Electrohydrodynamic Mixing-Mediated Nanoprecipitation for Polymer Nanoparticle Synthesis

As nanomaterials move toward commercial applications, methods of scalable, solution-based manufacturing of polymer nanoparticles are increasingly important. Flash nanoprecipitation (FNP) is a popular approach to producing relatively monodisperse NPs that encapsulate hydrophobic cargo with high efficiency. In conventional FNP, rapid turbulent mixing is generated by high velocity flows that may not be suitable for delicate or expensive cargo. Here, we developed an alternate approach to synthesize block copolymer (BCP) nanoparticles that relies on rapid mixing induced by electrohydrodynamics (EHD): EHD mixing (EM) mediated-nanoprecipitation (NP). For poly(caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) and poly(styrene)-b-PEO (PS-b-PEO) model polymers and over the range of conditions investigated, EM-NP yielded polymer NPs that were similar to 20 nm in diameter with polydispersity (standard deviation * mean(-1)) of similar to 0.1 to 0.2. NP sizes were insensitive to changes in flow rate and BCP concentration but were slightly sensitive to changes in applied voltage. As voltage decreased the mean NP size and polydispersity remained unchanged but a small number of outlier worm-like micelles or larger spherical structures appeared. EM-NP was used to encapsulate hydrophobic cargos, including superparamagnetic iron oxide nanoparticles (SPIONs) or quantum dots (QDs), materials useful in biomedical imaging and cell separations. BCP nanocomposite size (similar to 20 nm) and polydispersity remained relatively unchanged with hydrophobic cargo encapsulation; however, the tail of the distribution extended to larger particle sizes. Although BCP-QD composites synthesized via EM-NP demonstrated an similar to 20% decline in QD fluorescence in the first 24 h, they remained stable for the remaining 6 days of the study. Thus, EM-NP provides an important alternative to conventional FNP for generating monodisperse NPs that does not require high flow rates and that is superior to aerosol-mediated or sonication-mediated interfacial instability approaches. This process may enable commercial scale production of polymeric nanoparticles encapsulating delicate cargoes, such as quantum dot bioimaging agents.