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Epigenetic alterations hold great promise as biomarkers for early stage cancer diagnosis. Nevertheless, direct identification of rare methylated DNA in the genome remains challenging. Here, we report an ultrasensitive framework nucleic acid-based electrochemical sensor for quantitative and highly selective analysis of DNA methylation. Notably, we can detect 160 fg of methylated DNA in million-fold unmethylated DNA samples using this electrochemical methylation-specific polymerase chain reaction (E-MSP) method. The high sensitivity of E-

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