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Lab on a chip (LOC) platform for drug screening against the intracellular forms of Trypanosoma cruzi

Abstract:

Trypanosoma cruzi is the etiological agent of Chagas disease, endemic in Latin America with recent spreading to non-endemic areas due to human migration. The low efficacy and substantial prevalence of side effects of the approved medications benznidazole (BZN) and nifurtimox observed mainly during the chronic phase of Chagas disease, when most patients receive their diagnosis, demonstrate the need to find new therapeutic compounds to address this neglected global health disease. Here, we developed a platform for screening the antitrypanosomal activity of compounds over intracellular amastigotes using microfluidics, LOC devices, and advanced image analysis algorithms. This platform allows the simultaneous testing of six different concentrations of a compound and the automatic and high-precision processing of the images obtained during the experimental phase, providing quickly and easily a multitude of statistical data for the screening of new drugs. To assess the developed platform, we analyzed the effects of BZN as a reference drug and compared the dose–response curves with those obtained with a flow cytometry-based method, obtaining similar IC50 results. Furthermore, a collection of compounds obtained by chemical synthesis from a combinatorial library was tested over intracellular amastigotes in infected Vero cells.