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  • Articles  (30)
  • bioreactor
  • Springer  (30)
  • Oxford University Press
  • 2020-2023
  • 1995-1999  (30)
  • 1
    Electronic Resource
    Electronic Resource
    Synthesis and secretion of the mouse whey acidic protein in transgenic sheep (1996)
    Springer
    Transgenic research 5 (1996), S. 67-72 
    Details
    ISSN: 1573-9368
    Keywords: whey acidic protein gene ; transgenic sheep ; bioreactor ; mammary gland
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The synthesis of foreign proteins can be targeted to the mammary gland of transgenic animals, thus permitting commercial purification of otherwise unavailable proteins from milk. Genetic regulatory elements from the mouse whey acidic protein (WAP) gene have been used successfully to direct expression of transgenes to the mammary gland of mice, goats and pigs. To extend the practical usefulness of WAP promoter-driven fusion genes and further characterize WAP expression in heterologous species, we introduced a 6.8 kb DNA fragment containing the genomic form of the mouse WAP gene into sheep zygotes. Two lines of transgenic sheep were produced. The transgene was expressed in mammary tissue of both lines and intact WAP was secreted into milk at concentrations estimated to range from 100 to 500 mg/litre. Ectopic WAP gene expression was found in salivary gland, spleen, liver, lung, heart muscle, kidney and bone marrow of one founder ewe. WAP RNA was not detected in skeletal muscle and intestine. These data suggest that unlike pigs, sheep may possess nuclear factors in a variety of tissues that interact with WAP regulatory sequences. Though the data presented are based on only two lines, these findings suggest WAP regulatory sequences may not be suitable as control elements for transgenes in sheep bioreactors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01979923
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  • 2
    Electronic Resource
    Electronic Resource
    Bioreactor seaweed cell culture for production of bioactive oxylipins (1995)
    Springer
    Journal of applied phycology 7 (1995), S. 187-198 
    Details
    ISSN: 1573-5176
    Keywords: algal cell culture ; bioreactor ; hydroxy fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Liquid cell suspension cultures derived from marine plants have the potential to biosynthesize novel biomedicinal compounds in a controlled environment. Of particular interest are the eicosanoids and related oxylipins emanating from the 15-lipoxygenase manifold of the arachidonic acid cascade, which is active in the brown algaLaminaria saccharina. Filamentous cell clumps ofL. saccharina isolated from female gametophytes were cultured in an illuminated bubble-column bioreactor in GP2 artificial seawater nutrient medium at 13 °C and air flow rate of 0.35 L air min−1 L−1 culture (vvm). Growth kinetics and biomass productivity data were obtained as a function of incident light intensity (2.4 to 98μmol photon m−2 s−1) and initial cell density (27 to 149 mg DCW L−1). Maximum cell densities exceeded 1200 mg DCW L−1 after a 20 day cultivation time at optimal conditions of 98μmol photon m−2 s−1 and 118 mg DCW L−1 initial cell density. Qualitative analysis of chloroform/methanol extracts of the cell culture biomass by GC-MS confirmed the presence of the hydroxy fatty acids 13-HODTA and 13-HOTE, the likely products of 15-lipoxygenase catalyzed oxidation of linoleic or linolenic acids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00693067
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  • 3
    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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  • 4
    Electronic Resource
    Electronic Resource
    Continuous antibiotic production by an immobilized cyanobacterium in a seaweed-type bioreactor (1995)
    Springer
    Journal of applied phycology 7 (1995), S. 135-139 
    Details
    ISSN: 1573-5176
    Keywords: continuous culture ; cyanobacterium ; Scytonema ; antibiotic ; bioreactor ; immobilization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The filamentous cyanobacterium,Scytonema sp. TISTR 8208, which produces a cyclic peptide antibiotic, was cultivated for 20 d in a seaweed-type bioreactor containing anchored polyurethan foam strips. Cells immobilized onto the foam strips produced the antibiotic for only several days, and the secreted antibiotic disappeared very rapidly from the medium. Cells accumulated the antibiotic intracellularly in a growth-related manner, and secreted it in the stationary phase. Since the antibiotic has a stable physico-chemical nature, the cells seem to take it up and metabolize it. When continuous cultivation was attempted, stable production of the antibiotic was maintained in the bioreactor for 16 d at a dilution rate of 0.01 h−1. Three times more antibiotic was produced in the continuous culture than in the batch culture by the 16th day.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00693059
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  • 5
    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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  • 6
    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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  • 7
    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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  • 8
    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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  • 9
    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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  • 10
    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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  • 11
    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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  • 12
    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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  • 13
    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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  • 14
    Electronic Resource
    Electronic Resource
    Generalized predictive control based on neural networks (1996)
    Springer
    Neural processing letters 4 (1996), S. 107-112 
    Details
    ISSN: 1573-773X
    Keywords: bioreactor ; generalized predictive control ; neural networks ; nonlinear systems
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract This paper presents the Generalized Predictive Control (GPC) strategy based on Artificial Neural Network (ANN) plant model. To obtain the step and the free process responses which are needed in the generalized predictive control strategy we iteratively use a multilayer feedforward ANN as a one-step-ahead predictor. A bioprocess was chosen as a realistic nonlinear SISO system to demonstrate the feasibility and the performance of this control scheme. A comparison was made between our approach and the adaptive GPC (AGPC).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00420619
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  • 15
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    Electronic Resource
    Continuous culture with deep seawater of a benthic food diatom Nitzschia sp. (1997)
    Springer
    Hydrobiologia 358 (1997), S. 245-249 
    Details
    ISSN: 1573-5117
    Keywords: deep seawater ; benthic diatom ; Nitzschia sp. ; continuous culture ; bioreactor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A continuous culture system for a benthic food diatom Nitzschia sp. wasestablished by using properties of high nutrient and clean of deep seawater(DSW). DSW collected from 320 m depth in Muroto City, Japan, was introducedinto a glass-pipe bioreactor (14 cm length, 3 cm diam.) containing glassbeads of 0.5 cm diam. as substrata for the alga, and it was incubated at18°C · 80μEm−2sec−1 · L:D=14:10. The chlorophyll a yield of benthicdiatoms in a reactor as a unit of surface area of the substratum was only0.001–0.003 μg cm−2 when the flow rate of DSW was 0(batch culture conditions). However, when DSW was supplied continuously to areactor, the yield increased to 1.4 μg-chl.a cm−2 alongwith the increase in flow rate of DSW. Moreover, amounts of chl.a washed outof the system were negligible, 0.0014 to 0.0045%, even though theflow rate of DSW was as much as 25 times h−1, suggesting thatsloughing of benthic diatoms from the substratum was minimized. Although theyield of diatoms fluctuated significantly at the time that the DSW wascollected, the variation could be minimized by increasing the flow rate ofDSW. These results indicate that the continuous culturing system with DSWsupports the stable and effective mass culture of benthic food diatom.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1003141104693
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  • 16
    Electronic Resource
    Electronic Resource
    Bioreactors for surface-immobilized cells (1995)
    Springer
    Plant cell, tissue and organ culture 42 (1995), S. 81-90 
    Details
    ISSN: 1573-5044
    Keywords: Adhesion ; bioreactor ; immobilization ; plant cell culture ; secondary metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Surface immobilization of plant cells avoids the problem of hydrodynamic or shear stress, which tends to be characteristic of suspended cells cultured in typical, mechanically agitated bioreactor systems. Surface immobilization also promotes the natural tendency for plant cells to aggregate, which may improve the synthesis and accumulation of secondary metabolites. In addition, exchange of medium is made simple in surface-immobilized systems, and extracellular secondary products are easily recovered on a continuous basis. However, problems related to regulation of the thickness of the immobilized cell layer, maintenance of the biomass in a productive condition, and vacuolar retention of secondary products have yet to be resolved satisfactorily. This review focusses on two surface-immobilization technologies, differing primarily in the nature and the configuration of the inert support. Prototypes of these designs have been applied to a variety of plant cell systems at bioreactor volumes up to 20 litres. Results obtained with several alternative technologies are also summarized.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00037685
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  • 17
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    Monitoring of haploid maize cell suspension culture conditions in bioreactors (1995)
    Springer
    Plant cell, tissue and organ culture 43 (1995), S. 123-126 
    Details
    ISSN: 1573-5044
    Keywords: bioreactor ; dissolved oxygen ; haploid cell suspension ; pH ; Zea mays
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Maize (Zea mays L.) haploid cells were cultivated in a 1500 ml aerated and stirred batch bioreactor using modified BM medium. Cell growth was highly affected by pH and dissolved oxygen, and we observed two fairly distinct growth phases. During the first two days after inoculation at pH 5.8, oxygen consumption was high and the cells lowered the pH to a value around 4.3. After this period the pH stabilized at 4.5 and the dissolved oxygen reached a steady level. Decreasing dissolved oxygen concentration leads to lower growth rate and to higher pH. Both events mean stress conditions for the cell culture and probably result in increased genetic variability, and the loss of regeneration capacity. The stress condition during the adaptation phase can be eliminated by decreasing the pH of the medium to 4.7 before inoculation and by keeping dissolved oxygen above 40%. These conditions provide prolonged exponential growth dynamics and the cell suspensions could be the basis of large scale cultures also.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00052166
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  • 18
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    Relationship between production of carrot somatic embryos and dissolved oxygen concentration in liquid culture (1999)
    Springer
    Plant cell, tissue and organ culture 57 (1999), S. 29-38 
    Details
    ISSN: 1573-5044
    Keywords: bioreactor ; carrot ; dissolved oxygen ; plant micropropagation ; somatic embryo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract To evaluate the relationship between somatic embryogenesis and dissolved oxygen concentration, somatic embryo cultures of carrot (Daucus carota L.) were cultured under various dissolved oxygen concentration levels (bubble free aeration with 4%, 7%, 20%, 30%, and 40% oxygen in flasks). The system used allows dissolved oxygen concentration control without bubble aeration or mixing speed modification. The total number of somatic embryos was not affected by the dissolved oxygen (DO) concentration tested. Even if globular-stage embryos were induced at a low level of oxygen aeration, heart-stage embryo formation was still repressed. Oxygen enrichment (20%, 30% and 40% oxygen) enhanced torpedo and cotyledonary-stage embryo production. The oxygen-enriched aeration was effective in promoting the growth of the late developmental stages. Sugar consumption did not increase when the oxygen concentration was enriched above the ambient level. The number of heart-stage embryos increased as oxygen concentration increased up to the 7% level, while above the 20% level no change in production was observed. The production of cotyledonary-stage embryos was directly related to oxygen concentration. These results support that oxygen-enriched aeration provides oxygen to the low oxygen areas in somatic embryo. After the heat-stage embryos, which were grown at the 7% level were transferred to a flask with ambient, they developed an elongated root part and eventually grew to normal plantlets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006267002706
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  • 19
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    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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    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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    Application of whole cell rhodococcal biocatalysts in acrylic polymer manufacture (1998)
    Springer
    Antonie van Leeuwenhoek 74 (1998), S. 107-118 
    Details
    ISSN: 1572-9699
    Keywords: amidase ; biocatalyst ; bioreactor ; nitrilase ; polyacrylamide ; Rhodococcus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Rhodococci are ubiquitous in nature and their ability to metabolise a wide range of chemicals, many of which are toxic, has given rise to an increasing number of studies into their diverse use as biocatalysts. Indeed rhodococci have been shown to be especially good at degrading aromatic and aliphatic nitriles and amides and thus they are very useful for waste clean up where these toxic chemicals are present. The use of biocatalysts in the chemical industry has in the main been for the manufacture of high-value fine chemicals, such as pharmaceutical intermediates, though investigations into the use of nitrile hydratase, amidase and nitrilase to convert acrylonitrile into the higher value products acrylamide and acrylic acid have been carried out for a number of years. Acrylamide and acrylic acid are manufactured by chemical processes in vast tonnages annually and they are used to produce polymers for applications such as superabsorbents, dispersants and flocculants. Rhodococci are chosen for use as biocatalysts on an industrial scale for the production of acrylamide and acrylic acid due to their ease of growth to high biomass yields, high specific enzyme activities obtainable, their EFB class 1 status and robustness of the whole cells within chemical reaction systems. Several isolates belonging to the genus Rhodococcus have been shown in our studies to be among the best candidates for acrylic acid preparation from acrylonitrile due to their stability and tolerance to high concentrations of this reactive and disruptive substrate. A critical part of the selection procedure for the best candidates during the screening programme was high purity product with very low residual substrate concentrations, even in the presence of high product concentrations. Additionally the nitrile and amide substrate scavenging ability which enables rhodococci to survive very successfully in the environment leads to the formation of biocatalysts which are suitable for the removal of low concentrations of acrylonitrile and acrylamide in waste streams and for the removal of impurities in manufacturing processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1001716332272
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  • 22
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    Two-liquid-phase bioreactors for enhanced degradation of hydrophobic/toxic compounds (1999)
    Springer
    Biodegradation 10 (1999), S. 219-233 
    Details
    ISSN: 1572-9729
    Keywords: bioavailability ; biodegradation ; bioreactor ; biotreatment ; NAPL ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Two-liquid-phase culture systems involve the addition of a water-immiscible, biocompatible and non-biodegradable solvent to enhance a biocatalytic process. Two-liquid-phase bioreactors have been used since the mid-seventies for the microbial and enzymatic bioconversion of hydrophobic/toxic substrates into products of commercial interest. The increasing popularity of bioremediation technologies suggests a new area of application for this type of bioreactor. The toxicity and the limited bioavailability of many pollutants are important obstacles that must first be overcome in order to improve biodegradation processes. Two-liquid-phase bioreactors have the potential to resolve both limitations of biotreatment technologies by the enhancement of the mass-transfer rate of compounds with low bioavailability, and by the controlled delivery of apolar toxic compounds. This technology can also be useful in accelerating the enrichment of microorganisms degrading problematic pollutants. In this paper, we discuss the application of two-liquid-phase bioreactors to enhance the biodegradation of toxic/poorly bioavailable contaminants. Important microbial mechanisms involved in this type of system are described. Uptake of the substrates can be achieved by microorganisms freely dispersed in the aqueous phase and/or bound at the interface between the aqueous and the immiscible phases. Production of surface-active compounds and adhesion abilities are microbial features involved in the process. General guidelines for the design of two-liquid-phase bioreactors for biodegradation purposes are presented. Solvent selection should be established on specific criteria, which depend on the characteristics of target compound(s) and the microorganism(s) implicated in the biodegradation process. The central importance of maximizing the interfacial surface area is highlighted. The potential of this approach as an alternative to current biotreatment technologies is also discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008311430525
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    Enhancement of somatic embryogenesis of Ipomoea batatas in solid eultures and production of mature somatic embryos in liquid cultures for application to a bioreactor production system (1995)
    Springer
    Plant cell, tissue and organ culture 41 (1995), S. 1-8 
    Details
    ISSN: 1573-5044
    Keywords: atmosphere ; bioreactor ; Ipomoca batatas ; somatic embryogenesis ; suspension culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Somatic embryos of Ipomoea batatas Lam. (sweet potato cv. ‘White Star’) were produced in an airlift bioreactor. This work describes the optimization of the embryogenic system on semisolid medium, followed by transfer of the system to liquid cultures and ultimately to the airlift bioreactor. The physiological age of embryogenic callus influenced the number and overall morphology of the embryo population in both semisolid and liquid medium. Maximum mature embryo production (35 embryos 10 mg-1 inoculum) was obtained from six-week-old callus at 30°C. Somatic embryogenesis occurred in liquid cultures containing 20 mM NH4NO3 and 30 mM KCl. Globular embryos formed and continued development in suspension producing viable, mature cotyledonary embryos by day 14. Embryo formation and development was limited in the bioreactor. Although shear stress was responsible for some embryogenic damage, the effect of purging the system with fresh air needed to be investigated. To isolate aeration effects from shear stress effects, atmospheric determinations were performed on shaker flask cultures. Initially the gas composition within the Erlenmeyer headspace was that of room air. Ethylene increased to a maximum of 6.4 ppm (day 16), maximum CO2, 21.2%, was also evident on day 16, and oxygen was depleted to a minimum of 8.1% by day 14. Purging the cultures with fresh air reduced the number of embryos formed; however, they were significantly longer than those formed in closed flasks. The gas response model of Ipomoea batatas will enable atmosphere replenishment in the bioreactor mimicking that of the shaker flask environment. Once the damaging effects of shear stress have been overcome, the regulation of bioreactor gasses should allow somatic embryo formation in the bioreactor comparable to that in shaker flasks.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00124080
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    In vitro multiplication in liquid culture of Syngonium contaminated with Bacillus spp. and Rathayibacter tritici (1996)
    Springer
    Plant cell, tissue and organ culture 45 (1996), S. 277-280 
    Details
    ISSN: 1573-5044
    Keywords: bioreactor ; contamination ; medium filtration ; micropropagation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Contaminated Syngonium clusters were multiplied in an air lift bioreactor in liquid medium containing sucrose with the medium being circulated through a sterilizing filter. After 30 days, the culture in filtered medium produced 19.5 shoot initials per gram fresh weight of inoculum compared to 8.7 shoot initials produced in unfiltered medium. Transfer to an elongation medium with 30 mg l-1 Rifampicin produced shoots on 67% of the clusters, while transfer to elongation medium without Rifampicin poduced shoots on 40% of the clusters. Clusters grown for three subcultures in a reactor without medium filtration had lost their multiplication ability. Clusters grown for three subcultures in a reactor with filtration, however, continued to show a two-three fold increase in fresh weight and shoot production.
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    URL: http://dx.doi.org/10.1007/BF00043643
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    A plant cell bioreactor with medium-perfusion for control of somatic embryogenesis in liquid cell suspensions (1996)
    Springer
    Plant growth regulation 20 (1996), S. 53-56 
    Details
    ISSN: 1573-5087
    Keywords: medium exchange ; plant cell suspension culture ; bioreactor ; somatic embryogenesis ; Picea sitchensis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The Braun Biostat BF2 bioreactor system employs a novel aeration and agitation system, designed to enhance gaseous exchange and reduce shear stresses on submerged cell suspension cultures. The Biostat BF2 bioreactor employs a central pivoting spindle, around which the aeration tubing is wound forming a large paddle-type structure suspended from the top-plate and swung in a circle by a solid-state magnetic stirrer. The aeration tubing is a polypropylene capillary membrane, which has a unique microporous structure and is ideal for aeration, permitting two-way, bubble-free, gaseous exchange of the medium. This tubing can be rendered porous and can be used in the perfusion of aqueous solutions, enabling cell-free media exchange to be conducted. Thin-walled silicone rubber tubing, although gas permeable to a degree, cannot be made porous to aqueous solutions. The bioreactor was inoculated with a suspension culture of Sitka spruce (Picea sitchensis [Bong.] Carr.) known to be embryogenic and capable of maturing to plantlets on solidified medium. The perfusion capability of the bioreactor was employed to replace the inital proliferation medium with maturation medium in order to induce the development of the somatic embryos in submerged cell culture. The size ratio of the somatic embryo heads was monitored over 7 weeks. This cell line was found to mirror just the initial elongation, previously observed in shake-flask culture.
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    URL: http://dx.doi.org/10.1007/BF00024058
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    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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    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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    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008022828736
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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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008025016272
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    Stable Production of Human Insulin-like Growth Factor 1 (IGF-1) in the Milk of Hemi- and Homozygous Transgenic Rabbits Over Several Generations (1998)
    Springer
    Transgenic research 7 (1998), S. 437-447 
    Details
    ISSN: 1573-9368
    Keywords: bioreactor ; gene farming ; genetic engineering ; mammary gland ; milk composition ; recombinant protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract One transgenic rabbit line was generated carrying a fusion gene consisting of the cDNA for human IGF-1 fused to a mammary gland specific expression cassette derived from bovine alpha-S1-casein sequences. Transgene expression was shown to be strictly tissue and lactation period specific. The transgenic rabbit line was bred for six generations. All transgenic animals showed stable production of biologically active IGF-1 over the generations and no apparent effect on the physiological or reproductive performance was observed. The absence of adverse effects on homozygous transgenic rabbits suggested the absence of insertional mutagenesis. Eight hemizygous transgenic offspring analysed produced on average 363 ± 12μg/ml (ranging from 223 ± 61 to 484 ± 39 μg/ml) mature human IGF-1 in their milk, whereas three homozygous animals produced on average 543 ± 41 μg/ml (ranging from 360 ± 15 to 678 ± 80 μg/ml). Homozygous huIGF-1 females clearly showed a significantly increased production performance of the recombinant protein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008831028620
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