Microfluidic concentration-on-demand combinatorial dilutions

Abstract

We present a microfluidic network-based combinatorial dilution device to generate on-demand combinatorial dilutions of all input samples in the range of a 3D simplex-centroid. The device consists of an initial concentration control module and a combinatorial dilution module. In the initial concentration control module, the concept of using a single common channel has been incorporated to generate desirable concentrations of each sample, diluted independently in response to variable input flow. Then, the diluted samples flow into the combinatorial dilution module to generate a full set of seven combinations from the three samples. First, we investigated the performance of the initial concentration controller by computational simulation (CFD-ACE(+)). The simulated output concentrations are extremely close to the expected theoretical values. Further, a PDMS-based initial concentration controller was fabricated, and its linearity and independency were tested with fluorescent dye. Then, we designed, simulated, and tested a combinatorial dilution device integrated with the initial concentration controller. Finally, as proof-of-concept, we performed a simple combinatorial cytotoxicity test with three drugs (Mitomycin C, Doxorubicin, and 5-FU) for MCF-7 cancer cells.