A rapid prototyping method for the fabrication of microstructures in polymer substrates has been developed, using a combination of laser direct-write patterning of silicon membrane contact masks and vacuum-ultraviolet (VUV) pulsed laser ablation. The process allows the flexible and rapid prototyping of microreactors and microchannel systems with submicrometer resolution. Thanks to the high photon energy of the VUV (7.9 eV) irradiation, PMMA and also other polymers can be ablated without leaving behind carbonated and/or fluorescent surfaces. Fluences of ≅ 100 mJ/cm2 lead to etch rates of ≅ 140 nm/pulse and result in very smooth surfaces with a roughness in the nanometer range on a micrometer lateral scale. The structured substrates are sealed with a PMMA foil by means of a newly developed low temperature technique without adhesives.