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  • Articles  (24)
  • bioreactor  (24)
  • 1990-1994  (24)
  • 1950-1954
  • Process Engineering, Biotechnology, Nutrition Technology  (24)
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  • 1
    ISSN: 1573-0778
    Keywords: Cell culture ; high cell density ; oxygen consumption ; bioreactor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract In a continuous culture with cell retention the perfusion rate must be adjusted dynamically to meet the cellular demand. An automated mechanism of adjusting the perfusion rate based on real-time measurement of the metabolic load of the bioreactor is important in achieving a high cell concentration and maintaining high viability. We employed oxygen uptake rate (OUR) measurement as an on-line metabolic indicator of the physiological state of the cells in the bioreactor and adjusted the perfusion rate accordingly. Using an internal hollow fiber microfiltration system for total cell retention, a cell concentration of almost 108 cells/mL was achieved. Although some aggregates were formed during the cultivation, the viability remained high as examined with confocal microscopy after fluorescent vital staining. The results demonstrate that on-line OUR measurement facilitates automated dynamic perfusion and allows a high cell concentration to be achieved.
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  • 2
    ISSN: 1573-0778
    Keywords: Ammonia ; animal cell ; bioreactor ; fed-batch culture ; feeding strategy ; lactate ; medium design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract In our previous work (Xie and Wang, 1994a), a simplified stoichiometric model on energy metabolism for animal cell cultivation was developed. Fed-batch experiments were performed in T-flasks using this model in supplemental medium design (Xie and Wang, 1994b). In this work, the major pathways of glucose and glutamine metabolism were incorporated into the stoichiometric model. Fed-batch culture was conducted in a 2-liter bioreactor with appropriate process control strategies. Nutrient concentrations, especially glucose and glutamine, were maintained at constant but low levels through the automated feeding of a supplemental medium formulated using the improved stoichiometric model. The formation of toxic byproducts, such as ammonia and lactate (Hassellet al., 1991), was greatly reduced. The specific lactate production rate was decreased by 62-fold compared with batch culture in bioreactor and by 8-fold compared to fed-batch culture in T-flask using the previous stoichiometric model. Ammonia formation was also decreased compared with both the batch and fed-batch cultures. Most importantly, the monoclonal antibody concentration reached 900 mg l−1, an increase of 17- and 1.6-fold compared with the batch and fed-batch cultures respectively.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    World journal of microbiology and biotechnology 8 (1992), S. 106-109 
    ISSN: 1573-0972
    Keywords: Adecanol ; adhesion ; anthocyanin ; bioreactor ; foaming ; Perilla frutescens ; plant cell ; silicone ; surfactant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The effects of surfactants, adecanol LG-294 and silicone A, on anthocyanin accumulation and the growth ofPerilla frutescens cells in suspension cultures were studied. Production of the red pigment was remarkably reduced from about 1.9 g/l to 0.4 g/l by adecanol LG-294 at 0.06 ml/l but not by silicone A up to 0.4 ml/l. Several repeated shake-flask cultures also demonstrated no adverse effects of silicone A on the metabolite accumulation by the suspended cells. Furthermore, the addition of silicone A to a culture in a stirred bioreactor produced a three-fold higher growth rate and a seven-fold increase in anthocyanin compared with surfactant-free cultures. The improvement was due to the substantial reduction or prevention of foaming and of cell adhesion to the bioreactor wall.
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  • 4
    ISSN: 1573-0778
    Keywords: collagen ; animal cell ; bioreactor ; cell immobilization ; cell entrapment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract A new bioreactor for animal cell cultivation employs two compartments for cells and medium respectively. The two chambers are separated by an ultrafiltration membrane. Cells and solution of collagen or collagen/chitosan mixture were loaded to the cell chamber and were allowed to form gel inside. Contraction of the cell-laden gel occurred subsequently to create a new zone in the cell chamber. In such a bioreactor cells are retained in the reactor, the high molecular product(s) accumulate in the cell chamber, while the small molecular weight nutrients and metabolites are replenished and removed from the medium chamber. By adjusting the flow rates for cell and medium chambers, the resident time for cells, high and low molecular weight components of the system can be manipulated separately. The new bioreactor, in both flat-bed and hollow-fiber configurations, was used to cultivate recombinant human cell, 293, for Protein C production over 60 to 90 days.
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  • 5
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 37 (1991), S. 834-842 
    ISSN: 0006-3592
    Keywords: microalgae ; bioreactor ; CO2 ; absorption ; KLa ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: For the characterization of CO2 absorption in aerated microalgal culture systems, a different approach based on KLa(O2) determination and transformation was studied. To confirm the validity of this method, the influence of reactions between CO2 and compounds (OH-, H2O, and NH3) present in the culture medium upon the absorption mechanism was evaluated under different physical and chemical culture conditions. Under these conditions, knowledge of the relative magnitudes of the diffusion and reaction kinetics permitted the evaluation of their relative importance. For the determination of the parameters required for the calculation of the CO2 absorption constant, empirical correlations for KL0 and a were used that had been previously verified with experimental data for O2 absorption. Since, for the conditions studied, the absorption rate was shown to be independent of the chemical reactions taking place in the liquid phase, the KLa for CO2 could be directly related to the KLa for O2 by a simple factor that took into account the difference in aqueous diffusivity of the two gases. Thus, using methods developed for determining O2 absorption in gas-liquid contactors, it is possible to adequately characterize CO2 absorption for laboratory and pilot scale algal production systems.
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  • 6
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    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 40 (1992), S. 465-474 
    ISSN: 0006-3592
    Keywords: propionic acid fermentation ; Propionibacterium acidipropionici ; immobilized ; bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Continuous propionic acid fermentations of lactate by Propionibacterium acidipropionici were studied in spiral wound fibrous bed bioreactors. Cells were imobilized by natural attachment to fiber surfaces and entrapment in the void volume within the fibrous matrix. A high cell density of ∼37 g/L was attained in the reactor and the reactor productivity was ∼4 times higher than that from a conventional batch fermentation. The bioreactor was able to operate continuously for 4 months without encountering any clogging, degeneration, or contamination problems. Also, the reactor could accept low-nutrient and low-pH feed without sacrificing much in reactor productivity. This new type of immobilized cell bioreactor is scalable and thus is suitable for industrial production of propionate. © 1992 John Wiley & Sons, Inc.
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  • 7
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    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 39 (1992), S. 707-716 
    ISSN: 0006-3592
    Keywords: Mixing ; two phase ; bioreactor ; perfluorochemical ; LLR ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The liquid-impelled loop reactor is a new column-type bioreactor. The design of this device is based on the principle of the air-lift loop reactor. In the external-loop configuration used in this work, descending perfluorochemical drops bring about circulation of the continuous aqueous phase. Mixing of this continuous phase is characterized per section of the rector. Axial-dispersion coefficients for the tube with two-phase flow are determined and correlated with the energy dissipation in the tube. Comparisons with similar systems such as bubble columns and air-lift loop reactors are made. Overall mixing parameters are derived and used for calculation of the number of circulatins needed to achieve a certain degree of mixing. The hydrodynamic model from previous work is tested for the reactor configurations of this work. It can be useful to calculate circulation times.
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  • 8
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    Biotechnology and Bioengineering 39 (1992), S. 697-706 
    ISSN: 0006-3592
    Keywords: anchorage-dependent mammalian cells ; immobilization ; fibers ; bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Anchorage-dependent HeLa cells were successfully cultured on two fibrous materials (A07 and R100) with porosities of 75-125 and 40 μm, void fractions of 92% and 81%, and fiber diameters of 7.6 and 10.2 μm, respectively, in 100-mL spinner flasks and 2-L stirred tank bioreactors. The matrix was formed into a fixed vertical spiral configuration. All cultures displayed rapid (≤2-3 h) attachment of inoculated cells (≥95%) to the matrix, uniform coverage of the immobilizing area with viable cells, and no significant amount of cell debris in the medium. Spinner flask cultures indicated that the denser material R100 showed better results in terms of final cell density. The growth of HeLa cells on material R100 in both culture systems was similar to that observed in tissue culture dishes (specific growth rate ∼0.03-0.04 h-1, maximum cell density of 8 × 106-9 × 106 cells · mL-1, and yields of 0.4 × 108 cells · mM-1 on glucose and 2 × 108-3 × 108 cells · mM-1 on glutamine). Scale-up of this culture technique in a 2-L bioreactor under perfusion with pH and dissolved oxygen (DO) control yielded cell densities of up to 1.6 × 106 cells · mL-1. Two other anchorage-dependent mammalian cells (ADC) known to be cultured with difficulty in roller bottles or with micro carriers were easily grown on material R100 in spinner flasks. The performance of this culture technique was compared to other ADC culture systems.
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  • 9
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 40 (1992), S. 1403-1411 
    ISSN: 0006-3592
    Keywords: aromatic solvents ; bioreactor ; benzene ; toluene ; xylene ; biodegradation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A novel bioreactor for the biodegradation of toxic aromatic solvents, such as benzene, toluene, and xylenes in liquid effluent stream, was developed. Silicon tubing was immersed in the completely mixed and aerated bioreactor, and liquid toluene as a model solvent was circulated within the tubing. Toluene diffused out of the tube wall and was transferred at high rate into the culture broth, where biodegradation occurred. The effect of operating parameters on the toluene transfer rate was investigated. During continuous operation, the biodegradation rate was considerably higher than those obtained using conventional methods. A mathematical model was established for continuous biodegradation, and simulation results coincided with the experimental results. The performance and operational criteria of the bioreactor were analyzed on the basis of both the experimental and simulation results. © 1992 John Wiley & Sons, Inc.
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  • 10
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    Biotechnology and Bioengineering 42 (1993), S. 357-366 
    ISSN: 0006-3592
    Keywords: bioreactor ; insect cell culture ; high-density cell culture ; recombinant baculovirus ; chloramphenicol acetyltransferase ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A two-stage bioreactor scheme was developed for the large-scale production of recombinant proteins using a genetically engineered baculovirus/insect cell system. The first bioreactor was employed for cell growth and the second for cell infection. Silkworm Bm5 cells were infected with a recombinant baculovirus, BmNPV/P5.cat, containing a bacterial chloramphenicol acetyltransferase (CAT) gene under the control of the polyhedrin gene promoter of Bombyx mori nuclear polyhedrosis virus (BmNPV). This recombinant baculovirus has been used as an expression vector for the production of recombinant CAT enzyme. A specific productivity of 82 to 90 μg CAT/(106 cells) was obtained using the BmNPV/Bm5 expression system, a yield similar to that achieved using the AcNPV/Sf expression system. Repeated infection of high-density cell cultures did not reduce the specific productivity of the CAT enzyme. Most importantly, the problems associated with the infection of high-density cell cultures were resolved by means of controlled infection conditions and appropriate replenishment of spent culture medium following infection. The glucose uptake rate by the cells following infection was 50% higher than that by the cells before infection. Not only did the infection of high-density cell cultures result in consistent yields of 250 mg/L of CAT enzyme, but also the two-stage bioreactor system was proven to be reliable for a long-term operation beyond 600 h. © 1993 John Wiley & Sons, Inc.
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  • 11
    ISSN: 0006-3592
    Keywords: bioreactor ; tower loop bioreactor ; yeast ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The local properties of the dispersed gas phase (gasholdup, bubble diamater, and bubble velocity) were measured and evaluated at different positions in the riser and downcomer of a pilot plant reactor and, for comparison, in a laboratory reactor. These were described in Parts I and II of this series of articles during yeast cultivation and with model media. In the riser of the pilot plant reactor, the local gas holdup and bubble velocities varied only slightly in axial direction. The gas holdup increased considerably, while the bubble velocity increased only slightly with aeration rate. The bubble size diminished with increasing distance from the aerator in the riser, since the primary bubble size was larger than the equilibrium bubble size. In the downcomer, the mean bubble size was smaller than in the riser. The mean bubble size varied only slightly, the bubble velocity was accelerated, and the gas holdup decreased from top to bottom in the downcomer. In pilot plant at constant aeration rate, the properties of the dispersed phase were nearly constant during the batch cultivation, i.e., they depended only slightly on the cell concentration. In the laboratory reactor, the mean bubble sizes were much larger than in the pilot plant reactor. In the laboratory reactor, the bubble velocities in the riser and downcomer increased, and the mean gas holdup and bubble diameter in the downcomer remained constant as the aeration rate was increased.
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  • 12
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    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 37 (1991), S. 762-769 
    ISSN: 0006-3592
    Keywords: animal cell culture ; bioreactor ; airlift ; fiber-bed bioreactor ; oxygen transfer ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A simple hydrodynamic model is introduced to describe the airlift fiber-bed bioreactor, which can enhance the volumetric productivity of anchorage-dependent animal cell cultures. By applying the model, liquid flow rates and volumetric mass transfer coefficients are predicted and are in agreement with experimental measurements. Consequently, the optimal reactor configuration giving the maximal oxygen supply is derived. Also, theoretical scaleup potential of this concentric internal loop reactor is considered for volumes ranging from 10 to 67,000 L with which cell densities of 5.1 × 107 and 1.2 × 107 cells/cm3, respectively, can be maintained.
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  • 13
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    Biotechnology and Bioengineering 38 (1991), S. 331-339 
    ISSN: 0006-3592
    Keywords: Thalictrum rugosum ; alkaloid production ; berberine ; bioreactor ; airlift ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Airlift bioreactor operations have been studied for the growth-associated production of secondary metabolites from plant cell suspension cultures. The model system used in this work was Thalictrum rugosum producing berberine, an isoquinoline alkaloid. The airlift system was well suited for growth of Thalictrum cell suspension cultures unless the cell density was high. At high cell density, the airlift system with a draught tube was not adequate due to large aggregates clogging the recirculation paths. This was overcome by use of a cell scraper in the reactor. For berberine production, gas-stripping also played a significant role and it was discovered that CO2 and ethylene were important for product formation. By supplying a mixture of CO2 and ethylene into the airlift system, the specific berberine content was increased twofold. It is evident that continuous gas sparging was harmful for the production of berberine without supplementation with other gases.
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  • 14
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    Biotechnology and Bioengineering 39 (1992), S. 314-319 
    ISSN: 0006-3592
    Keywords: affinity chromatographic reactor ; dynamic affinity ; coenzyme regeneration ; NAD regeneration ; bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The affinity chromatographic reactor (ACR) is a bioreactor which utilizes the dynamic interaction or the dynamic affinity between a free coenzyme and immobilized enzymes for the highly efficient regeneration of dissociable coenzymes. Dynamic affinity between free NAD and immobilized alcohol dehydrogenase (ADH) in ACR was investigated by three different methods. ADH catalyzed both oxidation and reduction of NAD, consuming propionaldehyde and ethanol. The theoretical model under consideration elucidated a criterion for the expression of the dynamic affinity as a relationship among the affinity constants and the concentrations of a coenzyme and immobilized enzyme. This criterion was confirmed experimentally by the measurements of the retention time of NAD and the half-life period of the reactor activity after one-shot pulse injection of NAD to ACR. In the stability measurement of the immobilized enzyme, it became clear that ADH was more stable at the higher concentration in immobilization. Although the present case of coenzyme cycling by a single enzyme is very special, with limited chance for the direct application, the results obtained here provide a theoretical basis for ACR with multienzymes-which is of more general use.
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  • 15
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    Biotechnology and Bioengineering 39 (1992), S. 511-521 
    ISSN: 0006-3592
    Keywords: plant cell ; Catharanthus roseus ; suspension ; culture ; mixing ; helical ribbon impeller ; bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A double helical-ribbon impeller (HRI) bioreactor with a 11-L working volume was developed to grow high-density Catharanthus roseus cell suspensions. The rheological behavior of this suspension was found to be shear-thinning for concentrations higher than 12 to 15 g DW · L-1. A granulated agar suspension of similar rheological properties was used as a model fluid for these suspensions. Mixing studies revealed that surface baffling and bottom profiling of the bioreactor and impeller speeds of 60 to 150 rpm ensured uniform mixing of suspensions. The HRI power requirement was found to increase singnificantly for agar suspensions higher than 13 g DW · L-1, in conjunction with the effective viscosity increase. Oxygen transfer studies showed high apparent surface oxygen transfer coefficients (kLa ∼4 to 45 h-1) from agar suspensions of 30 g DW · L-1 to water and for mixing speeds ranging from 120 to 150 rpm. These high surface kIa values were ascribed to the flow pattern of this bioreactor configuration combined with surface bubble generation and entrainment in the liquid phase caused by the presence of the surface baffles. High-density C. roseus cell suspension cultures were successfully grown in this bioreactor without gas sparging. Up to 70% oxygen enrichment of the head space was required to ensure sufficient oxygen supply to the cultures so that dissolved oxygen concentration would remain above the critical level (≥10% air saturation). The best mixing speed was 120 rpm. These cultures grew at the same rate (∼0.4 d-1) and attained the same high biomass concentrations (∼25 to 27 g DW · L-1, 450 to 500 g filtered wet biomass · L-1, and 92% to 100% settled wet biomass volume) as shake flask cultures. The scale-up potential of this bioreactor configuration is discussed.
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  • 16
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    Biotechnology and Bioengineering 44 (1994), S. 1288-1294 
    ISSN: 0006-3592
    Keywords: D-amino acid oxidase ; bioreactor ; α-keto acid ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The study reports on the development of a bioreactor for the production of α-keto acids from D,L- or D-amino acids using Rhodotorula gracilis D-amino acid oxidase. D-Amino acid oxidase was co-immobilized with catalase on Affi-Gel 10 matrix, and the reactor was operated as a continuous-stirred tank reactor (CSTR) or stirred tank with medium recycling conditions. The optimum substrate concentration and quantity of biocatalyst were determined (5 mM and 1.2 mg/L, respectively). Under optimum operating conditions, product formation was linearly related to both substrate and enzyme concentration, showing the system to be highly flexible. Under these conditions, in a stirred tank, over 90% conversion was achieved in 30 min with a maximum production of 0.23 g of pyruvic acid/day/enzyme units. Product was recovered by ion exchange chromatography. The operational stability of the reactor was high (up to 9.5 h of operation without loss of activity) and the inactivation half-life was not reached even after 18 h or 36 bioconversion cycles. This represents the first case of a reactor developed successfully with a D-amino acid oxidase. © 1994 John Wiley & Sons, Inc.
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  • 17
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    Biotechnology and Bioengineering 44 (1994), S. 1315-1324 
    ISSN: 0006-3592
    Keywords: static mixer ; MRC-5 ; anchorage dependent ; hepatitis A ; animal cell culture ; bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The titanium static mixer reactor, demonstrated for a variety of vaccine processes during the late 197s, was investigated for the production of attenuated hepatitis A virus antigen from anchorage-dependent MRC-5 cells. This reactor system used Charles River Biotechnological Services cabinets for monitoring and process control. Cell inoculation protocols, using 6000-10,000 cells/cm2, resulted on over 95% attachment at both the laboratory and pilot scales. Indirect monitoring techniques using oxygen, glucose, L-serine, and L-glutamine uptake rates were indicative of cell growth prior to virus inoculation as well as environmental and/or nutrient limitations. Seven laboratory-scale (3900 cm2) runs and one pilotscale (265,000 cm2) run were conducted to investigate refeeding regiments, parallel versus perpendicular element orientation, increased element surface area per unit volume, and scale-up performance. In general, lysate antigen yields achieved were similar to those of parallel T-flasks cultivated under similar conditions. © 1994 John Wiley & Sons, Inc.
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  • 18
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    Biotechnology and Bioengineering 44 (1994), S. 930-943 
    ISSN: 0006-3592
    Keywords: Eschscholtzia californica ; embryogenesis ; somatic embryos ; bioreactor ; macronutrients ; kinetics ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Embryogenic cultures of a transformed Eschscholtzia californica cell line were carried out in a 11-L helical ribbon impeller bioreactor operated under various conditions to evaluate the performance of this equipment for somatic embryo (SE) production. All bioreactor cultures produced SE suspensions with maximum concentrations at least comparable to those obtained from flask control cultures (∼8-13 SE · mL-;1). However, an increase of the mixingspeed, from 60 to 100 rpm, and low sparging rate (∼0.05 VVM, kL a ∼ 6.1 h-;1) for dissolved oxygen concentration (DO) control yielded poorer quality embryogenic cultures. The negative effects on SE production were attributed mainly to the low but excessive shear experienced by the embryogenic cells and/or embryoforming aggregates. High DO (∼60% of air saturation) conditions favored undifferentrated biomass production and high nutrient uptake rates at the expense of the slower SE differentiation process in both flask and bioreactor cultures. Too low DO (-5-10%) inhibited biomass and SE production. The best production of SE (∼44 SE · mL-1 or ∼757 SE · g dw-1 · d-1) was achieved by operating the bioreactor at 60 rpm while controlling DO at ∼20%by surface oxygenation only (0.05 VVM, kL a ∼ 1.4 h-;1). This production was found to be a biomass production/growth-associated process and was mainly limited by the availability of extracellular phosphate, magnesium, nitrogen salts, and carbohydrates. © 1994 John Wiley & Sons, Inc.
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  • 19
    ISSN: 0006-3592
    Keywords: bioreactor ; tower loop bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Investigations were carried out in a 9 m high, 4 m3 volume, pilot plant airlift tower loop bioreactor with a draft tube. The reactor was characterized by measuring residence time distributions of the gas phase using pseudostochastic tracer signals and a mass spectrometer and by evaluating the mixing in the liquid phase with single-pulse tracer inputs. The local gas holdup and the bubble size (piercing length) were measured with two-channel electrical conductivity probes. The mean residence times and the intensities of the axial mixing in the riser and downcomer and the circulation times of the phases as well as the fraction of the recirculated gas phase were evaluated. The gas holdup in the riser is nearly uniform along the reactor. In the downcomer, it diminishes from top to bottom. The liquid phase dispersion coefficients, DL, are smaller than those measured in the corresponding bubble columns. In the pilot plant with tap water the following relationship was found: DLr = cwSGn; with c = 203.4; n = 0.5;DLr(cm2 s-1;) and WSG(cm s-1) where DLr is the longitudinal dispersion coefficient in the riser and WSG is the superficial gas velocity. The gas phase dispersion coefficients in the riser of the pilot plant, DGr, are also enlarged with increasing superficial gas velocity, WSG, however, no simple relationship exists. Parameter DGr is the highest in the presence of antifoam agents, intermediate in tap water, and the smallest in ethanol solution.
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  • 20
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    Biotechnology and Bioengineering 40 (1992), S. 1056-1068 
    ISSN: 0006-3592
    Keywords: cell culture ; bioreactor ; ceramic matrix ; hybridoma cells ; oxygen transfer ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A single-pass, plug-flow bioreactor has been developed in which oxygen is supplied to entrapped hybridoma cells via sllicone tubes threaded through the square channels of a macroporous ceramic monolith. Oxygen diffuses from the gas phase, through the silicone tubing, across the open square channel, and into the pores of the ceramic wall where it is consumed by entrapped cells. Advantages of such a reactor include higher product yields, protection of cells from detrimental hydrodynamic effects, no internal moving parts to compromise asepsis, and simplicity of operation. A prototype bioreactor was constructed and operated over a range of residence times. A side-by-side experimental comparison with a conventional recycle bioreactor was performed by inoculating both bioreactors with cells from the same stock culture and feeding medium from the same reservoir. Final antibody titers were 80% higher in the single-pass bioreactor at a residence time of 200 minutes compared with those of the recycle bioreactor at a residence time of 800 minutes. A theoretical analysis of oxygen transport in this bioreactor is developed to highlight important design criteria and operating strategies for scale-up. © 1992 John Wiley & Sons, Inc.
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  • 21
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    Biotechnology and Bioengineering 41 (1993), S. 118-128 
    ISSN: 0006-3592
    Keywords: intracellular pH ; 9-aminoacridine ; bioreactor ; on-line measurement ; yeast ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A method has been developed to continuously measure the intracellular pH (pHi) of cells cultivated in a bioreactor in an on-line fashion over extend time periods. The methods is attractive in its simplicity and involves the use of a fluorescent pHi indicator 9-aminoacridine (9A A) which is a week base. An expression has been derived to calculate changes in pHi from measured 9AA-fluorescence changes. The indicator 9AA was found t be nontoxic to yeast cells at concentrations used to measure pHi (7 μM). The fluorescence of nicotinamide adenine dinucleotide (NADH) molecules did not interfere significantly with the measurement of 9AA-fluorescence. The pHi change in yeast cell following the addition of a proton ionophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP) measured by 9AA compared favorably with that measured by the well-established pHi, indicator (which is however unsuitable for on-line applications in a bioreactor) bis-carboxyethyl carboxy fluorescein (BCECF). The pHi of yeast under substrate starved conditions was 6.4 units. The responses of pHi of yeast cells to induced metabolic transitions were studied. Under aerobic condition, pHi increased by 0.12 unit following a 100-ppm glucose pulse addition and by 0.25 unit following a 300-ppm ethanol pulse addition. Under anaerobic condition, pHi increased by 0.1 unit following a 500-ppm glucose pulse addition. Comparison of pHi with other indicators of cellular metabolic state suggests that pHi is a cellular metabolic state indicator. © 1993 John Wiley & Sons, Inc.
    Additional Material: 14 Ill.
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  • 22
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 42 (1993), S. 724-728 
    ISSN: 0006-3592
    Keywords: bioreactor ; pulse bioreactor ; oxygen transfer ; animal cells ; vibration ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Oxygen transfer in a novel pulse bioreactor has been evaluated. The agitator consists of a series of alternately fixed and movable parallel plates mounted so that the movable plates vibrate at 30 Hz causing a pulsating fluid motion. Pure oxygen, at pressures up to 5 atm, diffuses through silicone rubber tubing that also vibrates at 30 or 60 Hz. The main feature of this bioreactor is high oxygen transfer with low shear to prevent damage to fragile animal cell membranes. We estimate that sufficient oxygen can be supplied to support over 108 cells/mL of human diploid foreskin cells growing on microcarriers. © 1993 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
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  • 23
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 41 (1993), S. 194-203 
    ISSN: 0006-3592
    Keywords: artificial liver ; bioreactor ; hepatocytes ; cell entrapment-liver, artificial ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: We have developed a hepatocyte entrapment hollow fiber bioreactor for potential use as a bioartificial liver. Hepatocytes were entrapped in collagen gel inside the lumen of the hollow fibers. Medium was perfused through the intraluminal region after contraction of the hepatocyte-entrapment gel. Another medium stream, comparable to the patient's blood during clinical application, passed through the extracapillary space. Viability of hepatocytes remained high after 5 days as judged by the rate of oxygen uptake and viability staining. Urea and albumin synthetic activities were also sustained. Transmission electron microscopic examination demonstrated normal ultrastructural integrity of hepatocytes in such a bioreactor. With its sort-term, extracorporeal support of acute liver failure, the current bioreactor warrants further investigation. © 1993 John Wiley & Sons, Inc.
    Additional Material: 9 Ill.
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  • 24
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 39 (1992), S. 1133-1140 
    ISSN: 0006-3592
    Keywords: mass transfer ; bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Liquid-phase mass transfer coefficient in bioreactors have been examined. A theoretical model based on the surface renewal concept has been devloped. The predicted liquid-phase mass transfer coefficients are compared with the experimental data for a mycelial fermentation broth (Chaetomium cellulolyticum) and model media (carboxymethyl cellulose) in a bench-scale bubble column reactor. The liquid-phase mass transfer coefficient is evaluated by dividing the volumetric mass transfer coefficient obtained experimentally by the specific surface area estimated using the available correlations. The available literature data in bubble column and stirred tank bioreactors is also used to test the validity of the proposed model. A reasonable agreement between the model and the experimental data is found.
    Additional Material: 4 Ill.
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