Electrocatalysis of cerium metal-organic frameworks for ratiometric electrochemical detection of telomerase activity.

A ratiometric electrochemical biosensor was constructed to detect telomerase activity based on electrocatalysis of cerium-based metal-organic frameworks (CeMOFs) and conformation switch of hairpin DNA. First, the CeMOFs were synthesized using Ce as nodes and 1,3,5-benzenetricarboxylic acid as linker in a green method, and then functionalized with gold nanoparticles. The resulted Au@CeMOF tags demonstrated an excellent electrocatalysis toward hydroquinone oxidation. Meanwhile, a methylene blue (MB) modified hairpin probe was designed with telomerase primer (TP) hybridized "stem" and immobilized on the electrode surface via Au-S chemistry. In the presence of the dNTPs and telomerase, the extended TP can open the hairpin DNA and keep the MB away from the electrode surface, resulting in a decrease of electrochemical signal. In the meantime, the TP-extended part could capture the Au@CeMOF-cDNA tags on the electrode surface via hybridization, leading to the increase electrochemical signal of hydroquinone oxidation catalyzed by Au@CeMOF-cDNA tags. Thus, a ratiometric signal output mode was developed for the electrochemical detection of telomerase activity. This biosensor showed wide dynamic correlation of telomerase activity from 2 × 102 to 2 × 106 cells mL-1 with the limit of detection of 27 cells mL-1, and was applied to evaluate telomerase activity in single cell. The ratiometric electrochemical strategy based on the catalysis of MOFs provides a new avenue on signal transduction in telomerase detection.