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Sensor-based cell and tissue screening for personalized cancer chemotherapy

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Abstract

Personalized tumor chemotherapy depends on reliable assay methods, either based on molecular “predictive biomarkers” or on a direct, functional ex vivo assessment of cellular chemosensitivity. As a member of the latter category, a novel high-content platform is described monitoring human mamma carcinoma explants in real time and label-free before, during and after an ex vivo modeled chemotherapy. Tissue explants are sliced with a vibratome and laid into the microreaction chambers of a 24-well sensor test plate. Within these ≈23 μl volume chambers, sensors for pH and dissolved oxygen record rates of cellular oxygen uptake and extracellular acidification. Robot-controlled fluid system and incubation are parts of the tissue culture maintenance system while an integrated microscope is used for process surveillance. Sliced surgical explants from breast cancerous tissue generate well-detectable ex vivo metabolic activity. Metabolic rates, in particular oxygen consumption rates have a tendency to decrease over time. Nonetheless, the impact of added drugs (doxorubicin, chloroacetaldehyde) is discriminable. Sensor-based platforms should be evaluated in explorative clinical studies for their suitability to support targeted systemic cancer therapy. Throughput is sufficient for testing various drugs in a range of concentrations while the information content obtained from multiparametric real-time analysis is superior to conventional endpoint assays.

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Authors and Affiliations

  1. Heinz Nixdorf-Lehrstuhl für Medizinische Elektronik, Technische Universität München, Theresienstrasse 90/N3, 80333, Munich, Germany

    Regina Kleinhans, Martin Brischwein, Pei Wang, Bernhard Becker, Franz Demmel, Tobias Schwarzenberger, Marlies Zottmann, Peter Wolf & Bernhard Wolf

  2. HP Medizintechnik GmbH, Bruckmannring 19, 85764, Oberschleißheim, Germany

    Peter Wolf

  3. Pathologie Hamburg-West, Lornsenstraße 4, 22767, Hamburg, Germany

    Axel Niendorf

Authors
  1. Regina Kleinhans
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  2. Martin Brischwein
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  3. Pei Wang
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  4. Bernhard Becker
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  5. Franz Demmel
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  6. Tobias Schwarzenberger
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  7. Marlies Zottmann
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  8. Peter Wolf
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  9. Axel Niendorf
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  10. Bernhard Wolf
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Corresponding authors

Correspondence to Martin Brischwein or Bernhard Wolf.

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Kleinhans, R., Brischwein, M., Wang, P. et al. Sensor-based cell and tissue screening for personalized cancer chemotherapy. Med Biol Eng Comput 50, 117–126 (2012). https://doi.org/10.1007/s11517-011-0855-7

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  • DOI: https://doi.org/10.1007/s11517-011-0855-7

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