Laser-cut paper-based device for the detection of dengue non-structural NS1 protein and specific IgM in human samples
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The incidence of flavivirus infections has increased dramatically in recent decades in tropical and sub-tropical areas worldwide, affecting hundreds of millions of people each year. Dengue viruses are typically transmitted by mosquitoes and can cause a wide range of symptoms from flu-like fever to organ impairment and death. Although conventional diagnostic tests can provide early diagnosis of acute dengue infections, access to these tests is often limited in developing countries. Consequently, there is an urgent need to develop affordable, simple, rapid, and robust diagnostic tools that can be used at ‘Point of Care’ settings. Early diagnosis is crucial to improve patient management and reduce the risk of complications. In the present study, a novel laser-cut device made of glass-fiber paper was designed and tested for the detection of the dengue Non Structural 1 (NS1) viral protein and specific IgM in blood and plasma. The device, called PAD, was able to detect around 25 ng/mL of NS1 protein in various sample types in 8 minutes, following a few simple steps. The PAD was also able to detect specific IgM in human plasmas in less than 10 minutes. The PAD appears to have all the potential to assist health workers in early diagnosis of dengue fever or other tropical fevers caused by flaviviruses.
Authors wish to thank Marc Bossus, Celine Roesch, Michèle Guillote (Immunoassays department of bioMérieux) for antibody productions; Florence Bettworth, Blandine Le Levreur and Marie-Claire Cavaud (Immunoassays department of bioMérieux) for antibody purification and labeling. Special thanks to Maxime Combe and Fabien Fulmar for providing various raw materials. The final manuscript has been red and corrected by RWS life science, Lausane, CH.
All of the authors contributed to the study conception. AR and FF carried out the PAD design and manufacturing. GT, AR and FB performed research. FB, GT and AR wrote the manuscript. All of the authors analyzed data, read, corrected and approved the final manuscript. FB, PD, ILG and CR performed the study coordination and funding.
Compliance with ethical standards
This study was funded by BioMerieux SA and Agence Nationale de la Recherche et de la Technologie (G. Theillet’s grant CIFRE no 2015/0514).
Conflict of Interest
All the authors (except I. Leparc -Goffart) are employed by bioMerieux SA.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 2.Alcon S, Talarmin A, Debruyne M, Falconar A, Deubel V, Flamand M (2002) Enzyme-linked immunosorbent assay specific to Dengue virus type 1 nonstructural protein NS1 reveals circulation of the antigen in the blood during the acute phase of disease in patients experiencing primary or secondary infections. J Clin Microbiol 40:376–381CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Granger D, Leo YS, Lee LK, Theel ES Serodiagnosis of dengue virus infection using commercially available antibody and NS1 antigen ELISAsGoogle Scholar
- 35.Saswat T, Kumar A, Kumar S, Mamidi P, Muduli S, Debata NK, Pal NS, Pratheek BM, Chattopadhyay S, Chattopadhyay S (2015) High rates of co-infection of Dengue and Chikungunya virus in Odisha and Maharashtra, India during 2013. Infect Genet Evol J Mol Epidemiol Evol Genet Infect Dis 35:134–141Google Scholar
- 43.Steinhagen K, Probst C, Radzimski C, Schmidt-Chanasit J, Emmerich P, van EM, Schinkel J, Grobusch MP, Goorhuis A, Warnecke JM, Lattwein E, Komorowski L, Deerberg A, Saschenbrecker S, Stocker W, Schlumberger W (2016) Serodiagnosis of Zika virus (ZIKV) infections by a novel NS1-based ELISA devoid of cross-reactivity with dengue virus antibodies: a multicohort study of assay performance, 2015 to 2016. In: Euro surveillance: bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. https://doi.org/10.2807/1560-7917.ES.2016.21.50.30426
- 44.Tsai WY, Youn HH, Brites C, Tsai JJ, Tyson J, Pedroso C, Drexler JF, Stone M, Simmons G, Busch MP, Lanteri M, Stramer SL, Balmaseda A, Harris E, Wang WK (2017) Distinguishing secondary dengue virus infection from Zika virus infection with previous dengue by a combination of 3 simple serological tests. Clin Infect Dis 65:1829–1836CrossRefPubMedGoogle Scholar