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Ion Torrent Chips Ready to Seek Out New Life, Boldly Go Where No Man Has Gone Before

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This article was originally published Aug. 5.

Ion Torrent's sequencing chips appear to be hardy enough to survive the harsh conditions of space, allowing scientists to hunt for DNA- or RNA-based life on Mars and maybe elsewhere, according to researchers from Harvard Medical School and Life Technologies.

In a paper recently published in Astrobiology, the scientists, led by Gary Ruvkun, a professor of genetics at Harvard Medical School, exposed Ion Torrent PGM sequencing chips to radiation equivalent to what they would encounter on a two-year mission to Mars. They found that irradiation did not affect the electrical performance of the chips and had no measurable effect on sequencing quality.

Based on these results, the researchers are now working on a benchtop model of a sequencer that could eventually go into space to detect and characterize life.

According to Ruvkun, he and his colleagues have been thinking about looking for DNA in space since the early 1990s, when it became clear that the genetic code is universal and highly conserved, and that it can be used to trace the evolutionary history of life. "If there is a method of choice for looking for divergent life on Earth, why not use that on a different planet?" Ruvkun said.

The project, called Search for Extraterrestrial Genomes, or SETG for short, hinges on the assumption that life on Mars, or elsewhere in space, is based on DNA or RNA. According to Ruvkun, it is more likely that genetic material was transferred between Mars and Earth through meteorites than that life developed independently on both planets, and life elsewhere might very well be based on nucleic acids as well. In addition, life-detection approaches that do not assume DNA are much harder to implement than DNA detectors. "You'd feel kind of stupid to build a life detector that's universal only to discover that it's DNA," he said. "You might as well first assume it's DNA and then be stupid."

The initial idea, which they proposed to NASA in 2001, was to send a PCR thermal cycler to Mars, a project his group pursued in collaboration with Maria Zuber, a professor of geophysics and planetary science at MIT, and PCR-firm MJ Research, whose co-founder Mike Finney was a postdoc in Ruvkun's lab. But "as genomics progressed, and especially as the Ion Torrent chip was developed, you could actually talk about doing deep sequencing remotely," he said.

Sequencing would be able to distinguish immediately between DNA from space and contaminating material from Earth, "the biggest problem in this whole business," Ruvkun said, similar to ancient DNA sequencing. By the time a sequencer might go into space — on the order of 20 years or so from now — every genome on Earth will likely be sequenced, so it will be easy to distinguish between contaminants and truly extraterrestrial DNA. Also, "by deep sequencing, you can deal with 99 percent contamination, you just look for the 1 percent that's not," he said.

Sequencing in space would be preferable over retrieving samples and sending them back to Earth because they could decay during the journey. Scientists have already shown that sequencing reagents have a long enough shelf life for a mission to Mars, and that they still function after being irradiated.

Ruvkun's team approached Ion Torrent when the firm's semiconductor sequencing technology became available and has been collaborating with the company on the space project.

Other sequencers that use optical detection are not suitable for sequencing in space, he said, because they are too large and heavy and not robust enough. "The instrument needs to be stripped down, it needs to be a kilogram or a megabyte of data, it has to be tiny," Ruvkun said. "You can't afford high-end optics on this."

Emerging technologies, though, that are not yet commercially available might also fit the bill. "Nanopores would be fantastic, because then we would not have to purify the DNA," Ruvkun said, noting that his team is closely watching developments in this area.

For their study of the Ion Torrent chips, they used a total of 40 PGM Ion 314 chips. Twenty chips were tested electrically – quantifying gain, reference voltage, and pH sensitivity for each ion-sensitive field-effect transistor sensor – before and after irradiation. Of the other 20 chips, 12 were used for sequencing the E. coli genome after irradiation and eight for sequencing without irradiation.

They used three different types of irradiation that resemble those encountered during a Mars mission — proton, oxygen, and iron ions — at two different doses each, which they applied at the NASA Space Radiation Lab, using the 200 MeV Linear Accelerator for protons and the Electron Beam Ion Source for oxygen and iron ions. In the future, they also plan to study the effects of gamma rays.

Overall, they found that the irradiation did not affect the electrical performance of the chips. In the sequencing experiment, all chips successfully generated data and there was no impact from irradiation on sequence accuracy.

Those results were not much of a surprise, "but it's a necessary step to show that you can really do it," Ruvkun said. "NASA really cares about this — you have to show that whatever you bring up there can survive the radiation that happens during interplanetary travel."

The scientists are now developing a benchtop model of a DNA sequencer that could be sent into space. This does not yet have to be miniaturized, Ruvkun explained, but should be the "closest mimic" of the final platform.

It would include a sample prep device to extract and purify DNA from soil, based on commercially available modules that are modified. Library preparation and amplification are likely going to differ from how they are done today, no longer involving emulsion PCR.

"If you can show that you can put dirt in at one end and get sequence out at the other on a benchtop at sort of five times the weight that you'll eventually have, that's the next step," he said. "That shows to NASA that you are at a technical readiness level for them to give you a grant to actually develop the instrument."

NASA's funding for the project, however, which has been going on for about a decade, has recently dried up, and it is unclear whether the project will keep going. "We're not on their fast list to fly," Ruvkun said.

The cost of a Mars mission would increase significantly if a life detection instrument was on board, he explained, because the spacecraft would need to be sterilized and precautions against contamination would need to be taken. "It's a big decision for them to say 'yes' to this."

In the meantime, a DNA sequencer in space could serve other purposes, for example to survey the microbiome that has developed over the years on the International Space Station, he said.

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