Recent Developments in Manufacturing Micro- and Nanoparticlesfrom Emulsion Droplets (original) (raw)
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Controlled production of emulsions and particles by milli-and microfluidic techniques
The recent developments of soft lithography and microfluidic techniques now permit the manipulation of small quantities of fluids with very good control and reproducibility. These advances open a new "bottom-up" route to emulsification that paves the way to the fabrication of calibrated hierarchically organized emulsions and particles. In this article, we describe the microfluidic techniques elaborated for engineering emulsions and new dispersed materials and discuss their advantages over "top-down" approaches. We review and comment the high potentialities these techniques offer to emulsion and colloid science, to the development of high-throughput set-ups for chemistry, physics and biology. We illustrate them through a few examples taken from the current literature.
Recent advances in the production of controllable multiple emulsions using microfabricated devices
Particuology, 2016
This review focuses on recent developments in fabrication of multiple emulsions in microscale systems, such as membrane, microchannel array and microfluidic emulsification devices. Membrane and microchannel emulsification offer great potential in manufacturing multiple emulsions with uniform drop sizes and high encapsulation efficiency of encapsulated actives. Microfluidic devices enable unprecedented level of control over the number, size and type of internal droplets at each hierarchical level but suffer from low production scales. Microfluidic methods can be exploited to generate high-order multiple emulsions (triple, quadruple and quintuple), non-spherical (discoidal and rod-like) drops and drops with asymmetric properties such as Janus and ternary drops, composed of two or three distinct regions on the surface. Multiple emulsion droplets generated in microfabricated devices can be used as templates for vesicles (polymersomes, liposomes, colloidosomes) with multiple inner compartments for simultaneous encapsulation and release of incompatible actives or reactants.
Production of uniform droplets using membrane, microchannel and microfluidic emulsification devices
Microfluidics and Nanofluidics, 2012
This review provides an overview of major microengineering emulsification techniques for production of monodispersed droplets. The main emphasis has been put on membrane emulsification using Shirasu Porous Glass (SPG) and microsieve membrane, microchannel emulsification using grooved-type and straight-through microchannel plates, microfluidic junctions and flow focusing microfluidic devices. Microfabrication methods for production of planar and 3D poly(dimethylsiloxane) (PDMS) devices, glass capillary microfluidic devices and single crystal silicon microchannel array devices have been described including soft lithography, glass capillary pulling and microforging, hot embossing, anisotropic wet etching and deep reactive ion etching. In addition, fabrication methods for SPG and microseive membranes have been outlined, such as spinodal decomposition, reactive ion etching and ultraviolet LIGA (Lithography, Electroplating, and Moulding) process. The most widespread application of micromachined emulsification devices is in the synthesis of monodispersed particles and vesicles, such as polymeric particles, microgels, solid lipid particles, Janus particles, and functional vesicles (liposomes, polymersomes and collloidosomes). Glass capillary microfluidic devices are very suitable for production of core/shell drops of controllable shell thickness and multiple emulsions containing a controlled number of inner droplets and/or inner droplets of two or more distinct phases. Microchannel emulsification is a 2 very promising technique for production of monodispersed droplets with droplet throughputs of up to 100 litres per hour.
Microfluidic Production of Multiple Emulsions
Micromachines, 2017
Microfluidic devices are promising tools for the production of monodispersed tuneable complex emulsions. This review highlights the advantages of microfluidics for the fabrication of emulsions and presents an overview of the microfluidic emulsification methods including two-step and single-step methods for the fabrication of high-order multiple emulsions (double, triple, quadruple and quintuple) and emulsions with multiple and/or multi-distinct inner cores. The microfluidic methods for the formation of multiple emulsion drops with ultra-thin middle phase, multi-compartment jets, and Janus and ternary drops composed of two or three distinct surface regions are also presented. Different configurations of microfluidic drop makers are covered, such as co-flow, T-junctions and flow focusing (both planar and three-dimensional (3D)). Furthermore, surface modifications of microfluidic channels and different modes of droplet generation are summarized. Non-confined microfluidic geometries used for buoyancy-driven drop generation and membrane integrated microfluidics are also discussed. The review includes parallelization and drop splitting strategies for scaling up microfluidic emulsification. The productivity of a single drop maker is typically <1 mL/h; thus, more than 1000 drop makers are needed to achieve commercially relevant droplet throughputs of >1 L/h, which requires combining drop makers into twodimensional (2D) and 3D assemblies fed from a single set of inlet ports through a network of distribution and collection channels.
Structured microparticles with tailored properties produced by membrane emulsification
Advances in Colloid and Interface Science, 2015
This paper provides an overview of membrane emulsification routes for fabrication of structured microparticles with tailored properties for specific applications. Direct (bottom-up) and premix (top-down) membrane emulsification processes are discussed including operational, formulation and membrane factors that control the droplet size and droplet generation regimes. A special emphasis was put on different methods of controlled shear generation on membrane surface, such as cross flow on the membrane surface, swirl flow, forward and backward flow pulsations in the continuous phase and membrane oscillations and rotations. Droplets produced by membrane emulsification can be used for synthesis of particles with versatile morphology (solid and hollow, matrix and core/shell, spherical and non-spherical, porous and coherent, composite and homogeneous), which can be surface functionalised and coated or loaded with macromolecules, nanoparticles, quantum dots, drugs, phase change materials and high molecular weight gases to achieve controlled/targeted drug release and impart special optical, chemical, electrical, acoustic, thermal and magnetic properties. The template emulsions including metal-in-oil, solid-in-oil-in-water, oil-in-oil, multilayer, and Pickering emulsions can be produced with high encapsulation efficiency of encapsulated materials and narrow size distribution and transformed into structured particles using a variety of different processes, such as polymerisation (suspension, mini-emulsion, interfacial and in-situ), ionic gelation, chemical crosslinking, melt solidification, internal phase separation, layer-by-layer electrostatic deposition, particle self-assembly, complex coacervation, spray drying, sol-gel processing, and molecular imprinting. Particles fabricated from droplets produced by membrane emulsification include nanoclusters, colloidosomes, carbon aerogel particles, nanoshells, polymeric (molecularly imprinted, hypercrosslinked, Janus and core/shell) particles, solder metal powders and inorganic particles. Membrane Ca 2+
Designer emulsions using microfluidics
Materials Today, 2008
An emulsion is a mixture of two immiscible liquids, where one liquid is dispersed in the form of small drops in another liquid that forms a continuous phase 1-4 . Common types of emulsions include oil-in-water (o/w), such as milk, and water in oil (w/o), like butter. They are extremely important for a variety of applications such as macromolecular delivery 5-8 , oil recovery 9,10 , food processing 11,12 , and hazardous material handling 13 . The presence of a native or added surfactant is necessary for the long-term stability of emulsions: the surfactant molecules migrate to the liquid-liquid interface and inhibit droplet coalescence 1,2 .
A microfluidic platform for formation of double-emulsion droplets
Microfluidics and Nanofluidics, 2009
A new method for actively controlling the number of internal droplets of water-in-oil-in-water (W/O/ W) double-emulsion droplets was demonstrated. A new microfluidic platform for double-emulsion applications has been developed, which integrates T-junction channels, moving-wall structures, and a flow-focusing structure. Inner water-in-oil (W/O) single-emulsion droplets were first formed at a major T-junction. Then the droplets were subdivided into smaller uniform droplets by passing through a series of secondary T-junctions (branches). The moving-wall structures beside the secondary T-junctions were used to control the number of the subdivided droplets by selectively blocking the branches. Finally, doubleemulsion droplets were formed by using a flow-focusing structure downstream. Experimental data demonstrate that the inner and outer droplets have narrow size distributions with coefficient of variation (CV) of less than 3.5% and 5.7%, respectively. Double-emulsion droplets with 1, 2, 3, and up to 10 inner droplets have been successfully formed using this approach. The size of the inner droplets and outer droplets could be also fine-tuned with this device. The development of this new platform was promising for drug delivery applications involving double emulsions.
Journal of Controlled Release, 2010
The present paper describes the production, using a microfluidic approach, of microparticles (constituted of cellulose acetate) and O/ W emulsions (constituted of PEG-6 corn oil droplets). The general production strategy is based on the formation of water-in-oil multiphase flow by a focusing mechanism (X-junction chip). The innovative aspect of the work is represented by the fabrication procedure for the microfluidic chip production. The chips were designed and fabricated by a low cost approach using a shrinkable biocompatible polymer.
Microemulsion extrusion technique: a new method to produce lipid nanoparticles
Solid lipid nanoparticles (SLN) and nano- structured lipid carriers (NLC) have been intensively investigated for different applications, including their use as drug and gene delivery systems. Different techniques have been employed to produce lipid nanoparticles, of which high pressure homogenization is the standard technique that is adopted nowadays. Although this method has a high efficiency, does not require the use of organic solvents, and allows large- scale production, some limitations impede its applica- tion at laboratory scale: the equipment is expensive, there is a need of huge amounts of surfactants and co- surfactants during the preparation, and the operating conditions are energy intensive. Here, we present the microemulsion extrusion technique as an alternative method to prepare lipid nanoparticles. The parameters to produce lipid nanoparticles using microemulsion extru- sion were established, and the lipid particles produced (SLN, NLC, and liposomes) were characterized with regard to size (from 130 to 190 nm), zeta potential, and drug (mitoxantrone) and gene (pDNA) delivery prop- erties. In addition, the particles’ in vitro co-delivery capacity (to carry mitoxantrone plus pDNA encoding the phosphatase and tensin homologue, PTEN) was tested in normal (BALB 3T3 fibroblast) and cancer (PC3 prostate and MCF-7 breast) cell lines. The results show that the microemulsion extrusion technique is fast, inexpensive, reproducible, free of organic solvents, and suitable for small volume preparations of lipid nano- particles. Its application is particularly interesting when using rare and/or costly drugs or ingredients (e.g., cationic lipids for gene delivery or labeled lipids for nanoparticle tracking/diagnosis).