The first human genome sequence took 13 years and cost $3 billion — now, less than a decade later, a new company promises to sequence a full genome in 15 minutes for a song. If this exponential increase in efficiency and drop in price sounds like something out of the computing industry, that’s because it is. Multicore processors and customizable clusters are coming to gene sequencing, threatening to disrupt one of the most important industries in modern medicine.
Oxford Nanopore Technologies Ltd. says its new micro-sequencers — one of which is USB-powered and will retail for $900 — could be used quickly and easily in the field, identifying anything from viruses at airports to new species in the deep jungle. Here’s how it works.
To determine how nucleotide bases are arranged, most sequencing machines break a DNA strand apart and replicate it, amplifying it by several orders of magnitude. Computers suss out the nucleotide arrangements using a variety of methods, from dyes to other chemicals. Take the forthcoming $1,000-per-genome Ion Proton chip, for instance. It attaches DNA fragments to microscopic beads and spins them in microwells on a semiconductor chip. The wells are flooded with each of the DNA nucleotides, and the machine looks for matchups. When there’s a match, a positive hydrogen ion is released, and algorithms interpret the resulting voltage change to determine which bases matched, thereby building a chart of base arrangements.Instead, Oxford Nanopore's technology keeps the purified DNA strand intact, passing it through a nanoscale biological “pore” made from a protein. Nanopores first entered the scene in the 1990s, but haven’t yet made it to market for a variety of reasons. Oxford Nanopore says recent advances in polymer chemistry have made its design possible.
The heart of the company’s design is a custom-designed nanopore, inserted into a polymer membrane that rests on top of a microwell. The membrane has a high electrical resistance, and a voltage is applied so a current passes through the nanopore. Each microwell has its own electrode. A user would pour some purified DNA into the cartridge, where it would flow over the membrane and through the nanopores. As the DNA strand passes through a pore, each of its nucleotides interrupts the current in a measurable way. This change in conductivity can be used to identify the nucleotide.
Whole arrays of nanopores and their microwells are embedded onto chips, using typical semiconductor manufacturing techniques, and these are inserted into a disposable cartridge. Each cartridge is built so the nanopores are tuned to sense specific molecules — like DNA, or maybe proteins, drugs or other compounds. A user inserts the cartridge into the sequencing node of choice: either the GridION node, which looks like an old-school VCR, or the MinION system, which is a slightly fat USB stick.
Each nanopore analyzes its sample independently of the others. This massively parallel approach allows for faster analysis, according to the company — the nanopores can read nucleotides in real time with low error rates. What’s more, the GridION nodes can be used as a customizable cluster, in the same way computers can — if you have two machines, you can either use them as two machines, or as one machine running twice as fast, as a company spokeswoman describes it. Users will be able to determine the configurations they want. The MinION devices can work in clusters, too, using the company’s software and a USB hub.
"Oxford Nanopore is as much an electronics company as a biotechnology company,” company CEO Gordon Sanghera said.
The company tried it out with the Phi X phage, a bacterial virus, sequencing the virus’ entire 54,000-base, or 5.4 kilobase, genome in one fell swoop. The first GridION machines to go on sale this year will read 100 kilobases, which is far longer than the DNA snippets used by most current sequencers. This will give a more accurate glimpse of DNA’s structure, the company says.
Initially, the GridION system will feature a node containing 2,000 nanopores, which can read DNA at hundreds of kilobases per second. The MinION cartridge can run 150 megabases per hour over its six-hour lifetime. By 2013, the company plans to start selling 8,000-nanopore nodes, each reading hundreds of kilobases. A cluster of 20 of these nodes would theoretically be able to sequence the 3.2 billion base pairs in a human genome within 15 minutes, Sanghera said.