Magnetic beads-assisted split DNAzyme cleavage-driven assembly of functionalized covalent organic frameworks for highly sensitive electrochemical detection of microRNA

Specific and sensitive detection of microRNA is significant for early diagnosis of cancer. In this work, a novel electrochemical biosensor was proposed for microRNA-155 detection based on target-triggered magnetic beads (MBs)-assisted split DNAzyme cleavage-driven assembly of functionalized covalent organic frameworks (COFs). COFs were served as efficient nanocarriers of DNA and signal molecules, which acted as electroactive probe with good hybridization ability and cargo loading ability. The MBs-assisted split DNAzyme held the features of easy manipulation, excellent anti-interference ability and increased of the load capacity of DNAzyme for signal amplification. With the presence of target, the cleavage activity of Mg2+-dependent split DNAzyme on MBs was triggered, resulting in the generation of DNA fragments (A1) and the recycling of target. The released A1 participated in the catalytic hairpin assembly process on the electrode, leading to large amount of COFs probe assembled on the electrode to achieve amplified signal output. Using miRNA-155 as a model target, the proposed electrochemical biosensor realized highly sensitive detection of miRNA-155 with a wide liner range from 10 fM to 5 nM and a low detection limit of 1.2 fM. The proposed multiple-amplified biosensing platform demonstrated a novel method for miRNA analysis, holding potential application in early diagnosis of disease.