Towards High Throughput Cell Growth Screening: A New CMOS 8 $\times$ 8 Biosensor Array for Life Science Applications

In this paper we present a CMOS capacitive sensor array as a compact and low-cost platform for high-throughput cell growth monitoring. The proposed biosensor, consists of an array of 8 × 8 CMOS fully differential charge-based capacitive measurement sensors. A DC-input ΣΔ modulator is used to convert the sensors' signals to digital values for reading out the biological/chemical data and further signal processing. To compensate the mismatch variations between the current mirror transistors, a calibration circuitry is proposed which removes the output voltage offset with less than 8.2% error. We validate the chip functionality using various organic solvents with different dielectric constants. Moreover, we show the response of the chip to different concentrations of Polystyrene beads that have the same electrical properties as the living cells. The experimental results show that the chip allows the detection of a wide range of Polystyrene beads concentrations from as low as 10 beads/ml to 100 k beads/ml. In addition, we present the experimental results from H1299 (human lung carcinoma) cell line where we show that the chip successfully allows the detection of cell attachment and growth over capacitive electrodes in a 30 h measurement time and the results are in consistency with the standard cell-based assays. The capability of proposed device for label-free and real-time detection of cell growth with very high sensitivity opens up the important opportunity for utilizing the device in rapid screening of living cells.