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Stable Graphene/gas/Cu bubbles are formed by the spontaneous oxidation at room conditions of the Cu substrates used as the catalyst agent in chemical vapor deposition growth of graphene. The non homogeneous copper oxidation produces discontinuous Cu2O films where atmospheric molecules get trapped by the impermeable graphene layer forming bubbles. Raman Interference effects are calculated both for graphene and Cu2O phonons in graphene/Cu2O/Cu system using the transfer matrix method finding that Cu2O thickness is limited to 20 nm and maximum Raman enhancement of graphene is 10. Nevertheless, enhancement values up to 60 are detected for micrometric graphene bubbles on copper which, according to the simulations, are 70 nm height. AFM measurements confirm the bubble dimensions and show that they are mechanically softer than graphene on copper. Consistently, the Raman characteristics of the graphene bubbles coincide with free standing undoped graphene with small strain, in the range 0-0.3%, while graphene on Cu2O presents hole doping and larger strain fields. The simulations indicate that interference Raman enhancement can reach values > 104 in graphene/dielectric/Aluminum trilayers (dielectric = gas, oxide or polymer). These systems are therefore interesting platforms for optical sensing where graphene is the adequate bio-compatible layer for metallic nanoparticles and molecules deposition. (C) 2016 Elsevier Ltd. All rights reserved.