期刊
ACS NANO
卷 14, 期 6, 页码 6743-6751出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b10085
关键词
DNA methylation; methylation profiling graphene field-effect transistor; DNA tweezers; Dirac voltage
类别
资金
- National Institute of Aging [4R01AG028709-10]
- Department of Mechanical and Aerospace Engineering, UCSD
DNA methylation is one of the principal epigenetic mechanisms that control gene expression in humans, and its profiling provides critical information about health and disease. Current profiling methods require chemical modification of bases followed by sequencing, which is expensive and time-consuming. Here, we report a direct and rapid determination of DNA methylation using an electric biosensor. The device consists of a DNA-tweezer probe integrated on a graphene field-effect transistor for label-free, highly sensitive, and specific methylation profiling. The device performance was evaluated with a target DNA that harbors a sequence of the methylguanine-DNA methyltransferase, a promoter of glioblastoma multiforme, a lethal brain tumor. The results show that we successfully profiled the methylated and nonmethylated forms at picomolar concentrations. Further, fluorescence kinetics and molecular dynamics simulations revealed that the position of the methylation site(s), their proximity, and accessibility to the toe-hold region of the tweezer probe are the primary determinants of the device performance.
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