Bioimpedance microelectronics in a 24-microwell plate with metabolic-sensors for testing chemosensitivity of tumor cells and tissues

Living cells react to external influences such as pharmacological agents in an intricate manner due to their complex internal signal processing. Cell reactions are an impact on vitality, cell-cell or cell-matrix interaction and morphological changes. A number of published techniques on impedance spectroscopy (IS) of adherent cells with planar electrodes address these changes. However, IS can merely serve as an indicator of cellular events rather than provide detailed information on a specific cell process. Thus our approach is a 24-microwell sensor-plate with impedance-electrodes in parallel to pH-and O₂-sensors, capable of being integrated into a fully automated screening system. For the purpose of IS, high precision impedance-electronics have been developed based on integrated circuits and validated against a Solartron 1260 impedance analyzer. IS data is correlated to the metabolic-sensors and additionally compared with cell images shot by an inverse optical microscope which is also part of the screening system. Proof of principle is demonstrated by experimental growth monitoring of a MCF-7 culture and cellular response to chemotherapeutics. Furthermore, the potential to monitor living tissue probes is presented for the first time.