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GenapSys Continues Development of Nanoelectronic Sequencer with $4M in NHGRI Grants

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This article has been updated with additional information from GenapSys.

Armed with almost $4 million in grant funding from the National Human Genome Research Institute this year, GenapSys continues to develop a low-cost electronic DNA sequencer that it believes will have advantages in cost, speed, and data quality over existing platforms.

The money comes from two grants, both awarded to the company this summer. One award, through the NHGRI's Advanced Sequencing Technology program, provides the company with $3.38 million over three years for a project titled "Low Cost Sequencing with Re-usable Magnetic Arrays and Nanoelectronic Sensors." The principal investigator is Hesaam Esfandyarpour, GenapSys' founder and CEO.

The other grant, awarded to principal investigator Kosar Parizi, provides the company with about $611,000 over one year for the fabrication of a dual nano-biosensor for accurate sensitive and inexpensive electronic sequencing.

The California-based company, which recently moved from Menlo Park to Redwood City, is still in stealth mode, according to Esfandyarpour, and therefore does not provide details about its technology, funding, or business development plans. The firm wants to stay out of the limelight for now in order to avoid creating hype about its technology before it has finished developing it, he told In Sequence last week.

According to the two NHGRI grant abstracts, GenapSys' goal is to develop a platform that can sequence "a genome" — presumably human — at a consumables cost of $50, generate average read lengths of up to 1,000 bases, and provide a "pre-assembly accuracy" of more than 99.7 percent, "with similar cost reduction and simplification for sample preparation."

The system will consist of "several innovative sample preparation and sequencing modules that are being developed in parallel."

A core component of the sequencing module will be "two novel electric nano-biosensors that enable label-free, accurate, and sensitive detection of the pH change as an 'electrical signature' of the polymerization reaction during 'sequencing by synthesis,'" one of the abstract states.

Using two independently operating nanosensors "will generate significantly more accurate sequencing data at lower cost, while reducing the need for highly redundant sequence coverage," the researchers wrote. The two sensors will detect a steady state signal, or 'nanoneedle,' and a transient signal, or 'nanobridge,' which they say provides a "higher level of confidence and improves base calling accuracy, as two orthogonal sensing mechanisms with the two sensors are reporting the same event."

The goal of the funded project is "to demonstrate the feasibility of dual sensing for electronic DNA sequencing using the nanobridge and nanoneedle biosensors and developing a design for the dual sensor detection module."

While the description of the technology in the two abstracts is vague, it sounds similar in principle to the approach used by Ion Torrent, as both appear to make use of bead-based DNA amplification and pH-based electronic detection. But, according to Esfandyarpour, GenapSys' technology is "quite different" from Ion Torrent's, using "a novel approach" that his team has developed over the past eight years, both at Stanford University and at the company.

As a PhD student with Ron Davis at Stanford University, Esfandyarpour developed an electronic sequencing method that is based on direct heat or pH measurements. Ion Torrent licensed the pH sequencing technology non-exclusively from Stanford in 2010 (IS 3/6/2012).

While he declined to provide further details on the technology, Esfandyarpour did comment on some basic design choices the company has made. For example, he said it is not pursuing a single-molecule technique because those generally suffer from high error rates.

Also, the firm is targeting a read length of about 1,000 base pairs because that is sufficient for more than 90 percent of sequencing applications. While the technology would support longer read lengths, he said, there is a tradeoff between read length and throughput because longer bead-bound DNA molecules take up more space.

According to the grant abstracts, the firm will work toward integrating sample preparation and enrichment steps with the sequencing module. "In lieu of a reverse emulsion we are developing an easy-to-use, chip-based approach that will combine multiple sample processing steps in a single device," one of the abstracts states.

"For clinical applications, it's very important to have an easy-to-use device," Esfandyarpour said, adding that integrating several steps will make it "more useful to both researchers and for clinical applications."

GenapSys has also increased its management and development team this year, growing "in a normal fashion" for a startup company, Esfandyarpour said. According to its website, the firm has added Hamid Rategh, vice president of engineering; Mirna Jarosz, director of sequencing chemistry and molecular biology; and Leila Rastegar, director of business development and strategy (see Paired Ends).

Jarosz previously led the molecular biology and sequencing group at Foundation Medicine, a diagnostics firm that is developing a next-generation sequencing-based assay for the analysis of clinical tumor samples. Prior to that, she was manager of sequencing development at Helicos Biosciences.

In addition, GenapSys added Ali Mani, an assistant professor of flow physics and computation in Stanford's mechanical engineering department, to its scientific advisory board.

Esfandyarpour declined to comment on the company's fundraising efforts at this time.

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