Skip to main content

Advertisement

Log in

A review of non-invasive optical-based image analysis systems for continuous bioprocess monitoring

  • Original Paper
  • Published:
Bioprocess and Biosystems Engineering Aims and scope Submit manuscript

Abstract

To observe and control cultivation processes, optical sensors are used increasingly. Important variables for controlling such processes are cell count, cell size distribution and the morphology of cells. Among turbidity measurement methods, imaging procedures are applied for determining these process values. A disadvantage of most previously developed imaging procedures is that they are only available offline, which requires sampling. On the other hand, available imaging inline probes can only deliver a limited number of process values so far. This contribution gives an overview of optical procedures for the inline determination of cell count, cell size distribution and other variables. In particular, by in situ microscopy, an imaging procedure will be described, which allows the determination of direct and non-direct cell variables in real time without sampling.

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

Access this article

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. Konstantinov K, Chuppa S, Sajan E, Tsai Y, Yoon SJ, Golini F (1994) Trends Biotechnol 12:324

    Article  CAS  Google Scholar 

  2. Scheper T, Brandes W, Grau C, Hundeck HG, Reinhardt B, Rüther F, Plötz F, Schelp C, Schügerl K, Schneider KH, Giffhorn F, Rehr B, Sahm H (1991) Applications of biosensor systems for bioprocess monitoring. Anal Chim Acta 249:25

    Article  CAS  Google Scholar 

  3. Lee SJ, Scheper T, Bückmann AF (1994) Application of a flow injection fibre optic biosensor for the analyses of different amino acids. Biosens Bioelectron 9:29

    Article  Google Scholar 

  4. Scheper T, Gebauer A, Sauerbrei A, Niehoff A, Schügerl K (1984) Measurement of biological parameters during fermentation processes. Anal Chim Acta 163:111

    Article  CAS  Google Scholar 

  5. Scheper T, Lorenz T, Schmidt W, Schügerl K (1987) On-line measurement of culture fluorescence for process monitoring and control of biotechnological processes. Ann NY Acad Sci 506:431

    Article  CAS  Google Scholar 

  6. Beyer M, Menzel C, Quack R, Scheper T, Schügerl K, Treichel W, Voigt H, Ullrich M, Ferretti R (1994) Development and application of a new enzyme sensor type based on the EIS-capacitance structure for bioprocess control. Biosens Bioelectron 9:17

    Article  CAS  Google Scholar 

  7. Scheper T, Hilmer JM, Lammers F, Müller C, Reinicke M (1996) Biosensors in bioprocess monitoring. J Chromat 725:3

    Article  Google Scholar 

  8. Harris CM, Kell DB (1985) Biosensors 1:17

    Article  CAS  Google Scholar 

  9. Kell DB, Markx GH, Davey CL, Todd RW (1990) Trends Anal Chem 9:190

    Article  Google Scholar 

  10. Sonnleitner B, Locher G, Fiechter A (1992) J Biotechnol 25:5

    Article  CAS  Google Scholar 

  11. Barrett P, Glennon B (1999) Part Part Syst Charact 16:207

    Article  CAS  Google Scholar 

  12. Heath AR, Fawell PD, Bahri PA, Swift JD (2002) Part Part Syst Charact 19:84

    Article  Google Scholar 

  13. Heffels C, Polke R, Radle M, Sachweh B, Schafer M, Scholz N (1998) Part Part Syst Charact 15:211

    Article  CAS  Google Scholar 

  14. Tadayyon A, Rohani S (1998) Part Part Syst Charact 15:127

    Article  CAS  Google Scholar 

  15. Schirg P, Wissler P (2001) Chemie Ingenieur Technik 73:377

    Article  CAS  Google Scholar 

  16. De Clercq B, Lant PA, Vanrolleghem PA (2004) J Chem Technol Biotechnol 79:610

    Article  Google Scholar 

  17. Simmons MJH, Azzopardi BJ (2001) Int J Multiph Flow 27:843

    Article  CAS  Google Scholar 

  18. Pearson AP, Glennon B, Kieran PM (2003) Biotechnol Prog 19:1342

    Article  CAS  Google Scholar 

  19. Pearson AP, Glennon B, Kieran PM (2004) J Chem Technol Biotechnol 79:1142

    Article  CAS  Google Scholar 

  20. Jeffers P, Raposo S, Lima-Costa ME, Connolly P, Glennon B, Kieran PM (2003) Biotechnol Lett 25:2023

    Article  CAS  Google Scholar 

  21. Jeffers PT, Raposo S, Lima-Costa ME, Kieran P, Glennon B (2003) Abstr Pap Am Chem Soc 225:U188

    Google Scholar 

  22. Konan (1990) Fermend Scope, compact submerged microscope, Konan Camera Research Institute Inc. (Konan Medical, Inc.), Hyogo, Japan

  23. Kumada J, Takahashi T, Nakatani K, Nagami K (1981) 18th European Brewery Convention (EBC). Kopenhagen, Dänemark, p 293

    Google Scholar 

  24. Suhr H, Speil P, Wehnert G, Storhas W (1991) In situ Mikroskopsonde und Meßverfahren, DE 40 32 002 A1 (Anmeldetag 09.10.1990)

  25. H- Suhr, Wehnert G, Schneider K, Bittner C, Scholz T, Geissler P, Jähne B, Scheper T (1995) Biotechnol Bioeng 47:106

    Article  Google Scholar 

  26. Schneider K (1995) In situ Mikroskopie—Entwicklung und Einsatz eines Auflicht-Fluoreszenzsensors zur Bestimmung der Zellkonzentration in Bioprozessen, Universität Hannover

  27. Scholz T (1995) Ein Depth from Focus-Verfahren zur Online-Bestimmung der Zellkonzentration bei Fermentationsprozessen, Universität Heidelberg

  28. Barrett P, Glennon B (2002) Chem Eng Res Des 80:799

    Article  CAS  Google Scholar 

  29. Kougoulos E, Jones AG, Jennings KH, Wood-Kaczmar MW (2005) J Cryst Growth 273:529

    Article  CAS  Google Scholar 

  30. O’Sullivan B, Barrett P, Hsiao G, Carr A, Glennon B (2003) Org Process Res Dev 7:977

    Article  Google Scholar 

  31. Bittner C (1994) In situ-Mikroskopie—Ein neues Verfahren zur On-line-Bestimmung der Biomasse bei Kultivierungsprozessen, Universität Hannover

  32. Bittner C, Wehnert G, Scheper T (1998) Biotechnol Bioeng 60:24

    Article  CAS  Google Scholar 

  33. Frerichs JG (2000) Entwicklung eines In situ Mikroskops zur bildgestützten Online-Überwachung von Bioprozessen, Universität Hannover

  34. Frerichs JG, Joeris K, Konstantinov K, Scheper T (2002) Chemie ingenieur technik 74:1629

    Article  CAS  Google Scholar 

  35. Joeris K, Frerichs JG, Konstantinov K, Scheper T (2002) Cytotechnology 38:129

    Article  CAS  Google Scholar 

  36. Martinez G, Frerichs JG, Joeris K, Kontantinov K, Scheper T (2005) IEEE international conference on acoustics, speech and signal processing (ICASSP), vol 2. IEEE CNF, Philadelphia, p 497

    Google Scholar 

  37. Brückerhoff T, Frerichs JG, Joeris K, Konstantinov K, Scheper T (2005) Animal Cell Technology Meets Genomics. In: Godia F, Fussenegger M (eds) Proceedings of the 18th ESACT Meeting, Granada, Spain, May 11–14, 2003. Springer, p 589

  38. Brückerhoff T (2006) Bildbasiertes Inline-Monitoring von Kultivierungsprozessen mit einem optimierten In situ Mikroskopsystem, Universität Hannover

  39. Larsson C, Vonstockar U, Marison I, Gustafsson L (1993) J Bacteriol 175:4809

    CAS  Google Scholar 

  40. Camisard V, Brienne JP, Baussart H, Hammann J, Suhr H (2002) Biotechnol Bioeng 78:73

    Article  CAS  Google Scholar 

  41. Guez JS, Cassar JP, Wartelle F, Dhulster P, Suhr H (2004) J Biotechnol 111:335

    Article  CAS  Google Scholar 

  42. Hetland G, Ohno N, Aaberge IS, Lovik M (2000) FEMS Immunol Med Microbiol 27:111

    CAS  Google Scholar 

  43. Ohno N (2000) Nippon Saikingaku Zasshi 55:527

    CAS  Google Scholar 

  44. Ohno N, Miura NN, Nakajima M, Yadomae T (2000) Biol Pharm Bull 23:866

    CAS  Google Scholar 

  45. Rudolph G, Lindner P, Gierse A, Bluma A, Martinez G, Hitzmann B, Scheper T (2007) Biotechnol Bioeng 98:313

    Article  Google Scholar 

  46. Espinoza E, Martinez G, Frerichs J-G, Scheper T (2006) 3rd IEEE international symposium on biomedical imaging. IEEE CNF, ISBI 2006, Arlington, Virginia, USA p 542

  47. Martinez G, Frerichs JG, Joeris K, Konstantinov K, Scheper T (2006) IEEE international conference of acoustics, speech and signal processing (ICASSAP 2006), vol 2. IEEE CNF, ICASSP 2006, Tolouse, France p 581

  48. Wei N, You J, Friehs K, Flaschel E, Nattkemper TW (2007) Biotechnol Lett 29:373

    Article  CAS  Google Scholar 

  49. Wei N, You J, Friehs K, Flaschel E, Nattkemper TW (2007) Biotechnol Bioeng 97:1489

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tim Höpfner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Höpfner, T., Bluma, A., Rudolph, G. et al. A review of non-invasive optical-based image analysis systems for continuous bioprocess monitoring. Bioprocess Biosyst Eng 33, 247–256 (2010). https://doi.org/10.1007/s00449-009-0319-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00449-009-0319-8

Keywords

Navigation