Report
Teaser, summary, work performed and final results
Periodic Reporting for period 1 - BIOCUDET (Identify and detect key ocular biomarkers towards personal medicine)
Teaser
What is the problem/issue being addressed?More than 83 M European citizens are already affected by ocular diseases. Since the incidence of many of these conditions dramatically increases with age, the overall prevalence of these conditions is bound to steadily increase in...
Summary
What is the problem/issue being addressed?
More than 83 M European citizens are already affected by ocular diseases. Since the incidence of many of these conditions dramatically increases with age, the overall prevalence of these conditions is bound to steadily increase in Europe and elsewhere. The overall burden of Dry Eye Disease (DED) alone has been estimated at $55.4 B respectively for the United States and is bound to grow as the population ages. DED is among the most inimical of ocular diseases in terms of indirect costs in the EU, resulting in tens of billions of euros per year lost in productivity. Eye infections concern millions of EU citizens every year, also resulting in billions of euros in direct and indirect costs. In fact, the economic and societal burdens of eye disease now reach 70% of that of cancer.
Why is it important for society?
Today’s practice in ophthalmology is limited to a visual control of general symptoms associated to a statistical prediction that can be quite difficult to interpret as the illustration on the right depicts. The aetiologia of the infection is not known and the treatments are provided empirically depending on practitioner’s skills or beliefs. As an example, Betadine is a known specific treatment that gives good results to shorten Adenoviral infections. However, 70% of practitioners in the US still do not use it, mainly because they don’t know when to use appropriate treatment even if it could save weeks of productive days for their patient and limit epidemic episodes drastically. In the same way, 40% of ocular antibiotics are prescribed when unnecessary. Besides toxic effects for the patients which can lead to allergic reactions or even complications as DED, this unnecessary prescription of antibiotics also speed up the antibiotic resistance of the strains in a threatening way.
Regarding DED, the puzzle is even worse as there is today no clear diagnosis procedure to solve the chronic pain of this disease. This lack of biomarker-based methodology leads the patient to go through a lengthy and costly “trial and error†approach to find the appropriate treatment. This also makes the development of pharmaceutical solutions more difficult, as the recruitment of homogeneous population is difficult, and the monitoring of drugs effect depends on highly qualitative rather than quantitative appreciations. With the quantification of up to 30 Biomarkers of inflammation, BIOCUDET will finally provide a clear image of the inflammation of the patient conjunctiva and as a result allow appropriate prescription as well as quantified measurement of the treatment’s efficiency.
What are the overall objectives?
The main objective of our project is thus to develop and validate the commercial prototype of the first generic, affordable, ultrafast, multiplex, easy-to-use nucleic acid-based detection PoCT dedicated to ocular disease biomarker measurement. This platform will be used with its first set of dedicated kits by non-specialist practitioners who will be able to perform a simultaneous test on more than 30 biomarkers in less than 10 min at the start of the patient’s visit or in the emergency ward. The BIOCUDET PoCT will be based on FASTGENE technology. To adapt it to ocular diseases, we will interface it with an already marketed and recognised ocular sampling device (EYEPRIM technology) to deliver a new “sample in – answer out†device focused on the diagnosis and monitoring of ocular diseases.
 
Work performed
In order to define the technical specification of the solution, we made use of the standard System Engineering methodology. First, we collected the user requirements, then conducted a functional analysis, from which we derived the system requirement specifications. We structured these requirements into a preliminary functional architecture, providing a detailed overview of each subunit function.
We first focused on the sampling device, the sample preparation process and the module in charge of implementing it. We identified an already commercialised and CE marked device, named “EYEPRIMâ€, and manufactured by the OPIA Company. A demonstrator of the sample processing module that could be interfaced with this device was subsequently built up. This module is able to concentrate, wash and lyse the bacteria eluted from the sampling device.
In order to optimize the qPCR module prototype, we reasoned that it would be easier to assess and improve the quality of the thermic exchange between the thermal module and the PCR chip if we could image the PCR reaction instead of just measuring the fluorescence intensity averaged on the PCR chamber volume. We therefore adapted our Fastgene prototype so that it could image the quantitative PCR reaction in real time with a sufficient spatial resolution. We took advantage that the format of our PCR chip is already compatible with 2D imaging. With the optic module we designed we were able to image the PCR reaction taking place within this chip in real time with a spatial resolution better than 30 µm. The resulting innovative design was described in a patent that was filed as a PCT under the reference WO 2018/114625 A1.
We then did the assessment of the performance of the whole process, using laboratory samples representatives of ocular samples.
Final results
The resulting innovative design was described in a patent that was filed as a PCT under the reference WO 2018/114625 A1.
With our technology, we were able to detect the presence of as few as 500 bacteria in a liquid sample in less than 15 minutes. This technology will thus help identifying fastly the kind of bacteria involved in the disease and will thus improve patient care.