A photoelectrochemical biosensor based on ZnIn2S4@AuNPs coupled with circular bipedal DNA walker for signal-on detection of circulating tumor DNA

The circulating tumor DNA (ctDNA) is a crucial cancer marker, its sensitive monitoring is useful for early diagnose and therapy of tumor-related diseases. Herein, a bipedal DNA walker with multiple recognition sites is designed through the transition of dumbbell-shaped DNA nanostructure to realize the dual amplification of the signal and achieve ultrasensitive photoelectrochemical (PEC) detection of ctDNA. Initially, the ZnIn2S4@AuNPs is obtained by combining the drop coating method with electrodeposition method. When the target is present, the dumbbell-shaped DNA structure transforms into an annular bipedal DNA walker that can walk unrestrictedly on the modified electrode. After the cleavage endonuclease (Nb.BbvCI) was added to the sensing system, the ferrocene (Fc) on the substrate is released from the electrode surface, and the transfer efficiency of photogenerated electron-hole pairs is extremely improved, enabling the "signal on" testing of ctDNA. The detection limit of the prepared PEC sensor is 0.31 fM, and the recovery of actual samples varied between 96.8 and 103.6% with an average relative standard deviation of about 8%. Meaningfully, the prepared PEC biosensor with an innovative bipedal DNA walker has potential application value for ultrasensitive detection of other nucleic acid-related biomarker.