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Large-Eddy Simulations of microcarrier exposure to potentially damaging eddies inside mini-bioreactors Collignon, Marie-Laure ; ; Calvo, Sébastien et al in Biochemical Engineering Journal (in press) Mechanically stirred vessels equipped with rotating impellers generate heterogeneous transitional or turbulent flows. However, some cells as animal or human mesenchymal stem cells (hMSC) adhered on ... [more ▼] Mechanically stirred vessels equipped with rotating impellers generate heterogeneous transitional or turbulent flows. However, some cells as animal or human mesenchymal stem cells (hMSC) adhered on microcarriers, are reputed sensitive to hydromechanical stresses arising from stirring. Many publications, especially using Computational Fluid Dynamics, characterize spatial fields of velocity and turbulence inside bioreactors but the exposure frequency to these stresses is never taken into account in the case of animal cell culture bioreactor description. To fill this gap, this study used both CFD Reynolds-Averaged and Large-Eddy Simulations to characterize the hydrodynamics inside 250 mL mini-bioreactors, which is a relevant volume for hMSC cultures. Five impeller geometries were studied. From the velocity and turbulence fields calculated, an energy dissipation/circulation function, related to both frequency and intensity of potentially damaging hydrodynamic events for the cells, was determined for various operating conditions. Based on the simulation results, the marine propeller operating in up-pumping mode seems to be the most adapted condition, since it exhibits a low frequency of exposure to an acceptable intensity of the turbulent dissipation rate. From a general point of view, the new methodology proposed should be used in the future to screen the most adapted bioreactor geometry to biological constraints. [less ▲] Detailed reference viewed: 36 (10 ULg)NUMERICAL AND EXPERIMENTAL CHARACTERIZATION OF SOLID-LIQUID HYDRODYNAMICS ENCOUNTERED IN HUMAN MESENCHYMAL STEM CELL CULTURE BIOREACTORS. Delafosse, Angélique ; Collignon, Marie-Laure ; et al Conference (2015, September 30) Detailed reference viewed: 7 (0 ULg)Euler–Lagrange approach to model heterogeneities in stirred tank bioreactors – Comparison to experimental flow characterization and particle tracking Delafosse, Angélique ; Calvo, Sébastien ; Collignon, Marie-Laure et al in Chemical Engineering Science (2015), 134 The aim of this work is the validation of an Euler–Lagrange modeling approach coupling a CFD-based compartment model (Eulerian approach) and a stochastic model based on a Continuous-Time Markov Chain ... [more ▼] The aim of this work is the validation of an Euler–Lagrange modeling approach coupling a CFD-based compartment model (Eulerian approach) and a stochastic model based on a Continuous-Time Markov Chain (Lagrangian approach). The turbulent flow structure and the mixing process in a bioreactor stirred by an axial Mixel TT impeller is characterized by PIV and tracer experiments. Comparison between experimental and numerical data shows that the CFD-based compartment model is able to reproduce accurately the spatial heterogeneities inside the bioreactor. The trajectory of a small tracer particle which perfectly follows the fluid flow is measured by optical trajectography. It is then simulated by a stochastic model which is either based on an homogeneous or on an inhomogeneous Continuous Time Markov Chain (CTMC). Comparison of residence and circulation time distributions in three zones defined inside the bioreactor shows that the inhomogeneous CTMC model predicts with an excellent accuracy the particle trajectories inside the bioreactor. The modeling approach proposed here could be an useful tool to design scale-down bioreactors in order to reproduce at lab-scale the stress levels encountered in large-scale production bioreactors and to characterize and compare different bioreactor configurations. [less ▲] Detailed reference viewed: 25 (3 ULg)Euler–Lagrange approach to model heterogeneities in stirred tank bioreactors – Comparison to experimental flow characterization and particle tracking Delafosse, Angélique ; Calvo, Sébastien ; Collignon, Marie-Laure et al in Chemical Engineering Science (2015), 134 The aim of this work is the validation of an Euler–Lagrange modeling approach coupling a CFD-based compartment model (Eulerian approach) and a stochastic model based on a Continuous-Time Markov Chain ... [more ▼] The aim of this work is the validation of an Euler–Lagrange modeling approach coupling a CFD-based compartment model (Eulerian approach) and a stochastic model based on a Continuous-Time Markov Chain (Lagrangian approach). The turbulent flow structure and the mixing process in a bioreactor stirred by an axial Mixel TT impeller is characterized by PIV and tracer experiments. Comparison between experimental and numerical data shows that the CFD-based compartment model is able to reproduce accurately the spatial heterogeneities inside the bioreactor. The trajectory of a small tracer particle which perfectly follows the fluid flow is measured by optical trajectography. It is then simulated by a stochastic model which is either based on an homogeneous or on an inhomogeneous Continuous Time Markov Chain (CTMC). Comparison of residence and circulation time distributions in three zones defined inside the bioreactor shows that the inhomogeneous CTMC model predicts with an excellent accuracy the particle trajectories inside the bioreactor. The modeling approach proposed here could be an useful tool to design scale-down bioreactors in order to reproduce at lab-scale the stress levels encountered in large-scale production bioreactors and to characterize and compare different bioreactor configurations. [less ▲] Detailed reference viewed: 5 (0 ULg)Surface aeration in baffled stirred tanks: hydrodynamics, mixing and mass transfer characteristics de Lamotte, Anne ; Delafosse, Angélique ; Calvo, Sébastien et al Poster (2015, September) Biotechnological and chemical processes often need a supply of gas for acceptable product formation. In some applications - where either gas requirements/reactor volumes are relatively low, or bubbles are ... [more ▼] Biotechnological and chemical processes often need a supply of gas for acceptable product formation. In some applications - where either gas requirements/reactor volumes are relatively low, or bubbles are undesirable - aeration through the liquid free-surface is enough to meet the demand. In case of sparged stirred tanks, aeration through the liquid free-surface is a factor to be determined when scaling-up /down processes. Gas-liquid transfer is strongly influenced by the hydrodynamic conditions. Two phenomena, occurring at different scales, can be coupled in order to explain mass transfer : (i) circulation (macroscale) and (ii) mixing/homogenization (microscale). Mixing/homogenization takes into consideration the small eddies responsible for the rippled liquid free-surface and for the concentration gradients surrounding it. Circulation determines the fluid path across the reactor as well as its contribution of the surface aeration and leads to periodic and local deformation of the liquid free-surface. Circulation also accounts for the design of the reactor, where the scaling problems are focused. The objective of this work is to develop an experimental approach able to fully (global and local quantities) characterize a chosen agitation configuration in terms of hydrodynamics, mixing and transfer, in order to assess the capability of computational methods to predict gas-liquid mass transfer due to aeration through the liquid free-surface. [less ▲] Detailed reference viewed: 44 (12 ULg)VALIDATION OF AN EULER-LAGRANGE COMPARTMENT MODEL FOR THE DESIGN OF SCALE-DOWN BIOREACTOR USED IN ANIMAL CELL CULTURES Delafosse, Angélique ; Calvo, Sébastien ; Collignon, Marie-Laure et al in Proceeding of the 15th European Conference on Mixing (2015, June) Detailed reference viewed: 5 (1 ULg)REVISITING THE DETERMINATION OF HYDROMECHANICAL STRESSES ENCOUNTERED BY MICROCARRIERS IN STEM CELL CULTURE BIOREACTORS. Delafosse, Angélique ; Collignon, Marie-Laure ; et al in BMC Proceedings 2015 (2015, June) Detailed reference viewed: 36 (8 ULg)Hydrodynamics, mixing and mass transfer in baffled stirred tanks de Lamotte, Anne ; Delafosse, Angélique ; Calvo, Sébastien et al Conference (2015, June) The present work presents CFD simulations of hydrodynamics, mixing and mass transfer in a surface-aerated baffled stirred tank. The modelling of the multiphase flow is realized via an Euler-Euler approach ... [more ▼] The present work presents CFD simulations of hydrodynamics, mixing and mass transfer in a surface-aerated baffled stirred tank. The modelling of the multiphase flow is realized via an Euler-Euler approach. Three closure models are tested for the resolution of the RANS equations. When fully-developed flow field is reached, gas-liquid transfer is implemented with a local mass transfer coefficient estimated by the eddy cell model, and the temporal evolution of dissolved gas concentration is predicted.Hydrodynamic and mixing quantities as well as mass transfer parameters for the different turbulence models are compared with experimental data available for the same geometrical and operating features. A critical analysis of the prediction results allow to assess the models capabilities and to highlight the possible critical issues of the simulations. [less ▲] Detailed reference viewed: 77 (20 ULg)CFD Large Eddy Simulation of the hydrodynamics of stirred mini-bioreactors operating with stem cell culture mixing conditions Collignon, Marie-Laure ; ; Toye, Dominique et al Poster (2015, January 18) The expansion of hMSC adhered on microcarriers is a proven technology to allow the production of quantitatively (cell density and growth rate) and qualitatively (preservation of cell stemness) the amounts ... [more ▼] The expansion of hMSC adhered on microcarriers is a proven technology to allow the production of quantitatively (cell density and growth rate) and qualitatively (preservation of cell stemness) the amounts of cells required for clinical applications. In that context of process optimization, a platform of 6 parallel 250 mL stirred minibioreactors have been designed and fully equipped for hMSC cultivation on microcarriers. The local hydrodynamics in these bioreactors have been characterized using CFD simulations and experimental measurements. GOALS: 1) Evaluation of the flexibility of the platform for extensively studying the coupling between hydrodynamics and hMSC physiological response (growth, stemness) by changing agitation conditions. 2) Evaluation of the scale down ability of platform as prediction tool of the hMSC behavior in larger bioreactor scale. [less ▲] Detailed reference viewed: 64 (7 ULg)HYDRODYNAMICS IN A DISPOSABLE RECTANGULAR PARALLELEPIPED STIRRED BIOREACTOR WITH ELLIPTIC PENDULUM MOTION PADDLE Collignon, Marie-Laure ; ; Delafosse, Angélique et al in Biochemical Engineering Journal (2015), 93 Stainless steel bioreactors increasingly fall behind to their disposable counterparts in pharma research as they do not require cleaning or sterilization. This led company ATMI LifeSciences to develop the ... [more ▼] Stainless steel bioreactors increasingly fall behind to their disposable counterparts in pharma research as they do not require cleaning or sterilization. This led company ATMI LifeSciences to develop the “Nucleo™”. Original in design, this disposable bioreactor comprises a rectangular parallelepiped plastic bag stirred by a paddle revolving in elliptic pendulum motion. Studies covering this bioreactor showed good homogeneity of culture medium as well as good productivity for animal cell cultures. To further explain these good performances, the flow inside the “Nucleo™” had to be resolved. This paper focuses on the mean flow description, computed from stereo-PIV measurements performed in 20 verticals covering the whole volume of a 50 dm3 Nucleo™ bioreactor. As the flow is already turbulent in the chosen agitation conditions, its dimensionless mean velocity field does not vary with the paddle rotational speed. Mean flow pattern exhibits an axial symmetry – same flow is observed in opposite quarters of the tank – and can be described as a three-dimensional helix coiled on itself to form a distorted horizontal torus which covers the whole tank volume. Mean velocity value is on average doubled in the cone swept by the paddle, and its two horizontal components are twice higher than its vertical ones. However, mean velocity remains significant everywhere and, in particular, no stagnant area is observed in tank corners. Our results thus confirm previous studies observations. [less ▲] Detailed reference viewed: 68 (20 ULg)CFD Comparison of hydrodynamics between BIOSTAT® Cultibag STR and standard Stirred Cell Culture Bioreactors Calvo, Sébastien ; Delafosse, Angélique ; Crine, Michel et al Poster (2014, September 10) Single-use bioreactors have been increasingly used for animal cell cultures on microcarriers in screening experiments. Because of their manufacturing process, the shape of these kinds of vessels such as ... [more ▼] Single-use bioreactors have been increasingly used for animal cell cultures on microcarriers in screening experiments. Because of their manufacturing process, the shape of these kinds of vessels such as the BIOSTAT® Cultibag STR one, is limited. For example, technical constraints on weld seams limit angles to 30° and no baffle may be installed. The shape of standard re-usable vessels may thus not be exactly reproduced and the flow structure may thus significantly differs from the flow structure in standard bioreactors. [less ▲] Detailed reference viewed: 55 (11 ULg)RANS and Large Eddy Simulation of the hydrodynamics inside mini-bioreactors designed for stem cell culture Collignon, Marie-Laure ; ; et al Conference (2014, September 07) Detailed reference viewed: 54 (9 ULg)Outils d’étude pour caractériser l’impact de l’ hydrodynamique sur la culture de cellules animales adhérentes cultivées sur microporteurs en bioréacteurs à cuve agitée Collignon, Marie-Laure Conference (2014, July 10) Cette présentation montre l'importance du choix des conditions d'agitation lors de la culture de cellules animales adhérentes sur microporteurs en bioréacteurs à cuve agitée. Elle montre des exemples d ... [more ▼] Cette présentation montre l'importance du choix des conditions d'agitation lors de la culture de cellules animales adhérentes sur microporteurs en bioréacteurs à cuve agitée. Elle montre des exemples d'outils pour caractériser à l'échelle locale l'hydrodynamique au sein de ces bioréacteurs et une approche Euler-Lagrange qui a terme permettra de faire le lien entre l'hydrodynamique et la réponse cellulaire grâce à l'établissement de l'historique de conditions rencontrées localement par les cellules. [less ▲] Detailed reference viewed: 35 (9 ULg)Mise en suspension et contraintes hydrodynamiques sur microporteurs en procédés de cultures adhérentes Collignon, Marie-Laure Scientific conference (2014, April 17) Detailed reference viewed: 30 (8 ULg)CFD-based Compartment model for description of mixing in bioreactors Delafosse, Angélique ; Calvo, Sébastien ; Collignon, Marie-Laure et al in Chemical Engineering Science (2014), 106 In most bioprocesses, it is fundamental to accurately predict the hydrodynamics behavior of bioreactors of different size and its interaction with the biological reaction. Computational Fluid Dynamics can ... [more ▼] In most bioprocesses, it is fundamental to accurately predict the hydrodynamics behavior of bioreactors of different size and its interaction with the biological reaction. Computational Fluid Dynamics can provide detailed modeling about hydrodynamics and mixing. However, it is computationally intensive, especially when reactions are taken into account. Another way to predict hydrodynamics is the use of “Compartment” or “Network-of-zones” model which are much less demanding in computation time than CFD. However, compartments and fluxes between them are often defined by considering global quantities not representative of the flow complexity. To overcome the limitations of these two methods, a solution is to combine compartment modeling and CFD simulations. The aim of this study is to propose a compartment model where the flow rates between two adjacent compartments are easily computed from the velocity fields obtained by CFD. The mixing evolution predicted by the CFD-based compartment model have been then compared with mixing experiment results. Unlike a CFD mixing simulation and a classical compartment model, the CFD-based compartment model proposed in this work reproduces with a good accuracy the spatial distribution of concentrations during the mixing process and this, without any adjustable parameters. [less ▲] Detailed reference viewed: 93 (29 ULg)Développement d'un dispositif de trajectographie optique nécessaire pour la caractérisation expérimentale par une approche Euler-Lagrange des écoulements dans des bioréacteurs à cuve agitée Collignon, Marie-Laure ; Delafosse, Angélique ; Delvigne, Frank et al in Récents Progrès en Génie des Procédés (2013, October) Les bioréacteurs à cuve agitée sont des dispositifs largement utilisés dans l’industrie pharmaceutique. Les performances globales des cultures menées dans ces bioréacteurs dépendent fortement de ... [more ▼] Les bioréacteurs à cuve agitée sont des dispositifs largement utilisés dans l’industrie pharmaceutique. Les performances globales des cultures menées dans ces bioréacteurs dépendent fortement de l’environnement physico-chimique et hydrodynamique local rencontré par les microorganismes et ce au cours du temps. Pour parvenir à caractériser cet historique de conditions locales rencontrées, une approche Euler-Lagrange doit être adoptée. La difficulté dans ce type d’approche est d’être capable de mesurer de manière fiable la trajectoire suivie par le microorganisme au sein du bioréacteur. Pour ce faire, le Laboratoire de Génie Chimique de l’Université de Liège a conçu un dispositif de trajectographie optique. L’objectif de cet article est de présenter ce dispositif, les développements qui ont été nécessaire à sa mise en œuvre et les résultats obtenus. Le dispositif se compose de deux caméras observant selon deux axes de l’espace un bioréacteur rétro-éclairé par des panneaux leds. La trajectoire suivie par une particule noire en gel d’alginate de calcium de 491 µm de diamètre est construite à partir des images acquises par ces deux caméras préalablement modélisée par un modèle pinhole et traitées par une approche rationnée. La validité des trajectoires mesurées a été prouvée dans un bioréacteur de 20 L mélangé par une hélice TTP en comparant les champs de vitesse moyen et d’énergie cinétique turbulent extraits de la trajectoire avec ceux obtenus par la technique eulérienne Stéréo P.I.V. La convergence de ces deux champs avec le temps d’acquisition de la trajectoire a également été démontrée. [less ▲] Detailed reference viewed: 107 (35 ULg)Caractérisation expérimentale et modélisation des conditions de mise en suspension homogène d’un solide dans une cuve agitée industrielle Calvo, Sébastien ; Delafosse, Angélique ; Collignon, Marie-Laure et al in Récents Progrès en Génie des Procédés (Cd-ROM) (2013, September) In this work, we study the conditions needed to reach homogeneous distribution of solid particles of aluminium salts in water inside a GRC bottom shape stirred tank of 70L equipped with Pfaudler RCI type ... [more ▼] In this work, we study the conditions needed to reach homogeneous distribution of solid particles of aluminium salts in water inside a GRC bottom shape stirred tank of 70L equipped with Pfaudler RCI type impeller and three equispaced vertical baffles. The aim of the present study is to develop a CFD model describing the quality of particle distribution at the industrial scale. This model, validated with experimental data, is afterward used to developed scale-up and scale-down correlation to predict the minimum impeller speed needed to reach homogeneous solid distribution Nhs. The commercial CFD tool Fluent 14 is used to model the fluid flow and the solid particle distribution in the tank. The 3D geometry of the tank and the associated mesh are realized respectively by Ansys 14 DesignModeler and Meshing. The Sliding-Mesh approach is used to take into account the impeller motion. Assuming that only the continuous phase is present, the fluid flow dynamics may be simulated independently using the wellknown k-ε turbulence model. The behaviour of the liquid-solid mixture is then described implementing the Eulerian Mixture model. Liquid velocity fields simulated by CFD have been validated by comparison with PIV (Particle Image Velocimetry) measurements. Computed Nhs is well compared to experimental data obtained with a nephelometric probe. Results obtained at different scales allowed correlating Nhs and volumetric power consumption. [less ▲] Detailed reference viewed: 61 (8 ULg)Experimental characterisation and modelling of homogeneous solid suspension in an industrial stirred tank Calvo, Sébastien ; Delafosse, Angélique ; Collignon, Marie-Laure et al in Advances in Mechanical Engineering (2013), Volume 2013 In this work, we study the conditions needed to reach homogeneous distribution of aluminium salts particles in water inside a torispherical bottom shaped stirred tank of 70 L equipped with a Pfaudler RCI ... [more ▼] In this work, we study the conditions needed to reach homogeneous distribution of aluminium salts particles in water inside a torispherical bottom shaped stirred tank of 70 L equipped with a Pfaudler RCI type impeller and three equispaced vertical baffles. The aim of the present study is to develop a CFD model describing the quality of particle distribution in industrial scale tanks. This model, validated with experimental data, is used afterwards to develop scale-up and scale-down correlations to predict the minimum impeller speed needed to reach homogeneous solid distribution Nhs.The commercial CFD software Fluent 14 is used to model the fluid flow and the solid particle distribution in the tank. Sliding Mesh approach is used to take the impeller motion into account. Assuming that the discrete solid phase has no influence on the continuous liquid phase behaviour, the fluid flow dynamics is simulated independently using the well-known k-ε turbulence model. The liquid-solid mixture behaviour is then described by implementing the Eulerian Mixture model. Computed liquid velocity fields are validated by comparison with PIV measurements. ComputedNhs were found to be in good agreement with experimental measurements. Results fromdifferent scales allowed correlating Nhs values to the volumetric power consumption. [less ▲] Detailed reference viewed: 66 (17 ULg)CFD Modelisation of homogeneous distribution of solid particles in a stirred tank Calvo, Sébastien ; Delafosse, Angélique ; Collignon, Marie-Laure et al Poster (2013, April 24) In this work, we study the conditions needed to reach homogeneous distribution of solid particles of aluminium salts in water inside a torospherical bottom shaped stirred tank reactor of 70L equipped with ... [more ▼] In this work, we study the conditions needed to reach homogeneous distribution of solid particles of aluminium salts in water inside a torospherical bottom shaped stirred tank reactor of 70L equipped with a Pfaudler RCI type impeller and three equi-spaced vertical baffles. The aim of the present study is to develop a CFD model describing the quality of particle distribution in industrial scale tanks. This model, validated with experimental data, is afterward used to developed scale-up and scale-down correlations to predict the minimum impeller speed needed to reach homogeneous solid distribution Nhs. The commercial CFD software Fluent 14 is used to model the fluid flow and the solid particle distribution in the tank. The 3D geometry of the tank and the associated mesh are respectively realized by Ansys 14 DesignModeler and Meshing. The Sliding-Mesh approach is used to take the impeller motion into account. Assuming that the discrete solid phase has no influence on the continuous liquid phase behaviour, the fluid flow dynamics may be simulated independently using the well-known k-ε turbulence model. The behaviour of the liquid-solid mixture is then described by implementing the Eulerian Mixture model. Liquid velocity fields simulated by CFD have been validated by comparison with PIV (Particle Image Velocimetry) measurements. Computed values of Nhs are compared with good agreement to experimental data obtained with a nephelometric probe. Results obtained at different scales allowed correlating the Nhs value to the volumetric power consumption. [less ▲] Detailed reference viewed: 70 (9 ULg)Development of optical trajectography device for the lagangian study of turbulent flow inside a stirred tank used in pharmaceutical industry Collignon, Marie-Laure ; Delafosse, Angélique ; Delvigne, Frank et al Poster (2012, September 10) Stirred tanks are devices that are widely used in various process steps of the pharmaceutical industry. The performance of these processes (animal cell culture, crystallization, flocculation …) strongly ... [more ▼] Stirred tanks are devices that are widely used in various process steps of the pharmaceutical industry. The performance of these processes (animal cell culture, crystallization, flocculation …) strongly depend on the physico-chemical and hydrodynamic environment present locally in these tanks. To fully describe this local environment, an Eulerian - Lagrangian approach must be adopted in order to establish history of conditions met by a particle as a cell, a crystal or a floc. This approach implies to determine the trajectory followed by the particle. To this aim, the Chemical Laboratory of Liege University has developed a prototype of optical trajectography device. The objective of this paper is to present the device, developments that were necessary for its use and the results obtained. The device is composed of two cameras modeled by a pinhole model which record the position of a bead that has a size equal to 490 µm and that perfectly follows local flow structures. The measured trajectory has been validated by comparing average time velocity fields deduced from it to those measured, in the same operating conditions, by particle image velocimetry (P.I.V.). [less ▲] Detailed reference viewed: 41 (13 ULg) |
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