CMOS Impedance Measurement Array for Cell Sensing

Abstract

Impedance measurement plays a vital role in determining the physical and chemical properties of live cells under different environmental conditions and aids in the development of cellular models for life science research and new medicines to fight disease. In order to improve the fidelity and spatial resolution of bio-impedance measurement systems, cell sensing platforms are being constructed using silicon chips where live cells interact with integrated microelectronic sensors through an on-chip electrode array. Our proposed complementary metal-oxide-semiconductor (CMOS) sensor array measures the impedance of complex cellular samples using a mixed-signal-based frequency response analysis (FRA) approach to extract and convert the real and imaginary parts of the cell impedance. The system is implemented using a synchronous voltage-to-frequency converter designed to operate over an input frequency range from 0.7 Hz to 2 kHz with a programmable nominal resolution up to 16 bits. Unlike previous work, we apply a switched-capacitor-based offset correction scheme to reduce the effect of multiplying integrator input offset on the sensor interface. The chip features an 8×6 surface electrode array of individually-addressable working electrodes connected to four independent impedance extraction channels for parallel data readout. The device is fabricated in a standard 0.18 µm CMOS technology, where each sensor channel consumes only 94 µW from a 1.8 V supply, and has been experimentally verified to provide linear conversion over an input current amplitude range from 40 pA to 60 nA.