DNA sequencing improved by slowing down

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.

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

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.

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.