TY - JOUR
T1 - Lab on a chip (LOC) platform for drug screening against the intracellular forms of Trypanosoma cruzi
AU - Cadena, María Fernanda
AU - Rosero-Yanez, Gustavo
AU - Isa-Jara, Ramiro
AU - Belaunzarán, Maria Laura
AU - Giulianotti, Marc A.
AU - Pinilla, Clemencia
AU - Alba Soto, Catalina D.
AU - Perez, Maximiliano
AU - Lerner, Betiana
AU - Gimenez, Guadalupe
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/8
Y1 - 2024/8
N2 - 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.
AB - 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.
KW - Chagas disease
KW - Drug screening
KW - Image analysis
KW - Machine learning
KW - Microscopy
KW - Trypanosoma cruzi
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UR - http://www.scopus.com/inward/citedby.url?scp=85194923710&partnerID=8YFLogxK
U2 - 10.1016/j.microc.2024.110870
DO - 10.1016/j.microc.2024.110870
M3 - Article
AN - SCOPUS:85194923710
SN - 0026-265X
VL - 203
JO - Microchemical Journal
JF - Microchemical Journal
M1 - 110870
ER -