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Researchers Explore MoS2 as Promising Material for Solid-State Nanopore Sequencing

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NEW YORK (GenomeWeb) – Over the last few years, researchers have been exploring various materials, including silicon nitride, graphene, and boron nitride, for solid-state nanopore sequencing. Recently, at least two groups have turned their attention to a new material, molybdenum disulfide, MoS2, that has a number of favorable properties for sequencing, some of which appear to exceed those of graphene.

Like graphene, a single-atom layer of graphite, single-layer MoS2 is less than one nanometer thick, reducing the number of bases present inside the nanopore at a time and promising sequencing with single-base resolution.

Earlier this year, a group at the Swiss Federal Institute of Technology in Lausanne published a study in ACS Nano showing that they can drill nanopores ranging from about 2 nanometers to 20 nanometers in diameter through thin MoS2 membranes, using a transmission electron microscope, and translocate double-stranded DNA through those pores.

Measuring the ion current blockage, they found the sensitivity of the pores to be higher than that of silicon nitride nanopores, which are thicker, and similar to the sensitivity previously seen for graphene nanopores. They also observed good signal-to-noise ratios of greater than 10. In addition, unlike graphene, MoS2 required no special surface treatment to prevent DNA from sticking to its surface.

"Sticking behavior of DNA, observed in graphene nanopores, is reduced in MoS2 nanopores due to the Mo-rich surface achieved after [transmission electron microscope] irradiation," Aleksandra Radenovic, the study's senior author, told In Sequence. "In addition, single-layer MoS2 has a direct band gap of at least 1.8 eV, which is essential for electronic base detection in field-effect transistors, thus making MoS2 a promising material for single-nucleotide detection."

In a paper published online in ACS Nano last week, researchers from the University of Illinois at Urbana-Champaign employed two types of computational simulations to further explore the use of single-layer MoS2 nanopores for DNA sequencing, either by measuring ionic current or by recording transverse tunneling currents.

"We were quite surprised how well this material was doing, at least in computations," Narayana Aluru, a professor in the department of mechanical science and engineering and the senior author of the study, told In Sequence. "We got quite good signal-to-noise ratios compared to anything that has been reported so far," and did not find DNA to be sticking to the pore.

For their study, they performed molecular dynamic simulations of double-stranded DNA translocating through a 2.3-nanometer MoS2 pore. They found four conductance states, compared to only two for graphene pores of the same size, which they said is "not enough to distinguish all the bases in the pore." The reason why MoS2 has more conductance states, they wrote, is that it contains both hydrophobic sulfur atoms and hydrophilic molybdenum atoms.

They also found the calculated signal-to-noise ratio of MoS2 nanopores to be higher, 15, than for graphene nanopores, where it was 3. For MoS2, the ratio was close to the experimental results from the Lausanne group, Aluru said. Overall, they wrote, the architecture of MoS2 nanopores makes them "amenable for ionic current measurements with lower noise" than other types of pores.

MD simulations for both MoS2 and graphene nanopores also revealed that DNA sticks to graphene but not MoS2. Further computations showed that the more molybdenum atoms are exposed in the pore, the less the DNA interacts with it. The pore, they wrote, could be further adapted to optimize DNA translocation. "You can engineer what is exposed to DNA and what is not," Aluru explained. "That makes it a little more promising material than graphene."

Besides MD, the researchers performed Density Functional Theory simulations to model the transverse tunneling current that occurs when DNA bases are trapped inside the pore, a signal that could be exploited for electronic base detection.

They found that the band gap of MoS2 − the energy difference between electron states − is "significantly changed" compared to graphene and other materials when DNA bases are placed on top of MoS2 or an armchair MoS2 nanoribbon, "thus making MoS2 a promising material for base detection via transverse current tunnel measurement."

"I believe this is an important theoretical work that helps in framing the relevant research questions, and it sets the chart for potential implementations," said Slaven Garaj, an assistant professor at the National University of Singapore, who was not affiliated with the study and has been working on graphene nanopore sequencing.

"However, the theoretical models oftentimes fail to predict all the complexities and surprises concocted by nature − the devil is always in the experiment," he cautioned. "It will be exciting to see how future experiments will measure against this work."

Garaj also noted that MoS2, though thin, is still thicker than graphene, which "could lead to averaging of the signal from the neighboring nucleobases within the translocating DNA molecule."

Aluru said that while theoretical studies do not always provide accurate insights, the fact that his team's study came up with a similar signal-to-noise ratio for MoS2 as the Lausanne group's experimental study "gave us a lot of confidence that our calculations are indeed in the right direction."

Regarding the thickness of MoS2, "if you really want to go to a single-atom-thick pore, then graphene is perhaps the way to do it," he said. "But right now, based on what we're observing, we feel like MoS2 is perhaps better than graphene, from a DNA sequencing point of view."

Going forward, Aluru plans to conduct further theoretical studies to see whether MoS2 can yield complete resolution at very high sensitivity. "We're not there yet − we observe only four conduction levels," he said.

In addition, his group is collaborating with experimentalists at the University of Illinois and plans to connect with others working with MoS2.

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