In research, pharmacologic drug-screening and medical diagnostics, the trend towards the utilization of functional assays using living cells is persisting. Research groups working with living cells are confronted with the problem, that common endpoint measurement methods are not able to map dynamic changes. With consideration of time as a further dimension, the dynamic and networked molecular processes of cells in culture can be monitored. These processes can be investigated by measuring several extracellular parameters. This paper describes a high-content system that provides real-time monitoring data of cell parameters (metabolic and morphological alterations), e.g., upon treatment with drug compounds. Accessible are acidification rates, the oxygen consumption and changes in adhesion forces within 24 cell cultures in parallel. Addressing the rising interest in biomedical and pharmacological high-content screening assays, a concept has been developed, which integrates multi-parametric sensor readout, automated imaging and probe handling into a single embedded platform. A life-maintenance system keeps important environmental parameters (gas, humidity, sterility, temperature) constant.
Cells are organic microsystems with functional compartments interconnected by complex signal chains. Intracellular signaling routes and signal reception from the extracellular environment are characterized by redundancy, i.e., parallel pathways exist. If a cell is exposed to an external "signal input", the signal processing elements within the cell provide a response that will be a pattern of reactions manifest as a metabolic, morphologic or electric "signal output". Cell-chip hybrid structures are miniaturized analytical systems with the capability to monitor such cell responses in real time and under continuous control of the environmental conditions. A system analysis approach gives an idea of how the biological component of these hybrid structures works. This is exemplified by the putative role of the microenvironmental pH as a parameter of the utmost importance for the malignant "mode" of tumor cells, which can be monitored and modeled on such hybrid structures.
Mit Mikrosensoren sind Messungen zellphysiologischer Parameter von lebenden Zellen möglich. Die Sensormessung ist extrazellulär und so angelegt, dass sie keine Beeinträch-tigung oder Störung des zellulären Lebens bewirkt. Dabei reicht das Spektrum der testbaren zellulären Proben sehr weit.
Mit Zellkulturen auf Sensorchips lassen sich metabolische und morphologische Parameter der Zellen online und in Realzeit erfassen. Die Anwendungen reichen von Chemosensitivitätstests über die Toxizitätsanalyse bis zum pharmakologischen Wirkstoffscreening.
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