Scale-up of virus-like particles production: effects of sparging, agitation and bioreactor scale on cell growth, infection kinetics and productivity

Maranga, Luís; Cunha, António E.; Clemente, João J.; Cruz, Pedro; Carrondo, Manuel J.T.

doi:10.1016/j.jbiotec.2003.09.012

Cited by 59 publications

(38 citation statements)

References 34 publications

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“…A successful scaling-up of suspension cultures of insect cells will be always the result of a compromise between the satisfaction of an adequate mixing and the preservation of the structural and functional cellular integrity. Stirred tank reactors, where agitation is performed mechanically through impellers, have demonstrated to be useful to cultivate insect cells at large scale (Maranga et al, 2004). The agitation rate should be carefully controlled in stirred reactors, especially when cultures are aerated by sparging, due to deleterious effects on cell functionality and viability that occurs when cultures are stirred at speeds over 300 rpm with Rushton turbines (Cruz et al, 1998).…”

Section: Bioreactors In Insect Cell Culturesmentioning

confidence: 99%

Production of Insecticidal Baculoviruses in Insect Cell Cultures: Potential and Limitations

Claus¹,

Gioria²,

Micheloud³

et al. 2012

Insecticides - Basic and Other Applications

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Section: Bioreactors In Insect Cell Culturesmentioning

confidence: 99%

Production of Insecticidal Baculoviruses in Insect Cell Cultures: Potential and Limitations

Claus¹,

Gioria²,

Micheloud³

et al. 2012

Insecticides - Basic and Other Applications

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“…The baculovirus-insect cell system is considered as a powerful biotechnological tool to produce various valuable biotechnological products (Maranga et al 2004;Van Lier et al 1996;Cruz et al 1998;Negrete and Kotin 2007;Szewczyk et al 2006). However, considering that the technology for the in vitro protein expression is well-established (Agathos 1996), the in vitro production of baculovirus is an attractive cost-effective alternative (Enden et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Adaptation of the Se301 insect cell line to suspension culture. Effect of turbulence on growth and on production of nucleopolyhedrovius (SeMNPV)

et al. 2011

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As chemical pesticides are being banned as control agents for agricultural pests, the use of the highly specific, safe to non-target organisms baculoviruses has been proposed. These viruses can be produced either in vivo or in vitro. In vitro production requires appropriated host insect cell lines with the ability for growing as freely-suspended cells. In this work, the Spodoptera exigua Se301 cell line was used to produce the commercially available S. exigua nucleopolyhedrovirus (SeMNPV) in suspension. Se301 cells showed to be very sensitive to the hydrodynamic shear rates developed in bioreactors. A process of progressive adaptation to freely-suspended cultures using protective additives against shear stress and disaggregant was proposed. The best combinations were polyvinyl alcohol (PVA) or polyvinyl pyrrolidone (PVP) with the disaggregant dextran sulfate (DS). Both static and freely-suspended Se301 cell cultures were successfully infected with the SeMNPV baculovirus. Production of occluded baculovirus (OB) increased with the multiplicity of infection (MOI [ 0.1).

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“…The second method is based on the estimation of the maximal shear stress generated in the medium. The operating conditions are defined to remain the maximal shear stress in the medium below the limited shear stress tolerated by the cells (Maranga et al 2004). This method does not take into account the exposition time of the cell to the flow and the induced shear stresses.…”

Section: Introductionmentioning

confidence: 99%

Computational Fluid Dynamics Characterization of a Bioreactor Mixing Device for the Animal Cell Culture

Gelbgras¹,

Wylock²,

Drugmand³

et al. 2011

Chemical Product and Process Modeling

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During a cell culture in a bioreactor, the cells are exposed to the shear stresses mainly generated in the culture medium by the mixing device. Beyond a critical shear stress, this exposition induces cell damages. Therefore, the limitation of the shear stress is an important criterion for the design of bioreactors. An accurate modeling of the flow and the induced shear stresses in the medium is a tool to achieve an effective design of a bioreactor. In this work, a new design of a mixing device is considered. The aims of this work are to develop a methodology to study the flow and the induced shear stresses in the device, to study and to model the relation between the flow, the induced shear stresses and the cell viability, to use the developed model as an optimization tool, and to study the design of the bioreactor mixing device and its scale-up. In a first step, the flow and the induced shear stresses in the device are simulated by Computational Fluid Dynamics. In a second step, the model of the influence of the flow and the induced shear stresses on the cell viability is established by a comparison between the computed flow and the induced shear stresses and experimental measurements of cellular viabilities for different impeller rotation speeds. Finally, the influence of another design of the mixing device on the cell viability is studied.KEYWORDS: flow and shear stress acting on the cells, cell viability, computational fluid dynamics

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Scale-up of virus-like particles production: effects of sparging, agitation and bioreactor scale on cell growth, infection kinetics and productivity

Cited by 59 publications

References 34 publications

Production of Insecticidal Baculoviruses in Insect Cell Cultures: Potential and Limitations

Production of Insecticidal Baculoviruses in Insect Cell Cultures: Potential and Limitations

Adaptation of the Se301 insect cell line to suspension culture. Effect of turbulence on growth and on production of nucleopolyhedrovius (SeMNPV)

Computational Fluid Dynamics Characterization of a Bioreactor Mixing Device for the Animal Cell Culture

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