NEW YORK (GenomeWeb) – If they are ever to see large-scale adoption, point-of-care molecular diagnostics systems need to be rapid and easy to use, but also relatively inexpensive with a broad test menu. These constraints sometimes limit POC MDx developers to using sample types with an abundance of target and a simple matrix.
Now, a startup in Scotland hopes to provide instrument developers with a sound wave-based technology to help overcome the bottleneck of sample preparation, potentially enabling a broader variety of targets and sample types to be tested at a lower cost.
Founded four and a half years ago, SAW Dx is in the early stages of development, but so far, the progress has been intriguing. It has developed methods for in-droplet centrifugation and sound wave-based nucleic acid amplification for which it projects a very low manufacturing cost.
The company has also internally tested its methods on challenging samples, such as swabs from patients with sexually transmitted infections, with positive, albeit unpublished, results.
At its core, the technology — called surface acoustic waves, or SAW — uses high-frequency sound waves to manipulate tiny droplets on the textured surface of a polymer chip.
The methods, which have been licensed from the University of Glasgow and developed further in house, use acoustic waves in the range of about 10 megahertz or more that then impact droplets of about 10 microliters.
SAW Dx CEO Iain Miller noted in an interview that the firm's two-dimensional design differs from a typical lab-on-a-chip device, which essentially involves moving droplets through a maze of channels, micro-capillaries, pumps, and actuators.
"What we do is create patterns on the surface of an inexpensive polymer or other material, and by tuning the frequency and the positioning of the origin of the waves, we can do a bunch of different things with a little droplet of raw sample," Miller said.
For example, sound can be used to push a droplet around the surface of the chip or mix it with reagents. Sound can even be used to whip a droplet around so fast that it causes lysis of whole cells, in as little as 10 seconds. The technique also pushes unwanted cellular debris out to the edge of the droplet, leaving purified nucleic acid behind, Miller said.
The method was used in a 2015 study to detect nucleic acids of sexually transmitted infections using loop-mediated isothermal amplification. Since then, Miller said, the firm has also developed it to do PCR on nucleic acids in microdroplets using only sound waves.
The surface acoustic wave method creates thermal effects, he said, basically as a byproduct. These can be directed and localized to within the droplets, and, because the droplets are so small, they can be heated and cooled very quickly.
"The normal effect would be movement — pushing something or spinning something around — but the side effect can be a degree of heating, [and] if we tune the frequency correctly, we can cause heating and then cooling, and we can do that for 40 cycles, for example, to see a relatively rare target," he said.
Potential corporate partners might already have a proprietary amplification method as their core technology, but Miller said the sound wave-based PCR is another option, and it is roughly as fast as current POC MDx amplification technologies.
Although the firm is still in the development phases and does not yet have an integrated product, Miller believes the low cost of goods will be intriguing to potential partners.
"We have to prove this when we manufacture at scale, but it can, we believe, have a very low cost of goods, and therefore enable low-cost testing," he said. Specifically, Miller said the firm is targeting its development to support a $10 to $20 selling price for MDx cartridges that license the SAW Dx technology.
The firm has a lot of proof-of-principle work in place already, and recently secured new funding to support integrating the various steps. "We've done all of these things, but we haven't put them all together and automated them on the same chip surface yet," Miller explained.
SAW Dx has, however, taken sexually transmitted infection samples through the steps, performing PCR amplification of chlamydia and gonorrhea from patient samples, demonstrating "good concordance with central lab systems on the detection side," he said.
Going forward, the company will likely keep its core know-how, involving building the so-called phononic crystals or chips that direct the high-frequency waves, as well as the consumable overlays, in house. But the different architectures with which to present the system may be outsourced. SAW Dx is currently collaborating with Sagentia, a Cambridge, UK-based firm that will develop some of its components, Miller said.
In addition to the new funding, the firm has raised roughly $2.5 million to date, and is also now raising private funding to further accelerate integration and automation of a "manufacturable, low-cost cartridge architecture," Miller said.
In terms of getting to market, Miller said the firm sees itself collaborating and licensing to corporate partners. It is also considering partnering with companies that need purified nucleic acids as part of a tool kit to democratize research, for example, and it sees opportunity in applied markets, like veterinary or forensics testing.
"It is kind of an OEM model in a sense, where we could have part or all of our workflow inside someone else's box," Miller said.
The firm has had a few collaborative research and development projects with corporations in the diagnostics and research sector thus far, he said, but has yet to consummate a long-term agreement.
The POC MDx space
Within the POC MDx space, there are currently a handful of systems that are cleared by the US Food and Drug Administration and CLIA waived. Most of these can only run a few CLIA-waived tests, focusing on respiratory infections — like influenza, respiratory syncytial virus, and Strep A — that tend to have a simpler sample prep component.
Cepheid has a somewhat broader menu for its instrument, Miller noted, but not all of that menu is CLIA waived. It is also debatable whether the XpertXpress instrument could be called point-of-care or near-patient, since it is a bit larger than competitors like the Abbott ID Now or Roche Liat, although the firm recently launched a smaller instrument, called the Edge, internationally.
In general, it is also unclear whether POC MDx technology is really being adopted on a large scale, but Miller said the fact that corporations in America like CVS and CareMark are building out clinics within their retail pharmacy settings indicates a growing demand for decentralized diagnostics.
While decentralizing molecular testing is a very logical progression, and there ought to be a demand for it, it hasn't seemed to come to fruition yet, perhaps because of a barrier beyond the boiler plate rationale of POC MDx being a disruptive technology or a seasonal market.
Indeed, to be used by non-experts at the point of care, "You've really got to have a straightforward product," Miller said. In his opinion, nothing currently on the market is simple and inexpensive enough. SAW Dx will be focusing its proof-of-concept development on detection of sexually transmitted infections, respiratory, and hospital-acquired infections. "It speaks to the diversity of what we think we can do — for sexual health, there aren't any CLIA waived tests on the market today," Miller said.
The firm will need to be able to extract nucleic acids from swabs of different body sites as well as urine for sexually transmitted infection applications. So far, it has worked with swabs, but not yet urine. However, the firm has been able to use its methods on stool samples and whole blood, and urine is theoretically a simpler sample type. Generally speaking, "If we can work with the hardest sample types, we think that will speak volumes to people," Miller said.
SAW Dx will also continue to build an integrated product, but Miller noted that this will be more of a demonstrator instrument, to show corporate collaborators what the technology can do.
Miller said that SAW sees STI clinics as a likely initial starting point, as well as scenarios where the testing currently involves multi-day send-out of samples. "Retail would be at the end of that journey, not necessarily the first port of call," he said.
Cepheid has had some success with STI clinics adopting its system for CT/NG, albeit for same-day turn-around rather than strict point-of-care or bedside testing. A CT/NG test had reportedly been in development on the Alere i system, now known as the Abbott ID Now, but there have been no recent updates on the progress of that assay development.
Whether or not the SAW Dx technology can change point-of-care molecular testing remains to be seen, of course, but Miller sees promise in the firm's technology. "What we hope we've got going for us is a really low-cost architecture that can do something new in sample prep, and that can take us into a number of markets with our partners," he said.