Oxonica’s Bid to Reshape POC Diagnostics:
Michael J. Natan Describes Evolutionary and Revolutionary Technologies

By Malorye Allison

Michael Natan has spent years souping up an established technology he says could now revolutionize the point-of-care (POC) testing world. "POC is laden with 100-year old technologies," Natan explains. "There’s nothing really new that’s even close to market."

Oxonica’s twist on SERS (surface enhanced Raman scattering) is both those things, he maintains. Natan is president and chief technical officer at Oxonica, which aims to commercialize new tests based on a well-documented physical effect – the change in frequency that occurs in photons when they are bounced off different types of particles. Those particle-specific frequencies are unique enough to serve as molecular "fingerprints."

Unfortunately, such particles are typically promiscuous and bind many molecules at once. "SERS using uncoated nanoparticles is extremely sensitive and not specific," Natan says. As a result, early efforts to use SERS as a signal detector bombed.

Natan was fascinated with the technology, however, and as a professor at Penn State, he came up with a neat way around this problem: He coats the particles with different reporter molecules and then encapsulates them with a glass shield. Analyte-binding molecules, such as antibodies, are then attached to the glass. The different particles still emit their own signature frequencies, but now the particles bind only to their targets.

Today, Oxonica is developing a range of Nanoplex products using its proprietary 50-nm silica-coated gold nanoparticles. It’s a completely new type of signaling based upon a very well-documented effect, and Natan believes it has the power to transform many key diagnostic assays. "If major diagnostics players pick up this technology, it would become ubiquitous," he says.

Oxonica’s researchers are working on two major applications. First, they are using their nanoparticles to try and dramatically improve lateral flow immunoassays (LFIs) – those handy and widespread little sticks that can detect pregnancy, ovulation, and scores of other biological states. Natan’s group is also aiming even higher though. He says they could "redefine" how POC testing is done with a no-wash assay that requires just one step, but delivers a strong enough signal it can even be carried out in substances like blood or urine.

The lateral flow immunoassay tactic could have a big payoff by itself. Natan points out that LFI goes off-patent in the next few years, which means that profits will start shrinking. Meanwhile, the main drawback to LFI is its lack of sensitivity.

With their approach, Natan says Oxonica can improve LFI’s sensitivity by at least 10 fold and possibly by as much as 100 fold. The glass coating insulates the particles from the assay’s basic surface chemistry. As a result, a Nanoplex-based LFI device can use brighter particles, providing a much clearer signal. In addition, multiple particles can be used, so LFI could finally be multiplexed.

"People are already very comfortable with lateral flow immunoassays," says Natan. "If you offer improvements without requiring any other changes, why wouldn’t they adopt it?"

Natan calls Oxonica’s LFI approach "game changing" but adds that it is only an "evolutionary" development. "Our no-wash assay, meanwhile, is truly revolutionary," he says. "It’s a disruptive technology, and so it’s going to be a bigger challenge to get it adopted."

The no-wash assay uses the Nanoplex biotags along with magnetic beads that carry antibodies. The biotags complex with the beads, which are then pulled down to the bottom of a tube over a period of 30 minutes. The test uses near-infrared detection and can be carried out in complex samples and multiplexed.

Getting a disruptive technology onto the market requires money and muscle. Oxonica will thus lean on investors and key partners. "Every collaboration takes time to manage, so we have to be careful about how thin we spread ourselves," Natan says. He adds that currently, "Our major limiting resource is time for new assay development." The more assays available using the technology, the more likely it is for the tool to get widespread adoption.

The company’s next milestones are to demonstrate cGMP manufacturing of the material and to get some products out – either on their own or through partners, such as Becton Dickinson, which already has a non-exclusive license to certain diagnostic applications. "At the end of the day we will be judged on the quality of our particles," Natan says.

While the challenges facing a new technology platform are myriad, Natan says he is pleased by the market’s reaction to his tools and the lack of relevant competitors. "But what’s been most encouraging is the FDA’s responsiveness to new assay platforms, and in particular those involving multiplexing" he says. The drive toward multiplexing will not just enable testing of multiple analytes, it will also help some single-analyte assays be improved by use of internal calibration. Oxonica’s first product may do multiple tests for the same analyte, as well as incorporate standards, to improve precision.

While POC will be their first target, overall, Natan sees a huge range of opportunities ahead, including histopathology, in vivo and point-of-use testing for things like avian flu and E. coli. He says his platform is like PCR, "but broader," and that life scientists are starting to agree with him. "Increasingly, I hear people saying ‘that will work for my assay’," Natan says. "That tells me we are barking up the right tree."

Oxonica's proprietary Nanoplex particles.