title: Sensor-based cell and tissue screening for personalized cancer chemotherapy.
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.
authors.affiliation: Heinz Nixdorf-Lehrstuhl für Medizinische Elektronik, Technische Universität München, Theresienstrasse 90/N3, 80333 Munich, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Kleinhans
authors.forename: Martin
authors.initials: M
authors.lastname: Brischwein
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.forename: Bernhard
authors.initials: B
authors.lastname: Becker
authors.forename: Franz
authors.initials: F
authors.lastname: Demmel
authors.forename: Tobias
authors.initials: T
authors.lastname: Schwarzenberger
authors.forename: Marlies
authors.initials: M
authors.lastname: Zottmann
authors.forename: Peter
authors.initials: P
authors.lastname: Wolf
authors.forename: Axel
authors.initials: A
authors.lastname: Niendorf
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wolf
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015374:Biosensing Techniques / Q000379:methods*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D010101:Oxygen Consumption / Q000502:physiology; D057285:Precision Medicine / Q000379:methods*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents