Abstract: Method of manufacturing a microfluidic device comprising an inflexible polymeric substrate, one or more flexible polymeric substrate(s) and one or more microfluidic channel(s) enclosed between the substrates comprising a) providing a master form including rim protrusions defining an enveloping shape for the microfluidic channel(s) to be produced and enclosed between the substrates, b) placing one or more flexible polymeric substrate(s) each having a layer thickness of less than 800 ?m onto the master form, wherein one flexible polymeric substrate is in contact with the rim protrusions of the master form, c) placing an inflexible polymeric substrate with a layer thickness of equal to or more than 800 ?m onto the flexible polymeric substrate(s), and d) ultrasonically welding the one or more flexible polymeric substrate(s) and the inflexible polymeric substrate at the rim protrusions. By the inventive method microfluidic devices via ultrasonic welding without using energy directors can be obtained.