A Host-Guest Interaction-Based and Metal-Organic Gel-Based Biosensor with Aggregation-Induced Electrochemiluminescence Enhancement for Methyltransferase Assay.


Cui L(1), Zhao MH(1), Li CC(1)(2), Wang Q(3), Luo X(2), Zhang CY(1).
Author information:
(1)College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, China.
(2)Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE; Shandong Key Laboratory of Biochemical Analysis; Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong; and College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, P. R. China.
(3)Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology
(Shandong Academy of Sciences), Jinan, Shandong 250014, China.


Metal-organic gels (MOGs) are new soft materials with the characteristics of high colloidal stability, superb luminescence properties, and facile synthesis. Herein, we develop for the first time a host-guest interaction-based and MOG-based biosensor with aggregation-induced electrochemiluminescence (ECL) enhancement for M.SssI methyltransferase (M.SssI MTase) assay. This biosensor employs a MOG as the luminophor and potassium persulfate as the coreactant, and the formation of the Ag-MOG from the aggregation of silver nanoclusters can induce significant ECL enhancement. Two complementary single-stranded DNAs (ssDNAs, i.e., biotinylated DNA-1 and Fc-labeled DNA-2) that contain specific recognition sequence 5'-CCGG-3' can form a double-stranded DNA (dsDNA) probe. In the absence of M.SssI MTase, the dsDNA probe will be digested by restriction endonuclease HpaII, leading to the release of Fc from magnetic beads (MBs). The β-CD can specifically recognize the released Fc through guest-host interaction, resulting in the quenching of an ECL signal. In contrast, the presence of M.SssI MTase enables the formation of fully methylated dsDNA, which cannot be cleaved by HpaII, making Fc remain on the MB surface and consequently generating an improved ECL signal. This biosensor can specifically detect M.SssI MTase with a linear range of 0.05-100 U mL-1 and a limit of detection of 3.5 × 10-3 U mL-1, and it enables accurate detection of M.SssI MTase in human serum. In addition, it can be used for inhibitor screening, with wide applications in drug discovery and disease diagnosis.