Detection of bladder cancer related DNA biomarkers using silicon microring resonators

DNA biomarkers have been demonstrated as an important diagnostic factor for detection of early stage in human cancers. To date, many genetic alterations of biomarkers have been identified in urothelial cell carcinoma of the bladder. Among the several alterations, the mutations of FGFR 3 (fibroblast growth factor receptor 3) and HRAS (Harvey RAS) are associated with early stage of bladder cancer. The genetic events of the genes are mutually exclusive in urothelial cells. We have recently reported highly sensitive silicon based microring resonators, which was applied to bio-molecules (protein, nucleic acid and so on) sensing by monitoring a shift in the resonant wavelength. Silicon microring resonators are essentially refractive index-based optical sensors that provide highly sensitive, label-free, real-time, and multiplexed detection of bio-molecules near the sensor surface. Furthermore, the devices are fabricated by the standard CMOS technology, which ensures low-cost and scale-up capability of the sensor fabrication. In this study, we present a nucleic acid sensor based on silicon microring resonators to detect DNA biomarkers (FGFR3 and HRAS), which used as targets of bladder cancer detection. DNA probes complementary to the part of the target oligonucleotides of FGFR3 (116bp) and HRAS (160bp) are immobilized on silicon surface with amine modification method. We show the wild type probes of FGFR3, and HRAS genes can completely capture the wild type targets compared to non-specific target probe. Furthermore, the mutant types of FGFR3 (R249C) and HRAS (G13R) genes can be strongly detected by using silicon microring resonators. Therefore, our sensor can be used to detect the DNA biomarker for early detection of bladder cancers.