Mn-MOF catalyzed multi-site atom transfer radical polymerization electrochemical sensing of miRNA-21

A green electrochemical biosensor was developed based on metal-organic framework (MOF)-catalyzed atom transfer radical polymerization (ATRP) for quantifying miRNA-21, used as the proof-of-concept analyte. Unlike conventional ATRP, Mn-PCN-222 (PCN, porous coordination network) could be used as an alternative for green catalyst to substitute traditional catalysts. First, poly (diallyldimethylammonium chloride) (PDDA) was fixed on the surface of the indium tin oxide (ITO) electrode, and then the Mn-PCN-222 was linked to ITO electrode via electrostatic binding with PDDA. Next, aminated ssDNA (NH₂-DNA) was used to modify the electrode further by amide reaction with Mn-PCN-222. Then, the recognition and hybridization of NH₂-DNA with miRNA-21 prompt the generation of DNA-RNA complexes, which further hybridize with Fc-DNA@β-CD-Br₁₅ and permit the initiator to be immobilized on the electrode surface. Accordingly, β-CD-Br₁₅ could initiate the polymerization of ferrocenylmethyl methacrylates (FcMMA) under the catalysis of MOF to complete the ATRP reaction. FcMMA presented a distinct electrochemical signal at ~ 0.33 V. Taking advantage of the unique multi-site properties of β-CD-Br₁₅ and the efficient catalytic reaction induced by Mn-PCN-222, ultrasensitive detection of miRNA-21 was achieved with a detection limit of 0.4 fM. The proposed electrochemical biosensor has been applied to the detection of miRNA-21 in serum samples. Therefore, the proposed strategy exhibited potential in early clinical biomedicine.