Bioprocess and Biosystems Engineering

, Volume 41, Issue 5, pp 679–695 | Cite as

Hydrodynamic performance of a single-use aerated stirred bioreactor in animal cell culture: applications of tomography, dynamic gas disengagement (DGD), and CFD

  • Argang Kazemzadeh
  • Cynthia Elias
  • Melih Tamer
  • Farhad Ein-Mozaffari
Research Paper

Abstract

The hydrodynamics of gas–liquid two-phase flow in a single-use bioreactor were investigated in detail both experimentally and numerically. Electrical resistance tomography (ERT) and dynamic gas disengagement (DGD) combined with computational fluid dynamics (CFD) were employed to assess the effect of the volumetric gas flow rate and impeller speed on the gas–liquid flow field, local and global gas holdup values, and Sauter mean bubble diameter. From the results obtained from DGD coupled with ERT, the bubble sizes were determined. The experimental data indicated that the total gas holdup values increased with increasing both the rotational speed of impeller and volumetric gas flow rate. Moreover, the analysis of the flow field generated inside the aerated stirred bioreactor was conducted using CFD results. Overall, a more uniform distribution of the gas holdup was obtained at impeller speeds ≥ 100 rpm for volumetric gas flow rates ≥ 1.6 × 10−5 m3/s.

Keywords

Bioreactor Mixing Hydrodynamics Computational fluid dynamics (CFD) Electrical resistance tomography (ERT) Dynamic gas disengagement (DGD) Gas holdup 

Abbreviations

Nomenclature

\(d_{\text{s}}\)

Sauter mean bubble diameter (m)

D

Impeller diameter (m)

Ds

Shaft diameter (m)

H

Vertical distance above gas distributor (m)

Hl

Liquid height (m)

Ht

Tank height (m)

HIb

Impeller blade height (m)

K

Disengagement classes (dimensionless)

N

Impeller speed (rpm)

M

Corrected torque (N.m)

P

Power consumption (W)

Re

Reynolds number (dimensionless)

\(Q_{\text{g}}\)

Volumetric gas flow rate (m3/s)

t

Time (s)

ti

Bubble rising time (s)

tIb

Impeller blade thickness (m)

T

Tank diameter (m)

V

Fluid volume (m3)

Vb

Bubble volume (m3)

Vθ

Tangential velocity (m/s)

ub

Bubble rise velocity (m/s)

wIb

Impeller blade width (m)

Greek letters

\(\mu_{\text{l}}\)

Liquid viscosity (Pa s)

\(\mu_{\text{g}}\)

Gas viscosity (Pa s)

\(\rho_{\text{l}}\)

Liquid density (kg/\({\text{m}}^{3}\))

\(\varPhi_{\text{g}}\)

Total gas holdup (dimensionless)

\(\bar{\varPhi }_{\text{g}}\)

Average gas holdup (dimensionless)

\(\varPhi_{\text{gi}}\)

Local gas holdup (dimensionless)

α

Shaft angle (\(^\circ\))

σ

Surface tension (mN/m)

\(\sigma_{1}\)

Conductivity of contentious fluid (mS/cm)

\(\sigma_{2}\)

Conductivity of dispersed phase (mS/cm)

\(\sigma_{\text{mc}}\)

Measured mixture conductivity (mS/cm)

\(\bar{\sigma }_{\text{mc}}\)

Average measured mixture conductivity (mS/cm)

π

Constant

Notes

Acknowledgements

The financial support of the Natural Sciences and Engineering Research Council of Canada (NSERC) is gratefully acknowledged. The authors would like to thank HPCVL (High performance Computing Virtual Laboratory) for providing the high performance computing facility. The authors also acknowledge the support from Francois Collins, Heather Scott, and the technical staff of Thermo Fisher Scientific.

References

  1. 1.
    Kaiser SC (2015) Characterization and optimization of single-use bioreactors and biopharmaceutical production processes using computational fluid dynamics. Doctoral Thesis, Technische Universitat BerlinGoogle Scholar
  2. 2.
    Zhou T-C, Zhou W-W, Hu W, Zhong J-J, Flickinger MC (2009) Bioreactors, cell culture, commercial production. Encyclopedia of Industrial Biotechnology. Wiley, New YorkGoogle Scholar
  3. 3.
    Nienow AW (2003) Aeration-biotechnology. In: Kirk Othmer encyclopedia of chemical technology, 5th end. Wiley, New York, published in the on-line edition of the Encyclopedia on April 18thGoogle Scholar
  4. 4.
    Nienow AW (2006) Reactor engineering in large scale animal cell culture. Cytechnology 9–23Google Scholar
  5. 5.
    Wang S-J, Zhong J-J (2007) Chapter 6—Bioreactor engineering A2-Yang, Shang-Tian, bioprocessing for Value-Added Products from Renewable Resources. Elsevier, Amsterdam, pp 131–161CrossRefGoogle Scholar
  6. 6.
    Zhu Y, Bandopadhayay PC, Wu JIE (2001) Measurement of gas–liquid mass transfer in an agitated vessel—a comparison between different impellers. J Chem Eng Jpn 34:579–584CrossRefGoogle Scholar
  7. 7.
    Puthli MS, Rathod VK, Pandit AB (2005) Gas–liquid mass transfer studies with triple impeller system on a laboratory scale bioreactor. Biochem Eng J 23:25–30CrossRefGoogle Scholar
  8. 8.
    Zhong J-J, Yoshida M, Fujiyama K, Seki T, Yoshida T (1993) Enhancement of anthocyanin production by Perilla frutescens cells in a stirred bioreactor with internal light irradiation. J Ferment Bioeng 75:299–303CrossRefGoogle Scholar
  9. 9.
    Zhu Y, Cuenca JV, Zhou W, Varma A (2008) NS0 cell damage by high gas velocity sparging in protein-free and cholesterol-free cultures. Biotechnol Bioeng 101:751–760CrossRefGoogle Scholar
  10. 10.
    Yang J-D, Lu C, Stasny B, Henley J, Guinto W, Gonzalez C, Geason J, Fung M, Collopy B, Benjamino M, Gangi J, Hanson M, Ille E (2007) Fed-Batch bioreactor process scale-up from 3 L to 2500 L scale for monoclonal antibody production from cell culture. Biotechnol Bioeng 98(1):141–154CrossRefGoogle Scholar
  11. 11.
    Koynov A, Tayggvason G, Khinast J G (2007) Characterization of localized hydrodynamic shear forces and dissolved oxygen distribution in sparged bioreactors 97(2):317–331Google Scholar
  12. 12.
    Amano K, Haga R, Murakami S (2008) Expressions of mass transfer coefficient of bubbles and free surface of culture tanks using the k–e turbulence model. J Ind Microbio Biotechnol 35:525–531CrossRefGoogle Scholar
  13. 13.
    Jain E, Kumar A (2008) Upstream processes in antibody production: evaluation of critical parameters 26:46–72Google Scholar
  14. 14.
    Frahm B, Brod H, Langer U (2009) Improving bioreactor cultivation conditions for sensitive cell lines by dynamic membrane aeration. Cytotechnology 59:17–30CrossRefGoogle Scholar
  15. 15.
    Matsunaga N, Kano K, Maki Y, Dobashi T (2009) Culture scale-up studies as seen from the viewpoint of oxygen supply and dissolved carbon dioxide stripping. J Biosci Bioeng 107(4):412–418CrossRefGoogle Scholar
  16. 16.
    Joshi JB, Elias CB, Patole MS (1996) Role of hydrodynamic shear in the cultivation of animal, plant and microbial cells. Bio Chem Eng J 62:121–141CrossRefGoogle Scholar
  17. 17.
    Odeleye AOO, Marsh DTJ, Osborne MD, Lye GJ, Micheletti M (2014) On the fluid dynamics of a laboratory scale single-use stirred bioreactor. Chem Eng Sci 111:299–312CrossRefGoogle Scholar
  18. 18.
    Wu J, Zhu Y, Pullum L (2001) Impeller geometry effect on velocity and solids suspension. Chem Eng Res Des 79:989–997CrossRefGoogle Scholar
  19. 19.
    Li M, White G, Wilkinson D, Roberts KJ (2005) Scale up study of retreat curve impeller stirred tanks using LDA measurements and CFD simulation. Chem Eng J 108:81–90CrossRefGoogle Scholar
  20. 20.
    Hashemi N, Ein-Mozaffari F, Upreti SR, Huwang DK (2016) Analysis of mixing in aerated reactor equipped with the coaxial mixer through electrical resistance tomography and response surface method. Chem Eng Res Des 109:734–752CrossRefGoogle Scholar
  21. 21.
    Hashemi N, Ein-Mozaffari F, Upreti SR, Huwang DK (2016) Experimental investigation of bubble behavior in an aerated coaxial mixing vessel through electrical resistance tomography (ERT). Chem Eng J 289:402–412CrossRefGoogle Scholar
  22. 22.
    Kaiser SC, Eibl R, Eibl D (2011) Engineering characteristics of a single-use stirred bioreactor at bench-scale: the Mobius Cell Ready 3L bioreactor as a case study. Eng Life Sci 11:359–368CrossRefGoogle Scholar
  23. 23.
    Kaiser SC, Löffelholz C, Eibl D, Werner S (2011b) CFD for characterizing standard and single-use stirred cell culture bioreactors. INTECH Open Access PublishGoogle Scholar
  24. 24.
    Kaiser S, Jossen V, Schirmaier C, Eibl D, Brill S, van den Bos C, Eibl R (2013) Fluid flow and cell proliferation of mesenchymal adipose-derived stem cells in small-scale, stirred, single-use bioreactors. Chem Ing Tec 85:95–102CrossRefGoogle Scholar
  25. 25.
    Freshney RI (2016) Culture of animal cells: a manual basic techniques and specialized applications, 7th edn. Wiley-BlackwellGoogle Scholar
  26. 26.
    Oh SKW, Nienow AW, Al-Rubeai M, Emery AN (1989) The effect of the agitation intensity with and without continuous sparging on the growth and antibody production of hybridoma cells. J Biotechnol 22:245–270CrossRefGoogle Scholar
  27. 27.
    Elias CB, Desha RB, Patole MS, Joshi JB, Mashelcar RA (1995) Turbulnt shear stress- effect on mammalian cell culture and measurement using laser Doppler anemometer. Chem Eng Sci 50(15):2431–2440CrossRefGoogle Scholar
  28. 28.
    Pakzad L, Ein-Mozaffari F, Upreti SR, Lohi A (2013) A novel and energy-efficient coaxial mixer for agitation of non-Newtonian fluids possessing yield stress. Chem Eng Sci 101:642–654CrossRefGoogle Scholar
  29. 29.
    Pakzad L, Ein-Mozaffari F, Upreti S, Lohi A (2013) Evaluation of the mixing of non-Newtonian biopolymer solutions in the reactors equipped with coaxial mixers through tomography and CFD. Chem Eng J 215:279–296CrossRefGoogle Scholar
  30. 30.
    Babaei R, Bonakdarpour B, Ein-Mozaffari F (2015) Analysis of gas characteristics and mixing performance in an activated sludge bioreactor using electrical resistance tomography. Chem Eng J 279:874–884CrossRefGoogle Scholar
  31. 31.
    Babaei R, Bonakdarpour B, Ein-Mozaffari F (2015) The use of electrical resistance tomography for characterization of gas holdup inside of bubble column bioreactor containing activated slug. Chem Eng J 268:260–8269CrossRefGoogle Scholar
  32. 32.
    Kazemzadeh A, Ein-Mozaffari F, Lohi A, Pakzad L (2016) Effect of the rheological properties on the mixing of Herschel–Bulkley fluids with the coaxial mixers: applications of tomography, CFD and response Surface methodology. Can J Chem Eng 94:2394–2406CrossRefGoogle Scholar
  33. 33.
    Kazemzadeh A, Ein-Mozaffari F, Lohi A, Pakzad L (2016) Investigation of hydrodynamic performances of coaxial Mixers in agitation of yield-pseudoplasitc fluids: single and double central impellers in combination with the Anchor. Chem Eng J 294:417–430CrossRefGoogle Scholar
  34. 34.
    Kazemzadeh A, Ein-Mozaffari F, Lohi A, Pakzad L (2016) A new perspective in the evaluation of the mixing of biopolymer solutions with different coaxial mixers comprising of two dispersing impellers and a wall scraping anchor. Chem Eng Res Des J 114:202–219CrossRefGoogle Scholar
  35. 35.
    Kazemzadeh A, Ein-Mozaffari F, Lohi A, Pakzad L (2016) Intensification of mixing of shear-thinning fluids possessing yield stress with the coaxial mixers composed of two different central impellers and an anchor. Chem Eng Process Process Intensification 111:101–114CrossRefGoogle Scholar
  36. 36.
    Khalili F, Jafari Nasr MR, Kazemzadeh K, Ein-Mozaffari F (2017) Hydrodynamic performance of the ASI impeller in an aerated bioreactor containing the biopolymer solution through tomography, CFD. Chem Eng Res Des 125:190–203CrossRefGoogle Scholar
  37. 37.
    Khalili F, Nasr MRJ, Kazemzadeh K, Ein-Mozaffari F (2017) Analysis of gas holdup and bubble behavior in a biopolymer solution inside a bioreactor using electrical resistance tomography and dynamic gas disengagement. J Chem Technol and Biotechnol.  https://doi.org/10.1002/jctb.5356 Google Scholar
  38. 38.
    Maxwell JC (1954) A treatise on electricity and magnetism, Unabridged Third. Dover publications, New YorkGoogle Scholar
  39. 39.
    Jin H, Wang M, Williams R (2007) Analysis of bubble behavior in bubbles columns using electrical resistance tomography. Chem Eng J 130(2):179–185CrossRefGoogle Scholar
  40. 40.
    Calderbank PH (1958) Physical rate processes in industrial fermentation. Part 1: The interfacial area in gas-liquid contacting with mechanical agitation. Trans Inst Chem Eng 36(5):433–440Google Scholar
  41. 41.
    Hashemi N, Ein-Mozaffari F, Ureti SR, Hwang DK (2017) Hydrodynamic characteristics of an aerated coaxial mixing vessel equipped with pitched blade turbine and an anchor. J Chem Technol Biotechnol.  https://doi.org/10.1002/jctb.5367 Google Scholar
  42. 42.
    Letellier B, Xuereb C, Swaels P, Hobbes P (2002) Scale-up in laminar and transient regimes of multi-stage stirrer, a CFD approach. Chem Eng Sci 57:4617–4632CrossRefGoogle Scholar
  43. 43.
    Jahoda M, Tomaškova L, Moštěk M (2009) CFD prediction of liquid homogenization in a gas-liquid stirred tank. Chem Eng Res Des 87:460–467Google Scholar
  44. 44.
    Montante G, Paglianti A, Magelli F (2007) Experimental modeling of gas-liquid stirred vessels. Trans IChemE A Chem Eng Res Des 85(A5):647–653CrossRefGoogle Scholar
  45. 45.
    Khopkar AR, KASAT GR, Pandit AB and Ranade VV (2006) CFD simulation of mixing in tall gas-liquid stirred vessel: role of local flow patterns. Chem Eng Sci 61:2921–2929Google Scholar
  46. 46.
    Versteeg HK, Malalasekera W (2007) An introduction to computational fluid dynamic the finite volume method, 2nd edn. Longman, Group ltd, LondonGoogle Scholar
  47. 47.
    Valery J, Birch J (1999) Reactor design for large-scale suspension animal cell culture. Cytotechnology 29:177–205CrossRefGoogle Scholar
  48. 48.
    Löffelholz C, Husemann U, Greller g, Meusel W, Kauling J, Ay P, Kraume M, Eibl R, Eibl D (2013) Bioengineering parameters for single-use bioreactors: overview and evaluation of suitable methods and evaluation of suitable methods. Chem Ing Tech 85(I-2):40–56Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Argang Kazemzadeh
    • 1
  • Cynthia Elias
    • 2
  • Melih Tamer
    • 2
  • Farhad Ein-Mozaffari
    • 1
  1. 1.Department of Chemical EngineeringRyerson UniversityTorontoCanada
  2. 2.Sanofi Pasteur CompanyTorontoCanada

Personalised recommendations