A hygienic environment for deep space exploration vehicles is vital to the health and functionality of crew members and the hardware. Previous missions have shown the pervasive problem of fine particulate including obscuring optical systems, scratching surfaces, and potential long-term health impacts. The current International Space Station (ISS) Environmental Control and Life Support (ECLS) system architecture employs traditional High-Efficiency Particulate Air (HEPA) filters to combat sub-micron particles, but these require frequent cleaning and ultimate replacement as particles embed within the filters and are unable to be removed. As missions return to planetary bodies, particulate becomes an even larger challenge as frequent migration of crew members to and from the vehicle will cause sub-micron lunar regolith particles to permeate throughout the pressurized cabin. Mainstream Engineering has been developing a cyclone-based system for sub-micron particulate capture that integrates with the central HVAC system. In this work, we present our computational fluid dynamics (CFD) model development, rapid prototyping process, and validated system design to achieve an in-place regenerable system with high-efficiency sub-micron particle collection and a comparable pressure drop to HEPA filters. The results of this work can aid in the reduction of consumable filtration devices and provide a longer service life than the filters that are currently in use on deep space exploration vehicles.