In this study, we explore the potential of poly-dimethylsiloxane (PDMS)-based phase-shift lithography (PPSL) for the fabrication of nanofluidic devices. We establish that this technology, which was already shown to allow for the generation of 100 nm linear or punctual features over squared centimeter surfaces with conventional photolithography systems, is readily adequate to produce some of the most popular nanofluidic systems, namely nanochannels and nanoposts arrays. We also demonstrate that PPSL technology enables to generate PDMS and silicon nanofluidic systems. This technological achievement allows us to perform single DNA molecule manipulation experiments in PDMS and silicon nano-channels, and we observe an unexpectedly slow migration of DNA in PDMS devices, which is independent on salt or pH conditions. Our data in fact hint to the existence of an anomalous response of DNA in PDMS nanofluidic devices, which is likely associated to transient nonspecific interactions of DNA with PDMS walls. Overall, our work demonstrates the efficiency and the performances of PPSL for prototyping nanofluidic systems.