Ultrasensitive electrochemical detection of microRNA-21 with wide linear dynamic range based on dual signal amplification

Abnormal expression of microRNAs is closely related to human diseases. Ultrasensitive detection of microRNAs with wide linear dynamic range is necessary as the concentrations of microRNAs distributed in biological samples usually range from fM to nM. Here, we constructed an ultrasensitive electrochemical sensor for microRNA-21 based on the integration of a dual signal amplification strategy of hybridization chain reaction (HCR) and enzyme-induced metallization (EIM) with anodic stripping voltammetry (ASV). MicroRNA-21 was captured by capture probe H1 (CP H1) modified magnetic nanobeads (MBs) and amplified by HCR. Multiple alkaline phosphatases (ALP) were coupled based on the specific reaction of biotin and streptavidin. A dual amplification strategy of HCR and EIM enhanced electrochemical signal by approximately 120-fold from the perspectives of target amplification and detection signal amplification, which decreased the detection limit of microRNA-21 to 0.12 fM. Compared to the reports previously reported, a wider linear dynamic range of 2.5 fM to 25 nM spanning 7 orders of magnitude was obtained. The method provides high sensitivity, specificity and a wider linear dynamic range, which shows a great potential in the early diagnosis of diseases.