Untersuchung einer neuen Methode zur Integration von angebundenen Doppellipidschichten in CMOS-Strukturen zur Realisierung bioelektrischer Sensoren

The present work deals with the field of biosensors for the detection of tumor markers. Most of the conventional methods for cancer diagnosis in humans are imaging techniques. As with the methods only relatively large tumors can be reliably determined, it is desirable to develop methods that are able to detect cancer at an earlier stage of growth to offer efficient therapy. This is facilitated by the detection of the so-called tumor markers in body fluids such as blood, urine and saliva. Since the existing laboratory analysis is very complex and time-consuming, new detection methods are being investigated to provide an inexpensive, fast and easy to handle alternative. The biosensor principle developed in the present work is based on the analysis of a capacitive effect. The sensor consists of a readout circuit and an electrode with an attached tethered bilayer lipid membrane, which has the ability to absorb Valinomycin peptides. Valinomycin is an ion carrier, which transports ions across the membrane. Through the increase of the ion concentration in the region between membrane and electrode, the so-called spacer region, the capacitance increases due to an increase of the permittivity. This effect has not been used for biosensor applications, yet. To further examine the application of this effect in biosensors the relation between the Spacer capacitance and the Valinomycin concentration has been first investigated with electrochemical impedance spectroscopy. A "switched-capacitor circuit" has been developed to implement a readout circuitry in CMOS. The function of the sensor chip after fabrication has been checked with a test circuit that mimics the membrane. It shows a good consistence between simulation and measurement within the measurement accuracy. Thus it is confirmed that the chip can read out the expected capacitance changes. Further a change in concentration of 100 nM Valinomycin has been detected with the CMOS readout circuit. A rough estimation gives a detection limit for the Valinomycin concentration of about 10 pM. The novel biosensor principle is marker-free and allows a quantitative interpretation of the concentration of the analytes in the sample. This is an advantage compared to optical methods, such as fluorescence spectroscopy. Moreover, the measurement result can be read out directly. There is no need for further extraction of the measured data from a theoretical fitting, such as in the electrochemical impedance spectroscopy. Fast measurements are achieved by running the CMOS chip in the kilohertz range. Based on the results of the present study the field of biosensors is extended by a novel biosensor principle, which in combination with artificially modified ion channels is a promising tool for cancer diagnosis.


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