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A self-purifying microfluidic system for identifying drugs acting against adult schistosomes

The discovery of novel antihelmintic molecules to combat the development and spread of schistosomiasis, a disease caused by several Schistosoma flatworm species, mobilizes significant research efforts worldwide. With a limited number of biochemical assays for measuring the viability of adult worms,...

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Autores principales: Girod, Vincent, Houssier, Robin, Sahmer, Karin, Ghoris, Marie-José, Caby, Stéphanie, Melnyk, Oleg, Dissous, Colette, Senez, Vincent, Vicogne, Jérôme
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709518/
https://www.ncbi.nlm.nih.gov/pubmed/36465675
http://dx.doi.org/10.1098/rsos.220648
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author Girod, Vincent
Houssier, Robin
Sahmer, Karin
Ghoris, Marie-José
Caby, Stéphanie
Melnyk, Oleg
Dissous, Colette
Senez, Vincent
Vicogne, Jérôme
author_facet Girod, Vincent
Houssier, Robin
Sahmer, Karin
Ghoris, Marie-José
Caby, Stéphanie
Melnyk, Oleg
Dissous, Colette
Senez, Vincent
Vicogne, Jérôme
author_sort Girod, Vincent
collection PubMed
description The discovery of novel antihelmintic molecules to combat the development and spread of schistosomiasis, a disease caused by several Schistosoma flatworm species, mobilizes significant research efforts worldwide. With a limited number of biochemical assays for measuring the viability of adult worms, the antischistosomicidal activity of molecules is usually evaluated by a microscopic observation of worm mobility and/or integrity upon drug exposure. Even if these phenotypical assays enable multiple parameters analysis, they are often conducted during several days and need to be associated with image-based analysis to minimized subjectivity. We describe here a self-purifying microfluidic system enabling the selection of healthy adult worms and the identification of molecules acting instantly on the parasite. The worms are assayed in a dynamic environment that eliminates unhealthy worms that cannot attach firmly to the chip walls prior to being exposed to the drug. The detachment of the worms is also used as second step readout for identifying active compounds. We have validated this new fluidic screening approach using the two major antihelmintic drugs, praziquantel and artemisinin. The reported dynamic system is simple to produce and to parallelize. Importantly, it enables a quick and sensitive detection of antischistosomal compounds in no more than one hour.
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spelling pubmed-97095182022-12-02 A self-purifying microfluidic system for identifying drugs acting against adult schistosomes Girod, Vincent Houssier, Robin Sahmer, Karin Ghoris, Marie-José Caby, Stéphanie Melnyk, Oleg Dissous, Colette Senez, Vincent Vicogne, Jérôme R Soc Open Sci Engineering The discovery of novel antihelmintic molecules to combat the development and spread of schistosomiasis, a disease caused by several Schistosoma flatworm species, mobilizes significant research efforts worldwide. With a limited number of biochemical assays for measuring the viability of adult worms, the antischistosomicidal activity of molecules is usually evaluated by a microscopic observation of worm mobility and/or integrity upon drug exposure. Even if these phenotypical assays enable multiple parameters analysis, they are often conducted during several days and need to be associated with image-based analysis to minimized subjectivity. We describe here a self-purifying microfluidic system enabling the selection of healthy adult worms and the identification of molecules acting instantly on the parasite. The worms are assayed in a dynamic environment that eliminates unhealthy worms that cannot attach firmly to the chip walls prior to being exposed to the drug. The detachment of the worms is also used as second step readout for identifying active compounds. We have validated this new fluidic screening approach using the two major antihelmintic drugs, praziquantel and artemisinin. The reported dynamic system is simple to produce and to parallelize. Importantly, it enables a quick and sensitive detection of antischistosomal compounds in no more than one hour. The Royal Society 2022-11-30 /pmc/articles/PMC9709518/ /pubmed/36465675 http://dx.doi.org/10.1098/rsos.220648 Text en © 2022 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Engineering
Girod, Vincent
Houssier, Robin
Sahmer, Karin
Ghoris, Marie-José
Caby, Stéphanie
Melnyk, Oleg
Dissous, Colette
Senez, Vincent
Vicogne, Jérôme
A self-purifying microfluidic system for identifying drugs acting against adult schistosomes
title A self-purifying microfluidic system for identifying drugs acting against adult schistosomes
title_full A self-purifying microfluidic system for identifying drugs acting against adult schistosomes
title_fullStr A self-purifying microfluidic system for identifying drugs acting against adult schistosomes
title_full_unstemmed A self-purifying microfluidic system for identifying drugs acting against adult schistosomes
title_short A self-purifying microfluidic system for identifying drugs acting against adult schistosomes
title_sort self-purifying microfluidic system for identifying drugs acting against adult schistosomes
topic Engineering
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709518/
https://www.ncbi.nlm.nih.gov/pubmed/36465675
http://dx.doi.org/10.1098/rsos.220648
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