By Kevin Davies
February 22, 2012 | SAN FRANCISCO – In his first public presentation since the dramatic announcement of a next-gen sequencing (NGS) breakthrough by Oxford Nanopore last week, Stefan Roever, CEO of rival nanopore sequencing company Genia Technologies, said his company was targeting the launch of a sequencing device with up to 1 million nanopores in 2013.
Speaking at CHI’s Molecular Medicine Tri-Conference, Roever said Genia’s nanopore sequencer married attributes of two rival NGS platforms -- the long-read capability of Oxford Nanopore with the scalability of an Ion Torrent.
Drawing a distinction between the two nanopore platforms, Roever said that the Oxford Nanopore system “uses a passive sensor array [rather than] a chip-based model to do integration… They mechanically have to make these passive arrays. They’re not leveraging CMOS manufacturing technology,” as Ion Torrent does in its PGM and forthcoming Ion Proton machine, for example.
“Combine these two processes – you get Genia!” he said.
Linking each pore to the chip in a mechanical manner doesn’t really scale, Roever said. “If you put [pores] on an integrated circuit, the electronics are embedded in the chip under the electrode… The only way to get to this density is if you put electronics on the chip.”
Roever, who gave his first in-depth interview to Bio-IT World last year, currently has 15 employees and has raised more than $10 million in angel funding, including a sizeable investment from Life Technologies.
“We’re developing the platform but the chemistry has been around for a while,” said Roever. “We integrate on chip… We put up to 1 million nanopores on a single integrated circuit. We automate the setup of the nanopore/bilayer complex and increase the sensitivity of the electronics” to measure current and deduce the DNA sequence.
In order to differentiate between about 10 atoms from nucleotide to nucleotide, Rover said Genia needed to resolve “a couple thousand more electrons to make the [base] call.”
Genia’s platform features an active CMOS chip custom made by a foundry in Taiwan. He showed a picture of the prototype device with 200 sensors, each one addressed individually. “The ultimate product will be a low-cost reader you can connect via USB,” he said, presumably similar to Oxford Nanopore’s MinION device.
For now, Genia is using natural lipid bilayers. “We have automated the bilayer/pore setup, which allows for scalability and ease of use,” he said. “The commercial version shipping next year will have 1 million pores.” (Oxford Nanopore plans to release arrays this year with 2,000 pores, growing to 8,000 in 2013.)
Software on the chip controls the insertion of the nanopores into the bilayer. Roever said his team had demonstrated the ability to pull 50,000 DNA strands through the pore in succession, but did not present any sequence data.
Roever said Genia was experimenting with two modes of DNA transfer, only one of which was enzyme dependent. He did divulge which enzyme they were using. He also suggested that raw read accuracy was not the key metric. Moving the DNA template through the pore multiple times would determine the ultimate [accuracy] rate, he said.
Roever argued that the road to personalized diagnostics will be dominated by single-molecule DNA sequencing. The Genia platform would appeal to the diagnostics industry, he said, for many reasons, including accuracy, throughput, time to answer, ease of use, and cost.
The molecular diagnostics industry is not scaled to support personalized medicine, he said. In the United States, there are hundreds of companies and some 1,500 labs running dozens of technology platforms offering thousands of individual tests. Genetic testing is usually hypothesis driven, resulting in uneven application, poor patient outcomes, and high cost to payors.
“We believe the answer to that is to sequence everything,” he said. “Run all possible tests whenever one test is ordered… The analysis is done in software.”
Roever spoke of a “first mover advantage” to the companies and organizations that can offer the $1,000 or even the $100 genome in the next year or two. “This will revolutionize diagnostics,” he said. “Those first movers will grab a huge amount of market share in the diagnostics industry.”
Roever made the analogy to a standard CBC blood test, which costs $89 and includes dozens of specific assays, even if the physician is only interested in the red blood count or cholesterol level. “It’s cheaper to just process everything the same way,” he said. In the same manner, before long the cost of a comprehensive sequencing test will drop to $100, informing the physician about a host of possible disorders and finding applications from newborn screening to infectious disease to personal genomics.