Liquid State Bioreactor

  • Ercan Yatmaz
  • Irfan TurhanEmail author
Part of the Learning Materials in Biosciences book series (LMB)


Liquid culture and solid culture fermentation are widely used to produce a range of metabolites. Despite the use of solid culture fermentation in some cases, most fermentations are carried out in a liquid broth. This type of production is called liquid state fermentation or submerged fermentation. Most fermentation processes are performed on aseptic conditions, with aeration and agitation, while some fermentations, such as beer and wine production, are carried out with no need of aseptic conditions, aeration, and agitation. This chapter will discuss liquid state fermentation principles.


Submerged fermenters Fermentation kinetics Microbial growth Upstream process 


  1. 1.
    Asadi A, Zinatizadeh AA, van Loosdrecht M. Effects of operational models (batch, continuous and CFID modes) on the performance of a single A2O airlift bioreactor for treatment of milk processing wastewater. Chem Eng Res Des. 2017;125:471–82.CrossRefGoogle Scholar
  2. 2.
    Aslam M, McCarty PL, Shin C, Bae J, Kim J. Low energy single-staged anaerobic fluidized bed ceramic membrane bioreactor (AFCMBR) for wastewater treatment. Bioresour Technol. 2017;240:33–41.PubMedCrossRefGoogle Scholar
  3. 3.
    Badenes SM, Fernandes TG, Rodrigues CAV, Diogo MM, Cabral JMS. Microcarrier-based platforms for in vitro expansion and differentiation of human pluripotent stem cells in bioreactor culture. J Biotechnol. 2016;234:71–82.PubMedCrossRefGoogle Scholar
  4. 4.
    Banerjee A, Ghoshal AK. Biodegradation of real petroleum wastewater by immobilized hyper phenol-tolerant strains of Bacillus cereus in a fluidized bed bioreactor. 3 Biotech. 2016;6:137.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Campani G, Gonçalves da Silva G, Zangirolami TC, Perencin de Arruda Ribeiro M. Recombinant Escherichia coli cultivation in a pressurized airlift bioreactor: assessment of the influence of temperature on oxygen transfer and uptake rates. Bioprocess Biosyst Eng. 2017;40:1621–33.PubMedCrossRefGoogle Scholar
  6. 6.
    Chan Z, Zhong T, Yi Z, Xiao J, Zeng R. A pH shift feeding strategy for increased enduracidin production during fed–batch fermentation by a deep–sea, bacterium, Streptomyces sp. MC079. Biotechnol Bioprocess E. 2015;20:908–14.CrossRefGoogle Scholar
  7. 7.
    Chen H-C, Hu Y-C. Bioreactors for tissue engineering. Biotechnol Lett. 2006;28:1415–23.PubMedCrossRefGoogle Scholar
  8. 8.
    Demming S, Vila-Planas J, Zadeh SA, Edlich A, Franco-Lara E, Radespiel R, Büttgenbach S, Llobera A. Poly(dimethylsiloxane) photonic microbioreactors based on segmented waveguides for local absorbance measurement. Electrophoresis. 2011;32:431–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Demming S, Peterat G, Llobera A, Schmolke H, Bruns A, Kohlstedt M, Al-Halhouli A, Klages C-P, Krull R, Büttgenbach S. Vertical microbubble column – a photonic lab-on-chip for cultivation and online analysis of yeast cell cultures. Biomicrofluidics. 2012;6:034106.PubMedCentralCrossRefGoogle Scholar
  10. 10.
    Dermenoudis S, Missirlis YF. Bioreactors in tissue engineering. Adv Eng Mater. 2010;12(11):592–608.CrossRefGoogle Scholar
  11. 11.
    Driouch H, Sommer B, Wittman C. Morphology engineering of Aspergillus niger for improved enzyme production. Biotechnol Bioeng. 2010;109(2):462–71.CrossRefGoogle Scholar
  12. 12.
    Driouch H, Hänsch R, Wucherpfennig T, Krull R, Wittman C. Improved enzyme production by bio-pellets of Aspergillus niger: targeted morphology engineering using titanate microparticles. Biotechnol Bioeng. 2012;105(6):1058–68.Google Scholar
  13. 13.
    Edlich A, Magdanz V, Rasch D, Demming S, Zadeh SA, Segura R, Radespiel R, Büttgenbach S, Franco-Lara E, Krull R. Microfluidic reactor for continuous cultivation of Saccharomyces cerevisiae. Biotechnol Prog. 2010;26:1259–70.PubMedCrossRefGoogle Scholar
  14. 14.
    Ercan D, Demirci A. Current and future trends for biofilm reactors for fermentation processes. Crit Rev Biotechnol. 2015;35(1):1–14.PubMedCrossRefGoogle Scholar
  15. 15.
    Fan R, Ebrahimi M, Czermak P. Anaerobic membrane bioreactor for continuous lactic acid fermentation. Membranes. 2017;7:26.PubMedCentralCrossRefGoogle Scholar
  16. 16.
    Geed SR, Kureel MK, Giri BS, Singh RS, Rai BN. Performance evaluation of Malathion biodegradation in batch and continuous packed bed bioreactor (PBBR). Bioresour Technol. 2017;227:56–65.PubMedCrossRefGoogle Scholar
  17. 17.
    Gmati D, Chen J, Jolicoeur M. Development of a small-scale bioreactor: application to in vivo NMR measurement. Biotechnol Bioeng. 2005;89(2):138–47.PubMedCrossRefGoogle Scholar
  18. 18.
    Gogate PR, Beenackers AACM, Pandit AB. Multiple-impeller systems with a special emphasis on bioreactors: a critical review. Biochem Eng J. 2000;6:109–44.PubMedCrossRefGoogle Scholar
  19. 19.
    Hatzinger PB, Lewis C, Webster TS. Biological treatment of N-nitrosodimethylamine (NDMA) and N-nitrodimethylamine (NTDMA) in a field-scale fluidized bed bioreactor. Water Res. 2017;126:361–71.PubMedCrossRefGoogle Scholar
  20. 20.
    Hölker U, Höfer M, Lenz J. Biotechnological advantages of laboratory-scale solid-state fermentation with fungi. Appl Microbiol Biotechnol. 2004;64:175–86.PubMedCrossRefGoogle Scholar
  21. 21.
    Hülsen T, Barry EM, Lu Y, Puyol D, Keller J, Batstone DJ. Domestic wastewater treatment with purple phototrophic bacteria using a novel continuous photo anaerobic membrane bioreactor. Water Res. 2016;100:486–95.PubMedCrossRefGoogle Scholar
  22. 22.
    Jamshidi N, Mostoufi N. Measurement of bubble size distribution in activated sludge bubble column bioreactor. Biochem Eng J. 2017;125:212–20.CrossRefGoogle Scholar
  23. 23.
    Jones SMJ, Brighton MB, Harrison STL. Exploring the tension between energy consumption, light provision and CO2 mass transfer through varying gas velocity in the airlift bioreactor. Algal Res. 2016;19:381–90.CrossRefGoogle Scholar
  24. 24.
    Karimi A, Golbabaei F, Mehrnia MR, Neghab M, Mohammad K, Nikpey A, Pourmand MR. Oxygen mass transfer in a stirred tank bioreactor using different impeller configurations for environmental purposes. Iranian J Environ Health Sci Eng. 2013;10:6.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Kaup BA, Ehrich K, Pescheck M, Schrader J. Microparticle-enhanced cultivation of filamentous microorganisms: increased chloroperoxidase formation by Caldariomyces fumago as an example. Biotechnol Bioeng. 2008;99(3):491–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Kumar RN, Vinod AV. Oxygen mass transfer in bubble column bioreactor. Chem Eng. 2014;58(1):21–30.Google Scholar
  27. 27.
    Lee J, Lee SY, Park S, Middelberg APJ. Control of fed-batch fermentations. Biotechnol Adv. 1999;17:29–48.PubMedCrossRefGoogle Scholar
  28. 28.
    Longanesi L, Frascari D, Spagni C, DeWever H, Pinelli D. Succinic acid production from cheese whey by biofilms of Actinobacillus succinogenes: packed bed bioreactor tests. J Chem Technol Biotechnol. 2018;93:246–56.CrossRefGoogle Scholar
  29. 29.
    Lu Y, Yu J. Gas mass transfer with microbial CO2 fixation and poly(3-hydroxybutyrate) synthesis in a packed bed bioreactor. Biochem Eng J. 2017;122:13–21.CrossRefGoogle Scholar
  30. 30.
    Madigan MT, Martinko JM. Brock biology of microorganisms. Upper Saddle River: Prentice Hall PTR; 2006.Google Scholar
  31. 31.
    Mahboubi A, Ylitervo P, Doyen W, De Wever H, Molenberghs B, Taherzadeh MJ. Continuous bioethanol fermentation from wheat straw hydrolysate with high suspended solid content using an immersed flat sheet membrane bioreactor. Bioresour Technol. 2017;241:296–308.PubMedCrossRefGoogle Scholar
  32. 32.
    Majors PD, McLean JS, Scholten JCM. NMR bioreactor development for live in-situ microbial functional analysis. J Magn Reson. 2008;192:159–66.PubMedCrossRefGoogle Scholar
  33. 33.
    Martin I, Wendt D, Heberer M. The role of bioreactors in tissue engineering. Trends Biotechnol. 2004;22(2):80–6.PubMedCrossRefGoogle Scholar
  34. 34.
    McClure DD, Kavanagh JM, Fletcher DF, Barton GW. Characterizing bubble column bioreactor performance using computational fluid dynamics. Chem Eng Sci. 2016;144:58–74.CrossRefGoogle Scholar
  35. 35.
    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.PubMedCrossRefGoogle Scholar
  36. 36.
    Moreno-Medina CU, Poggi-Varaldo HM, Breton-Deval L, Rinderknecht-Seijas N. Effect of sudden addition of PCE and bioreactor coupling to ZVI filters on performance of fluidized bed bioreactors operated in simultaneous electron acceptor modes. Environ Sci Pollut Res. 2017;24:25534–49.CrossRefGoogle Scholar
  37. 37.
    Nielsen J, Villadsen J. Bioreactors: description and modelling. In: Stephanopulos G, editor. Biotechnology, 2nd completely, vol. 3. Revised ed. New York: VCH; 1993. p. 77–104.Google Scholar
  38. 38.
    Oliveira F, Salgado JM, Abrunhosa L, Pérez-Rodríguez N, Domínguez JM, Venâncio A, Belo I. Optimization of lipase production by solid-state fermentation of olive pomace: from flask to laboratory-scale packed-bed bioreactor. Bioprocess Biosyst Eng. 2017;40:1123–32.PubMedCrossRefGoogle Scholar
  39. 39.
    Patel BP, Kumar A. Biodegradation of 4-chlorophenol in an airlift inner loop bioreactor with mixed consortium: effect of HRT, loading rate and biogenic substrate. 3 Biotech. 2016;6:117.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Rahnama F, Vasheghani-Farahani E, Yazdian F, Shojaosadati SA. PHB production by Methylocystis hirsuta from natural gas in a bubble column and a vertical loop bioreactor. Biochem Eng J. 2012;65:51–6.CrossRefGoogle Scholar
  41. 41.
    Rasoulnia P, Mousavi SM. Maximization of organic acids production by Aspergillus niger in a bubble column bioreactor for V and Ni recovery enhancement from power plant residual ash in spent-medium bioleaching experiments. Bioresour Technol. 2016;216:729–36.PubMedCrossRefGoogle Scholar
  42. 42.
    Rocha AA, Wilde C, Hu Z, Nepotchatykh O, Nazarenko Y, Ariya PA. Development of a hybrid photo-bioreactor and nanoparticle adsorbent system for the removal of CO2, and selected organic and metal co-pollutants. J Environ Sci. 2017;57:41–53.CrossRefGoogle Scholar
  43. 43.
    Rossi MJ, Nascimento FX, Giachini AJ, Oliveira VL, Furigo A Jr. Transfer and consumption of oxygen during the cultivation of the extomycorrhizal fungus Rhizopogon nigrescens in an airlift bioreactor. Appl Microbiol Biotechnol. 2017;101:1013–24.PubMedCrossRefGoogle Scholar
  44. 44.
    Russel PD. Fermenter and bioreactor design. In: King RD, Cheetham PSJ, editors. Food biotechnology-1. New York: Elsevier; 1987. p. 1–48.Google Scholar
  45. 45.
    Seo I, Lee I, Hwang H, Hong S, Bitog JP, Kwon K, Lee C, Kim Z, Cuello JL. Numerical investigation of a bubble-column photo-bioreactor design for microalgae cultivation. Biosyst Eng. 2012;113:229–41.CrossRefGoogle Scholar
  46. 46.
    Shetty K, Paliyath G, Pometto A, Levin RE. Food biotechnology second edition. Boca Raton: CRC Press; 2006.Google Scholar
  47. 47.
    Skoneczny S, Stryjewski W, Bizon K, Tabiś B. Three-phase fluidized bed bioreactor modelling and stimulation. Biochem Eng J. 2017;121:118–30.CrossRefGoogle Scholar
  48. 48.
    Smith JE. Biotechnology. 4th ed. New York: Cambridge University Press; 2004.CrossRefGoogle Scholar
  49. 49.
    Stanbury PF, Whitaker A, Hall SJ. Principles of fermentation technology. 2nd ed. Burlington: Butterworth-Heinemann; 2003.Google Scholar
  50. 50.
    Sur DH, Mukhopadhyay M. Process aspects of three-phase inverse fluidized bed bioreactor: a review. J Environ Chem Eng. 2017a;5:3518–28.CrossRefGoogle Scholar
  51. 51.
    Sur DH, Mukhopadhyay M. COD reduction of textile effluent in three-phase fluidized bed bioreactor using Pseudomonas aureofaciens and Escherichia coli. 3 Biotech. 2017b;7:141.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Tang Y-J, Zhang W, Zhong J-J. Performance analyses of a pH-shift and DOT-shift integrated fed-batch fermentation process for the production of ganoderic acid and Ganoderma polysaccharides by medicinal mushroom Ganoderma lucidum. Bioresour Technol. 2009;1000:1852–9.CrossRefGoogle Scholar
  53. 53.
    Tunai N. Mikrobiyoloji. Ankara: Pelin Ofset; 2009. p. 448.Google Scholar
  54. 54.
    Velugula-Yellela SR, Williams A, Trunfio N, Hsu C-J, Chavez B, Yoon S, Agarabi C. Impact of media and antifoam selection on monoclonal antibody production and quality using a high throughput micro-bioreactor system. Biotechnol Prog. 2018;34(1):262–70.PubMedCrossRefGoogle Scholar
  55. 55.
    Yao P, Xiao Z, Chen C, Li W, Deng Q. Cell growth of Clostridium acetobutylicum in a pervaporation membrane bioreactor for butanol fermentation. Biotechnol Appl Biochem. 2016;63(1):101–5.PubMedCrossRefGoogle Scholar
  56. 56.
    Yatmaz E, Karahalil E, Germec M, Ilgin M, Turhan I. Controlling filamentous fungi morphology with microparticles to enhanced b-mannanase production. Bioprocess Biosyst Eng. 2016;39:1391–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Xia JY, Wang YH, Zhang SL, Chen N, Yin P, Zhuang YP, Chu J. Fluid dynamics investigation of variant impeller combinations by simulation and fermentation experiment. Biochem Eng J. 2009;43:252–60.CrossRefGoogle Scholar
  58. 58.
    Zambrano J, Nehrenheim E. Light and duty cycle optimization of a photo-bioreactor in batch mode. Energy Procedia. 2017;105:773–9.CrossRefGoogle Scholar
  59. 59.
    Zhang Z, Zhou X, Hu J, Zhang T, Zhu S, Zhang Q. Photo-bioreactor structure and light-heat-mass transfer properties in photo-fermentative bio-hydrogen production system: a mini review. Int J Hydrog Energy. 2017;42:12143–52.CrossRefGoogle Scholar
  60. 60.
    Zhu X, Li M, Zheng W, Liu R, Chen L. Performance and microbial community of a membrane bioreactor system — treating wastewater from ethanol fermentation of food waste. J Environ Sci. 2017;53:284–92.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Akdeniz University, Göynük Culinary Arts Vocational SchoolAntalyaTurkey
  2. 2.Akdeniz University, Faculty of Engineering, Department of Food EngineeringAntalyaTurkey

Personalised recommendations