A new method for sealing PMMA-based microfluidic devices utilizing low azeotropic solvent, named DE-20, is developed. The bonding process can be achieved in 7 min at room temperature and can successfully bond microchannels as small as 40 μm in width without clogging. Results show the bonding strength and the increased roughness of the surface after the bonding process are 3.8 ±0.31 MPa (n = 8) and 10 nm respectively. The achieved bonding strength is 17-fold larger than the conventional thermal bonding. Furthermore, the proposed method can seal a 3-mm wide microfluidic channel without collapsing the channels since no heating process is required in the bonding process. The bonding performance is confirmed by using a zigzag type passive microfluidic mixer. Results present a high mixing efficiency can be achieved under a high driven pressure. More importantly, no leakage is observed under such high pressure.