Published On: Thu, Dec 7th, 2017

Taking DNA sequencing into the field

DEVICES for analysing DNA used to be big, clunky and not very good. Hundreds were required for the initial sequencing of the human genome, a project that started in the late 1990s and took over a decade to complete at a cost of at least $ 500m. Since then, sequencing a human genome has become a routine process; prices have fallen to below $ 1,000. Although the machines that do the job have got better and more compact, they still cost several hundred thousand dollars. Various groups are trying to make them smaller and cheaper.

The first device small enough to put in your pocket is already on the market. It comes from Oxford Nanopore, a maker of DNA-sequencing equipment based in the eponymous English city. It is about the size of a chunky mobile phone. Although the machine is swathed in patents, other miniature devices are bound to follow in time.

The MinION, as the device is called, is first plugged into a laptop. It works by sucking strands of DNA through a “flow cell”, made up of an array of tiny holes that are just a few nanometres (billionths of a metre) in diameter. The way that electricity flows across the surface of such a hole changes, depending upon the shape of the molecule passing through it. As strands of DNA are composed of four types of sub-unit, called bases, which have different shapes, nanopore sequencing permits the order of these bases to be determined—and with it the message carried by a gene.

Nanopore’s device is not a direct competitor to the bigger, more complex machines able to deliver the high levels of accuracy demanded by busy laboratories. Rather, the MinION is designed to take gene-sequencing out into the field. The device itself costs $ 1,000 and the flow-cell cartridges it uses, each of which lasts a few months, cost around $ 500 if purchased in bulk. So far, MinIONs have been used to sequence the DNA of microbes scraped out of the snow in Antarctica, swabbed off glaciers in Svalbard or sucked out of stagnant ponds in the bowels of disused coalmines in Wales. The technology was also employed to profile the virus behind an outbreak of Ebola in west Africa in 2015.

It is not, though, as simple as popping a sample in one end and getting the answer. To provide a truly portable gene-sequencing device, it is necessary to miniaturise and automate the preparation of samples. To extract DNA, biological samples must have their cells broken open, a process called lysing. The extracted DNA needs to be of sufficient purity that the readings are not contaminated. This is a tricky task, and one that requires some biochemical training and often the use of centrifuges and expensive reagents. Although the firm is keeping the details close to its chest, Oxford Nanopore is working on a small device called Zumbador, which it claims will be able to prep samples automatically.

For now, many users are happy to prepare samples themselves, often because by using a MinION they do not have to wait for a laboratory to send back results. Mars, a large food company, is testing the device on production lines in China, looking for particular bacterial pathogens such as Salmonella and E. coli. It already scrutinises its equipment and products closely for such contamination, but according to Robert Baker, who is in charge of food safety at the firm, the current arrangements can take days or weeks to return results. His hope is that once automated preparation is available, real-time monitoring will be able to spot problems almost instantly. It will also extend the range of bugs that can be detected; current tests are for specific pathogens, whereas sequencing can identify whatever bug might turn up. Early results, says Mr Baker, are promising.

The provenance of food is also a good candidate for genomic investigation. Following a scandal in some British supermarkets, in which meat marked as beef was found to contain material from horses, there is demand for tests that can verify the origin and species of meat products. Cranswick, a British supplier of cooked meats, is working in partnership with the University of Warwick on the use of the hand-held sequencers to analyse samples of DNA extracted from packaged meat and confirm the species from which it hails.

The benefits of on-the-spot sequencing may be greater still in the developing world. Agricultural researchers in Tanzania and Uganda plan to use Oxford Nanopore’s devices to help identify the viruses that plague cassava crops. Some 550m people, most of them African, rely on cassava as a staple, but scourges such as brown streak virus, spread by whitefly, can reduce yields by a factor of 40. Both the Mikocheni Agricultural Research Institute (MARI) in Dar es Salaam and the National Crops Resources Research Institute in Kampala already gather samples, in an effort to identify the strains of virus and to help farmers plant resistant crops. But these have to be sent abroad to laboratories in Australia, South Korea or Switzerland for sequencing—a process that can take months. In a pilot project in September, Laura Boykin, an agronomist at the University of Western Australia, and Joseph Ndunguru, MARI’s director, used hand-held sequencers to return strain data to farmers within 48 hours.

As portable sequencing devices get even faster and more accurate, Clive Brown, Oxford Nanopore’s chief technology officer, raises the prospect of a device that anyone can use to understand the genomic profile of the world around them. The user will merely touch the device to something, whether it is blood, spit or a supermarket chicken, and get a genomic profile in return. Gene sequencing used to be the work of years; soon enough it may be ubiquitous and quotidian.

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Taking DNA sequencing into the field