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Modelling of hollow fiber membrane bioreactor for mammalian cell cultivation using computational hydrodynamics

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Abstract

The hollow fiber membrane bioreactor (HFMB) has been investigated for the cultivation of mammalian Chinese hamster ovary cell expansion. The experiments were carried out in Petri’s dishes and in the hollow fiber membrane bioreactor having 20 fibers (S2025 from FiberCell Systems). The approach to HFMB modelling which combines the model of cell growth kinetics and hydrodynamics has been proposed. The hydrodynamic model is made using ANSYS Fluent software. The mathematical model of HFMB was developed, allowing the study of the hydrodynamics into the lumen and the extracapillary spaces, the filtration through the membrane fiber with the cell expansion on outer membrane surface. The direct nutrient medium flow variant into the extracapillary space was suggested. Based on the numerical simulations, the optimal parameters were selected for daily changes in the medium flow-rate into the lumen space. The HFMB scaling up was performed for the larger size HFMB (60 fibers).

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Abbreviations

G :

Acceleration of gravity, m/s2

I :

Mass flow depending on cell consumption of nutrient medium and metabolites flow per one cell, kg/m s

J :

Mass flow passed through membrane, kg/m s2

K :

Population capacity (parameter for the limitation of the number of cells in population)

L :

Membrane thickness, m

n :

Number of pores on membrane surface, 1/m2

N :

Count of cells at timepoint t, cell

P :

Pressure, Pa

Q :

Medium flow-rate into the lumen space in mode 3

q c :

Consumption of nutrient medium for one cell, m3/s

q met :

Consumption of metabolites released by one cell, m3/s

r por :

Pore radius, m

S :

Membrane surface area, m2

t :

Time, s

v :

Medium velocity along the axes, m/s

α :

Membrane permeability coefficient, m2

δ :

Relative calculation error,  %

μ :

Dynamic viscosity, Pa s

µ cell :

Cell-specific growth rate, days−1

ρ :

Medium density, kg/m3

φ :

Pore tortuosity

1:

Lumen space

2:

Extracapillar space

cal:

Data from calculation results

exp:

Data from experiment

in:

Input

m:

Membrane

out:

Output

x, y, z :

Coordinates on axes, m

w:

Wall

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Acknowledgements

This research was supported by the Ministry of Science and Higher Education of the Russian Federation within the framework of Basic Component of the State Assignment (no 10.4658.2017/6.7).

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Authors and Affiliations

  1. Department of Cybernetics of Chemical Processes, Faculty of Information Technologies and Chemical Engineering, Mendeleev University of Chemical Technology of Russia, Miusskaya Sq., 9, 125047, Moscow, Russia

    Natalia V. Menshutina, Elena V. Guseva & Ruslan R. Safarov

  2. Laboratoire Réactions et Génie des Procédés, University of Lorraine, CNRS, LRGP, 54000, Nancy, France

    Joseph Boudrant

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  1. Natalia V. Menshutina
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  2. Elena V. Guseva
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  3. Ruslan R. Safarov
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Correspondence to Elena V. Guseva.

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Natalya V. Menshutina, Elena V. Guseva, Ruslan R. Safarov and Joseph Boudrant declare that they have no conflict of interest.

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Menshutina, N.V., Guseva, E.V., Safarov, R.R. et al. Modelling of hollow fiber membrane bioreactor for mammalian cell cultivation using computational hydrodynamics. Bioprocess Biosyst Eng 43, 549–567 (2020). https://doi.org/10.1007/s00449-019-02249-9

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