A new circular-shape microfluidic network for generating gradients of multiple substances -design, demonstration and application

In this paper we aimed to figure out an effective platform for generating gradients of three or more substances and designed an original microfluidic network with circular shape controlling diffusive mixing of fluids. The generated gradients were calculated by a theoretical treatment using a CFD model and verified in the fluorescence experiments, certifying that they maintained a spatially and temporally stable linearity under the flow rate of 2 mu L/min. Finally, we applied the platform for generating gradients on study of the drug synergism. 5-fluorouracil and tanshinone IIA (Tan IIA) were used for biological applicability via stimulation of single or multidrug combination on A549 cells. Consistent with the traditional MTT assays, both of the two drugs inhibited the cancer cell growth effectively and the IC50 values of 5-fluorouracil and Tan IIA were 20.37 and 44.78 mg/L, while their combination was superior. This microfluidic network is a simple and reliable platform as a gradient generator for investigating the possible combination of multiple drug candidates and their optimum dosage.