Electroanalytical chemistry has been widely developed and applied to the study of neurochemical systems. This then leads to a better understanding of many aspects of neurotransmission, for example, neural circuitry and neural substrates of compulsive drug use. This feasibility partly stems from the ease of oxidative detection of many neurotransmitters including dopamine, acetylcholine, norepinephrine, serotonin, glutamic acid and γ–aminobutyric acid. At the same time, this has also stimulated the development of structurally small electrodes for applications to the detection of neurotransmitters in biological microenvironments. In this respect, the small dimension of such electrodes permits minimal tissue damage upon implantation and, of equal importance, permits very careful selection of the region of tissue where measurements can be performed. In addition, the inherent fast response time of structurally small electrodes makes it feasible to follow biochemical events frequently taking place on a millisecond time scale (e.g. neuronal firing).
Various electrode materials used to construct structurally small electrodes of different geometries and sizes have hitherto been reported. Common electrode materials both modified and otherwise, include metals such as tungsten and aluminium, gold nanoparticledeposited aluminium, various forms of carbon e.g. doped diamond, nanocrystalline diamond, pyrolysed carbon, carbon fibres, and gold nanoparticles deposited onto glassy carbon.
A common problem encountered while performing in vivo electrochemical analyses of neurotransmitters is the adsorption of lipids, peptides and high molecular weight proteins present in biological matrices on the electrode surface. Formation of these layers leads to electrode fouling which distorts the voltammetric signal and suppresses the sensitivity of the electrode. Considerable research effort has been devoted to addressing electrode fouling problems. Approaches ranging from fast scan voltammetry, immobilising a protective organic film on the electrode surface, completely altering the surface termination, fabrication of nanocrystalline diamond coated electrodes, or of doped diamond electrodes, to gold electrodes modified with gold nanorod and gold nanoparticles have been developed. Apart from overcoming fouling, the latter methods have also demonstrated other advantages such as wider potential windows, greater durability, increased robustness and enhanced sensitivity.
In this paper, we aim to thoroughly review the techniques used in developing structurally small electrodes of different geometries, which were then applied to the detection of neurotransmitters. We will also pay special emphasis on the strategies used to minimize electrode fouling during electrochemical detection of neurotransmitters at these electrodes. A comparison of these methods and possible future directions in the development of structurally small electrodes for detection of neurotransmitters will conclude the review
