Polymer particles with various shapes and morphologies produced in continuous microfluidic reactors

We report a novel approach to continuous and scalable production of core-shell droplets and polymer capsules in microfluidic devices. The described method is also useful in the synthesis of polymer particles with nonspherical shapes. We used capillary instability-driven break-up of a liquid jet formed by two immiscible fluids. Precise control of emulsification of each liquid allowed for the production of highly monodisperse core-shell droplets with a predetermined diameter of cores and thickness of shells. We also achieved control over the number of cores per droplet and the location of cores in the droplet. We carried out fast throughput photopolymerization of the monomeric shells and obtained polymer particles with various shapes and morphologies, including spheres, truncated spheres and, hemispheres, and single and multicore capsules.     

Microfluidics: from dynamic lattices to periodic arrays of polymer disks

We used coupling of flow and geometric confinement to assemble emulsion droplets in two-dimensional gliding lattices with a high degree of order and symmetry. Highly monodisperse discoid droplets with circular shapes were generated in a microfluidic flow-focusing device. Originally, close-packed lattices formed from these circular discoid droplets. Progressive confinement led to the gradual deformation of the circular disks: first, they elongated in the direction parallel to the direction of flow and then transformed into hexagons. Assembly driven by the combination of flow and confinement also allowed for the formation of lattices from droplets with a bimodal size distribution. We used photopolymerization of the monomer droplets to trap the lattice structure in the solid state and produce highly periodic arrays of solid polymer disks.     

Multi-step microfluidic polymerization reactions conducted in droplets: the internal trigger approach

We report the application of the "internal trigger" approach to multistep microfluidic polymerization reactions conducted in droplets, namely, polyaddition and polycondensation. We hypothesized and experimentally established that heat generated in an exothermic free radical polymerization of an acrylate monomer (Reaction 1) triggers the polycondensation of the urethane oligomer (Reaction 2). Completion of two microfluidic polymerization reactions led to the continuous synthesis of polymer particles with an interpenetrating polymer network (IPN) structure. Use of this microfluidic synthesis allowed us (i) to conduct efficient screening of the compositions of the monomer mixtures; (ii) to achieve control of the stoichiometric ratios of reactants in Reaction 2 by varying the flow rates of liquids; (iii) to reach control over the morphology of the resulting particles; and (iv) to produce polymer particles with a narrow size distribution and a predetermined size.     

Synthesis of monodisperse polymer microspheres by photopolymerization of microdroplets

We have examined photopolymerization of highly monodisperse microdroplets of monomer solutions under UV-light radiation. Microdroplets were generated using a modified vibrating aerosol generator, and the diameter of the droplets can be tuned to any size between 5 to 100 m. Polymer particles derived from the droplets were characterized by optical microscopy and SEM. The results show that the polymer particles, under optimum conditions, can be highly spherical and monodisperse. The diameter and morphology of resulting microspheres depend on the diameter of the monomer solution droplets, monomer concentration, photopolymerization reaction temperature, residence time, and droplet dispersion.     

A predictive approach of the influence of the operating parameters on the size of polymer particles synthesized in a simplified microfluidic system

Monodisperse and size-controlled spherical polymer particles were synthesized by in situ photopolymerization of O/W monomer emulsions. Monomer droplets were produced without surfactant or pretreatment at a needle tip in a simplified axisymmetric microfluidic device. The effect of the viscosity of the continuous phase on the particle size was studied. The system operated in the dripping mode, at a low Reynolds number. A dimensionless master curve describes the particle diameter as a function of the needle inner diameter as well as velocity and viscosity ratios of continuous and dispersed phases. An empirical law predicts the particle size. The normalized particle diameter depends upon the ratio of the capillary numbers of continuous and dispersed phases with an exponent equal to -0.22.     

Raman spectroscopic monitoring of droplet polymerization in a microfluidic device

Microfluidic methodologies are becoming increasingly important for rapid formulation and screening of materials, and development of analytical tools for multiple sample screening is a critical step in achieving a combinatorial 'lab on a chip' approach. This work demonstrates the application of Raman spectroscopy for analysis of monomer composition and degree of conversion of methacrylate-based droplets in a microfluidic device. Droplet formation was conducted by flow focusing on the devices, and a gradient of component composition was created by varying the flow rates of the droplet-phase fluids into the microchannels. Raman data were collected using a fiber optic probe from a stationary array of the droplets/particles on the device, followed by partial least squares (PLS) calibration of the first derivative (1600 cm(-1) to 1550 cm(-1)) allowing successful measurement of monomer composition with a standard error of calibration (SEC) of +/-1.95% by volume. Following photopolymerization, the percentage of double bond conversion of the individual particles was calculated from the depletion of the normalized intensity of the C[double bond, length as m-dash]C stretching vibration at 1605 cm(-1). Raman data allowed accurate measurement of the decrease in double bond conversion as a function of increasing crosslinker concentration. The results from the research demonstrate that Raman spectroscopy is an effective, on-chip analytical tool for screening polymeric materials on the micrometre scale.     

Microfluidic-based synthesis of non-spherical magnetic hydrogel microparticles

Spherical and non-spherical magnetic hydrogel particles were synthesized in a microfluidic device containing an embedded UV light reflector. Monodisperse magnetic emulsion droplets were generated in a T-junction and allowed to relax into spheres, disks, and plugs in confining microchannel geometries. Particle morphology was locked-in via UV-initiated photopolymerization. The role of the reflector in the microchannel is to provide a uniform distribution of UV energy to the magnetic emulsion droplets and to increase the UV flux, which significantly improves UV polymerization conditions for microfluidic-based particle synthesis. Magnetic nanoparticles were uniformly encapsulated in the hydrogel, giving the microparticles superparamagnetic behavior. Additionally, the non-spherical particles show anisotropic responses under an applied external magnetic field.     

Biopolymer microparticle and nanoparticle formation within a microfluidic device

This paper reports a novel microfluidic method for the production of cross-linked alginate microparticles and nanoparticles. We describe a continuous process relying on both thermodynamic and hydrodynamic factors to form microdroplets. A rapid cross-linking reaction thereafter allows solidification of the polymer droplets either within the microfluidic device or "off-chip" to form alginate micro- and nanoparticles. Monodisperse droplets are generated by extruding an aqueous alginate solution using an axisymmetric flow-focusing design. As they flow downstream in the channel, due to water and the continuous phase being partially miscible, the water diffuses very slowly out of the polymeric droplets into the transport fluid, which causes the shrinkage of the drops and the condensation of the polymer phase. The resulting size of the solid particles depends on the polymer concentration and the ensuing balance between the kinetics of the cross-linking reaction and the volume loss due to solvent diffusion. This work details both a single-step microfluidic technique for the formation of alginate microparticles of sizes ranging from 1 to 50 microm via near-equilibrium solvent diffusion within a microfluidic device and thereafter a two-step method, which was shown to generate biopolymer nanoparticles of sizes ranging from 10 to 300 nm. These novel methodologies are extremely flexible and can be extended to the preparation of micro- and nanoparticles from a wide range of single or mixed synthetic and biologically derived polymers.     

Amphiphilic crescent-moon-shaped microparticles formed by selective adsorption of colloids

We use a microfluidic device to prepare monodisperse amphiphilic particles in the shape of a crescent-moon and use these particles to stabilize oil droplets in water. The microfluidic device is comprised of a tapered capillary in a theta (θ) shape that injects two oil phases into water in a single receiving capillary. One oil is a fluorocarbon, while the second is a photocurable monomer, which partially wets the first oil drop; silica colloids in the monomer migrate and adsorb to the interface with water but do not protrude into the oil interface. Upon UV-induced polymerization, solid particles with the shape of a crescent moon are formed; removal of fluorocarbon oil yields amphiphilic particles due to the selective adsorption of silica colloids. The resultant amphiphilic microparticles can be used to stabilize oil drops in a mixture of water and ethanol; if they are packed to sufficient surface density on the interface of the oil drop, they become immobilized, preventing direct contact between neighboring drops, thereby providing the stability.     

Continuous Electroformation of Gold Nanoparticles in Nanoliter Droplet Reactors

Gold nanoparticles (AuNPs) are employed in numerous applications, including optics, biosensing and catalysis. Here, we demonstrate the stabilizer-free electrochemical synthesis of AuNPs inside nanoliter-sized reactors. Droplets encapsulating a gold precursor are formed on a microfluidic device and exposed to an electrical current by guiding them through a pair of electrodes. We exploit the naturally occurring recirculation flows inside confined droplets (moving in rectangular microchannels) to prevent the aggregation of nanoparticles after nucleation. Therefore, AuNPs with sizes in the range of 30 to 100 nm were produced without the need of additional capping agents. The average particle size is defined by the precursor concentration and droplet velocity, while the charge dose given by the electric field strength has a minor effect. This method opens the way to fine-tune the electrochemical production of gold nanoparticles, and we believe it is a versatile method for the formation of other metal nanoparticles.     

手性丙烯酸酯液晶原位光聚合反应

手性丙烯酸酯液晶原位光聚合反应何流，张树范，金顺子，漆宗能，王佛松（中国科学院化学研究所北京１０００８０）关键词手性丙烯酸酯，原位光聚合，双折射，近晶相手性侧链液晶高分子显示近晶Ｓ！相，具有铁电性，在光电功能材料和非线性光学材料方面有潜在的应用前景’...     

Janus and ternary particles generated by microfluidic synthesis: design, synthesis, and self-assembly

This paper reports a microfluidic method for fast continuous synthesis of Janus particles and three-phase particles with narrow size distribution. Synthesis of particles included emulsification of monomer liquids and in-situ photoinitiated polymerization of multiphase droplets. We show the strategy for precise control over the structure of Janus particles and their structure-dependent assembly in clusters. We demonstrate an asymmetric chemical modification of the surface of JPs by conjugating them with protein molecules. The Janus and ternary particles were synthesized from largely immiscible liquids and had a sharp interface between the constituent phases.     

Microfluidic large-scale integration on a chip for mass production of monodisperse droplets and particles

In this study, we report the mass production of monodisperse emulsion droplets and particles using microfluidic large-scale integration on a chip. The production module comprises a glass microfluidic chip with planar microfabricated 16-256 droplet-formation units (DFUs) and a palm-sized stainless steel holder having several layers for supplying liquids into the inlets of the mounted chip. By using a module having 128 cross-junctions (i.e., 256 DFUs) arranged circularly on a 4 cm x 4 cm chip, we could produce droplets of photopolymerizable acrylate monomer at a throughput of 320.0 mL h(-1). The product was monodisperse, having a mean diameter of 96.4 microm, with a coefficient of variation (CV) of 1.3%. Subsequent UV polymerization off the module yielded monodisperse acrylic microspheres at a throughput of approximately 0.3 kg h(-1). Another module having 128 co-flow geometries could produce biphasic Janus droplets of black and white segments at 128.0 mL h(-1). The product had a mean diameter of 142.3 microm, with a CV of 3.3%. This co-flow module could also be applied in the mass production of homogeneous monomer droplets.     

Sterically stabilized emulsion polymerization of styrene: Pseudo‐semicontinuous approach

The sterically stabilized emulsion polymerization of styrene initiated by a water‐soluble initiator at different temperatures has been investigated. The rate of polymerization (R_p) versus conversion curve shows the two non‐stationary‐rate intervals typical for the polymerization proceeding under non‐stationary‐state conditions. The shape of the R_p versus conversion curve results from two opposite effects—the increased number of particles and the decreased monomer concentration at reaction loci as the polymerization advances. At elevated temperatures the monomer emulsion equilibrates to a two‐phase or three‐phase system. The upper phase is transparent (monomer), and the lower one is blue colored, typical for microemulsion. After stirring such a multiphase system and initiation of polymerization, the initial coarse polymer emulsion was formed. The average size of monomer/polymer particles strongly decreased up to about 40% conversion and then leveled off. The initial large particles are assumed to be highly monomer‐swollen particles formed by the heteroagglomeration of unstable polymer particles and monomer droplets. The size of the “highly monomer” swollen particles continuously decreases with conversion, and they merge with the growing particles at about 40–50% conversion. The monomer droplets and/or large highly monomer‐swollen polymer particles also serve as a reservoir of monomer and emulsifier. The continuous release of nonionic (hydrophobic) emulsifier from the monomer phase increases the colloidal stability of primary particles and the number of polymer particles, that is, the particle nucleation is shifted to the higher conversion region. Variations of the square and cube of the mean droplet radius with aging time indicate that neither the coalescence nor the Ostwald ripening is the main driving force for the droplet instability. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 804–820, 2003     

Microgels for the encapsulation and stimulus-responsive release of molecules with distinct polarities

A microfluidic strategy for the encapsulation and stimulus-responsive release of molecules with distinct polarities from the interior of microgels is reported. The approach relies on (i) the generation of a primary O/W emulsion by the ultrasonication method, (ii) MF emulsification of the primary emulsion, and (iii) photopolymerization of the monomer present in the aqueous phase of the droplets, thereby transforming them into microgels. Non-polar molecules are dissolved in oil droplets embedded in the microgels. Polar molecules are physically associated with the hydrogel network. Upon heating, the microgels contract and release polar and non-polar cargo molecules. The approach paves the way for stimuli-responsive vehicles for multiple drug delivery.     

A simplified PDMS microfluidic device with a built-in suction actuator for rapid production of monodisperse water-in-oil droplets

We previously established an automatic droplet-creation technique that only required air evacuation of a PDMS microfluidic device prior to use. Although the rate of droplet production with this technique was originally slow (∼10 droplets per second), this was greatly improved (∼470 droplets per second) in our recent study by remodeling the original device configuration. This improvement was realized by the addition of a degassed PDMS layer with a large surface area-to-volume ratio that served as a powerful vacuum generator. However, the incorporation of the additional PDMS layer (which was separate from the microfluidic PDMS layer itself) into the device required reversible bonding of five different layers. In the current study, we aimed to simplify the device architecture by reducing the number of constituent layers for enhancing usability of this microfluidic droplet generator while retaining its rapid production rate. The new device consisted of three layers. This comprised a degassed PDMS slab with microfluidic channels on one surface and tens of thousands of vacuum-generating micropillars on the other surface, which was simply sandwiched by PMMA layers. Despite its simplified configuration, this new device created monodisperse droplets at an even faster rate (>1000 droplets per second).     

Microfluidic preparation of dual stimuli-responsive microparticles and light-directed clustering

We present a simple fabrication of photo- and thermoresponsive microparticles with a narrow size distribution in the PDMS-based microfluidic device. The monodisperse water-in-oil (W/O) droplets of poly(N-isopropylacrylamide-co-spironaphthoxazine methacryloyl) (PNIPA-SPO) were formed at the T-junction channel of the device by adjusting the flow conditions of two immiscible solutions. Subsequently, the droplets were polymerized downstream of the channel under 365 nm UV irradiation in the presence of 2,2'-diethoxyacetophenone (DEAP, photoinitiator) and N,N'-methylenebisacrylamide (MBA, monomer and cross-linker). Being photosensitive, the polymerized microparticles progressively change their color when subjected to UV-vis irradiation. Above the LCST of the copolymer, the microparticles exhibited volume shrinkage accompanied by color deterioration. In addition, the UV light-driven clustering of the PNIPA-SPO copolymer was observed within the W/O droplet in the absence of photoinitiator, which contributed to variable microstructures from Janus to acorn-like and snowman-like morphologies. This work is the first attempt to unveil the photocontrolled asymmetric particle morphology by using the photoresponsive polymer.     

Continuous and size-dependent sorting of emulsion droplets using hydrodynamics in pinched microchannels

In this report, a microfluidic system is presented for continuous and size-dependent separation of droplets utilizing microscale hydrodynamics. The separation scheme is based on laminar-flow focusing and spreading in a pinched microchannel, referred to as "pinched flow fractionation (PFF)", which was previously developed for the size-dependent separation of solid particles, such as polymer microparticles or cells. By simply introducing emulsion and the continuous phase into a microchannel, continuous separation could be achieved without using complicated operations or devices. We first examined whether this scheme could be applied for droplets, by using a pinched microchannel with one outlet, and observed the behaviors of monodisperse droplets generated at the upstream T-junction. Analysis via high-speed imaging revealed that the length of the pinched segment is critical for precise separation of droplets. Then, separation of a polydisperse oil-in-water emulsion that was prepared previously was demonstrated using a microfluidic device equipped with multiple outlets. These results showed the ability of the presented system to sort or select specific-sized droplets easily and accurately, which would be difficult to achieve using normal-scale schemes, such as centrifugation or filtration.     

Styrene emulsion polymerization: Kinetics and particle size distributions in highly swollen latex systems

The results are reported of studies on the kinetics and the time evolution of the particle size distribution in seeded styrene emulsion polymerization systems wherein the seed latex particles were highly swollen with monomer as a result of prior swelling by dodecane. Conditions were such that no new latex particles were formed nor was a significant number of monomer droplets present (“Interval III”). The data were fitted to obtain values for the rate coefficients for entry and exit (desorption) of free radicals. It was found that, during the early part of the polymerization (when the polymer:monomer ratio in the latex particles is considerably less then in an equivalent emulsion polymerization system without dodecane), the entry rate coefficient was much smaller than that measured in systems without dodecane. This effect is consistent with an entry mechanism wherein entering free radicals must displace surfactant molecules from the latex particles.     

Reduced UV light scattering in PDMS microfluidic devices

Microfluidic devices which consist of polydimethylsiloxane (PDMS) are used extensively for the production of polymer microparticles through the use of droplet templating and on-chip photopolymerization. However, in existing methods, spatial confinement of the photochemical droplet solidification is impaired by UV light scattering inside the PDMS elastomer. We present a technique to load PDMS microfluidic devices with a fluorescent dye that absorbs the scattered UV light and shifts it to longer wavelengths. By this means, the stray light is no longer harmful, and UV exposure can be limited to a desired region on the microfluidic chip.