Researchers Find Faster Way to Sequence DNA

January 15, 2008

Sequencing DNA provides researchers with loads of data on how our bodies work and how diseases develop. But to sequence the thousands of genes and billions of base pairs – the rungs that make up a DNA ladder – that make up our complete set of DNA takes millions of dollars, bulky machinery and several years of work.

But researchers at Northwestern University hope to help make DNA sequencing faster and cheaper, and a recent breakthrough in one lab shows the process could potentially be sped up by using a new technique.

Principal investigator Annelise Barron, a former professor of chemical engineering at Northwestern's McCormick School of Engineering who is now affiliated with Stanford University, worked with six Northwestern graduate students on results published online Jan. 9 by the Proceedings of the National Academy of Sciences (PNAS).

”I believe that Northwestern now holds the record for the fastest long-read DNA sequencing ever accomplished,” Barron said. “This is of course a considerable feat in itself, however, the implications for low-cost, high-throughput sequencing technology are what is really exciting.”

To sequence DNA, researchers use a chemical process to replicate the DNA, in small pieces, and label it with fluorescent dyes. The DNA is then put in a polymer solution and pushed through a sieve by an electric field – which causes the smaller DNA to come through first, the largest last – and then a computer reads the labels and separates the DNA into its sequence of bases.

Chris Fredlake, a chemical engineering Ph.D. student who co-authored the paper, says their lab focuses on the separation aspect of the process, using a glass microchip filled with highly tailored polymer solutions.

Using a microchip to separate the DNA has already proven to be faster than other separating technologies. But the team created a new polymer solution that has greatly increased speed of the separation. Using a chemical process, researchers increased the size of polymers in the solution, making the polymer molecules act like noodles in a pot of boiling water – they tangle together and form networks, and the DNA is separated very efficiently as it tries to find its way through the networks.

Though others have used this process to separate DNA before, Northwestern researchers have made the process much faster by using different polymers and running the process under certain conditions that give very narrow DNA peaks.

“This molecular mechanism that we’ve proposed is new relative to how people understand how DNA moves through this network,” Fredlake said. “This will hopefully foster ideas for what the next generation break-through will be.”

The result was getting base pair sequences three times faster than anyone else using microchips for DNA separation. The paper reported a speed of 600 bases in 6.5 minutes. This is also 10 times faster than the currently used technology for high-throughput DNA sequencing, capillary array electrophoresis.

“There is something new going on that no one else has really talked about and that may be what’s giving us this better performance,” said chemical engineering PhD student Daniel Hert, who also co-authored the paper.

The results of the research are the latest step toward the ultimate goal of being to sequence a genome (a complete set of DNA) for $1,000 – a cost that would make the technology widely available to people who want to get their entire genomes read for susceptibility to a wide variety of potential diseases – and being able to do so in a reasonable time frame.

Other authors on the paper were Cheuk-Wai Kan, Thomas Chiesl, Brian Root and Ryan Forster. Their work was funded by the NIH’s National Human Genome Research Institute.