Methylation of DNA is a type of epigenetic signatures that define the eukaryotic cell’s identity by regulating gene expression. Aberrant methylation in the genome can deregulate the gene expression pathways leading to cancer. Thus DNA methylation has been regarded as one of the most important biomarkers for cancer. Recent years have seen tremendous advancement in methylation based biomarker discovery providing abundant information about the genomic printing. However, cancer is a versatile disease that often needs multiple biomarker analysis for accurate detection. Current practice in detecting methylation biomarkers in the clinic is widely affected by expensive sequencing technique. Recent advancements in electrochemical and optical biosensors have shown great promise in developing an inexpensive multiplex platform. Despite their significant improvement in sensitivity, these methods are restricted by major technological challenges including functionalization of sensor surface, long analysis procedure and invasive sampling.i,ii Recently Trau group have developed an interfacial biosensing technique to identify DNA methylation using gold-DNA affinity thus obviates the sensor surface modification. This project aims to develop a novel multiplex micro-device comprising an array of microelectrodes for directly detecting the genomic methylation biomarkers with the mechanism of interfacial adsorption between DNA and metal surfaces. These microelectrodes can significantly increase the assay sensitivity due to the high signal to noise ratio. We believe that this micro-fabricated multiplex platform will find broad applications as a simple diagnostic tool in the clinic.
This interdisciplinary project will provide an excellent opportunity for students to acquire diverse skills in chemistry, molecular biology, and nanotechnology.
i Ferrari, Mauro. "Cancer nanotechnology: opportunities and challenges."Nature reviews. Cancer 5.3 (2005): 161.
ii Wee, Eugene JH, et al. "μ-eLCR: a microfabricated device for electrochemical detection of DNA base changes in breast cancer cell lines."Lab on a Chip 13.22 (2013): 4385-4391.
Scheme of DNA-gold affinity interactions approach for DNA methylation detection
