Microfluidics enables the manipulation of liquids at the picoliter (or less) scale and proves to be superior over conventional bulk methods for mixing and reaction. The ability of microfluidic systems to rapidly mix reagents to provide homogeneous reaction environments, to vary the reaction conditions continuously, and to even allow reagent addition during the progress of a reaction, makes it attractive for nanoparticle synthesis. However, the low production rate limits its practical applications. Different approaches have been developed to achieve higher yield but most of them rely on the design of complex devices. Herein, we investigated fundamentally the throughput capacities of hydrodynamic flow focusing microfluidics for producing poly (lactide-co-glycolide)-b-polyethylene glycol (PLGA-PEG) nanoparticles with uniform size ranging from 50-150 nm. The effects of different factors of microfluidic design, including channel width, channel depth, channel structure and flow rate ratios, on particle size, size distribution, and production throughput were studied and compared. In contrast to the widely used microfluidic device which has a production rate of 1.8 mg/h, our simple approach is capable of increasing the production rate of nanoparticles by more than two orders of magnitude up to 288 mg/h using a single simple device. This study demonstrated the potentials of using simple 2D microfluidic devices for largescale production of polymeric nanoparticles that could eliminate the need for designing and fabricating complex microfluidic devices. (C) 2017 Elsevier Ltd. All rights reserved.