Miniaturization and modularization are fast growing fields in chemical engineering in recent years. Fast and flexible production processes for microstructured devices are desirable to meet the requirements of rapid prototyping and flexible chip manufacturing. Reactive ion etching provides a structuring process which leads to a highly precise and anisotropic etching behavior. A new manufacturing process for polyimide-based microstructured devices with low surface roughness was developed and applied on reactor geometry for liquid-liquid two-phase-flow. The fabricated chip geometry is designed for creating droplets via flow focusing as the dispersed phase is incised by two continuous phase inlet streams. The droplets are created in the widening channel. In order to keep the pressure loss for the developed reactor geometry and the production time as small as possible, the manufacturing process was optimized with a view to minimize surface roughness and maximizing the etching rate by using Design of Experiments. The corresponding pressure drop was measured for flow rates from 0.05 ml min−1 to 0.5 ml min−1.