Design a programmable clock generator for a unique Pixelated Capacitive Biosensor chip

Label-free biosensors for the study of cell biology have finally come of age. Recent developments have transformed biosensors from low throughput, high maintenance research tools to high throughput, low maintenance screening platforms. In parallel, biosensors have evolved from analytical tools designed exclusively for the analysis of molecular interactions to powerful platforms for the study of cell biology at the whole-cell level. Despite these successes, however, bioelectronics has not yet succeeded in developing a widely applicable all-electronics biosensor platform. This is partly because in the most promising CMOS-based capacitive biosensors, DC or low-frequency signals cannot be used to probe beyond the electrical double layer formed by shielding salt ions, which means that under physiological conditions the sensing of a target analyte is located even at a short distance from the sensor (∼1 nm) is severely hampered. The PT2 biosensor platform, originally developed by NXP Semiconductors, offers massively parallel, label-free biosensing that can, in principle, be created by combining all-electrical detection with low-cost integrated circuits. It has been demonstrated that high-frequency impedance spectroscopy can be used to detect and image microparticles and living cells under physiological salt conditions. The test uses a large-scale, high-density array of nanoelectrodes integrated with CMOS electronics on a single chip. The response of the sensor depends on the electrical properties of the analyte, enabling impedance-based fingerprinting. The PT2 biosensor platform allows real-time imaging of the dynamic attachment and micromotion of BEAS, THP1, and MCF7 cancer cell lines with sub-micrometer resolution in growth medium. This demonstrates the potential of the platform for label/tracer-free high-throughput screening of e.g. novel drug candidates for cancer treatment. However, this platform with its current control system, can only reliably operate the biosensor chip up to a switching frequency of 70 MHz. But the chip itself can run up to at least 350 MHz. At this frequency, biosensing measurements will suffer less from false signals caused by non-specific binding of molecules to the nanoelectrodes. Also, at higher frequencies, the clock pulses are distorted too much because of non-optimal impedance matching conditions and cross-talk in the long clock wires. With a new clock generator chip, we want to unlock this extended frequency range and overcome the problems. In this thesis, we report the design of a non-overlapping clock generator chip for frequencies up to 500 MHz. The chip also generates an ADC clock for the on-chip ADCs of the PT2 sensor chip, and a reference clock for frequency calibration. The main features of the clock signals are coarsely programmable, i.e. pulse width, non-overlap delay, and clock pulse amplitudes. The non-overlapping clock generator can be configured by writing configuration bits via a serial interface. Apart from the functional parts, the chip also has ESD protection, with special attention for the high-frequency pins, i.e. the ESD protection should not disturb the clock pulses.