DNA sequencing improved by slowing down

September 21, 2015, Ecole Polytechnique Federale de Lausanne
A graphic illustration shows single nucleotides passing through a molybdenum disulfide nanopore film while controlled with a viscous room-temperature ionic liquid. Credit: Aleksandra Radenovic/EPFL

EPFL scientists have developed a method that improves the accuracy of DNA sequencing up to a thousand times. The method, which uses nanopores to read individual nucleotides, paves the way for better - and cheaper - DNA sequencing.

DNA sequencing is a technique that can determine exact sequence of a DNA molecule. One of the most critical biological and medical tools available today, it lies at the core of genome analysis. Reading the exact make-up of genes, scientists can detect mutations, or even identify different organisms. A powerful DNA sequencing method uses tiny, nano-sized pores that read DNA as it passes through. However, "nanopore sequencing" is prone to high inaccuracy because DNA usually passes through very fast. EPFL scientists have now discovered a viscous liquid that slows down the process up to a thousand times, vastly improving the method's resolution and accuracy. The breakthrough is published in Nature Nanotechnology.

Reading too fast

DNA is a long molecule made up of four repeating different building-blocks. These are called "" and are strung together in various combinations that contain the cell's genetic information, such as genes. Essentially, the four nucleotides compose all genetic language. DNA sequencing seeks to decipher this language, breaking it back down to individual letters.

In nanopore sequencing, DNA passes through a tiny pore in a membrane, much like a thread goes through a needle. The pore also contains an electrical current. As each of the four nucleotides pass through the pore, they block the current in individual ways that can be used to identify them. Though powerful, the method suffers from high speed: DNA goes through the pore too quickly to be read with enough accuracy.

Slowing things down

The lab of Aleksandra Radenovic at EPFL's Institute of Bioengineering has now overcome the problem of speed by using a thick, that slows the passage of DNA two to three orders of magnitude. As a result, sequencing accuracy improves down to single nucleotides.

The research was carried out by Jiandong Feng and Ke Liu, working with colleagues in Andras Kis's lab at EPFL. The two researchers developed a film made of molybdenum disulfide (MoS2), only 0.7 nm in thickness. This is already an innovation over attempts in the field that use graphene: DNA is a fairly sticky molecule and MoS2 is considerably less adhesive than graphene. The team then created a nanopore on membrane, almost 3 nm wide.

The next step was to dissolve DNA in a thick liquid that contained charged ions and whose molecular structure can be fine-tuned to change its thickness, or "viscosity gradient". The liquid belongs to the class of "room-temperature ionic liquids", which are basically salts dissolved in a solution. The EPFL scientists exploited the liquid's tunability to bring it to an ideal viscosity gradient - enough to slow down DNA.

Finally, the team tested their system by passing known nucleotides, dissolved in the liquid, through the nanopore multiple times. This allowed them to take an average reading for each one of the four nucleotides, which can be used to identify them later on.

Although still at a testing stage, the team is aiming to continue their work by testing entire DNA strands. "We are seeking opportunities to commercialize this technique, which is promising for sequencing with solid-state nanopores," says Jiandong Feng.

The scientists also predict that using high-end electronics and control of the viscosity gradient of the liquid could further optimize the system. By combining ionic liquids with nanopores on thin films, they hope to create a cheaper DNA sequencing platform with a better output.

The work offers an innovative way that can improve one of the best DNA sequencing methods available. "In years to come, sequencing technology will definitely shift from research to clinics," says Aleksandra Radenovic. "For that, we need rapid and affordable DNA sequencing - and nanopore technology can deliver."

Explore further: New material could enhance fast and accurate DNA sequencing

More information: Feng J, Liu K, Bulushev RD, Khlybov S, Dumcenco D, Kis A, Radenovic A. Identification of single nucleotides in MoS2 nanopores. Nature Nanotechnology 21 September 2015. DOI: 10.1038/nnano.2015.219

Related Stories

The gene sequencing that everyone can afford in future

December 6, 2013

DNA sequencing is important to science. While Professor Qian Linmao and his group from Tribology Research Institute, Southwest Jiaotong University, were working on the optimization of the third-generation sequencing technique ...

Recommended for you

Quantum bits in two dimensions

March 20, 2018

Two novel materials, each composed of a single atomic layer and the tip of a scanning tunneling microscope, are the ingredients for a novel kind of quantum dot. These extremely small nanostructures allow delicate control ...

Rubbery carbon aerogels greatly expand applications

March 19, 2018

Researchers have designed carbon aerogels that can be reversibly stretched to more than three times their original length, displaying elasticity similar to that of a rubber band. By adding reversible stretchability to aerogels' ...

Scientists have a new way to gauge the growth of nanowires

March 19, 2018

In a new study, researchers from the U.S. Department of Energy's (DOE) Argonne and Brookhaven National Laboratories observed the formation of two kinds of defects in individual nanowires, which are smaller in diameter than ...

Plasmons triggered in nanotube quantum wells

March 16, 2018

A novel quantum effect observed in a carbon nanotube film could lead to the development of unique lasers and other optoelectronic devices, according to scientists at Rice University and Tokyo Metropolitan University.

Zero field switching (ZFS) effect in a nanomagnetic device

March 16, 2018

An unexpected phenomenon known as zero field switching (ZFS) could lead to smaller, lower-power memory and computing devices than presently possible. The image shows a layering of platinum (Pt), tungsten (W), and a cobalt-iron-boron ...

Imaging technique pulls plasmon data together

March 16, 2018

Rice University scientists have developed a novel technique to view a field of plasmonic nanoparticles simultaneously to learn how their differences change their reactivity.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.