By feeding individual strands of DNA through nanometre-sized holes, researchers in the Netherlands say they have proved the principle of a revolutionary new DNA sequencing technique. The breakthrough is part of a worldwide race to develop fast and low-cost strategies to analyse these codes that underpin the chemistry of life.
The genetic profile – or “genome” – of an organism is determined by recording the full sequence of acid base pairs that make up its DNA. In 2003, the Human Genome Project made history by determining the entire human genetic code – 3 billion DNA base pairs that took 13 years to analyse using a technique that has changed very little since the late 1970s.
This pioneering project used a “shotgun” approach, which first isolates a DNA strand and forces it to copy itself millions of times over in a chemical reaction. These strands are then “blasted” into tiny fragments because current techniques can only analyse very short sections of DNA. Finally, a supercomputer matches up overlapping base patterns to piece together the full genome.
However, with the promise of personalized medicine, scientists are working to develop new technologies that could rapidly sequence an individual’s genetic make-up. In addition to the human genome there are also slight variations in DNA sequences and processes that give people their phenotypes such as “blue eyes” or “blond hair”.
In 2008, physicsworld.com reported one promising idea that involves passing DNA through tiny punctures in a sheet of graphene – an extremely strong sheet of carbon just one atom thick. A voltage is applied along the graphene surface as DNA strands are passed slowly through the slit one base at a time. The idea is that each of the four bases – A, C, G and T – will have a unique effect on the conductance of graphene across the gap.
Now, Cees Dekker and his colleagues at the Kavli Institute of Nanoscience are the first team to demonstrate DNA motion through graphene, although their technique cannot yet read the genetic code.
They create a series of pores ranging from 5 to 25 nm in diameter by placing flakes of graphene over a silicon nitride membrane and drilling nanosized holes in the graphene using an electron beam. By applying a voltage of 200 mV across the graphene membrane, a series of spikes are observed in an electric current that scales the gap. These, say the researchers, correspond to drops in conductance when DNA strands slide across the gap via a biochemical process known as translocation.
The researchers intend to develop their research by identifying which spikes correspond to particular bases. Dekker told physicsworld.com that one area of science that could benefit in particular from ultrafast sequencing is epigenetics – that is, the study of changes in phenotypes that are not related to changes in underlying DNA sequences.
Henk Postma, a researcher at California State University, Northridge, who is also developing nanopore sequencing, is excited by the result. “They have demonstrated that DNA does indeed go through little holes in graphene, and that it does so with great speed. Both of these are important advancements towards using graphene for DNA sequencing,” he says.
This research is published in Nano Letters.