Label-free DNA sensor for detection of bladder cancer biomarkers in urine

Abstract

This study aims to establish a DNA sensor based on a silicon microring resonator for the label-free detection of bladder cancer biomarkers in human urine samples. DNA biomarkers in voided urine are important diagnostic and prognostic indicators for bladder cancer. To date, many genetic alterations have been identified in urothelial cell carcinomas in the bladder. In particular, mutations of FGFR3 (fibroblast growth factor receptor 3) and HRAS (Harvey RAS) are associated with early-stage bladder cancer. Silicon microring resonators are refractive-index-based optical sensors that provide highly sensitive, label-free, real-time multiplexed detection of biomolecules near the sensor surface. In this study, we developed a nucleic acid sensor that uses silicon microring resonators to detect DNA biomarkers (FGFR3 and HRAS) for bladder cancer in urine samples. Single-mutation probes for FGFR3 and HRAS completely captured their mutant targets S249C (codon 249 substituting cysteine for serine) and G13R (codon 13 substituting arginine for glycine), respectively, when compared with a nonspecific probe. Furthermore, the sensor selectively discriminated between target DNA and non-target DNA in spiked urine, which has inhibitory components such as low pH, urea, and other unknown components. Because of the intrinsic advantage of silicon fabrication and its use as an optical sensor in urine, our proposed approach can provide a highly sensitive and specific platform for genetic analysis in cancer diagnostics and surveillance.