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Hand Held DNA Sequencer

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Point-of-Care DNA Sequencer Inching Closer to Widespread Use as Beta-Testers Praise Oxford Technologies’ Pocketsize, Portable Nanopore Device

November 4, 2015

MinION could help achieve NIH’s goal of $1,000 human genome sequencing and in remote clinics and outbreak zones shift testing away from medical laboratories

Point-of-care DNA sequencing  technology is edging ever closer to widespread commercial use as the Oxford Nanopore MinION sequencer  draws praise and registers successes in pre-release testing.

A pocketsize gene-sequencing machine such as the MinION could transform the marketplace by shifting DNA testing to remote clinics and outbreak zones while eliminating the need to return samples to clinical laboratories for analysis. Such devices also are expected to increase the need for trained genetic pathologists andmedical technologists.

After Much Anticipation, MinION Delivers on Promises

The MinION, produced by United Kingdom-based Oxford Nanopore Technologies, is a miniaturized instrument about the size of a USB memory stick that plugs directly into a PC or laptop computer’s USB port. Unlike bench-top sequencers, the MinION uses nanopore “strand sequencing” technology to deliver ultra-long-read-length single-molecule sequence data.

“The USB-powered sequencer contains thousands of wells, each containing nanopores—narrow protein channels that are only wide enough for a single strand of DNA. When DNA enters the channels, each base gives off a unique electronic signature that can be detected by the system, providing a readout of the DNA sequence,” reported

After several years of unfulfilled promises, Oxford began delivering the MinION in the spring of 2014 to researchers participating in its early access program called MAP . For a $1,000 access fee, participants receive a starter kit and may purchase consumable supplies. The current price for additional flow cells ranges from $900 for one to $500 per piece when purchased in 48-unit quantities.

 

Nick Loman, an Independent Research Fellow in the Institute for Microbiology and Infection at the University of Birmingham, UK, had questioned if MinION’s promise would ever be realized. But the USB-size sequencer won him over after he used it to detect Salmonella within 15 minutes in samples sent from a local hospital.

 

Loman received the MinION in May 2014 as part of the MAP program and quickly tested its usefulness. After using the device to sequence a strain of Pseudomonas aeruginosa, a common hospital-acquired infection (HAI), he next helped solve the riddle of an outbreak of Salmonella infection in a Birmingham hospital that had affected 30 patients and staff.

“The hospital wanted to understand quickly what was happening,” Loman stated. “But routine genome sequencing is quite slow. It usually takes weeks or even months to get information back.”

Using MinION, Loman detected Salmonella in some of the samples sent from the hospital in less than 15 minutes. Ultimately, the main source of the outbreak was traced to a German egg supplier.

“The MinION just blew me away,” Loman stated in Wired. “The idea that you could do sequencing on a sort of USB stick that you can chuck around does stretch credulity.”

Portable Sequencing Opens Up Intriguing Possibilities for Pathologists

In May 2015, Oxford released a second version of the device, the MinION MkI. According to the company website, the updated MinION is a “full production device featuring improvements of performance and ease of use,” such as improved temperature control and updated mechanism to engage the device with the consumable flow cells.

“The bench-top sequencers opened up the market to a certain degree,” Loman says. “You started seeing [them] in intensive research groups and in the clinic. But what if anyone could have this hanging off their key ring and go do sequencing? That’s an insane idea, and we don’t really know what it’s going to mean in terms of the potential applications. We’re very much at the start of thinking about what we might be able to do, if anyone can just sequence anything, anywhere they are.”

 

Joshua Quick, a PhD candidate at the University of Birmingham, UK believes Oxford Nanopore Technologies’ portable and inexpensive device will change the gene sequencing landscape.

 

Accuracy One Trade-off for Portability

Beta-testers have shown that the miniature device can read out relatively long stretches of genetic sequence with increasing accuracy, but according to the report in the journal Nature , the MinION MkI will need to correct several shortcomings found in the original sequencer:

• It is not practical to sequence large genomes with the device, with some experts estimating it would take a year for the original version to sequence the equivalent of a human genome.

• The machine has a high error rate compared with those of existing full-sized sequencers, misidentifying DNA sequence 5%–30% of the time.

• It also has difficulties reading sections of genome that contain long stretches of a single DNA base.

Yet researchers who have used the device remain enthusiastic about the future of this fourth-generation sequencing technique, which may have the potential to achieve the $1,000-per-human-genome goal set by the National Institutes of Health  (NIH).

“This is the democratization of sequencing,” Joshua Quick, a PhD candidate at the University of Birmingham, told Nature. “You don’t have to rely on expensive infrastructure and costly equipment.”

News accounts did not provide information about Oxford Nanopore’s plans to obtain an EU mark for its MinION device. That will be the next step to demonstrating that the device is ready for widespread clinical use. At the same time, clinical laboratory managers and pathologist should take note of the capabilities of the MinION MkI as described above. Researchers are already finding it useful to identify infectious diseases in clinical setting where other diagnostic methods have not yet identified the agent causing the infection.

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