Ligand-regulated PEDOT-based nanoelectrochemical sensor for ultrasensitive and in situ detection of dopamine in single living cells.

In situ measurement of dopamine at single-cell resolution is critical for elucidating neurotransmitter-mediated biological mechanisms and neurodegenerative disorders. Owing to its non-invasive implantation capability and ultra-small tip size, nanoelectrode has broad application prospects in single-cell analysis. However, non-specific adsorption tends to passivate microelectrode activity, compromise specificity and lead to false-positive outcomes. Herein, we developed a novel nanoelectrochemical sensor by combining ligand-regulated poly-3,4-ethylenedioxythiophene with DNA double strands encapsulated with Ru(NH3)6Cl3 to achieve ultrasensitivity and specificity of dopamine detection in single living cells. Due to its hydrophilic, negatively charged and stable structure, ligand-modified poly-3,4-ethylenedioxythiophene as antifouling membrane was fabricated by one-step electrodeposition. This membrane effectively prevented non-specific adsorption compared with the reported zwitterionic materials and covalent organic framework materials, significantly enhanced signal response by approximately 6.9-fold and maintained over 92 % of the current response after 2 h. Taking advantage of the excellent anti-fouling capability, the proposed nanosenor could be employed for long-term monitoring and quantitative analysis of dopamine within individual living Pheochromocytoma cells. Moreover, it demonstrated high sensitivity, good stability and remarkable precision with an RSD of less than 1.68 % for repeated measurements. Before and after stimulating cells by L-DOPA, it witnessed the growth of the output signals of the single-cell analysis and the dopamine concentrations rose from 0.4 μM to 0.8 μM, indicating that the proposed sensor had outstanding detection capabilities. This research offers a powerful tool for the diagnosis and drug screening of neurodegenerative diseases.