Abstract: 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)-bpoly( 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 ∼20 nm in diameter with polydispersity (standard deviation * mean−1) of ∼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 (∼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 ∼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.

Abstract: Quantum dots (QDs) are increasingly employed in biologic imaging applications; however, anecdotal reports suggest difficulties in QD bioconjugation. Further, the stability of commercial QDs during bioconjugation has not been systematically evaluated. Thus, we examined fluorescence losses resulting from aggregation and declining photoluminescence quantum yield (QY) for commercial CdSe/ZnS QD products from four different vendors. QDs were most stable in the aqueous media in which they were supplied. The largest QY declines were observed during centrifugal filtration, whereas the largest declines in colloidal stability occurred in 2-(N-morpholino)ethanesulfonic acid (MES) buffer. These results enable optimization of bioconjugation protocols.

Abstract: Quantum dots (QDs) have tremendous potential for biomedical imaging, including superresolution techniques that permit imaging below the diffraction limit. However, most QDs are produced via organic methods, and hence require surface treatment to render them water-soluble for biological applications. Previously, we reported a micelle-templating method that yields nanocomposites containing multiple core/shell ZnS–CdSe QDs within the same nanocarrier, increasing overall particle brightness and virtually eliminating QD blinking. Here, this technique is extended to the encapsulation of Mn-doped ZnSe QDs (Mn–ZnSe QDs), which have potential applications in super-resolution imaging as a result of the introduction of Mn2+ dopant energy levels. The size, shape and fluorescence characteristics of these doped QD-micelles were compared to those of micelles created using core/shell ZnS–CdSe QDs (ZnS–CdSe QDmicelles). Additionally, the stability of both types of particles to photo-oxidation was investigated. Compared to commercial QDs, micelle-templated QDs demonstrated superior fluorescence intensity, higher signal-to-noise ratios, and greater stability against photooxidization, while reducing blinking. Additionally, the fluorescence of doped QD-micelles could be modulated from a bright ‘on’ state to a dark ‘off’ state, with a modulation depth of up to 76%, suggesting the potential of doped QD-micelles for applications in super-resolution imaging.