Multiparametric sensor chips for chemosensitivity testing of sensitive and resistant tumor cells.

Abstract

Many different assays have been developed for testing the chemosensitivity of tumor cells in vitro, usually based on a single biochemical or cellular parameter. A multiparametric test system has been developed that accommodates on a single chip numerous sensors for metabolic parameters, deltapH and deltapO2, as well as for morphological changes. The cells grow directly on the chips and can be continuously monitored online up to several days. The effects of various chemotherapeutic drugs on the metabolic profile of several tumor cell lines have been investigated. In colon carcinoma-derived LS174T cells, cytochalasin B markedly increased oxygen consumption while decreasing the rate of extracellular acidification. These effects, which reflect the biochemical action of cytochalasin B, were reversible on drug removal. In contrast, chloroacetaldehyde markedly reduced respiration, which recovered when the drug was removed. Primary breast cancer cells also responded to chloroacetaldehyde with a marked reduction in deltapO2, followed by a reduced rate of acidification. Comparing the metabolism of doxorubicin-sensitive and -resistant mouse sarcoma S180 cells, the rates of acidification and respiration were inhibited by doxorubicin only in the sensitive cells, whereas in the resistant cells oxygen consumption even increased. These examples demonstrate that this chip-based test system provides rapid and important information for assessing chemosensitivity of tumor cells.