This article has been corrected from a previous version that stated that Axxin disclosed in January that it is developing the NAT analyzer and iNAT platforms. In fact, Alere disclosed that it is developing these platforms.
Anticipating a market influx of molecular tests based on isothermal nucleic acid amplification technologies, Australian OEM firm Axxin is developing a pair of instrument platforms — one for the benchtop and one for the point of care — designed to rapidly and inexpensively perform such tests and provide actionable results.
Axxin, which also has a US office in San Diego, already has agreements in place with several US companies — at least two of which are in the clinical diagnostics market — to produce instrument platforms to run their isothermal amplification-based assays, Paul Lambotte, Axxin's CSO, told PCR Insider recently.
And although Lambotte declined to identify any of Axxin's OEM customers, citing confidentiality agreements, he said that several of the platforms will likely be commercially launched later this year.
Lambotte disclosed his company's product-development plans last month at Cambridge Healthtech Institute's Future Diagnostics meeting in Irvine, Calif.
In his presentation, Lambotte outlined many of the hurdles that have been holding back the commercialization of true point-of-care nucleic acid testing, noting that there are currently no CLIA-waived POC NAT systems on the market.
One of the technology categories with the greatest potential to change this, he said, is isothermal nucleic acid amplification, which brings the major benefit of requiring only a single reaction temperature instead of thermal cycling, which can drastically reduce the cost of a molecular diagnostic platform.
Despite some early industry success with isothermal amplification-based tests — Gen-Probe's transcription-mediated amplification and BioMérieux's nucleic acid sequence-based amplification, for example — Lambotte said that the technology is still "a well-kept secret."
Axxim is developing two instruments designed to take advantage of the relative simplicity of isothermal amplification. The first instrument, called the T16 Isothermal Instrument, is a touchscreen, benchtop system that can read three fluorescent signals simultaneously.
The second system, called the T2 Isothermal Instrument, is more compact, designed to be used at the point of care, and can run one or two samples at a time.
Otherwise, both instruments are relatively similar in that they can be inexpensively made, offer true walk-away operation, consume low amounts of power, have barcoding for sample tracking, and offer connectivity to other instruments for laboratory networking.
In an interview following the Future Diagnostics conference, Lambotte told PCR Insider that both instruments "allow any isothermal method to be amplified on their heat block. The T16 certainly is a benchtop instrument, because it can handle two rows of eight PCR tubes, using common PCR tube strips. That instrument is not meant to be portable."
The T2, meantime, "is really intended for the pharmacy, the doctor's office, field testing in agriculture, et cetera — point of collection or point of care," Lambotte said.
Both instruments are also standalone, meaning they do not require an external computer for operation. However, Axxin will also offer PC-based applications to develop assay protocols. "So for R&D purposes, a company that is putting their tests on our reader can use that very elaborate software to optimize their reactions, calculate the necessary algorithms, visualize curves in real time."
Lambotte said that Axxin could sell the readers directly to users, but is choosing to go the OEM route for the time being.
"For the isothermal instruments … any clinical lab that runs isothermal amplifications could buy the readers and run their tests on them, because it's easy to put the protocol in place," he said. "You set the temperature, and you just decide what wavelength you need to read in fluorescence detection."
Lambotte noted that Axxin has inked agreements to make branded readers for several companies, most of which do not yet market isothermal assays. "There aren't many isothermal tests on the market yet," Lambotte said. "Three of the [partnering companies] are licensing access in order to do isothermal products, but they don't have products on the market yet. So it's going to be new for them."
Two of the companies are in the medical diagnostics field, and one of them currently has "one excellent rapid test" based on other nucleic acid amplification methods, "and I think they're going to complement it with an isothermal test," Lambotte said.
Two other partnering companies play in applied markets, particularly agriculture, he added. "Broadly speaking, this includes testing for GMOs in plants; testing for food contaminations by bacteria, like Listeria, E. coli, Salmonella; and also looking for plant viruses. Those are just a few examples," Lambotte said.
One of the only commercial isothermal amplification-based series of tests on the market is Meridian Bioscience's Illumigene brand, which uses loop-mediated isothermal amplification technology licensed from Japan's Eiken Chemical. Meridian currently offers Illumigene tests for C. difficile and group B Streptococcus, and markets its own incubator/reader, called Illumipro.
Quidel, in partnership with BioHelix, has developed a handheld isothermal amplification-based platform called AmpliVue. Quidel has received US Food and Drug Administration 510(k) approval for an AmpliVue test for herpes simplex virus; and has received the CE mark and plans to file for FDA approval for a C. difficile assay.
AmpliVue uses BioHelix's isothermal amplification method, called helicase-dependent amplification, a technology that BioHelix is offering to license to interested parties for assay development.
"BioHelix makes a great technology, and we make instruments, and I hope somebody will use the BioHelix technology on our instruments," Lambotte said. "We are not working with BioHelix … but they license the technology out, so I hope that many companies will license it."
Another company developing isothermal amplification-based assays is UK-based Lumora, which is combining Eiken's LAMP technology with its own bioluminescent assay in real time, or BART, reporter system. Lumora has partnered with 3M in the area of food safety testing; and has been exploring agricultural testing and molecular diagnostic applications, and has developed multiple instrument platforms to run its tests.
One possible partner for Axxin is healthcare firm Alere, which in 2010 acquired a pair of companies specializing in isothermal amplification technology — TwistDx, which has recombinase polymerase amplification technology; and Ionian Technologies, which has nicking enzyme reaction technology.
In January, at the JP Morgan Healthcare conference in San Francisco, Alere disclosed that it is developing two molecular diagnostic platforms: The NAT Analyzer for multiplexed blood-based testing; and the iNAT platform, which is designed for low-cost molecular POC testing, and presumably uses one or both of the isothermal technologies it acquired with TwistDx and Ionian.
Lambotte said that he believes the tipping point is coming soon for isothermal amplification technology.
"I think that it's going to take one or two companies to show that isothermal really works, and that it is rapid and reliable," he said. "It's like anything — for instance, if you look at lateral flow test readers, [the industry has been] talking about that for 10 years, and manufacturers have waited until … they cannot do without those readers to put them on the market."
The same holds true for the fluorescent version of lateral flow strip detection, which Quidel uses in some of its assays. "I have heard from manufacturers of those fluorescent beads that since Quidel launched its reader, many other companies are buying fluorescent beads to try and adapt their tests to the same technology as Quidel," Lambotte said. "So I hope something similar will happen in the field of isothermal amplification."
Axxin isn't putting all its eggs in the isothermal amplification basket, however. It is also developing a line of readers for tests based on lateral flow strip detection, primarily immunoassays. Those readers are "very compact, can be held in the hand, and can read lateral flow tests with visible lines or with fluorescence," and are expected to be on the market also later this year, Lambotte said.