Living cells possess complex non-linear signal processing structures, thus enabling them to react to external influences. The presented system allows detecting changes in these structures by measuring the vitality and morphology of living cells in an easy and effective manner.
Therefore the interference of active agents with cellular processes can be monitored. Possible applications include pharmaceutical drug screening, toxicity testing and environmental monitoring. Due to the application of automation technology (robotic and controls) 24 experiments per assay can be performed in parallel. Experiments are repeatable and lack the risk of contamination or manual processing errors.
IMR - Fields of application |
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Pharmaceutical research, biology, cyto- / histopathology |
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Toxicity testing, drug discovery, “dose-response-relationships” |
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Morphological and metabolic investigations |
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Medical diagnostics |
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REACH-Tests |
Technology |
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Cultivation of up to 24 cells or tissue samples in modified micro-well-plates |
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Long term experiments beyond days or weeks |
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Liquid handling system with 24 channel pipetting head |
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Dynamic display of measurement values in real-time |
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Incubator for constant temperature, humidity and gas concentrations |
High-content screening-system
Up to 24 experiments in parallel on one plate
Imaging with an inverse (fluorescence) microscope
Detection of extracellular pH and pO2 by optical means for vitality classification
Measurement of adherence by electrical impedance provides additional information on cell density, number of cells and cell morphology
The system was designed for dynamic long-term experiments of several days or weeks, whereas the pipetting robot serves for medium and agent supply for the cell- or tissue assay. Measurement data (pH, pO2, bioimpedance) are read out from integrated sensors which are placed in a modified micro-well-plate multiple times per minute and displayed in the user control interface.
Relevance of the measured parameters
It is beneficial to evaluate multiple parameters in order to characterize cellular vitality, cellular activity and number of cells. Measured signals on pH or pO2 expose information on cellular metabolic activity. Additionally, bioimpedance measurements give information on cell-density and cell morphology. The microscope provides auxiliary image data.
As essential parameters of cellular physiology are evaluated a broad range of applications is possible.
Modified micro-well-plate
A sensor-equipped micro-well-plate is utilized for measurements of extracellular parameters in conjunction with a micro-fluidic system. Each plate consists of 24 wells which are supplied by two neighboring chambers. The central chamber is reduced in volume by a displacement cover in order to increase sensitivity. pH- and pO2 are detected optically whereas bioimpedance is measured electrically.
Results
Currently the system is applied for investigations on chemosensitivity of tumor cells. For a sample experiment, 4●104 cells (MCF-7) per well were seeded and pre-incubated for 2 days. At this time, about 60% of the total surface area of a well was covered with cells. The micro-well-plates were placed into the system and treated with the chemotherapeutic agents Doxorubicin and Cisplatin for 51 hours (beginning at 00:00:00).
Rates of oxygen consumption are plotted in the curves to the right. The wells were treated with 2 μM and 5 μM Doxorubicin respectively. Clearly a decrease in the metabolic activity (consumption of O2) in dependence on the dispensed concentration is observable.
In contrast, a control experiment without drugs that was carried out in parallel exhibits an increasing consumption of oxygen. The agent’s impact on acidification rate (pH) and cell density (bioimpedance, plot on the right) could be shown, too.
Perspective
A preclinical trial on chemosensitivity testing is currently performed with the measurement system on cell-lines and tissue samples. In the future, an individual tumor therapy will be available, as effective and non-effective drugs can be distinguished. Thus, these tests could improve cancer treatment and save expenses as well as adverse effects in chemotherapies.
Produktvideo IMR
