Herein, an enzyme-free "ON-OFF" electrochemiluminescence (ECL) biosensor for ultrasensitive detection of fusion gene PML/RARα is constructed based on a simple target-switched DNA nanotweezer as hemin concentration controller. In this biosensor, the hemin concentration is primarily controlled by the conversion of "opened-closed" DNA nanotweezers and low concentration hemin is first used as electrochemically regenerable enhancer. In the absence of the target, the nanotweezers are in an opened state which lead to a low concentration of hemin in the solution, resulting in an enhanced Ru(bpy) 3 2+ ECL signal. In the presence of the target, the closed nanotweezers absorbed onto the surface of electrode can capture the hemin, which achieves a high concentration of hemin and then quenches the ECL signal. The developed method achieves ultrasensitive detection of PML/RARα with a wide linear range from 1 fM to 1 nM and limit of detection as low as 0.125 fM. In addition, the ECL biosensor shows excellent specificity to the other subtypes of PML/RARα (subtype "S", "V"), "PML", and "RARα". Moreover, due to the high designable character of DNA nanotweezer, this method might provide a pragmatic Ru(bpy) 3 2+ ECL platform for ultrasensitive detection of nucleic acid in the future.

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