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Specific electroanalysis of neurotransmitters in the brain, bloodstream, cerebrospinal fluid (CSF), or at the cellular level critically depends on the availability of miniaturized electrodes for aptasensing. Yet, with electrode miniaturization, sensitivity of analysis and limits of detection (LOD) can be compromised. Here, we adapted the RNA-aptamer-based macroelectrode assay for dopamine to the microelectrode format, by using gold-plated carbon fiber microelectrodes (CFE), modified via thiol chemistry with cysteamine and an RNA aptamer, for specific dopamine detection. The sensitivity of analysis with gold-plated cylindrical microelectrodes improved 90-fold, to 9.75 μA μM −1 cm −2 (at +0.100 V) vs. 108 nA μM −1 cm −2 (at optimal +0.185 V) shown with gold disk macroelectrodes, with LOD being 60 and 100 nM, in PBS and in artificial CSF, respectively. Yet, epinephrine interfered at 0.1 V. At 0.05 V, the sensitivity dropped to 4.62 μA μM −1 cm −2 but the RNA-aptamer/cysteamine-modified CFEs demonstrated excellent selectivity for dopamine over epinephrine, norepinephrine, L-DOPA, DOPAC, and uric and ascorbic acids. These findings suggest a straightforward strategy for constructing biospecific aptamer-based microelectrodes. However, in matrices more complex than CSF, such as serum, dopamine oxidation was inhibited. Therefore, effective monitoring of dopamine levels in blood using aptamer microelectrodes will likely require the use of protective membranes. • 5 μm carbon fiber microelectrode (CFE) is Au plated and RNA aptamer/cysteamine-modified. • Modified CFE selectively detects dopamine over related neurotransmitters. • Sensitivity of detection is improved 90-fold compared to macroelectrodes, LOD being 60 nM. • In matrices more complex than CSF, such as serum, dopamine oxidation is inhibited. • Suggested design requires using protective membranes for in vivo–targeting applications.
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Bache et al. (2026) studied this question.
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