Oxygen Transfer in Stirred Bioreactors Under Animal Cell Culture Conditions

Langheinrich, Ch.; Nienow, Alvin W.; Eddleston, T.; Stevenson, N.C.; Emery, A. N.; Clayton, Tim; Slater, Nigel K.H.

doi:10.1205/096030802753479098

Cited by 21 publications

(12 citation statements)

References 12 publications

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“…These values cover results from 8 m 3 (Langheinrich et al 2002) to 20 m 3 (Hoeks et al 2004) and the latter study showed the applicability of Eq. (7) across the scales in 12 L, 500 L and 20,000 L bioreactors using animal cell culture media.…”

Section: Mass Transfer Performance and Oxygen Demandsupporting

confidence: 84%

“…ð" e T Þ g and v s must together (Langheinrich et al 2002) be sufficient to produce the necessary k L a where…”

Section: Mass Transfer Performance and Oxygen Demandmentioning

confidence: 99%

“…(7) across the scales in 12 L, 500 L and 20,000 L bioreactors using animal cell culture media. Typical k L a values Langheinrich et al 2002;Hoeks et al 2004;Meier 2005) in animal cell culture media are in the range 1-15 h )1 .…”

Section: Mass Transfer Performance and Oxygen Demandmentioning

confidence: 99%

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Reactor Engineering in Large Scale Animal Cell Culture

2006

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This article mainly addresses the issues associated with the engineering of large-scale free suspension culture in agitated bioreactors >10,000 L because they have become the system of choice industrially. It is particularly concerned with problems that become increasingly important as the scale increases. However, very few papers have been written that are actually based on such large-scale studies and the few that do rarely address any of the issues quantitatively. Hence, it is necessary very often to extrapolate from small-scale work and this review tries to pull the two types of study together. It is shown that 'shear sensitivity' due to agitation and bursting bubbles is no longer considered a major problem. Homogeneity becomes increasingly important with respect to pH and nutrients at the largest scale and sub-surface feeding is recommended despite 'cleaning in place' concerns. There are still major questions with cell retention/recycle systems at these scales, either because of fouling, of capacity or of potential and different 'shear sensitivity' questions. Fed-batch operation gives rise to cell densities that have led to the use of oxygen and enriched air to meet oxygen demands. This strategy, in turn, gives rise to a CO 2 evolution rate that impacts on pH control, pCO 2 and osmolality. These interactions are difficult to resolve but if higher sparge and agitation intensities could be used to achieve the necessary oxygen transfer, the problem would largely disappear. Thus, the perception of 'shear sensitivity' is still impacting on the development of animal cell culture at the commercial scale. Microcarrier culture is also briefly addressed. Finally, some recommendations for bioreactor configuration and operating strategy are given.

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Section: Mass Transfer Performance and Oxygen Demandsupporting

confidence: 84%

“…ð" e T Þ g and v s must together (Langheinrich et al 2002) be sufficient to produce the necessary k L a where…”

Section: Mass Transfer Performance and Oxygen Demandmentioning

confidence: 99%

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Reactor Engineering in Large Scale Animal Cell Culture

2006

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“…This is due to the fragile nature of animal cells, which can be damaged under conditions of high turbulence [26,27]. Hence, in mammalian cell culture the objectives of maximizing oxygen transfer rates must be balanced with the maintenance of the integrity of the cell membrane [28,29].…”

Section: Discussionmentioning

confidence: 99%

Production of Adenoviral Vectors in 293 Cells: A Case Study of the Adaptation of Attached Cells to Grow in Suspension

Negrete¹,

Ling²,

Lyddiatt³

2008

TOBIOTJ

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A study of the production of adenoviral vectors in suspension 293 cells has been explored. A defined serumfree medium (293 SFM II) formulated without human or animal origin components from Invitrogen was used for the suspension adapted 293 cells. It was demonstrated that the 293 cells can be adapted to grow in suspension using serum free medium. The effect of different cell culture parameters was determined. The production technique demonstrated here is expected to simplify purification processes and circumvents the problems associated with serum containing medium.

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“…This could, however, be justified if influences of a fluctuating temperature or prevalence of contaminants in the ambient air are critical. In particular, if the purpose with the design is to apply principles of QbD and PAT [21,[36][37][38] or advanced process control [34] these parts need to be detailed at a significantly higher resolution in the design.…”

Section: Figurementioning

confidence: 99%

Scale‐up of cell culture bioreactors using biomechatronic design

Mandenius

Björkman

2012

Biotechnology Journal

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An alternative approach for scale-up of cell culture bioreactors based on biomechatronic design methodology is suggested.The approach differs from traditional biochemical engineering methodology by applying a sequential design procedure where the needs of the users and alternative design solutions based on the biological and technical functions of the scaled-up bioreactor are derived in functional maps, concept generation charts and scoring and interaction matrices. Basic reactor engineering properties, such mass and heat transfer and kinetics are integrated in the procedure. Examples are provided from production of monoclonal antibody and recombinant protein.

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Oxygen Transfer in Stirred Bioreactors Under Animal Cell Culture Conditions

Cited by 21 publications

References 12 publications

Reactor Engineering in Large Scale Animal Cell Culture

Reactor Engineering in Large Scale Animal Cell Culture

Production of Adenoviral Vectors in 293 Cells: A Case Study of the Adaptation of Attached Cells to Grow in Suspension

Scale‐up of cell culture bioreactors using biomechatronic design

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