Arizona State University's Biodesign Institute said today that it will collaborate with Life Technologies to develop a real-time PCR-based platform to rapidly assess an individual's exposure to radiation in the event of a nuclear incident.
As part of the agreement, researchers from the Biodesign Institute are designing a multi-gene assay panel that would run on real-time PCR systems from Life Tech such as the Applied Biosystems 7500 Fast Dx and QuantStudio Dx, and would identify individuals exposed to abnormal levels of radiation.
If successful, the team would then seek regulatory approval for the assay from the US Food and Drug Administration. According to members of the ASU Biodesign Institute team, the fact that Life Tech has experience in this process and offers several instrument platforms that either already are or are expected to be approved by the US Food and Drug Administration made the company an attractive choice as a partner.
"With the implementation of this program in the government, it's not exactly sure … when this program finishes a few years down the road what [instrument platforms] will actually be in the field and available for use," Lee Cheatham, deputy director of the ASU Biodesign Institute, told PCR Insider this week.
"The idea is that these assays would be run in a laboratory that already has this equipment in place," he added. "Part of this is … hedging bets a little bit … [and] making sure there is an [FDA]-cleared platform that can be used … and that for the new platforms coming down the road that are not yet cleared, but might be a few years down the road, how this assay might be [used on] one of those."
The Applied Biosystems 7500 Fast Dx platform received FDA 510(k) clearance in 2008 and has become a mainstay of laboratories wishing to develop their own in vitro molecular diagnostic tests. Meantime, Life Tech launched the QuantStudio Dx, its next-generation molecular diagnostics platform, in Europe in November, and filed for FDA clearance of the device in December (PCR Insider, 11/29/2012).
The ASU Biodesign Institute project is entering a $9.33 million contract option as part of a five-year, $35.44 million project funded by the Biomedical Advanced Research and Development Authority, within the Office of the Assistant Secretary for Preparedness and Response of the US Department of Health and Human Services. Of the eleven project teams launched in 2010, the ASU group is one of six continuing development.
Since the project launched, ASU has led research activities demonstrating that gene expression is a viable approach to directly measure radiation exposure, including identifying and validating biomarker signatures to provide an accurate indication of the level of absorbed radiation.
According to Cheatham, this work was the first priority of the project, and its completion then led the group to begin considering what type of assay format and technology platform would be best suited to implementing the assay.
"There were two or three parts to this project," Cheatham said. "The first one was: Can we get the gene expression process to work at all? Can we measure exposed dose over time with a gene expression process? We were about 18 months into the project when we could convince ourselves and BARDA and others that it actually worked. At that point we were looking at whether any kind of platform would work. However, over the last year or so that's evolved a lot more … [as] BARDA brought more of the operational requirements into the project. So settling on PCR happened within the last 12 months."
And, Cheatham added, after reviewing available technology platforms on the market and undergoing an internal review process, the ASU team identified Life Tech's instruments as the best matches. "It was mostly based on the requirements of BARDA, and it's a fairly unique set of requirements — different from any drug screening or diagnostic assays that you might be doing."
Kristin Gillis, a senior scientific project manager at ASU's Biodesign Institute that is spearheading the effort, noted that "one of the biggest requirements that was a big discriminator with the different platforms [we looked at] was high throughput. BARDA has a requirement that we are able to analyze 2,000 samples in a 24-hour shift."
While the 7500 Fast Dx may fall short of those throughput requirements — it is a five-color real-time PCR system that is compatible with 96-well plates and eight-tube strips — the QuantStudio Dx accommodates 96- or 384-well plates, as well as qPCR microfluidic cards, which can perform 48 tests on eight samples simultaneously.
What's more, Gillis said that her group expects the final gene panel for its test to contain between 10 and 20 genes, and will "preferably not be a multiplexing assay." Instead, the group envisions that each well of the assay consumable would contain a single gene probe set, and the assays for the multiple targets would be run in parallel.
"Remember, this is an operational scenario we're talking about, where if there is an incident, we're going to have to deal with a whole bunch of people very quickly, maybe as many as hundreds of thousands over a few days, and in perhaps a challenging environment for logistics," Cheatham said. "So many of the requirements — in addition to, of course, whether we can reliably measure the levels of expression — have to do with how does this fit into the operational scenario? Is it available in a laboratory? Do people already know how to use it?"
As Cheatham's comments underscore, the potential market for the dosimetry assay will generally only be in the case of a nuclear incident — for instance, the Fukushima Daiichi nuclear disaster that occurred in Japan in the wake of the 2011 Tohoku earthquake and tsunami.
"There are certainly those kinds of radiological incidents that happen more often than we would like, but they're not enough to build a business around," Cheatham noted.
However, he said that once ASU and Life Tech complete their work, "you can imagine there are medical applications for radiation-based therapeutics, for example. Down the road we'll certainly be looking at whether the technology can be a differentiator for those sorts of things. We haven't started doing that yet, but we believe that there probably are some areas where this could be beneficial."
Other collaborators on the project include Joshua LaBaer, director of the Biodesign Institute's Virginia G. Piper Center for Personalized Diagnostics, who is leading the biomarker effort; and Sally Amundson of New York's Columbia University Medical Center, who is helping to identify radiation-responsive genes and biodosimetry measurements, ASU said.
Researchers from the Translational Genomics Institute in Phoenix, HTG Molecular in Tucson, and the University of Arizona have also contributed to early stages of the project, ASU said.