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  • 1
    Electronic Resource
    Electronic Resource
    On-line and in-situ monitoring technology for cell density measurement in microbial and animal cell cultures (1994)
    Springer
    Bioprocess and biosystems engineering 10 (1994), S. 195-207 
    Details
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Commercially available on-line and in-situ devices for monitoring cell density are reviewed in this article. Principles of operation are described as well as capabilities of these probes in specific measurement applications based on literature reports. Pilot-scale experimental observations from three optical density probes, the Cerex, Monitek and Wedgewood designs, have been included for Escherichia coli fermentations. Requirements for future on-line and in-situ instruments are discussed as well as the impact of current limitations on widespread application.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00369530
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Modified microbial fermenter performance in animal cell culture and its implications for flexible fermenter design (1994)
    Springer
    Bioprocess and biosystems engineering 11 (1994), S. 57-63 
    Details
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Modified microbial fermenters were adapted for use in animal cell cultivations within an active microbial pilot plant rapidly and inexpensively. Multiple batches of Jurkat cells (human T-lymphoma) and Spodoptera frugiperda (using a baculovirus expression vector) were conducted in modified 75 L Chemap fermenters and a 280 L pilot plant seed vessel. These retrofitted reactors were evaluated for suitable temperature control, local hot spots, surface aeration capability, open-pipe sparging, impeller type and impeller speed. Influences of these operating factors on cell growth rate, cell density, glucose uptake and protein yield were quantified. Implications for the flexible design of fermenters for operation in multiuse campaign facilities are discussed. Adaption of existing microbial fermenters was found to be an attractive route for initial implementation of cell culture capacity in a research organization.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00389561
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Maintenance, equipment and operational improvements within an established Fermentation Pilot Plant (1995)
    Springer
    Bioprocess and biosystems engineering 13 (1995), S. 279-287 
    Details
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The Merck Research Laboratories' Fermentation Pilot Plant was constructed and commissioned in the early 1980's. It is a highly instrumented and automated facility which serves to maximize data collection for a variety of experimental batches. To continue successful and versatile operation as the facility ages, various improvements in equipment, maintenance, instrumentation, cleaning and sterility have been implemented. The goals were to improve flexibility, minimize down time, increase measurement accuracy and reduce contamination to enhance facility output for process development and clinical material production.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00369558
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Influence of impeller type on power input in fermentation vessels (1998)
    Springer
    Bioprocess engineering 18 (1998), S. 401-412 
    Details
    ISSN: 0178-515X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Prior investigations comparing radial flow Rushton impellers with axial flow hydrofoil impellers (Maxflo T and A315) were extended at the pilot scale. Six types of impellers (disk-style Rushton, Prochem Maxflo T hydrofoils of three diameters pumping downwards and A315 hydrofoils pumping upwards and downwards) were compared for qualitative differences in power number behavior with Reynolds' number, single versus double impeller power draw, gassed power reduction with aeration number and gas hold-up. Power measurements were obtained using watt transducers which, although limited in accuracy and prone to interferences, were able to provide useful qualitative monitoring results. Measurements were conducted using three model liquid systems: water, glycerol and Melojel (soluble starch). Apparent viscosities for actual Streptomyces cultivations were estimated using measured gassed power values and the experimental relationships obtained for gassed/ungassed power to aeration number and power number to Reynolds' number for the glycerol model system. Results confirmed the lower power number and lower shear environment for hydrofoil impellers, yet suggested useful trends for various process parameters and process fluids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004490050463
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Maintenance, equipment and operational improvements within an established Fermentation Pilot Plant (1995)
    Springer
    Bioprocess engineering 13 (1995), S. 279-287 
    Details
    ISSN: 0178-515X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  The Merck Research Laboratories’ Fermentation Pilot Plant was constructed and commissioned in the early 1980’s. It is a highly instrumented and automated facility which serves to maximize data collection for a variety of experimental batches. To continue successful and versatile operation as the facility ages, various improvements in equipment, maintenance, instrumentation, cleaning and sterility have been implemented. The goals were to improve flexibility, minimize down time, increase measurement accuracy and reduce contamination to enhance facility output for process development and clinical material production.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00369558
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    Paper (German National Licenses)
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  • 6
    Electronic Resource
    Electronic Resource
    Process optimization for large-scale production of TGF-α-PE40 in recombinant Escherichia coli: effect of medium composition and induction timing on protein expression (1997)
    Springer
    Journal of industrial microbiology and biotechnology 18 (1997), S. 260-266 
    Details
    ISSN: 1476-5535
    Keywords: Keywords: E. coli; fermentation; induction; recombinant; expression; scale-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The effects of medium composition and induction timing on expression of a chimeric fusion protein TGF-α -PE40 (TP-40) in Escherichia coli strain RR1 were examined using a complex medium at several fermentor scales. Two distinctive phases in E. coli catabolism were identified during fermentation based on preferential utilization between protein hydrolysate and glycerol. Maximum specific and volumetric productivities were achieved by inducing the culture when the cells were switching substrate utilization from protein hydrolysate to glycerol. By increasing the yeast extract concentration in the production medium, initiation of the catabolic switch was delayed until high cell mass was achieved. The final titer of TP-40 at the 15-L fermentation scale was doubled from 400 mg L−1 to 850 mg L−1 by increasing the yeast extract concentration from 1% to 4% (w/v) and delaying the time of induction. This fermentation process was rapidly scaled up in 180-L and 800-L fermentors, achieving TP-40 titers of 740 and 950 mg L−1, respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/sj.jim.2900382
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  • 7
    Electronic Resource
    Electronic Resource
    Influence of strain and medium composition on filtration of escherichia coli suspensions (1994)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 44 (1994), S. 539-548 
    Details
    ISSN: 0006-3592
    Keywords: cross-flow filtration ; Escherichia coli ; cell harvesting ; fermentation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Cross-flow filtration of Escherichia coli strains was examined at the laboratory and pilot scales using Romicon 500,000 molecular-weight-cutoff hollow fiber membranes. Both the series resistance and macrosolute polarization models were employed to compare performances. Total dissolved solids content above 90 g/L and viscosity above 1.1 × 10-3 paċ s of cell-free culture media were found to decrease average filtration fluxes by over 60% both in the absence and presence of cells. Broth filtration with culture media of dissolved solids levels below 80 g/L were influenced to a greater extent by harvest cell density. The collodial nature of the complex nutrient responsible for the total solids increase affected prediction of filtration performance. Differences in strain filterability were observed with JM109 preferred over DH5 in high solids-containing media and RR1 preferred over JM109 in low dissolved solids-containing media. Their research demonstrates the importance of cell strain and media selection in the performance of early downstream processing steps. © 1994 John Wiley & Sons, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260440418
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    Paper (German National Licenses)
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  • 8
    Electronic Resource
    Electronic Resource
    Cultivation of virus antigen in fibroblast cells using a glass fiber bed reactor (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 42 (1993), S. 635-642 
    Details
    ISSN: 0006-3592
    Keywords: MRC-5 ; anchorage-dependent ; fibers ; cell culture ; hepatitis A ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The anchorage-dependent cell line, MRC-5, was cultivated successfully on glass fibers with diameters ranging from 24 to 120 μm, despite vast differences in substrate curvature. Multilayer cell growth was observed, particularly for fiber diameters 30 μm and below, which differed from the typical monolayer growth observed in T-flask cultivations. Cells were maintainable at a reduced incubation temperature and were demonstrated to support virus replication for the 21-day antigen production period. Direct microscopic observation, along with indirect calculations, indicated that only a small fraction (about 10%) of the total available fiber surface area was occupied by cells. Thus, productivity per unit surface area was replaced by productivity per unit medium volume when evaluating fiber bed performance. Antigen and protein yields, as well as nutrient uptakes, were 1.5- to 2.5-fold greater than parallel T-flask cultures when compared on this basis. Corresponding available surface area-based values were 10- to 15-fold lower for the fiber bed reactor. The multilayer cell morphology obtained in the fiber bed was attractive for antigen production when immobilized in a column reactor system. © 1993 John Wiley & Sons, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260420512
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  • 9
    Electronic Resource
    Electronic Resource
    Cultivation of attenuated hepatitis A virus antigen in a titanium static mixer reactor (1994)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 44 (1994), S. 1315-1324 
    Details
    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.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260441107
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  • 10
    Electronic Resource
    Electronic Resource
    Development of a recovery and recycle process for a pseudomonas lipase used for large-scale enzymatic synthesis (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 42 (1993), S. 487-493 
    Details
    ISSN: 0006-3592
    Keywords: enzyme ; lipase ; recovery ; recycle ; filtration ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Enzymes are potential catalysts for a wide range of large-scale chemical synthesis steps, particularly when the creation of a specific chiral center is desired. The efficient recycling of the enzyme catalyst and the removal of carryover impurities were crucial factors in the improvement of a stereoselective ester hydrolysis step used in the synthesis of a selective leukotriene antagonist. In this enzymatic reaction step, the substrate and product were both largely insoluble, while the enzyme was soluble in the aqueous reaction mixture. Microfiltration and ultrafiltration of the slurry reaction mother liquor indicated near 100% enzyme protein recovery, while activity recovery was about 70% to 80%. These activity losses might be accounted for by enzyme degradation (1 to 2 mg/L · h) during the 40-hour reaction period. Dissolved impurities, principally a diacid byproduct, in the enzyme recycling stream were reduced 60% to 70% by either lowering the solution pH to 4.0 or raising the solution ionic strength to 1 M. © 1993 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260420412
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