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Register a new userNext Generation Epigenetic Detection Technique:Identifying Methylated DNA using Graphene Nanopore
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DNA methylation plays a pivotal role in the genetic evolution of both embryonic and adult cells. For adult somatic cells, location and dynamics of methylation has been very precisely pinned down with the 5-cytosine markers on cytosinephosphate- guanine (CpG) units. Unusual methylation on CpG islands are identified as one of the prime causes for silencing the tumor suppressant genes. Early detection of such methylation can diagnose the potentially harmful oncogenic evolution of cells, and provide a promising guideline for cancer prevention. With this motivation, we propose a cytosine methylation detection technique.Our hypothesis is that electronic signatures of DNA acquired as a molecule translocates through a nanopore, would be significantly different for methylated and non-methylated bases. This difference in electronic fingerprints would allow for reliable real-time differentiations of methylated DNA. We calculate transport currents through a punctured graphene membrane while the cytosine and methylated cytosine translocate through the nanopore. We also calculate the transport properties for uracil and cyanocytosine for comparison. Our calculations of transmission, current, and tunneling conductance show distinct signatures in their spectrum for each molecular type. Thus, in this work, we provide a theoretical analysis that points to a viability of our hypothesis.
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We report an accurate method to determine DNA barcodes from the dwell time measurement of protein tags (barcodes) along the DNA backbone using Brownian dynamics simulation of a model DNA and use a recursive theoretical scheme which improves the measurements to almost 100 % accuracy. The heavier protein tags along the DNA backbone introduce a large speed variation in the chain that can be understood using the idea of non-equilibrium tension propagation theory. However, from an initial rough characterization of velocities into fast (nucleotides) and slow (protein tags) domains, we introduce a physically motivated interpolation scheme that enables us to determine the barcode velocities rather accurately. Our theoretical analysis of the motion of the DNA through a cylindrical nanopore opens up the possibility of its experimental realization and carries over to multi-nanopore devices used for barcoding.
The potential of a double nanopore system to determine DNA barcodes has been demonstrated experimentally. By carrying out Brownian dynamics simulation on a coarse-grained model DNA with protein tag (barcodes) at known locations along the chain backbone, we demonstrate that due to large variation of velocities of the chain segments between the tags, it is inevitable to under/overestimate the genetic lengths from the experimental current blockade and time of flight data. We demonstrate that it is the tension propagation along the chains backbone that governs the motion of the entire chain and is the key element to explain the non uniformity and disparate velocities of the tags and DNA monomers under translocation that introduce errors in measurement of the length segments between protein tags. Using simulation data we further demonstrate that it is important to consider the dynamics of the entire chain and suggest methods to accurately decipher barcodes. We introduce and validate an interpolation scheme using simulation data for a broad distribution of tag separations and suggest how to implement the scheme experimentally.
In this study, we examine the mechanism of nanopore-based DNA sequencing using a voltage bias across a graphene nanoribbon. Using density functional theory and a non-equilibrium Greens function approach, we determine the transmission spectra and current profile for adenine, guanine, cytosine, thymine, and uracil as a function of bias voltage in an energy minimized configuration. Utilizing the transmission current, we provide a general methodology for the development of a three nanopore graphene-based device that can be used to distinguish between the various nucleobases for DNA/RNA sequencing. From our analysis, we deduce that it is possible to use different transverse currents across a multi-nanopore device to differentiate between nucleobases using various voltages of 0.5, 1.3, and 1.6 V. Overall, our goal is to improve nanopore design to further DNA/RNA nucleobase sequencing and biomolecule identification techniques.
Plasmons, collective oscillations of electron systems, can efficiently couple light and electric current, and thus can be used to create sub-wavelength photodetectors, radiation mixers, and on-chip spectrometers. Despite considerable effort, it has proven challenging to implement plasmonic devices operating at terahertz frequencies. The material capable to meet this challenge is graphene as it supports long-lived electrically-tunable plasmons. Here we demonstrate plasmon-assisted resonant detection of terahertz radiation by antenna-coupled graphene transistors that act as both plasmonic Fabry-Perot cavities and rectifying elements. By varying the plasmon velocity using gate voltage, we tune our detectors between multiple resonant modes and exploit this functionality to measure plasmon wavelength and lifetime in bilayer graphene as well as to probe collective modes in its moire minibands. Our devices offer a convenient tool for further plasmonic research that is often exceedingly difficult under non-ambient conditions (e.g. cryogenic temperatures and strong magnetic fields) and promise a viable route for various photonic applications.
We investigate the dynamics of DNA translocation through a nanopore using 2D Langevin dynamics simulations, focusing on the dependence of the translocation dynamics on the details of DNA sequences. The DNA molecules studied in this work are built from two types of bases $A$ and $C$, which has been shown previously to have different interactions with the pore. We study DNA with repeating blocks $A_nC_n$ for various values of $n$, and find that the translocation time depends strongly on the {em block length} $2n$ as well as on the {em orientation} of which base entering the pore first. Thus, we demonstrate that the measurement of translocation dynamics of DNA through nanopore can yield detailed information about its structure. We have also found that the periodicity of the block sequences are contained in the periodicity of the residence time of the individual nucleotides inside the pore.
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