Skip to main content

Euler-Lagrangian Simulations: A Proper Tool for Predicting Cellular Performance in Industrial Scale Bioreactors

  • Chapter
  • First Online:
Digital Twins

Abstract

Eulerian-Lagrangian approach to investigate cellular responses in a bioreactor has become the center of attention in recent years. It was introduced to biotechnological processes about two decades ago, but within the last few years, it proved itself as a powerful tool to address scale-up and -down topics of bioprocesses. It can capture the history of a cell and reveal invaluable information for, not only, bioprocess control and design but also strain engineering. This way it will be possible to shed light on the actual environment that cell experiences throughout its lifespan. Lifelines of a microorganism in a bioreactor can serve as the missing link that encompasses the biological timescales and the physical timescales. For this purpose digitalization of bioreactors provides us with new insights that are not achievable in industrial reactors easily if at all, namely, substrate and product gradients; high-shear regions are among the most interesting factors that can be reproduced adequately with help of a digital twin. In this chapter basic principles of this method will be introduced, and later on some practical aspects of particle tracking technique will be illustrated. In the final section, some of the advantages and challenges associated with this method will be discussed.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lara AR, Galindo E, Ramírez OT, Palomares LA (2006) Living with heterogeneities in bioreactors: understanding the effects of environmental gradients on cells. Mol Biotechnol 34(3):355–381. https://doi.org/10.1385/MB:34:3:355

    Article  CAS  PubMed  Google Scholar 

  2. Zieringer J, Takors R (2018) In silico prediction of large-scale microbial production performance: constraints for getting proper data-driven models. Comput Struct Biotechnol J 16:246–256. https://doi.org/10.1016/j.csbj.2018.06.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Breuer M, Lakehal D, Rodi W (1995) Flow around a surface mounted cubical obstacle: comparison of les rans-results. In: IMACS/COST conference on CFD, 3D complex flows, Lausanne 1995

    Google Scholar 

  4. Larsson G, Törnkvist M, Ståhl Wernersson E, Trägårdh C, Noorman H, Enfors SO (1996) Substrate gradients in bioreactors: origin and consequences. Bioprocess Eng 14(6):281–289. https://doi.org/10.1007/BF00369471

    Article  CAS  Google Scholar 

  5. Buchholz J, Graf M, Freund A, Busche T, Kalinowski J, Blombach B, Takors R (2014) CO 2 /HCO 3− perturbations of simulated large scale gradients in a scale-down device cause fast transcriptional responses in Corynebacterium glutamicum. Appl Microbiol Biotechnol 98(20):8563–8572. https://doi.org/10.1007/s00253-014-6014-y

    Article  CAS  PubMed  Google Scholar 

  6. Löffler M, Simen JD, Jäger G, Schäferhoff K, Freund A, Takors R (2016) Engineering E. coli for large-scale production – strategies considering ATP expenses and transcriptional responses. Metab Eng 38:73–85. https://doi.org/10.1016/j.ymben.2016.06.008

    Article  CAS  PubMed  Google Scholar 

  7. Neubauer P, Häggström L, Enfors S-O (1995) Influence of substrate oscillations on acetate formation and growth yield in Escherichia coli glucose limited fed-batch cultivations. Biotechnol Bioeng 47(2):139–146. https://doi.org/10.1002/bit.260470204

    Article  CAS  PubMed  Google Scholar 

  8. Oosterhuis NMG, Kossen NWF (1984) Dissolved oxygen concentration profiles in a production-scale bioreactor. Biotechnol Bioeng 26(5):546–550. https://doi.org/10.1002/bit.260260522

    Article  CAS  PubMed  Google Scholar 

  9. Simen JD, Löffler M, Jäger G, Schäferhoff K, Freund A, Matthes J, Müller J et al (2017) Transcriptional response of Escherichia coli to ammonia and glucose fluctuations. Microb Biotechnol 10(4):858–872. https://doi.org/10.1111/1751-7915.12713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Teleki A, Sánchez-Kopper A, Takors R (2015) Alkaline conditions in hydrophilic interaction liquid chromatography for intracellular metabolite quantification using tandem mass spectrometry. Anal Biochem 475:4–13. https://doi.org/10.1016/j.ab.2015.01.002

    Article  CAS  PubMed  Google Scholar 

  11. von Wulffen J, Ulmer A, Jäger G, Sawodny O, Feuer R (2017) Rapid sampling of Escherichia coli after changing oxygen conditions reveals transcriptional dynamics. Genes 8(3). https://doi.org/10.3390/genes8030090

  12. Haringa C, Deshmukh AT, Mudde RF, Noorman HJ (2017a) Euler-Lagrange analysis towards representative down-scaling of a 22 M3 Aerobic S. cerevisiae fermentation. Chem Eng Sci 170:653–669. https://doi.org/10.1016/j.ces.2017.01.014

    Article  CAS  Google Scholar 

  13. Haringa C, Mudde RF, Noorman HJ (2018a) From industrial fermentor to CFD-guided downscaling: what have we learned? Biochem Eng J 140(April):57–71. https://doi.org/10.1016/j.bej.2018.09.001

    Article  CAS  Google Scholar 

  14. Haringa C, Noorman HJ, Mudde RF (2017b) Lagrangian modeling of hydrodynamic–kinetic interactions in (bio)chemical reactors: practical implementation and setup guidelines. Chem Eng Sci 157:159–168. https://doi.org/10.1016/j.ces.2016.07.031

    Article  CAS  Google Scholar 

  15. Kuschel M, Siebler F, Takors R (2017) Lagrangian trajectories to predict the formation of population heterogeneity in large-scale bioreactors. Bioengineering 4(4):27. https://doi.org/10.3390/bioengineering4020027

    Article  CAS  PubMed Central  Google Scholar 

  16. Wang G, Haringa C, Tang W, Noorman H, Chu J, Zhuang Y, Zhang S (2020) Coupled metabolic-hydrodynamic modeling enabling rational scale-up of industrial bioprocesses. Biotechnol Bioeng 117(3):844–867. https://doi.org/10.1002/bit.27243

    Article  CAS  PubMed  Google Scholar 

  17. Nieß A, Löffler M, Simen JD, Takors R (2017) Repetitive short-term stimuli imposed in poor mixing zones induce long-term adaptation of E. Coli cultures in large-scale bioreactors: experimental evidence and mathematical model. Front Microbiol 8(Jun):1–9. https://doi.org/10.3389/fmicb.2017.01195

    Article  Google Scholar 

  18. Zieringer J, Takors R (2020) Data-driven in-silico prediction of regulation heterogeneity and ATP demands of Escherichia coli in large-scale bioreactors

    Google Scholar 

  19. Morchain J, Gabelle JC, Cockx A (2014) A coupled population balance model and CFD approach for the simulation of mixing issues in lab-scale and industrial bioreactors. AICHE J 60(1):27–40. https://doi.org/10.1002/aic.14238

    Article  CAS  Google Scholar 

  20. Morchain J, Pigou M, Lebaz N (2017) A population balance model for bioreactors combining interdivision time distributions and micromixing concepts. Biochem Eng J 126:135–145. https://doi.org/10.1016/j.bej.2016.09.005

    Article  CAS  Google Scholar 

  21. Pigou M, Morchain JÔ (2015) Investigating the interactions between physical and biological heterogeneities in bioreactors using compartment, population balance and metabolic models. Chem Eng Sci 126(April):267–282. https://doi.org/10.1016/j.ces.2014.11.035

    Article  CAS  Google Scholar 

  22. Haringa C, Tang W, Wang G, Deshmukh AT, van Winden WA, Chu J, van Gulik WM, Heijnen JJ, Mudde RF, Noorman HJ (2018b) Computational fluid dynamics simulation of an industrial P. chrysogenum fermentation with a coupled 9-pool metabolic model: towards rational scale-down and design optimization. Chem Eng Sci 175:12–24. https://doi.org/10.1016/j.ces.2017.09.020

    Article  CAS  Google Scholar 

  23. Haringa C, Vandewijer R, Mudde RF (2018c) Inter-compartment interaction in multi-impeller mixing: part i. experiments and multiple reference frame CFD. Chem Eng Res Des 136(June):870–885. https://doi.org/10.1016/j.cherd.2018.06.005

    Article  CAS  Google Scholar 

  24. Haringa C, Vandewijer R, Mudde RF (2018d) Inter-compartment interaction in multi-impeller mixing. Part ii. Experiments, sliding mesh and large eddy simulations. Chem Eng Res Des 136(June):886–899. https://doi.org/10.1016/j.cherd.2018.06.007

    Article  CAS  Google Scholar 

  25. Siebler F, Lapin A, Hermann M, Takors R (2019) The impact of CO gradients on C. ljungdahlii in a 125 m3 bubble column: mass transfer, circulation time and lifeline analysis. Chem Eng Sci 207:410–423. https://doi.org/10.1016/j.ces.2019.06.018

    Article  CAS  Google Scholar 

  26. Kuschel M, Takors R (2020) Simulated oxygen and glucose gradients as a prerequisite for predicting industrial scale performance a priori

    Google Scholar 

  27. Heins AL, Fernandes RL, Gernaey KV, Lantz AE (2015) Experimental and in silico investigation of population heterogeneity in continuous Saccharomyces cerevisiae scale-down fermentation in a two-compartment setup. J Chem Technol Biotechnol 90(2):324–340. https://doi.org/10.1002/jctb.4532

    Article  CAS  Google Scholar 

  28. Wang T, Wang J, Jin Y (2005) Population balance model for gas - liquid flows: influence of bubble coalescence and breakup models. Ind Eng Chem Res 44(19):7540–7549. https://doi.org/10.1021/ie0489002

    Article  CAS  Google Scholar 

  29. Venneker BCH, Derksen JJ, Van den Akker HEA (2002) Population balance modeling of aerated stirred vessels based on CFD. AICHE J 48(4):673–685. https://doi.org/10.1002/aic.690480404

    Article  CAS  Google Scholar 

  30. Lapin A, Schmid J, Reuss M (2006) Modeling the dynamics of E. coli populations in the three-dimensional turbulent field of a stirred-tank bioreactor-A structured-segregated approach. Chem Eng Sci 61(14):4783–4797. https://doi.org/10.1016/j.ces.2006.03.003

    Article  CAS  Google Scholar 

  31. Dehbi A (2008) A CFD model for particle dispersion in turbulent boundary layer flows. Nucl Eng Des 238(3):707–715. https://doi.org/10.1016/j.nucengdes.2007.02.055

    Article  CAS  Google Scholar 

  32. Haringa C, Tang W, Deshmukh AT, Xia J, Reuss M, Heijnen JJ, Mudde RF, Noorman HJ (2016) Euler-Lagrange computational fluid dynamics for (bio)reactor scale down: an analysis of organism lifelines. Eng Life Sci 16(7):652–663. https://doi.org/10.1002/elsc.201600061

    Article  CAS  PubMed  Google Scholar 

  33. Liu Y, Wang ZJ, Xia JY, Haringa C, Liu YP, Chu J, Zhuang YP, Zhang SL (2016) Application of Euler–Lagrange CFD for quantitative evaluating the effect of shear force on Carthamus tinctorius L. cell in a stirred tank bioreactor. Biochem Eng J 114:209–217. https://doi.org/10.1016/j.bej.2016.07.006

    Article  CAS  Google Scholar 

  34. Gunyol O, Mudde RF (2009) Computational study of hydrodynamics of a standard stirred tank reactor and a large-scale multi-impeller fermenter. Int J Multiscale Comput Eng:559–576. https://doi.org/10.1615/IntJMultCompEng.v7.i6.60

  35. Coroneo M, Montante G, Paglianti A, Magelli F (2011) CFD prediction of fluid flow and mixing in stirred tanks: numerical issues about the RANS simulations. Comput Chem Eng 35(10):1959–1968. https://doi.org/10.1016/j.compchemeng.2010.12.007

    Article  CAS  Google Scholar 

  36. Lapin A, Müller D, Reuss M (2004) Dynamic behavior of microbial populations in stirred bioreactors simulated with Euler-Lagrange methods: traveling along the lifelines of single cells. Ind Eng Chem Res 43(16):4647–4656. https://doi.org/10.1021/ie030786k

    Article  CAS  Google Scholar 

  37. Ducci A, Yianneskis M (2005) Direct determination of energy dissipation in stirred vessels with two-point LDA. AICHE J 51(8):2133–2149. https://doi.org/10.1002/aic.10468

    Article  CAS  Google Scholar 

  38. Chaouat B (2017) The state of the art of hybrid RANS/LES modeling for the simulation of turbulent flows. Flow Turbul Combust 99(2):279–327. https://doi.org/10.1007/s10494-017-9828-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Fröhlich J, von Terzi D (2008) Hybrid LES/RANS methods for the simulation of turbulent flows. Prog Aerosp Sci 44(5):349–377. https://doi.org/10.1016/j.paerosci.2008.05.001

    Article  Google Scholar 

  40. Sweere APJ, Janse L, Luyben KCAM, Kossen NWF (1988a) Experimental simulation of oxygen profiles and their influence on Baker’s yeast production: II. Two-fermentor system. Biotechnol Bioeng 31(6):579–586. https://doi.org/10.1002/bit.260310610

    Article  CAS  PubMed  Google Scholar 

  41. Sweere APJ, Giesselbach J, Barendse R, de Krieger R, Honderd G, Luyben KCAM (1988c) Modelling the dynamic behaviour of Saccharomyces cerevisiae and its application in control experiments. Appl Microbiol Biotechnol 28(2):116–127. https://doi.org/10.1007/BF00694298

    Article  CAS  Google Scholar 

  42. Sweere APJ, Matla YA, Zandvliet J, Ch K, Luyben AM, Kossen NWF (1988d) Experimental simulation of glucose fluctuations - the influence of continually changing glucose concentrations on the fed-batch Baker’s yeast production. Appl Microbiol Biotechnol 28(2):109–115. https://doi.org/10.1007/BF00694297

    Article  CAS  Google Scholar 

  43. Pham HTB, Larsson G, Enfors SO (1998) Growth and energy metabolism in aerobic fed-batch cultures of Saccharomyces cerevisiae: simulation and model verification. Biotechnol Bioeng 60(4):474–482. https://doi.org/10.1002/(SICI)1097-0290(19981120)60:4<474::AID-BIT9>3.0.CO;2-J

    Article  CAS  PubMed  Google Scholar 

  44. Serio M, Di RT, Santacesaria E (2001) A kinetic and mass transfer model to simulate the growth of Baker’s yeast in industrial bioreactors. Chem Eng J 82(1–3):347–354. https://doi.org/10.1016/S1385-8947(00)00353-3

    Article  Google Scholar 

  45. Wright MR, Bach C, Gernaey KV, Krühne U (2018) Investigation of the effect of uncertain growth kinetics on a CFD based model for the growth of S. cerevisiae in an industrial bioreactor. Chem Eng Res Des 140:12–22. https://doi.org/10.1016/j.cherd.2018.09.040

    Article  CAS  Google Scholar 

  46. Sokolichin A, Eigenberger G, Lapin A, Lübbert A (1997) Dynamic numerical simulation of gas-liquid two-phase flows: Euler/Euler versus Euler/Lagrange. Chem Eng Sci 52(4):611–626. https://doi.org/10.1016/S0009-2509(96)00425-3

    Article  CAS  Google Scholar 

  47. Ireland PJ, Desjardins O (2017) Improving particle drag predictions in Euler–Lagrange simulations with two-way coupling. J Comput Phys 338:405–430. https://doi.org/10.1016/j.jcp.2017.02.070

    Article  CAS  Google Scholar 

  48. Linkès M, Fede P, Morchain JÔ, Schmitz P (2014) Numerical investigation of subgrid mixing effects on the calculation of biological reaction rates. Chem Eng Sci 116:473–485. https://doi.org/10.1016/j.ces.2014.05.005

    Article  CAS  Google Scholar 

  49. Löffler M, Simen JD, Müller J, Jäger G, Laghrami S, Schäferhoff K, Freund A, Takors R (2017) Switching between nitrogen and glucose limitation: unraveling transcriptional dynamics in Escherichia coli. J Biotechnol 258(April):2–12. https://doi.org/10.1016/j.jbiotec.2017.04.011

    Article  CAS  PubMed  Google Scholar 

  50. Liné A, Gabelle JC, Morchain J, Anne-Archard D, Augier F (2013) On POD analysis of PIV measurements applied to mixing in a stirred vessel with a shear thinning fluid. Chem Eng Res Des 91(11):2073–2083. https://doi.org/10.1016/j.cherd.2013.05.002

    Article  CAS  Google Scholar 

  51. Noorman H (2011) An industrial perspective on bioreactor scale-down: what we can learn from combined large-scale bioprocess and model fluid studies. Biotechnol J 6(8):934–943. https://doi.org/10.1002/biot.201000406

    Article  CAS  PubMed  Google Scholar 

  52. Clift R, Grace JR, Weber ME (2005) Bubbles, drops, and particles. In: Clift R, Grace JR, Weber ME (eds) Dover books on engineering. Dover, Mineola

    Google Scholar 

  53. Lamont JC, Scott DS (1970) An eddy cell model of mass transfer into the surface of a turbulent liquid. AICHE J 16(4):513–519. https://doi.org/10.1002/aic.690160403

    Article  CAS  Google Scholar 

  54. Roels JA (1983) Roels JA (ed) Energetics and kinetics in biotechnology. Elsevier Biomedical Press, Amsterdam

    Google Scholar 

  55. Senn H, Lendenmann U, Snozzi M, Hamer G, Egli T (1994) Biochi ~ Mic ~ a et biophysica A ~ Ta the growth of Escherichia coli in glucose-limited chemostat cultures: a re-examination of the kinetics. Sci Technol 1201:424–436

    Google Scholar 

  56. Kita K, Konishi K, Anraku Y (1984) Terminal oxidases of Escherichia coli aerobic respiratory chain. J Biol Chem 259(5):3368–3374

    Article  CAS  Google Scholar 

  57. Valgepea K, Adamberg K, Vilu R (2011) Decrease of energy spilling in Escherichia coli continuous cultures with rising specific growth rate and carbon wasting. BMC Syst Biol 5. https://doi.org/10.1186/1752-0509-5-106

  58. Jain R, Srivastava R (2009) Metabolic investigation of host/pathogen interaction using MS2-infected Escherichia coli. BMC Syst Biol 3. https://doi.org/10.1186/1752-0509-3-121

  59. Hewitt CJ, Von Caron GN, Axelsson B, McFarlane CM, Nienow AW (2000) Studies related to the scale-up of high-cell-density E. coli fed-batch fermentations using multiparameter flow cytometry: effect of a changing microenvironment with respect to glucose and dissolved oxygen concentration. Biotechnol Bioeng 70(4):381–390. https://doi.org/10.1002/1097-0290(20001120)70:4<381::AID-BIT3>3.0.CO;2-0

    Article  CAS  PubMed  Google Scholar 

  60. Takors R (2012) Scale-up of microbial processes: impacts, tools and open questions. J Biotechnol 160(1–2):3–9. https://doi.org/10.1016/j.jbiotec.2011.12.010

    Article  CAS  PubMed  Google Scholar 

  61. Ankenbauer A, Schäfer RA, Viegas SC, Pobre V, Voß B, Arraiano CM, Takors R (2020) Pseudomonas putida KT2440 is naturally endowed to withstand industrial-scale stress conditions. Microb Biotechnol:635536. https://doi.org/10.1111/1751-7915.13571

  62. Delvigne F, Takors R, Mudde R, van Gulik W, Noorman H (2017) Bioprocess scale-up/down as integrative enabling technology: from fluid mechanics to systems biology and beyond. Microb Biotechnol 10(5):1267–1274. https://doi.org/10.1111/1751-7915.12803

    Article  PubMed  PubMed Central  Google Scholar 

  63. George S, Larsson G, Enfors SO (1993) A scale-down two-compartment reactor with controlled substrate oscillations: metabolic response of Saccharomyces cerevisiae. Bioprocess Eng 9(6):249–257. https://doi.org/10.1007/BF01061530

    Article  CAS  Google Scholar 

  64. Sweere APJ, Mesters JR, Janse L, Luyben KCAM, Kossen NWF (1988b) Experimental simulation of oxygen profiles and their influence on Baker’s yeast production: I. One-fermentor system. Biotechnol Bioeng 31(6):567–578. https://doi.org/10.1002/bit.260310609

    Article  CAS  PubMed  Google Scholar 

  65. Enfors SO, Jahic M, Rozkov A, Xu B, Hecker M, Jürgen B, Krüger E et al (2001) Physiological responses to mixing in large scale bioreactors. J Biotechnol 85(2):175–185. https://doi.org/10.1016/S0168-1656(00)00365-5

    Article  CAS  PubMed  Google Scholar 

  66. Delvigne F, Lejeune A, Destain J, Thonart P (2006) Stochastic models to study the impact of mixing on a fed-batch culture of Saccharomyces cerevisiae. Biotechnol Prog 22(1):259–269. https://doi.org/10.1021/bp050255m

    Article  CAS  PubMed  Google Scholar 

  67. Sastre R, Rosa ZC, Perner-Nochta I, Fleck-Schneider P, Posten C (2007) Scale-down of microalgae cultivations in tubular photo-bioreactors-A conceptual approach. J Biotechnol 132(2):127–133. https://doi.org/10.1016/j.jbiotec.2007.04.022

    Article  CAS  Google Scholar 

  68. Neubauer P, Junne S (2010) Scale-down simulators for metabolic analysis of large-scale bioprocesses. Curr Opin Biotechnol 21(1):114–121. https://doi.org/10.1016/j.copbio.2010.02.001

    Article  CAS  PubMed  Google Scholar 

  69. Paul K, Herwig C (2020) Scale-down simulators for mammalian cell culture as tools to access the impact of inhomogeneities occurring in large-scale bioreactors. Eng Life Sci 20(5–6):197–204. https://doi.org/10.1002/elsc.201900162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Tang W, Deshmukh AT, Haringa C, Wang G, van Gulik W, van Winden W, Reuss M et al (2017) A 9-pool metabolic structured kinetic model describing days to seconds dynamics of growth and product formation by Penicillium chrysogenum. Biotechnol Bioeng 114(8):1733–1743. https://doi.org/10.1002/bit.26294

    Article  CAS  PubMed  Google Scholar 

  71. Lei F, Rotboll M, Jorgensen SB (2001) A biochemically structured model for Saccharomyces cerevisiae. J Biotechnol 88(3):205–221. https://doi.org/10.1016/S0168-1656(01)00269-3

    Article  CAS  PubMed  Google Scholar 

  72. Rizzi M, Baltes M, Theobald U, Reuss M (1997) In vivo analysis of metabolic dynamics in Saccharomyces cerevisiae: II. Mathematical model. Biotechnol Bioeng 55(4):592–608. https://doi.org/10.1002/(SICI)1097-0290(19970820)55:4<592::AID-BIT2>3.0.CO;2-C

    Article  CAS  PubMed  Google Scholar 

  73. Vanrolleghem PA, De Jong-Gubbels P, Van Gulik WM, Pronk JT, Van Dijken JP, Heijnen S (1996) Validation of a metabolic network for Saccharomyces cerevisiae using mixed substrate studies. Biotechnol Prog 12(4):434–448. https://doi.org/10.1021/bp960022i

    Article  CAS  PubMed  Google Scholar 

  74. Bailey J, Bailey JE, Ollis DF, Simpson RJ, Ollis DF (1986) Biochemical engineering fundamentals. McGraw-Hill chemical engineering series. McGraw-Hill. https://books.google.de/books?id=KM9TAAAAMAAJ

Download references

Acknowledgments

This work was partially supported by the German Federal Ministry of Education and Research (BMBF), grant number: FKZ 031B0629.

Abbreviations and Nomenclatures

CFD:

Computational fluid dynamics

DNS:

Direct numerical simulation

DO:

Dissolved oxygen

EL:

Euler-Lagrange

LES:

Large eddy simulation

NSE:

Navier-Stokes equations

PBM:

Population balance model

PFR:

Plug flow reactor

RANS:

Reynolds-averaged Navier-Stokes

STR:

Stirred tank reactor

UDF:

User-defined function

a :

Bubble surface

C glucose :

Glucose concentration

\( {C}_{O_2} \) :

Dissolved oxygen concentration

\( {C}_{O_2}^{\ast } \) :

Equilibrium oxygen concentration

C x :

Biomass concentration

d p :

Bubble diameter

D :

Diffusion coefficient

k :

Turbulent kinetic energy

k l :

Mass transfer coefficient

K glucose :

Saturation constant for glucose

K oxygen :

Saturation constant for oxygen

N :

Agitation rate

P :

Bioreactor power input

q s :

Specific substrate uptake rate

q s, max :

Maximum specific substrate uptake rate

\( {q}_{O_2} \) :

Specific oxygen uptake rate

\( {q}_{O_2,\max } \) :

Maximum specific oxygen uptake rate

St :

Stokes number

V :

Bioreactor volume

\( {Y}_{\frac{x}{s}} \) :

Biomass yield

\( {Y}_{\frac{o}{s}} \) :

Oxygen yield

ε :

Turbulent kinetic energy dissipation rate

μ :

Growth rate

μ max :

Maximum growth rate

μ liquid :

Molecular viscosity

ν :

Kinematic viscosity

ρ p :

Bubble density

τ mix :

Bioreactor mixing time

τ fluid :

Fluid timescale

τ p :

Bubble timescale

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ralf Takors .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hajian, C.S.S., Zieringer, J., Takors, R. (2020). Euler-Lagrangian Simulations: A Proper Tool for Predicting Cellular Performance in Industrial Scale Bioreactors. In: Herwig, C., Pörtner, R., Möller, J. (eds) Digital Twins. Advances in Biochemical Engineering/Biotechnology, vol 177. Springer, Cham. https://doi.org/10.1007/10_2020_133

Download citation

Publish with us

Policies and ethics