Dual-current signal high-sensitivity detection of telomerase using signal amplified DNA functionalized metal-organic frameworks in glass nanopipettes

As a biomarker for early cancer diagnosis, the quantitative and sensitive detection of telomerase is very hot topic in the field of biological detection. In this work, we reported a novel telomerase assay strategy-based glass nanopipettes (GNs) which were constructed with DNA functionalized metal-organic frameworks (MOFs, PCN-224, C144H112N12O64Zr15) as composite probes (DNA-PCN-224, DNA-PCN-224-MB (methylene blue)). The composite probes provided more probe binding sites, so the aggregation behavior of the composite probes would occur obviously in nanopores restricted domain space under the recognition and amplification of telomerase. The relative size of the GNs reduced due to the size effect of MOFs. This size effect exhibits a good signal-to-noise ratio in large pores, resulting in signal amplification. With different modifications of the GNs, on the one hand, the reduction of the relative pore size amplified the ionic current signal; on the other hand, the electrolytic current signal further verified the reliability of this signal amplification, which originated from the transfer of electrons occurring on the gold layer by the electroactive substance MB. The former quantified the assay, allowing a telomerase detection range of 0-10,000 Hela cells/mL and a detection limit of 100 Hela cells/mL. This work provided a detection platform for detecting related telomerase diseases and opened a new detection method of double signals.