Real-time, Voltammetric Co-Detection of Serotonin and Glucose at Carbon-Fiber Microbiosensors

Glucose is the major fuel source for the brain. As such, glucose availability and metabolism are inextricably linked to neurotransmission and, thus, to circuit function. Serotonin (5-HT) is a neurochemical of interest because it has been implicated in diverse neuropsychiatric disorders including mood disorders (anxiety and depression), schizophrenia, and substance abuse. However, it remains unknown how local glucose availability modulates 5-HT transmission at discrete release sites. In this work, carbon-fiber microelectrodes were modified with a chitosan matrix containing glucose oxidase, which generates electroactive hydrogen peroxide selectively in the presence of glucose. These microbiosensors are coupled with fast-scan cyclic voltammetry to allow for the real-time, simultaneous detection of 5-HT and glucose in rat brain tissue. This approach is completely different from the traditional biosensing paradigm which couples amperometry with biosensors that are specifically designed to exclusively evaluate only one analyte at a time. Our voltammetric strategy exploits the unique chemical signature from each analyte to allow for identification of many electroactive components in a complex mixture, at the same time, without the use of size- or charge-selective polymeric exclusion membranes. The voltammetric microbiosensors have been characterized for stability, selectivity, and sensitivity to glucose and 5-HT, and have been assessed on their ability to distinguish a range of potential interferents including dopamine, norepinephrine, 5-hydroxyindole acetic acid, histamine, and non-enzymatically produced hydrogen peroxide. The ability to simultaneously record rapid fluctuations of glucose and 5-HT at a single location promises to provide a new perspective that links neurotransmission with metabolic activity, and ultimately to inform improved therapeutic treatment strategies for a wide range of disorders in which both 5-HT transmission and glucose metabolism are altered.