Spontaneous generation of emulsion droplets by autonomous fluid-pumping using the gas permeability of poly(dimethylsiloxane) (PDMS)

Conventional droplet-based microfluidic systems require expensive, bulky external apparatuses, such as electric power supplies and pressure-driven pumps for fluid transportation. This study demonstrates an alternative way to produce emulsion droplets by autonomous fluid-handling based on the gas permeability of poly(dimethylsiloxane) (PDMS). Furthermore, basic concepts of fluid-handling are expanded to control the direction of the microfluid in the microfluidic device. The alternative pumping energy resulting from the high gas permeability of PDMS is used to generate water-in-oil (W/O) emulsions, which require no additional structures apart from microchannels. We can produce emulsion droplets by simple loading of the oil and aqueous solutions into the inlet reservoirs. During the operation of the microfluidic device, changes in droplet size, volumetric flow rate, and droplet generation frequency were quantitatively analyzed. As a result, we found that changes in the wetting properties of the microchannel greatly influence the volumetric flow rate and droplet generation frequency. This alternative microfluidic approach for preparing emulsion droplets in a simple and efficient manner is designed to improve the availability of emulsion droplets for point of care bioanalytical applications, in situ synthesis of materials, and on-site sample preparation tools.     

EMULSION POLYMERIZATION IN A SEED-FED CONTINUOUS STIRRED-TANK REACTOR

A numerical method has been developed to predict the particle size distribution (PSD) of the product latex from a steady-state polydisperse-seeded continuous reactor. Simulations have been carried out for the emulsion polymerization of vinyl chloride based on the experimental conditions reported by Berens(l). The simulation results can be reasonably well fitted to the PSD data published by Berens. The radical desorption constant, k_d, for Berens’ vinyl chloride emulsion polymerization can be estimated by fitting the simulated PSD to experimental measurements. The simulation work presented in this article demonstrates that the combination of mathematical modeling and PSD measurements can be a useful tool in studying radical transport rates and aqueous phase termination phenomena. The simulation results also indicate that the continuum diffusion theory for free radical absorption by the particles leads to a better PSD fit than a model based on equal diffusion rates per unit area.     

Increasing the throughput and productivity of Caco-2 cell permeability assays using liquid chromatography-mass spectrometry: application to resveratrol absorption and metabolism

The Caco-2 cell monolayer permeability assay has become a standard model of human intestinal absorption and transport. This paper reviews recent progress in increasing the throughput of Caco-2 cell monolayer assays and in expanding the scope of this assay to include modeling intestinal drug metabolism. The state-of-the-art in Caco-2 cell monolayer permeability assays combines multi-well plates fitted with semi-permeable inserts on which Caco-2 cells have been cultured with liquid chromatography-mass spectrometry (LC-MS) or LC-tandem mass spectrometry (LC-MS-MS) for the quantitative analysis of test compounds and the identification of their intestinal metabolites. After reviewing the progress in increasing the throughput of Caco-2 cell monolayer assays for both modeling human intestinal permeability or transport and the metabolism of xenobiotic compounds, we demonstrate the application of LC-MS and LC-MS-MS to the measurement of resveratrol permeability and metabolism in the Caco-2 model. trans-Resveratrol (trans-3,5,4'-trihydroxystilbene) is a polyphenolic compound occurring in grapes, peanuts and other food sources, that is under investigation as a cancer chemoprevention agent. The apparent permeability coefficient for apical (AP) to basolateral (BL) movement of resveratrol was 2.0 x 10(-5)cm/sec. Resveratrol was not a substrate for P-glycoprotein or the multi-drug resistance associated proteins (MRP). No phase I metabolites were observed, but the phase II conjugates resveratrol-3-glucuronide and resveratrol-3-sulfate was identified based on LC-MS and LC-MS-MS analysis and comparison with synthetic standards. Although these data indicate that resveratrol diffuses rapidly across the intestinal epithelium, extensive phase II metabolism during absorption might reduce resveratrol bioavailability.     

Hollow latex particles: synthesis and applications

One of the major developments in emulsion polymerization over the last two decades has been the ability to make hollow latex particles. This has contributed many fundamental insights into the synthesis and the development of structure in particles. Hollow latex particles also enhance the performance of industrial coatings and potentially are useful in other technologies such as microencapsulation and controlled release. Ever since the publication of the initial process patents describing these particles, there has been a global R&D effort to extend the synthetic techniques and applications. One prominent synthetic approach to hollow particles is based on osmotic swelling. This dominates the literature, and usually starts with the synthesis of a structured latex particle containing an ionizable core that is subsequently expanded with the addition of base. Fundamental to this approach are a sophisticated control of transport phenomena, chemical reactivity within the particle, and the thermoplastic properties of the polymer shell. Hydrocarbon encapsulation technology has also been employed to make hollow latex particles. One approach involves a dispersed ternary system that balances transport, conversion kinetics, and phase separation variables to achieve the hollow morphology. Other techniques, including the use of blowing agents, are also present in the literature. The broad range of approaches that affords particles with a hollow structure demonstrates the unique flexibility of the emulsion polymerization process.     

Evaluation of permeability of microporous media, using the modified random-trajectory approach

The random trajectory approach derived recently for the purpose of evaluation of the percolation threshold is modified and applied to the modeling of permeability. The main modification consists in probabilistic accounting of possible trajectories, the total permeability being evaluated as a sum over all available percolation trajectories, without any preferences in orientation. Results of calculations of permeability vs porosity, sample thickness, and other structural factors are presented. It is concluded that the qualitative tendencies regarding permeability do not significantly differ from those found before for percolation.     

细乳液聚合制备阳离子型含氟烷基丙烯酸酯共聚物乳液

采用细乳液聚合技术制备得到稳定的阳离子型甲基丙烯酸甲酯/甲基丙烯酸十八烷基酯/含氟烷基丙烯酸酯共聚物乳液,考察了均质强度(振幅)、均质时间以及难溶助剂十六烷(HD)用量对阳离子型FA共聚物乳胶粒尺寸及形貌的影响.结合TEM和纳米粒度及电位分析仪测试数据分析发现,均质条件的改变明显影响该阳离子型FA共聚物乳胶粒的粒径大小,粒径在80～150nm之间变化.细乳液聚合技术得到内部形态多样的乳胶粒,长链的含氟烷基链微相分离,更有助于提高该FA共聚物乳胶膜的憎水性,水滴在经阳离子型FA细乳液处理后的棉布上的平衡静态接触角最高可达150°.     

Formulation development of a filter-sterilizable lipid emulsion for lipophilic KW-3902, a newly synthesized adenosine A1-receptor antagonist

KW-3902 (a newly synthesized adenosine A1-receptor antagonist) has potent diuretic and renal protective activities. The objective of the present study was to develop an injectable formulation of KW-3902, that was water-insoluble and less than 1 microg/ml, and so lipid emulsion was selected as a favorable formulation. Changing the mixing ratio of oil to lecithin, the particle size of the lipid emulsion was controlled, and by adjusting the mixing ratio of oil/lecithin=1:1, the weight ratio, a lipid emulsion with a mean particle size of 130 nm was prepared. This small particle size makes this emulsion filter-sterilizable, which is a favorable feature for heat labile products. The stability of the KW-3902 lipid emulsion was assessed from the viewpoint of the electrostatic repulsion, and by including the oleic acid a stable lipid emulsion was developed, which was stable for at least 12 months at 10 and 25 degrees C and for 3 months at 40 degrees C. The feature of this small particle size emulsion was also characterized by comparing it with a conventional emulsion (oil/lecithin=1:0.12, the weight ratio, particle size is 220 nm). The release of KW-3902 from the oil particles was measured and the apparent permeability of KW-3902 was calculated from the equation according to Fick's theory. The apparent permeability, P, of KW-3902 was not affected by the particle size of the emulsion (1.78x10(-11) cm/s for the small emulsion and 1.76x10(-11)cm/s for the conventional emulsion). The distribution mode of KW-3902 in the lipid emulsion was also discussed by considering the findings of the permeability and solubility of KW-3902.     

Simulations of a dielectrophoretic membrane filtration process for removal of water droplets from water-in-oil emulsions

A novel separation technique based on simultaneous application of AC dielectrophoresis and preferential transport through a semipermeable hydrophilic membrane is proposed for separation of small amounts of emulsified water droplets from a water-in-oil emulsion. Embedding an array of parallel microelectrodes on a membrane matrix, followed by application of an AC potential to these electrodes, can result in capturing the water droplets onto the membranes from the emulsion during a crossflow filtration process. The present paper describes the theoretical principles underlying such a process, and describes a simple mathematical framework based on trajectory analysis for assessing the separation efficiency of such a technique. The results indicate that superimposition of an AC dielectrophoretic field can significantly enhance the preferential transport of the emulsified water through the membrane in a crossflow filtration device. This can lead to a highly efficient continuous separation process for dilute emulsions.     

Modeling of emulsion co- and terpolymerizations: Will it ever be possible?

In this paper some of the problematic aspects of modeling emulsion copolymerizations will be discussed, giving a retrospective and a perspective on the area. In order to describe the fundamental processes in emulsion polymerization, like entry and exit of radicals in emulsion copolymerizations, many basic kinetic and thermodynamic constants are needed but still lacking. It will be shown that in the past dramatically deviating parameters were applied in modeling emulsion copolymerization. The most important of these parameters will be discussed and some of the outstanding problems will be highlighted.     

Modeling composite emulsion polymerization kinetics

The conversion profiles of a number of factorial designed experiments used to study composite emulsion polymerization were modeled using a deterministic mathematical construct as well as an empirical neural network approach. In the deterministic modeling approach, existing mechanistic models for emulsion polymerization were employed for which estimates of rate constants were obtained from established literature sources as well as experiments. Fitting of the kinetic data was done using nonlinear fitting algorithms to adjust the estimated rate constants to provide the best fit of the conversion profiles. In the case of the empirical modeling using neural networks, the neural net inputs were in the form of the factor levels of the various experimental designs. Several nonrelated experimental designs could be combined in this way to serve as the input, whereas the conversion profiles were targeted as outputs. Following the successful implementation of both modeling strategies, a hybrid modeling approach was tested by combining the neural network predictive power to estimate values for rate constants while retaining the aforementioned mechanistic models to fit the data. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 45: 101–117, 2013     

Liquid membrane transport: a survey

The literature pertaining to facilitated transport and liquid membrane separations is reviewed and summarized, especially work reported since 1977. Liquid membranes of all geometries are discussed, including immobilized liquid membranes and liquid surfactant or emulsion liquid membranes. Emphasis is placed on facilitated, or carrier-mediated transport in both configurations although other mechanisms such as coupled-transport and transport due to solubility differences are discussed. Mathematical modeling and analytical solutions for facilitated transport models are summarized. The possibility of industrial application of liquid membrane technology is mentioned and the most important experimental techniques for liquid membrane research are discussed. Also, directions for future research are recommended.     

A hydrodynamic approach to the measurement of the permeability of small molecules across artificial membranes

An in situ analytical approach to the measurement of supported liquid membrane permeability is reported. The method consists of a spectrophotometric method to measure transport through a membrane-supported lipid solution, using a rotating-diffusion cell configuration to overcome limits arising from transport through the aqueous solution boundary layer in stationary systems. Rotation frequencies are almost two orders of magnitude higher than those employed previously for rotating-diffusion studies of membrane transport. The method is illustrated with the transport of warfarin [1-(4'-hydroxy-3'-coumarinyl)-1-phenyl-3-butanone]. The use of the rotating-diffusion approach permits accurate calculation of the aqueous phase boundary layer thickness, which has hitherto been treated as an adjustable parameter in studies of membrane permeability. Further, it is shown that the analyte diffusion coefficient can be determined readily using liquid-liquid electrochemistry.     

Modeling gas transport in packaging applications

The barrier to gas transport provided by the container material is an important consideration in many packaging applications. This paper considers cases where a simple steady-state or pseudosteady-state analysis does not adequately represent the transport situation and, thus, the dynamics of the diffusion process must be considered. In these cases, a simple permeability coefficient is not sufficient to describe the barrier characteristics but detailed knowledge of the solubility and diffusion processes must be known. The adequacy of the phenomenological model used to represent these processes and various mathematical approximations in their application in modeling packaging problems have been considered. A specific example involving prediction of shelf-life of carbonated beverages in plastic bottles is given. In addition, the question of the approach to steadystate in transient permeation experiments is analyzed. The familiar rule of three time lags is seen to provide a conservative criterion for glassy polymers obeying the dual sorption, dual mobility model.     

Oxalate Precipitation in Emulsion: from the Drop Scale to the Industrial Process

An original process of actinides coprecipitation, based on either pulsed or Taylor-Couette flows column, is studied. The novelty of this process lies in the confinement of the aqueous reagents in droplets, dispersed in an inert organic phase (W/O emulsion). Besides the implementation of well-known technologies of the nuclear industry, the emulsion process is particularly convenient for the control of supersaturation, and ensures the sticky precipitates confinement within drops, thereby limiting the fouling risk and its adverse consequences on productivity and safety. A thorough understanding of the precipitation mechanisms and their interactions with the hydrodynamic conditions prevailing around and inside the drops is essential for the process optimization. In this context, numerical simulations were conducted, accompanying experiments, to study the process sensitivity. Different levels were considered in the modeling task, going from the emulsion behavior inside the column, to the reagents mixing and precipitation within the drops. Regarding the drops scale, on which we focus in this paper, population balance equations (PBE) were coupled to fluid dynamics simulation. Different methods of resolution of the PBE were tested. The behavior of the precipitate was also assessed using a Lagrangian approach. Thanks to these drop scale simulations, process experiments were discussed and analyzed.     

Core–shell morphology as a model for the study of gas permeation in composite systems

Structured latex particles prepared by emulsion polymerization were used as a model to simulate the interphase region between two phases. Multiphase polymer films comprised of high and low permeability polymers of various compositions were used. The model system consisted of a poly(n-butyl methacrylate) (PBMA) matrix and a discontinuous phase with core and shell morphology. The structured particle had a PBMA core and a vinylidene chloride – n-butyl methacrylate (VDC–BMA) copolymer shell. The shell transport characteristics wer altered by changing the (VDC–BMA) copolymer molar ratio. The physical and transport properties for each individual component were measured. Nitrogen was the probe gas. Films used for permeation experiments were prepared by latex casting. The results showed that the morphology of a heterogeneous polymeric system and the transport characteristics of their components had a considerable effect on the magnitude of the transport properties. Experimental data also showed the dependence of the gas global permeability coefficient on the nature of the simulated interphase region, the shell, and the weight percentage of such interphase in the heterogeneous polymeric films. Upon increasing the VDC content in the VDC–BMA copolymer, the gas permeability decreased. The data were fitted to the electrical analogs of conductivity in composite systems. For the matrix filled with structured particles the overall permeability coefficient could best be described when the individual permeabilities were considered as the inverse resistances in parallel.     

Determination of the pore radius of regenerated cellulose membranes by a dyeing technique

Membrane structure strongly affects the transport of solutes through dialysis membranes. This suggests that knowledge of membrane structure and its effects on permeability is required in order to improve the membranes. Solute transport in membrane pores is limited by steric hindrance at the pore entrances, frictional resistance of the pore walls, and the tortuosity of the pores. Differences in dyeing properties are found among the various tubular dialysis membranes made of regenerated cellulose (RC) that are commercially available. The objective of the present study is to determine intramembrane diffusivity for dyes, and from this the pore radius of RC membranes based on pore model calculations. Values of the pore radius of RC membranes obtained from intramembrane diffusivity data are in disagreement with our previously reported values obtained from solute and pure water permeability data. This indicates that RC membranes are of asymmetrical structure and slightly tight near the outside surfaces.     

Prediction of emulsion particle sizes using a computational fluid dynamics approach

For many food products emulsification processes play an important role. Examples are ice cream, spreads, sauces, etc. As is well known, droplet break-up and coalescence phenomena are the local processes underlying the control of particle size in an emulsion process. Quite a number of studies have generated scaling laws which can be easily applied and which are useful in the design of a process. However, the prediction of particle sizes in an inhomogeneous flow, where the flow velocity is changing spatially in strength and direction and with time, is not yet well established. For one-phase flows computational fluid dynamics (CFD) methodologies are in use to predict details on the flow with quite some success. This methodology has been extended to capture the dispersed phase in an efficient way. The essence is that break-up and coalescence processes determine source terms in a transport equation for the moments of the particle size distribution, while velocity vectors as obtained in the one-phase CFD simulation determine the convective term. This method allows particle size prediction in any equipment. The approach is illustrated for the particle size evolution of an oil-in-water emulsion, for a phase-separated biopolymeric mixture (a so-called water-in-water emulsion) and for the escape of the included oil droplets from a double emulsion of the type oil-in-water-in-oil. In all cases experimental results are compared with simulation results, which match very well. This shows the strength of the method.     

Stability and permeability of amphiphile bilayers

In this review the rupture and permeability of bilayers are considered on the basis of a mechanism of the formation of microscopic holes as fluctuations in the bilayers. The hole formation is treated as a nucleation process of a new phase in a two-dimensional system with short-range intermolecular forces. Free rupture and deliberate rupture (by α-particles) of foam bilayers (Newtonian black films) are discussed. A comparison is made between the rupture of foam and emulsion bilayers. Experimental methods for obtaining foam and emulsion bilayers from thin liquid films are considered. Methods for investigating the stability and permeability of foam bilayers, which are based on a microscopic model allowing the use of amphiphile solutions with very low concentrations, are described. Experimental dependences of the lifetime of bilayers, the probability of observing the foam bilayer in a foam film, the gas permeability of bilayers, etc. on the concentration of amphiphile molecules in the solution are reported. The influence of temperature and external impact (e.g. α-particle irradiation) have also been experimentally studied. A good agreement between theory and experiment is established, allowing determination of several characteristics of foam and emulsion bilayers obtained from ionics or non-ionics: the specific edge energy of bilayer holes, equilibrium surfactant concentration below which the bilayer is thermodynamically metastable, work for the formation of a nucleus hole, number of vacancies in the nucleus hole, coefficient of gas diffusion through the bilayer, etc. On the basis of the effect of temperature on the rupture of foam bilayers the binding energy of a surfactant molecule in the bilayer is determined. The adsorption isotherm of surfactant vacancies in the foam bilayer is obtained which shows a first-order phase transition. Some applications to scientific, technological and medical problems are considered. The foam bilayer is used as a model for investigating short-range forces in biological structures, the interaction between membranes and cell fusion. It is also shown that the foam bilayer is a suitable model for studying the alveolar surface and stability. On that basis a clinical diagnostic method is developed for assessment of the human foetal lung maturity.     

Effect of microstructure on molecular oxygen permeation through condensed phospholipid monolayers

A method is presented that allows novel measurement of the effect of microstructure on the oxygen permeability of highly condensed, polycrystalline phospholipid monolayers. Oxygen permeability of the polycrystalline shell coating a stationary microbubble is measured directly using an apposing microelectrode in the induced transfer mode and modeling oxygen flux through the shell and intervening aqueous medium. Varying cooling rate through the phospholipid main phase transition permits control of shell microstructure by manipulation of crystalline domain size and shape. Domain boundary density, defined as the ratio of the mean domain perimeter to the mean domain area, of the microbubble shell is determined by fluorescence microscopy. Oxygen permeability was shown to increase linearly with domain boundary density at a constant phospholipid acyl chain length and, accordingly, was shown to decrease exponentially with increasing chain length at a constant domain boundary density. Modification of the energy barrier theory to account for microstructural effects, in terms of the domain boundary density, provides a general equation to model passive transport through polycrystalline monolayer films. Results from this method show promise in determining the gas transport kinetics of medical microbubbles and the gas exchange characteristics of biological monolayers.