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Twistnostics Nets $600K NIH Award to Develop Automated Gram-negative Bacteria Microarray Test

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NEW YORK (GenomeWeb) — The National Institutes of Health recently awarded Twistnostics a two-year, $600,000 grant to support the development of a fully automated, inexpensive microarray-based test for drug resistant gram-negative bacteria.

Twistnostics CEO Alfredo Celedon told BioArray News this week that the Baltimore-based technology company aims to have a US Food and Drug Administration-cleared test on the market by 2017. Given the indication, the diagnostic will compete directly with similar automated tests sold by Nanosphere and BioFire Diagnostics. GenMark Diagnostics, another potential competitor, aims to submit to the FDA a gram-negative bacteria test together with its NexGen platform sometime next year.

Yet even though Twistnostics is three years away from product launch, it still feels optimistic about its prospects because of a perceived technical edge. "This is a very competitive market, but we believe that we can reduce the time of the test significantly," said Celedon. "The advantages that we hope to have are speed and cost. That is what I think will differentiate us at the end of the day."

According to Celedon, Twistnostics aims to deliver to market a system that costs less than $5,000 with assays that cost less than $20, and that can be run from sample to result within a half hour, roughly a quarter of the assay time of Nanosphere's current, FDA-cleared test for drug resistant gram-negative bacteria. He said that it is the nature of the company's platform that makes such price points attainable.

Twistnostics' core technology is its Twist-Biosensor, which relies on DNA supercoiling to convert the nucleic acid hybridization of a single DNA molecule into a mechanical signal that can be detected using standard semiconductors. As the bound targets are subjected to disrupting torsional stress, the rate of detection is increased and background noise is reduced, according to the company.

"Our tests are based on single-molecule detection, which reduces the cost of equipment and tests significantly," said Celedon. "Since we detect single molecules, the amount of reagents required are minimal," he said. "And instead of having high density oligos on our array, as Nanosphere does, we have a handful of single-molecule sensors," Celedon added. "That makes it extremely inexpensive, because our array can be 1,000 molecules, a small number when you talk about molecular biology."

Twistnostics' selection of drug resistant gram-negative bacteria testing as a market of interest is based on demand. In its NIH grant abstract, it noted that the prevalence of such bacteria is increasing, complicating treatment of infected patients. In particular, carbapenem-resistant Enterobacteriaceae, organisms associated with a high mortality rate of greater than 40 percent, have become more prevalent. According to Twistnostics, current detection tools are not fast enough to serve patients' needs, as some can take up to 24 hours and require trained personnel. And while automated nucleic acid hybridization-based platforms do exist, the firm portrayed the tests offered by Nanosphere and BioFire as expensive.

With its new grant, Twistnostics aims to develop an array that is capable of detecting multiple carbapenemase genes in a procedure with minimum hands on time and a shorter processing time. According to the abstract, the company hopes to both demonstrate that its Twist-Sensor technology is capable of detecting a resistance determinant in bacterial cultures without DNA amplification and to develop a Twist-Sensor detection mechanism that is "easy to automate, inexpensive, and has high throughput." The company will subsequently create a multiplex assay for the detection of the most prevalent carbapenemases – KPC, NDM, OXA-48, VIM, and IMP.

"In phase 1, we will use a broth sample spiked with bacterial samples and demonstrate that we can detect within two hours the presence of the gram negative resistance, in particular carbapenemases," said Celedon. "We are also developing an extraction method where we are adapting methods to work with our specific microarray system and detecting those with our microarrays," he said.

All of the prototype work will be done within Twistnostics, though it does plan to outsource manufacture of the system "to one of the many companies that specialize in automation" at a later date, Celedon noted. The goal is to have a system ready for sale by 2016, with FDA clearance expected the following year.

Twistnostics is not only interested in gram-negative bacteria though. The company also has a test for tuberculosis in development that should also become available as an FDA-cleared diagnostic around the same time. "We believe that this is a huge opportunity for us because our platform can detect TB without a PCR reaction," said Celedon. "That will bring a real difference to the diagnostics market," he said. He noted that Twistnostics' planned TB and drug resistance gram-negative bacteria tests will run on the same instrument.

The company is also at work on a pharmacogenomic assay. Last year, the National Human Genome Research Institute awarded Twistnostics $150,000 to develop a test that can detect three SNPs in the CYP2D6 gene associated with variations in human drug metabolism. The firm also intends to develop its technology to support the creation of 50- to 100-SNP microarrays for pharmacogenomic genotyping.

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