Gradient-driven microfluidic framework for the screening of ratiometric drug combinations towards precision oncology in paediatric leukaemia
Cet article présente un dispositif microfluidique permettant d'évaluer la synergie ainsi que l'efficacité de plusieurs médicaments et de prédire la réponse thérapeutique chez les patients atteints d'une leucémie lymphoblastique aiguë à haut risque
Improving outcomes for high-risk acute lymphoblastic leukaemia (ALL) patients requires increasingly personalized treatment strategies that leverage molecular and omics-based assays as well as functional screens. However, to date, only a few of these approaches are clinically actionable and easily adopted in clinical settings. To that end, we report a combination drug screening assay (GradientScreen) that correlates with clinical outcomes using standard paediatric ALL treatment protocols. This assay uses a microfluidic device to generate overlapping drug gradients and implements an analysis framework that characterizes drug synergy and efficacy in a ratiometric manner. Using partial least squares regression, we show that our combination response metrics correlate with both minimal residual disease (MRD) following initiation of treatment and later clinical end-points. Here, we further demonstrate that this system could be used to evaluate response to experimental therapeutic regimens in patients who did not respond to standard treatment. This assay can serve as a research-enabling tool for the field, with potential to integrate into clinical pathology workflows to identify difficult-to-treat ALL patients and screen for alternative treatment strategies at diagnosis.
Nature Biomedical Engineering , résumé, 2026