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, the anti-schistosomicidal activity of molecules is usually evaluated by 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..., Microfluidic chip design
The geometrical features of the chips were designed by using COMSOL MULTIPHYSICS (Comsol AB, Stockholm, Sweden) to obtain a single microfluidic chamber, the fluid flow was calculated with the microfluidic module using laminar flow conditions assuming a very low Reynolds number (see Supplementary Table S3). The 3D FEM model is made of about 2 106 192 degrees of freedom using the predefined ‘extra fine’ mesh refinement. In the fluid flow model, non-slip initial condition was imposed to all surfaces corresponding to a solid/liquid interface. A fixed flow rate (between 0.05 and 3.4 ml.min-1) was used for the inlet and a fixed pressure (P = 0 Pa) for the outlet. The equations were solved in 900 s requiring 7.5 Go using an Intel Core i7-7500U CPU cadenced at 2.7 Ghz with 16 Go RAM configuration.
Analysis of viability in various media and sera
The viability of the worms was evaluated by observing the parasites with a macroscope (OPTIKA, SZ6745TR, Italy) and using a vis..., Programs required to visualize and analyse data:
Videos: mp4 file player
Tables: Excel 2019 or any software compatible .xlsx file
Scripts: Rstudio (1.1463)
Fluidic simulations: Comsol Multiphysics (v.5.6)
IC50 data and graphs: SigmaPlot (v.15)