Traditional processes to manufacture micro-fluidic devices include standard lithography, electron beam writing and photo-patterning. These techniques are well established but most are limited to surface micro-fabrication. Laser micro-machining provides an alternative for microfabrication of devices. This paper presents Design of Experiment models for the fabrication of micro-channel structures with four different types of glass, soda-lime, fused-silica, borosilicate and quartz. A 1.5kW CO2 laser with 90 μm spot size was used to fabricate micro-channels on the surface of glass sheets. Power, P, pulse repetition frequency, PRF, and translation speed, U, were set as control parameters. The resulting geometry of the channel (depth and width) and transmission capabilities were measured and analyzed. A comparison of the results of this experimental testing with the four glass types showed that quartz and fused-silica glasses would have better channel topologies for chemical sensing applications.