Microfluidic emulsification

T. Watanabe and Y. Kimura, Continuous fabrication of monodisperse polylactide microspheres by droplet—Particle technology using microfluidic emulsification and. Soft Matter, 1, 9894-9897, 2011. 

Direct emulsification Emulsion coalescence Emulsion destabilization Microfluidic emulsification Premix emulsification Spontaneous emulsification... 

Various direct microfluidic emulsification geometries are discussed in literature, e.g., (straight-through) microcharuiels and T- and Y-junctions (see Eig. 1). Two droplet formation mechanisms can be distinguished one uses Laplace pressure differences for spontaneous droplet generation and the other uses shear to form droplets. 

Emulsion Preparation with Microstructured Systems, Fig. 1 Outline of some microfluidic emulsification geometries, (a) Cross section of a microchannel with a depth difference at the junction. The dispersed phase is pushed onto the terrace (indicated by the arrow) and an emulsion droplet is formed when the dispersed phase falls from the terrace into the deeper well (see also Fig. 2). (b) Top view of a T-Junction with a uniform... 

Li W, Nie ZH, Zhang H, et al Screening of the effect of surface energy of microchannels on microfluidic emulsification, Latt mMiV 23 8010—8014, 2007. 

It has been stated that the development of emulsification methods for production of mono-sized droplets must be rooted in one of two possible manufacturing approaches (Williams et al., 2001a) (1) reduction of process length scales of the turbulent perturbations and enhancement of their uniformity in the mixing processes that rupture the liquids, and (2) the creation of droplets individually (drop by drop). The production of emulsions using membrane and microfluidic devices represents a typical example of the second approach. This chapter aims to introduce the latest development on the utilization of the membrane and microfluidic emulsification techniques for the preparation of double emulsions, as well as micro- and nanoparticles from double-emulsion precursors. 

Formation of Hposomal vesicles under controlled conditions of emulsification of Hpids with phosphoHpids has achieved prominence in the development of dmgs and cosmetics (42). Such vesicles are formed not only by phosphoHpids but also by certain nonionic emulsifying agents. Formation is further enhanced by use of specialized agitation equipment known as microfluidizers. The almost spontaneous formation of Hposomal vesicles arises from the self-assembly concepts of surfactant molecules (43). Vesicles of this type are unusual sustained-release disperse systems that have been widely promoted in the dmg and cosmetic industries. 

The top-down approach involves size reduction by the application of three main types of force — compression, impact and shear. In the case of colloids, the small entities produced are subsequently kinetically stabilized against coalescence with the assistance of ingredients such as emulsifiers and stabilizers (Dickinson, 2003a). In this approach the ultimate particle size is dependent on factors such as the number of passes through the device (microfluidization), the time of emulsification (ultrasonics), the energy dissipation rate (homogenization pressure or shear-rate), the type and pore size of any membranes, the concentrations of emulsifiers and stabilizers, the dispersed phase volume fraction, the charge on the particles, and so on. To date, the top-down approach is the one that has been mainly involved in commercial scale production of nanomaterials. For example, the approach has been used to produce submicron liposomes for the delivery of ferrous sulfate, ascorbic acid, and other poorly absorbed hydrophilic compounds (Vuillemard, 1991 ... 

In the microfluid dynamics approaches the continuity and Navier-Stokes equation coupled with methodologies for tracking the disperse/continuous interface are used to describe the droplet formation in quiescent and crossflow continuous conditions. Ohta et al. [54] used a computational fluid dynamics (CFD) approach to analyze the single-droplet-formation process at an orifice under pressure pulse conditions (pulsed sieve-plate column). Abrahamse et al. [55] simulated the process of the droplet break-up in crossflow membrane emulsification using an equal computational fluid dynamics procedure. They calculated the minimum distance between two membrane pores as a function of crossflow velocity and pore size. This minimum distance is important to optimize the space between two pores on the membrane... 

Although the premix membrane emulsification can yield larger fluxes with respect to direct membrane emulsification neither methods using surface-energy minimization nor microfluid dynamics approaches have been until now reported on the theoretical treatment of the premix membrane emulsification. 

In high force dispersion devices, ultrasonication is used today especially for the homogenization of small quantities, whereas rotor-stator dispersers with special rotor geometries, microfluidizers, or high-pressure homogenizers are best for the emulsification of larger quantities. 

Microfluidic techniques have been recently used for the synthesis of microgel particles with dimensions of 1-30 pm. In these methods, microfluidic devices are used that provide emulsification of polymer solutions followed by physical [27, 28] or chemical [29] crosslinking. 

Maa YF, Hsu CC (1999) Performance of sonication and microfluidization for liquid-liquid emulsification. Pharm Dev Technol 4 233-240... 

Importantly, in practically all common techniques of formation of drops and bubbles, the liquids are deformed geometrically with the use of a force of choice, and then they spontaneously break into smaller bits by the action of the interfacial tension. As we will discuss it below, emulsification in microfluidic devices constitutes a very different route to emulsification. 

In the first demonstration of formation of monodisperse droplets in a microfluidic T-junction [9], on the basis of the experimental results on scaling of the droplet size with the rate of flow of the continuous fluid, it was hypothesized that the droplets are sheared off from the junction by the flow of the continuous fluid, similarly to the classical models of shear-driven emulsification. However, the fact that the break-up occurs in a confined geometry of the microchannels, and that the droplet growing off the inlet of the fluid-to-be-dispersed usually occupies a significant fraction of the cross-section of the main channel, suggest that the pressure drop along a growing droplet may be an important factor in the process. 

Microdroplets can be generated within microfluidic devices using different methods such as electric fields [134], micro-injectors [135] and needles [136]. However, the most widely used methods for droplet generation rely on flow instabdities between immiscible fluids that lead to the so-called multiphase flow. Any fluid flow consisting of more than one phase or component (e.g., emulsions and foams) are examples of multiphase fluids. Traditional emulsification methods are based on the agitation of immiscible fluids and result in the formation of a polydisperse collection of droplets. By... 

Some preparation methods specific to the formation of nanoparticle suspensions are provided in References [20,62,63]. Many such methods are simply conventional colloidal suspension preparation methods that have been extended to produce smaller particle sizes, but others involve novel approaches. Some ofthese involve making nanoemulsions as a first step. For example, membrane, microfluidic and nanofluidic devices have been used to make nanoscale emulsions of all kinds, as already noted earlier, and the emulsion droplets so generated can be used in turn to make sohd microparticles and nanoparticles. If the nanoparticles are intended to encapsulate other materials, then a double emulsification technique can be used, at elevated temperature, to prepare a multiple emulsion (i.e. 

Figure 14.25 Schematics of multiple modular microfluidics (M ) reactors, (a) An individual microfluidic reactor for the synthesis of polymer particles comprising an emulsification and a polymerization compartments (b) A module comprising 16 individual microfluidic reactors connected by symmetric...

Microfluidic devices can be used for either premix emulsification (a method in which a coarse emulsion is broken up by passing it through a geometry) or direct emulsification (a method in which oil and water are introduced separately in the device and the emulsion is formed at their point of contact). Depending on the surface properties of the microfluidic device or other microstructured devices (e.g., membrane) either oil in water (hydrophilic device) or water in oil (hydrophobic device), emulsions are formed. Also related products, such as double emulsions, particles, and capsules, are reported in literature. Eor an extensive description of the construction of various microfluidic devices for emulsion preparation, and the various products that have... 

The effects of flow rate(s), monodispersity, energy input, and ease of parallelization are evaluated to indicate the potential of microfluidic techniques for large-scale application. Cross-flow membrane emulsification will be used as benchmark technology as it is already available and relatively easy to scale up by using several membranes in series or in parallel. Table 1 shows a summary of various effects of which more detailed information is given in the remainder of this section. 

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