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  • Articles  (35)
  • bioreactor  (35)
  • 1995-1999  (35)
  • 1975-1979
  • Process Engineering, Biotechnology, Nutrition Technology  (35)
  • 1
    Electronic Resource
    Electronic Resource
    Analysis of CHO-K1 cell growth in a fixed bed bioreactor using magnetic resonance spectroscopy and imaging (1999)
    Springer
    Cytotechnology 30 (1999), S. 121-132 
    Details
    ISSN: 1573-0778
    Keywords: bioreactor ; cell volume ; imaging ; magnetic resonance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Non-invasive magnetic resonance imaging and spectroscopy techniques have been used to monitor the growth and distribution of Chinese hamster ovary K1 cells growing in a fixed bed bioreactor composed of macroporous carriers. Diffusion-weighted 1H magnetic resonance spectroscopy was used to monitor the volume fraction of the bioreactor occupied by the cells and diffusion-weighted 1H magnetic resonance imaging was used to map cell distribution. The imaging measurements demonstrated that cell growth in the bioreactor was heterogeneous, with the highest cell densities being found at the surface of the carriers. The increase in the volume fraction occupied by the cells during cell growth showed a close correlation with bioreactor ATP content measured using 31P magnetic resonance spectroscopy. These magnetic resonance measurements, in conjunction with measurements of bioreactor glucose consumption, allowed estimation of the specific glucose consumption rate. This declined during the culture, in parallel with medium glucose concentration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008039011960
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  • 2
    Electronic Resource
    Electronic Resource
    Degradative activities in a recombinant chinese hamster ovary cell culture (1996)
    Springer
    Cytotechnology 22 (1996), S. 43-52 
    Details
    ISSN: 1573-0778
    Keywords: recombinant CHO cells ; insulin degradative activity ; glycosidase ; bioreactor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Two degradative activities were found in a recombinant Chinese hamster ovary cell culture. These activities became more dominant under high cell density and extended running time, as achieved in a semi-continous perfusion culture. The first, insulin degradative activity caused a growth upset in the 3rd cycle of the perfusion culture and shortened the length of the bioreactor process. The second activity, derived from the neutral pH stable sialidase, was found to affect the integrity of the carbohydrate structure of the recombinant protein, causing increase in heterogeneity in molecular weight and pI of the glycoforms. The most efficient way to overcome these problems may be the use of genetically altered ‘designer cells’ as the production cell line.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00353923
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  • 3
    Electronic Resource
    Electronic Resource
    Human diploid fibroblast growth on polystyrene microcarriers in aggregates (1996)
    Springer
    Cytotechnology 22 (1996), S. 111-117 
    Details
    ISSN: 1573-0778
    Keywords: aggregation ; bioreactor ; cell growth ; diploid fibroblasts ; microcarriers ; suspension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Polystyrene microcarriers were prepared in four size ranges (53–63 μm, 90–125 μm, 150–180 μm and 300–355 μm) and examined for ability to support attachment and growth of human diploid fibroblasts. Cells attached rapidly to the microcarriers and there was a direct relationship between cell attachment and microcarrier aggregation. Phasecontrast and scanning electron microscopic studies revealed that while aggregation was extensive, most of the aggregate consisted of void volume. Cell growth studies demonstrated that human diploid fibroblasts proliferated well in microcarrier aggregates, reaching densities of 2.5–3×106 cells per 2 ml dish after 6 days from an inoculum of 0.5×106 cells per dish. When cells were added to the microcarriers at higher density (up to 5×106 cells per 2-ml culture), there was little net growth but the cells remained viable over a 7-day period. In contrast, cells died when plated under the same conditions in monolayer culture. When the microcarriers were used in suspension culture, rapid cell attachment and rapid microcarrier aggregation also occurred. In 100-ml suspension culture, a cell density of 0.7×106 cells per ml was reached after 7 days from an inoculum of 0.1×106 cells. Based on these data, we conclude that microcarrier aggregation is not detrimental to fibroblast growth. These data also indicate that small microcarriers (53–63 μm) (previously thought to be too small to support the growth of diploid fibroblasts) can support fibroblast growth and this occurs primarily because microcarriers in this size range efficiently form aggregates with the cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00353930
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  • 4
    Electronic Resource
    Electronic Resource
    Hybridoma cell behaviour in continuous culture under hyperosmotic stress (1999)
    Springer
    Cytotechnology 29 (1999), S. 71-84 
    Details
    ISSN: 1573-0778
    Keywords: bioreactor ; continuous culture ; hybridoma cells ; hyperosmolality ; monoclonal antibody production ; non-producing subpopulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract In this paper, we propose an alternative strategy to the ones proposed before (Oh et al., 1993; Øyaas et al., 1994a) to get real increases of global final antibody titer and production at hyperosmotic stress, by reducing the detrimental effect of such a stress on cell growth, and conserving the stimulating effect on antibody production. It consists of cultivating the cells in continuous culture and increasing the osmolality stepwise. In this way, the cells could progressively adapt to the higher osmolality at each step and antibody titers could be nearly doubled at 370 and 400 mOsm kg-1, compared to the standard osmolality of 335 mOsm kg-1. Surprisingly, the stimulation of antibody production was not confirmed for higher osmolalities, 425 and 450 mOsm kg- 1, despite the minor negative effect on cell growth. Intracellular IgG analysis by flow cytometry revealed at these osmolalities a significant population of non-producing cells. However, even when taking into account this non-producing population, a stimulating effect on antibody production could not be shown at these highest osmolalities. It seems to us that osmolality has a significant effect on the appearance of these non-producing cells, since they were not observed in continuous cultures at standard osmolality, of comparable duration and at an even higher dilution rate. The appearance of the non-producing cells coincides furthermore with modifications of the synthesised antibody, as shown by electrophoretic techniques. It is however not really clear if these two observations reflect actually the same phenomenon. Hyperosmolality affects the cell behaviour in continuous culture in multiple ways, independently of the growth rate, counting all at least partially for the observed stimulation of antibody production: acceleration of the amino acid, and in particular the glutamine metabolism, increase of the cell volume, increase of the intracellular pH and accumulation of cells in the G1 cell cycle phase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008014909474
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  • 5
    Electronic Resource
    Electronic Resource
    Development of a fixed bed bioreactor for the expansion of human hematopoietic progenitor cells (1999)
    Springer
    Cytotechnology 30 (1999), S. 227-234 
    Details
    ISSN: 1573-0778
    Keywords: bioreactor ; cord blood ; expansion ; hematopoieticcells ; porous carrier ; stromal cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The ex vivo expansion of hematopoietic progenitor cells is of great interest for a variety of clinical applications, e.g. bone marrow transplantation or gene therapy. Therefore it is of general interest to develop a culture system, able to mimic the in vivo hematopoesis, which is a prerequisite for long-term hematopoietic culture. Our approach was to modify a continuously perfused bioreactor for cultivation and expansion of human hematopoietic stem cells. Therefore we immobilized stromal cells (human primary stromal cells or the murine cell line M2-10B4) in porous glass carriers in a fixed bed reactor and cocultivated human hematopoietic progenitor cells for several weeks. After inoculation of mononuclear cells derived from umbilical cord blood or peripheral blood stem cells both adherent and non adherent cells were harvested and analyzed by flow cytometry and short-term colony assays. During cultivation there was a permanent production of progenitor cells and mature blood cells derived from the immobilized cells in the carriers. We could demonstrate the immobilization of hematopoietic progenitor cells of the myeloid system detectable in short-term colony assays. Additionally we could observe the expansion of very early progenitor cells (CFU-GEMM) up to 4.2-fold and later progenitor cells (CFU-GM and BFU-E) up to 7-fold and 1.8-fold, respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008085932764
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  • 6
    Electronic Resource
    Electronic Resource
    Are we prepared for animal cell technology in the 21st century? (1995)
    Springer
    Cytotechnology 18 (1995), S. 3-8 
    Details
    ISSN: 1573-0778
    Keywords: bioreactor ; cellular therapies ; gene therapy ; therapeutic proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Large scale animal cell culture for the production of complex therapeutic proteins has been a major success of the biotechnology industry. Today, approximately half of the $ 5 billion annual turnover of the biotechnology industry is based upon this technology, in many cases with reactors of more than 10 m3. As we look towards the 21 st century, however, we can see novel approaches to the production of therapeutic proteins, by means of gene and cellular therapies. These technologies present new engineering challenges to the animal cell technologist. Are we prepared to meet these challenges? The needs include: small-scale reactors for the preparation of autologous cell lines, methods for the production of viruses to be used as vectors in gene therapy, artificial organ and the processing of xenogenic cell lines and tissues for cellular implants in humans. More attention should be given to three-dimensional cell cultures. Mass transfer considerations need to be extended beyond just oxygen transfer, to include cellular communication in small systems; this is becoming increasingly important for the control and optimise growth and product formation. Apart from improvements of large-scale systems, substantial advantages could be gained by studying new methods for the production and delivery of therapeutic proteins, using small-scale cell culture systems. We should adapt teaching, regulatory, patent and clinical infrastructure to meet this challenge in a harmonious way.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00744313
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  • 7
    Electronic Resource
    Electronic Resource
    Oxygen gradients in animal-cell bioreactors (1995)
    Springer
    Cytotechnology 18 (1995), S. 27-34 
    Details
    ISSN: 1573-0778
    Keywords: Air lift reactor ; bubble column ; bioreactor ; oxygen gradients ; scale-up ; stirred vessel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract An estimation is made of oxygen gradients in animal-cell bioreactors, using straightforward engineering calculations. Three types of bioreactor are considered: stirred vessel, bubble column and air lift, of sizes between 0.01 and 10 m3. First, the gradient is estimated in the stagnant layer surrounding a cell (15 μm), a microcarrier (185 μm) with 300 cells attached to it, a macroporous support (1.25 mm) containing 185,00 cells and one (6 mm) containing 4.25 million cells. It is assumed that oxygen consumption is 10−16 mole O2·cell−1·s−1, while mass transfer coefficients are obtained from Sherwood relations. Circulation and liquid-retention times of the bioreactors are compared with the oxygen-exhaust times of suspensions with 1012, 1013 and 1014 cells/m3 to estimate if oxygen gradients are likely to exist in the bulk-liquid phase. Finally, the gradient in the liquid film surrounding air bubbles is estimated using k l A-values obtained from empirical correlations. It is clear from all these estimations that in many situations severe gradients can be expected. The question remains, however, whether gradients should be avoided as much as possible, or may be tolerated to a certain extent or even created on purpose because of possible beneficial effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00744317
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  • 8
    Electronic Resource
    Electronic Resource
    Batch control system vaccines: BCSV (1995)
    Springer
    Cytotechnology 18 (1995), S. 57-66 
    Details
    ISSN: 1573-0778
    Keywords: Automation ; bioreactor ; optimisation ; process control ; software sensors ; validation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The Batch Control System for Vaccines (BCSV), a new Man Machine Interface (MMI) for the control of cultivations in bioreactors, was developed according to SP-88. SP-88 is the ISA standard for Batch Control Systems. Among others, SP-88 supplied the concept of recipes, which organize and specify the monitoring and control requirements for manufacturing. Process optimisation and compliance to GMP rules and regulations were the main objectives for this development. The most important features of the BCSV interface include: - implementation at production, pilot and R & D scale to assure easy transfer of knowledge and experience at the various stage of process development; - independency of underlying hardware to ensure similar “look and feel” for different pieces of equipment; - in-house development and maintenance of recipes to have maximum control over applications; - interactive communication between operator and BCSV during recipe execution. GMP compliance was assured not only by considering governing sets of GMP regulations, but also by taking up the interface in a overall Information & Automation strategy and by setting up a QA strategy for the entire life cycle of the system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00744320
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  • 9
    Electronic Resource
    Electronic Resource
    Ex vivo expansion of primitive hematopoietic cells for cellular therapies: An overview (1995)
    Springer
    Cytotechnology 18 (1995), S. 133-146 
    Details
    ISSN: 1573-0778
    Keywords: ex vivo expansion ; hematopoietic culture ; bioreactor ; clinical therapies ; cytokines ; stroma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Sources of hematopoietic cells for bone marrow transplantation are limited by the supply of compatible donors, the possibility of viral infection, and autologous (patient) marrow that is depleted from prior chemo- or radiotherapy or has cancerous involvement. Anex vivo system to amplify hematopoietic progenitor cells could increase the number of patients eligible for autologous transplant, allow use of cord blood hematopoietic cells to repopulate an adult, reduce the amount of bone marrow and/or mobilized peripheral blood stem and progenitor cells required for transplantation, and reduce the time to white cell and platelet engraftment. The cloning of hematopoietic growth factors and the identification of appropriate conditions has enabled the development of successfulex vivo hematopoietic cell cultures. Purification systems based on the CD34 marker (which is expressed by the most primitive hematopoietic cells) have proven an essential tool for research and clinical applications. Present methods for hematopoietic cultures (HC) on stromal (i.e. accessory cells that support hematopoiesis) layers in flasks lack a well-controlled growth environment. Several bioreactor configurations have been investigated, and a first generation of reactors and cultures has reached the clinical trial stage. Our research suggests that perfusion conditions improve substantially the performance of hematopoietic reactors. We have designed and tested a perfusion bioreactor system which is suitable for the culture of non-adherent cells (without stromal cells) and readily scaleable for clinical therapies. Eliminating the stromal layer eliminates the need for a stromal cell donor, reduces culture time, and simplifies the culture system. In addition, we have compared the expansion characteristics of both mononuclear and CD34+ cells, since the latter are frequently assumed to give a superior performance for likely transplantation therapies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00744329
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  • 10
    Electronic Resource
    Electronic Resource
    Comparison of manufacturing techniques for adenovirus production (1999)
    Springer
    Cytotechnology 30 (1999), S. 169-172 
    Details
    ISSN: 1573-0778
    Keywords: adenovirus ; bioreactor ; microcarriers ; serum-free medium ; 293 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract We have compared three different production methods, which may be suitable for the large scale production of adenovirus vectors for human clinical trials. The procedures compared 293 cells adapted to suspension growth in serum-free medium in a stirred tank bioreactor, 293 cells on microcarriers in serum-containing medium in a stirred tank bioreactor, and 293 cells grown in standard tissue culture plasticware. With a given virus, yields varied between 2000 and 10,000 infectious units/cell. The stirred tank bioreactor routinely produced between 4000 and 7000 infectious units/cell when 293 cells were grown on microcarriers. The 293 cells adapted to suspension growth in serum-free medium in the same stirred tank bioreactor yielded between 2000 and 7000 infectious units/cell. Yields obtained from standard tissue culture plasticware were up to 10,000 infectious units/cell. Cell culture conditions were monitored for glucose consumption, lactate production, and ammonia accumulation. Glucose consumption and lactate accumulation correlated well with the cell growth parameters. Ammonia production does not appear to be significant. Based on virus yields, ease of operation and linear scalability, large-scale adenovirus production seems feasible using 293 cells (adapted to suspension/serum free medium or on microcarriers in serum containing medium) in a stirred tank bioreactor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008040221630
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  • 11
    Electronic Resource
    Electronic Resource
    Xanthomonas campestris as a host for the production of recombinantPseudomonas aeruginosa lipase (1996)
    Springer
    Journal of industrial microbiology and biotechnology 16 (1996), S. 22-28 
    Details
    ISSN: 1476-5535
    Keywords: lipase ; recombinantXanthomonas ; fed-batch ; bioreactor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Recombinant plasmid pBP13, which expresses the alkaline lipase fromPseudomonas aeruginosa IGB83 under thetac promoter was transferred toXanthomonas campestris pvcampestris IBT148. Different fermentation conditions were tested for lipase productivity by strain IBT148 carrying plasmid pBP13, and a fermentation process was established in an instrumented bioreactor, where lipase production was increased more than 12-fold with respect to the initial culture conditions in shake flasks. Xanthan gum stabilized the activity of the alkaline lipase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01569917
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  • 12
    Electronic Resource
    Electronic Resource
    Production, extraction and purificationof violacein: an antibiotic pigment producedby Chromobacterium violaceum (1998)
    Springer
    World journal of microbiology and biotechnology 14 (1998), S. 685-688 
    Details
    ISSN: 1573-0972
    Keywords: Antibiotic ; bioreactor ; Chromobacterium violaceum ; pigment ; violacein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract A procedure for the production, extraction, and purification of violacein was developed using Chromobacterium violaceum (CCT 3496) cultivated on cotton, in modified 1 litre Roux bottles. A surface tray bioreactor was built to perform these experiments. Violacein was extracted with commercial ethanol, and purified by filtration, Soxhlet extraction, crystallization and high performance liquid chromatography. The violacein was analysed and identified by proton and carbon-13 NMR spectroscopies, thermogravimetric analysis, mass spectrometry, UV-VIS spectroscopy and infrared spectroscopy. It was concluded that the product was highly purified violacein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008809504504
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  • 13
    Electronic Resource
    Electronic Resource
    High-density perfusion culture of insect cells with a BioSep ultrasonic filter (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 59 (1998), S. 351-359 
    Details
    ISSN: 0006-3592
    Keywords: bioreactor ; high density ; insect cells ; perfusion ; Sf9 ; ultrasonic filter ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The baculovirus/insect cell expression system has provided a vital tool to produce a high level of active proteins for many applications. We have developed a very high-density insect cell perfusion process with an ultrasonic filter as a cell retention device. The separation efficiency of the filter was studied under various operating conditions. A cell density of over 30 million cells/mL was achieved in a controlled perfusion bioreactor and cell viability remained greater than 90%. Sf9 cells from a high-density culture and a spinner culture were infected with two recombinant baculoviruses expressing genes for the production of human chitinase and monocyte-colony inhibition factor. The protein yield on a cell basis from infecting high-density Sf9 cells was the same as or higher than that from the spinner Sf9 culture. Virus production from the high-density culture was similar to that from the spinner culture. The results show that the ultrasonic filter did not affect insect cells' ability to support protein expression and virus production following infection with baculovirus. The potential applications of the high-density perfusion culture for large-scale protein expression from Sf9 cells are also highlighted. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 59:351-359, 1998.
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  • 14
    Electronic Resource
    Electronic Resource
    On-line monitoring of respiration in recombinant-baculovirus infected and uninfected insect cell bioreactor cultures (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 50 (1996), S. 36-48 
    Details
    ISSN: 0006-3592
    Keywords: insect cell culture ; Sf-9 cells ; respiration ; bioreactor ; on-line monitoring ; baculovirus expression vector system ; recombinant proteins ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Respiration rates in Spodoptera frugiperda (Sf-9) cell bioreactor cultures were successfully measured on-line using two methods: The O2 uptake rate (OUR) was determined using gas phase pO2 values imposed by a dissolved oxygen controller and the CO2 evolution rate (CER) was measured using an infrared detector. The measurement methods were accurate, reliable, and relatively inexpensive. The CER was routinely determined in bioreactor cultures used for the production of several recombinant proteins. Simple linear relationships between viable cell densities and both OUR and CER in exponentially growing cultures were used to predict viable cell density. Respiration measurements were also used to follow the progress of baculoviral infections in Sf-9 cultures. Infection led to increases in volumetric and per-cell respiration rates. The relationships between respiration and several other culture parameters, including viable cell density, cell protein, cell volume, glucose consumption, lactate production, viral titer, and recombinant β-galactosidase accumulation, were examined. The extent of the increase in CER following infection and the time postinfection at which maximum CER was attained were negatively correlated with the multiplicity of infection (MOI) at multiplicities below the level required to infect all the cells in a culture. Delays in the respiration peak related to the MOI employed were correlated with delays in the peak in recombinant protein accumulation. DO levels in the range 5-100% did not exert any major effects on viable cell densities, CER, or product titer in cultures infected with a baculovirus expressing recombinant β-galactosidase. © 1996 John Wiley & Sons, Inc.
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  • 15
    Electronic Resource
    Electronic Resource
    Kinetic studies of fusarium solani pisi cutinase used in a gas/solid system: Transesterification and hydrolysis reactions (1997)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 56 (1997), S. 1-8 
    Details
    ISSN: 0006-3592
    Keywords: transesterification ; hydrolysis ; water activity ; cutinase ; gas ; bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Fusarium solani cutinase supported onto Chromosorb P was used to catalyze transesterification (alcoholysis) and hydrolysis on short volatile alcohols and esters in a continuous gas/solid bioreactor. In this system, a solid phase composed of a packed enzymatic preparation was continuously percolated with carrier gas which fed substrates and removed reaction products simultaneously. A kinetic study was performed under differential operating conditions in order to get initial reaction rates. The effect of the hydration state of the biocatalyst on the kinetics was studied for 3 conditions of hydration (aw = 0.2, aw = 0.4 and aw = 0.6), the alcoholysis of propionic acid methyl ester with n-propanol, and for 5 hydration levels (from aw = 0.2 to aw = 0.6) for the hydrolysis of propionic acid methyl, ethyl or propyl esters. F. solani cutinase was found to have an unusual kinetic behavior. A sigmoid relationship between the rate of transesterification and the activity of methyl propionate was observed, suggesting some form of cooperative activation of the enzyme by one of its substrate. For the hydrolysis of short volatile propionic acid alkyl esters, threshold effects on the reaction rate, highly depending on the water activity and the substrate polarity, are reported. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 1-8, 1997.
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  • 16
    Electronic Resource
    Electronic Resource
    Perfusion bioreactors for the production of recombinant proteins in insect cells (1996)
    Springer
    Cytotechnology 20 (1996), S. 191-198 
    Details
    ISSN: 1573-0778
    Keywords: insect cell culture ; perfusion culture ; membrane perfusion ; crossflow microfiltration ; baculovirus ; bioreactor ; fluidized bed ; packed bed ; recombinant protein production
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Conclusion High density perfusion culture of insect cells for the production of recombinant proteins has proved to be an attractive alternative to batch and fed-batch processes. A comparison of the different production processes is summarized in Table 3. Internal membrane perfusion has a limited scale-up potential but appears to the method of choice in smaller lab-scale production systems. External membrane perfusion results in increased shear stress generated by pumping of cells and passing through microfiltration modules at high velocity. However, using optimized perfusion strategies this shear stress can be minimized such that it is tolerated by the cells. In these cases, perfusion culture has proven to be superior to batch production with respect to product yields and cell specific productivity. Although insect cells could be successfully cultivated by immobilization and perfusion in stationary bed bioreactors, this method has not yet been used in continuous processes. In fluidized bed bioreactors with continuous medium exchange cells showed reduced growth and protein production rates. For the cultivation of insect cells in batch and fedbatch processes numerous efforts have been made to optimize the culture medium in order to allow growth and production at higher cell densities. These improved media could be used in combination with a perfusion process, thus allowing substantially increased cell densities without raising the medium exchange rate. However, sufficient oxygen supply has to be guaranteed during fermentation in order to ensure optimal productivity.
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    URL: http://dx.doi.org/10.1007/BF00350399
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  • 17
    Electronic Resource
    Electronic Resource
    Development of a versatile computer integrated control system for bioprocess controls (1998)
    Springer
    Cytotechnology 26 (1998), S. 227-236 
    Details
    ISSN: 1573-0778
    Keywords: bioreactor ; computer control ; data acquisition ; glucose control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract A general approach is described for the implementation of a networked multi-unit computer integrated control system. The use of data acquisition hardware and graphical programming tools alleviates tedious programming and maintains potency and flexibility. One application of the control system, the control of a mammalian cell perfusion culture based on a key nutrient glucose concentration, was demonstrated. The control system offers customized user interface for all process control parameters and allows the flexibility for continued improvement and implementation of new tailored functions. The temperature, pH, dissolved oxygen and glucose level were accurately controlled.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007948313304
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  • 18
    Electronic Resource
    Electronic Resource
    A microcarrier-based cell culture process for the production of a bovine respiratory syncytial virus vaccine (1999)
    Springer
    Cytotechnology 29 (1999), S. 135-149 
    Details
    ISSN: 1573-0778
    Keywords: anchorage dependent ; animal cell ; bioreactor ; Cultispher S ; Cytodex 3 ; microcarrier ; respiratory syncytial virus ; vaccine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Veterinary viral vaccines generally comprise either attenuated or chemically inactivated viruses which have been propagated on mammalian cell substrates or specific pathogen free (SPF) eggs. New generation vaccines include chemically inactivated virally-infected whole cell vaccines. The NM57 cell line is a bovine nasal turbinate persistently infected (non-lytic infection) with a strain of the respiratory syncytial virus (RSV). The potential of microcarrier technology for the cultivation in bioreactors of this anchorage dependent cell line for RSV vaccine production has been investigated. Both Cytodex 3 and Cultispher S microcarriers proved most suitable from a selection of microcarriers as growth substrates for this NM57 cell line. Maximum cell densities of 4.12×105 cells ml-1and 5.52×105 cells ml-1 respectively were obtained using Cytodex 3 (3 g l-1) and and Cultispher S (1 g l-1) in 5 l bioreactor cultures. The fact that cell growth was less sensitive to agitation rate when cultured on Cultispher S microcarriers, and that cells were efficiently harvested from this microcarrier by an enzymatic method, suggested Cultispher S is suitable for further evaluation at larger bioreactor scales (〉5 l) than that described here.
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    URL: http://dx.doi.org/10.1023/A:1008022828736
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  • 19
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    Disposable bioreactor for cell culture using wave-induced agitation (1999)
    Springer
    Cytotechnology 30 (1999), S. 149-158 
    Details
    ISSN: 1573-0778
    Keywords: bioreactor ; cell culture ; disposable ; wave agitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract This work describes a novel bioreactor system for the cultivation of animal, insect, and plant cells using wave agitation induced by a rocking motion. This agitation system provides good nutrient distribution, off-bottom suspension, and excellent oxygen transfer without damaging fluid shear or gas bubbles. Unlike other cell culture systems, such as spinners, hollow-fiber bioreactors, and roller bottles, scale-up is simple, and has been demonstrated up to 100 L of culture volume. The bioreactor is disposable, and therefore requires no cleaning or sterilization. Additions and sampling are possible without the need for a laminar flow cabinet. The unit can be placed in an incubator requiring minimal instrumentation. These features dramatically lower the purchase cost, and operating expenses of this laboratory/pilot scale cell cultivation system. Results are presented for various model systems: 1) recombinant NS0 cells in suspension; 2) adenovirus production using human 293 cells in suspension; 3) Sf9 insect cell/baculovirus system; and 4) human 293 cells on microcarrier. These examples show the general suitability of the system for cells in suspension, anchorage-dependent culture, and virus production in research and GMP applications.
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    URL: http://dx.doi.org/10.1023/A:1008025016272
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    Working at controlled water activity in a continuous process: The gas/solid system as a solution (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 45 (1995), S. 387-397 
    Details
    ISSN: 0006-3592
    Keywords: transesterification ; water activity ; lipolytic enzymes ; gas ; bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Fusarium solani cutinase and Candida cylindracea lipase were used to catalyze a transesterification reaction in a continuous gas/solid bioreactor. In this system, a solid phase composed of a packed enzymatic preparation was continuously percolated with carrier gas which fed substrate and removed reaction products simultaneously. Different conditions of immobilization were used and compared to the results obtained with a nonsupported enzyme. The enzymatic activity was found to be highly dependent of a key parameter: water activity (aw). Biocatalyst stability was greatly influenced by water activity and the choice of immobilization technique for the enzymatic material. For free and adsorbed enzymes, water requirements exhibited optima which corresponded to the complete hydration coverage of the protein. These optima presented a good correlation with the isotherm sorption curves obtained for the different preparations. In this work are reported the results concerning the possibility of using a continuous system able to operate at controlled water activity in a heterogeneous medium. Lipolytic enzyme in such a system appears to be a new process for the biotransformation of volatile esters. © 1995 John Wiley & Sons, Inc.
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    URL: http://dx.doi.org/10.1002/bit.260450503
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    Implantable hollow fiber bioreactor as a potential treatment for hypercholesterolemia: Characterization of the catalytic unit (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 48 (1995), S. 36-41 
    Details
    ISSN: 0006-3592
    Keywords: hollow fiber ; bioreactor ; immobilized enzymes ; porosity ; phospholipase A2 ; low densitylipoprotein ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Previous studies have shown that the modification of low density lipoprotein (LDL) by the enzyme phospholipase A2(PLA2)results in a reduction of cholesterol levels in the plasma of hypercholesterolemic rabbits, due to accelerated clearance of the modified LDL. In the current study, we established techniques and optimized the ratio of enzyme to support for the immobilization of PLA2 on a polymeric support. Hollow fiber bioreactors made from polytetrafluoroethylene (PTFE) polymers were used to encapsulate immobilized PLA2. This design was adopted to eliminate hemolysis of red blood cells by the enzyme. Characterization of the resulting immobilized enzyme in terms of its activity, Michaelis-Menten kinetic constants, and the variation of its activity with incubation time is presented. The enzyme activity was not significantly altered upon incubation at 37°C in lipoprotein-deficient serum (LPDS), over the course of 2 months. The Michaelis-Menten kinetics constants are KM = 8.9 mM, Vmax = 6434.2 for the free enzyme and KappM = 16.7 mM, Vappmax = 619.7 for the immobilized enzyme. These data suggest that a system based on immobilized PLA2 in conjunction with hollow fiber bioreactors (HFBs) may be a good candidate for lowering LDL levels in plasma. © 1995 John Wiley & Sons, Inc.
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    URL: http://dx.doi.org/10.1002/bit.260480107
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    Protein-free human-human hybridoma cultures in an intercalated-spiral alternate-dead-ended hollow fiber bioreactor (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 47 (1995), S. 384-400 
    Details
    ISSN: 0006-3592
    Keywords: hollow fiber ; bioreactor ; hybridoma ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Batch cell cultures of a human-human hybridoma line in a convective flow dominant intercalated-spiral altetnate-dead-ended hollow fiber are compared with those using conventional axial-flow hollow fiber bioreactors and a stirred-tank bioreactor. Relatively short-term fed-batch and perfusion cell cultures were also employed for the intercalated-spiral bioreactor. When operating conditions of a batch intercalated-spiral bioreactor were properly chosen, the cell growth and substrate consumption paralleled that of a batch stirred-tank culture. The results verified the premise of the intercalated-spiral hollow fiber bioreactor that nutrient transport limitations can be eliminated when the convective flux through the extracapillary space is sufficiently high.© John Wiley & Sons, Inc.
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    URL: http://dx.doi.org/10.1002/bit.260470312
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    Transient and stationary operating conditions on performance of lactic acid bacteria crossflow microfiltration (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 49 (1996), S. 78-86 
    Details
    ISSN: 0006-3592
    Keywords: crossflow microfiltration ; hydrodynamics ; fouling ; bioreactor ; Lactobacillus helveticus ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A filtration rig equipped with a tubular alumina membrane was used to study the performance of crossflow microfiltration of Lactobacillus helveticus. Experiments were performed at constant permeation flux. High cell concentrations and fast transient conditions to the stationary J adversely affected permeability. Membrane fouling was due to a fast irreversible layer formation and to a reversible cell cake. This microbial deposit characteristics were dependent on the ratio permeation flux/wall shear stress, J/τw. Fouling was faster and more severe when J/τw was greater than a critical value of 1.15 L-1 · h-1 · m-2 · Pa-1. The disordered structure of this cell cake seemed to lead to a macromolecule deposit between the cells which adversely affected the membrane permeability. © 1996 John Wiley & Sons, Inc.
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    Cell growth and differentiation on feeder layers is predicted to be influenced by bioreactor geometry (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 50 (1996), S. 479-492 
    Details
    ISSN: 0006-3592
    Keywords: stem cell ; bioreactor ; stromal layer ; Graetz number ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Tissue function is comprised of a complex interplay between biological and physicochemical rate processes. The design of bioreactors for tissue engineering must account for these processes simultaneously in order to obtain a bioreactor that provides a uniform environment for tissue growth and development. In the present study we consider the effects of fluid flow and mass transfer on the growth of a tissue in a parallel-plate bioreactor configuration. The parenchymal cells grow on a preformed stromal (feeder) layer that secretes a growth factor that stimulates parenchymal stem cell replication and differentiation. The biological dynamics are described by a unilineage model that describes the replication and differentiation of the tissue stem cell. The physicochemical rates are described by the Navier-Stokes and convective-diffusion equations. The model equations are solved by a finite element method. Two dimensionless groups govern the behavior of the solution. One is the Graetz number (Gz) that describes the relative rates of convection and diffusion, and the other a new dimensionless ratio (designated by P) that describes the interplay of the growth factor production, diffusion, and stimulation. Four geometries (slab, gondola, diamond, and radial shapes) for the parallel-plate bioreactor are analyzed. The uniformity of cell growth is measured by a two-dimensional coefficient of variance. The concentration distribution of the stroma-derived growth factor was computed first based on fluid flow and bioreactor geometry. Then the concomitant cell density distribution was obtained by integrating the calculated growth factor concentration with the parenchymal cell growth and unilineage differentiation process. The spatiotemporal cell growth patterns in four different bioreactor configurations were investigated under a variety of combinations of Gz (10-1, 100, and 101) and P(10-2, 10-1, 100, 101, and 102). The results indicate high cell density and uniformity can be achieved for parameter values of P = 0.01, …, 0.1 and Gz = 0.1, …, 1.0. Among the four geometries investigated the radial-flow-type bioreactor provides the most uniform environment in which parenchymal cells can grow and differentiate ex vivo due to the absence of walls that are parallel to the flow paths creating slow flowing regions. © 1996 John Wiley & Sons, Inc.
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    Hollow fiber bioartificial liver utilizing collagen-entrapped porcine hepatocyte spheroids (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 52 (1996), S. 34-44 
    Details
    ISSN: 0006-3592
    Keywords: hepatocyte spheroid ; porcine hepatocyte ; hollow fiber ; bioartificial liver ; collagen ; bioreactor ; ureagenesis ; albumin synthesis ; glucuronidation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A xenogeneic hollow fiber bioreactor utilizing collagen-entrapped dispersed hepatocytes has been developed as an extracorporeal bioartificial liver (BAL) for potential treatment of acute human fulminant hepatitis. Prolonged viability, enhanced liver-specific functions, and differentiated state have been observed in primary porcine hepatocytes cultivated as spheroids compared to dispersed hepatocytes plated on a monolayer. Entrapment of spheroids into the BAL can potentially improve performance over the existing device. Therefore, studies were conducted to evaluate the feasibility of utilizing spheroids as the functionally active component of our hybrid device. Confocal microscopy indicated high viability of spheroids entrapped into cylindrical collagen gel. Entrapment of spheroids alone into collagen gel showed reduced ability to contract collagen gel. By mixing spheroids with dispersed cells, the extent of collagen gel contraction was increased. Hepatocyte spheroids collagen-entrapped into BAL devices were maintained for over 9 days. Assessment of albumin synthesis and ureagenesis within a spheroid-entrapment BAL indicated higher or at least as high activity on a per-cell basis compared to a dispersed hepatocyte-entrapment BAL device. Clearance of 4-methylumbelliferone to its glucuronide was detected throughout the culture period as a marker of phase II conjugation activity. A spheroid-entrapment bioartificial liver warrants further studies for potential human therapy. © 1996 John Wiley & Sons, Inc.
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    Biodegradation of paint stripper solvents in a modified gas lift loop bioreactor (1997)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 55 (1997), S. 163-169 
    Details
    ISSN: 0006-3592
    Keywords: bioreactor ; paint stripper solvents ; biodegradation ; model ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Paint stripping wastes generated during the decontamination and decommissioning of former nuclear facilities contain paint stripping organics (dichloromethane, 2-propanol, and methanol) and bulk materials containing paint pigments. It is desirable to degrade the organic residues as part of an integrated chemical-biological treatment system. We have developed a modified gas lift loop bioreactor employing a defined consortium of Rhodococcus rhodochrous strain OFS and Hyphomicrobium sp. DM-2 that degrades paint stripper organics. Mass transfer coefficients and kinetic constants for biodegradation in the system were determined. It was found that transfer of organic substrates from surrogate waste into the air and further into the liquid medium in the bioreactor were rapid processes, occurring within minutes. Monod kinetics was employed to model the biodegradation of paint stripping organics. Analysis of the bioreactor process was accomplished with BIOLAB, a mathematical code that simulates coupled mass transfer and biodegradation processes. This code was used to fit experimental data to Monod kinetics and to determine kinetic parameters. The BIOLAB code was also employed to compare activities in the bioreactor of individual microbial cultures to the activities of combined cultures in the bioreactor. This code is of benefit for further optimization and scale-up of the bioreactor for treatment of paint stripping and other volatile organic wastes in bulk materials. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 163-169, 1997.
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    Mixing power, external convection, and effectiveness in bioreactors (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 51 (1996), S. 131-140 
    Details
    ISSN: 0006-3592
    Keywords: mixing power ; convection ; fermentation ; bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The phenomena of mixing and mass transfer of substrates to microorganisms greatly affect the biochemical reactions which take place in fermentation processes. The effect that agitation power has on the observable reaction kinetics involved in beer fermentation has been studied in different types of bioreactors, from laboratory to industrial scale. With this aim in mind, an effectiveness factor, η, is introduced which is defined as the relation between the existing rate of reaction, whichever bioreactor is considered, and the reaction rate in the well-mixed, and therefore presumably homogeneous, bioreactor with no diffusional limits. The limitation to homogeneously supplying nutrient material to the cells produces a decrease in this effectiveness factor, which has been correlated to the energy dissipation rate with a similar slope to that which appears in an existing correlation in the literature between this energy and the mass transfer coefficient. Additionally, a dimensionless reaction-convection number, NRC, which is a function of the power input per unit volume, is proposed, which has been appropriately employed in correlating the effectiveness factor for the types of processes in which convection may be the key resistance factor. © 1996 John Wiley & Sons, Inc.
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    Effect of particle loading on GM-CSF production by Saccharomyces cerevisiae in a three-phase fluidized bed bioreactor (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 51 (1996), S. 229-236 
    Details
    ISSN: 0006-3592
    Keywords: bioreactor ; fluidized bed ; murine granulocyte-macrophage colony stimulating factor ; Saccharomyces cerevisiae ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Continuous production of a recombinant murine granulocyte-macrophage colony-stimulating factor (MuGM-CSF) by immobilized yeast cells, Saccharomyces cerevisiae strain XV2181 (a/a, Trp1) containing plasmid pαADH2, in a fluidized bed bioreactor was studied at a 0.03 h-1 dilution rate and various particle loading rates ranging from 5% to 33% (v/v). Cells were immobilized on porous glass beads fluidized in an air-lift draft tube bioreactor. A selective medium containing glucose was used to start up the reactor. After reaching a stable cell concentration, the reactor feed was switched to a rich, nonselective medium containing ethanol as the carbon source for GM-CSF production. GM-CSF production increased initially and then dropped gradually to a stable level. During the same period, the fraction of plasmid-carrying cells declined continuously to a lower level, depending on the particle loading. The relatively stable GM-CSF production, despite the large decline in the fraction of plasmid-carrying cells, was attributed to cell immobilization. As the particle loading rate increased, the plasmid stability also increased. Also, as the particle loading increased from 5% to 33%, total cell density in the bioreactor increased from 16 to 36 g/L, and reactor volumetric productivity increased from 0.36 to 1.31 mg/L·h. However, the specific productivity of plasmid-carrying cells decreased from 0.55 to 0.07 mg/L·g cell. The decreased specific productivity at higher particle loading rates was attributed to reduced growth efficiency caused by nutrient limitations at higher cell densities. Both the reactor productivity and specific cell productivity increased by two- to threefold or higher when the dilution rate was increased from 0.03 to 0.07 h-1. © 1996 John Wiley & Sons, Inc.
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    The application of membrane biological reactors for the treatment of wastewaters (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 49 (1996), S. 601-610 
    Details
    ISSN: 0006-3592
    Keywords: aerobic ; anaerobic ; biomass separation ; bioreactor ; bubbleless ; oxygen mass transfer ; extraction of organic pollutants ; membrane ; wastewaters ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Combining membrane technology with biological reactors for the treatment of municipal and industrial wastewaters has led to the development of three generic membrane processes within bioreactors: for separation and recycle of solids; for bubbleless aeration of the bioreactor; and for extraction of priority organic pollutants from hostile industrial wastewaters. Commercial aerobic and anaerobic membrane separation bioreactors already provide a small footprint alternative to conventional biological treatment methods, producing a high-quality effluent at high organic loading rates. Both the bubbleless aeration and extractive membrane bioreactors are in the development stages. The former uses gas-permeable membranes to improve the mass transfer of oxygen to the bioreactor by providing bubbleless oxygen. By using a silicone membrane process, extractive membrane bioreactors transfer organic pollutants from chemically hostile wastewaters to a nutrient medium for subsequent biodegradation. All three membrane bioreactor (MBR) processes are comparatively and critically reviewed. © 1996 John Wiley & Sons, Inc.
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    Application of light-emitting diodes in bioreactors: Flashing light effects and energy economy in algal culture (Chlorella pyrenoidosa) (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 50 (1996), S. 98-107 
    Details
    ISSN: 0006-3592
    Keywords: algal culture ; bioreactor ; bioregenerative system ; energy economy ; light-emitting diode (LED) ; microsecond pulse modulation ; Chlorella pyrenoidosa ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Light-emitting diodes (LEDs) were used as the sole light source in continuous culture of the green alga Chlorella pyrenoidosa. The LEDs applied show a peak emission at 659 nm with a half-power bandwidth of 30 nm. Selection of this wavelength range, which is optimal for excitation of chlorophylls a and b in their “red” absorption bands makes all photons emitted potentially suitable for photosynthesis. No need for additional supply of blue light was found. A standardized panel with 2 LEDs cm-2 fully covered one side of the culture vessel. At standard voltage in continuous operation the light output of the diode panel appeared more than sufficient to reach maximal growth. Flash operation (5-μs pulse duration) enables potential use of higher operating voltages which may render up to three times more light output. Flat airlift fermentor-type continuous culture devices were used to estimate steady state growth rates of Chlorella pyrenoidosa as a function of the light flux (μmol photons · m-2 · s-1) and the flashing frequency of the light-emitting diodes (which determines the duration of the dark “off” time between the 5-μs “on” pulses). At the fixed voltage and turbidostat setting applied a 20-kHz frequency, which equals dark periods of 45 μs, still permitted the maximum growth rate to become nearly reached. Lower frequencies fell short of sustaining the maximal growth rate. However, the light flux decrease resulting from lowering of the flash frequency appeared to reduce the observed growth rates less than in the case of a similar flux decrease with light originating from LEDs in continuous operation. Flash application also showed reduction of the quantum requirement for oxygen evolution at defined frequencies. The frequency domain of interest was between 2 and 14 kHz. LEDs may open interesting new perspectives for studies on optimization of mixing in mass algal culture via the possibility of separation of interests in the role of modulation on light energy conversion and saturation of nutrient supply. Use of flashing LEDs in indoor algal culture yielded a major gain in energy economy in comparison to luminescent light sources. © 1996 John Wiley & Sons, Inc.
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    Soil immobilization: New concept for biotreatment of soil contaminants (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 57 (1998), S. 471-476 
    Details
    ISSN: 0006-3592
    Keywords: soil immobilization ; soil pollutants ; bioremediation ; bioreactor ; biofilm ; pentachlorophenol ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A new concept for the development of microbial consortia for the degradation of persistent soil pollutants and for pollutant treatment is proposed. The concept defined as “soil immobilization” is based on the entrapment of soil particles, showing microbial activity in degrading the target pollutant, into a solid membrane with a large pore size distribution. The particular hydrodynamic and mass transfer properties of this system result in a very efficient process. A new type of bioreactor is proposed for carrying out the immobilized soil process. The performance of the system was tested by developing a microbial system for the mineralization of pentachlorophenol (PCP). The results show that the volumetric efficiency of the process for PCP mineralization in the immobilized soil bioreactor is 1-3 orders of magnitude higher than reported literature values. Chlorine and carbon atoms of PCP are both nearly completely (99%) mineralized. ©1998 John Wiley & Sons, Inc. Biotechnol Bioeng 57: 471-476, 1998.
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    Polysaccharide concentration and molecular weight effects on the oxygen mass transfer in a reciprocating plate bioreactor (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 52 (1996), S. 507-517 
    Details
    ISSN: 0006-3592
    Keywords: oxygen mass transfer coefficient ; molecular weight ; polysaccharide fermentation ; bioreactor ; reciprocating plate ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: In most polysaccharide fermentations, the nature of the fermentation broth changes drastically with time and, as a result, the overall oxygen mass transfer coefficient (KLa) can vary by orders of magnitude. To obtain a better understanding of this phenomenon, an experimental program was devised to study the respective influence of molecular weight and concentration of dextran solutions on KLa. Experiments were conducted in a reciprocating plate bioreactor. This bioreactor uses a stack of perforated plates that is reciprocated axially in the column and it is therefore well suited for mixing viscous liquid broths and providing uniform overall mass transfer coefficients. The variation of KLa with the power input per unit volume and the superficial gas velocity were obtained for three ranges of molecular weights and five concentrations of dextran. In every medium, two regimes of operation were observed as a function of the power input per unit volume: a first regime, at low power inputs per unit volume where KLa remains constant until a threshold of power input is attained; and a second regime, which is characterized by a steep increase of KLa as a function of the power input per unit volume. The presence of dissolved biological macromolecules, not only because of their effect on the rheology of the medium but also because their effect on the gas-liquid interface, has a significant impact on KLa. It was found that, generally, small concentrations of polysaccharide favor oxygen mass transfer despite the increase in medium viscosity. However, the respective influence of polysaccharide concentration and molecular weight was different for the two regimes of operation. © 1996 John Wiley & Sons, Inc.
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    Production of a high viscosity polysaccharide, methylan, in a novel bioreactor (1997)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 54 (1997), S. 115-121 
    Details
    ISSN: 0006-3592
    Keywords: Methylobacterium organophilum ; high viscosity polysaccharide ; methylan ; multidisk mixer ; bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The effect of shear stress on the production of a high viscosity polysaccharide, methylan, from methanol by Methylobacterium organophilum was investigated by using a multidisk mixer. It was observed in the multidisk mixer with defined shear stresses that the specific production rate of methylan increased gradually with increasing shear stress up to 30 Pa, and the production rate was constant beyond 30 Pa. This result suggested that the limited mass transfer from the medium into cells reduced methylan production. A novel bioreactor that provided the large volume of a high shear region was used to increase methylan production. Fed-batch cultures in the novel bioreactor were performed by the dissolved oxygen-stat method of methanol. When 1.13 g/L ammonium ion was added, the concentrations of cells of methylan were 31 and 20.6 g/L, respectively. The productions of cells and methylan in our designed bioreactor were 20 and 50% higher than those obtained in a conventional fermentor. The methylan content reached a maximum of 20.7 g/L in the bioreactor and the viscosity of the fermentation broth was 127 Pa · s, which corresponds to 68 g/L as a xanthan. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54: 115-121, 1997.
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    Automated production of cultured epidermal autografts and sub-confluent epidermal autografts in a computer controlled bioreactor (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 59 (1998), S. 679-683 
    Details
    ISSN: 0006-3592
    Keywords: cultured epidermal autografts ; bioreactor ; keratinocyte cultures ; tissue engineering ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The objective of this work was to engineer an automated system for the production of cultured epidermal autografts and sub-confluent cultured epidermal autografts. Human epidermal cells were grown directly on a transparent FEP film, which was held in place and surrounded by a polycarbonate growth chamber. The growth chambers were stacked to accommodate various surface area requirements. To monitor the development of the grafts, the upper-most growth chamber in the stack was periodically placed on a standard phase contrast microscope. The growth chambers were connected to a multi-channel peristaltic pump, which was controlled automatically to manage fluid-handling operations. Sub-confluent graft production involved removing the epidermal-film composite from the growth chambers and cutting desired graft geometries. Producing cultured epidermal autografts involved (1) removing the confluent epidermal-film composite from the growth chambers, (2) treating the composites with dispase, and (3) clipping the detached cultured epidermis to a synthetic support. Twelve to fifteen days were required to produce sub-confluent grafts (total surface area 3500-4500 cm2 50% confluent) and 18 to 24 d were required to produce standard cultured epidermal autografts (total surface area 3500-4500 cm2). The system reduces the tedious manual labor associated with producing cultured epidermal autografts. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 59:679-683, 1998.
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    Characterization of gas transfer and mixing in a bubble column equipped with a rubber membrane diffuser (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 58 (1998), S. 633-641 
    Details
    ISSN: 0006-3592
    Keywords: bioreactor ; elastic sparger ; bubble size ; oxygen transfer efficiency ; characteristic mixing time ; wrinkled bubbles ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Gas transfer and mixing were characterized in a 32-L bubble column reactor equipped with a commercially available rubber membrane diffuser. The performance of the membrane diffuser indicates that the slits in the membrane are best described as holes with elastic lids, acting as valves cutting off bubbles from the gas stream. The membrane diffuser thus functions as a one-way valve preventing backflow of liquid. Our design of the bottom plate of the reactor enabled us to optimize the aeration by changing the tension of the membrane. We thereby achieved mass transfer coefficients higher than those previously reported in bubble columns. A strong dependence of mass transfer on gas holdup and bubble size was indicated by estimates based on these two variables. The microalga, Rhodomonas sp., sensitive to chemical and physical stress, was maintained for 8 months in continuous culture with a productivity identical to cultures grown in stirred tank reactors. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 58: 633-641, 1998.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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