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Study of hydrodynamics in wave bioreactors by computational fluid dynamics reveals a resonance phenomenon
KTH, School of Engineering Sciences (SCI).
KTH, School of Engineering Sciences (SCI).
KTH, School of Engineering Sciences (SCI).ORCID iD: 0000-0002-5370-4621
2019 (English)In: Chemical Engineering Science, ISSN 0009-2509, E-ISSN 1873-4405, Vol. 193, p. 53-65Article in journal (Refereed) Published
Abstract [en]

Culture of mammalian or human cells in Wave bioreactor is widely used for cell expansion or for biologics manufacturing. Wave bioreactor cultivation of sensitive cells such as stem cells, immune cells or anchorage-dependent cells, is recognized as an attractive option for culture in suspension or adherently on microcarriers. A systematic optimization of the mixing, oxygen transfer rate and shear stress, most favorable for the cells requires a deep understanding of the hydrodynamics inside the Wave bioreactor bag, i.e. cellbag. Numerical simulation by Computation Fluid Dynamics (CFD), is considered as an inexpensive and efficient tool for predicting the fluid behavior in many fields. In the present study, we perform numerical simulations by Ansys-FLUENT to characterize the flow conditions in a 10 L cellbag. The numerical simulations are carried out to investigate the fluid structures for nine different operating conditions of rocking speed and angle. The influence of these operating parameters on the mixing and the shear stress induced by the liquid motion are studied. We find that the mixing and shear stress increase with the cellbag angle from 4° to 7° but that increasing rocking speeds are not systematically associated with increasing mixing and shear stress. It is concluded that a resonance phenomenon is responsible for the fact that the lowest studied rocking speed, 15 rpm, generates the highest fluid velocity, mixing and shear stress compared to the higher speeds of 22 and 30 rpm.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 193, p. 53-65
Keywords [en]
Computation Fluid Dynamics (CFD), Hydrodynamic, Resonance, Volume of fluid (VOF), Wave bioreactor, Bioconversion, Bioreactors, Cytology, Hydrodynamics, Mammals, Mixing, Numerical models, Shear flow, Shear stress, Stem cells, Anchorage-dependent cells, Computation fluid dynamics, Different operating conditions, Operating parameters, Oxygen transfer rate, Systematic optimization, Volume of fluids, Wave bioreactors, Computational fluid dynamics
National Category
Mechanical Engineering
Identifiers
URN: urn:nbn:se:kth:diva-236330DOI: 10.1016/j.ces.2018.08.017ISI: 000447171800006Scopus ID: 2-s2.0-85052913142OAI: oai:DiVA.org:kth-236330DiVA, id: diva2:1264425
Funder
VINNOVA, 2016-05181
Note

QC 20181120

Available from: 2018-11-20 Created: 2018-11-20 Last updated: 2019-05-23Bibliographically approved
In thesis
1. Hydrodynamics considerations in cells systems from ocean flow to perfusion cultivation process
Open this publication in new window or tab >>Hydrodynamics considerations in cells systems from ocean flow to perfusion cultivation process
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Microorganisms and animal cells are grown surrounded by fluid, which is providing them with nutrients and removing their waste products. In nature and industry processes, cells/microbes can be subject to aggressive environments, such as turbulent flow or shear flow. Hydrodynamics force generated in these flows can affect the distribution of cells/microbes and even lead to cell damage. Understanding the mechanism and exploring the effect of hydrodynamic force in these environments could make the prediction of cells’ hydrodynamic response more systematic. In pharmaceutical industry, perfusion process is recognized as an attractive option for biologics production due to its high productivity. However, there are still some challenges and limitations for further process improvement due to lack of information of cell response to hydrodynamic force and nutrients. In both cases, hydrodynamics plays an important role and similar tool can be used to achieve a deeper understanding of these processes. This thesis is mainly aiming to elucidate the influence of hydrodynamic forces on microorganisms or cells in nature and during bioprocesses. In particular, shear stress in a natural environment and in a bioreactor operated in perfusion mode is studied.

This work mainly investigates hydrodynamics in nature and bioprocess including three flow cases. The first study investigates the effect of turbulence on marine life by performing direct numerical simulations (DNS) of motile micro-organisms in isotropic homogeneous turbulence. The clustering level of micro-organisms with one preferential swimming direction (e.g. gyrotaxis) is examined. The second study uses Computation Fluid Dynamics (CFD) to simulate the fluid flow inside a Wave bioreactor bag. The phenomenon of mixing, oxygen transfer rate and shear stress in nine different operating conditions of rocking speeds and angles are discussed. In the third study, the cellular response to shear force including growth and metabolism in a cell retention device such as hollow fiber filters during a perfusion process is analyzed. Theoretical calculations and experiment validation is performed to compare two filtration modes, tangential flow filtration (TFF) or alternating tangential flow filtration (ATF). Further optimizations regarding mixing and feeding are performed in a screening scale of in a perfusion system of stirred tank bioreactor with cell separation device.

The main findings can be summarized as that spherical gyrotaxis swimmers show significant clustering, whereas prolate swimmers remain more uniformly distributed due to their large sensitivity to the local shear. These results could explain how pure hydrodynamic effects can alter the ecology of micro-organisms for instance by varying shape and their preferential orientation (paper I). The simulations of Wave bioreactors show that the mixing and shear stress increase with the rocking angle but that increasing rocking speeds are not systematically associated with increasing mixing and shear stress. A resonance phenomenon is responsible for the fact that the lowest studied rocking speed generates the highest fluid velocity, mixing and shear stress (paper II). Theoretical velocity profile-based calculations suggested a lower shear stress for ATF by a factor 0.637 compared to TFF. This is experimentally validated by cultures of HEK (human embryonic kidney) 293 cells subjected to shear stress by a perfusion system that affects growth and metabolism using these cell separation devices (paper III). Thanks to optimization of mixing and oxygen transfer in a screening system for perfusion process, very high cell densities above 100 x 106 cells/mL of mammalian cells were achieved (paper IV).

Place, publisher, year, edition, pages
Stockholm, Sweden: KTH Royal Institute of Technology, 2019. p. 57
Series
TRITA-CBH-FOU ; 35
Keywords
Microorganism, cells, hydrodynamics, turbulence, numerical simulation, CFD, Resonance, Wave bioreactor, ATF, TFF, perfusion, design feeding strategy
National Category
Industrial Biotechnology
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-252023 (URN)978-91-7873-233-3 (ISBN)
Public defence
2019-06-14, FA32, Albanova, Department of Mechanics, Royal Institute of Technology, Stockholm, 13:00 (English)
Opponent
Supervisors
Funder
AstraZenecaKnut and Alice Wallenberg Foundation
Note

QC 2019-05-23

Available from: 2019-05-23 Created: 2019-05-23 Last updated: 2019-05-23Bibliographically approved

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Zhan, CaijuanHagrot, ErikaChotteau, Véronique

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