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Cytotechnology

, Volume 38, Issue 1–3, pp 129–134 | Cite as

In-situ microscopy: Online process monitoring of mammalian cell cultures

  • Klaus Joeris
  • Jan-Gerd Frerichs
  • Konstantin Konstantinov
  • Thomas Scheper
Article

Abstract

The in-situ microscope is a system developed to acquire images of mammalian cells directly inside a bioreactor (in-situ) duringa fermentation process. It requires only minimal operator intervention and it is well suited for either batch or long-termperfusion fermentation runs. The system fits into a 25 mm standard port and has a retractable housing, similar to the industry standard InTrac. Therefore, it can be cleaned and serviced without interruption of the process or risking contamination. A sampling zone inside the bioreactor encloses adefined volume of culture and an image sequence is taken. The height of the sampling zone is set by the control program and canbe adjusted during the cultivation to accommodate a wide range of change in cell density. The system has an infinity correctedoptical train and uses a progressive scan CCD camera to acquirehigh quality images. Process relevant information like cell density is extracted fromthe images by digital image processing software, currently in development for mammalian cells (CHO, BHK). The first version ofthe software will be able to estimate the cell density, cellsize distribution and to give information of the degree of aggregation (single and double cells, cell clusters).

image analysis in-situ microscopy online biomass estimation online bioprocess monitoring 

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References

  1. Bittner C, Wehnert G & Scheper T (1998) In-situ microscopy for online determination of biomass. Biotechnol Bioeng 60: 24–35.Google Scholar
  2. Frerichs, JG (2000) Entwicklung eines In-situ Mikroskops zur bildgestützten Online-Ñberwachung von Bioprozessen. Ph.D. Thesis, University of Hannover.Google Scholar
  3. Mettler-Toledo GmbH (2000) Retractable Housings InTrac 797, product information sheet. Process Analytics, Industrie Nord, CH-8902 Urdorf.Google Scholar
  4. Suhr H, Wehnert G, Schneider K, Bittner C, Scholz T, Geißler P, Jähne B & Scheper T (1995) In-situ microscopy for online characterisation of cell-populations in bioreactors, including cell concentration measurements by depth from focus. Biotechnol Bioeng 57.Google Scholar
  5. Suhr H (1997) In-situ Mikroskopsonde und Messverfahren. German patent DE 40 32 002 C2.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Klaus Joeris
    • 1
  • Jan-Gerd Frerichs
    • 2
  • Konstantin Konstantinov
    • 1
  • Thomas Scheper
    • 2
  1. 1.Pharmaceutical Division, Department of Cell Culture and Bioprocess EngineeringBayer CorporationBerkeleyUSA
  2. 2.Institut für Technische ChemieUniversity of HannoverHannoverGermany

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