Label-free methylation specific sensor based on silicon microring resonators for detection and quantification of DNA methylation biomarkers in bladder cancer

Detection and quantification of DNA methylation is important to provide an opportunity to resolve clinical issues such as cancer early detection, progression, and drug treatments. In spite of myriad current technologies for DNA methylation detection that have been developed in last decade, they are still complicated and inadequate to be used as in vitro clinical diagnostic device. This work presents the first methylation specific sensor based on the silicon microring resonators which achieves fast, simple and specific label-free detection of DNA methylation after the bisulfite conversion. The methylated promoter regions of three genes (DAPK, E-cadherin and RARβ), which have been widely studied as biomarkers for human cancers including bladder cancer, are used as the target DNA sequences. We show that the methylated targets are strongly captured by methylated probe compared to unmethylated probe or vice versa. The discrimination between methylated and unmethylated DNA sequences is achieved within 5min after hybridization between target and probe. Additionally, we have quantified DNA methylation density using various proportions (100, 75, 50, 25, and 0% of methylation sites) of methylation sequences of DAPK gene. Finally, we confirmed that the sensor can clearly detect the methylation of RARβ gene by using amplified target from genomic DNA of cancer cells. Therefore, our technique can be used to detect and quantify the methylation density in cancer biomarkers.