| Přispěvatelé: |
Individualité microbienne et infection - Microbial Individuality and Infection, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), This work was supported by: French Medical Research Foundation grant ING20160435202 (GM), French National Research Agency grant ANR-17-CE11-0007-01 (GM), French National Research Agency grant ANR-10-LABX-62-IBEID (GM), IMI 2 Joint Undertaking grant 853989, receiving support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and Global Alliance for TB Drug Development non-profit organization, Bill & Melinda Gates Foundation, University of Dundee (GM), Institut Pasteur core funding (GM), ANR-17-CE11-0007,PersisTB,Lutter contre l'épidémie mondiale de tuberculose: Exploiter la variation cellule à cellule afin d'entraver la persistance adaptative(2017), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 853989,H2020-JTI-IMI2-2018-15-two-stage,ERA4TB(2020) |
| Popis: |
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. |
