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Microfluidic droplets have been applied extensively as reaction vessels in a wide variety of chemical and biological applications. Typically, once the droplets are formed in a flow channel, it is a challenge to add new chemicals to the droplets for subsequent reactions in applications involving multiple processing steps. Here, we present a novel and versatile method that employs a high strength alternating electrical field to tunably transfer chemicals into microfluidic droplets using nanodroplets as chemical carriers. We show that the use of both continuous and cyclic burst square wave signals enables extremely sensitive control over the total amount of chemical added and, equally importantly, the rate of addition of the chemical from the nanodroplet carriers to the microfluidic droplets. An a priori theoretical model was developed to model the mass transport process under the convection-controlled scenario and compared with experimental results. We demonstrate an application of this method in the controlled preparation of gold nanoparticles by reducing chloroauric acid pre-loaded in microfluidic droplets with l-ascorbic acid supplied from miniemulsion nanodroplets. Under different field strengths, l-ascorbic acid is supplied in controllable quantities and addition rates, rendering the particle size and size distribution tunable. Finally, this method also enables multistep synthesis by the stepwise supply of miniemulsions containing different chemical species. We highlight this with a first report of a three-step Au-Pd core-shell nanoparticle synthesis under continuous flow conditions.

We present the first study of a novel, generalizable method that uses a water-in-oil nanoemulsion as the continuous phase to generate uniform aqueous micro-droplets in a capillary-based microfluidic system. We first study the droplet generation mechanism in this system and compare it to the more conventional case where a simple oil/solvent (with surfactant) is used as the continuous phase. Next, we present two versatile methods – adding demulsifying chemicals and heat treatment – to allow active online chemical interaction between the continuous and dispersed phases. These methods allow each generated micro-droplet to act as a well-mixed micro-reactor with walls that are ‘permeable’ to the nanoemulsion droplets and their contents. Finally, we demonstrate an application of this system in the fabrication of uniform hydrogel (alginate) micro-beads with control over particle properties such as size and swelling. Our work expands the toolbox of droplet-based microfluidics, enabling new opportunities and applications involving active colloidal continuous phases carrying chemical payloads, both in advanced materials synthesis and droplet-based screening and diagnostic methods. [ABSTRACT FROM AUTHOR]

Microfluidics is used in a wide array of applications including photonics, catalysis, optoelectronics, particle synthesis, bio-diagnosis and tissue engineering. Poly(dimethyl) siloxane (PDMS) is one of the most widely used materials for the fabrication of such devices. In many applications, applied flow gives rise to pressure variations along the length of the channel and a commensurate spatially varying channel height. We have previously performed a scaling analysis of the relaxation time of an initially deflected PDMS channel (Dendukuri et al 2007 Lab Chip 7 818-28). The prior study did not consider the dynamic evolution of the initially deflected channel and, being a scaling theory, required a fitting parameter for a priori predictions. In this paper, we analyze the dynamic behavior of a retracting PDMS wall after the removal of an external stress. For small deflections, the problem lends itself to a regular perturbation analysis that is analytically solvable at zeroth order.We find that the zeroth-order solution is very close to the numerically solved full solution for most situations of experimental interest. We further demonstrate that our model captures both qualitative and quantitative trends seen in the prior (Dendukuri et al 2007) and newly performed experiments. [ABSTRACT FROM AUTHOR]

Precisely shaped polymeric particles and structures are widely used for applications in photonic materials, MEMS, biomaterials and self-assembly. Current approaches for particle synthesis are either batch processes or flow-through microfluidic schemes that are based on two-phase systems, limiting the throughput, shape and functionality of the particles. We report a one-phase method that combines the advantages of microscope projection photolithography and microfluidics to continuously form morphologically complex or multifunctional particles down to the colloidal length scale. Exploiting the inhibition of free-radical polymerization near PDMS surfaces, we are able to repeatedly pattern and flow rows of particles in less than 0.1 s, affording a throughput of near 100 particles per second using the simplest of device designs. Polymerization was also carried out across laminar, co-flowing streams to generate Janus particles containing different chemistries, whose relative proportions could be easily tuned. This new high-throughput technique offers unprecedented control over particle size, shape and anisotropy. [ABSTRACT FROM AUTHOR]

We present a simple, potentiallygeneralizable method to createhighly monodisperse spherical microparticles (SMs) of ∼200μm size containing active pharmaceutical ingredient (API) crystalsand a macromolecular excipient, with unprecedented, highly specific,and selective control over the morphology and polymorphic outcome.The basic idea and novelty of our method is to control polymorphicselection within evaporating emulsion drops containing API–excipientmixtures via the kinetics of two simultaneously occurring processes:liquid–liquid phase separation and supersaturation generation,both governed by solvent evaporation. We demonstrate our method usingtwo model hydrophobic APIs: 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile(ROY) and carbamazepine (CBZ), formulated with ethyl cellulose (EC)as excipient. We dispense monodisperse oil-in-water (O/W) emulsionscontaining the API–excipient mixture on a flat substrate witha predispensed film of the continuous phase, which are subsequentlysubjected to evaporative crystallization. We are able to control thepolymorphic selection by varying solvent evaporation rate, which canbe simply tuned by the film thickness; thin (∼0.5 mm) and thick(∼2 mm) films lead to completely specificand differentpolymorphic outcomes for both model APIs: yellow(YT04) and orange (OP) for ROY, and form II and form III for CBZ respectively.Our method paves the way for simultaneous, bottom-up crystallizationand formulation processes coupled with unprecedented polymorphic selectionthrough process driven kinetics. [ABSTRACT FROM AUTHOR]

We present detailed experimentalstudies, supported by a theoreticalmodel, of dynamics and morphological outcomes in thin-film sphericalcrystallization of glycine from microfluidic emulsions. Specifically,the effects of droplet size, shrinkage rate, and temperature are studiedwith the aim of understanding and delineating, from a processing standpoint,crystallization conditions that ensure spherulitic crystal growthin individual droplets, ultimately yielding compactly packed sphericalcrystal agglomerates (SAs). Our experiments reveal the existence,under all processing conditions, of a critical concentration (supersaturation)beyond which droplet shrinkage due to evaporation is dramaticallyarrested. The morphological outcome of the crystallization then dependson whether a nucleation event in a droplet occurs before (yieldingloosely packed or faceted single crystals) or after (compactly packedSAs) this critical concentration is reached. We analyze our observationswithin the framework of a simple physical model based on classicalnucleation theory and the theory of nonstationary Poisson processes,which accurately captures the overall trends. Experiments were conductedin a temperature range of 45–85 °C, droplet diameter rangeof 50–160 μm, and film thickness range of 0.5–1.5mm. We found that smaller droplets and faster shrinkage rates (inthinner films) favor the formation of compact SAs at a given temperature,and lower temperatures generally favor compact SA formation at a fixeddrop size and shrinkage rate. This work builds on our recent demonstrationof spherical crystallization in microfluidic emulsions and providesvaluable guidelines for the design of spherical crystallization processesusing this method. [ABSTRACT FROM AUTHOR]

Emulsion-based crystallization to produce spherical crystallineagglomerates (SAs) is an attractive route to control crystal sizeduring downstream processing of active pharmaceutical ingredients(APIs). However, conventional methods of emulsification in stirredvessels pose several problems that limit the utility of emulsion-basedcrystallization. In this paper, we use capillary microfluidics togenerate monodisperse water-in-oil emulsions. Capillary microfluidics,in conjunction with evaporative crystallization on a flat heated surface,enables controllable production of uniformly sized SAs of glycinein the 35–150 μm size range. We report detailed characterizationof particle size, size distribution, structure, and polymorphic form.Further, online high-speed stereomicroscopic observations reveal severalclearly demarcated stages in the dynamics of glycine crystallizationfrom emulsion droplets. Rapid droplet shrinkage is followed by crystalnucleation within individual droplets. Once a nucleus is formed withina droplet, crystal growth is very rapid (<0.1 s) and occurs linearlyalong radially advancing fronts at speeds of up to 1 mm/s, similarto spherulitic crystal growth from impure melts. The spherulitic aggregatethus formed ages to yield the final SA morphology. Overall crystallizationtimes are on the order of minutes, as compared to hours in conventionalbatch processes. We discuss these phenomena and their implicationsfor the development of more generalized processes applicable to avariety of drug molecules. This work paves the way for microfluidics-enabledcontinuous spherical crystallization processes. [ABSTRACT FROM AUTHOR]