ISSN:0008-4034    

DOI:10.1002/cjce.5450690201

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1991

数据来源: WILEY

摘要:

AbstractThe current state of protein production by eukaryotic cells in culture is reviewed by a cell biologist with an eye towards areas that could benefit from more work by chemical engineers. The basic question of how the type of bioreactor influences cell productivity has not been answered. We are still learning how to optimize protein production in all types of bioreactors. Recent examples show that optimization can increase productivity over 10‐fold. Support work needs to be done to determine the limits of individual cell productivity. Basic cell metabolism work needs to be done in serum‐free medium to make it generally applicable. Only then can better bioreactors be designed with useful probes to monitor important substan

ISSN:0008-4034    

DOI:10.1002/cjce.5450690202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1991

数据来源: WILEY

摘要:

AbstractThe demand for animal cell derived products has stimulated the development of bioreactors in the last decade. Most of those developments allow a higher cell concentration to be achieved in the bioreactor than in the past, primarily by means of the continuous flow of culture medium and a mechanism of cell retention. The advantages and technological challenges of some of these developments are discussed. Lagging behind the bioreactor developments is the strategy for culture operation and optimization. The need for suitable kinetic models to describe animal cell growth is emphasized.

ISSN:0008-4034    

DOI:10.1002/cjce.5450690203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1991

数据来源: WILEY

摘要:

AbstractThis work has investigated high density CRL‐1606 hybridoma cell culture in the shell‐side of ultrafiltration hollow fiber bioreactors. Oxygen depletion was measured in the recycle stream, and has been identified as the critical, axial scale‐limiting factor in these reactors. The composition of the extracapillary space has been studied by rapidly freezing these reactors in liquid nitrogen to recover samples of the shell‐side environment. The accumulation of inhibitory metabolites should have only a marginal impact on growth and product formation of this hybridoma cell line. Oxygen depletion is expected to be the major limiting factor for both the axial and radial scale‐up of hollow fiber bi

ISSN:0008-4034    

DOI:10.1002/cjce.5450690204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1991

数据来源: WILEY

摘要:

AbstractExperimental data collected from bench‐scale chemostat cultures of mouse‐mouse hybridoma cells have been used for the development of a kinetic model of monoclonal antibody production. The specific antibody productivity was found to be proportional to the specific death rate, indicating a stimulating effect of stress on the ability of the cells to produce antibody. The death rate was found to be an exponential function of the average cell age in the culture. Furthermore, a Generalized Maintenance Energy (GME) model is proposed, to take account of the effects of culture stress on the nutrient uptake rates. The proposed relationships agreed very well with other mouse‐mouse hybridoma chemostat culture data in the liter

ISSN:0008-4034    

DOI:10.1002/cjce.5450690205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1991

数据来源: WILEY

摘要:

AbstractA new method for immobilizing hybridoma cells using chitosan‐stabilized calcium alginate beads was developed. The ionotropic gelation of chitosan and calcium with alginate resulted in the formation of highly cross‐linked, porous beads that were mechanically and chemically stable in phosphate buffered medium. Hybridomas entrapped in these beads were cultured semi‐continuously using periodic medium exchange. Viable population densities in the order of 5 × I07cells/mL were attained within the beads and up to two‐fold increases in volumetric monoclonal antibody (MAb) productivity over batch suspension cultures were observed. Oxygen mass transfer limitations within the chitosan‐alginate beads were evaluated by considering biokinetics and diffusive transport. Model equations were developed and used to evaluate the effect of bead diameter on the contained cells. The predictions were consistent with experimental observations of maximum viable population densities attained in beads of va

ISSN:0008-4034    

DOI:10.1002/cjce.5450690206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1991

数据来源: WILEY

摘要:

AbstractThe oxygen transfer capabilities of a hollow fiber oxygenator for intended use in bubble‐free aerated bioreactors have been evaluated experimentally. The oxygenator (480 mL), which is the main component of an artificial heart/lung unit used routinely in cardiopulmonary bypass procedures, was assessed for use in a recycle stream to determine if the oxygen requirements in bubble‐free hybridoma cell bioreactors could be supported on a large scale. Oxygen transfer to simulated medium in a 15 L bioreactor was found to depend primarily on the liquid recirculation rate (1 to 5 L/min) and was not seriously affected by the air flowrate in the oxygenator (0.5 to 15 L/min). Based on the experimentally determined mass transfer coefficient across the membrane, it was found that the oxygenator could support a 100 L fermentor at an average cell density of 2xl06cells/mL with a specific uptake rate of 4.8 mgO2/(109cells ‐ h).Furthermore, if oxygen enriched air were to be used in the oxygenator, a single unit could support cell densities beyond 8xl06cells/mL in a 100 L working volume ferm

ISSN:0008-4034    

DOI:10.1002/cjce.5450690207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1991

数据来源: WILEY

摘要:

AbstractThe large scale cultivation of insect cells will likely play an increasingly important role for the commercial production of bioproducts. While much research work has been done on the engineering aspects of insect cell suspension culture, many questions remain unanswered (i.e. the nature of bubble damage in sparged reactors, shear sensitivity and adaptation of cells; the use of serum‐free medium). In addition, insect cell immobilization may become a suitable technique for enhancing cell densities and product concentrations. This article presents a brief critical review of the development of insect cell suspension culture techniques for the production of insect pathogenic viruses and recombinant proteins.The problems of culturing microencapsulated insect cells, infected with a temperature sensitive baculovirus, also is discusse

ISSN:0008-4034    

DOI:10.1002/cjce.5450690208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1991

数据来源: WILEY

摘要:

AbstractThe growth characteristics of the BM‐5 insect cell line ofBombyx mori(silkworm) have been experimentally investigated in order to develop optimal growth protocols when these cells are used to produce large quantities of biopesticides or human proteins by recombinant baculoviruses. Experiments were performed in 2 mL wells and 200 mL spinner flasks. Spinner flasks were operated at 80 rpm with 0.3% methyl cellulose (MCL) added to the medium in order to protect the cells from liquid shear stress. In addition to the effect of agitation rate and amount ofMCLadded to the medium, the cell response during the adaptation to growth in suspension from stationary cultures is reported. Exposure of the cells to varying nutrient and metabolite concentrations is accomplished through batch and repeated‐batch modes in 2 mL wells. The results imply that glutamine is a limiting nutrient and lactate has an inhibitory effect on cell growth. Ammonia depletion from the medium was accompanied by uric acid accumulation, suggesting that ammonia is converted to this metabolic product by the “uricotelic” and “nucleicolytic” metabol

ISSN:0008-4034    

DOI:10.1002/cjce.5450690209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1991

数据来源: WILEY

摘要:

AbstractExperiments were conducted on air‐lift reactors with different liquid volumes, aspect ratios, and gas‐liquid separator configurations, with constant downcomer to riser cross‐sectional area ratio and riser/downcomer height. Reactor performance was highly dependent on the gas‐liquid separator design. By changing the latter, the mode of operation could be changed from that of a concentric tube reactor (with gas recirculation) to an external loop reactor (without gas recirculation). Liquid velocity and overall gas hold‐up data were correlated to the power per liquid volume and “Disengagement Ratio”, a geometric parameter describing the separator's configuration. During scale‐up, similar gas hold‐ups and liquid velocities were found in laboratory and pilot reactors. A modified air‐lift reactor with an enlarged channel for a gas‐liquid separ

ISSN:0008-4034    

DOI:10.1002/cjce.5450690210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1991

数据来源: WILEY