| Summary: | Much research has been done on biosensors employing microelectrode arrays for biomedical applications. An important application is the detection of circulating tumour cells for cancer diagnostics and treatment. This and many other applications require dealing with a large number of cells, leading to a need for large microelectrode arrays. Fast measurement approaches are required to process these large arrays in the available timeframe. One suitable approach is electrochemical impedance spectroscopy (EIS) if compelling results can be obtained from high frequencies. However, basic design approaches do not scale well with the growing number of electrodes. The increasing need for circuits providing addressing and signal processing leads to mounting parasitic couplings and intensifies the problem of matching between the individual electrodes. While the electrode/electrolyte system is well modelled in the literature, the overall system requires more detailed understanding to improve measurement quality. Moreover, methods need to be developed to improve the specificity of measurement results.
Two previously developed active CMOS biosensor chips were studied for this Thesis. The first of these designs was a basic architecture integrating an array of 96x96 microelectrodes and a tree structure for selecting individual electrodes. The second design featured an array of 104x104 microelectrodes, and improved selection scheme and amplifiers close to the electrodes to improve signal integrity. For comparison, passive biosensor chips made from gold electrodes on a glass substrate were studied. Analytical models were developed to improve understanding of the results, and simulations were done to support the findings. Surface treatments with aptamers were explored to improve the selectivity of the biosensor. A new CMOS biosensor incorporating lessons from the previous designs was developed. In this Thesis, the design and manufacturing of the used biosensor chips is described with emphasis on design principles and post-processing. Measurement results are presented and compared. Expanded models are derived to give an improved explanation of the observed results. Simulations results are presented that support the new models and indicate possible improvements of the electrode structure. Improved cell capture utilizing aptamers is described, as well as the effects of the aptamer layer on EIS results. Finally, the new biosensor design featuring source measurement units (SMU) for EIS is presented.
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