This is a guest blog post written by Dr. Konstantinos Mitsakakis, Project Coordinator
"Disc"...because it is like a CD.
"Gnosis" (Greek [γνώσις = knowledge])...because it allows to know what a patient suffers from.
"Discognosis" is about diagnosing infectious diseases at the point-of-care, in resource-limited areas, in a fully-automated way, and within less than 1 hour from sample collection to result.
In a village in Africa a 4-year-old boy cries in the middle of the night due to suddenly elevated fever, no other symptom.
The mother runs with her son to the rural health post. The doctor uses one strip test (Rapid Diagnostic Test - RDT) to check for malaria - the first reason one would naturally think of for the fever. Waiting 20 minutes…the result comes out and...negative!
The doctor feels the pressure: should he give an antimalarial drug (even though he knows it is not malaria) just to calm down the mother? Should he give an antibiotic? But how can he know if it is a bacterial infection (typhoid fever for example)? And what if it is dengue? That’s a virus, the antibiotic won’t help.
Next option? The nearest central hospital is some hundreds kilometres away...and the blood culture that can be done there takes up to 3 days to give a result.
(A) Democratic Republic of Congo (DRC). Nyankunde Medical Center at Bunia. (B) Patients’ rooms. (C) Investigation for malaria through microscopy. (D) Rapid Diagnostic Tests (RDTs) and microscope slides for blood smear tests for malaria. Copyright: Dr Samuel LEMERY NIGO/CME-Nyankunde, Bunia, DR Congo
Did you identify the challenges in the scenario?
- The infection may be caused by bacteria, viruses, or parasites, which all need a different type of treatment. However, fever as symptom, alone, is not enough to differentiate between the causes. Only molecular-based diagnosis (DNA/RNA and protein marker) can reveal the identity of the pathogen.
- In rural areas there are often no other available tools to detect multiple possible diseases, other than the cheap (and sometimes not sensitive/specific enough) RDTs, which are addressing only one infection (primarily malaria).
- Being far away from hospitals that can provide more advanced facilities, the patient needs diagnosis at the point-of-care.
- In lack of appropriate diagnosis and under the pressure of giving an answer, the doctor may provide a totally wrong treatment: not only will it not help the child, but it will increase its resistance to antimicrobial drugs.
(A) Senegal, field station in Kedougou, 700km east of capital Dakar. (B) Electricity source from vehicle battery. (C,D) Available facilities. Copyright:Dr. Manfred Weidmann
The response to the challenges
In 2012 the European Commission contributed with 3 Million Euro funding (FP7 ICT Programme) to the implementation of the Discognosis project to address scenarios like the one mentioned above, which are reality on a daily basis, primarily in Africa, but also in South-East Asia and Latin America (typically around the equator) where tropical infectious diseases prevail and manifest themselves with only symptom…the acute fever.
The 7-member consortium is committed to develop a diagnostic tool that will enable the doctor to specifically diagnose infectious diseases of different possible pathogens at the point-of-care, in a fully-automated way, and within less than 1 hour from sample collection to result.
Multidisciplinary teams of engineers, biologists, (bio)chemists, materials scientists and medical doctors have joined their forces towards this scope.
The tools to save a life: two drops of blood and a CD!
- Technically, the core of the diagnostic tool is a microfluidic platform, the Labdisk, which uses centrifugal forces, in combination with geometric, hydrophobic and (thermo)pneumatic valves and mixing principles, in order to handle liquids.
- 50µl of blood, collected after a finger-prick, contains the pathogens responsible for the disease. The pathogens' DNA/RNA must be identified but first it has to be extracted from the microorganisms and purified. These functions, which would typically need a microbiology lab, are performed in situ on the LabDisk by means of integrated pre-stored chemical liquids (buffers in "stickpacks") and magnetic beads.
- When the DNA/RNA of the pathogens is purified, it is distributed to reaction chambers where it is amplified by means of "molecular amplifiers" (the primers).
- Those who are familiar with the PCR (Polymerase Chain Reaction)...there is good news: no more thermocycling, but isothermal conditions (LAMP) are enough to amplify the DNA/RNA. Why is it important? The amplification signal (fluorescence) may come as fast as 15 minutes, in contrast to hours for PCR.
- And who handles the LabDisk? Just as a CD needs a CD Player, the LabDisk needs a "LabDisk Player", which is a portable device (up to 2 kg) with pre-stored frequency protocols that the end-user only needs to load and press "Start". Remote handling is also possible.
Left: Microfluidic “unit operations” are interfaced to combine several functions for “sample-to-answer” analysis. Right: The disc is made of flexible polymer foils, structured by means of microthermoforming. Copyright:IMTEK & Hahn-Schickard
Is the LabDisk suitable only for developing countries and tropical diseases? What about Europe?
The answer is in two words: "universality" and "adaptability".
The LabDisk has been designed in a modular way so as to easily adapt to:
- Nature of pathogens (parasites, bacteria, viruses,...)
- Number of targets (2, 3,...10,...)
- Sample matrix (whole blood, saliva, nasopharyngeal swab, sputum, urine,...)
Thus, global health issues can be addressed with the LabDisk, such as sexually transmitted diseases, oral infections, respiratory tract infections, antibiotic resistance, mother and child/neonatal care, etc.
Even food quality and environmental monitoring are feasible with the LabDisk.
Officially, October 2015 is the end of the project. However, due to the large health and socioeconomic impact, there is a big motivation for follow-up.
The first step has already been done: a collaboration was formed with Life Assay Diagnostics (Pty) Ltd, a Cape Town based Public-Private Partnership and point-of-care manufacturer. Starting from May 2015 and running for a 3-year period, the consortium will be funded by Anglo-American and SHIP/MRC, to develop a nucleic-acid-based disc that will detect viral versus bacterial pneumonia in African children.
Next steps include activities such as: clinical trials, electricity-independent operation of the LabDisk Player, higher diagnostic throughput (several patients monitored simultaneously), connection with central database and disease management systems. Funding for these is sought in public as well as private sources.
We welcome comments, instructions, suggestions, and opinions and we invite:
- curious followers to visit us in our website and give us their comments on how they see the potential of the LabDisk as a diagnostic tool
- open public to watch a video produced by the European Commission, a comprehensive technical presentation given by the project coordinator and two interviews regarding the necessity of point-of-care diagnosis, given by:
- Mr. Maurice Mutro Nigo, Dean of Institut Supérieur des Techniques Médicales, Nyankunde, Bunia, Democratic Republic of Congo (in French)
- Dr. Kelemu Desta, Feya Hospital, Sheshemane, Southern Ethiopia (in English)
- potential end-users and stakeholders (in Africa but also other areas) to advise us with their needs and help us improve our platform
A take-home exercise for our readers:
- Consider what would be for YOU the most important application and let us know, to see if we can handle it on the LabDisk!
- Let us know your experience with potential funding sources and investors for diagnostics in Low- and Middle-Income Countries (LMICs).
Dr. Konstantinos Mitsakakis, Project Coordinator
+49 761 203 73252 (office)
+49 15 22 29 28 510 (mobile)