In this study, the fabrication of microfluidic chips through the bonding of poly (methyl methacrylate) (PMMA) boards featuring designed patterns to create a three-dimensional sandwich structure with embedded microchannels was explored. A key focus was optimization of the interface quality of bonded PMMA pairs by adjusting the solvent, such as such as acetone, alcohol, and their mixture. Annealing was conducted below 50 °C to leverage the advantages of low-temperature bonding. Because of the differences in the chemical reactivity of PMMA toward acetone, alcohol, and their combinations, the resulting defect densities at the bonding interfaces differed significantly under low-temperature annealing conditions. To achieve the optimal sealing integrity, bonding pressures of 30 N, 40 N, and 50 N were evaluated. The interface was analyzed through microstructural examination via optical microscopy and stress measurements were determined using digital photoelasticity, while the bonding strength was assessed through tensile testing.