A designed locked nucleic acid-based nanopore for discriminating ctDNA and its coexisting analogue ncDNA

Circulating tumor DNA (ctDNA), carrying tumor-specific sequence mutations, is a promising biomarker for classification, diagnosis and prognosis of cancers. However, there is still a great challenge in discriminating single-base difference between ctDNA and its coexisting analogue (normal circulating DNA, ncDNA) at a serum sample. A locked nucleic acid (LNA) probe combined with α-HL nanopore sensor was designed, which achieved a high signal-to-background ratio (SBR) of ~8.34×10³, as well as a significant discrimination capability (~12.3 times) of single-base difference. The accurate discrimination strategy is label-free, convenient, selective and sensitive, which has great potential in the early diagnosis of diseases and biomedical research fields.