Design and scale-up of a superb micromixer with fan-shaped obstacles for synthesis of Dolutegravir intermediate

Abstract

Micromixer have received significant attention for fluid mixing enhancement, while traditional micromixers have long mixing times and unstable mixing effects, which has discouraged their commercial development. Herein, we report a methodology for the design, optimization, scale-up fabrication and performance evaluation of a novel micromixer. A combination of Solidworks modeling, Design of Experiments and Computational Fluid Dynamics numerical simulation is used to optimize the configuration of micromixer. Analysis and optimization of experimental results from CFD numerical simulations revealed the channel width had the greatest impact on the performance of the micromixer. Based on the DoE results, two optimized micromixers (FOM-A and FOM-B) were developed and subjected to a series of numerical simulations at Reynolds number 0.5 ≤ Re ≤ 100. Both micromixers had a high mixing index (> 94%) and maintained a low pressure drop. Next, the FOM-B was scaled up and used as a microreactor for the synthesis of Dolutegravir intermediate. A 98% yield was obtained at a residence time of 4 min. Furthermore, the mass transfer performance of the FOM-B microreactor was measured and a mass transfer coefficient of 0.5012 s−1 was obtained at liquid flow rate of 20 mL/min, which is double the value of other commercial microreactors.