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  • 1
    Electronic Resource
    Electronic Resource
    Effect of serum concentration on hybridoma viable cell density and production of monoclonal antibodies in cstrs and on shear sensitivity in air-lift loop reactors (1992)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 39 (1992), S. 891-897 
    Details
    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
    URL: http://dx.doi.org/10.1002/bit.260390902
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of dilution rate on growth, productivity, cell cycle and size, and shear sensitivity of a hybridoma cell in a continuous culture (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 41 (1993), S. 429-439 
    Details
    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
    URL: http://dx.doi.org/10.1002/bit.260410406
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Hydrodynamics and mixing in a multiple air-lift loop reactor (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 42 (1993), S. 994-1001 
    Details
    ISSN: 0006-3592
    Keywords: multiple air-lift loop reactor ; reactor series ; plug flow ; hydrodynamics ; modeling ; mixing ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A new bioreactor, in which a series of air-lift reactors with an internal loop is incorporated into one vessel, is introduced. With this multiple air-lift loop reactor (MAL) and approximation of an aerated plug-flow fermentor is strived for. Mixing, liquid velocity, and gas holdup were measured as a function of the gas flow rate in this new internal-loop reactor geometry. As a reference, hydrodynamics were also investigated in a conventional internal-loop reactor. A model description of the hydrodynamics in the second compartment of the MAL is given. This model is based on a two-phase, drift-flux model and a friction coefficient. Frictional losses were independent of the reactor bottom geometry, and were observed to increase with the gas flow rate as a result of the presence of stationary gas bubbles in the downcomer. The hydrodynamics and mixing of the second MAL compartment were comparable with those of conventional internal-loop reactors. © 1993 John Wiley & Sons, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260420810
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  • 4
    Electronic Resource
    Electronic Resource
    Death rate in a small air-lift loop reactor of vero cells grown on solid microcarriers and in macroporous microcarriers (1996)
    Springer
    Cytotechnology 21 (1996), S. 45-59 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00364836
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  • 5
    Electronic Resource
    Electronic Resource
    Hybridomas in a bioreactor cascade: modeling and determination of growth and death kinetics (1996)
    Springer
    Cytotechnology 21 (1996), S. 263-277 
    Details
    ISSN: 1573-0778
    Keywords: hybridomas ; serum-free medium ; monoclonal antibodies ; reactor series ; kinetics ; modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Hybridomas were cultured under steady-state conditions in a series of two continuous stirred-tank reactors (CSTRs), using a serum-free medium. The substrate not completely converted in the first CSTR, was transported with the cells to the second one and very low growth rates, high death rates, and lysis of viable cells were observed in this second CSTR. These conditions are hardly accessible in a single vessel, because such experiments would be extremely time-consuming and unstable due to a low viability. In contrast to what is often observed in literature, kinetic parameters could thus be derived without the neccessity for extrapolation to lower growth rates. Good agreement with literature averages for other hybridomas was found. Furthermore, showing that the reactor series is a valuable research tool for kinetic studies under extreme conditions, the possibility to observe cell death under stable and defined steady-state conditions offers interesting opportunities to investigate apoptosis and necrosis. Additionally, a model was developed that describes hybridoma growth and monoclonal antibody production in the bioreactor cascade on the basis of glutamine metabolism. Good agreement between the model and the experiments was found.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00365349
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  • 6
    Electronic Resource
    Electronic Resource
    Scale up aspects of sparged insect-cell bioreactors (1996)
    Springer
    Cytotechnology 20 (1996), S. 221-229 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00350402
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  • 7
    Electronic Resource
    Electronic Resource
    Death rate in a small air-lift loop reactor of vero cells grown on solid microcarriers and in macroporous microcarriers (1997)
    Springer
    Cytotechnology 23 (1997), S. 61-75 
    Details
    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
    URL: http://dx.doi.org/10.1023/B:CYTO.0000010399.23373.65
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    Paper (German National Licenses)
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