In this paper, we describe a novel technique to bond a poly(dimethylsiloxane) (PDMS) microfluidic device onto various thermoplastic films such as polyimide (PI), polyethylene naphthalate (PEN), and polyethylene terephthalate (PET) using (3-mercaptopropyl)trimethoxysilane (MPS) silane reagent. To our knowledge this is the first reported application of MPS to formulate the PDMS-polymer bonding. For the development of such devices, first, the polymers (PI, PEN, and PET) were hydrolyzed by potassium hydroxide (KOH) to generate hydrophilic groups on the polymer surface. This was followed by polymer immersion in MPS (0.3 M) solution which required a short incubation time at room temperature. Finally, a post-treatment by oxygen plasma was made to substitute the propyl-thiol chain with hydroxyl groups by cleaving the terminal groups on the MPS treated polymers. This created the required silanol groups (Si-OH) for PDMS adhesion, where an irreversible bond was formed without any pressure or high temperatures to initiate bonding. The polymer film surfaces were successfully modified by MPS and this was confirmed by surface characterization using contact angle measurement (CAM) and X-ray photoelectron spectroscopy (XPS) analysis. The PDMS-polymer bonding was observed by injection of a dye, and the liquid circulated inside the microchannel of the microfluidic device without any leakage. The device was also tested for longevity and the liquid remained inside the microchannel for one month without any noticeable deterioration. © 2013 Elsevier B.V. All rights reserved.