Researchers from EU-funded project 'RAIS' discuss collaboration with industry partners and potential market barriers for their point-of-care diagnostic system
RAIS is a research project funded by the Horizon 2020 Framework Programme of the European Union. Started in 2015, its objective is to develop a new, point-of-care, microarray platform based on an interferometric lens-free microscopy design, and to demonstrate its ability to detect specific sepsis biomarkers in blood samples, within 30 minutes.
In today's point-of-care (POC) diagnostics market, there is an ever-increasing demand for rapid and accurate solutions for the early diagnosis of diseases. For example, sepsis is a potentially fatal whole-body inflammatory reaction caused by severe infection, and is one of the 10 leading causes of death worldwide, responsible for around 20,000 deaths per day. Each hour of delayed treatment increases the mortality of patients by eight per cent. Therefore, the rapid detection of sepsis is critical, and RAIS proposes a disruptive microarray technology, similar to a miniature, large field-of-view differential interference contrast (DIC) microscope, to achieve it.
When patients contract sepsis or another disease, their bodies produce or contain biomarkers such as cells, molecules, and genes which are specific to the disease. To distinguish between different biomarkers, we use a microfluidic cartridge to bring a blood sample into contact with a transparent plate containing an array of protein dots, each designed to capture a different type of biomarker. Most biomarkers are very small (< 10nm), and present in low concentrations, making them almost entirely transparent and extremely difficult to detect. However, when light passes through them, it does experience a slight change of phase. This is why in RAIS we make use of the high phase-shift sensitivity of a DIC system1 to detect the presence or absence of biomarkers on the microarray plate (see Figure 1), and help clinicians decide on the best treatment as soon as possible.
Fig 1: Reading of a biomarker microarray using the RAIS technology.
(P: polarizer, SP: Savart plate, ISA: Image sensor array)
Optical components of the system, and desirable improvements
The RAIS microarray reader is based on simple optical and electronic components: An LED light source, a collimator, a pair of polarisers, a pair of birefringent elements called Savart plates, and a CMOS image sensor. Since the light used to image the microarray is collimated and not focused, the reader is a lens-free microscope. This makes the alignment easier, while allowing a large area to be imaged at any given time, which offers the ability to rapidly analyse large microarrays containing thousands of biomarkers. However, there is room for improvement in the price and size of the image sensor and light source we use. Our current image sensor (Aptina MT9P031) offers good performance, but it may have more features than strictly needed, and comes with large electronic boards which occupies a lot of space. Similarly, our light source is a 4-LED block (Mightex), which is relatively bulky and costly. We are now looking at cheaper alternatives for these elements.
Collaboration with industry
Almost half of the partners involved in the project come from industry. This is benefitting the project in several ways. First, Thermo Fisher Scientific BRAHMS, thanks to their leading position in the field of in-vitro diagnostic tests, is playing a very important role in ensuring that we understand the exact needs of the POC market, and keep our approach relevant.
Next, Trinean, which has already successfully commercialised micro-volume molecular spectroscopy instruments, is using its expertise in system integration to miniaturise the RAIS reader system, and significantly reduce the production cost. Also, DIESSE diagnostica senese is a manufacturer of innovative in vitro diagnostics systems and is utilising its in-house production of polyclonal and monoclonal antibodies and native and recombinant antigens for the project. Finally, microTEC has been active in the field of plastic micro-manufacturing for 14 years, and is responsible for the design and production of the RAIS disposable microfluidic cartridge.
Innovation challenges and potential market barriers
The main innovation challenge will be to detect the smallest biomarkers (< 1nm), since their interaction with light is minimal. The use of plasmonics to enhance the light-biomarker interaction is currently being investigated, and has already shown promising results. Potential market barriers include the fact that competing POC diagnostic systems are starting to appear on the market, which is not surprising given the importance of rapid sepsis detection. The RAIS platform is expected to compete in terms of costs, sensitivity, time to result, and importantly by multiplexing many biomarkers in a single test.
Impact on European industry, in particular optics companies
The POC medical market for detection of sepsis and other infectious diseases is worth more than €4 billion2, and is currently dominated by American companies. If the RAIS system was to be widely adopted in hospitals, it would strengthen European industry’s position in this market. Furthermore, before being applied to POC diagnostic testing, microarrays have traditionally been used for proteins and DNA sequencing, another market estimated at €3.5 billion in the year 20123. The RAIS technology also has the potential to enter this market. Since the optical readers and disposable cartridges developed in RAIS would all be manufactured in Europe, the success of the project can be expected to generate significant job creation.
Title: Scalable, point-of-care and label-free microarray platform for rapid detection of Sepsis
Period: 01/01/2015 to 31/12/2017
Partners: ICFO (ES) – EPFL (CH) - iXscient (UK) - Diesse (IT) – CSIC (ES) - microTEC (DE) – Trinean (NL) - Hospital Vall d’Hebron (ES) - Thermo Fischer Scientific BRAHMS (DE)
1 R. A. Terborg, J. Pello, I. Mannelli, J. P. Torres, V. Pruneri, Ultrasensitive interferometric on-chip microscopy of transparent objects. Sci. Adv. 2, e1600077 (2016).
2 Kalorama Information Report.
3 Global biochip markets: microarrays and lab-on-a-chip (BIO049C), BCC Research