A reusable laser wrapped graphene-Ag array based SERS sensor for trace detection of genomic DNA methylation.

Methylation is an important epigenetic DNA modification that governs gene expression. The genomic level of methylated DNA and its derivatives may serve as important indicators for the initiation and progression of cancers among other diseases. In this effort we propose a new laser wrapped graphene-Ag array as a highly sensitive Surface-enhanced Raman spectroscopy (SERS) sensor for the detection of methylated DNA (5-methylcytosine, 5mC) and its oxidation derivatives namely 5-hydroxymethylcytosine (5-hmC) and 5-carboxylcytosine (5-caC). Excellent sensitivity and reproducibility were achieved with the laser wrapped graphene-Ag array as a substrate, with the graphene layer acting as an enhancer of the SERS signal due to the effective coupling of the electromagnetic field. In summary, fast (less than 60min) and sensitive (at a limit of detection 0.2pgμL-1, ie. 1.8pmolL-1) detection of methylated DNA and its derivatives was realized with the ability to distinguish methylation levels from a mixture at 0.1%. The sensitive and accurate detection in DNA extracted from cells was also accomplished. Furthermore our graphene wrapped approach circumvents the direct interaction between Ag array and the analytes, thus improving the reusability of the SERS substrate even after five cycles of use.