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Dynamics of drug response in single mycobacterial cells by microfluidic dose-response assay

Abstract : Preclinical analysis of drug efficacy is critical for drug development. However, conventional bulk-cell assays statically assess the mean population behavior, lacking resolution on drugescaping cells. Inaccurate estimation of efficacy can lead to overestimation of compounds, whose efficacy will not be confirmed in the clinic, or lead to rejection of valuable candidates. Time-lapse microfluidic microscopy is a powerful approach to characterize drugs at high spatiotemporal resolution, but hard to apply on a large scale. Here we report the development of a microfluidic platform based on a pneumatic operating principle, which is scalable and compatible with long-term live-cell imaging and with simultaneous analysis of different drug concentrations. We tested the platform with mycobacterial cells, including the tubercular pathogen, providing the first proof of concept of a single-cell dose-response assay. This dynamic in-vitro model will prove useful to probe the fate of drug-stressed cells, providing improved predictions of drug efficacy in the clinic.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03697438
Contributor : Giulia MANINA Connect in order to contact the contributor
Submitted on : Thursday, June 16, 2022 - 7:15:40 PM
Last modification on : Friday, August 5, 2022 - 12:03:02 PM

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2022.04.03.486879v1.full.pdf
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Maxime Mistretta, Nicolas Gangneux, Giulia Manina. Dynamics of drug response in single mycobacterial cells by microfluidic dose-response assay. 2022. ⟨pasteur-03697438⟩

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