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Figure 1: Photonic biosensor chips with integrated light sources on printed circuit boards.

How to build a photonic biosensing diagnostics chip using vertical integration

This week, diagnostics company Surfix BV along with LioniX International and a consortium of Dutch partners announced an €8.5 investment for photonic biosensor development for covid-19 detection and early cancer diagnostics.

LioniX International play a key role in the partnership, which also includes Qurin Diagnostics BV, industry accelerator PhotonDelta and the East Netherlands Development Agency, Oost NL. Using vertically integrated expertise we have developed a technology platform that speaks to the pressing needs of the biosensing market.

But what exactly are those needs? And how does LioniX International’s approach to product development serve innovation in this cutting edge application? In this article we examine the drivers for biosensing innovation, the benefits of photonic biosensing and the unique mix of expertise LioniX International is contributing to its development.

The case for sensitive point of need testing 

Biosensors have the power to save lives through early and accurate diagnosis and effective treatment monitoring. Similarly, in veterinary, agriculture, feed and food production applications, biosensing can secure food safety and security, protect stocks and ensure animal welfare.

An effective test must provide accurate information and do so within a relevant timeframe or risk unacceptable consequences. On the other hand, testing speed is also paramount. In the diagnosis of sepsis – a leading cause of death in emergency wards – a delay of hours can severely increase the likelihood of death.

Meeting both the sensitivity and speed criteria with the same test is tricky. The most sensitive tests rely on central laboratories that can be far from the point of need. Moreover, tests that require specialist sample preparation increase turnaround time, rely on trained staff and introduce more possibilities for sample degradation.

Conversely, common point-of-need tests can lack the sensitivity and reliability required for certain applications. A greater issue is that they are fundamentally incapable of testing for a specific subset of biological markers. The technology for antibody or hormone-based lateral flow tests for example (such as the Covid-19 antibody test or home pregnancy test) will never be suitable for tests that look for specific DNA strands or for particularly low concentrations of biomolecules.

Photonic chip biosensing platforms promise not only sensitivity and speed but the flexibility to be configured to detect different analytes for applications from Covid-19 testing to water quality monitoring.

Biosensing basics

Biosensors detect particular biological compounds (or analytes) in a sample. To do this a biosensor combines two parts. The first, a biochemical component, is chosen for its ability to bind with the target analyte. The second is component that can detect and transmit information about the miniscule physical changes that result from this binding.

In photonic chip biosensing, the biochemical component is applied to the surface of a waveguide (think microscopic glass fibre fabricated on a chip) carrying a light signal. In this case, the binding of an analyte changes the way light travels through the waveguide, altering the light signal in way that can be read out by an instrument. Different components operate on different principles. Some detect changes in the absorption of light, others detect changes in the refractive index of the sensor material resulting from analyte binding.

A 100X increase in chip sensitivity for photonic biosensors 

In its collaboration with Surfix BV and Qurin Diagnostics LioniX International has developed the most sensitive chip-based photonic biosensing component that is up to 100 times more sensitive than the state of the art. The technology uses refractive index sensing based on a building block known as an asymmetric Mach Zehnder Interferometer (or aMZI).

The particular strength of such aMZIs building blocks for biosensing is that their sensitivity is partly a function of their dimensions. Therefore, with careful photonic engineering, LioniX International have maximised the component sensitivity in a way is not possible with other chip-based components.

Figure 3 (left): Close up of biochip surface showing the coiled waveguides individual aMZIs transducers. Figure 4 (right): The functionalised surface of the aMZI transducer with biorecognition agents applied on the waveguide surface. Image courtesy of Surfix BV.

Multiplexing is easy with photonic biosensors

The ease with which photonic transducers can be duplicated as sensor building blocks makes them particularly suited for an important biosensing technique called multiplexing. Multiplexing makes for more powerful diagnostic or prognostic testing by simultaneously targeting more than one specific analyte in a sample.

In a multiplexed photonic chip biosensor, any number of generic transducers can be functionalized with a different biochemical compounds, with no fundamental limitation to the compounds that can be used.

From design to device

To develop a technology platform that meets the very specific needs of the biosensing market, LioniX International have drawn on broad expertise from beyond photonics. This has required two approaches to knowledge integration: vertical integration of internal capabilities and horizontal integration of specialist partner expertise.

Vertical integration is the lifeblood of our development process. For the photonic biosensing platform developed for Surfix, we combined expertise in photonics with electronics, fluidics and instrument design. This approach enabled us to develop modules that help Surfix directly address market needs – usability, test reliability robustness and volume manufacturability. Vitally for a commercial product, this approach also ensures that modules are built with a view to volume scalability.

Our partnership with Surfix and Qurin also brought external expertise, vital for two reasons. Firstly, innovation at the forefront of a field relies on access to highly specialised knowledge. The expertise and intellectual property required from different domains like biochemistry, nanotechnology and photonics would be very nearly impossible for a single company to accumulate on its own.

Secondly, close collaboration is vital if LioniX International is to continually develop its understanding of how core capabilities can be applied to new challenges. For example, in collaborating on biochemical surface coatings for photonic chip biosensors, we have come to understand the parameters that limit this technology. By doing so we have been able to develop complimentary electronics fluidics, sample preparation and instrumentation solutions that would have not been possible otherwise. This not only benefits our biosensing partnership, but adds to the body of expertise we can rely on to support other customers bringing technology to market.

R&D for effective product development

To offer value to customers through vertically integrated product development, we need to ensure we can bring serious expertise to the table. The source of this expertise lies not only in product development experience, but also in our own research and development projects.

One such recent project, the EU-funded BioCDX, provided foundational knowledge for photonic biosensor cartridge development. In addition to novel photonic aspects of the sensor, the cartridge design included integrated fluidic syringes for liquid handling and sample preparation and integrated low-cost light sources on the biosensor chip for easy interfacing with a desktop reader.

Figure 5: A low cost injection moulded cartridge (left) with aMZI biosensor chip. The cartridge features integrated microfluidic interfaces (mechanical syringes), blood sample preparation and light source integrated on the biosensor chip. These features make for simple interfacing with a desktop reader instrument (right). Images courtesy of CSEM/BioCDX.

Summary

Integrated photonics is playing a vital role in exciting developments in biosensing. The combination of sensitivity, testing speed and compatibility with a range of target molecules make photonic biosensors attractive in a wide range of medical and non-medical applications.

Despite pressing needs and compelling applications, the use case for biosensors is complex. To develop a cost-effective solution that can outperform existing technology, LioniX International have had to capture expertise that has both high degrees of breadth and specialism. Both are a core aspect of how we do business.

Vertical integration provides the means to develop not just photonic chips, but whole technology solutions. These solutions come in the form of assembled modules incorporating photonics, fluidics and electronics.

Whilst vertical integration leverages internal expertise, partnerships drive the necessary understanding of application required to co-develop cutting edge products.

Whether in biosensing or beyond, this approach to innovation and product development has proven impact. Through vertical integration from design to device, LioniX International is bringing the power of integrated photonics to a range of demanding applications.

References

Chatzipetrou, M.; Gounaridis, L.; Tsekenis, G.; Dimadi, M.; Vestering-Stenger, R.; F. Schreuder, E.; Trilling, A.; Besselink, G.; Scheres, L.; van der Meer, A.; Lindhout, E.; G. Heideman, R.; Leeuwis, H.; Graf, S.; Volden, T.; Ningler, M.; Kouloumentas, C.; Strehle, C.; Revol, V.; Klinakis, A.; Avramopoulos, H.; Zergioti, I. A Miniature Bio-Photonics Companion Diagnostics Platform for Reliable Cancer Treatment Monitoring in Blood Fluids. Sensors2021, 21, 2230. https://doi.org/10.3390/s21062230

Source: Lionix International news

New investment in light-powered biosensor accelerates the availability of high quality – low cost tests for early detection of cancer, Covid-19 and other diseases

 Surfix announces an investment of € 8,5 million by a Dutch consortium consisting of companies Qurin Diagnostics and LioniX International, industry accelerator PhotonDelta and the East Netherlands Development Agency Oost NL for further development of Surfix’s plug-and-play diagnostics platform.

Surfix will use the investment to accelerate the development of its fast, reliable and attractive plug-and-play diagnostics platform for all sorts of point-of-care tests. The initial target applications are early cancer diagnosis, Covid-19 detection and tracing of pathogens in water for aquaculture. 

 Wageningen, The Netherlands, May 25th, 2021

Low cost tests available for the masses

The global Covid-19 pandemic underlines the need for fast and reliable point-of-care diagnostics anytime and anywhere. Also in areas where there is no hospital, clinic or trained medical staff available. A sample taken from the patient is tested on the spot, next to the hospital bed, in the doctor’s office or even at home. Within minutes the result is visible and appropriate action can be taken. It is convenient, in some cases lifesaving, and there is no time-consuming and expensive laboratory work or equipment involved. The availability of a quick and reliable test would mean a huge step forward in the fight against the current and future pandemics. The ultimate goal for Surfix is to make a test that is available for the masses and at the cost of only a few euros.

Unique diagnostics platform

The biosensor of Surfix consists of two significant elements: the most crucial part is the chip in which the actual sensing occurs. The other part is the microfluidics part, in which the biological assay takes place in a small sample volume.

In the sensing part light passes through the chip (comparable to a minuscule glass-fiber spiral) instead of electricity. Biomolecules attached to the surface of the chip can catch other biomolecules out of a sample (for instance blood or urine), based on biorecognition. This causes a change in the properties of the light that is traveling through the chip, which can be detected and read by the sensor system. This change is a measure of  the presence of the biomolecule in the sample one is looking for.

Before entering the sensing part of the sensor, any sample needs to be processed (comparable to a very small laboratory). This takes place in microfluidic channels which feed the sample into the sensing part.

For the sensing part Surfix has developed unique nano-coatings which enable the binding of biomolecules and enhance the sensitivity of the sensor, while the microfluidic part is covered with a different nano-coating that repels biomolecules and enhances the flow of the sample through the microfluidic channels.

The plug-and-play diagnostics platform can be used to detect viruses, DNA and RNA, proteins like antibodies and antigens, and other biomolecules.

Combination of Dutch technology

The plug-and-play diagnostics platform combines LioniX’s integrated photonics chip with Surfix’s nanocoatings for the proper functioning of both the sensing part and the microfluidics part. Integrated photonics is a revolutionary technology that allows the development of chips that can sense, capture and process huge amounts of data with light instead of electricity. Using light means that new types of devices and systems such as biosensors can be created that are radically cheaper, faster, smaller, more robust and reliable while using less energy. Qurin will be the launching customer for the platform in the field of cancer diagnostics in a screening setting on a regular basis for the entire adult population. This way Surfix hopes to contribute to the early detection and cure of the cancer patient. Qurin’s novel biomarker technology aims to detect most if not all  cancer types in urine, including lung cancer and cancer of the large bowel.

 

Maarten Buijs, CEO of Surfix, is excited about the investment: “With this development, we have deepened our relationship with parent companies LioniX and Qurin, both University of Twente spin-offs. With OostNL and PhotonDelta  on board our drive is to bring point-of-care diagnostics to the next level. In combination with the network and experience of the two Dutch public-private organizations, the leading-edge integrated photonics technology of LioniX and the medical knowledge of Qurin, the investment will allow us to take on the industrialization of our solution and clinically validate the exciting results in biomarker detection obtained to date”.

Senior Investment Manager Tech Pieter Klinkert of Oost NL shares the excitement: “The solution of Surfix supports the important ecosystem of photonic biochips and microfluidics which Oost NL acknowledges as key enabling technologies. Surfix can realize a breakthrough in the field of diagnostics based on photonics. Surfix is a spin-off company of Wageningen University & Research and is actively collaborating with WUR and the photonics cluster in Twente. This makes it a perfect fit for the network around photonics and MedTech in the east of the Netherlands.

To showcase the partners in the nanotechnology ecosytem, MinacNed has worked together with a number of member companies to shoot a promotional video about their company. These videos are now available on the partner profile pages. The video’s give a short pitch and insight in the technology and services that our MinacNed members have to offer to you.

If you are interested to learn more about the member company, you will find the contact information the member page. The following MinacNed members have published a video:

IamFluidics

Lionix International

Surfix

VSParticle

You will find the video via the company logo, which will open a video player in a new window. All videos are produced by Studio Lek.