High-throughput single cell multidrug resistance analysis with multifunctional gradients-customizing microfluidic device

Multidrug resistance analysis represents a great challenge in cancer chemotherapy, drug development and pathological study. In this paper, multifunctional gradients-customizing microfluidic devices were developed for high-throughput single-cell multidrug resistance (MDR) analysis. The gradient profile was determined by the lengths of the distribution microchannels regardless of flow rates and pressure, which provided good stability and remarkably reduced redundancy of microfluidic architecture. The drug of gradient concentrations consecutively stimulate upon the cells in the downstreaming cell cultivation chamber. Time-dependent drug efflux kinetics of HepG2 cells were firstly investigated on our device using both the different-single-cell and the same-single-cell strategies. Furthermore, hepatic polarized HepG2 cells, which collected the secreted cholephilic substances in the apical vacuoles, were used as model to investigate the inhibition of MDR-associated protein with secretion inhibitor cyclosporine A of varied concentrations on single organelle level. Finally, a high-throughput drug screening experiment was conducted to examine both the chemo-sensitizing effect and the cytotoxity of the potential chemo-sensitizing agents. Conclusively, the results confirmed that our method was a highly efficient way to analyze multidrug resistance (MDR) at single-cell or even single-organelle level with advantages of high-throughput, flexibility, stability and low sample consumption.

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