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A Microfluidic Chip for the Versatile Chemical Analysis of Single Cells
Published on: October 15, 2013
Microfluidic chip enables single-cell measurement for multidrug resistance in triple-negative breast cancer cells
Karan Parekh1,2, Hamideh Sharifi Noghabi1,2, Jose Alejandro Lopez3
1Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby V5A 1S6, Canada.
Abstract:
Aims: Triple-negative breast cancer patients are commonly treated with combination chemotherapy. Nonetheless, outcomes remain substandard with relapses being of a frequent occurrence. Among the several mechanisms that result in treatment failure, multidrug resistance, which is mediated by ATP-binding cassette proteins, is the most common. Regardless of the substantial studies conducted on the heterogeneity of cancer types, only a few assays can distinguish the variability in multidrug resistance activity between individual cells. We aim to develop a single-cell assay to study this. Methods: This experiment utilized a microfluidic chip to measure the drug accumulation in single breast cancer cells in order to understand the inhibition of drug efflux properties. Results: Selection of single cells, loading of drugs, and fluorescence measurement for intracellular drug accumulation were all conducted on a microfluidic chip. As a result, measurements of the accumulation of chemotherapeutic drugs (e.g., daunorubicin and paclitaxel) in single cells in the presence and absence of cyclosporine A were conducted. Parameters such as initial drug accumulation, signal saturation time, and fold-increase of drug with and without the presence cyclosporine A were also tested. Conclusion: The results display that drug accumulation in a single-cell greatly enhanced over its same-cell control because of inhibition by cyclosporine A. Furthermore, this experiment may provide a platform for future liquid biopsy studies to characterize the multidrug resistance activity at a single-cell level.
Insights
This study developed a microfluidic assay to measure drug resistance in individual triple-negative breast cancer cells. The assay successfully demonstrated how cyclosporine A inhibits drug efflux, enhancing chemotherapy effectiveness at the single-cell level.
Area of Science:
- Oncology
- Biochemistry
- Biotechnology
Background:
- Triple-negative breast cancer (TNBC) treatment often involves combination chemotherapy, but patient outcomes are frequently poor due to relapses.
- Multidrug resistance (MDR), mediated by ATP-binding cassette proteins, is a primary mechanism of chemotherapy failure in TNBC.
- Existing assays struggle to differentiate MDR variability among individual cancer cells, hindering personalized treatment strategies.
Purpose of the Study:
- To develop a novel single-cell assay for assessing multidrug resistance in breast cancer.
- To investigate the inhibition of drug efflux properties in individual cancer cells using a microfluidic platform.
- To quantify differences in chemotherapeutic drug accumulation within single cells with and without MDR modulators.
Main Methods:
- A microfluidic chip was employed to isolate and analyze single breast cancer cells.
- Chemotherapeutic drugs (daunorubicin, paclitaxel) were loaded into single cells, and intracellular accumulation was measured via fluorescence.
- Drug accumulation was assessed in the presence and absence of cyclosporine A, an inhibitor of ATP-binding cassette proteins.
Main Results:
- The microfluidic assay successfully enabled single-cell selection, drug loading, and fluorescence-based drug accumulation measurements.
- Significant enhancement of intracellular drug accumulation was observed in single cells treated with cyclosporine A compared to controls.
- Key parameters including initial drug uptake, signal saturation time, and fold-increase in drug accumulation were quantified.
Conclusions:
- Cyclosporine A effectively inhibits drug efflux in individual breast cancer cells, leading to increased intracellular drug accumulation.
- This microfluidic assay provides a valuable platform for characterizing single-cell multidrug resistance.
- The developed assay holds potential for future applications in liquid biopsies for personalized cancer therapy.
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