Separation-based sensors using microchip electrophoresis with microdialysis for monitoring glutamate and other bioactive amines

Abstract

Large increases in the release of glutamate (Glu) into the extracellular space of the brain have been shown to produce excitotoxicity, which can lead to long-term neuronal damage seen in many neurological disorders, including traumatic brain injury (TBI) and stroke. Therefore, methods for continuous monitoring of extracellular Glu concentrations in the brain can be very useful to clinicians for determining the best timing for pharmacological intervention. Microdialysis (MD) is an in vivo sampling method that, when coupled with a separation-based analytical method, makes it possible to monitor multiple analytes simultaneously with high temporal resolution. Very low flow rates are associated with this sampling method (typically between 0.1 and 1 μL/min), leading to very small sample volumes per unit time. To maximize the analysis of microdialysis samples with good temporal resolution, several methods for integrating MD with microchip electrophoresis (ME) have been described. Microdialysis coupled to microchip electrophoresis (MD-ME) can provide rapid analysis of complex samples using sample injection volumes less than 100 nL. However, the design and construction of MD-ME devices requires a high degree of planning and knowledge of microfabrication. The processes outlined in this chapter detail what we have found to be the best practices of design, construction, and operation of MD-ME devices.