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Med Biol Eng Comput (2012) 50:117126 DOI 10.1007/s11517-011-0855-7
ORIGINAL ARTICLE
Sensor-based cell and tissue screening for personalized cancer chemotherapy
Regina Kleinhans Martin Brischwein Pei Wang Bernhard Becker Franz Demmel
Tobias Schwarzenberger Marlies Zottmann Peter Wolf Axel Niendorf Bernhard Wolf
Received: 25 July 2011 / Accepted: 17 December 2011 / Published online: 31 January 2012 International Federation for Medical and Biological Engineering 2012
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 ll volume chambers, sensors for pH and dissolved oxygen record rates of cellular oxygen uptake and extracellular acidication. Robot-controlled uid 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 sufcient 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.
Keywords Targeted therapy Sensor Cancer tissue
Cell metabolism
1 Introduction
This work reports on an approach to testing human mamma carcinoma tissue for chemosensitivity by marker-free sensor records. Values of pH and dissolved oxygen reect not only the conditions of the cellular microenvironment but also cell metabolic activity which is impaired upon cytotoxic treatment. It is the rst time that a sensor-based measurement approach is applied systematically to cancerous human tissue.
Anticancer chemotherapy is scheduled based on the classication of the state of disease and the histopathological statement. It is well known, however, that therapeutical responses of equally categorized tumors may be totally different. Therefore, personalized predictive markers or assays for...