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Automated live cell screening system based on a 24-well-microplate with integrated micro fluidics

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Abstract

In research, pharmacologic drug-screening and medical diagnostics, the trend towards the utilization of functional assays using living cells is persisting. Research groups working with living cells are confronted with the problem, that common endpoint measurement methods are not able to map dynamic changes. With consideration of time as a further dimension, the dynamic and networked molecular processes of cells in culture can be monitored. These processes can be investigated by measuring several extracellular parameters. This paper describes a high-content system that provides real-time monitoring data of cell parameters (metabolic and morphological alterations), e.g., upon treatment with drug compounds. Accessible are acidification rates, the oxygen consumption and changes in adhesion forces within 24 cell cultures in parallel. Addressing the rising interest in biomedical and pharmacological high-content screening assays, a concept has been developed, which integrates multi-parametric sensor readout, automated imaging and probe handling into a single embedded platform. A life-maintenance system keeps important environmental parameters (gas, humidity, sterility, temperature) constant.

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References

  1. Arain S et al (2006) Characterization of microtiterplates with integrated optical sensors for oxygen and pH, and their applications to enzyme activity screening, respirometry, and toxicological assays. Sen Actuators B113:639–648

    Article  Google Scholar 

  2. Axelrod D (1983) Total internal inflection fluorescent microscopy. J Microsc 129:19–28

    Google Scholar 

  3. Berney C, Danuser G (2003) FRET or no FRET: a quantitative comparison. Biophys J 84:3992–4010

    Article  Google Scholar 

  4. Brakenhoff GJ et al (1979) Confocal scanning light microscopy with high aperture immersion lenses. J Microsc 117:219–232

    Google Scholar 

  5. Brischwein M, Grothe H, Otto AM, Stepper C, Motrescu E, Weyh T, Wolf B (2004) Living cells on chip: bioanalytical applications. In: Mirsky VM (ed) Ul-trathin electrochemical chemo- and biosensors. Springer, Berlin, pp 159–180

    Google Scholar 

  6. Brischwein M, Motrescu ER, Otto AM, Cabala E, Grothe H, Wolf B (2003) Functional cellular assays with multiparametric silicon sensor chips. Lab Chip 3(4):234–240

    Article  Google Scholar 

  7. Constans A (2004) Automated microscopy gets a new shape. Scientist 18:41–43

    Google Scholar 

  8. Denk W et al (1990) Two-photon laser scanning fluorescence microscopy. Science 248:73–76

    Article  Google Scholar 

  9. Ehret R et al (1996) Monitoring of cellular behavior by impedance measurements on interdigititated electrode structures. Biosens Bioelectron 12:29–41

    Article  Google Scholar 

  10. Entzeroth M (2003) Emerging trends in high-throughput screening. Curr Opin Pharmacol 3:522–529

    Article  Google Scholar 

  11. Geisler T et al (2006) Automated multiparametric platform for high-content and high-throughput analytical screening on living cells. IEEE Trans Autom Sci Eng 3:169–176

    Article  Google Scholar 

  12. Hertzberg RP et al (2000) High-throughput screening: new technology for the 21st century. Curr Opin Chem Biol 4:445–451

    Article  Google Scholar 

  13. Kraus M, Wolf B (1995) Structured biological modelling—a new approach to biophysical cell biology. CRC Press, Boca Raton

    Google Scholar 

  14. Lob V et al (2005) Cell-based assays: mikrosensorarray-basiertes screening an lebenden Zellen und Geweben. Biospektrum 11:511–512

    Google Scholar 

  15. Lob V et al (2006) Chip statt Maus: Mikrosensor-arrays zur Chemikalienprüfung. Nachrichten aus der Chemie 54:115–120

    Google Scholar 

  16. Moore K et al (2001) Cell-based versus isolated target screening: how lucky do you feel? J Biomol Screen 6:69–74

    Google Scholar 

  17. Trugnan G et al (2004) FRAP, FLIP, FRET, BRET, FLIM, PRIM...new techniques for a colourful life. Med Sci (Paris) 20:1027–1034

    Google Scholar 

  18. Wiest J et al (2005) Cellular assays with multiparametric bioelectronic sensor chips Chimia 59:243–246

    Article  Google Scholar 

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Acknowledgments

We would like to thank Heraeus Sensor Technology GmbH in Kleinostheim, Thermo Electron Corporation in Oberschleiβheim, Rawe Electronic GmbH in Weiler i. Allg., PreSens GmbH in Regenburg, TILL Photonics GmbH and the BioImaging Centre in Gräfelfing as well as Microcoat Biotechnology GmbH in Bernried for their cooperation.

We are grateful to the Bavarian Research Foundation (BFS), The Federal Ministry of Education and Research (BMBF), the Heinz Nixdorf Foundation and the Foundation of Industrial Research of their financial support.

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Correspondence to B. Wolf.

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Lob, V., Geisler, T., Brischwein, M. et al. Automated live cell screening system based on a 24-well-microplate with integrated micro fluidics. Med Bio Eng Comput 45, 1023–1028 (2007). https://doi.org/10.1007/s11517-007-0260-4

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  • DOI: https://doi.org/10.1007/s11517-007-0260-4

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