Nanoscale holes in solid-state membranes, so-called nanopores, furnish nanosensors for probing biological molecules such as DNA and protein. Under electric fields, charged molecules like DNA are pushed through these pores and the flow of ions surrounding the translocating DNA can be recorded to recognize individual DNA bases, and in turn, the sequence of DNA. Traditional nanopore sensors often use solid-state membranes, which are too thick to recognize single bases on a DNA strand. This limitation can be overcome by using two-dimensional materials such as graphene or MoS$_2$. Only a single base pair of DNA fits into the thin two-dimensional material nanopores at any time, such that these nanopores can potentially provide single-base resolution for DNA sensing. In addition, graphene and MoS$_2$ are both lectrically conductive, thereby allowing the use of electric current in the layer to detect and characterize the DNA in the pore. Instead of actually building and testing the device experimentally, molecular dynamics simulations can assist and enable a bottom-up design of two-dimensional material nanopore devices by unveiling the atomic-level processes occurring during nanopore sensing.
Characterizing the genetic makeup of individuals can help select the best
treatment for individuals, but requires that sequencing of the whole DNA of
patients can be achieved for less than $1000. Fortunately, recent discoveries in physics
promise help. Indeed, the discovery of the thinnest material known to
mankind, graphene, promises a new and cheaper way to sequence human DNA. As reported
in the December
2011 highlight, graphene pores can conduct electrophoretically
DNA through very small pores, so-called nanopores. A new study
has demonstrated that graphene, forming a single atomic layer thin stripe with
a nanopore in the middle, can conduct an electrical
current, the sheet current, around the pore. The sheet current is sensitive to
the DNA passing through the pore and may even sense the passing DNA's
sequence. In this case monitoring the current can establish a DNA sequence
reader. The sensitivity of the sheet current depends critically on
an orderly passage of DNA. Optimal sensitivity can arise when the passing DNA
is stretched mechanically. Molecular dynamics simulations using NAMD suggest conditions
for mechanically manipulating DNA for optimal sequence analysis.
More on our graphene
nanopore website.
Computer modeling in biotechnology, a partner in development.
Aleksei Aksimentiev, Robert Brunner, Jordi Cohen, Jeffrey Comer, Eduardo Cruz-Chu, David Hardy, Aruna Rajan, Amy Shih, Grigori Sigalov, Ying Yin, and Klaus Schulten. In Protocols in Nanostructure Design, Methods in Molecular Biology, pp. 181-234. Humana Press, 2008.
Beyond the gene chip.
J. B. Heng, A. Aksimentiev, C. Ho, V. Dimitrov, T. Sorsch, J. Miner, W. Mansfield, K. Schulten, and G. Timp. Bell Labs Technical Journal, 10:5-22, 2005.
Sizing DNA using a nanometer-diameter pore.
J. B. Heng, C. Ho, T. Kim, R. Timp, A. Aksimentiev, Y. V. Grinkova, S. Sligar, K. Schulten, and G. Timp. Biophysical Journal, 87:2905-2911, 2004.
