Correlation of Capacitance and Microscopy Measurements Using Image Processing for a Lab-on-CMOS Microsystem

Abstract

We present a capacitance sensor chip developed in a 0.35-μm complementary metal-oxide-semiconductor process for monitoring biological cell viability and proliferation. The chip measures the cell-to-substrate binding through capacitance-to-frequency conversion with a sensitivity of 590kHz/fF. In vitro experiments with two human ovarian cancer cell lines (CP70 and A2780) were performed and showed the ability to track cell viability in realtime over three days. An imaging platform was developed to provide time-lapse images of the sensor surface, which allowed for concurrent visual and capacitance observation of the cells. The results showed the ability to detect single-cell binding events and changes in cell morphology. Image processing was performed to estimate the cell coverage of sensor electrodes, showing good linear correlation and providing a sensor gain of 1.28 ± 0.29 aF/μm2, which agrees with values reported in the literature. The device is designed for unsupervised operation with minimal packaging requirements. Only a microcontroller is required for readout, making it suitable for applications outside the traditional laboratory setting.