Microphysiological testing for chemosensitivity of tumor cells with multiparametric microsensor-chips

A.M. Otto, Dr. rer. nat., M. Brischwein, Dr. rer. nat., H. Grothe, Dr. ing., E.M. Motrescu, Dipl. biol., B. Wolf, Dr. rer. nat.

Technical University of Munich, Munich, Germany

AIM: Unnecessary chemotherapeutic treatment could be avoided and potentially more effective drugs could be selected if the chemosensitivity of tumors were known before the beginning of a treatment. While many approaches have been employed to test for the sensitivity of the tumor to the drug in vitro, such assays are based on only a single cellular/biochemical parameter. Multiparametric microsensor chip-aided assays were developed for the detection of both morphological and metabolic changes in living cells. METHODS: Cells and tissues are grown directly on a glass- or silicon-based sensor chip. Presently three parameters are amenable to sensor-readings: changes in 1) extracellular pH and 2) p O2, reflecting metabolic activities, and changes in 3) impedance, reflecting morphological properties such as cell-cell and cell-matrix adhesion. A fluidic system mimics physiological conditions by providing nutrients (and drugs) and removing metabolic products. Further features of the set up are continuous data acquisition for up to several days, analysis before and after drug administration on the same specimen, and recordings on small amounts of cellular specimen. RESULTS: Data obtained with drug sensitive and resistant cell lines as well as with cancer explants shows that following chemotherapeutic drug exposure there is 1) a gradual reduction in medium acidification, 2) a marked, almost immediate reduction in O2 consumption and 3) changes in impedance correlating with morphological changes observed in the microscope. Drug-resistant cells do not show these changes. CONCLUSIONS: Drug-induced changes in energy metabolism and in morphology can be continuously monitored on living cells growing on microsensor chips.

For more information, contact

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Novel Therapies, Part 1.