Evaluating shear in perfusion rotary lobe pump using nanoparticle aggregates and computational fluid dynamics.
Cell Culture
Computational fluid dynamics
Perfusion
Rotary lobe pump
Shear
Journal
Bioprocess and biosystems engineering
ISSN: 1615-7605
Titre abrégé: Bioprocess Biosyst Eng
Pays: Germany
ID NLM: 101088505
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
05
04
2022
accepted:
12
07
2022
pubmed:
23
7
2022
medline:
26
8
2022
entrez:
22
7
2022
Statut:
ppublish
Résumé
Perfusion cell culture technology has gained a lot of interest in recent years in the biopharmaceutical industry. One common application is N-1 perfusion which is used to intensify fed batch production processes and increase facility output. Upon running our perfusion process for the first time at manufacturing scale, unexpected cell damage was observed. Reducing the recirculation pump speed resulted in improvements in cell viability which implied the impact of pump shear stress on cell viability. In this study, we used polymethyl methacrylate (PMMA) nanoparticles to determine the shear stress inside two different sized rotary lobe pumps used in N-1 perfusion. The results were used to validate a computational fluid dynamics (CFD) model to predict the maximum shear under different operating conditions of the pump. The CFD model identified the radial and mesh clearance zones as regions that experience the maximum shear stress inside the pump. The model was then used to evaluate the impact of different geometry modifications in the pump lobes, and it predicted a 17% reduction in the maximum shear stress by increasing the mesh and radial clearances by 0.08 mm and 0.13 mm, respectively. The study indicates that CFD can be a useful tool to predict shear stress inside rotary pumps. The results can be used to optimize the pump operating conditions or even customize the pump geometry to save time and cost of process scaling to manufacturing without compromising the preset operating conditions or critical scale-up parameters.
Identifiants
pubmed: 35869293
doi: 10.1007/s00449-022-02757-1
pii: 10.1007/s00449-022-02757-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1477-1488Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Bielser J-M, Wolf M, Souquet J, Broly H, Morbidelli MJB (2018) Perfusion mammalian cell culture for recombinant protein manufacturing–a critical review. Biotechnol Adv 36(4):1328–1340
doi: 10.1016/j.biotechadv.2018.04.011
Yang WC et al (2014) Perfusion seed cultures improve biopharmaceutical fed-batch production capacity and product quality. Biotechnol Prog 30(3):616–625
doi: 10.1002/btpr.1884
Hu W, Berdugo C, Chalmers JJJC (2011) The potential of hydrodynamic damage to animal cells of industrial relevance: current understanding. Cytotechnology 63(5):445
doi: 10.1007/s10616-011-9368-3
Vickroy B, Lorenz K, Kelly WJBP (2007) Modeling shear damage to suspended CHO cells during cross-flow filtration. Biotechnol Prog 23(1):194–199
doi: 10.1021/bp060183e
Westoby M, Rogers JK, Haverstock R, Romero J, Pieracci JJB (2011) Modeling industrial centrifugation of mammalian cell culture using a capillary based scale-down system. Biotechnol Bioeng 108(5):989–998
doi: 10.1002/bit.23051
Godoy-Silva R, Chalmers JJ, Casnocha SA, Bass LA, Ma NJB (2009) Physiological responses of CHO cells to repetitive hydrodynamic stress. Biotechnol Bioeng 103(6):1103–1117
doi: 10.1002/bit.22339
Senger RS, Karim MNJBP (2003) Effect of shear stress on intrinsic CHO culture state and glycosylation of recombinant tissue-type plasminogen activator protein. Biotechnol Bioeng 19(4):1199–1209
Keane JT, Ryan D, Gray PPJB (2003) Effect of shear stress on expression of a recombinant protein by Chinese hamster ovary cells. Biotechnol Bioeng 81(2):211–220
doi: 10.1002/bit.10472
Doane A, Hu W, Yang W, Wiltberger K, Peng H (2016) Implementation of a recirculating TFF N-1 perfusion system at manufacturing scale: conquering process hurdles and scaling challenges. In: Cell culture engineering XV
Padawer I, Ling WLW, Bai YJBP (2013) Case study: an accelerated 8-day monoclonal antibody production process based on high seeding densities. Biotechnol Prog 29(3):829–832
doi: 10.1002/btpr.1719
Woodgate JM (2018) Perfusion N-1 culture—opportunities for process intensification. Biopharmaceutical Processing. Elsevier, Amsterdam, pp 755–768
doi: 10.1016/B978-0-08-100623-8.00037-2
Gomme PT et al (2006) Effect of lobe pumping on human albumin: development of a lobe pump simulator using smoothed particle hydrodynamics 1. Biotechnol Appl Biochem 43(2):113–120
doi: 10.1042/BA20050188
Kamaraju H, Wetzel K, Kelly WJJBP (2010) Modeling shear-induced CHO cell damage in a rotary positive displacement pump. Biotechnol Prog 26(6):1606–1615
doi: 10.1002/btpr.479
(2002) Alfa-laval pump handbook, 2nd edn. Available: https://www.fwwebb.com/docs/pumps/Support/alfa-laval-pump-manual.pdf
Kelly W et al (2014) Understanding and modeling alternating tangential flow filtration for perfusion cell culture. Biotechnol Prog 30(6):1291–1300
doi: 10.1002/btpr.1953
Konstantinov K et al (2006) The “push-to-low” approach for optimization of high-density perfusion cultures of animal cells. Cell culture engineering. Springer, Berlin, pp 75–98
doi: 10.1007/10_016
Marx N (2015) Evaluation of scaling parameters towards an improved process development strategy for CHO cell perfusion cultures-step-wise scale-up from 15 mL to 5 L. Hochschule für angewandte Wissenschaften Hamburg, Hamburg
Raghunath B, Pattanaik P, Janssens JJBJ (2012) "Best practices for optimization and scale-up of microfiltration TFF processes. BioProcessing 11(1):30–40
doi: 10.12665/J111.Raghunath
Johnstone P, Mast E, Hughes E, Peng HJBP (2020) Development of a small-scale rotary lobe-pump cell culture model for examining cell damage in large-scale N-1 seed perfusion process. Biotechnol Prog 36(6):e3044
doi: 10.1002/btpr.3044
Wang S, Godfrey S, Ravikrishnan J, Lin H, Vogel J, Coffman JJJOB (2017) Shear contributions to cell culture performance and product recovery in ATF and TFF perfusion systems. J Biotechnol 246:52–60
doi: 10.1016/j.jbiotec.2017.01.020
Soos M, Ehrl L, Bäbler MUU, Morbidelli MJL (2010) Aggregate breakup in a contracting nozzle. Langmuir 26(1):10–18
doi: 10.1021/la903982n
M Kuschel (2021) Shedding light on large scale processes—application of CFD models in cell culture and validation procedures. In: presented at the BioTalk 2021
Falk RF, Marziano I, Kougoulos T, Girard KPJOPR (2011) Prediction of agglomerate type during scale-up of a batch crystallization using computational fluid dynamics models. Process Res Develop 15(6):1297–1304
doi: 10.1021/op200152u
Rathore A, Sharma C, Persad AA (2012) Use of computational fluid dynamics as a tool for establishing process design space for mixing in a bioreactor. Biotech Prog 28(2):382–391
doi: 10.1002/btpr.745
Sharma C, Malhotra D, Rathore AJBP (2011) Review of computational fluid dynamics applications in biotechnology processes. Bioteech Prog 27(6):1497–1510
doi: 10.1002/btpr.689
Villiger TK et al (2018) Experimental and CFD physical characterization of animal cell bioreactors: from micro-to production scale. Biochem Eng J 131:84–94
doi: 10.1016/j.bej.2017.12.004
Johnson C, Natarajan V, Antoniou CJBP (2014) Verification of energy dissipation rate scalability in pilot and production scale bioreactors using computational fluid dynamics. Biotechnol Prog 30(3):760–764
doi: 10.1002/btpr.1896
Babnik S, Erkalvec Zajec V, Oblak B, Likozar B, Pohar A (2020) A review of computational fluid dynamics (CFD) simulations of mixing in the pharmaceutical industry. Biomed J Sci Tech Res 3(27):20732–20736
Chisti YJC (2001) Hydrodynamic damage to animal cells. Crit Rev Biotechnol 21(2):67–110
doi: 10.1080/20013891081692
Amer M, Feng Y, Ramsey JDJBP (2019) Using CFD simulations and statistical analysis to correlate oxygen mass transfer coefficient to both geometrical parameters and operating conditions in a stirred-tank bioreactor. Biotechnol Prog 35(3):e2785
doi: 10.1002/btpr.2785
Ebrahimi M, Tamer M, Villegas RM, Chiappetta A, Ein-Mozaffari FJP (2019) Application of CFD to analyze the hydrodynamic behaviour of a bioreactor with a double impeller. Processes 7(10):694
doi: 10.3390/pr7100694
Gimbun J, Rielly CD, Nagy ZKJ (2009) Modelling of mass transfer in gas–liquid stirred tanks agitated by Rushton turbine and CD-6 impeller: a scale-up study. Chem Eng Res Des 87(4):437–451
doi: 10.1016/j.cherd.2008.12.017
Joshi J, Sahu A, Kumar P (1998) LDA measurements and CFD simulations of flow generated by impellers in mechanically agitated reactors. Sadhana 23(5):505–539
doi: 10.1007/BF02744577
Laakkonen M, Moilanen P, Alopaeus V, Aittamaa JJ (2007) Modelling local bubble size distributions in agitated vessels. Chem Eng Sci 62(3):721–740
doi: 10.1016/j.ces.2006.10.006
Laakkonen M, Moilanen P, Alopaeus V, Aittamaa JJ (2007) Modelling local gas–liquid mass transfer in agitated vessels. Chem Eng Res Des 85(5):665–675
doi: 10.1205/cherd06171
Löffelholz C, Kaiser SC, Werner S, Eibl D (2010) CFD as a tool to characterize single-use bioreactors. In: Eibl R, Eibl D (eds) Single-use technology in biopharmaceutical manufacture: Eibl/single-use. Wiley, Hoboken, pp 263–279
Placek J, Tavlarides LL, Smith G, Fořt I (1986) Turbulent flow in stirred tanks. Part II: a two-scale model of turbulence. AIChE J 32(11):1771–1786
doi: 10.1002/aic.690321103
Li Y-B, Guo D-S, Li X-B (2018) Mitigation of radial exciting force of rotary lobe pump by gradually varied gap. Eng Appl Comput Fluid Mech 12(1):711–723
Schiffer J (2012) A comparison of CFD-calculations and measurements of the fluid flow in rotating displacement pumps. In: International rotating equipment conference, 2012, pp 417–426
Villiger TK, Morbidelli M, Soos M (2015) Experimental determination of maximum effective hydrodynamic stress in multiphase flow using shear sensitive aggregates. AIChE J 61(5):1735–1744
doi: 10.1002/aic.14753
ANSYS FLUENT (2009) 12.0 Documentation Ansys Inc.
ANSYS CFX (2010) Release 11.0: ANSYS CFX-solver theory guide. ANSYS Inc., Canonsburg, PA, USA