April 06, 2006
Nanopore Design For Cheap DNA Sequencing Identified

A nanopore that has electrodes that can measure the electrical differences between genetic code letters could enable very cheap and fast DNA sequencing.

A team led by physicists at the University of California, San Diego has shown the feasibility of a fast, inexpensive technique to sequence DNA as it passes through tiny pores. The advance brings personalized, genome-based medicine closer to reality.

The paper, published in the April issue of the journal Nano Letters, describes a method to sequence a human genome in a matter of hours at a potentially low cost, by measuring the electrical perturbations generated by a single strand of DNA as it passes through a pore more than a thousand times smaller than the diameter of a human hair. Because sequencing a person’s genome would take several months and millions of dollars with current DNA sequencing technology, the researchers say that the new method has the potential to usher in a revolution in medicine.

“Current DNA sequencing methods are too slow and expensive for it to be realistic to sequence people’s genomes to tailor medical treatments for each individual,” said Massimiliano Di Ventra, an associate professor of physics at UCSD who directed the project. “The practical implementation of our approach could make the dream of personalizing medicine according to a person’s unique genetic makeup a reality.”

The physicists used mathematical calculations and computer modeling of the motions and electrical fluctuations of DNA molecules to determine how to distinguish each of the four different bases (A, G, C, T) that constitute a strand of DNA. They based their calculations on a pore about a nanometer in diameter made from silicon nitride—a material that is easy to work with and commonly used in nanostructures—surrounded by two pairs of tiny gold electrodes. The electrodes would record the electrical current perpendicular to the DNA strand as the DNA passed through the pore. Because each DNA base is structurally and chemically different, each base creates its own distinct electronic signature.

While these researchers have identified the needed configuration the nanopore electrodes they haven't yet built the device. But they say the problem might be solved soon.

The researchers caution that there are still hurdles to overcome because no one has yet made a nanopore with the required configuration of electrodes, but they think it is only a matter of time before someone successfully assembles the device. The nanopore and the electrodes have been made separately, and although it is technically challenging to bring them together, the field is advancing so rapidly that they think it should be possible in the near future.

The researchers also expect this method to have a lower error rate than the current Sanger method for sequencing DNA.

Cheap DNA sequencing will bring many benefits and changes. A massive comparison of the DNA sequences of millions of people along with recording a large quantity of other information about each person (physical shape, hair/eye/skin color, health records, IQ, education, values, preferences, etc) will lead to the fast identification of genetic variations that contribute to a huge range of human differences.

Share |      Randall Parker, 2006 April 06 10:12 PM  Biotech Advance Rates

AMac said at April 7, 2006 10:24 AM:

Efforts to supplant Sanger sequencing in at least some applications are already underway. 454/Curagen is trialing and selling machines (with Roche) right now. Solexa intends to have their 1G apparatus on the market in a few months. I'm not sure how far behind Helicos is.

The key questions for nanopore-based sequencing will be the same as for these more conventional optical programs.

--Ordered sequencing of huge genomes, or random? (almost certainly random).
--How long a string of sequence do you get from one DNA fragment (molecule or amplified clone; molecule for nano approach)? 20-25 bases is the low end of useful. 50 is pretty good, 100 base reads make reads through repetitive regions much more straightforward (piecing together the actual sequence correctly).
--Is the accuracy about as good as current dideoxy methods?
--Can you read from both ends of the DNA strands (paired-end reads)?

It's a tough road, but if the nano approach is potentially cheap and fast, it could compete.

Just the 2 cents of a technology-watcher. I'm not a sequencer, myself.

Randall Parker said at April 7, 2006 6:18 PM:


Seems to me we need the ability to read much longer sections in order to measure large copy variations. The problem is that a single gene or section of a gene can be duplicated few or many times. Just sequencing small fragments won't allow you to detect that. Large copy variations might be as important as single point mutations in making people genetically different from each other.

Ivan Kirigin said at April 8, 2006 6:13 PM:

The end goal should be manipulation. If we can't change people's genetic destiny, all this work will be a complicated method of discrimination. I'm not trying to associate the typical pejorative with the word "discrimination" -- discriminating those who are likely to have a certain disease from those that aren't is a very good thing.

But I feel bad for those who have bad genes. I would like them to be empowered.

Another issue is human enhancement, which is overall an important way to make sure AI doesn't take over the world.

Bob Badour said at April 8, 2006 8:00 PM:

"Pardon me if I don’t set policy based upon the nation’s laggards."

"But I feel bad for those who have bad genes. I would like them to be empowered."

Ivan, I really am having trouble finding anything resembling logical consistency in what you post.

Ivan Kirigin said at April 9, 2006 7:07 AM:

I didn't note Bob's double comment until now.

Immigration policy is about what we should do today. Genetic manipulation for enhancement is decades away.

Secondly, there is a difference between government policy about freedom of movement and employment vs. a technology generally which could help lots of people.

Thirdly, the '"nation's laggards" quote, in context, is saying that America's poor are far worse off than the poor of countries who send many emigrants. In that sense, a policy of limited and reasonable immigration is good -- it helps those who are absolutely poor while only marginally hurting those already in America who are doing fine.

Ivan Kirigin said at April 9, 2006 7:08 AM:

Sorry -- America's poor are _better_ off than those of 3rd world countries.

If you don't believe me, just note that median income in many european nations is below the poverty line in America. What do you think that tells you about Columbia?

detribe said at April 9, 2006 8:18 AM:

One problem might be ambiguity of direction of movement of dna going through the pore- meaning the sequence would be innacurate where the direction is ambiguous

Bob Badour said at April 9, 2006 11:39 AM:
What do you think that tells you about Columbia?

It tells me they have not yet raised their arbitrary definition of poverty to include many european nations.

Bob Badour said at April 9, 2006 1:29 PM:
Sorry -- America's poor are _better_ off than those of 3rd world countries.

Isn't that just another way of saying that citizenship is property and that American citizenship is worth more than 3rd world citizenship?

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