NEW YORK (GenomeWeb) – Nanobiosym Diagnostics obtained Emergency Use Authorization last month for a Zika assay that is now permitted for laboratory use on the firm's handheld test platform called Gene-Radar.
The Zika test is a molecular assay authorized for use only on serum samples from individuals meeting US Centers for Disease Control and Prevention clinical or epidemiological criteria, such as travel to a Zika-endemic area or certain signs and symptoms of infection.
In general, Nanobiosym's Gene-Radar system consists of a point-of-care platform and nanochip test cassettes that can potentially run using a drop of sample, such as serum, blood, or saliva. The system has been under development for several years by Nanobiosym CEO and founder Anita Goel, who is also an associate in the physics department at Harvard University.
The company has a few parallel arms, including a research institute focused on nanobiophysics, Goel said. "We look at polymerases as nanomachines and molecular motors that read and write DNA," she said. The commercial side of the firm is focused on Gene-Radar, a product that won a Nokia XPrize in 2013.
The new EUA is "one small fraction of a huge vision," Goel emphasized, and the Zika test is currently limited in its scope to serum testing on the Gene-Radar in a lab setting. However the firm has hopes to expand testing to other sample types and test environments, as well as to further develop its diagnostics test menu.
Existing FDA authorized Zika tests are either serology tests or traditional PCR tests. "Serology tests tend to have a high rate of false positives, and rapid antibody tests are generally a lot less sensitive than traditional PCR-based methods," Goel noted, highlighting that, to her knowledge, all of the serology tests with EUA so far also need to be used in a centralized lab.
Serology tests so far approved include the Liaison XL Zika Capture IgM Assay from DiaSorin, the ZIKV Detect IgM Capture ELISA from InBios International, and a Zika MAC-ELISA from the US Centers for Disease Control and Prevention.
PCR is the gold standard for sensitivity and specificity and is required for Zika detection in early stages. It can also be used on certain sample types that tend to harbor the virus longer, like urine or semen, enabling PCR testing for an extended window of time.
To date, the following PCR-based Zika tests have obtained EUA: the Zika ELITe MGB Kit U.S. from ELITech; the Abbott RealTime Zika from Abbott Molecular; the Zika Virus Detection by RT-PCR Test from ARUP Laboratories; the Sentosa SA ZIKV RT-PCR Test from Vela Diagnostics; the xMAP MultiFLEX Zika RNA Assay from Luminex; the Versant Zika RNA 1.0 Assay (kPCR) Kit from Siemens Healthcare Diagnostics; the Zika Virus Real-time RT-PCR Test from Viracor Eurofins; the Aptima Zika Virus Assay from Hologic; the RealStar Zika Virus RT-PCR Kit US from Altona Diagnostics; a Zika Virus RNA Qualitative Real-Time RT-PCR from Focus Diagnostics, and the CDC's Trioplex Real-time RT-PCR Assay, which also detects dengue and chikungunya viruses.
A test from Roche was authorized but was withdrawn by the company in March of this year "due to technical performance and business considerations," according to the FDA's website. Internationally, there are other tests in use, as well. One from Bioneer was made eligible for procurement by the World Health Organization recently, while a test from Coyote Bioscience has been used in airports in China to assess the health of travelers, for example.
But, EUA Zika PCR-based tests also tend to use traditional "large, bulky, expensive" machines for testing, Goel said.
The Nanobiosym platform, meanwhile, is 3.5 lbs. and is more of a "sexy, consumer electronics-looking device that sits in one hand," she said. However, she emphasized that the user footprint difference did not really apply for the FDA validation because the Nanobiosym test was validated against traditional tests in a lab setting with several the bells and whistles of the system turned off. So, although the test may be the first to be approved on a mobile device, the FDA has not given any authorization to use the test outside of a lab at this point.
The Nanobiosym test is also designed to detect Zika in serum, but the platform can potentially perform the test in urine and whole blood, for example, and the firm is in the process of running clinical trials for urine, Goel said.
"We're still talking to our collaborators, who are public health experts on the ground, to ascertain what they need," she said, particularly considering that preferred sample types could depend on whether a test is run in a lab or at the point of care.
Public health labs have been gearing up to run EUA Zika tests, and other diagnostics companies, like BioMérieux and OraSure, among others, are also developing tests for which they will seek emergency authorization.
Interestingly, Zika infection can be completely asymptomatic in up to 80 percent of people, and it is now known that it can be sexually transmitted. Since transmission to a fetus can cause severe birth defects, such as microcephaly, the CDC advises testing all women with Zika symptoms.
Between January 1, 2015 and April 12 of this year, there were 5,234 confirmed Zika cases in the US, with 223 cases acquired locally and 76 cases acquired through other routes, such as sexual transmission, congenital infection, or accidental laboratory transmission, according to the CDC. There have also been 36,383 locally-acquired cases in US territories during the same time span.
And neither PCR nor immunoassay tests are really broadly available in the US outside of centralized public health labs, Goel suggested. "One of our collaborators in Miami told us that in the last mosquito season it was taking pregnant women between one to five weeks to get a diagnosis," she said. Indeed, there was a widely-reported backlog in testing last autumn that coincided with the CDC subsequently purchasing $2.5 million in laboratory supplies to help local health department labs expand capacity.
Nanobiosym has signed a memorandum of understanding with the University of Miami to evaluate the real-world clinical and operational utility of the platform. "In the last mosquito season last summer they were testing up to 1,000 patients per month for Zika ... and one of the things we can provide is a faster turnaround time," Goel said. The test itself can currently provide results in one hour, although the first generation of the instrument does require sample preparation and setup by a technician, she said.
Furthermore, the firm has been talking with public health experts and, Goel said, "We think the only way to get at the 80 percent of infected people who are asymptomatic is to find ways to do more widespread screening and diagnosis." A rapid, decentralized test, which is the potential application of Gene-Radar, would be a step in that direction.
The Nanobiosym platform uses "physics and nanotechnology to enhance the amplification that you would do in a traditional way, to get a better signal to noise," Goel said.
Rather than shrink down PCR, as other companies have done, the firm is starting at the single-molecule level and building up from fundamental insights. She also noted that, while there are basic science papers on her molecular motors research, for example, there has been a long journey from those to the product that was just granted EUA, and designs have been modified with user experiences.
Goel said her team is planning to publish some of the underlying scientific work on the Gene-Radar platform. The group's basic research to understand molecular machines and the physics of living systems has also been funded by DARPA, the National Science Foundation, and NASA.
Nanobiosym is currently seeking clinical partners and distribution partners in the US, and is working with non-governmental organizations to satisfy a global humanitarian mission that is also fundamental to the company.
"Our vision is to mobilize, personalize, and decentralize an entire new generation of infrastructure needed to deliver diagnosis — we want to reach billions of people around the planet and make diagnosis faster, cheaper, and real time," Goel said.