Impedimetric detection of anticancer drug action on individual tumor cells using field-effect transistor devices

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This thesis describes an advancement in a new technique for measuring biological and electronic properties of individual cells on planar devices. The measuring principle of this technique is based on the impedance measurement of open-gate field-effect transistor (FET) devices. Due to the fact that the size of the transistor gate is comparable with the size of individual cells, FET devices can achieve a real single cell analysis. Thus, the application of FET devices for this technique can extend to cell cultures, which do not form confluent cell layers, such as nerve cells, individual cells of the immune system, etc. The aim of this work was to investigate the cell-substrate adhesion process at an individual cell level using FET devices and to develop and elaborate a model explanation for the spectra, since the cellular adhesion plays an important part for understanding cancer cell behaviour. We further used this technique to proof effects of anticancer drugs to individual tumor cells. In the context of this work, a new amplifier system was developed, which offered an increased bandwidth of the readout system and enabled measuring of impedance spectra at higher frequencies (up to 50 MHz). The impedance spectra recorded with this measurement setup were interpreted with an electrically equivalent circuit (EEC) model, for which an analytical expression was derived. The measured impedance spectra with the developed amplifier system were fitted with the derived analytical expression and cell-related parameters were extracted. The ability to extract the biological relevant data from these complex spectra might be very important for the future application of our novel technique in biological experiments. Moreover, we utilized this EEC model to extract the device-related parameters and to fabricate a new generation of FET devices with better performance in cell-substrate adhesion experiments. However, the FET devices based on silicon are complex, expensive to manufacture, and have the significant disadvantage in cell culture applications that they are not optically transparent. Due to this fact, devices based on organic semiconductor material were developed and fabricated in this work. The cellular adhesion experiments performed in this work eventually open up commercial opportunities for the Electrical Cell-substrate Impedance Sensing using field-effect transistors.

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