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BioNanomatrix Plans Beta-Launch of Single-Molecule DNA Analyzer for Q2 of 2010

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By Julia Karow

With more than $830,000 in additional grant funding from the National Human Genome Research Institute, startup BioNanomatrix is forging ahead to commercialize its single-molecule DNA imaging and analysis platform next year.

The Philadelphia-based Princeton University spinout plans to use the funding — two supplemental awards to an existing $2.08 million NHGRI Phase II Small Business Innovation Research grant — to prepare for beta-testing of its system, called the NanoAnalyzer, currently scheduled to start in the second quarter of next year.

The instrument, currently in alpha evaluation, will have a number of initial applications including genome assembly, structural variation mapping, and DNA damage analysis. Longer term, in collaboration with Complete Genomics and other partners, the company is also working on DNA sequencing and epigenetic mapping.

The system is based on nanochannel technology developed by Han Cao and colleagues at Princeton University. Individual DNA fragments, typically ranging in size between 50 and several 100 kilobases, are trapped inside the nanochannels, which are arrayed on a chip, imaged, and released before the next DNA fragments flow in. The DNA backbone is labeled and carries short, sequence-specific barcodes, usually spaced several thousand bases apart, that are labeled with two different colors. "The barcode patterns allow us to map that fragment back to the genome" and to assemble a map of the genome, explained Michael Boyce-Jacino, BioNanomatrix's CEO.

Last year, BioNanomatrix raised $5.1 million in Series A funding, which it said it was going to use to build out its R&D and business-development activities (see In Sequence 4/8/2008). As it gets closer to commercialization, it plans to raise more funding, but has not yet determined how much, he said.

In the meantime, the company has more than doubled in size — to about 25 employees — and has been advancing both its chips and its instrument, as well as, more recently, reagents and software tools, Boyce-Jacino said. The first commercial version of the system will have a three-sample chip with approximately 4,000 nanochannels per sample, each of which will be able to scan about 3 billion DNA bases in less than 10 minutes.

BioNanomatrixImage.JPGAt the moment, BioNanomatrix is working with several unnamed outside research groups to validate the system's data output and data analysis, and is finishing its software tools.

By mid-2010, the firm plans to start a beta-testing program, for which it has already identified or signed up four test sites — a "mixture of genome centers and clinical genetics labs," which could grow to as many as eight, according to Boyce-Jacino. This will be followed by a full commercial launch, targeted for the end of next year.

These beta sites plan to test the platform for several applications. One will focus on genome assembly, generating a reference map of a genome in a particular sample, against which sequence reads generated from that sample can be mapped.

Another application will be determining genome integrity, or damage that has occurred to the DNA as a result of certain treatments to the cells. Many cytogenetics labs, Boyce-Jacino explained, are using a variety of DNA imaging techniques today to obtain a picture of the organization of the genome, and BioNanomatrix's approach could complement those.

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One group interested in evaluating the platform is the Broad Institute, which has been following BioNanomatrix's progress for about a year, and has been in touch with the firm for about four months, according to Patrick Cahill, director of technology exploration at the Broad. "We feel that the BioNanomatrix platform, as presented to us, could be useful for scaffolding for assembly and for detection of large-scale DNA rearrangements," Cahill told In Sequence via e-mail this week.

However, he said that BioNanomatrix is not the only way to obtain that kind of genomic information. Technologies such as optical restriction maps, which OpGen provides as a service (see In Sequence 4/1/2008), "could deliver similar data, and we will continue to explore these as well as BioNanomatrix's platform," he said.

Chad Nusbaum, co-director of the Broad's genome sequencing and analysis program, added that BioNanomatrix's technology "seems like it has the potential to be a lot cheaper and faster than OpGen."

Long-Term Applications

Down the road, BioNanomatrix is looking at additional applications for its platform, including DNA sequencing.

Under a joint project with Complete Genomics that was funded with up to $8.8 million in grant money from the National Institute of Standards and Technology two years ago, the companies are working on adapting Complete's sequencing chemistry for use in BioNanomatrix's channels, with the goal of sequencing a human genome for $100.

"The nice thing about the chip is, it's basically a femtoliter single-molecule reaction chamber — the DNA is sitting in solution, and we can infuse reagents for analysis," Boyce-Jacino said. The barcodes the firm is currently using already yield "sort of a very low-resolution sequence map, where we are getting little blocks of sequence across long stretches of the genome," he said. "Developing the sequencing chemistries on top of that, the idea is to steadily increase the amount of sequence information we get to read from those spots. And eventually, we can get enough to read across the entire fragment."

The ultimate goal is to provide users with sequence information along with haplotype information, he said. BioNanomatrix and Complete Genomics have not yet decided, though, whether they will commercialize the technology as a service or an instrument for sale.

In addition, the instrument could potentially also provide information on DNA methylation. In collaboration with another, undisclosed partner, BioNanomatrix has been developing and validating DNA methylation-specific barcode reagents that would allow users to determine methylation patterns of a DNA fragment.

The company also has an ongoing partnership with Agilent Technologies, announced in 2007, to develop an instrument that will use its imaging technology and chips and a measurement platform from Agilent. "We are in discussions with them on a number of different application areas," Boyce-Jacino said, but did not elaborate.

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