Sensor technologies for monitoring metabolic activity in single cells-part II: nonoptical methods and applications

A review of solid-state chemical and electrochemical sensors to detect metabolic activity at the extracellular, single-cell level is presented in the context of the development of lab-on-a-chip research instrumentation. Metabolic processes in cells are briefly reviewed with the goal of quantifying the role of metabolites within the cell. Sensors reviewed include both research and commercial devices that can noninvasively detect extracellular metabolites, including oxygen, carbon dioxide, and glucose. Metabolic activity can also be sensed nonselectively by measuring pH gradients. Performance metrics, such as sensitivity, sensor size, drift, time response, and sensing range, are included when available. Highly suitable sensor technologies for monitoring cellular metabolic activity include electrochemical sensors, scanning electrochemical microscopy, ion-sensitive field effect transistor sensors, and solid-state light-addressable potentiometric sensors. Other less-suitable, but still potentially viable, solid-state sensing technologies are also reviewed briefly, including resonant chemical sensors (surface acoustic wave and quartz crystal microbalance), conductivity or impedance sensors, and sensors with multiple transduction stages. Specific biological applications which benefit from detection of extracellular metabolic events at the single-cell level are discussed to provide context to the practical use of these sensor technologies; these applications include case studies of various diseases (cancer, diabetes, mitochondrial disorders. etc.), cell and tissue differentiation; cell and tissue storage; cell life cycle and basic cellular processes; and developmental biology.