a small air-lift loop reactor. The death rate may be described by first-order death-rate kinetics. The first-order death-rate constant as calculated from the decrease in viable cells, the increase in dead cells and the increase in LDH activity is linear proportional to the gas flow rate, with a specific hypothetical killing volume in which all cells are killed of about 2·10−3 m3 liquid per m3 of air bubbles. In addition, an experiment was conducted in the same air-lift reactor with Vero cells grown inside porous Asahi microcarriers. The specific hypothetical killing volume calculated from this experiment has a value of 3·10−4 m3 liquid per m3 of air bubbles, which shows that the porous microcarriers were at least in part able to protect the cells against the detrimental hydrodynamic forces generated by the bubbles.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-0778
    Keywords: air lift ; macroporous ; microcarrier ; shear ; sparging ; Vero cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The death rate of Vero cells grown on Cytodex-3 microcarrierswas studied as a function of the gas flow rate in a smallair-lift loop reactor. The death rate may be described byfirst-order death-rate kinetics. The first-order death-rateconstant as calculated from the decrease in viable cells, theincrease in dead cells and the increase in LDH activity islinear proportional to the gas flow rate, with a specifichypothetical killing volume in which all cells are killed ofabout 2.10-3m3 liquid per m3 of air bubbles.In addition, an experiment was conducted in the sameair-lift reactor with Vero cells grown inside porous Asahimicrocarriers. The specific hypothetical killing volumecalculated from this experiment has a value of 3.10-4m3 liquid per m3 of air bubbles, which shows thatthe porous microcarriers were at least in part able to protectthe cells against the detrimental hydrodynamic forcesgenerated by the bubbles.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cytotechnology 20 (1996), S. 221-229 
    ISSN: 1573-0778
    Keywords: insect cells ; bioreactors ; shear ; stirred vessel ; buble column ; airlift ; scale-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Conclusion In this chapter we have attempted to evaluate the most important parameters which can be useful for the pur-pose of design and scale up. Insect cells and animal cells in general can be grown well in large vessels. However, none of the theories and parameters discussed in this chapter have been validated on a larger scale than laboratory and small pilot reactors. Selection of the most suitable design and scale-up method there-fore needs in particular studies in larger vessels. The Kolmogorov theory and the killing-volume model are in this respect the most promising approaches for the optimal design of large-scale animal-cell bioreactors.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0006-3592
    Keywords: air-lift loop reactor ; shear ; serum ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The death rate of hybridoma cells, grown in a continuous culture, has been studied in a small air-lift loop reactor as a function of reactor height and injected gas flow rate. The first-order death-rate constant was found to be proportional to the reciprocal height and to the gas flow rate, in accordance with the hypothetical killing volume model for insect cells in bubble columns. Furthermore, the effect of the serum concentration on viable cell concentration and cell productivity has been investigated in a continuous culture. A serum component became growth limiting when the serum concentration was decreased from 2% to 1%. No effect of the serum concentration on specific cell productivity could be measured. Samples from this culture were also studied in the air-lift loop reactor to determine the effect of serum concentration on the shear sensitivity. The cells' shear sensitivity increased with decreasing serum concentration. The protective effect of serum was found to be physical as well as physiological.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 40 (1992), S. 179-182 
    ISSN: 0006-3592
    Keywords: animal-cell culture ; hybridoma ; reduced serum content ; shear sensistivity ; bubble-column design ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: In a stirred culture of hybridoma cells, the effects of serum reduction from 2.5% to 0% on growth and monoclonal antibody porduction have been investigated. The shear sensitivity of cells from the same culture has been tested in a bubble column. Serum reduction does not greatly affect viable-cell concentrations, but cell specific monoclonal-antibody production rate shows a decreasing trend. A gradual increase in sensitivity for sparging, which is nor the result of a long-term biological effect, has beeen measured in a bubble column at decreasing fetal calf serum concentrations. Finally, the hypothetical killing-volume model describing the death rate of insect cells in bubble columns has now been completely validated for the pertinent hybridoma-cell line.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0006-3592
    Keywords: shear ; air-lift loop reactor ; growth rate ; cell size ; hybridoma cell ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: To study the effects of the growth rate of the hybridoma cell Mn12 on productivity, cell cycle, cell size, and shear sensitivity, six continuous cultures were run at dilution rate of 0.011, 0.021, 0.023, 0.030, 0.042, and 0.058 h-1. This particular hybridoma cell appeared to be unstable in continuous culture with respect to specific productivity, as a sudden drop occurred after about 30 generations in continuous culture, accompanied by the appearance of two populations with respect to the cytoplasmic lgG content. The specific productivity increased with increasing growth rate. The shear sensitivity of the cell, as measured in a small air-lift loop reactor, increased with increasing growth rate. The mean relative cell size, as determined with a flow cytometer, increased with increasing growth rates. Furthermore, the fraction of cells in the S phase increased, and the fraction of cells in the G1/G0 phase decreased with increasing growth rates. © 1993 John Wiley & Sons, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 48 (1995), S. 49-65 
    ISSN: 0006-3592
    Keywords: cell cycle ; apoptosis ; hybridoma ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The Model presented in this work demonstrates the combination of cell-cycle model with a model describing the growth and conversion kinetics of hybridoma cells in a steady-state continuous culture. The cell-cycle model is based upon a population balance model as described by Cazzador et al. and assumes the existence of a cycling-and apoptotic-cell population, which together form the viable-cell population. In this part the fraction of apoptotic cells, the age distribution of the cycling and apoptotic-cell population, the mean volume and biomass content per cell of the cycling, apoptotic, and viable cells, and the specific growth and death rates of the cells are calculated. The metabolic part consists of a Monod-type growth equation, four elemental balances, an equation assuming a constant yield of ammonia on glutamine, an equation for product formation, and the relation of Glacken for energy production. Furthermore, a maintenance-energy model for the consumption of glucose and glutamine is introduced, which combines the approaches of Herbert and Pirt into one model in a way similar to Beeftink et al. For energy consumption a Pirt model is assumed. The model is capable of predicting trends in steady-state vaues of a large number of variables of interest like specific growth rate, specific death rate, viability, cell numbers, mean viable-cell volume, and concentrations and conversion rates of product, glucose, glutamine, lactate, and ammonia. Also the concentrations and conversion rates of oxygen and carbon dioxide are qualitatively predicted. The values of the model predictions are generally close to experimental data obtained from literature. © 1995 John Wiley & Sons, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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