Osmo-solidification of all-aqueous emulsion with enhanced preservation of protein activity.

The encapsulation of bio-active ingredients, such as proteins, in solidified particles via emulsion templating frequently induces an irreversible loss of bioactivity, because of the use of non-aqueous solvents and unfavorable conditions during the solidification process. Herein, we introduce an "osmo-solidification" approach that solidifies all-aqueous emulsion droplets by the osmotic extraction of water for encapsulating proteins and demonstrate the superior preservation of their activity. The osmo-solidification approach combines the solidification of droplets to particles and protein encapsulation in one step. Proteins encapsulated preserve their activity after osmo-solidification better than conventional solidification approaches. To the best of our knowledge, this is the first time that the osmo-solidification of all-aqueous emulsion is introduced in the fabrication of emulsion-based particles and that the stability of encapsulated proteins can be enhanced to an unprecedentedly high level.

NANOPARTICLES. Production of amorphous nanoparticles by supersonic spray-drying with a microfluidic nebulator.

Amorphous nanoparticles (a-NPs) have physicochemical properties distinctly different from those of the corresponding bulk crystals; for example, their solubility is much higher. However, many materials have a high propensity to crystallize and are difficult to formulate in an amorphous structure without stabilizers. We fabricated a microfluidic nebulator that can produce amorphous NPs from a wide range of materials, even including pure table salt (NaCl). By using supersonic air flow, the nebulator produces drops that are so small that they dry before crystal nuclei can form. The small size of the resulting spray-dried a-NPs limits the probability of crystal nucleation in any given particle during storage. The kinetic stability of the a-NPs­on the order of months­is advantageous for hydrophobic drug molecules.

Rheological investigations on the creaming of depletion-flocculated emulsions.

Preventing creaming or sedimentation by the addition of thickeners is an important industrial challenge. We study the effect of the addition of a "free" nonadsorbing polymer (xanthan gum) on the stability against creaming of sterically stabilized O/W emulsions. Therefore, we analyze our samples using microscopy and rheological measurements. At low xanthan concentrations, the emulsions cream. However, above a certain concentration a three-dimensional network of droplets is formed, which can prevent creaming. We attribute the formation of this structure to depletion attraction. The rheological behavior of an emulsion that is macroscopically stable should be elastic, while it should be viscous for a creaming emulsion. In order to distinguish between stable and unstable samples, we measure their relaxation time by mechanical rheology and find a good correlation to the visual observation. However, the measured relaxation times are much shorter than the time-scales, on which we observe creaming. We hypothesize that the measured relaxation time is related to the droplet-droplet interaction. This determines the frequency at which microscopic rearrangements occur, which weaken the network structure prior to creaming. Based on this interpretation, the relaxation time gives direct access to the microstructural processes involved in creaming. We therefore suggest using it as a predictive parameter of creaming stability.

High throughput production of single core double emulsions in a parallelized microfluidic device.

Double emulsions are useful templates for microcapsules and complex particles, but no method yet exists for making double emulsions with both high uniformity and high throughput. We present a parallel numbering-up design for microfluidic double emulsion devices, which combines the excellent control of microfluidics with throughput suitable for mass production. We demonstrate the design with devices incorporating up to 15 dropmaker units in a two-dimensional or three-dimensional array, producing single-core double emulsion drops at rates over 1 kg day(-1) and with diameter variation less than 6%. This design provides a route to integrating hundreds of dropmakers or more in a single chip, facilitating industrial-scale production rates of many tons per year.

Enhanced encapsulation of actives in self-sealing microcapsules by precipitation in capsule shells.

Microcapsules with core-shell structures are excellent vehicles for the encapsulation of active ingredients; however, the actives often leak out of these structures over time, without observable damage to them. We present a novel approach to enhancing the encapsulation of active ingredients inside microcapsules. We use two components that can form solid precipitates upon mixing and add one each to the microcapsule core and to the continuous phase. The components diffuse through the shell in the same manner as the actives, but upon meeting, they precipitate to form solid particles within the shell; this significantly reduces leakage through the shell of the microcapsules. We show that the reduction in the leakage of actives is due to the blockage of channels or pores that exist in the shell of the capsules by the solid precipitates.

Microfluidic melt emulsification for encapsulation and release of actives.

A microfluidic melt emulsification method for encapsulation and release of actives is presented. Using a water-in-oil-in-water (W-O-W) double emulsion template, solid capsules can be formed by freezing the middle shell phase. Actives encapsulated inside the solid shell can be controllably and rapidly released by applying a temperature trigger to melt the shell. The choice of the shell materials can be chosen to accommodate the storage and release temperatures specific to the applications. In addition, we have also demonstrated the same concept to encapsulate multiple actives in multicompartment capsules, which are promising as multifunctional capsules and microreactors.

Photoreactive coating for high-contrast spatial patterning of microfluidic device wettability.

For many applications in microfluidics, the wettability of the devices must be spatially controlled. We introduce a photoreactive sol-gel coating that enables high-contrast spatial patterning of microfluidic device wettability.

Droplet-based microfluidic platforms for the encapsulation and screening of Mammalian cells and multicellular organisms.

High-throughput, cell-based assays require small sample volumes to reduce assay costs and to allow for rapid sample manipulation. However, further miniaturization of conventional microtiter plate technology is problematic due to evaporation and capillary action. To overcome these limitations, we describe droplet-based microfluidic platforms in which cells are grown in aqueous microcompartments separated by an inert perfluorocarbon carrier oil. Synthesis of biocompatible surfactants and identification of gas-permeable storage systems allowed human cells, and even a multicellular organism (C. elegans), to survive and proliferate within the microcompartments for several days. Microcompartments containing single cells could be reinjected into a microfluidic device after incubation to measure expression of a reporter gene. This should open the way for high-throughput, cell-based screening that can use >1000-fold smaller assay volumes and has approximately 500x higher throughput than conventional microtiter plate assays.

Glass coating for PDMS microfluidic channels by sol-gel methods.

Soft lithography using polydimethylsiloxane (PDMS) allows one to fabricate complex microfluidic devices easily and at low cost. However, PDMS swells in the presence of many organic solvents significantly degrading the performance of the device. We present a method to coat PDMS channels with a glass-like layer using sol-gel chemistry. This coating greatly increases chemical resistance of the channels; moreover, it can be functionalized with a wide range of chemicals to precisely control interfacial properties. This method combines the ease of fabrication afforded by soft-lithography with the precision control and chemical robustness afforded by glass.

The microwave absorption of emulsions containing aqueous micro- and nanodroplets: a means to optimize microwave heating.

The microwave absorption at frequencies between 10 MHz and 4 GHz is measured for aqueous brine droplets dispersed in a dielectric medium (epsilon(')=2.0). By varying the size of the droplets, ion type and ion concentration, it is found that the microwave absorption goes through a maximum which depends on the type of ions and their concentration. The absorption process is attributed to the polarization of the microdroplets through surface charges. Means to optimize microwave heating in emulsions is discussed.