Ultrasensitive assay of ctDNA based on DNA triangular prism and three-way junction nanostructures

Abstract Circulating tumor DNA (ctDNA) refers to a class of acellular nucleic acids carrying genetic features of primary tumor, which can be regarded as a promising noninvasive biomarker for cancer diagnosis. The development of ctDNA assay is an important component of liquid biopsy. In this study, we have fabricated a novel electrochemical strategy for ultrasensitive detection of ctDNA combining the merits of strand displacement amplification and DNA nanostructures. Stable DNA triangular prism is firstly self-assembled and modified on the electrode surface. After target initiated strand displacement polymerization reaction, the generated DNA product helps the formation of three-way junction nanostructure on triangular prism, which localizes electrochemical species. By carefully investigating the electrochemical responses, the limit of detection (LOD) for ctDNA assay as low as 48 amol/L is achieved. This proposed electrochemical biosensor shows great potential for clinical applications.