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  • 1
    Electronic Resource
    Electronic Resource
    High density fed-batch cultures for hybridoma cells performed with the aid of a kinetic model (1996)
    Springer
    Bioprocess and biosystems engineering 15 (1996), S. 117-124 
    Details
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Hybridoma fed-batch cultures with either standard medium as feed or concentrated medium as feed and removal of toxic metabolites through dialysis were performed by using model calculations for “a priori” determination of process parameters. In a first step a kinetic model for specific growth and death rate, respectively as well as for substrate uptake and metabolite production rates was formulated. In a bed-batch culture with standard medium as feed the appropriate time for start of the feeding pump and the increase of feed rate were determined “a priori”. The glutamine concentration was controlled at 0.04 mmoll−1. “A priori” calculation and course of the culture coincided rather well. A cell concentration of 3.2×106 cells ml−1, a MAb-concentration of 54 mg MAb l−1 and a MAb-time-space-yield of 0.53 mg MAb l−1h−1 were obtained. For further increase of the efficiency a high density fed-batch process was developed, where concentrated medium is fed to the cells and the accumulating toxic low molecular weight metabolites are removed through a dialysis membrane into a dialyizng fluid. In a membrane dialysis reactor consisting of a culture chamber and a dialyzing chamber, which are separated by a cylindrical dialysis membrane, again model calculations were used to determine feed rate and exchange rate of dialyzing fluid. A viable cell density of 1.2×107 cells ml−1 and a MAb concentration of 425 mg l−1 were reached in a culture with stepwise feeding of 10 x concentrated medium and exchange of dialyzing fluid for removal of low molecular metabolites. The course of the culture could be predicted “a priori” rather well. The MAb-time-space-yield was 2.47 mg MAb l−1h−1, appr. 5 times higher compared to fed-batch cultures with standard medium as feed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00369614
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    High density fed-batch cultures for hybridoma cells performed with the aid of a kinetic model (1996)
    Springer
    Bioprocess engineering 15 (1996), S. 117-124 
    Details
    ISSN: 0178-515X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Hybridoma fed-batch cultures with either standard medium as feed or concentrated medium as feed and removal of toxic metabolites through dialysis were performed by using model calculations for “a priori” determination of process parameters. In a first step a kinetic model for specific growth and death rate, respectively as well as for substrate uptake and metabolite production rates was formulated. In a bed-batch culture with standard medium as feed the appropriate time for start of the feeding pump and the increase of feed rate were determined “a priori”. The glutamine concentration was controlled at 0.04 mmol l-1. “A priori” calculation and course of the culture coincided rather well. A cell concentration of 3.2 * 106 cells ml-1, a MAb-concentration of 54 mg MAb  l-1 and a MAb-time-space-yield of 0.53 mg MAb  l-1 h-1 were obtained. For further increase of the efficiency a high density fed-batch process was developed, where concentrated medium is fed to the cells and the accumulating toxic low molecular weight metabolites are removed through a dialysis membrane into a dialyzing fluid. In a membrane dialysis reactor consisting of a culture chamber and a dialyzing chamber, which are separated by a cylindrical dialysis membrane, again model calculations were used to determine feed rate and exchange rate of dialyzing fluid. A viable cell density of 1.2 * 107 cells ml-1 and a MAb concentration of 425 mg l-1 were reached in a culture with stepwise feeding of 10×concentrated medium and exchange of dialyzing fluid for removal of low molecular metabolites. The course of the culture could be predicted “a priori” rather well. The MAb-time-space-yield was 2.47 mg MAb  l-1 h-1, appr. 5 times higher compared to fed-batch cultures with standard medium as feed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00369614
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Fixed-bed dialysis culture of a transfectoma cell line producing chimeric Fab-fragments with “nutrient-split”-feeding strategy (1998)
    Springer
    Biotechnology techniques 12 (1998), S. 501-505 
    Details
    ISSN: 1573-6784
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The very shear sensitive transfectoma cell line, FAB 10, producing a chimeric Fab-antibody fragment specific for the human carcinoembryonic antigen (CEA), was cultivated in fixed bed reactors where the cells were immobilized in macroporous carriers. As the cell line had a very low productivity, cultures with “process integrated product enrichment” were performed in a membrane dialysis bioreactor with integrated fixed bed, where low molecular weight metabolites are removed over the membrane and high molecular weight products are enriched. In a new “nutrient-split” feeding strategy for dialysis cultures concentrated medium was supplied directly to the fixed bed unit, whereas a buffer solution was used as dialysis fluid. With the dialysis technique up to 5800 μg Fab l−1 could be obtained, more than 10 times higher compared to fixed bed cultures without dialysis or batch cultures with suspended cells. The “nutrient-split”-feeding strategy reduced the amount of medium required per mg of antibody significantly. © Rapid Science Ltd. 1998
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008839127835
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    159. Scale-up und Reaktorgestaltung für Festbett-Zellkultur-Reaktoren zur Produktion monoklonaler Antikörper (1996)
    Weinheim : Wiley-Blackwell
    Chemie Ingenieur Technik - CIT 68 (1996), S. 1168-1168 
    Details
    ISSN: 0009-286X
    Keywords: Chemistry ; Industrial Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cite.3306809161
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    Paper (German National Licenses)
    Fulltext
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