Scale‐up of bioreactors for fermentation of mammalian cell cultures with special reference to oxygen supply and microcarrier mixing

Vorlop, Jürgen; Lehmann, Jürgen

doi:10.1002/ceat.270110123

Cited by 14 publications

(6 citation statements)

References 1 publication

(1 reference statement)

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“…Furthermore, adequate sorption of oxygen and desorption of carbon dioxide in the cultivation medium for the respiration of the cells is important given the low solubility of oxygen and the aim to decrease shear stress. Oxygenation of cells and the corresponding design of cell culture bioreactors has been a major topic of interest since the inception of cell culture technology (Aunins and Henzler 1993;Henzler and Kauling 1993;Fenge and Lüllau 2006;Aunins et al 1986; Vorlop and Lehmann 1988;Engasser 1988). Overviews are given in Aunins and Henzler (1993), Henzler and Kauling (1993) and Fenge and Lüllau (2006).…”

Section: Introductionmentioning

confidence: 97%

Improving bioreactor cultivation conditions for sensitive cell lines by dynamic membrane aeration

2009

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Although the importance of animal cell culture for the industrial (large scale) production of pharmaceutical products is continuously increasing, the sensibility of the cells towards their cultivation environment is still a challenging issue. In comparison to microbial cultures, cell cultures which are not protected by a cell wall are much more sensitive to shear stress and foam formation. Reactor design as well as the selection of 'robust' cell lines is particularly important for these circumstances. Nevertheless, even 'sensitive' cell lines are selected for certain pharmaceutical processes due to various reasons. These sensitive cell lines have even higher requirements regarding their cultivation environment. Important characteristics for the corresponding reactor design are a high (volumetric) gas mass transfer coefficient, low volumetric power input, low shear stress, low susceptibility to bio-fouling, the ability to cultivate sticky cells and sufficient mixing properties. Membrane aeration has been a long-known possibility to meet some of these requirements, but has not often been applied in recent years. The reasons lie mainly in low gas mass transfer rates, a limited installable volume-specific membrane surface area, restrictions in scalability and problems with membrane fouling. The dynamic membrane aeration bioreactor aeration is a simple concept for bubble-free oxygen supply of such sensitive cultures. It overcomes limitations and draw-backs of previous systems. Consisting of an oscillating, centrally arranged rotor (stirrer) that is wrapped with silicone membrane tubing, it enables doubling the gas mass transfer at the same shear stress in the investigated cultivation scales of 12, 20, 100, and 200 L. Continuous cultivation at these scales allows the same product output as fed-batch cultivation does at tremendously larger reactor volumes. Apart from introducing this novel technology, the presentation comprises selected cultivation results obtained for blood coagulation factor VIII in continuous mode and a therapeutic monoclonal antibody in fed-batch mode in comparison to reference trials.

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Section: Introductionmentioning

confidence: 97%

Improving bioreactor cultivation conditions for sensitive cell lines by dynamic membrane aeration

2009

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“…For microcarrier based processes, the use of mixing and suspension criteria as scale-up factors have been proposed for animal (Vorlop and Lehmann 1988;Thomassen et al 2012) and human (Duvar et al 1996;Hewitt et al 2011;Kaiser et al 2013) cells. The microcarriers have to be kept in suspension, at least for most of the batch time, if the available area is to be used effectively.…”

Section: Scale-up Of Processes Based On Su Bioreactorsmentioning

confidence: 99%

Single-Use Bioreactors for Animal and Human Cells

et al. 2014

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Single-use (SU) bioreactors are being increasingly used in production processes based on animal (i.e. mammalian and insect) and human cells. They are particularly suitable for the production of high-value products on small and medium scales, and in cases where fast and safe production is a requirement. Thus, it is not surprising that SU bioreactors have established themselves for screening studies, cell expansions, and product expressions where they are used for the production of pre-clinical and clinical samples of therapeutic antibodies and preventive vaccines. Furthermore, recent publications have revealed the potential of SU bioreactors for the production of cell therapeutics using human mesenchymal stem cells (hMSCs).This chapter provides a perspective on current developments in SU bioreactors and their main applications. After briefly introducing the reader to the basics of SU bioreactor technology (terminology, historical milestones and characteristics compared to their reusable counterparts) an overview of the categories of currently available SU bioreactor types is provided. SU bioreactor instrumentation is then examined, before discussing well-established and novel applications of SU bioreactors for animal and human cells. This includes descriptions of the engineering characteristics of often-used types of SU bioreactors, covering wave-mixed, stirred, orbitally shaken systems and fixed-bed systems. In this context, the scaling-up of geometrically and non-geometrically similar SU bioreactors is also addressed.

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“…11) was described by Vorlop and Lehmann in 1988 [99]. They use porous hollow-fiber Accurel polypropylene membranes for supplying O 2 to mammalian cultures coiled in the form of a basket or fixed to carriers.…”

Section: Membrane-aerated Bioreactorsmentioning

confidence: 99%

“…11 Diessel reactor with porous Accurel PP hollow-fiber membranes coiled and fixed on carriers [99]. In the production reactors with 20 and 150 l membrane coils were driven eccentrically (for 1 L scale a pendulous motion was applied) and to have homogeneous mixing of microcarriers a spiral agitator was fixed below the membrane carriers the resistance of the boundary layer adjacent to the membrane.…”

Section: Membrane-aerated Bioreactorsmentioning

confidence: 99%

Photobioreactors in Life Support Systems

Wagner

Braun

Slenzka³

et al. 2015

Microalgae Biotechnology

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Life support systems for long-term space missions or extraterrestrial installations have to fulfill major functions such as purification of water and regeneration of atmosphere as well as the generation of food and energy. For almost 60 years ideas for biological life support systems have been collected and various concepts have been developed and tested. Microalgae as photosynthetic organisms have played a major role in most of these concepts. This review deals with the potentials of using eukaryotic microalgae for life support systems and highlights special requirements and frame conditions for designing space photobioreactors especially regarding illumination and aeration. Mono- and dichromatic illumination based on LEDs is a promising alternative for conventional systems and preliminary results yielded higher photoconversion efficiencies (PCE) for dichromatic red/blue illumination than white illumination. Aeration for microgravity conditions should be realized in a bubble-free manner, for example, via membranes. Finally, a novel photobioreactor concept for space application is introduced being parameterized and tested with the microalga Chlamydomonas reinhardtii. This system has already been tested during two parabolic flight campaigns.

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Scale‐up of bioreactors for fermentation of mammalian cell cultures with special reference to oxygen supply and microcarrier mixing

Cited by 14 publications

References 1 publication

Improving bioreactor cultivation conditions for sensitive cell lines by dynamic membrane aeration

Improving bioreactor cultivation conditions for sensitive cell lines by dynamic membrane aeration

Single-Use Bioreactors for Animal and Human Cells

Photobioreactors in Life Support Systems

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