(752a) Controlled Synthesis of Nanoparticles Using a Coaxial Turbulent Jet Mixer

Nanoparticles have shown great promise for the diagnosis and therapy of major diseases such as cancer, cardiovascular, and infectious diseases. Use of microfluidics for synthesis of these nanoparticles has been of great interest due to controllability and reproducibility in their physicochemical properties. However, there are intrinsic limitations in conventional polydimethylsiloxane (PDMS) microfluidic systems for the synthesis of nanoparticles. First, only a handful of organic solvents are compatible with conventional PDMS microfluidic systems, which hinders PDMS microfluidic systems from serving as versatile platforms for synthesis of various types of nanoparticles. Second, productivity of microfluidic systems is lower than that of batch reactors due to low flow rates, making it challenging to produce large quantities of nanoparticles required for in vivo or clinical studies. Here, we report a novel coaxial turbulent jet mixer capable of synthesizing various types of functional nanoparticles with high production rates suitable for in vivo studies and clinical trials, while maintaining the controllability and reproducibility of PDMS microfluidic systems.

In the coaxial turbulent jet mixer, the inner flow stream containing raw materials is mixed with outer stream of non-solvent by turbulent jet flow for generation of uniform nanoparticles by rapid solvent exchange method called nanoprecipitation. The mixing of the inner and outer streams was visualized using phenolphthalein, a pH indicator. Two dimensionless parameters, flow velocity ratio and Reynolds number (Re), were used to classify the mixing behavior into flow regimes corresponding to laminar, transition, and turbulence regimes. Operating in the turbulence regime, the mixing time was tunable in the range of 1 - 40 ms by changing the Re. Nanoparticles obtained using the coaxial turbulent jet mixer at high Re (rapid mixing) were more homogeneous and smaller than those synthesized by bulk mixing, because the mixing time scale is more controllable and shorter than the characteristic aggregation time scale. Since the coaxial turbulent jet mixer is compatible with various organic solvents, it is versatile system where various types of nanoparticles including poly(lactide-co-glycolide)-b-polyethyleneglycol (PLGA-PEG) nanoparticles, iron oxide nanoparticles, lipid vesicles, and polystyrene nanoparticles can be made. In each case, the nanoparticle size decreased as mixing time decreased (i.e., as Re increased). Various functional agents including anticancer drug, insulin, and fluorescent dye could be loaded in the nanoparticles for diagnostic and therapeutic applications during the nanoprecipitation. The coaxial turbulent jet mixer developed in these studies can be used to make functional nanoparticles with high production rates and reproducible manner suitable for clinical studies and mass production.