Sensing cellular adhesion with a CMOS integrated impedance-to-frequency converter

Sensing cellular adhesion via impedance measurements provides a versatile and easily accessible means for monitoring in-vitro cell cultures. In this work we present a CMOS impedance-to-frequency converter integrated with biocompatible planar surface electrodes to make a compact and robust sensor chip for in-vitro cell monitoring. The system features an 8 × 8 array of individually addressable electrodes connected to four impedance-to-frequency converter circuits with square wave output. The impedance-to-frequency converter circuits consist of a switchable constant current source, two comparators, and associated logic for addressing the pixel array and generating control signals. In designing the electrodes and circuit components, special attention had to be paid to keeping the current density and polarization voltage at the electrode low enough to avoid damaging the cells or triggering unwanted electrochemical reactions. To this end, FEM simulation was used to optimize electrode layout and electrical circuit parameters, keeping the electrode current below 100 nA. We present measurement results with cells that demonstrate the successful operation of the system and show good agreement with models of the electrode and cell impedances.