High density CMOS electrode array for high-throughput and automated cell counting

A high-density electrical-impedance spectroscopy (EIS) biosensor array has been developed for high-throughput and automated counting of specific breast tumor MCF-7 cells. The biosensor array (96 × 96) consists of densely packed electrodes. Each of the square electrodes has an edge-length of 22 μm to capture single MCF-7 cell. The electrodes are electrically addressable by decoding circuit built underneath by 0.18 μm CMOS process. EIS spectra of electrodes were recorded over a wide frequency range with and without the presence of cell. Data were numerically fitted with the equivalent circuit model to extract important sensing parameters including cell impedance, electrode impedance, sealing resistance and spreading resistance. Results revealed a distinctive impedance increase from 50 kHz to 500 kHz, where the maximum (∼21% increment) occurs at 200 kHz. Enumeration of circulating tumor cells (CTCs) was performed by scanning an interrogation area of hundred electrodes at the optimum frequency. The developed EIS platform has demonstrated the electrical impedance detection with single cell resolution and enumeration with mapping accuracy of ∼90%.