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At AGBT, GenapSys Entices Audience with Lunchbox-Sized Electronic Sequencer; Leaves Open Questions

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This article was originally published February 17.

GenapSys has developed a small sequencing-by-synthesis sequencer with electronic detection that it claims will be low cost, easy to use, and able to generate gigabases of high-quality sequence data within a few hours.

At the Advances in Genome Biology and Technology meeting in Marco Island, Fla., last week, CEO Hesaam Esfandyarpour provided a first glimpse of the instrument, which he pulled out of a lunchbox during his presentation, though he left many questions about the technology inside unanswered.

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The company started an early-access program for the platform, called Genius, for Gene Electronic Nano-Integrated Ultra-Sensitive, last week and plans to ship out the first instruments within a few months, followed by a general commercial launch either this year or next year.

The system, about the size of a toaster turned on its side, has an opening in the front to insert a small, square semiconductor-based sequencing chip. A reusable reagent cartridge attaches to the back, and a computer for data processing is integrated.

For library preparation, the template DNA is clonally amplified on beads in an emulsion-free off-instrument process that requires no specialized equipment from the company, Esfandyarpour told In Sequence.

The template beads are then pipetted into the chip, which has "millions of sensors" and a flat surface with no wells. There, the beads assemble into an array-like pattern, with each bead being individually addressable.

This is followed by polymerase-based DNA synthesis where nucleotides are added sequentially. The system uses a "very simple" and "fundamentally robust" electronic detection method to identify which nucleotide was incorporated, but Esfandyarpour did not reveal the detection principle. He said it is not based on pH measurements, like the Ion Torrent technology.

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Esfandyarpour is an inventor on US patent No. 7,932,034, which covers DNA sequencing by measuring heat or pH, technology he developed as a graduate student in Ron Davis' lab at Stanford University, where he worked on electronic DNA sequencing. The other inventor on the patent is Mostafa Ronaghi, now Illumina's chief technology officer. Both Ion Torrent and Genapsys have licensed the patent from Stanford.

In addition, Esfandyarpour is the sole inventor of US patent No. 8,585,973, which covers nanosensor arrays.

Three types of chips will be available for the Genius, generating up to 1 gigabase, 20 gigabases, or 100 gigabases of data for targeted sequencing, exome sequencing, or whole-genome sequencing, respectively. A sequencing run will take "a few hours."

Estimated sequencing costs per gigabase will be $300 for the smallest chip, $10 for the middle chip, and $1 for the largest chip.

The instrument price has not been determined yet but will have "a cost structure that makes its embedded technology accessible to every researcher," according to the firm's website. Esfandyarpour explained that customers committing to high usage will be able to purchase the instrument for a lower price, similar to a cell phone sold with a usage plan.

He said that GenapSys has already generated sequence data on the platform, though he did not provide specifics. "We know the technology works," he said.

The data quality will be "equivalent or better than the best product out there," he said. The platform has been designed for read lengths of up to about 1,000 base pairs, sufficient for the applications the company is targeting, though there is no theoretical read length limit.

While the first version of the Genius will require separate sample and library preparation, the company plans to integrate sample prep into the platform eventually.

Esfandyarpour founded GenapSys in 2010, though the technology is based on work he conducted over the last 10 years or so. He holds an undergraduate degree in electrical engineering from Sharif University in Iran and MSc and PhD degrees in the same subject from Stanford.

The company's scientific advisory board boasts a number of high-profile names in genomics, including Ron Davis, Mike Snyder, and Steve Quake from Stanford, George Church from Harvard Medical School, and Eric Topol from the Scripps Translational Science Institute.

Last November, GenapSys raised $37 million in a Series B financing round from Decheng Capital, IPV Capital, technology investor Yuri Milner, the Stanford StartX Fund, and other private and institutional investors.

In addition, the company obtained almost $4 million in grant funding from the National Human Genome Research Institute in 2012, including $3.4 million through the institute's Advanced Sequencing Technology program to develop low-cost sequencing with reusable magnetic arrays and nanoelectronic sensors and about $600,000 for the fabrication of a dual nano-biosensor for electronic sequencing.

Last week, GenapSys started an early-access program, called "Genius Club," for the platform that is open to "individual researchers and industry professional around the globe," according to the firm's website.

"We aren’t looking just for a few famous names to lend credibility to our product," according to the company. "Instead, we’re looking to make widespread access to DNA sequencing a reality."

Customers chosen for the program will receive one or more Genius instruments, including base-calling software and consumables for up to 15 runs, in exchange for a $2,500 refundable deposit and a shipping fee. They can purchase additional consumables at discounted rates.

It is unclear when GenapSys plans to ship the first systems, but registration for the early-access program closes May 31.

The company will initially target the research market with its platform but believes that it will eventually be used "much more broadly," according to Esfandyarpour.

Several attendees of the AGBT meeting told In Sequence that while they were interested in the new Genius system, they were disappointed by the lack of details about the technology and sequencing data in the presentation, which many took as an indication that the platform might not be mature yet.