Monday, April 24, 2006

Nanopore will make for speedy DNA sequencing

17:15 10 April 2006 news service
Tom Simonite

A new technique harnessing a “nanopore” to detect electrical changes as a strand of DNA is passed through it could speed up DNA sequencing more than 200 times. The system could process the human genome in hours, researchers claim, compared with the 6 months it would take in today's best labs.
The technique has been tested theoretically by US physicists using a detailed computer simulation of over 100,000 interacting atoms. The DNA-sequencing nanopore is yet to be built, but you can view the simulation, here (mpeg format).
The device would work by running an electric current across a DNA strand as it is drawn through a nanopore, using electrodes built into the pore's sides. Detecting the changes in current that correspond to the four different bases, or "letters", that make up DNA would read off the sequence as it passed.
"Because we're all physicists working on this we've started at the very bottom – with atoms," explains Johan Lagerqvist, a physicist at the University of California, San Diego, US, who worked on the simulation. Lagerqvist and colleagues tested a virtual version of the system by modelling how 100,000 atoms in a short DNA strand, the silicon nitride nanopore, its electrodes and the surrounding chemical solution would all interact.
Multiple measurements
Because DNA is a kind of acid, it has a negative charge and can be drawn through a nanopore by a positive electrode on the other side. But the researchers found that to accurately record the sequence of the strand as it passes through, electrodes on the inside of the pore have to scan each base many times.
"The changes each base causes in the current are not always identical," explains Lagerqvist. "They overlap a little, but we can get around this by taking more than one measurement for each base as it passes." Taking the average of 70 readings from each base made the scanner 99.9% accurate.
In a lab dish, a piece of DNA like that used in the virtual model would take just microseconds to pass through a pore, but modelling the process took 40 high-powered computers around a week. "At a scale this small, each and every atom matters," said Lagerqvist. "We were able to prove that this system could work, and the components to make it already exist, all that's needed now is to put them together."
Nanotubes in nanopores
In fact, a separate team at Harvard University, Massachusetts, US, has been trying build such a nanopore. "Using a nanopore with a current running across it to look at DNA has enormous potential," says Daniel Branton, group leader of the nanopore group at Harvard.
"This technique could also be used for other polymers like proteins or for artificial molecules. And that information has all kinds of valuable uses. We and other groups have been interested in this for some time, but this new simulation gives specifics about how such a device might be used."
The Harvard group are experimenting with adding a carbon nanotube inside a nanopore – a pore left behind after depositing silicon nitride in a way that leaves a pore behind. The carbon nanotube would act as an electrode inside the pore. "We've managed to articulate these tubes and pores together," says Branton. "Because of the favourable electrical properties of the tubes they can function as the electrodes to run current across the molecule passing through the pore."
But although results are promising, rapid scanning of DNA is still dependent on solving a still difficult construction problem. "We have measured some proof of principle signals from molecules in pores," says Branton, "but we're talking about putting things together at the nano level, which is not easily done."