Ligating Dopamine as Signal Trigger onto the Substrate via Metal-Catalyst-Free Click Chemistry for “Signal-On” Photoelectrochemical Sensing of Ultralow MicroRNA Levels

The efficiency of photon-to-electron conversion is extremely restricted by the electron–hole recombinant. Here, a new photoelectrochemical (PEC) sensing platform has been established based on the signal amplification of click chemistry (CC) via hybridization chain reaction (HCR) for highly sensitive microRNA (miRNA) assay. In this proposal, a preferred electron donor dopamine (DA) was first assembled with designed ligation probe (probe-N₃) via amidation reaction to achieve DA-coordinated signal probe (P_DA-N₃). The P_DA-N₃ served as a flexible trigger to signal amplification through efficiently suppressing the electron–hole recombinant. Specifically, the P_DA-N₃ can be successfully ligated into the trapped hairpins (H1 and H2) via the superior ligation method of metal-catalyst-free CC, in which the electron donor DA was introduced into the assay system. Moreover, the enzyme-free HCR, employed as a versatile amplification way, ensures that lots of P_DA-N₃ can be attached to the substrate. This PEC sensing for miRNA-141 detection illustrated the outstanding linear response to a concentration variation from 0.1 fM to 0.5 nM and a detection limit down to 27 aM, without additional electron donors. The sensor is further employed to monitor miRNA-141 from prostate carcinoma cell (22Rv1), showing good quantitative detection capability. This strategy exquisitely influences the analytical performance and offers a new PEC route to highly selective and sensitive detection of biological molecules.