By Allison Proffitt
January 3, 2020 | When it comes to improving health care and care delivery, there are occasional big advances—great leaps forward in technology and our understanding of disease biology—and then there are the incremental advances that nonetheless change how we deliver care.
Mario Blanco believes he has one of those advances: a small change that just might change everything.
Last month NANOPEC Technologies announced MetaFluorex, a new class of proprietary nano-structured ceramic films, that the company says have shown to enhance fluorescent signals by factors as large as 100 times, depending on the assay, when compared to the glass slides currently used for in vitro diagnostic testing. Specifically designed for the manufacturing of in vitro diagnostics (IVD) kits, MetaFluorex offers significantly enhanced performance, cost of ownership, and safety benefits.
Laboratories use glass microscopy slides “without even thinking about it”, Blanco explains. “But when we go to assays that require the production and emission of light… [glass] doesn’t really provide much of a substrate that can really enhance the outcomes of fluorescence-based assays.”
Most IVDs use fluorescent light emitted by reporter molecules (tagged antibodies, fluorophores) to indicate the existence of an antigen: pathogens, gene mutations, or cancer. If the amount of fluorescent light produced by the reporter molecule is insufficient to yield a definitive positive test, the patient receives a false negative. A false negative can be caused by poor sample preparation or by low amounts of antigen such in the early onset of a disease such as cancer.
Glass, Blanco argues, isn’t the right substrate for accuracy in these types of tests. Its main advantage is that it is smooth and easy to clean, he says. Manufacturers use various coatings or other manipulations to improve slides including frosted slides, nitrocellulose, patterned slides, and dielectric modified films. Each of these changes increases the surface area of the slide. More surface area means more antibody can be present and fluorescence can increase.
But, Blanco points out, more antibody is also required. For early detection, that may not be possible. “Early on, when a disease is just about to show any major symptoms, the amount of biomarker in the blood or tissue is small. The amount of fluorescence may not reach the limit of detection. But early detection is the key to cure! If you can detect cancer early on, the outcome to the patient is much more positive.”
Fabricating An Affordable Slide
In seeking a better alternative, NANOPEC started with the porous ceramic film used for biofiltration but needed to tweak the fabrication process. “Traditional nanofabrication techniques wouldn’t work for an application of this scale,” Blanco says. “Because, of course, if you’re trying to replace microscope slides, you’re going to need a lot of [material]!” Blanco set out to find a new fabrication process that could be scaled and required no special equipment. He found that some academic labs were toying with the process, creating ceramic films with ordered pores, but the process they used required mercurous chloride and chromic acid to etch away aluminum.
One thing that concerned Blanco was the use of mercurous chloride, chromic acid, and chromates in the fabrication process. “I have lab staff to care about, so I spent almost a year getting rid of these materials. Finally, when I succeeded, I realized yeah, it was good for my staff and it was good for other reasons.”
Toxic chemicals are expensive to use, transport, and dispose of, Blanco explains. By removing toxic chemicals from the process, NANOPEC reduced costs by 30% and then added another 45% savings in process refinement.
The nano-structure and atomic composition of the MetaFluorex films gives the product the optical enhancement that the company believes can lead to earlier detection by reporting lower biomarker concentrations. MetaFluorex requires fewer antibodies and biomarkers to achieve superior signal to noise ratios than comparable diagnostics on modified glass substrates.
Blanco believes that the films can greatly decrease the probability that a patient will receive the wrong diagnosis when the fluorescence signal is too weak or the biomarker concentration too low to be detected.
The challenge, now, is getting the slides in the hands of the right users.
NANOPEC is in its second round of seed funding. The company has office and wet lab facilities at the University of Arizona Center for Innovation incubator and has an approved patent application for part of the fabrication process.
The company is already producing ceramic films, which are limited in size by the power source for one step, Blanco says. “We can produce this in 4.5 by 4.5 inch [wafers],” he says. We can produce hundreds of them, even thousands of them a month depends on the number of reactors we have.” The company does have material for sale and has filled ordered in the US, Asia and Europe, he says. In the future, Series A funding will help the company move into its own manufacturing facility.
Right now, one of Blanco’s challenges is identifying the right customer. The most reasonable target is IVD manufacturers, especially if the MetaFluorex makes their diagnostics more sensitive. But FDA re-certification could be a challenge. Delivering the material directly to hospitals and diagnostic clinics is another option. “If you have a fluorescence-boosting technology, can you cut down and use only 10% of that reagent, of that consumable,” Blanco says, saving the labs money but requiring, “some education on the differences between using glass and using our film.” Finally, Blanco believes the film could be a boon for companies doing high throughput drug screening. By boosting the fluorescence signal, he says, companies will be able to identify a larger number of drug candidates.
In any case, Blanco is hopeful about the outcomes that the ceramic films will enable. “We are very passionate about being able to develop technologies that can reduce healthcare costs, but also optimize the outcomes for patients,” he says. “NANOPEC technologies can do that.”