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Mycroarray Planning to Debut Ion Proton-based Sequencing Services, Upgrade Chip Production in 2014

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In an era where the microarray market seems to be concentrated in the hands of a few large vendors, some smaller companies continue to flourish.

In fact, the departure of major players such as Roche NimbleGen and CombiMatrix from the custom array market has arguably helped firms, such as Ann Arbor, Mich.-based Mycroarray, that may have been obscured by bigger competitors in the past.

"We are undeniably profiting from competitors such as CombiMatrix or NimbleGen pulling out of the array market," said Jean-Marie Rouillard, Mycroarray's CSO and co-founder. "While this market is said to be on the decline, we are still seeing a strong demand for arrays."

And that demand is increasingly overlapping with the market for new sequencing applications. In early 2014, Mycroarray plans to introduce services on Life Technologies' Ion Proton System, a genome-scale, benchtop sequencer. Rouillard portrayed these new services as a complement to the company's existing sequence capture offering, which in turn is based on its array synthesis technology.

Rouillard said that Mycroarray acquired the Ion Proton because of the "number of reads, the potential for greater output in the future, and cost to operate."

Ultimately, Mycroarray aims to have a "unique combination" of capture kit design, sequence capture, and sequencing service available to users in the coming year.

Mycroarray traces its origins to 2006 when it was founded to commercialize an array-fabrication technology developed by co-founder Erdogan Gulari, a professor of chemical engineering at the University of Michigan.

To make its arrays, Microarray relies on an internally modified light-directed oligonucleotide-synthesis approach. In standard oligo synthesis, the terminal acid-labile protective group of a growing oligomer is removed by a treatment with a strong acid. In contrast, Mycroarray's approach includes a photo-generated acid, which enables the synthesis of tens of thousands of oligos in parallel on the same substrate. Mycroarray also uses a digital micromirror device, rather than a mask. On its website, the firm claims that the digital photolithography approach allows it to make any custom microarray with "no upfront design cost or minimal order size."

Mycroarray has parlayed its core technology into a menu of product offerings. In addition to producing its eponymous catalogued and custom Mycroarrays, the company has also for a number of years provided MyBaits, a custom sequence capture kit offering. Rouillard said that Mycroarray recently expanded beyond offering focused kits to sell catalog kits targeted to, for instance, "ultraconserved elements for phylogeny studies or whole genomes for ancient DNA enrichment." The firm is also planning to release a number of exome capture panels next year, Rouillard noted.

To complement its MyBaits offering, Mycroarray a few years ago rolled out a sequencing service called MyReads on Roche's 454 Junior instrument for "pilot capture experiments." The company will now move its MyReads service to the Ion Proton, Rouillard said, in order to "meet the demand from our customer for larger studies we could not have performed before." Roche announced earlier this year that it would discontinue 454 sequencing products by mid-2016.

In addition to its array, MyBaits, and MyReads offerings, Mycroarray has over the past two years introduced three new services. For its MyLib oligonucleotide library synthesis service, the company relies on its array-making resources to produce pools of custom oligos, including molecular probes, padlock probes, sequence-specific primers, and aptamers. Rouillard said these probes can also be cloned into expression vectors to produce shRNA libraries, peptide libraries, and phage display libraries.

"There is not a month going by without a request from a scientist for a library to develop a new clever oligo-based technology," said Rouillard.

Another new offering is MyTags, custom fluorescent probes developed in cooperation with Harvard University's Ting Wu and featured last year in a publication in PNAS. The company has also introduced MyOligo, "error-free" oligonucleotides for the synthetic biology market. The offering is based on an internally developed method that allows the firm to extract and purify the "very best molecules from each spot on our arrays and deliver them sorted in microplates rather than as large pools," said Rouillard.

Mycroarray plans to move to a fully automated array synthesizer next year to support all of these services, Rouillard said. Each synthesis machine has a footprint of about 6 square feet and has the capacity to produce 100 million oligos or 6 gigabases per week. The company previously was producing 5 million oligos per week using a more labor-intensive approach.

"To give you an idea, this represents the equivalent of a human genome being synthesized every three and a half days," Rouillard said. "With a small footprint and automated operation, we can quickly ramp up production to meet demand."

But where is that demand coming from, especially for a firm whose offerings are matched by similar array products and services from a large multinational like Agilent Technologies?

One source of new business is non-academic clients, Rouillard said, who now account for more than 50 percent of the firm's sales, a change from the past when Mycroarray primarily did business with academics. Academics, though, do contribute to the firm's business growth. According to Mycroarray, 24 peer-reviewed papers have been published based on the firm's technology as of the end of the third quarter, up from 22 in 2012. Rouillard said that the increase in such papers "greatly increases our visibility."

Rouillard also credited the firm's smaller, intimate approach with its ability to win and retain customers.

"We know from feedback from our customer base that our products are well appreciated," said Roulliard. "They also enjoy the personalized service they get from Mycroarray, which is very important when you offer highly customized products."

In addition to its existing offerings, Mycroarray continues to eye an entry into the peptide microarray market. In 2011, Mycroarray won a $219,000 Small Business Innovation Research grant from the National Institutes of Health to commercialize an internally developed peptide synthesis technology. Rouillard said that this phase I funding allowed the firm to generate "promising results" and that it is now seeking additional funding for the project. He declined to provide a date for the technology's commercialization.

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