Skip to main content
Log in

Strategies and engineering aspects on the scale-up of bioreactors for different bioprocesses

  • Review
  • Published:
Systems Microbiology and Biomanufacturing Aims and scope Submit manuscript

Abstract

Bioreactors are central equipment used in the majority of bioprocesses. Different models of bioreactors have been developed for different processes, which can be applied either for submerged or for solid-state fermentation. Scale-up involves the development of bioprocess in bench, pilot, and industrial scales. Optimal conditions are first screened and determined in the bench scale and so that the process can be transferred to a larger scale. This transferring requires the proper reproduction of conditions and performance, being a major challenge since important aspects, such as aeration and agitation, are critical for cells development. In this case, scale-up strategies are employed to maintain bioprocesses’ performance. These strategies are based on geometric similarity aspects of bioreactors, agitation, and aeration conditions, which must follow the requirements of each bioprocess and the used microorganisms. Operational conditions significantly impact cell growth and, consequently, the biosynthesis of different biomolecules, which must then be reproduced at higher scales. For this purpose, one or more operating factors can be maintained constant during scale-up with the possibility to predict, for example, the power consumption of large-scale bioreactors or aeration conditions in an aerobic culture. This review presents the most employed bioreactors’ scale-up strategies. In addition, the scale-up of other bioreactors models, such as pneumatic and solid-state fermentation bioreactor and even photobioreactors, will also be described with some examples.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Availability of data and materials

Not applicable.

References

  1. Galimberti A, Bruno A, Agostinetto G, et al. Fermented food products in the era of globalization: tradition meets biotechnology innovations. Curr Opin Biotechnol. 2021;70:36–41. https://doi.org/10.1016/j.copbio.2020.10.006.

    Article  CAS  PubMed  Google Scholar 

  2. Kohli K, Prajapati R, Sharma BK. Bio-based chemicals from renewable biomass for integrated biorefineries. Energies (Basel). 2019. https://doi.org/10.3390/en12020233.

    Article  Google Scholar 

  3. de Vandenberghe LPS, Herrmann LW, de Penha RO, et al. Engineering aspects for scale-up of bioreactors. In: Current developments in biotechnology and bioengineering: advances in bioprocess engineering. Elsevier; 2022. p. 59–85. https://doi.org/10.1016/B978-0-323-91167-2.00002-2.

    Chapter  Google Scholar 

  4. Shao X, Lynd L, Bakker A, et al. Reactor scale up for biological conversion of cellulosic biomass to ethanol. Bioprocess Biosyst Eng. 2010;33:485–93. https://doi.org/10.1007/s00449-009-0357-2.

    Article  CAS  PubMed  Google Scholar 

  5. Lee K-M, DavidF G. Statistical experimental design for bioprocess modeling and optimization analysis. Appl Biochem Biotechnol. 2006;135:101–35.

    Article  CAS  PubMed  Google Scholar 

  6. Wynn JP, Hanchar R, Kleff S, et al. Biobased technology commercialization: the importance of lab to pilot scale-up. In: Metabolic engineering for bioprocess commercialization. Cham: Springer International Publishing; 2016. p. 101–19.

    Chapter  Google Scholar 

  7. Zhong JJ. Recent advances in bioreactor engineering. Korean J Chem Eng. 2010;27:1035–41. https://doi.org/10.1007/s11814-010-0277-5.

    Article  CAS  Google Scholar 

  8. Yang Y, Sha M. A beginner’s guide to bioprocess modes-batch, fed-batch, and continuous fermentation. Eppendorf. 2019;408:1–16.

    Google Scholar 

  9. Srivastava AK, Gupta S. Fed-batch fermentation—design strategies. 2nd ed. Elsevier B.V; 2011.

    Google Scholar 

  10. Mishra SS, Behera SS, Bari ML, et al. Microbial bioprocessing of health promoting food supplements. In: Microbial biotechnology in food and health. Academic Press; 2020. p. 113–41. https://doi.org/10.1016/B978-0-12-819813-1.00005-0.

    Chapter  Google Scholar 

  11. Doran PM. Bioprocess engineering principles. 2nd ed. Academic Press; 2013. https://doi.org/10.1016/C2009-0-22348-8.

    Book  Google Scholar 

  12. Behl M, Thakar S, Ghai H, et al. Basic biotechniques for bioprocess and chapter 21 - fundamentals of fermentation technology. Academic Press; 2023. p. 1–2.

    Google Scholar 

  13. Franco-Lara E, Weuster-Botz D. Estimation of optimal feeding strategies for fed-batch bioprocesses. Bioprocess Biosyst Eng. 2005;27:255–62. https://doi.org/10.1007/s00449-005-0415-3.

    Article  CAS  PubMed  Google Scholar 

  14. Mears L, Stocks SM, Sin G, Gernaey KV. A review of control strategies for manipulating the feed rate in fed-batch fermentation processes. J Biotechnol. 2017;245:34–46. https://doi.org/10.1016/j.jbiotec.2017.01.008.

    Article  CAS  PubMed  Google Scholar 

  15. Chang L, Liu X, Henson MA. Nonlinear model predictive control of fed-batch fermentations using dynamic flux balance models. J Process Control. 2016;42:137–49. https://doi.org/10.1016/j.jprocont.2016.04.012.

    Article  CAS  Google Scholar 

  16. Mitra S, Murthy GS. Bioreactor control systems in the biopharmaceutical industry: a critical perspective. Syst Microbiol Biomanuf. 2022;2:91–112. https://doi.org/10.1007/s43393-021-00048-6.

    Article  CAS  Google Scholar 

  17. Lindskog EK. The upstream process: principal modes of operation. Elsevier Ltd; 2018.

    Google Scholar 

  18. Foutch GL, Johannes AH. Reactors in process engineering. In: Encyclopedia of physical science and technology. Elsevier; 2003. p. 23–43.

    Chapter  Google Scholar 

  19. Zhu Y. Immobilized cell fermentation for production of chemicals and fuels. In: Bioprocessing for value-added products from renewable resources: new technologies and applications. Elsevier; 2006. p. 373–96. https://doi.org/10.1016/B978-044452114-9/50015-3.

    Chapter  Google Scholar 

  20. Ingledew WMM, Lin YH. Ethanol from starch-based feedstocks. 2nd ed. Elsevier B.V; 2011.

    Google Scholar 

  21. Fardelone LC, Silveira GC, de Jesus TSB, et al. Production of organic acids by batch fermentations. In: Smart innovation systems and technologies. Cham: Springer; 2021. p. 647–53.

    Google Scholar 

  22. Brautaset T, Ellingsen TE. Lysine: industrial uses and production. 2nd ed. Elsevier B.V; 2011.

    Google Scholar 

  23. Stanley A, Punil Kumar HN, Mutturi S, Vijayendra SVN. Fed-batch strategies for production of PHA using a native isolate of Halomonas venusta KT832796 strain. Appl Biochem Biotechnol. 2018;184:935–52. https://doi.org/10.1007/s12010-017-2601-6.

    Article  CAS  PubMed  Google Scholar 

  24. Kumar LR, Yellapu SK, Tyagi RD, Drogui P. Biodiesel production from microbial lipid obtained by intermittent feeding of municipal sludge and treated crude glycerol. Syst Microbiol Biomanuf. 2021;1:344–55. https://doi.org/10.1007/s43393-021-00030-2.

    Article  CAS  Google Scholar 

  25. Vallecilla-Yepez L, Wilkins MR. Continuous succinic acid production from corn fiber hydrolysate by immobilized Actinobacillus succinogenes in a hollow fiber membrane packed-bed biofilm reactor. Syst Microbiol Biomanuf. 2022. https://doi.org/10.1007/s43393-022-00149-w.

    Article  Google Scholar 

  26. Hwang JH, Kabra AN, Ji MK, et al. Enhancement of continuous fermentative bioethanol production using combined treatment of mixed microalgal biomass. Algal Res. 2016;17:14–20. https://doi.org/10.1016/j.algal.2016.03.029.

    Article  Google Scholar 

  27. Patel SKS, Gupta RK, Das D, et al. Continuous biohydrogen production from poplar biomass hydrolysate by a defined bacterial mixture immobilized on lignocellulosic materials under non-sterile conditions. J Clean Prod. 2021;287: 125037. https://doi.org/10.1016/j.jclepro.2020.125037.

    Article  CAS  Google Scholar 

  28. de Castro AM, dos Santos AF, Kachrimanidou V, et al. Solid-state fermentation for the production of proteases and amylases and their application in nutrient medium production. Elsevier B.V; 2018.

    Google Scholar 

  29. Mitchell DA, de Lima Luz LF, Krieger N, Berovič M. Bioreactors for solid-state fermentation. In: Comprehensive biotechnology. 2nd ed. Springer; 2011. p. 347–60. https://doi.org/10.1016/B978-0-08-088504-9.00107-0.

    Chapter  Google Scholar 

  30. Prakasham RS, Rao CS, Sarma PN. Green gram husk-an inexpensive substrate for alkaline protease production by Bacillus sp. in solid-state fermentation. Bioresour Technol. 2006;97:1449–54. https://doi.org/10.1016/j.biortech.2005.07.015.

    Article  CAS  PubMed  Google Scholar 

  31. Vandenberghe LPS, Pandey A, Carvalho JC, et al. Solid-state fermentation technology and innovation for the production of agricultural and animal feed bioproducts. Syst Microbiol Biomanuf. 2021;1:142–65. https://doi.org/10.1007/s43393-020-00015-7.

    Article  CAS  Google Scholar 

  32. Costa JAV, Treichel H, Kumar V, Pandey A. Advances in solid-state fermentation. Elsevier B.V; 2018.

    Book  Google Scholar 

  33. Sharma R, Oberoi HS, Dhillon GS. Fruit and vegetable processing waste: renewable feed stocks for enzyme production. Elsevier Inc.; 2016.

    Book  Google Scholar 

  34. Ucar D, Zhang Y, Angelidaki I. An overview of electron acceptors in microbial fuel cells. Front Microbiol. 2017;8:1–14. https://doi.org/10.3389/fmicb.2017.00643.

    Article  Google Scholar 

  35. Stanbury PF, Whitaker A, Hall SJ. Aeration and agitation. In: Principles of fermentation technology. Elsevier; 2017. p. 537–618.

    Chapter  Google Scholar 

  36. Yang C, Mao Z-S. Multiphase stirred reactors. Elsevier; 2014.

    Book  Google Scholar 

  37. Zhong J-J. Bioreactor engineering. In: Comprehensive biotechnology. 3rd ed. Elsevier; 2011. p. 257–69.

    Chapter  Google Scholar 

  38. Hölker U, Lenz J. Solid-state fermentation—are there any biotechnological advantages? Curr Opin Microbiol. 2005;8:301–6. https://doi.org/10.1016/j.mib.2005.04.006.

    Article  CAS  PubMed  Google Scholar 

  39. Doriya K, Jose N, Gowda M, Kumar DS. Solid-state fermentation vs submerged fermentation for the production of l-asparaginase. 1st ed. Elsevier Inc.; 2016.

    Google Scholar 

  40. Humbird D, Davis R, McMillan JD. Aeration costs in stirred-tank and bubble column bioreactors. Biochem Eng J. 2017;127:161–6. https://doi.org/10.1016/j.bej.2017.08.006.

    Article  CAS  Google Scholar 

  41. Garcia-Ochoa F, Gomez E, Santos VE, Merchuk JC. Oxygen uptake rate in microbial processes: an overview. Biochem Eng J. 2010;49:289–307. https://doi.org/10.1016/j.bej.2010.01.011.

    Article  CAS  Google Scholar 

  42. Suresh S, Srivastava VC, Mishra IM. Techniques for oxygen transfer measurement in bioreactors: a review. J Chem Technol Biotechnol. 2009;84:1091–103. https://doi.org/10.1002/jctb.2154.

    Article  CAS  Google Scholar 

  43. Garcia-Ochoa F, Gomez E. Bioreactor scale-up and oxygen transfer rate in microbial processes: an overview. Biotechnol Adv. 2009;27:153–76. https://doi.org/10.1016/j.biotechadv.2008.10.006.

    Article  CAS  PubMed  Google Scholar 

  44. Delvigne F, Lecomte J. Foam formation and control in bioreactors. In: Encyclopedia of industrial biotechnology. Wiley; 2010. p. 1–13. https://doi.org/10.1002/9780470054581.eib326.

    Chapter  Google Scholar 

  45. Sarubbo LA, da Silva MGC, Durval IJB, et al. Biosurfactants: production, properties, applications, trends, and general perspectives. Biochem Eng J. 2022. https://doi.org/10.1016/j.bej.2022.108377.

    Article  Google Scholar 

  46. Etoc A, Delvigne F, Lecomte JP, Thonart P. Foam control in fermentation bioprocess. In: Twenty-Seventh Symposium on Biotechnology for Fuels and Chemicals. Totowa: Humana Press; 2004. p. 392–404.

    Google Scholar 

  47. Germain E, Stephenson T. Biomass characteristics, aeration and oxygen transfer in membrane bioreactors: their interrelations explained by a review of aerobic biological processes. Rev Environ Sci Biotechnol. 2005;4:223–33. https://doi.org/10.1007/s11157-005-2097-3.

    Article  CAS  Google Scholar 

  48. Karimi A, Golbabaei F, Mehrnia MR, et al. Oxygen mass transfer in a stirred tank bioreactor using different impeller configurations for environmental purposes. J Environ Health Sci Eng. 2013;10:1–9.

    Google Scholar 

  49. Simpson R, Sastry SK. Chemical and bioprocess engineering: Fundamental concepts for first-year students. In: Chemical and bioprocess engineering: fundamental concepts for first-year students. Springer; 2013. p. 1–352. https://doi.org/10.1007/978-1-4614-9126-2.

    Chapter  Google Scholar 

  50. Palomares LA, Ramírez OT. Bioreactor scale-up. In: Encyclopedia of industrial biotechnology. Hoboken: Wiley; 2009. p. 195–205.

    Google Scholar 

  51. Spier MR, Vandenberghe LPDS, Medeiros ABP, Soccol CR (2011) Application of different types of bioreactors in bioprocesses

  52. Xia J, Wang G, Lin J, et al. Advances and practices of bioprocess scale-up. In: Advances in biochemical engineering/biotechnology. Berlin: Springer; 2015. p. 137–51.

    Google Scholar 

  53. Antonelli R, Astolfi A. Continuous stirred tank reactors: easy to stabilise? Automatica. 2003;39:1817–27. https://doi.org/10.1016/S0005-1098(03)00177-8.

    Article  Google Scholar 

  54. Schmidell W (2002) Biotecnolgia industrial, Volume 2, Engenharia Bioquímica

  55. Wang YH, Zhang X. Influence of agitation and aeration on growth and antibiotic production by Xenorhabdus nematophila. World J Microbiol Biotechnol. 2007;23:221–7. https://doi.org/10.1007/s11274-006-9217-2.

    Article  CAS  Google Scholar 

  56. Bandaiphet C, Prasertsan P. Effect of aeration and agitation rates and scale-up on oxygen transfer coefficient, kLa in exopolysaccharide production from Enterobacter cloacae WD7. Carbohydr Polym. 2006;66:216–28. https://doi.org/10.1016/j.carbpol.2006.03.004.

    Article  CAS  Google Scholar 

  57. Islam RS, Tisi D, Levy MS, Lye GJ. Scale-up of Escherichia coli growth and recombinant protein expression conditions from microwell to laboratory and pilot scale based on matched k La. Biotechnol Bioeng. 2008;99:1128–39. https://doi.org/10.1002/bit.21697.

    Article  CAS  PubMed  Google Scholar 

  58. Michel BJ, Miller SA. Power requirements of gas-liquid agitated systems. AIChE J. 1962;8:262–6. https://doi.org/10.1002/aic.690080226.

    Article  Google Scholar 

  59. Mantzouridou F, Roukas T, Kotzekidou P. Effect of the aeration rate and agitation speed on β-carotene production and morphology of Blakeslea trispora in a stirred tank reactor: mathematical modeling. Biochem Eng J. 2002;10:123–35. https://doi.org/10.1016/S1369-703X(01)00166-8.

    Article  CAS  Google Scholar 

  60. Yu H, Tan Z. New correlations of volumetric liquid-phase mass transfer coefficients in gas-inducing agitated tank reactors. Int J Chem Reactor Eng. 2012;10:8–10. https://doi.org/10.1515/1542-6580.1.

    Article  Google Scholar 

  61. Shin W-S, Lee D, Kim S, et al. Application of scale-up criterion of constant oxygen mass transfer coefficient (kla). J Microbiol Biotechnol. 2013;23:1445–53.

    Article  CAS  PubMed  Google Scholar 

  62. Xu S, Hoshan L, Jiang R, et al. A practical approach in bioreactor scale-up and process transfer using a combination of constant P/V and vvm as the criterion. Biotechnol Prog. 2017;33:1146–59. https://doi.org/10.1002/btpr.2489.

    Article  CAS  PubMed  Google Scholar 

  63. Norwood KW, Metzner AB. Flow patterns and mixing rates in agitated vessels. AIChE J. 1960;6:432–7. https://doi.org/10.1002/aic.690060317.

    Article  CAS  Google Scholar 

  64. Kantarci N, Borak F, Ulgen KO. Bubble column reactors. Process Biochem. 2005;40:2263–83. https://doi.org/10.1016/j.procbio.2004.10.004.

    Article  CAS  Google Scholar 

  65. Pino MS, Rodríguez-Jasso RM, Michelin M, et al. Bioreactor design for enzymatic hydrolysis of biomass under the biorefinery concept. Chem Eng J. 2018;347:119–36. https://doi.org/10.1016/j.cej.2018.04.057.

    Article  CAS  Google Scholar 

  66. Harriott P. Chemical reactor design. CRC Press; 2002.

    Book  Google Scholar 

  67. Abdulmohsin RS, Abid BA, Al-Dahhan MH. Heat transfer study in a pilot-plant scale bubble column. Chem Eng Res Des. 2011;89:78–84. https://doi.org/10.1016/j.cherd.2010.04.019.

    Article  CAS  Google Scholar 

  68. Abdel-Aziz MH, Nirdosh I, Sedahmed GH. Liquid-solid mass and heat transfer behavior of a concentric tube airlift reactor. Int J Heat Mass Transf. 2013;58:735–9. https://doi.org/10.1016/j.ijheatmasstransfer.2012.11.054.

    Article  CAS  Google Scholar 

  69. Zhong F, Xing Z, Cao R, et al. Flow regimes characteristics of industrial-scale center-rising airlift reactor. Chem Eng J. 2022;430: 133067. https://doi.org/10.1016/j.cej.2021.133067.

    Article  CAS  Google Scholar 

  70. Berouaken A, Rihani R, Marra FS. Study of sparger design effects on the hydrodynamic and mass transfer characteristics of a D-shape hybrid airlift reactor. Chem Eng Res Des. 2023;191:66–82. https://doi.org/10.1016/j.cherd.2022.12.048.

    Article  CAS  Google Scholar 

  71. Johansen ST, Boysan F. Fluid dynamics in bubble stirred ladles: part II Mathematical modeling. Metall Trans B. 1988;19:755–64. https://doi.org/10.1007/BF02650195.

    Article  Google Scholar 

  72. Levitsky I, Tavor D, Gitis V. Microbubbles, oscillating flow, and mass transfer coefficients in air-water bubble columns. J Water Process Eng. 2022;49: 103087. https://doi.org/10.1016/j.jwpe.2022.103087.

    Article  Google Scholar 

  73. Eibl R, Eibl D, Pörtner R, et al. Cell and tissue reaction engineering. Berlin, Heidelberg: Springer Berlin Heidelberg; 2009.

    Book  Google Scholar 

  74. Nienow AW. Reactor engineering in large scale animal cell culture. Cytotechnology. 2006;50:9–33. https://doi.org/10.1007/s10616-006-9005-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Li X, Zhang G, Zhao X, et al. A conceptual air-lift reactor design for large scale animal cell cultivation in the context of in vitro meat production. Chem Eng Sci. 2020;211: 115269. https://doi.org/10.1016/j.ces.2019.115269.

    Article  CAS  Google Scholar 

  76. Calvo EG, Letón P. A fluid dynamic model for bubble columns and airlift reactors. Chem Eng Sci. 1991;46:2947–51. https://doi.org/10.1016/0009-2509(91)85164-S.

    Article  Google Scholar 

  77. Chisti Y. Bioreactor design. In: Basic biotechnology. 3rd ed. Elsevier; 2006. p. 181–200. https://doi.org/10.1017/CBO9780511802409.009.

    Chapter  Google Scholar 

  78. de Jesus SS, Moreira Neto J, Maciel Filho R. Hydrodynamics and mass transfer in bubble column, conventional airlift, stirred airlift and stirred tank bioreactors, using viscous fluid: a comparative study. Biochem Eng J. 2017;118:70–81. https://doi.org/10.1016/j.bej.2016.11.019.

    Article  CAS  Google Scholar 

  79. Siegel MH, Robinson CW. Application of airlift gas–liquid–solid reactors in biotechnology. Chem Eng Sci. 1992;47:3215–29. https://doi.org/10.1016/0009-2509(92)85030-F.

    Article  CAS  Google Scholar 

  80. Sirohi R, Pandey A, Sim S, et al. Current developments in biotechnology and bioengineering. Elsevier; 2023.

    Google Scholar 

  81. Pruvost J, Le Borgne F, Artu A, et al. Industrial photobioreactors and scale-up concepts. Adv Chem Eng. 2016;48:257–310. https://doi.org/10.1016/bs.ache.2015.11.002.

    Article  CAS  Google Scholar 

  82. Kazbar A, Cogne G, Urbain B, et al. Effect of dissolved oxygen concentration on microalgal culture in photobioreactors. Algal Res. 2019;39: 101432. https://doi.org/10.1016/j.algal.2019.101432.

    Article  Google Scholar 

  83. Singh RN, Sharma S. Development of suitable photobioreactor for algae production—a review. Renew Sustain Energy Rev. 2012;16:2347–53. https://doi.org/10.1016/j.rser.2012.01.026.

    Article  CAS  Google Scholar 

  84. Sero ET, Siziba N, Bunhu T, et al. Biophotonics for improving algal photobioreactor performance: a review. Int J Energy Res. 2020;44:5071–92. https://doi.org/10.1002/er.5059.

    Article  CAS  Google Scholar 

  85. Kroumov AD (2015) Analysis of Sf/V ratio of photobioreactors linked with algal physiology closed tubular PBRs are potentially

  86. Legrand J, Artu A, Pruvost J. A review on photobioreactor design and modelling for microalgae production. React Chem Eng. 2021;6:1134–51. https://doi.org/10.1039/d0re00450b.

    Article  CAS  Google Scholar 

  87. Posten C. Design principles of photo-bioreactors for cultivation of microalgae. Eng Life Sci. 2009;9:165–77. https://doi.org/10.1002/elsc.200900003.

    Article  CAS  Google Scholar 

  88. Gupta PL, Lee SM, Choi HJ. A mini review: photobioreactors for large scale algal cultivation. World J Microbiol Biotechnol. 2015;31:1409–17. https://doi.org/10.1007/s11274-015-1892-4.

    Article  CAS  PubMed  Google Scholar 

  89. Acién Fernández FG, Fernández Sevilla JM, Sánchez Pérez JA, et al. Airlift-driven external-loop tubular photobioreactors for outdoor production of microalgae: assessment of design and performance. Chem Eng Sci. 2001;56:2721–32. https://doi.org/10.1016/S0009-2509(00)00521-2.

    Article  Google Scholar 

  90. Molina Grima E, Garcia Carnacho F, Sanchez Perez JA, et al. in light-limited chemostat culture. J Chem Technol Biotechnol. 1994;61:167–73. https://doi.org/10.1002/jctb.280610212.

    Article  CAS  Google Scholar 

  91. Molina Grima E, Camacho FG, Pérez JAS, et al. Evaluation of photosynthetic efficiency in microalgal cultures using averaged irradiance. Enzyme Microb Technol. 1997;21:375–81. https://doi.org/10.1016/S0141-0229(97)00012-4.

    Article  Google Scholar 

  92. Díaz JP, Inostroza C, Acién Fernández FG. Fibonacci-type tubular photobioreactor for the production of microalgae. Process Biochem. 2019;86:1–8. https://doi.org/10.1016/j.procbio.2019.08.008.

    Article  CAS  Google Scholar 

  93. Luzi G, McHardy C. Modeling and simulation of photobioreactors with computational fluid dynamics—a comprehensive review. Energies (Basel). 2022;15:1–63. https://doi.org/10.3390/en15113966.

    Article  CAS  Google Scholar 

  94. Brindley C, Jiménez-Ruíz N, Acién FG, Fernández-Sevilla JM. Light regime optimization in photobioreactors using a dynamic photosynthesis model. Algal Res. 2016;16:399–408. https://doi.org/10.1016/j.algal.2016.03.033.

    Article  Google Scholar 

  95. Molina Grima E, Fernández FGA, Garcia Camacho F, Chisti Y. Photobioreactors: light regime, mass transfer, and scaleup. J Biotechnol. 1999;70:231–47. https://doi.org/10.1016/S0168-1656(99)00078-4.

    Article  CAS  Google Scholar 

  96. Carvalho AP, Silva SO, Baptista JM, Malcata FX. Light requirements in microalgal photobioreactors: an overview of biophotonic aspects. Appl Microbiol Biotechnol. 2011;89:1275–88. https://doi.org/10.1007/s00253-010-3047-8.

    Article  CAS  PubMed  Google Scholar 

  97. Gervais P, Molin P. The role of water in solid-state fermentation. Biochem Eng J. 2003;13:85–101. https://doi.org/10.1016/S1369-703X(02)00122-5.

    Article  CAS  Google Scholar 

  98. Pandey A. Solid-state fermentation. Biochem Eng J. 2003;13:81–4. https://doi.org/10.1016/S1369-703X(02)00121-3.

    Article  CAS  Google Scholar 

  99. Mitchell DA, Von Meien OF, Krieger N. Recent developments in modeling of solid-state fermentation: heat and mass transfer in bioreactors. Biochem Eng J. 2003;13:137–47. https://doi.org/10.1016/S1369-703X(02)00126-2.

    Article  CAS  Google Scholar 

  100. Bhargava S, Sanjrani MA, Javed S (2008) Solid-state fermentation : an overview solid-state fermentation : an overview

  101. Lonsane BK, Saucedo-Castaneda G, Raimbault M, et al. Scale-up strategies for solid state fermentation systems. Process Biochem. 1992;27:259–73. https://doi.org/10.1016/0032-9592(92)85011-P.

    Article  CAS  Google Scholar 

  102. Prabhakar A, Krishnaiah K, Janaun J, Bono A. An overview of engineering aspects of solid state fermentation. Malays J Microbiol. 2005;1:10–6. https://doi.org/10.21161/mjm.120502.

    Article  Google Scholar 

  103. Couto SR, Sanromán MÁ. Application of solid-state fermentation to food industry—a review. J Food Eng. 2006;76:291–302. https://doi.org/10.1016/j.jfoodeng.2005.05.022.

    Article  CAS  Google Scholar 

  104. Rux G, Mahajan PV, Geyer M, et al. Application of humidity-regulating tray for packaging of mushrooms. Postharvest Biol Technol. 2015;108:102–10. https://doi.org/10.1016/j.postharvbio.2015.06.010.

    Article  Google Scholar 

  105. Mitchell DA, Pandey A, Sangsurasak P, Krieger N. Scale-up strategies for packed-bed bioreactors for solid-state fermentation. Process Biochem. 1999;35:167–78. https://doi.org/10.1016/S0032-9592(99)00048-5.

    Article  CAS  Google Scholar 

  106. United Nations (2015) Adoption of the Paris Agreement.

  107. IEA Bioenergy (2019) Drop-in biofuels: the key role that co-processing will play in its production. In: IEA Bioenergy. https://www.ieabioenergy.com/blog/publications/new-publication-drop-in-biofuels-the-key-role-that-co-processing-will-play-in-its-production/. Accessed 13 Jul 2023

  108. IEA Bioenergy (2014) The potential and challenges of drop-in biofuels.

  109. IEA Bioenergy (2022) International Energy Agency - Bioenergy: Task 42 Biorefining in a circular economy. In: IEA Bioenergy. https://task42.ieabioenergy.com/. Accessed 13 Jul 2023.

  110. Balachandar G, Varanasi JL, Singh V, et al. Biological hydrogen production via dark fermentation: a holistic approach from lab-scale to pilot-scale. Int J Hydrogen Energy. 2020;45:5202–15. https://doi.org/10.1016/j.ijhydene.2019.09.006.

    Article  CAS  Google Scholar 

  111. Adam R, Pollex A, Zeng T, et al. Systematic homogenization of heterogenous biomass batches—industrial-scale production of solid biofuels in two case studies. Biomass Bioenergy. 2023. https://doi.org/10.1016/j.biombioe.2023.106808.

    Article  Google Scholar 

  112. Werner H (2009) Method and apparatus for producing fuel from moist biomass.

  113. Yoon KP (2019) Method for pretreatment and saccharification of biomass for production of biofuels or bioplastics.

  114. Hu C, Luo J, Li M et al (2023) System and method for producing cellulosic ethanol by means of saccharification and fermentation of biomass.

  115. Santa Anna LMM, Freire DMG, Kronemberger de FA, et al (2012) System for obtaining biological produtcts.

  116. Harper Jr. CL (2020) Methods and systems for large scale carbon dioxide utilization from Lake Kivu via a CO2 industrial HUB integrated with eletric power production and optional cryoenergy storage.

  117. Steinkraus K. Industrialization of indigenous fermented foods, revised and expanded. CRC Press; 2004.

    Book  Google Scholar 

  118. SuzuyoKogyo (2023) Natto Production Equipment. In: SuzuyoKogyo. https://suzuyokogyo.com/english/natto/. Accessed 13 Jul 2023.

  119. Moo-Young M, Chisti Y, Vlach D. Fermentation of cellulosic materials to mycoprotein foods. Biotechnol Adv. 1993;11:469–79. https://doi.org/10.1016/0734-9750(93)90015-F.

    Article  CAS  PubMed  Google Scholar 

  120. Tang YJ, Zhu LW, Li HM, Li DS. Submerged culture of mushrooms in bioreactors—challenges, current state-of-the-art, and future prospects. Food Technol Biotechnol. 2007;45:221–9.

    CAS  Google Scholar 

  121. Koutinas AA, Athanasiadis I, Bekatorou A, et al. Kefir yeast technology: scale-up in SCP production using milk whey. Biotechnol Bioeng. 2005;89:788–96. https://doi.org/10.1002/bit.20394.

    Article  CAS  PubMed  Google Scholar 

  122. Rakicka-Pustułka M, Mirończuk AM, Celińska E, et al. Scale-up of the erythritol production technology—process simulation and techno-economic analysis. J Clean Prod. 2020. https://doi.org/10.1016/j.jclepro.2020.120533.

    Article  Google Scholar 

  123. Elsayed EA, Othman NZ, El Enshasy HA. Bioprocess optimization of Xanthan production by Xanthomonas campestris using semi-defined medium in batch and fed-batch culture. Pharm Lett. 2016;8:288–96.

    CAS  Google Scholar 

  124. Rončević Z, Grahovac J, Dodić S, et al. Utilisation of winery wastewater for xanthan production in stirred tank bioreactor: bioprocess modelling and optimisation. Food Bioprod Process. 2019;117:113–25. https://doi.org/10.1016/j.fbp.2019.06.019.

    Article  CAS  Google Scholar 

  125. Gürler HN, Erkan SB, Ozcan A, et al. Scale-up processing with different microparticle agent for β-mannanase production in a large-scale stirred tank bioreactor. J Food Process Preserv. 2021;45:1–12. https://doi.org/10.1111/jfpp.14915.

    Article  CAS  Google Scholar 

  126. Colla E, Santos LO, Deamici K, et al. Simultaneous production of amyloglucosidase and exo-polygalacturonase by Aspergillus niger in a rotating drum reactor. Appl Biochem Biotechnol. 2017;181:627–37. https://doi.org/10.1007/s12010-016-2237-y.

    Article  CAS  PubMed  Google Scholar 

  127. Elsayed EA, Danial EN, Wadaan MA, El-Enshasy HA. Production of β-galactosidase in shake-flask and stirred tank bioreactor cultivations by a newly isolated Bacillus licheniformis strain. Biocatal Agric Biotechnol. 2019;20: 101231. https://doi.org/10.1016/j.bcab.2019.101231.

    Article  Google Scholar 

  128. Deng L, Liu Y, Zheng D, et al. Application and development of biogas technology for the treatment of waste in China. Renew Sustain Energy Rev. 2017;70:845–51. https://doi.org/10.1016/j.rser.2016.11.265.

    Article  CAS  Google Scholar 

  129. Martinez-Burgos WJ, Sydney EB, de Paula DR, et al. Biohydrogen production in cassava processing wastewater using microbial consortia: process optimization and kinetic analysis of the microbial community. Bioresour Technol. 2020;309: 123331. https://doi.org/10.1016/j.biortech.2020.123331.

    Article  CAS  PubMed  Google Scholar 

  130. Rosa D, Medeiros ABP, Martinez-Burgos WJ, et al. Biological hydrogen production from palm oil mill effluent (POME) by anaerobic consortia and Clostridium beijerinckii. J Biotechnol. 2020;323:17–23. https://doi.org/10.1016/j.jbiotec.2020.06.015.

    Article  CAS  PubMed  Google Scholar 

  131. Basri MF, Yacob S, Hassan MA, et al. Improved biogas production from palm oil mill effluent by a scaled-down anaerobic treatment process. World J Microbiol Biotechnol. 2010;26:505–14. https://doi.org/10.1007/s11274-009-0197-x.

    Article  CAS  Google Scholar 

  132. Yacob S, Shirai Y, Hassan MA, et al. Start-up operation of semi-commercial closed anaerobic digester for palm oil mill effluent treatment. Process Biochem. 2006;41:962–4. https://doi.org/10.1016/j.procbio.2005.10.021.

    Article  CAS  Google Scholar 

  133. Heffernan B, Van Lier JB, Van Der Lubbe J. Performance review of large scale up-flow anaerobic sludge blanket sewage treatment plants. Water Sci Technol. 2011;63:100–7. https://doi.org/10.2166/wst.2011.017.

    Article  CAS  PubMed  Google Scholar 

  134. Wehrs M, Tanjore D, Eng T, et al. Engineering robust production microbes for large-scale cultivation. Trends Microbiol. 2019;27:524–37. https://doi.org/10.1016/j.tim.2019.01.006.

    Article  CAS  PubMed  Google Scholar 

  135. Elsayed EA, Farid MA, El-Enshasy HA. Enhanced Natamycin production by Streptomyces natalensis in shake-flasks and stirred tank bioreactor under batch and fed-batch conditions. BMC Biotechnol. 2019;19:1–13. https://doi.org/10.1186/s12896-019-0546-2.

    Article  CAS  Google Scholar 

  136. Huang K, Zhang B, Chen Y, et al. Enhancing the production of amphotericin B by Strepyomyces nodosus in a 50-ton bioreactor based on comparative genomic analysis. 3Biotech. 2021;11:1–13. https://doi.org/10.1007/s13205-021-02844-2.

    Article  Google Scholar 

  137. Corbin JM, McNulty MJ, Macharoen K, et al. Technoeconomic analysis of semicontinuous bioreactor production of biopharmaceuticals in transgenic rice cell suspension cultures. Biotechnol Bioeng. 2020;117:3053–65. https://doi.org/10.1002/bit.27475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Maiorano AE, da Silva ES, Perna RF, et al. Effect of agitation speed and aeration rate on fructosyltransferase production of Aspergillus oryzae IPT-301 in stirred tank bioreactor. Biotechnol Lett. 2020;42:2619–29. https://doi.org/10.1007/s10529-020-03006-9.

    Article  CAS  PubMed  Google Scholar 

  139. Manan MA, Webb C. Newly designed multi-stacked circular tray solid-state bioreactor: analysis of a distributed parameter gas balance during solid-state fermentation with influence of variable initial moisture content arrangements. Bioresour Bioprocess. 2020. https://doi.org/10.1186/s40643-020-00307-9.

    Article  Google Scholar 

  140. Kiefer D, Tadele LR, Lilge L, et al. High-level recombinant protein production with Corynebacterium glutamicum using acetate as carbon source. Microb Biotechnol. 2022;15:2744–57. https://doi.org/10.1111/1751-7915.14138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Zhou J, Huo T, Sun J, et al. Response of amino acid metabolism to decreased temperatures in anammox consortia: strong, efficient and flexible. Bioresour Technol. 2022;352: 127099. https://doi.org/10.1016/j.biortech.2022.127099.

    Article  CAS  PubMed  Google Scholar 

  142. Motolinía-Alcántara EA, Castillo-Araiza CO, Rodríguez-Monroy M, et al. Engineering considerations to produce bioactive compounds from plant cell suspension culture in bioreactors. Plants. 2021;10:2762. https://doi.org/10.3390/plants10122762.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Ganeshan S, Kim SH, Vujanovic V. Scaling-up production of plant endophytes in bioreactors: concepts, challenges and perspectives. Bioresour Bioprocess. 2021. https://doi.org/10.1186/s40643-021-00417-y.

    Article  PubMed  PubMed Central  Google Scholar 

  144. Pereira H, Páramo J, Silva J, et al. Scale-up and large-scale production of Tetraselmis sp. CTP4 (Chlorophyta) for CO2 mitigation: from an agar plate to 100–m3 industrial photobioreactors. Sci Rep. 2018;8:1–11. https://doi.org/10.1038/s41598-018-23340-3.

    Article  CAS  Google Scholar 

  145. Bito T, Okumura E, Fujishima M, Watanabe F. Potential of chlorella as a dietary supplement to promote human health. Nutrients. 2020;12:1–21. https://doi.org/10.3390/nu12092524.

    Article  CAS  Google Scholar 

  146. Paladino O, Neviani M. Scale-up of photo-bioreactors for microalgae cultivation by π-theorem. Biochem Eng J. 2020;153: 107398. https://doi.org/10.1016/j.bej.2019.107398.

    Article  CAS  Google Scholar 

  147. de Carvalho JC, Molina-Aulestia DT, Martinez-Burgos WJ, et al. Agro-industrial wastewaters for algal biomass production, bio-based products, and biofuels in a circular bioeconomy. Fermentation. 2022. https://doi.org/10.3390/fermentation8120728.

    Article  Google Scholar 

  148. Kumar AK, Sharma S, Dixit G, et al. Techno-economic analysis of microalgae production with simultaneous dairy effluent treatment using a pilot-scale High Volume V-shape pond system. Renew Energy. 2020;145:1620–32. https://doi.org/10.1016/j.renene.2019.07.087.

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico do Brasil (CNPq) for the Project fundings and research scholarship

Funding

Projects funding and research scholarship are provided by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Author information

Authors and Affiliations

Authors

Contributions

AFMdM conceptualization, writing—original draft, writing—review. LPdSV conceptualization, writing—original draft, writing—review. LWH conceptualization, writing—original draft. LAJL conceptualization, writing—original draft. WJMB writing—original draft. TS writing—original draft. MCM writing—original draft. PZdO writing—original draft. CRS project administration, funding acquisition.

Corresponding author

Correspondence to Luciana Porto de Souza Vandenberghe.

Ethics declarations

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical approval and consent to participate

Not applicable.

Consent for publication

All authors have read and agreed to publish the final version of the manuscript.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 429 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Mello, A.F.M., de Souza Vandenberghe, L.P., Herrmann, L.W. et al. Strategies and engineering aspects on the scale-up of bioreactors for different bioprocesses. Syst Microbiol and Biomanuf 4, 365–385 (2024). https://doi.org/10.1007/s43393-023-00205-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43393-023-00205-z

Keywords

Navigation