This paper discusses a flexible layout design method of passive micromixers based on the topology optimization of fluidic flows. Being different from the trial and error method, this method obtains the detailed layout of a passive micromixer according to the desired mixing performance by solving a topology optimization problem. Therefore, the dependence on the experience of the designer is weaken, when this method is used to design a passive micromixer with acceptable mixing performance. Several design disciplines for the passive micromixers are considered to demonstrate the flexibility of the layout design method for passive micromixers. These design disciplines include the approximation of the real 3D micromixer, the manufacturing feasibility, the spacial periodic design, and effects of the Péclet number and Reynolds number on the designs obtained by this layout design method. The capability of this design method is validated by several comparisons performed between the obtained layouts and the optimized designs in the recently published literatures, where the values of the mixing measurement is improved up to 40.4% for one cycle of the micromixer.