Developing a novel biosensor for detection of neurochemicals in blood

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The central aspect of neural communication in the central nervous system is chemical signalling involving amino acids and their derivatives. Amino acids glutamate and aspartate and the derivative N-acetyl aspartate (NAA), are present in high concentrations in the neurons and glial cells. Glutamate and NAA produce the largest peak in a proton magnetic resonance spectroscopy (MRS) scan of a healthy human brain, and their levels are reduced in neuropathologies and psychotic disorders. It has been shown that in age-related neurodegenerative diseases, levels of these amino acids drop dramatically in the brain as they leak into the extra cellular space and into the bloodstream. These compounds can therefore be employed as biomarkers for neuronal health, as they provide insight into the extent of ischaemic damage or brain injury. L-Asparte Oxidase (LAO) is the enzyme known to metabolise L-aspartate. LAO oxidises L-aspartate to iminoasparate, simultaneously producing H2O2. Because of substrate specificity, it can be used in conjunction with other enzymes in discriminating the presence of brain specific amino acids in the blood. Purified enzyme can be immobilised on the surface of the microelectrode, where the presence of H2O2 induces changes in the current which can be measured. The goal of the project is to integrate these enzymes into a microelectrode biosensor, that can detect and measure levels of neuroactive chemicals in vitro. To date measurements are made only through proton MRS, or microdialysis and High-Pressure Liquid Chromatography (HPLC); techniques which are both expensive and time consuming, and often produce signals that are contaminated by the presence of one or other amino acid because of their abundance. An electrochemical biosensor that can provide rapid measurement and directly give an indication of metabolic changes would potentially serve as a novel diagnostic tool for monitoring levels of amino acids in different disease conditions.