Low-cost, ultra-fast DNA sequencing brings diagnostic use closer

May 19, 2010

Sequencing DNA could get a lot faster and cheaper -- and thus closer to routine use in clinical diagnostics - thanks to a new method developed by a research team based at Boston University. The team has demonstrated the first use of solid state nanopores -- tiny holes in silicon chips that detect DNA molecules as they pass through the pore -- to read the identity of the four nucleotides that encode each DNA molecule. In addition, the researchers have shown the viability of a novel, more efficient method to detect single DNA molecules in nanopores.

"We have employed, for the first time, an optically-based method for DNA sequence readout combined with the nanopore system," said Boston University biomedical engineer Amit Meller, who collaborated with other researchers at Boston University, and at the University of Massachusetts Medical School in Worcester. "This allows us to probe multiple pores simultaneously using a single fast digital camera. Thus our method can be scaled up vastly, allowing us to obtain unprecedented DNA sequencing throughput."

The research is detailed in . The National Institutes of Health are currently considering a four-year grant application to further advance Meller's nanopore sequencing project.

This low-cost, ultra-fast DNA sequencing could revolutionize both healthcare and biomedical research, and lead to major advances in drug development, preventative medicine and personalized medicine. By gaining access to the entire sequence of a patient's genome, a physician could determine the probability of that patient developing a specific genetic disease.

The team's findings show that nanopores, which can analyze extremely long DNA molecules with superior precision, are uniquely positioned to compete with current, third-generation DNA sequencing methods for cost, speed and accuracy. Unlike those approaches, the new nanopore method does not rely on enzymes whose activity limits the rate at which can be read.

"This puts us in the unique advantageous position of being able to claim that our sequencing method is as fast as the rapidly evolving photographic technologies," said Meller. "We currently have the capability of reading out about 200 bases per second, which is already much faster than other commercial third-generation methods. This is only the starting point for us, and we expect to increase this rate by up to a factor of four in the next year."
Licensing intellectual property from Boston University and Harvard University, Meller and his collaborators recently founded NobleGen Biosciences to develop and commercialize nanopore sequencing based on the new method.

"I believe that it will take three to five years to bring cheap DNA sequencing to the medical marketplace, assuming an aggressive research and development program is in place," said Meller.

Explore further: Next generation biomarker detects tumour cells and delivers anti-cancer drugs

More information: Research paper: http://pubs.acs.org/doi/abs/10.1021/nl1012147

Provided by Boston University College of Engineering

5 /5 (9 votes)

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jc1
not rated yet May 19, 2010
Fast?

At 3,000,000,000 base pairs in human dna it would take about 6 months to sequence one persons dna.
devcayer
not rated yet May 20, 2010
this method is not optimal and will not be practical to sequence dna. they use molecular beacon technology, which only allows them to hybridize to stretches of sequence, not individual base pairs. therefore, in a controlled setting like what they utilize, they are able to sequence stretches of A/T/G/or C. This in no way advances the field, and will not lead to cheaper dna sequencing technology. The authors comment on nanopore's are enzymes in their intro which can discriminate single base, and this system could sequence an entire dna strand. The whole point of using enzymes is to see the translocation event of the polymerase as it grabs the dna and slides one bp at a time.
eachus
not rated yet May 20, 2010
At 3,000,000,000 base pairs in human dna it would take about 6 months to sequence one persons dna.


I get about a week if you sequence the 46 chromosomes in parallel. Start reading each chromosome from both ends, add the factor of four speedup, and you are at under a day.

Current methods cut chromosomes into lots of pieces, sequence those, and then solve the puzzle to find the original sequence. You cut two or more sets of chromosomes at different specific sequences then work back and forth to find which piece goes next. With computers, that doesn't take much effort, but you need to sequence thousands of fragments in parallel.

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