High Throughput Genomics, a Tucson, Ariz., startup that makes low-density universal arrays on microplates, has taken over patents and array-making equipment from bankrupt array maker Genometrix of the Woodlands, Texas, HighThroughput said this week.
Genometrix had been looking for asset buyers after it shut its doors at the end of June last year. Eventually the company went into Chapter 11, and High Throughput used proceeds of a $1.25 million Series A funding round closed in January to buy the assets out of the bankruptcy estate, according to Bruce Seligman, CEO of High Throughput.
“We think that it was a good value for the IP and the majority of their tangible assets, “ said Seligman, adding that Genometrix retained its printing instruments and the intellectual property for printing.
High Throughput, which was founded in December 2000, has since sold off some of the equipment, and is using other equipment to begin producing its plate-based arrays, called ArrayPlates, for a small but growing list of customers.
Among these new customers is Psychiatric Genomics of Gaithersburg, Md., which signed an agreement Monday with High-Throughput to purchase the company’s ArrayPlates, as well as its array imager. Psychiatric Genomics is using the arrays and imager to develop assay kits for genes linked to psychiatric illness. The company plans to integrate these kits into its own platform for discovery of novel treatments for mental disorders.
High Throughput also has a service contract with Signal Pharmaceuticals of San Diego to perform assays on cell samples.
Generic Probes, Tricky Assay
To be true to its name, High-Throughput intends to focus on screening large numbers of samples against 100 or fewer genes. The company’s ArrayPlate consists of 96-well plates, in which 16 oligonucleotides of a synthetic nucleic acid are spotted in each well.
“Once researchers using an Affymetrix chip have seen 100 genes [expressed differentially], it is easy to format them in an array plate to validate them, to figure out which cell lines are expressing the genes under which treatment condition, or to use many patient samples to see ‘are these genes universally relevant’ and ‘in what stage of the disease?’” Seligman said.
The oligo probes the company uses in its plates are generic, allowing it to mass produce the plates. The assay involves lysing the cell, then adding the lysate to synthetic oligos designed to hybridize to the target molecule. This synthetic probe-target complex is protected against digestion by S1 nuclease. The nuclease digests unbound probe and RNA, leaving the complexes. A following hydrolysis step destroys the RNA, leaving the probes intact. These probes, which have chemiluminescent labels, are then added to the complementary probes in the ArrayPlate wells.
For detection of each new gene, a new probe and a new set of “linkers” that bind to the oligonucleotide on the plate and to the detection probe must be designed.
“What we do is radically different from the rest of the industry,” said Seligman. “We can create a reagent set for each gene that’s out there.”
A number of other companies have recently been developing universal arrays. But Seligman claimed High Throughput’s technology is distinctive because of its patented nuclease protection chemistry and the Genometrix patent.
One advantage of the plate array, according to the company, is that its ArrayPlates can be manufactured all at once without regard to the particular assay in which they will be later used, saving on costs. The plates cost around $700 each.
Another advantage, according to Seligman, is the sensitivity of the hybridization and detection chemistry used. The chemiluminescient labels, unlike fluorophores, have almost no background, he said. The company claims its arrays are able to detect as little as a 10 percent variation in expression levels with an overall coefficient of variation between three and 13 percent per gene, and that they require as little as 0.001 micrograms of total RNA.
Currently, the company has seven full-time staff and four part- timers completing pilot studies for 12 potential customers, and has secured revenues of over $2 million for the year, said Seligman.
While Seligman admits to competition from RT-PCR and branch DNA, neither allows multiplex gene analysis, he pointed out. But “in terms of array products, I don’t think there’s any real competition,” he said. “They are all competitors, the low- and medium-density players, but they can’t approach our reproducibility and sensitivity.”