In the researchers’ first conception of the system, the entire strand of DNA would pass through as a whole. In theory, DNA could pass through the nanopore at a rate of a million per second, but that’s much too fast to generate a discernible signal. So Hagan Bayley, Oxford Nanopore’s founder and an Oxford University chemical biologist who developed some of the technology the company has licensed, added another component to the system: an exonuclease, an enzyme that slices the DNA strand into individual bases and directs them through the nanopore. Each base passes through the nanopore individually and sequentially, slowing the overall rate down to between 10 and 50 bases every second, giving the electrical equipment time to read the signal, which is in the range of a picoamp, a trillionth of an amp.
The company will speed up the analysis of DNA by putting an array of these nanopore setups on a silicon chip. Sanghera says they’ll start with several hundred nanopores per chip, and then eventually expand to tens of thousands.
Though the company has demonstrated the individual pieces of the system, it still has to put them all together. It’s working on ways to attach the exonuclease to the protein and trying to marry the biological part to the sensing electronics and the silicon chip. The company doesn’t have to invent any new electronics, but it does need to design custom chips, which can be complex. “The challenge is system integration, and it’s a big challenge,” Sanghera says.
Though he won’t reveal a specific launch date, he says the company is planning to keep pace with Pacific Biosciences, which aims to have a sequencing device on the market in about two years.
The researchers are aiming for the $1,000 genome. The hope is that by bringing the price of sequencing down to that range, individuals could afford to have their genomes recorded, allowing doctors to tailor treatments to their particular genetic makeup. Sanghera sees the next generation of nanopore technology replacing the biological nanopores with artificial ones. Ultimately, the goal is to make the system solid-state, built wholly in silicon the way computer chips are.
NHGRI has long championed cheap gene sequencing. It has given more than $12 million to the researchers whose technology Oxford Nanopore licensed, including a recent $6.5 million grant to Daniel Branton and Jene Golovchenko of Harvard. The institute’s initial goal was to achieve the $1,000 genome by 2014. “I think that’s turning out to be a pretty good estimate,” Schloss says.