CMOS Capacitance Biosensors to Monitor Cell Viability

Monitoring cell viability and proliferation is a ubiquitous goal with many applications in industries such as environmental science, food safety, and drug discovery. Conventional approaches to observe viability involve using dyes or chemical labels to identify healthy and unhealthy cells. However, these markers could potentially introduce side-effects and are typically endpoint assays: they cannot provide high-temporal resolution data that could reveal the dynamics of cell growth and death. Capacitance biosensors have been developed to tackle this challenge. These devices use complementary metal-oxide semiconductor technology to build arrays of sensors that can interface directly with cells and detect cell-substrate capacitance coupling which is indicative of cell health. This chapter presents an overview of the capacitance sensor chips developed to monitor cell viability. Front-end designs and system integration challenges are discussed. A specific example of an oscillator-based sensor design is then examined. Results of in vitro experiments are presented and show the ability to monitor cell proliferation and response to cytotoxic drugs over several days, with the sensitivity required to observe single-cell morphological events.