The current study describes the development of a disposable paper-based microfluidic system, which unlike its predecessors that are only capable of processing a small amount of fluid, can continuously process the fluid at a high flow rate of up to 1.5 mL/min. The fabrication procedure was clean-room-free and robust, involving the use of a CO2 laser to engrave the microchannels on a paper substrate, followed by alkenyl ketene dimer treatment to hydrophobize the paper and lamination. The microchannel down to a minimum depth of ∼80 μm with an average roughness of ∼8 μm was engraved on the substrate. As a proof of concept, the applicability of this system to enrich the microparticles based on the inertial focusing mechanism was tested. This new generation of paper-based microfluidic system can be potentially used for the diagnostic applications where the analyte is low in quantity and processing a large volume of fluid sample is required.