A fluorescence-electrochemiluminescence dual-mode sensor based on a "switch" system for highly selective and sensitive K-ras gene detection

Herein, an fluorescence (FL)−electrochemiluminescence (ECL) dual-mode biosensor is constructed based on the dual-signal “turn-on” strategy of functionalized metal-organic frameworks nanosheets (RuMOFNSs)-tetraferrocene for K-ras gene detection, and the mechanism of bursting through front-line orbital theory is explained for the first time. Amino-functionalized tetraferrocene-labeled probe DNA molecules are linked to RuMOFNSs by covalent amide bonds, acting as FL and ECL intensity switches. The target DNA, complementary to the probe DNA, triggers cyclic amplification of the target by nucleic acid exonuclease III (Exo III), repelling tetraferrocene reporter groups away from RuMOFNSs and inhibiting the electron transfer process and photoinduced electron transfer (PET) effect. These phenomena induce a double turn-on of FL and ECL signals with a high signal-to-noise ratio. The developed FL-ECL dual-mode sensing platform provides sensitive detection of the K-ras gene with detection limits of 0.01 fM (the detection range is 1 fM to 1 nM) and 0.003 fM (the detection range is 0.01 fM to 10 pM), respectively. In addition, the proposed dual-mode sensor can be easily extended to detect other disease-related biomarkers by changing the specific target and probe base sequences , depicting potential applications in bioanalysis and early disease diagnosis.