Microelectrode array biosensor for high-resolution measurements of extracellular glucose in the brain

Direct measurement of glucose in the brain extracellular space with high spatial and temporal resolution is needed for understanding of brain energy metabolism. In this work we developed and extensively characterized an amperometric glucose microbiosensor using ceramic-based platinum multisite microelectrode arrays (MEAs) for measuring extracellular glucose in the rat brain in vivo. Glucose-oxidase (GOx) was immobilized at the microelectrode surface by cross-linking with glutaraldehyde in the presence of BSA. The in vitro evaluations supported the high analytical performance of these microbiosensors for application in the brain, including high selectivity and sensitivity, adequate linear range and limit of detection, good operational stability and response time, minimal oxygen-, pH- and temperature-dependencies. The microbiosensors were successfully used for measurements of glucose with high temporal and spatial resolution in the hippocampus of anesthetized rats in response to systemic, local glucose changes and upon glutamatergic stimulation. Overall, the results support the suitability of these microbiosensors for measuring rapid changes of extracellular glucose in the rat brain.