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Hydrodynamic investigation of a novel shear-generating device for the measurement of anchorage-dependent cell adhesion intensity

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Abstract

Proliferation of anchorage-dependent cells occurs after adhesion to a suitable surface. Thus, quantitative information about the force of cells adhesion to microcarriers at early culture phases is vital for scaling up such system. In this work, a newly designed shear-generating device was proposed, based on a previously proposed contraction flow device designed for suspended cells. A design equation for the new device was also proposed to correlate the generated energy dissipation rate (EDR) with the cross-sectional area and flow rate. Microscopic-particle image velocimetry was measured to validate the simulation results, and good agreement was achieved. The newly designed device was then used to measure the adhesion force of MDCK and PK cells, and the results showed that the critical EDR was 3000 W/m3 for MDCK and 5000 W/m3 for PK cells. This quantitative information is of great value for better understanding shearing effects during the scaling up of anchorage-dependent cell cultures.

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References

  1. Ursache RV, Thomassen YE, van Eikenhorst G, Verheijen PJT, Bakker WAM (2015) Mathematical model of adherent Vero cell growth and poliovirus production in animal component free medium. Bioprocess Biosyst Eng 38:543–555

    Article  CAS  PubMed  Google Scholar 

  2. Heathman TRJ, Glyn VAM, Picken A, Rafiq QA, Coopman K, Nienow AW, Kara B, Hewitt CJ (2015) Expansion, harvest and cryopreservation of human mesenchymal stem cells in a serum-free microcarrier process. Biotechnol Bioeng 112:1696–1707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chalmers JJ (2015) Mixing, aeration and cell damage, 30+ years later: what we learned, how it affected the cell culture industry and what we would like to know more about. Curr Opin Chem Eng 10:94–102

    Article  Google Scholar 

  4. Pawar SB (2018) Computational fluid dynamics (CFD) analysis of airlift bioreactor: effect of draft tube configurations on hydrodynamics, cell suspension, and shear rate. Bioprocess Biosyst Eng 41:31–45

    Article  CAS  PubMed  Google Scholar 

  5. Al-Rubeai M, Singh RP, Goldman MH, Emery AN (1995) Death mechanisms of animal cells in conditions of intensive agitation. Biotechnol Bioeng 45:463–472

    Article  CAS  PubMed  Google Scholar 

  6. Mahajan KD, Nabar GM, Xue W, Anghelina M, Moldovan NI, Chalmers JJ, Winter JO (2017) Mechanotransduction effects on endothelial cell proliferation via CD31 and VEGFR2: implications for immunomagnetic separation. Biotechnol J 12

  7. Moore LR, Williams PS, Chalmers JJ, Zborowski M (2017) Tessellated permanent magnet circuits for flow-through, open gradient separations of weakly magnetic materials. J Magn Magn Mater 427:325–330

    Article  CAS  PubMed  Google Scholar 

  8. Serrano-Carreon L, Galindo E, Rocha-Valadez JA, Holguin-Salas A, Corkidi G (2015) Hydrodynamics, fungal physiology, and morphology. In: Krull R, Bley T (eds) Filaments in bioprocesses. Springer, Berlin

    Google Scholar 

  9. Kolmogorov AN (1991) The local structure of turbulence in incompressible viscous fluid for very large Reynolds numbers. Proc R Soc Lond A 434:9–13

    Google Scholar 

  10. Nienow AW, Hewitt CJ, Heathman TRJ, Glyn VAM, Fonte GN, Hanga MP, Coopman K, Rafiq QA (2016) Agitation conditions for the culture and detachment of hMSCs from microcarriers in multiple bioreactor platforms. Biochem Eng J 108:24–29

    Article  CAS  Google Scholar 

  11. Maddah S, Navidbakhsh M (2015) A cell damages study in pulsatile blood flow through two- and three-dimensional obstructed vessels Using the Cosserat continuum approach. J Dispersion Sci Technol 36:496–509

    Article  CAS  Google Scholar 

  12. Wu L-H, Chang H-C, Ting P-C, Wang DL (2018) Laminar shear stress promotes mitochondrial homeostasis in endothelial cells. J Cell Physiol 233:5058–5069

    Article  CAS  PubMed  Google Scholar 

  13. Rayat A, Chatel A, Hoare M, Lye GJ (2016) Ultra scale-down approaches to enhance the creation of bioprocesses at scale: impacts of process shear stress and early recovery stages. Curr Opin Chem Eng 14:150–157

    Article  Google Scholar 

  14. Gregoriades N, Clay J, Ma N, Koelling K, Chalmers JJ (2000) Cell damage of microcarrier cultures as a function of local energy dissipation created by a rapid extensional flow. Biotechnol Bioeng 69:171–182

    Article  CAS  PubMed  Google Scholar 

  15. Ma N, Koelling KW, Chalmers JJ (2002) Fabrication and use of a transient contractional flow device to quantify the sensitivity of mammalian and insect cells to hydrodynamic forces. Biotechnol Bioeng 80:428–437

    Article  CAS  PubMed  Google Scholar 

  16. Mollet M, Godoy-Silva R, Berdugo C, Chalmers JJ (2007) Acute hydrodynamic forces and apoptosis: a complex question. Biotechnol Bioeng 98:772–788

    Article  CAS  PubMed  Google Scholar 

  17. Mollet M, Godoy-Silva R, Berdugo C, Chalmers JJ (2008) Computer simulations of the energy dissipation rate in a fluorescence-activated cell sorter: implications to cells. Biotechnol Bioeng 100:260–272

    Article  CAS  PubMed  Google Scholar 

  18. Hu W, Berdugo C, Chalmers JJ (2011) The potential of hydrodynamic damage to animal cells of industrial relevance: current understanding. Cytotechnology 63:445–460

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tran TT, Lee EG, Lee IS, Woo NS, Han SM, Kim YJ, Hwang WR (2016) Hydrodynamic extensional stress during the bubble bursting process for bioreactor system design. Korea Aust Rheol J 28:315–326

    Article  Google Scholar 

  20. Godoy-Silva R, Mollet M, Chalmers JJ (2009) Evaluation of the effect of chronic hydrodynamical stresses on cultures of suspensed CHO-6E6 cells. Biotechnol Bioeng 102:1119–1130

    Article  CAS  PubMed  Google Scholar 

  21. Jasperson BA, Jeon Y, Turner KT, Pfefferkorn FE, Qu WL (2010) Comparison of micro-pin-fin and microchannel heat sinks considering thermal-hydraulic performance and manufacturability. Ieee Trans Components Packaging Technol 33:148–160

    Article  Google Scholar 

  22. Favero JL, Secchi AR, Cardozo NSM, Jasak H (2010) Viscoelastic fluid analysis in internal and in free surface flows using the software OpenFOAM. Comput Chem Eng 34:1984–1993

    Article  CAS  Google Scholar 

  23. Lysenko DA, Ertesvåg IS, Rian KE (2012) Large eddy simulation of the flow over a circular cylinder at Reynolds number 3900 using the OpenFOAM toolbox. Flow Turbul Combust 89:491–518

    Article  CAS  Google Scholar 

  24. Silva LFLR., Lage PLC (2011) Development and implementation of a polydispersed multiphase flow model in OpenFOAM. Comput Chem Eng 35:2653–2666

    Article  CAS  Google Scholar 

  25. Jasak H (2009) OpenFOAM: Open source CFD in research and industry. Int J Nav Archit Ocean Eng 1:89–94

    Google Scholar 

  26. Ferziger JH, Peric M (2012) Computational methods for fluid dynamics. Springer, New York. ISBN 3-540-42074-6

    Google Scholar 

  27. Santiago JG, Wereley ST, Meinhart CD, Beebe DJ, Adrian RJ (1998) A particle image velocimetry system for microfluidics. Exp Fluids 25:316–319

    Article  CAS  Google Scholar 

  28. Icardi M, Gavi E, Marchisio DL, Barresi AA, Olsen MG, Fox RO, Lakehal D (2011) Investigation of the flow field in a three-dimensional confined impinging jets reactor by means of microPIV and DNS. Chem Eng J 166:294–305

    Article  CAS  Google Scholar 

  29. Li H, Ewoldt R, Olsen MG (2005) Turbulent and transitional velocity measurements in a rectangular microchannel using microscopic particle image velocimetry. Exp Therm Fluid Sci 29:435–446

    Article  CAS  Google Scholar 

  30. Raghavan RV, Friend JR, Yeo LY (2010) Particle concentration via acoustically driven microcentrifugation: microPIV flow visualization and numerical modelling studies. Microfluid Nanofluid 8:73–84

    Article  CAS  Google Scholar 

  31. Wereley ST, Gui L, Meinhart CD (2002) Advanced algorithms for microscale particle image velocimetry. AIAA J 40:1047–1055

    Article  Google Scholar 

  32. Su Z-Z, Dou J, Xu Z-P, Guo Q-L, Zhou C-L (2012) A novel inhibitory mechanism of baicalein on influenza A/FM1/1/47 (H1N1) virus: interference with mid-late mRNA synthesis in cell culture. Chin J Nat Med 10:415–420

    Article  CAS  Google Scholar 

  33. Zhu B, Xu F, Li J, Shuai J, Li X, Fang W (2012) Porcine circovirus type 2 explores the autophagic machinery for replication in PK-15 cells. Virus Res 163:476–485

    Article  CAS  PubMed  Google Scholar 

  34. Shiragami N, Hakoda M, Enomoto A, Hoshino T (1997) Hydrodynamic effect on cell attachment to microcarriers at initial stage of microcarrier culture. Bioprocess Eng 16:399–401

    Article  CAS  Google Scholar 

  35. Vennapusa RR, Aguilar O, Mintong JMB, Helms G, Fritz J, Lahore MF (2010) Biomass-adsorbent adhesion forces as an useful indicator of performance in expanded beds. Sep Sci Technol 45:2235–2244

    Article  CAS  Google Scholar 

  36. Hakoda M, Shiragami N (2000) Effects of ion exchange capacities on attachment and growth of anchorage-dependent HeLa cell. Bioprocess Biosyst Eng 23:523–527

    Article  CAS  Google Scholar 

  37. Wu SC (1999) Influence of hydrodynamic shear stress on microcarrier-attached cell growth: cell line dependency and surfactant protection. Bioprocess Eng 21:201–206

    Article  CAS  Google Scholar 

  38. Ng YC, Berry JM, Butler M (1996) Optimization of physical parameters for cell attachment and growth on macroporous microcarriers. Biotechnol Bioeng 50:627–635

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Financial support from the State Key Development Program of Basic Research of China (973 Program, Grant no. 2013CB733600), the National High Technology Research and Development Program of China (863 Program, Grant no. 2012AA021201), and the China Ministry of Science and Technology under Contract (Grant no. 2012BAI44G00) and the Major Projects of Science and Technology in Anhui Province (Grant no. 17030801036) are gratefully acknowledged.

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Authors and Affiliations

  1. Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, P.O. Box 1138, Comprehensive Laboratory Building, 350 Shushanhu Road, Hefei, 230031, Anhui, People’s Republic of China

    Han Wang, Zhiming Zheng & Peng Wang

  2. University of Science and Technology of China, Hefei, 230026, People’s Republic of China

    Han Wang

  3. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, P.O. Box 329#, 130 Meilong Road, Shanghai, 200237, People’s Republic of China

    Han Wang, Jianye Xia, Ying-Ping Zhuang, Xiaoping Yi & Dahe Zhang

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  1. Han Wang
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  2. Jianye Xia
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  3. Zhiming Zheng
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  4. Ying-Ping Zhuang
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  5. Xiaoping Yi
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  6. Dahe Zhang
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  7. Peng Wang
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Correspondence to Jianye Xia or Zhiming Zheng.

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Wang, H., Xia, J., Zheng, Z. et al. Hydrodynamic investigation of a novel shear-generating device for the measurement of anchorage-dependent cell adhesion intensity. Bioprocess Biosyst Eng 41, 1371–1382 (2018). https://doi.org/10.1007/s00449-018-1964-6

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  • DOI: https://doi.org/10.1007/s00449-018-1964-6

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