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  • 1990-1994  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Bioprocess and biosystems engineering 5 (1990), S. 155-164 
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract A total cell recycling suspension perfusion reactor has been constructed for investigation of specific monoclonal antibody secretion rate of the 9.2.27 murine hybridoma under conditions of a very low growth rate. By rapidly recycling hybridoma cells using a thermostated tangential flow filter, 3.6 mg cell dry weight/cm3 could be maintained at growth rate of 〈0.05 μmax for over 250 h. Under these conditions, secretion of lactate, ammonia and l-alanine were directly related to the rate of l-glutamine supply. Monoclonal antibody accumulated in the reactor to levels in excess of 1400 μg/ cm3. Surprisingly, as specific growth rate decreased, the specific immunoglobulin secretion rate remained constant, implying that monoclonal antibody synthesis could be uncoupled from growth.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Bioprocess and biosystems engineering 5 (1990), S. 143-153 
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The batch productivity (Q TM) of the production of the nucleoside antibiotic toyocamycin (TM) by Streptomyces chrestomyceticus was increased ten-fold by selection of a UV generated mutant, optimization of pH, increasing incubation temperature from 28 °C to 36 °C, and addition of soy oil. Initial high oxygen transfer rates stimulated Q TM maxima two-fold. Antibiotic production by the mutant strain, U190, however, appeared more shear sensitive than the parent culture FCRF 341 with maximum antibiotic titer being inversely related to impellor tip velocity, T v . For this reason, scale-up could not be done at constant P/V or constant volumetric oxygen transfer. Instead, programming of impeller speed was evaluated in order to maintain optimal impeller tip velocity during scale-up. It was found that a low constant T v maintained in scale-up in geometrically similar vessels was most beneficial for duplication of optimal antibiotic productivity, Q TM. Pilot fermentations (120 dm3 scale) were used to determine coefficients of Q TM variation from oxygen uptake rate (OUR) and total CO2 evolution data for monitoring of Q TM variation during scale-up to the 12,000 dm3 scale. This technique allowed for on-line prediction of antibiotic titer and Q TM from fermentor exhaust gas data.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: An initial structured unsegregated kinetic model describing monoclonal antibody synthesis by a murine hybridoma cell line (9.2.27) grown in 1 liter batch cultures is described. The model is based on the intracellular balances of the heavy and light chain coding mRNAs, the intracellular balances of heavy and light chains and the description of the kinetics of heavy and light chain assembly. Model parameters were varied with specific growth rate in order to account for changes in the rates of antibody synthesis and secretion with entrance of the cells from the exponential into the stationary phase of growth. The parameters were varied based. on experimental data obtained in our laboratory on the variation of total cellular RNA content and the half-lives of heavy (H) and light (L) chain mRNAs with specific growth rate, and data from other investigators on immunoglobulin synthesis and secretion. The model successfully predicts the experimentally observed decrease in the intracellular heavy and light chain mRNA levels with entrance of 9.2.27 cells from the exponential into the stationary phase of growth, as well as the extracellular accumulation of antibody (IgG2a) during batch culture.
    Additional Material: 19 Ill.
    Type of Medium: Electronic Resource
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