Paul van Gerven
15 June

Dutch companies Lionix, Qurin and Surfix, along with public-private partnership Photondelta, have set out to unlock the potential of integrated photonics for corona testing. Their ultimate goal: a fast, reliable, yet inexpensive corona test.

It’s considered the holy grail of medical diagnostics: point-of-care testing. A sample taken from the patient is tested on the spot, next to the hospital bed, in the general practitioner’s office or even at home, and within minutes the result is in. It’s convenient, in some cases life saving, and there’s no time-consuming and expensive lab work involved. Imagine what the availability of such a quick and reliable test for the SARS-CoV-2 virus (colloquially known as the coronavirus) would mean in the fight against the current pandemic.

Developing such a test is exactly what three Dutch companies, co-financed and supported by public-private organization Photondelta (see sidebar “Photondelta’s growth strategy”), have set out to do. Combining Lionix International’s integrated photonics technology with Surfix’s nanocoatings and Qurin Diagnostics’ biomedical expertise, they aim to have SARS-CoV-2 testing devices in doctors’ offices by the end of next year. The ultimate goal, however, is to make a test for the masses: a widely available, disposable test that only costs a few euros.

Photograph of a series of fully assembled optical sensor chips, including a low-cost light source and detector array, mounted on PCBs, ready for implementation. Credit: Lionix

Top-notch

Before teaming up on corona, the companies were already working closely together: Lionix and Qurin last year acquired Surfix to accelerate their efforts to develop a photonic biochip for early cancer detection. The corona test will be based on the same underlying principle. In fact, this principle can be used to detect many different entities: not just viruses, but also DNA and RNA, proteins and other (bio)molecules. The partners fully intent to exploit that feature by developing not one, but two corona tests: one that tells if you have the disease and another that indicates whether you’ve had it.

In broad strokes, the biochip works on the basis that the characteristics of light are altered when it passes through a waveguide that’s coated with ‘hooks’ for whatever is being tested for. If a sample solution is brought into contact with the waveguide and contains a species that attaches itself to the hooks, this will be detected through the change in properties of the light that’s being led through the waveguide.

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For diagnosing COVID-19, the disease associated with SARS-CoV-2 infection, the hooks are receptors for the virus particle. Thus, the presence of the virus is detected directly, as opposed to the current standard testing method, which entails destroying the virus’s shell and looking for the presence of released genetic material. Since this requires quite time-consuming processing, people currently have to wait a day or so to get their test results back. Direct detection of the virus, however, does away with a lot of the processing and is inherently much quicker – perhaps as quickly as a few minutes.

The same principle can just as easily be applied to look for antibodies, ie proteins produced by the immune system that are the tell-tale sign of whether or not someone has been infected with SARS-CoV-2 in the past – perhaps without realizing it. This is ‘simply’ a matter of placing antibody receptors on the waveguide, instead of the virus receptors.

Importantly, the biochip is extremely sensitive, meaning the test results will be reliable. “I don’t know of any label-free direct-detection methods that obtain a higher sensitivity,” says cofounder and CTO René Heideman of Lionix. Label-free means without chemically attaching ‘beacons’ to the virus or other species being tested for – a procedure that adds complexity and costs. “There are comparable optical options, but because these aren’t based on integrated photonics technology, they will not develop into a compact, low-cost solution any time soon.” In other words, the partners are doing two things in parallel: developing tests that both yield top-notch results and will be low cost.

Revolution

Achieving such a feat in such a short time requires the underlying technology to be at an advanced stage already. For its part, Lionix has been developing integrated photonics since 2002. Initially targeting the telecom market, the Enschede-based company broadened its scope with biosensing and metrology applications along the way. Surfix has been perfecting its nanocoatings for life science applications ever since it was spun off from Wageningen University & Research in 2011. For the past two years, the photonics biochip has been its main focus, along with microfluidics, which will also be part of the test devices.

“This pandemic is a terrible thing, of course, but there’s beauty in the fact that – thanks to years of hard work and investment – all the necessary elements are ready to be put together to make a difference in managing the spread of the disease,” says Surfix CTO Luc Scheres. Heideman chimes in: “We’re going to see a lot of claims of revolutionary new sensor technologies that will fight COVID-19. Most of them will be baseless. Our partnership stands out because we’ve been working on these technologies for many years already. It’s very mature.”

“The Netherlands has played a pioneering role in integrated photonics,” Heideman continues. “The rest of the world is catching up, but we recently moved up a gear by establishing Photondelta. This organization fosters collaboration among relevant local companies, thus creating a well-oiled ecosystem that spans the entire value chain. This, too, allows us to accelerate our current efforts to develop our biochip.”

“This is exactly the kind of initiative we set out to bolster,” confirms Photondelta’s Maarten Buijs, who’s currently developing a roadmap for biosensors based on integrated photonics (again, see sidebar “Photondelta’s growth strategy”). “It’s work in progress, but we see a lot of potential for mass-producible integrated photonic sensors in a wide range of point-of-care applications where biomolecules and bioparticles need to be detected. This endeavor of Lionix, Surfix and Qurin might very well start that revolution.”

Cheap

Let’s have a look at what the partners bring to the table exactly. Diving a little deeper into the inner workings of the sensor, the light passing through the waveguide isn’t completely confined by it. Part of it ‘sticks out’ – the so-called “evanescent field” – allowing it to interact with Surfix’s nanocoating that’s loaded with receptors (the ‘hooks’) provided by Qurin. Receptors holding on to ‘guests’ cause the refractive index to change, which induces a phase change in the light. This phase change, through a number of manipulations, can be detected as an intensity differential.

Artist impression of the biochip in development. Receptors (Y-shaped, in yellow) are attached to a coated waveguide (in cyan) while holding on to virus particles (purple spheres). The rest of the surface is coated with biomolecule repellent nanocoating (in blue). Credit: Surfix

Surfix’s main challenge was to ensure that the receptors are attached to the waveguides exclusively. “All common coating methods would coat the entire chip, so the analyte would attach itself anywhere on the chip’s surface. The waveguides take up only 1 percent of that. We can’t detect anything that isn’t attached to the waveguide and because we’re working with such small amounts, we simply can’t afford to leave most of it undetected,” Scheres explains.

The company, headquartered in Wageningen, therefore developed a protocol that applies two coatings: one for the waveguides to attach the receptors and another one for the rest of the chip’s surface. Scheres: “The latter, in fact, repels biomolecules, basically making sure nothing sticks to it. This increases the signal-to-noise ratio. Depending on several factors, our coating protocol lowers the detection limit by a factor of 10-100. This makes all the difference.”

When it comes to sensitivity and detection limits, Lionix’s most important job is to maximize the interaction of the light with the receptor-guest complexes. As it turns out, the specific integrated photonics ‘recipe’ the company has employed for almost two decades, is ideally suited for that job. Heideman: “Our silicon nitride-based Triplex platform features very low light losses. This means we can make relatively long waveguides. In addition, we can feed multiple waveguides with a single light source, allowing for multiple sensors on a single chip. And, finally, we have a very efficient evanescent field: about a quarter of the light sticks out. All these elements contribute to better signal generation.”

Another very helpful feature of Triplex is its compatibility with a wide range of wavelengths. Lionix chose an 850 nm light source because these are widely available and cheap (they’re also used in the computer mouse), but also because sensitivity at this wavelength is higher by a factor of three to four, compared to employing the 1550 nm light most commonly used in integrated photonics. At 850 nm, the required detectors are low cost as well.

A lot to gain

Backed by investments from Lionix and Qurin and a commercial loan from Photondelta, the partners have given themselves six months to demonstrate to the world that their sensor is the real deal. In parallel, they will start putting together a large-scale production process and find additional investors to finance setting that up. If all goes well, a desktop testing device – which isn’t as cost sensitive – should be available in 18 months. The introduction of the disposable will take another year or so.

But with vaccines and treatments in development, wouldn’t the tests be a little late to the party? Heideman and Scheres aren’t worried about that at all. “Even if it comes to that, our technology can be used for a wide range of applications, even outside the medical domain. If there’s anything positive about this pandemic, it’s that it showed the world that there’s still a lot to gain in point-of-care testing. Our partnership will gladly work to make that progress happen,” says Scheres.