Nanopore Method Could Revolutionize Genome Sequencing

Apr 06, 2006
Nanopore Method Could Revolutionize Genome Sequencing
DNA and Nanopore from Above. Credit: Johan Lagerqvist

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.

Previous attempts to sequence DNA using nanopores were not successful because the twisting and turning of the DNA strand introduced too much noise into the signal being recorded. The new idea takes advantage of the electric field that drives the current perpendicular to the DNA strand to reduce the structural fluctuations of DNA while it moves through the pore, thus minimizing the noise.

“If nature was very unkind, then the DNA would always fluctuate so much as it passes through the nanopore that measuring the current would not give us any information about what base is present at a particular location,” explained Michael Zwolak, a graduate student in physics at the California Institute of Technology who contributed to the study. “However, we have identified a particular way to operate the nanopore/electrode system that suppresses some of the fluctuations so they aren't so great as to destroy the distinguishability of the bases.”

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.

In addition to the speed and low cost of the nanopore method, the researchers calculate that it will ultimately be significantly less error-prone than current methods.

“The DNA sequencing method we propose has the potential of having fewer errors than the present method, which is based on the Sanger method,” said Johan Lagerqvist, a graduate student in physics at UCSD and the lead author on the paper. “It should be possible to sequence strands of DNA that are tens of thousands of base pairs in length, possibly as long as an entire gene, in one pass through the nanopore. With the Sanger method it is necessary to chop the DNA into smaller pieces, copy the DNA and use multiple sequencing machines, which introduces additional sources of error.”

The study was funded by the National Science Foundation and by the National Human Genome Research Institute at the National Institutes of Health. The NIH funds are from a program launched in 2004 to encourage researchers to pursue a wide range of ideas to sequence a mammal-sized genome for $1,000. The researchers say that as physicists they take a unique approach to the problem.

“We don’t think of it as DNA, we view it as a bunch of atoms and electrons that behave in ways we can predict and manipulate,” said Di Ventra.

Source: University of California, San Diego

Explore further: Researchers obtain first direct observation of facet formation in nanocubes

add to favorites email to friend print save as pdf

Related Stories

Scientists fold RNA origami from a single strand

Aug 14, 2014

RNA origami is a new method for organizing molecules on the nanoscale. Using just a single strand of RNA, many complicated shapes can be fabricated by this technique. Unlike existing methods for folding DNA ...

Statistical model predicts performance of hybrid rice

Aug 13, 2014

Genomic prediction, a new field of quantitative genetics, is a statistical approach to predicting the value of an economically important trait in a plant, such as yield or disease resistance. The method works ...

An easier way to manipulate malaria genes

Aug 11, 2014

Plasmodium falciparum, the parasite that causes malaria, has proven notoriously resistant to scientists' efforts to study its genetics. It can take up to a year to determine the function of a single gene, ...

Recommended for you

Cut flowers last longer with silver nanotechnology

23 hours ago

Once cut and dunked in a vase of water, flowers are susceptible to bacterial growth that shortens the length of time one has to enjoy the blooms. A few silver nanoparticles sprinkled into the water, might be the answer to ...

Relaxing DNA strands by using nano-channels

Aug 20, 2014

A simple and effective way of unravelling the often tangled mass of DNA is to 'thread' the strand into a nano-channel. A study carried out with the participation of the International School for Advanced Studies ...

User comments : 0