Electrochemical biosensing of circulating microRNA-21 in cerebrospinal fluid of medulloblastoma patients through target-induced redox signal amplification.

Monitoring of cerebrospinal fluid (CSF) microRNAs (miRs) offers a promising option for the diagnosis and management of patients with central nervous system tumors. However, the sensitive detection of miRs in clinical CSF samples has been hindered by the ultra-low abundance of target miRs. Here, we report an electrochemical biosensor for the highly sensitive label-free detection of CSF miR-21 relying on target-induced redox signal amplification (eTIRSA). The biosensor was developed by covalently assembling the capture stands partially complementary to miR-21 on the gold nanoparticle-coated glassy carbon electrode. In the presence of miR-21, the short capture stand hybridized with the partial bases of miR-21, allowing the rest sequence of the target molecule to further bind with a long guanine-rich sequence which could specifically adsorb a number of methylene blue indicators, thus generating an amplified electrochemical redox signal, typically at a working potential of - 0.19 V (vs. SCE). The response of the surface-bound methylene blue indicators was positively correlated to the concentration of miR-21, providing a dynamic range of 0.5-80 pM and a limit of detection down to 56 fM. Moreover, the eTIRSA biosensor had high specificity with single-base resolution and exhibited good performance for label-free quantification of miR-21 in medulloblastoma cell extracts and clinical CSF samples and for accurate discrimination of medulloblastoma against non-cancer controls, indicating its potential application in CSF miR-based liquid biopsy of brain cancers.