Ultrasensitive Electrochemiluminescence Detection of MicroRNA via One-Step Introduction of a Target-Triggered Branched Hybridization Chain Reaction Circuit

High sensitivity and accuracy are two key issues that are critical for electrochemiluminescence (ECL) detection, especially for low-abundance nucleic acid detection. However, research on the construction of biosensors has mainly been through a step-by-step approach, which will increase the systematic error and affect the accuracy of the detection. Here we propose a novel strategy of introduction of a branched hybridization chain reaction (bHCR) circuit to a terbium(II) organic gel (TOG) modified electrode in one step to achieve both sensitive detection and simplified modification steps. The sensitivity of the biosensor was elevated by the cascade bHCR circuit that was activated by miRNA-141 and operated like a molecular machine to form hyperbranched DNA nanostructures. Benefiting from molecular programming, the obtained nanostructures carried a large number of dopamine molecules, which can effectively quench the ECL signal of emitters and achieve a low limit of detection (0.18 fM). Impressively, the proposed one-step approach was almost the easiest way to modify nucleic acids to electrodes. In this way, the introduction of a high-molecular-weight DNA structure in one step avoided the errors that may result from the stepwise modification of low-molecular-weight nucleic sequences into the electrode. Considering the accessible operation, favorable performance, and high universality of this strategy, this work may be used to analyze other microRNAs and further clinical diagnosis.