Tuesday, October 28, 2008

Graphene could accelerate genomics

Oct 28, 2008
DNA moving through a graphene nanogap

Artist's impression of a DNA molecule (helix) moving through a tiny slit in a graphene sheet (shown in blue). (Courtesy: Henk Postma)

The “wonder material” graphene could soon be used to analyse DNA at a record-breaking pace. That’s the claim of a physicist in the US who has proposed a new way of reading the sequence of chemical bases in a DNA strand by sending the molecule through a tiny slit in a graphene sheet.

While the technique has yet to be verified experimentally, if successful it could be eligible for the $10 million X Prize for Genomics, which has set the challenge of developing a new rapid and low-cost sequencing technology.

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 “shotgun” approach first isolates a DNA strand and forces it to copy itself millions of times over in a chemical reaction. These are then “blasted” into tiny fragments because current techniques for sequence reading can detectors can only analyse very short sections of DNA. Finally, a supercomputer matches up overlapping base patterns to piece together the full genome.

No processing required

Now, Henk Postma at California State University Northridge has proposed a way of sequencing an entire DNA strand without the need for blasting or computer processing (arXiv:0810.3035v1 ).

Rapid Sequencing of Individual DNA Molecules in Graphene Nanogaps

The technique involves cutting a very narrow slit or “nanogap” along the length of a piece of graphene — an extremely strong sheet of carbon just one atom thick. A voltage is applied perpendicular to the graphene’s surface, which causes the DNA strand to pass slowly through the slit one base at a time.

A second voltage is applied across slit and electrons are able to “tunnel” across the nanogap via the base that happens to be passing through the slit. There are four different types of base in a DNA molecule, and each should support a different tunnelling current — allowing the base type to be identified.

While the idea of sequencing DNA by sending it through a tiny gap is not new, previous schemes had relied on using separate materials for the membrane and electrodes — and aligning the two materials has proved to be a considerable challenge. Postma’s design gets around this problem by having the graphene function as both membrane and electrode.

Postma believes that detector could be made from a graphene sheet sandwiched between glass plates that are held together by van der Waals forces.

Technology should be possible

According to Changgu Lee, a mechanical engineer at Colombia University, some of the technology to realize Postma’s design may be available already. “Creating the nanogaps in graphene was demonstrated this year using both STM [scanning tunnelling microscopy] and catalytic cutting with metal particles”, he said.

Postma told physicsworld.com that traditional sequencing techniques are limited to determining about 800 base pairs per recording. By contrast, he estimates his design could yield 100,000 bases per recording, and if run continuously it would read the whole human genome in two and a half hours. He also believes that his technique could lead to sequencing devices that are smaller and cheaper than existing systems.

If successful, Postma's system could be a contender for the X Prize for Genomics, which aims to award $10m to the inventor of a device that can sequence 100 human genomes within 10 days or less,to a specified accuracy and costing no more than $10,000 per genome.

Postma said he is continuing to develop his design, but added: “I published the paper to get feedback from the scientific community, in the open, because I believe that will lead to the best possible technology.”

And it seems DNA experts are ready for a new technology. Geoffrey Baldwin, a molecular biologist from Imperial College in the UK said “to truly develop health care we need the profile of 100s of genomes not just the few we have at the moment”. He added “there is now a great opportunity for a new technique to become the standard in base sequencing”.

About the author

James Dacey is a science journalist based in the UK


Strikes me as a DNA computer in the making.