CMOS Capacitive Sensor for Cellular and Molecular Monitoring

This thesis focuses on the design and implementation of complementary metal-oxide-semiconductor (CMOS) based capacitive sensors for life science applications. The use of CMOS capacitive sensors has shown to be effective in a variety of applications, including chemical solvent monitoring, cellular monitoring, and DNA analysis. Despite significant advances, major challenges still exist with the current CMOS capacitive biosensing technologies including extending the dynamic range of detection, diminishing the sensitivity to remnants, and rapid high-throughput monitoring.

In the second chapter, a fully integrated capacitive sensor with a wide input dynamic range (IDR) and a digital output is proposed. The design concepts and constraints, functionality, characterization, and experimental results with chemical solvents are also demonstrated in this chapter. With this novel topology, a significant increase in the IDR has been achieved which is discussed in the same chapter. Furthermore, in this chapter, we have proposed a novel calibration-free capacitive sensing technique. The proposed technique allows for uncovering the sudden changes due to the remnants as well as gradual changes due to target molecules and cells. The input dynamic range of the system is 400fF based on the post-layout simulation results. the measured resolution of the sensor is equal to 416 aF with up to 1.27 pF input offset adjustment range using the programmable bank of capacitors with a resolution of 10 fF.

In the third chapter, we present a fully integrated capacitive sensor array for life science applications. This sensing device consists of an array of 16 × 16 interdigitated electrodes (IDEs) integrated with a charge-based readout and multiplexing circuitries on the same chip. This sensing device has a wide IDR of about 100 fF and a resolution of 150 aF, and the capability of temporal, spatial, and dielectric sensing. It makes it possible to develop a low-cost, calibration-free sensing platform for life science applications. In this chapter, the functionality and applicability of the proposed sensing device have been demonstrated and discussed by introducing various chemical solvents including ethanol, methanol, and pure water. The simulation and experimental results achieved in this work have taken us one step closer to a fully automated calibration-free capacitive sensing platform for high-throughput monitoring in life science applications.

In the fourth chapter, the applicability of the proposed CMOS capacitive sensor for monitoring dried DNA mass has been demonstrated with experimental results. These experiments enabled us to measure the linear effect of five different concentrations with a resolution of 45 ng/μl DNA mass in ultra-pure water. With this novel application of the CMOS capacitive sensor, we can monitor the dried DNA for DNA storage monitoring purposes. Based on the results, the detection range of sub-pico mol has been achieved which is compatible with the concentrations of DNA used in DNA memory technologies.

In the fifth chapter, a rapid and accurate assessment of oral cells using our CMOS capacitive sensor chips has been demonstrated. This kind of diagnostics allows for the early detection and control of periodontal and gum diseases. the experimental and simulation results demonstrate the functionality and applicability of the proposed sensor for monitoring oral cells in a small volume of 1 µl saliva samples. These results reveal that the hydrophilic adhesion of oral cells on the chip alters the capacitance of IDEs. The presented results in this chapter set a new stage for the emergence of sensing platforms for testing oral samples.