A multiple aptasensor for ultrasensitive detection of miRNAs by using covalent-organic framework nanowire as platform and shell-encoded gold nanoparticles as signal labels

We report herein a novel multiple electrochemical aptasensor based on covalent–organic framework (COF) for sensitive and simultaneous detection of miRNA 155 and miRNA 122, by using shell-encoded gold nanoparticles (Au NPs) as signal labels ( [email protected] and Cu 2 [email protected] , respectively, NCs  = nanoclusters). A new COF nanowire was synthesized via condensation polymerization of 1,3,6,8-tetra(4-carboxylphenyl)pyrene and melamine (represented by TBAPy-MA–COF–COOH) for multiple aptasensor fabrication. The nanowire was then used as a platform for anchoring single-strand DNA (ssDNA), which was hybridized with the complementary aptamer (cApt) probes of miRNA 155 and miRNA 122. [email protected] and Cu 2 [email protected] modified with cApts show separated differential pulse voltammetry (DPV) peaks at 0.08 and −0.1 V, respectively. The signal labels immobilized with cApts were released from the hybridized DNA complex and bound to their corresponding targets when contacting miRNAs. This phenomenon results in the substantial decline of the DPV peak current density of the signal labels. The developed TBAPy-MA–COF–COOH-based aptasensor has superior performance for sensing miRNA 155 and miRNA 122 simultaneously, with ultrasensitive low detection limits of 6.7 and 1.5 fM (S/N = 3), respectively, a wide linear range of 0.01–1000 pM, and high selectivity and applicability for serum samples. The proposed TBAPy-MA-based aptasensor demonstrates potential for simultaneous detection of multiple cancer biomarkers by replacing other ssDNA and aptamer strands.