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- guani
ne (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.
Nanopore based sequencing has demonstrated significant potential for the development of fast, accurate, and cost-efficient fingerprinting techniques for next generation molecular detection and sequencing. We propose a specific multi-layered graphene-
based nanopore device architecture for the recognition of single DNA bases. Molecular detection and analysis can be accomplished through the detection of transverse currents as the molecule or DNA base translocates through the nanopore. To increase the overall signal-to-noise ratio and the accuracy, we implement a new multi-point cross-correlation technique for identification of DNA bases or other molecules on the molecular level. We demonstrate that the cross-correlations between each nanopore will greatly enhance the transverse current signal for each molecule. We implement first-principles transport calculations for DNA bases surveyed across a multi-layered graphene nanopore system to illustrate the advantages of proposed geometry. A time-series analysis of the cross-correlation functions illustrates the potential of this method for enhancing the signal-to-noise ratio. This work constitutes a significant step forward in facilitating fingerprinting of single biomolecules using solid state technology.
