Release date: 2015-09-25
Scientists from the Federal Institute of Technology in Lausanne (EPFL) in Switzerland have developed a method to increase the accuracy of DNA sequencing by a factor of 1000. The use of nanopores to read a single nucleotide paves the way for better and cheaper DNA sequencing.
DNA sequencing is a technique that determines the exact sequence of a DNA molecule. As one of the most important biological and medical tools available today, it forms the core of genomic analysis. By identifying the exact composition of a gene, scientists can detect mutations and even identify different organisms.
A powerful DNA sequencing method utilizes tiny nanopores to read through the DNA. However, since DNA tends to pass through the nanopore at an extremely fast rate, the "nanopore sequencing" error rate is very high. EPFL scientists have now discovered that a viscous liquid can slow the process by a factor of 1000, greatly increasing the resolution and accuracy of this method. This breakthrough result was published in the journal Nature Nanotechnology.
Read too fast
DNA is a long molecule composed of four different repeating members. These components, called "nucleotides", are grouped together in various combinations that contain genetic information about the cells, such as genes. Basically, these four nucleotides make up all the genetic languages. DNA sequencing is done by trying to decipher the language and breaking it down into individual bases.
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During nanopore sequencing, DNA passes through tiny pores in the membrane as the thread passes through the needle. This channel contains electrical currents, and as each nucleotide passes through this channel, they block the current in their respective ways, thereby recognizing these nucleotides. Although this method is powerful, it suffers from high speed: the speed of DNA passing through the tunnel is too fast to read it with sufficient accuracy.
Slow down
The Aleksandra Radenovic laboratory of the EPFL Bioengineering Institute has now overcome this problem by using a viscous liquid to slow the passage of DNA by 2-3 orders of magnitude. Thereby, the sequencing precision is improved to a single nucleotide.
The study was done by colleagues from Jiandong Feng, Ke Liu, and the Andras Kis lab. Two researchers have developed a film consisting of molybdenum disulfide (MoS2) with a thickness of only 0.7 nm. The team then fabricated nanopores about 3 nm wide on the membrane.
The next step is to dissolve the DNA in a mucus containing charged ions. The researchers can fine-tune the molecular structure of the mucus to change its "viscosity gradient." This liquid belongs to a "room temperature ionic liquid" which is actually a salt solution. EPFL scientists have taken advantage of the tunability of liquids to achieve an ideal viscosity gradient sufficient to slow DNA.
Finally, the team tested their system by passing the known nucleotides dissolved in the liquid multiple times through the nanopore. This allows the researcher to obtain an average reading of each nucleotide and then use the reading to identify them.
Although still in the testing phase, the research team intends to continue their research work to test the complete DNA strand. Feng Jiandong said: "We are looking for opportunities to commercialize this technology."
Scientists predict that this system can be further optimized by using high-end electronics and controlling the viscosity gradient of the liquid. By combining ionic liquids and molybdenum disulfide thin film nanopores, they hope to build a cheaper DNA sequencing platform that yields better output.
This work provides an innovative way to improve one of the best DNA sequencing technologies available today. "In the next few years, sequencing technology will definitely shift from research to clinical. Therefore, we need fast and affordable DNA sequencing - nanopore technology can achieve this goal," Aleksandra Radenovic said.
Source: Biopass
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