Disposable 600-mL orbitally shaken bioreactor for mammalian cell cultivation in suspension

Monteil, Dominique T.; Tontodonati, Giulia; Ghimire, Saroj; Baldi, Lucia; Hacker, David L.; Bürki, Cédric A.; Wurm, Florian Μ.

doi:10.1016/j.bej.2013.04.008

Cited by 27 publications

(24 citation statements)

References 28 publications

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“…Single‐use cell culture technology is playing an important role in biopharmaceutical manufacturing because of the commercial availability of a wide variety of disposable bioreactors and of the need for greater flexibility in production processes . Disposable orbitally shaken bioreactors (OSRs) with working volumes from small (<2 L) to large scale (<2000 L) have been used to cultivate animal cells in suspension . In contrast to stirred‐tank bioreactors (STRs) that require the sparging of pure oxygen into the liquid phase, it is possible with OSRs to adequately supply oxygen for high‐density animal cell cultures with air only, providing the gas passively or actively into the head space over the liquid phase without a sparger.…”

Section: Introductionmentioning

confidence: 99%

Studies on fluid dynamics of the flow field and gas transfer in orbitally shaken tubes

Zhu

Wang

Monteil

et al. 2016

Biotechnology Progress

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Orbitally shaken cylindrical bioreactors [OrbShake bioreactors (OSRs)] without an impeller or sparger are increasingly being used for the suspension cultivation of mammalian cells. Among small volume OSRs, 50-mL tubes with a ventilated cap (OSR50), originally derived from standard laboratory centrifuge tubes with a conical bottom, have found many applications including high-throughput screening for the optimization of cell cultivation conditions. To better understand the fluid dynamics and gas transfer rates at the liquid surface in OSR50, we established a three-dimensional simulation model of the unsteady liquid forms (waves) in this vessel. The studies verified that the operating conditions have a large effect on the interfacial surface. The volumetric mass transfer coefficient (k a) was determined experimentally and from simulations under various working conditions. We also determined the liquid-phase mass transfer coefficient (k ) and the specific interfacial area (a) under different conditions to demonstrate that the value of a affected the gas transfer rate more than did the value of k . High oxygen transfer rates, sufficient for supporting the high-density culture of mammalian cells, were found. Finally, the average axial velocity of the liquid was identified to be an important parameter for maintaining cells in suspension. Overall these studies provide valuable insights into the preferable operating conditions for the OSR50, such as those needed for cell cultures requiring high oxygen levels. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:192-200, 2017.

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Section: Introductionmentioning

confidence: 99%

Studies on fluid dynamics of the flow field and gas transfer in orbitally shaken tubes

Zhu

Wang

Monteil

et al. 2016

Biotechnology Progress

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“…In addition, TubeSpin 1 bioreactor 50 and 600 tubes, 50-mL and 600-mL centrifugation tubes with a vented cap, have been developed for working volumes of 2-20 mL and 100-500 mL, respectively [17,18]. For cultures of 10-200 L, disposable orbitally shaken bioreactors of 50-L and 200-L have recently been introduced [19,20].…”

Section: Host Cells and Their Cultivation In Suspensionmentioning

confidence: 99%

Recombinant protein production from stable mammalian cell lines and pools

Hacker

Balasubramanian

2016

Current Opinion in Structural Biology

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“…At shaking frequencies suitable for cell culture, all the OSRs mentioned above have mixing times (the time needed to mix to homogeneity) under 20 s [74]. Importantly, efficient mixing can be achieved with a low power input, resulting in less shear stress on cells, by an order of magnitude, than observed in STRs [25,70,[75][76][77].…”

Section: Cell Cultivation Systemmentioning

confidence: 99%

“…Despite these successes, there may be perceptions that TGE is unaffordable for many academic labs and that the cultivation of mammalian cells in suspension is technically difficult. Fortunately, the production yields from transiently transfected mammalian cells have improved considerably in the last decade, and innovative cost-effective, non-instrumented cultivation systems for suspension-adapted mammalian cells have been developed [24][25][26]. These technical improvements have dramatically reduced protein production costs.…”

Section: Introductionmentioning

confidence: 99%

Polyethyleneimine-based transient gene expression processes for suspension-adapted HEK-293E and CHO-DG44 cells

Hacker

Kiseljak

Rajendra

et al. 2013

Protein Expression and Purification

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Transient gene expression (TGE) from mammalian cells is an increasingly important tool for the rapid production of recombinant proteins for research applications in biochemistry, structural biology, and biomedicine. Here we review methods for the transfection of human embryo kidney (HEK-293) and Chinese hamster ovary (CHO) cells in suspension culture using the cationic polymer polyethylenimine (PEI) for gene delivery.

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Disposable 600-mL orbitally shaken bioreactor for mammalian cell cultivation in suspension

Cited by 27 publications

References 28 publications

Studies on fluid dynamics of the flow field and gas transfer in orbitally shaken tubes

Studies on fluid dynamics of the flow field and gas transfer in orbitally shaken tubes

Recombinant protein production from stable mammalian cell lines and pools

Polyethyleneimine-based transient gene expression processes for suspension-adapted HEK-293E and CHO-DG44 cells

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