Fluid flow devices have been algorithmically designed through optimization methods, and this task is relatively complex for flow machines. Particularly, one recent development is the use of the topology optimization method for this task, which is capable of achieving possibly non-intuitive geometries and even auxiliary structures, such as splitter blades without ever imposing them as a condition for the design. The design of the rotating part of the rotor has already been previously considered. However, in the presence of stationary parts surrounding the rotor, such as diffuser blades, the fluid flow behavior may change, meaning that it may be interesting to consider this different dynamic in the design. One possible approach for this is the Multiple Reference Frame approach, which considers the fluid flow dynamics inside the rotor being computed in the rotating reference frame, whilst the fluid flow dynamics outside the rotor is being computed in the stationary reference frame. In particular, this implies the need for some changes in the topology optimization formulation, also impacting the choice of objective functions. Therefore, here the topology optimization method is formulated for the Multiple Reference Frame approach, and a new combination for the multi-objective function is proposed. The discrete design variable configuration from the Topology Optimization of Binary Structures approach is adopted with some adjustments to account for the Multiple Reference Frame approach. The fluid flow is chosen to be laminar or turbulent. Numerical examples are presented in 2D for the rotor-diffuser in order to consider some aspects that affect the overall topology optimization design.