Mass production of highly monodisperse polymeric nanoparticles by parallel flow focusing system

Nanoparticles can be prepared through nanoprecipitation by mixing polymers dissolved in organic solvents with anti-solvents. However, due to the inability to precisely control the mixing processes during the synthesis of polymeric nanoparticles, its application is limited by a lack of homogeneous physicochemical properties. Here, we report that this obstacle can be overcome through rapid and controlled mixing by parallel flow focusing outside the microfluidic channels. Using the nanoprecipitation of methoxyl poly-(ethylene glycol)-poly-(lactic-co-glycolic acid) (MPEG-PLGA) block copolymers as an example, we prove that our parallel flow focusing method is a robust and predictable approach to synthesize highly monodisperse polymeric nanoparticles, and demonstrate that it improves the production speed of nanoparticles by an order of magnitude or more compared with previous microfluidic systems. Possible aggregation on the surface of PDMS wall and clogging of microchannels reported previously were avoided in the synthesis process of our method. This work is a typical application combining the advantages of microfluidics with nanoparticle technologies, suggesting that microfluidics may find applications in the development and mass production of polymeric nanoparticles with high monodispersity in large-scale industrial production field.