Analytical and Bioanalytical Chemistry

, Volume 395, Issue 3, pp 679–695 | Cite as

Application of microbioreactors in fermentation process development: a review

  • Daniel Schäpper
  • Muhd Nazrul Hisham Zainal Alam
  • Nicolas Szita
  • Anna Eliasson Lantz
  • Krist V. Gernaey
Review

Abstract

Biotechnology process development involves strain testing and improvement steps aimed at increasing yields and productivity. This necessitates the high-throughput screening of many potential strain candidates, a task currently mainly performed in shake flasks or microtiter plates. However, these methods have some drawbacks, such as the low data density (usually only end-point measurements) and the lack of control over cultivation conditions in standard shake flasks. Microbioreactors can offer the flexibility and controllability of bench-scale reactors and thus deliver results that are more comparable to large-scale fermentations, but with the additional advantages of small size, availability of online cultivation data and the potential for automation. Current microbioreactor technology is analyzed in this review paper, focusing on its industrial applicability, and directions for future research are presented.

Keywords

Microbioreactor Fermentation Bioprocess monitoring Microfluidic suspension culture 

References

  1. 1.
    Weuster-Botz D, Hekmat D, Puskeiler R, Franco-Lara E (2007) Adv Biochem Eng Biotechnol 105(205):247Google Scholar
  2. 2.
    Shuler ML, Kargi F (2002) Bioprocess engineering: basic concepts. Prentice Hall, Upper Saddle RiverGoogle Scholar
  3. 3.
    Lye GJ, Ayazi-Shamlou P, Baganz F, Dalby PA, Woodley JM (2003) Trends Biotechnol 21(1):29–37CrossRefGoogle Scholar
  4. 4.
    Kumar S, Wittmann C, Heinzle E (2004) Biotechnol Lett 26:1–10CrossRefGoogle Scholar
  5. 5.
    Betts JI, Baganz F (2006) Microb Cell Fact 5:21Google Scholar
  6. 6.
    Micheletti M, Lye GJ (2006) Curr Opin Biotechnol 17:611–618CrossRefGoogle Scholar
  7. 7.
    Szita N, Boccazzi P, Zhang Z, Boyle P, Sinskey AJ, Jensen KF (2005) Lab Chip 5:819–826Google Scholar
  8. 8.
    Zhang Z, Boccazzi P, Choi HG, Perozziello G, Sinskey AJ, Jensen KF (2006) Lab Chip 6:906–913Google Scholar
  9. 9.
    Lee HLT, Boccazzi P, Ram RJ, Sinskey AJ (2006) Lab Chip 6:1229–1235Google Scholar
  10. 10.
    Zanzotto A, Szita N, Boccazzi P, Lessard P, Sinskey AJ, Jensen KF (2004) Biotechnol Bioeng 87(2):243–254CrossRefGoogle Scholar
  11. 11.
    De Jong J (2008) Application of membrane technology in microfluidic devices (Ph.D. thesis). University of Twente, TwenteGoogle Scholar
  12. 12.
    Zhao YG, Lu WK, Kim SS, Ho ST, Marks TJ (2000) Appl Phys Lett 77(19):2961–2963CrossRefGoogle Scholar
  13. 13.
    Fleger M, Neyer A (2006) Microelectron Eng 83:1291–1293CrossRefGoogle Scholar
  14. 14.
    Becker H, Gärtner C (2008) Anal Bioanal Chem 390:89–111CrossRefGoogle Scholar
  15. 15.
    Tsao CW, Devoe DL (2009) Microfluid Nanofluid 6:1–16CrossRefGoogle Scholar
  16. 16.
    Mcdonald JC, Whitesides GM (2002) Acc Chem Res 35(7):491–499CrossRefGoogle Scholar
  17. 17.
    Huang C-W, Lee G-B (2007) J Micromech Microeng 17:1266–1274Google Scholar
  18. 18.
    Anvari M, Khayati G (2009) J Ind Microbiol Biotech 36:313–317CrossRefGoogle Scholar
  19. 19.
    Zautsen RRM, Maugeri-Filho F, Vaz-Rossell CE, Straathof AJJ, van der Wielen LAM, de Bont JAM (2009) Biotechnol Bioeng 102:1354–1360CrossRefGoogle Scholar
  20. 20.
    Purcell EM (1977) Am J Phys 45(1):3–11CrossRefGoogle Scholar
  21. 21.
    Hessel V, Löwe H, Schönfeld F (2005) Chem Eng Sci 60:2479–2501CrossRefGoogle Scholar
  22. 22.
    Hardt S, Schönfeld F (2007) Microfluidic technologies for miniaturized analysis systems. Springer, New YorkGoogle Scholar
  23. 23.
    Maharbiz MM, Holtz WJ, Howe RT, Keasling JD (2004) Biotechnol Bioeng 85(4):376–381CrossRefGoogle Scholar
  24. 24.
    Strook AD, Dertinger SKW, Ajdari A, Mezić I, Stone HA, Whitesides GM (2002) Science 295:647–651CrossRefGoogle Scholar
  25. 25.
    Li X, van der Steen G, van Dedem GWK, van der Wielen LAM, van Leeuwen M, van Gulik WM, Heijnen JJ, Krommenhoek EE, Gardeniers JGE, van den Berg A, Ottens M (2008) Chem Eng Sci 63:3036–3046CrossRefGoogle Scholar
  26. 26.
    Berthier E, Warrick J, Hongmeiy Y, Beebe DJ (2008) Lab Chip 8:852–859Google Scholar
  27. 27.
    Boccazzi P, Zhang Z, Kurosawa K, Szita N, Bhattacharya S, Jensen KF, Sinskey AJ (2006) Biotechnol Prog 22:710–717CrossRefGoogle Scholar
  28. 28.
    Olsson A, Stemme G, Stemme E (1996) Sens Actuators A 137:143Google Scholar
  29. 29.
    Jeong OC, Park SW, Yang SS, Pak JJ (2005) Sens Actuators A 123:453Google Scholar
  30. 30.
    Fredrickson CK, Fan ZH (2004) Lab Chip 4:526–533Google Scholar
  31. 31.
    Perozziello G (2006) Doctoral thesis. Technical University of Denmark, LyngbyGoogle Scholar
  32. 32.
    Kortmann H, Blank LM, Schmid A (2009) Lab Chip 9:1455–1460Google Scholar
  33. 33.
    Vojinović V, Cabral JMS, Fonseca LP (2005) Sens Actuators B 114:1083–1091Google Scholar
  34. 34.
    Petronis S, Stangegaard M, Christensen CBV, Dufva M (2006) Biotechniques 40:368–376CrossRefGoogle Scholar
  35. 35.
    Maiti TK (2006) IEEE Sens J 6(6):1454–1458CrossRefGoogle Scholar
  36. 36.
    Krommenhoek EE, van Leeuwen M, Gardeniers H, van Gulik WM, van den Berg A, Li X, Ottens M, van der Wielen LAM, Heijnen JJ (2008) Biotechnol Bioeng 99(4):884–892CrossRefGoogle Scholar
  37. 37.
    Vervliet-Scheebaum M, Ritzenthaler R, Normann J, Wagner E (2008) Ecotoxicol Environ Saf 69:254–262CrossRefGoogle Scholar
  38. 38.
    Gimbun J, Radiah ABD, Chuah TG (2004) Food Eng 64:277–283CrossRefGoogle Scholar
  39. 39.
    Assael MJ, Antoniadis KD, Wu J (2008) Int J Thermophys 29:1257–1266CrossRefGoogle Scholar
  40. 40.
    Shin YS, Cho K, Lim SH, Chung S, Park SJ, Chung C, Han DC, Chang JK (2003) J Micromech Microeng 13:768–774Google Scholar
  41. 41.
    Liu L, Peng S, Niu X, Wen W (2006) Appl Phys Lett 89:223521CrossRefGoogle Scholar
  42. 42.
    Yamamoto T, Nojima T, Fujii T (2002) Lab Chip 2:197–202Google Scholar
  43. 43.
    van Leeuwen M, Heijnen JJ, Gardeniers H, Oudshoorn A, Noorman H, Visser J, van der Wielen LAM, van Gulik WM (2009) Chem Eng Sci 64:455–458CrossRefGoogle Scholar
  44. 44.
    Isett K, George H, Herber W, Amanullah A (2007) Biotechnol Bioeng 98:1017–1028CrossRefGoogle Scholar
  45. 45.
  46. 46.
    Microsens (2009) Ion-sensitive field-effect transistor. http://www.microsens.ch/products/chemical.htm. Accessed 9 March 2009
  47. 47.
    John GT, Goelling D, Klimant I, Schneider H, Heinzle E (2003) J Dairy Res 70:327–333CrossRefGoogle Scholar
  48. 48.
    Zhang Z, Perozziello G, Boccazzi P, Sinskey AJ, Geschke O, Jensen KF (2007) J Assoc Lab Automat 12(3):143–151Google Scholar
  49. 49.
    Krommenhoek EE, Gardeniers JGE, Bomer JG, Li X, Ottens M, van Dedem GWK, van Leeuwen M, van Gulik WM, van der Wielen LAM, Heijnen JJ, van den Berg A (2007) Anal Chem 79(15):5567–5573CrossRefGoogle Scholar
  50. 50.
    Buchenauer A, Hofmann MC, Funke M, Büchs J, Mokwa W, Schnakenberg U (2009) Biosens Bioelecton 24:1411–1416CrossRefGoogle Scholar
  51. 51.
    Wu MH, Huang SB, Cui Z, Cui Z, Lee GB (2008) Biomed Microdevices 10(2):309–319CrossRefGoogle Scholar
  52. 52.
    Applikon Biotechnology (2009) Micro 24 bioreactor. http://www.applikon-bio.com/index.php?option=com_content&view=article&id=80&catid=43&Itemid=17. Accessed 9 March 2009
  53. 53.
    Jensen KH, Alam MN, Scherer B, Lambrecht A, Mortensen NA (2008) Opt Commun 281:5335–5339CrossRefGoogle Scholar
  54. 54.
    Cervera AE, Petersen N, Eliasson Lantz A, Larsen A, Gernaey KV (2009) Biotechnol Progr (in press). doi:10.1021/bp.280
  55. 55.
    Sartorius BBI Systems (2009) Sartorius FUNDALUX II turbidity sensor. http://www.sartorius-stedim.com/index.php?id=1999. Accessed 9 March 2009
  56. 56.
    Villain L, Meyer L, Kroll S, Beutel S, Scheper T (2008) Biotechnol Prog 24:367–371CrossRefGoogle Scholar
  57. 57.
    Papkovsky DB (1995) Sens Actuators B 29:213–218Google Scholar
  58. 58.
    Islam RS, Tisi D, Levy MS, Lye GJ (2007) Biotechnol Bioeng 99(5):1128–1139CrossRefGoogle Scholar
  59. 59.
    Ge X, Kostov Y, Rao G (2004) Biotechnol Bioeng 89(3):329–334CrossRefGoogle Scholar
  60. 60.
    Liebsch G, Klimant I, Frank B, Holst G, Wolfbeis OS (2000) Appl Spectrosc 54(4):548–559CrossRefGoogle Scholar
  61. 61.
    Scarff M, Arnold SA, Harvey LM, McNeil B (2006) Crit Rev Biotechnol 26:17–39CrossRefGoogle Scholar
  62. 62.
    Lee HLT, Boccazzi P, Gorret N, Ram RJ, Sinskey AJ (2004) Vib Spectrosc 35:131–137CrossRefGoogle Scholar
  63. 63.
    Cao E, Firth S, McMillan PF, Gavriilidis A (2007) Catal Today 126:119–126CrossRefGoogle Scholar
  64. 64.
    Ferstl W, Klahn T, Schweikert W, Billeb G, Schwarzer M, Loebbecke S (2007) Chem Eng Technol 30(3):370–378CrossRefGoogle Scholar
  65. 65.
    Biomass R&D, Technical Advisory Committee (2006) Vision for bioenergy and biobased products in the United States. http://www.brdisolutions.com/default.aspx Accessed 9 March 2009
  66. 66.
    European Technology Platform for Sustainable Chemistry, Industrial Biotechnology Section (2005) Homepage. http://www.suschem.org. Accessed 9 March 2009
  67. 67.
    Riesenberg D, Guthke R (1999) Appl Microbiol Biotechnol 51:422–430CrossRefGoogle Scholar
  68. 68.
    Åkesson M, Hagander P, Axelsson JP (1999) Biotechnol Tech 13:523–528CrossRefGoogle Scholar
  69. 69.
    de Maré L, Cimander C, Elfwing A, Hagander P (2007) Bioprocess Biosyst Eng 30:13–25CrossRefGoogle Scholar
  70. 70.
    Sartorius BBI Systems (2009) Biostat Cultibag. http://www.sartorius-stedim.com/index.php?id=4387. Accessed 7 March 2009
  71. 71.
    Sathuluri RR, Yamamura S, Tamiya E (2008) Adv Biochem Eng Biotechnol 109:285–350Google Scholar
  72. 72.
    Lennox B, Montague GA, Hiden HG, Kornfeld G, Goulding PR (2001) Biotechnol Bioeng 74:125–135CrossRefGoogle Scholar
  73. 73.
    Sundström H, Enfors S-O (2008) Bioprocess Biosyst Eng 31:145–152CrossRefGoogle Scholar
  74. 74.
    Zhang Z, Szita N, Boccazzi P, Sinskey AJ, Jensen KF (2005) Biotechnol Bioeng 92(2):286–296CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Daniel Schäpper
    • 1
  • Muhd Nazrul Hisham Zainal Alam
    • 1
    • 2
  • Nicolas Szita
    • 3
  • Anna Eliasson Lantz
    • 4
  • Krist V. Gernaey
    • 1
  1. 1.Department of Chemical and Biochemical EngineeringTechnical University of DenmarkLyngbyDenmark
  2. 2.Department of Bioprocess Engineering, Faculty of Chemical and Natural Resources EngineeringUniversiti Teknologi MalaysiaJohoreMalaysia
  3. 3.Department of Biochemical EngineeringUniversity College LondonLondonUK
  4. 4.Department of Systems BiologyTechnical University of DenmarkLyngbyDenmark

Personalised recommendations