Analysis of drug action on tumor cell metabolism using electronic sensor chips.

Chemotherapeutic drugs affect the metabolism of tumor cells regardless of the specific target of action. Basic parameters of cell metabolism are extrusion of acids into the microenvironment and oxygen consumption. To analyze these changes on living cells in real-time, a test system based on multiparametric chips with an array of sensors for monitoring pH and O(2) as well as electric impedance has been developed. Cells are cultivated on these chips and supplied with medium by a fluid perfusion set-up which mimics microphysiological conditions and allows for drug addition and removal. Human colon carcinoma cells LS174T were used as a model to test the effect of drugs. Cells growing on chips were monitored for 24 h and longer. Untreated cells showed a continuous increase in the rate of acidification, while the rate of respiration remained fairly constant. Addition of chloroacetaldehyde (50 microM) rapidly attenuated O(2) consumption with a gradual decrease in acidification following. In contrast, with cisplatin (16.7 microM) a delayed and gradual decrease in both the rates of acidification and respiration effect occurred over 2-3 days. These results provide insights to the mechanisms of action of these drugs, which are coherent with those already known. Thus, multiparametric sensor chips provide elementary information on drug action.