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      Detection of methylation on dsDNA using nanopores in a MoS2 membrane

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          Abstract

          Methylation in DNA has been shown to be a reliable diagnostic biomarker for carcinogenesis.

          Abstract

          Methylation at the 5-carbon position of the cytosine nucleotide base in DNA has been shown to be a reliable diagnostic biomarker for carcinogenesis. Early detection of methylation and intervention could drastically increase the effectiveness of therapy and reduce the cancer mortality rate. Current methods for detecting methylation involve bisulfite genomic sequencing, which are cumbersome and demand a large sample size of bodily fluids to yield accurate results. Hence, more efficient and cost effective methods are desired. Based on our previous work, we present a novel nanopore-based assay using a nanopore in a MoS 2 membrane, and the methyl-binding protein (MBP), MBD1x, to detect methylation on dsDNA. We show that the dsDNA translocation was effectively slowed down using an asymmetric concentration of buffer and explore the possibility of profiling the position of methylcytosines on the DNA strands as they translocate through the 2D membrane. Our findings advance us one step closer towards the possible use of nanopore sensing technology in medical applications such as cancer detection.

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          Most cited references 41

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          Targeted mutation of the DNA methyltransferase gene results in embryonic lethality

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            NAMD2: Greater Scalability for Parallel Molecular Dynamics

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              DNA translocation through graphene nanopores.

              We report on DNA translocations through nanopores created in graphene membranes. Devices consist of 1-5 nm thick graphene membranes with electron-beam sculpted nanopores from 5 to 10 nm in diameter. Due to the thin nature of the graphene membranes, we observe larger blocked currents than for traditional solid-state nanopores. However, ionic current noise levels are several orders of magnitude larger than those for silicon nitride nanopores. These fluctuations are reduced with the atomic-layer deposition of 5 nm of titanium dioxide over the device. Unlike traditional solid-state nanopore materials that are insulating, graphene is an excellent electrical conductor. Use of graphene as a membrane material opens the door to a new class of nanopore devices in which electronic sensing and control are performed directly at the pore.
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                Author and article information

                Journal
                NANOHL
                Nanoscale
                Nanoscale
                Royal Society of Chemistry (RSC)
                2040-3364
                2040-3372
                2017
                2017
                : 9
                : 39
                : 14836-14845
                Affiliations
                [1 ]Department of Biomedical Engineering
                [2 ]Rowan University
                [3 ]Glassboro
                [4 ]USA
                [5 ]Department of Material Science and Engineering
                [6 ]University of Illinois at Urbana – Champaign
                [7 ]Urbana
                [8 ]State Key Laboratory of Mechanics and Control of Mechanical Structures
                [9 ]Nanjing University of Aeronautics and Astronautics
                [10 ]Nanjing
                [11 ]China
                [12 ]Department of Electrical Engineering
                [13 ]Stanford University
                [14 ]Stanford
                [15 ]Boise State University
                [16 ]Boise
                [17 ]Department of Physics and Beckman Institute
                [18 ]Department of Bioengineering
                [19 ]Micro and Nanotechnology Laboratory
                Article
                10.1039/C7NR03092D
                5890527
                28795735
                © 2017
                Product
                Self URI (article page): http://xlink.rsc.org/?DOI=C7NR03092D

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