Model-based design of a microfluidic pervaporation device for intensified VOC separation

• Microfluidic pervaporation system enables efficient VOC removal in flow. • 3D-printed design allows rapid prototyping with integrated PDMS membrane. • Predictive model requires no fitting and guides system optimization. • Acetone and acetophenone removed under biologically relevant conditions. • Time-scale analysis reveals membrane diffusion as key rate limitation. Downstream separation remains a major bottleneck in the development of continuous bioprocesses, particularly in the removal of volatile organic by-products such as acetone and acetophenone. Here we present a novel microfluidic pervaporation device developed for efficient VOC extraction from aqueous media under steady-state conditions. The system integrates a 3D-printed channel architecture with a PDMS membrane and leverages a first-principles mathematical model that does not require customised parameters. Experimental validation with acetone–water and acetophenone-buffer mixtures demonstrated excellent separation performance with a separation efficiency of over 97 %. A detailed time scale analysis confirmed that membrane diffusion is the dominant transport resistance, guiding optimization strategies toward geometric design and membrane material selection. The predictive power of the developed mathematical model enabled a rational tuning of geometry and flow conditions, while the modular fabrication approach ensures adaptability and scalability. This work highlights the potential of combining microfluidics, modeling and additive manufacturing to intensify separations and enable seamless integration into upstream biocatalytic or pharmaceutical production systems.