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Updated: Apr 1, 2026
Generation of Heterogeneous Drug Gradients Across Cancer Populations on a Microfluidic Evolution Accelerator for Real-Time Observation
Published on: September 19, 2019
Phenotypic drug profiling in droplet microfluidics for better targeting of drug-resistant tumors
S Sarkar1, N Cohen1, P Sabhachandani1
1Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, 02115 MA, USA. t.konry@neu.edu.
Abstract:
Acquired drug resistance is a key factor in the failure of chemotherapy. Due to intratumoral heterogeneity, cancer cells depict variations in intracellular drug uptake and efflux at the single cell level, which may not be detectable in bulk assays. In this study we present a droplet microfluidics-based approach to assess the dynamics of drug uptake, efflux and cytotoxicity in drug-sensitive and drug-resistant breast cancer cells. An integrated droplet generation and docking microarray was utilized to encapsulate single cells as well as homotypic cell aggregates. Drug-sensitive cells showed greater death in the presence or absence of Doxorubicin (Dox) compared to the drug-resistant cells. We observed heterogeneous Dox uptake in individual drug-sensitive cells while the drug-resistant cells showed uniformly low uptake and retention. Dox-resistant cells were classified into distinct subsets based on their efflux properties. Cells that showed longer retention of extracellular reagents also demonstrated maximal death. We further observed homotypic fusion of both cell types in droplets, which resulted in increased cell survival in the presence of high doses of Dox. Our results establish the applicability of this microfluidic platform for quantitative drug screening in single cells and multicellular interactions.
Insights
This study introduces a droplet microfluidics method to analyze drug resistance in single breast cancer cells. The platform reveals how drug uptake, efflux, and cell interactions impact chemotherapy effectiveness.
Area of Science:
- Oncology
- Biotechnology
- Cell Biology
Background:
- Acquired drug resistance is a major challenge in chemotherapy, often driven by intratumoral heterogeneity.
- Single-cell variations in drug uptake and efflux can be missed by bulk assays.
Purpose of the Study:
- To develop and apply a droplet microfluidics platform for assessing drug dynamics at the single-cell level.
- To investigate drug uptake, efflux, and cytotoxicity in drug-sensitive and drug-resistant breast cancer cells.
- To analyze multicellular interactions and their role in drug resistance.
Main Methods:
- Utilized a droplet microfluidics system with integrated droplet generation and docking microarray.
- Encapsulated single cells and homotypic cell aggregates for analysis.
- Quantified Doxorubicin (Dox) uptake, efflux, and cell death in sensitive and resistant cells.
Main Results:
- Drug-sensitive cells exhibited higher Dox-induced death than resistant cells.
- Observed heterogeneous Dox uptake in sensitive cells and uniform low uptake in resistant cells.
- Identified distinct subsets of resistant cells based on efflux properties and found increased survival through homotypic fusion.
Conclusions:
- The microfluidic platform enables quantitative drug screening at the single-cell and multicellular levels.
- Demonstrated the role of single-cell heterogeneity and cell-cell interactions in acquired drug resistance.
- Provides a novel tool for understanding and potentially overcoming chemotherapy resistance.
