Hydrodynamic stress in orbitally shaken bioreactors

Tissot, Stéphanie; Reclari, Martino; Quinodoz, Samuel; Dreyer, Matthieu; Monteil, Dominique T.; Baldi, Lucia; Hacker, David L.; Farhat, Mohamed; Discacciati, Marco; Quarteroni, Alfio; Wurm, Florian Μ.

doi:10.1186/1753-6561-5-s8-p39

Cited by 7 publications

(6 citation statements)

References 2 publications

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“…showed that PBS‐VW bioreactor exhibited a greater degree of fluid dynamic homogeneity and that the turbulent kinetics energy (TKE) generated at higher wheel speeds is lower when compared with Mobius™ CellReady 3 L ST bioreactor and wave motion Cultibag RM bioreactor from Sartorius . Vertical‐Wheel bioreactors, together with orbital shaken technology bioreactors, are described as low shear stress bioreactors even under maximum agitation capacities …”

Section: Resultsmentioning

confidence: 99%

“…37 Vertical-Wheel bioreactors, together with orbital shaken technology bioreactors, are described as low shear stress bioreactors even under maximum agitation capacities. 32,38 In order to evaluate the suitability of PBS-VW bioreactors for microcarrier applications, key hydrodynamic parameters were estimated, namely (i) specific power input (SPI), (ii) mixing time (t m ), (iii) KLS, and (iv) shear stress, and compared with the values determined for ST bioreactors (Table 3).…”

Section: Bioreactors Configuration Hydrodynamics Parameters and Opementioning

confidence: 99%

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Production of oncolytic adenovirus and human mesenchymal stem cells in a single‐use, Vertical‐Wheel bioreactor system: Impact of bioreactor design on performance of microcarrier‐based cell culture processes

Sousa

Silva

Giroux

et al. 2015

Biotechnology Progress

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Anchorage-dependent cell cultures are used for the production of viruses, viral vectors, and vaccines, as well as for various cell therapies and tissue engineering applications. Most of these applications currently rely on planar technologies for the generation of biological products. However, as new cell therapy product candidates move from clinical trials towards potential commercialization, planar platforms have proven to be inadequate to meet large-scale manufacturing demand. Therefore, a new scalable platform for culturing anchorage-dependent cells at high cell volumetric concentrations is urgently needed. One promising solution is to grow cells on microcarriers suspended in single-use bioreactors. Toward this goal, a novel bioreactor system utilizing an innovative Vertical-Wheel™ technology was evaluated for its potential to support scalable cell culture process development. Two anchorage-dependent human cell types were used: human lung carcinoma cells (A549 cell line) and human bone marrow-derived mesenchymal stem cells (hMSC). Key hydrodynamic parameters such as power input, mixing time, Kolmogorov length scale, and shear stress were estimated. The performance of Vertical-Wheel bioreactors (PBS-VW) was then evaluated for A549 cell growth and oncolytic adenovirus type 5 production as well as for hMSC expansion. Regarding the first cell model, higher cell growth and number of infectious viruses per cell were achieved when compared with stirred tank (ST) bioreactors. For the hMSC model, although higher percentages of proliferative cells could be reached in the PBS-VW compared with ST bioreactors, no significant differences in the cell volumetric concentration and expansion factor were observed. Noteworthy, the hMSC population generated in the PBS-VW showed a significantly lower percentage of apoptotic cells as well as reduced levels of HLA-DR positive cells. Overall, these results showed that process transfer from ST bioreactor to PBS-VW, and scale-up was successfully carried out for two different microcarrier-based cell cultures. Ultimately, the data herein generated demonstrate the potential of Vertical-Wheel bioreactors as a new scalable biomanufacturing platform for microcarrier-based cell cultures of complex biopharmaceuticals.

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Section: Resultsmentioning

confidence: 99%

Section: Bioreactors Configuration Hydrodynamics Parameters and Opementioning

confidence: 99%

Production of oncolytic adenovirus and human mesenchymal stem cells in a single‐use, Vertical‐Wheel bioreactor system: Impact of bioreactor design on performance of microcarrier‐based cell culture processes

Sousa

Silva

Giroux

et al. 2015

Biotechnology Progress

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“…Many investigations using CFD have been done with stirred bioreactors [ 15 , 18 – 20 ] and orbitally shaken bioreactors [ 16 , 17 , 21 – 25 ]. However, to get measured data to validate the CFD simulation proves to be a big challenge.…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional (3D) evaluation of liquid distribution in shake flask using an optical fluorescence technique

Azizan

Büchs

2017

J Biol Eng

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Background: Biotechnological development in shake flask necessitates vital engineering parameters e.g. volumetric power input, mixing time, gas liquid mass transfer coefficient, hydromechanical stress and effective shear rate. Determination and optimization of these parameters through experiments are labor-intensive and time-consuming. Computational Fluid Dynamics (CFD) provides the ability to predict and validate these parameters in bioprocess engineering. This work provides ample experimental data which are easily accessible for future validations to represent the hydrodynamics of the fluid flow in the shake flask. Results: A non-invasive measuring technique using an optical fluorescence method was developed for shake flasks containing a fluorescent solution with a waterlike viscosity at varying filling volume (V L = 15 to 40 mL) and shaking frequency (n = 150 to 450 rpm) at a constant shaking diameter (d o = 25 mm). The method detected the leading edge (LB) and tail of the rotating bulk liquid (TB) relative to the direction of the centrifugal acceleration at varying circumferential heights from the base of the shake flask. The determined LB and TB points were translated into three-dimensional (3D) circumferential liquid distribution plots. The maximum liquid height (H max ) of the bulk liquid increased with increasing filling volume and shaking frequency of the shaking flask, as expected. The toroidal shapes of LB and TB are clearly asymmetrical and the measured TB differed by the elongation of the liquid particularly towards the torus part of the shake flask.

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“…Furthermore, advanced parameters concerning shear stress and turbulent energy were predicted in single wells of microtiter plates (Zhang et al 2008a), in TubeSpin® bioreactors , shake flasks (Zhang et al 2005), and shaken bottles (Tissot et al 2011b). …”

Section: Orbitally Shaken 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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Hydrodynamic stress in orbitally shaken bioreactors

Cited by 7 publications

References 2 publications

Production of oncolytic adenovirus and human mesenchymal stem cells in a single‐use, Vertical‐Wheel bioreactor system: Impact of bioreactor design on performance of microcarrier‐based cell culture processes

Production of oncolytic adenovirus and human mesenchymal stem cells in a single‐use, Vertical‐Wheel bioreactor system: Impact of bioreactor design on performance of microcarrier‐based cell culture processes

Three-dimensional (3D) evaluation of liquid distribution in shake flask using an optical fluorescence technique

Single-Use Bioreactors for Animal and Human Cells

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