On-Chip Capacitance Sensing for Cell Monitoring Applications

We describe an integrated circuit for sensing the substrate coupling capacitance of anchorage-dependent living cells in a standard culture environment. Capacitance is measured using charge redistribution in response to weak, low frequency electric field excitations. The underlying biophysical phenomenon results primarily from the insulating nature of the cell structure and the counterionic polarization in the surrounding aqueous medium. The measured capacitance depends on a variety of factors related to the cell, its growth environment and the supporting substrate. These include membrane integrity, morphology, extracellular ionic concentration, adhesion strength, and substrate proximity. The measured capacitance is an indication of both the interaction between cells and substrate and cell health. The capacitance sensor uses the principle of charge sharing and translates sensed capacitance values to output voltages. The sensor chip has been fabricated in a commercially available 0.5-μm, 2-poly 3-metal CMOS technology. The sensing technique does not require direct electrical connection to the aqueous culture medium. We report results from experiments demonstrating on-chip tracking of cell adhesion as well as long term monitoring of cell viability in vitro.