Recent advances in simulation capabilities coupled with advanced manufacturing can be leveraged to create highly efficient compact reactors with low emissions, low cost, high reliability, and high flexibility for energy conversion. This type of reactor is especially important for conversion of bio-mass, a storable, renewable and fast-growing energy source, considering the distributed nature of raw material and cost of biomass collection and transportation. To achieve this goal, it is critical to developing new process technologies that are significantly more efficient than traditional processes for which the added manufacture provides a fast way of realization and evaluation. Based upon the flagship MFiX multiphase computational fluid dynamic software suite, NETL has developed an Optimization Toolset to facilitate the CFD simulation based reactor design and optimization, and process intensification. This technical report presents the recent development and application of the Optimization Toolset and the framework for process optimization of particle separation in batch and continuous processes. In these processes, a fluidized bed reactor under proper operating condition was used to separate particles of different physical properties. MFiX-DEM simulations were conducted for a batch system to simulate the process covering a wide range of superficial gas velocities from which the optimal operational parameter can be determined through analyzing the system response. After successful demonstration of the framework, a continuous system for particle separation was designed based on CFD simulations. Similar optimization exercises were conducted for the continuous particle separation considering multiple operating parameters. The design was then fabricated in the laboratory through 3D printing for testing. The particle separation performance was carefully measured through high-speed video for particle tracking. Quantitative comparison between numerical results and experimental measurements were conducted for confirmation and validation.