Along with the expansion of microfluidics into many areas of applications such as sensors, microreactors and analytical tools, many other materials besides poly(dimethylsiloxane) (PDMS) have been suggested such as poly(imide) (PI) or poly(ethylene terephthalate) (PET). However, the sealing methods for these materials are not reliable in that many of the methods are specific to the substrate materials. Here, we report a novel robust doubly cross-linked nano-adhesive (DCNA) for bonding of various heterogeneous substrates. By depositing 200 nm of epoxy-containing polymer, poly(glycidyl methacrylate), via initiated chemical vapour deposition (iCVD) onto various substrates and cross-linking them with ethylenediamine, a strong adhesion was obtained between the substrates. This adhesive system was not only able to bond various difficult-to-bond substrates, such as PET or PI, but it could also preserve the complicated morphology of the surfaces owing to the thin nature of the DCNA system. The DCNA allowed fabrication of microfluidic devices using both rigid substrates, such as silicon wafer and glass, and flexible substrates, such as PDMS, PET and PI. The burst pressure of the devices sealed with DCNA exceeded 2.5 MPa, with a maximum burst pressure of 11.7 MPa. Furthermore, the adhesive system demonstrated an exceptional chemical and thermal resistance. The adhesion strength of the adhesive sandwiched between glass substrates remained the same even after a 10 day exposure to strong organic solvents such as toluene, acetone, and tetrahydrofuran (THF). Also, exposure to 200 °C for 15 h was not able to damage the adhesion strength. Using the high adhesive strength and flexibility of DCNA, flexible microfluidic devices that can be completely folded or rolled without any delamination during the operation were fabricated. The DCNA bonding is highly versatile in the sealing of microfluidic systems, and is compatible with a wide selection of materials, including flexible and foldable substrates, even upon sealing few-μm-sized channels.