Correlation of capacitance and microscopy measurements using image processing for a lab-on-CMOS microsystem
We present a capacitance sensor chip developed in a 0.35 μm CMOS process for monitoring biological cell viability and proliferation. The chip measures cell-to-substrate binding through capacitance-to-frequency conversion with a sensitivity of 590 kHz/fF. In vitro experiments with two human ovarian cancer cell lines (CP70, A2780) were performed and showed the ability to track cell viability in real-time 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. Results showed the ability to detect single cell binding events and changes in cell morphology. Image processing was performed to estimate 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 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.