Since its original description in the 1970’s microdialysis sampling of the brain has become in important method to find out about the pattern of neurochemical changes underlying neuronal activity. The key problem limiting the application of microdialysis to particular areas of neuroscience has always been linked to advances in analytical methodologies. Microdialysis flow rates are low (typically 1 µL/min) and neurochemical concentrations often very low often in the µM to nM range, leading to a requirement for very high mass-sensitivity. Initially this was overcome by collecting sufficient dialysate volume to exceed the assay limit of quantification, this is turn limited microdialysis to situations where neurochemical changes took place on the timescale of 10’s minutes to hours – for example the effects of local drug application on levels of neurotransmitters. Analysis of the microdialysis stream on-line is now pushing this timescale to 10’s seconds to minutes, suitable for investigation brain physiology and pathology.<br/><br/>This presentation describes our work to improve the temporal resolution of microdialysis with the aim of allowing us to monitor dynamic neurochemical changes in the human brain (and other organs) in response to pathological stimulae. We have optimised both electrochemical and optical sensors and biosensors give high sensitivity in microchannels produced by micro-milling or 3D printing, scaled for microdialysis flow rates. As real-world biosensors loose sensitivity over time great attention has been paid to easy replacement of a single sensor in, for example, a panel of 4 sensors. Low-volume connections are also vital. As the measurement timescale moves to sub-minute Taylor dispersion in the connecting tubes between patient and bedside instrument becomes a limiting factor. We have addressed this in two ways: Firstly, we have designed and built wireless battery powered miniature tri-potentiostats allowing us to place our 3D printed chips next to the microdialysis probe outlet beside the patient; Secondly, we have built a novel screw-driven microdialysis pump that reliable produces multiphase droplet flow, allowing us to digitise the dialysate stream as it exits the patient.

Faster neurochemical measurements using continuous on-line microdialysis: Towards microdialysis 2.0

253rd National Meeting (2017)

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