Nanowire-transistor based ultra-sensitive DNA methylation detection

Accurate detection of DNA methylation at specific gene transcription sites is important to identify potential tumor formation since this epigenetic alteration may result in silencing of tumor suppressor genes that protect against tumor formation or that repair damaged DNA. Current technologies used in DNA methylation detection are complicated and time consuming. This work presents the first nanowire field effect transistor (FET) based biosensor technology which achieves simple and ultra-sensitive electronic DNA methylation detection and avoids complicated bisulfite treatment and PCR amplification. The promoter of the p16(INK) gene, a tumor suppressor gene, is the target DNA in the detection model. The target DNA was captured and concentrated with magnetic beads, and released to the sensing surface of a nano-FET through a reversible binding process. The methylated p16(INK) promoter was recognized and bound to monoclonal anti-5-methylcytosine antibodies which were immobilized on the nano-FET sensing surface. The presence of the target DNA molecules induced electronic charge and changed the electronic properties of the nano-transistor from which detectable electronic signals are generated. The electronic charge based DNA methylation detection is simple and ultra-sensitive with the potential for low cost. The detection sensitivity was achieved at 2.5 x 10(-19) mol with no false positives observed. (C) 2007 Published by Elsevier B.V.