Oil Microdroplets Research Articles

Fabrication and mechanical properties of microchambers made of polyelectrolyte multilayers

A highly ordered array of hollow chambers ranging from 2 to 25 μm in size are fabricated using the layer-by-layer assembly of poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) on sacrificial templates with imprinted patterns of wells. Polyelectrolyte multilayer (PEM) chambers collapse if made of shells that are thinner than a critical value. This critical thickness of the shells is measured experimentally and is found to depend on the chambers geometry. Euler's model of critical stress is used to describe the collapse of the chambers. Adhesive contact of the chamber’s roof with the support is suggested as a major mechanism responsible for the collapse. Deformation of individual PEM chambers made of thicker shells is studied using a sharp indenter and varying the loading speed. At loading speeds of less than 0.33 mN s−1, the elastic theory describes the experimental data well for small deformations, yielding a Young's modulus of 4 ± 1 GPa for the PEM shell, while further deformation causes severe plastic buckling of the chamber. If the loading speed exceeds 0.33 mN s−1, the sharp indenter starts to pierce the chamber's roof and the size of the resulted hole can be precisely controlled by changing the penetration depth of the indenter. Filling the PEM chambers with oil micro-droplets by solvent-exchange method is also demonstrated.

Facile creation of hierarchical PDMS microstructures with extreme underwater superoleophobicity for anti-oil application in microfluidic channels

Composition modification and surface microstructures have been widely utilized in interface science to improve the surface performance. In this paper, we observed a significant improvement of oil contact angle (CA) from 66 ± 2° to 120 ± 4° by introducing a radical silanol group on a flat PDMS surface through oxygen plasma pretreatment. By combining surface microstructures and plasma modification, we produced three kinds of superoleophobic surfaces: 20 μm pitch micropillar arrays, 2.5 μm pitch micropillar arrays and gecko foot-like hierarchical microstructures. Among them, the hierarchical surface with high surface roughness showed extreme underwater superoleophobicity, which featured ultrahigh CA (175 ± 3°) and ultrasmall sliding angle (<1°). Quantitative measurements demonstrated that these superoleophobic surfaces exhibited distinct adhesive behaviors, by which they were interpreted as Wenzel's, Cassie's and the Lotus state, respectively. A microfluidic channel with superoleophobic microstructures was further created by novel curve-assisted imprint lithography, and the characterization based on anti-oil contamination applications was carried out and discussed. We believe that the superoleophobic surfaces will power broad applications in oil microdroplet transportation, anti-oil channels and droplet microfluidic systems.

Flow cytometry: A promising technique for the study of silicone oil-induced particulate formation in protein formulations

Subvisible particles in formulations intended for parenteral administration are of concern in the biopharmaceutical industry. However, monitoring and control of subvisible particulates can be complicated by formulation components, such as the silicone oil used for the lubrication of prefilled syringes, and it is difficult to differentiate microdroplets of silicone oil from particles formed by aggregated protein. In this study, we demonstrate the ability of flow cytometry to resolve mixtures comprising subvisible bovine serum albumin (BSA) aggregate particles and silicone oil emulsion droplets with adsorbed BSA. Flow cytometry was also used to investigate the effects of silicone oil emulsions on the stability of BSA, lysozyme, abatacept, and trastuzumab formulations containing surfactant, sodium chloride, or sucrose. To aid in particle characterization, the fluorescence detection capabilities of flow cytometry were exploited by staining silicone oil with BODIPY 493/503 and model proteins with Alexa Fluor 647. Flow cytometric analyses revealed that silicone oil emulsions induced the loss of soluble protein via protein adsorption onto the silicone oil droplet surface. The addition of surfactant prevented protein from adsorbing onto the surface of silicone oil droplets. There was minimal formation of homogeneous protein aggregates due to exposure to silicone oil droplets, although oil droplets with surface-adsorbed trastuzumab exhibited flocculation. The results of this study demonstrate the utility of flow cytometry as an analytical tool for monitoring the effects of subvisible silicone oil droplets on the stability of protein formulations.

Antioxidant Coating of Micronsize Droplets for Prevention of Lipid Peroxidation in Oil-in-Water Emulsion

Fast lipid peroxidation in emulsified oils results in carcinogens formation and product rancidity. Prevention of oxidative degradation in oil-in-water emulsion has been achieved by encapsulating of each droplet of dispersed phase in antioxidant multilayer coating shell. The fabrication comprised placing a surface-active ionic emulsifier at the oil/water interface followed by stepwise alternate adsorption a biocompatible polyelectrolyte and antioxidant layers. Uncoupled polyelectrolyte macromolecules and antioxidant were thoroughly removed from formulation, thus the protection was entirely attributed to the droplets' shell. The experiments were performed using linseed oil, the richest source of highly unstable omega-3 alpha linolenic essential fatty acid. Bovine serum albumin (BSA) was exploited as an anionic emulsifier. The biodegradable coating shell was formed of poly-l-arginine (PARG) and dextran sulfate (DS) applied as a polycation and a polyanion respectively. Tannic acid (TA) known as a natural antioxidant and possessing antimicrobial properties was used as a protective remedy. Oil microdroplets coated with TA-containing shell displayed physical-chemical and mechanical stability in aqueous phase and over freeze-drying process as determined by ζ-potential measurements, dynamic light scattering (DLS), and confocal laser scanning microscopy (CLSM). Oxidation of emulsified oil was monitored by formation of malondialdehyde (MDA) in the samples quantified by Thiobarbituric Acid Reactive Substances (TBARS) assay. Coating shell with an incorporated layer of TA effectively suppressed oxidation in water-dispersed oil droplets and affected iron-catalyzed oxidation over 15 days of incubation at 37 °C in 0.3 mM FeBr2 solution. Antioxidant activity of TA-containing shell assembled around each oil droplet was found to be higher than that of mixed tocopherols (MT) added to linseed oil in concentration of 10000 ppm.

Electrocoalescence Mechanisms of Microdroplets Using Localized Electric Fields in Microfluidic Channels

Electrocoalescence of water-in-oil microdroplets in microfluidic channels is an active technique that enables droplet-based mixing functionalities to be achieved in lab-on-a-chip applications. In this work, a characterization of the electrocoalescence mechanisms of water microdroplets in oil is presented, using localized electric field systems. We report a theoretical and experimental description of the electrocoalscence behavior of droplet pairs by varying the physical and fluid dynamic conditions of the phases. Our results demonstrate that localized electric field systems can be reliably used to merge droplets in pairs, regardless of the distance between the drops. The coalescence behavior was dependent upon the viscosity of the continuous phase for water droplets that were separated by a thick layer of oil and upon interfacial tension for droplets that were in close proximity. We showed that these systems have the potential to be used for high-throughput applications and that, unlike other examples of active systems in the literature, the need of droplet synchronization and the application of high voltages is considerably reduced.

Protein adsorption and excipient effects on kinetic stability of silicone oil emulsions

The effect of silicone oil on the stability of therapeutic protein formulations is of concern in the biopharmaceutical industry as more proteins are stored and delivered in prefilled syringes. Prefilled syringes provide convenience for medical professionals and patients, but prolonged exposure of proteins to silicone oil within prefilled syringes may be problematic. In this study, we characterize systems of silicone oil‐in‐aqueous buffer emulsions and model proteins in formulations containing surfactant, sodium chloride, or sucrose. For each of the formulations studied, silicone oil‐induced loss of soluble protein, likely through protein adsorption onto the silicone oil droplet surface. Excipient addition affected both protein adsorption and emulsion stability. Addition of surfactant stabilized emulsions but decreased protein adsorption to silicone oil microdroplets. In contrast, addition of sodium chloride increased protein adsorption and decreased emulsion stability. Silicone oil droplets with adsorbed lysozyme rapidly agglomerated and creamed out of suspension. This decrease in the kinetic stability of the emulsion is ascribed to surface charge neutralization and a bridging flocculation phenomenon and illustrates the need to investigate not only the effects of silicone oil on protein stability, but also the effects of protein formulation variables on emulsion stability. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1721–1733, 2010

A microdroplet-based shift register

A microfluidic device is presented for the serial formation, storage and retrieval of water microdroplets in oil. The principle of operation is similar to that of an electronic shift register. Droplets, considered as units of information, can be arrayed and serially shifted within the device, allowing the controllable positioning of the emulsions and the creation of interfaces between drops. Using this passive system, by exploiting the balance between hydrodynamic pressure and surface tension across a drop due to the device design, droplet networks can be readily arrayed in a series of elements and cascaded within the microchannels in an automatable and high throughput fashion. The results showed the suitability of the system to be used for the formation of artificial lipid bilayers and for the study of biological dynamic processes based on the diffusion of molecules through interfaces.

Encapsulation of Pediococcus acidilactici cells in corn and olive oil microcapsules emulsified by peptides and stabilized with xanthan in oil-in-water emulsions: Studies on cell viability under gastro-intestinal simulating conditions

Three different encapsulation systems were developed in the form of oil-in-water acidic emulsions (pH 3.0) with the oil phase in the form of microdroplets in which Pediococcus acidilactici cells were enclosed. The first emulsion contained corn oil microdroplets (mean diameter 1.5 μm) emulsified with peptides and stabilized with SDS. The other two, were food grade systems with microdroplets of corn or olive oil (m.d. 2.1 and 2.2 μm, respectively) emulsified with peptides and stabilized with xanthan. In all systems, meat peptone, a rich source of peptides and amino acids, was provided in aqueous solution in which the cultures were suspended. Peptone derived peptides acted as emulsifiers and at the same time as nutrient substrates and osmoprotectants for cells. Emulsions were stored for 30 days at 4 °C. During this period, samples were examined for physical stability and viability of the encapsulated and freely suspended microorganisms present in the emulsions. Examinations were made through phase contrast microscopy and subsequent image capture and analysis with an automatic image analysis system. Viable and non-viable cells were discriminated on the basis of color differences produced through staining with trypan blue. The method permitted extraction of a large amount of information and produced large amounts of data through automated measurements on images. Emulsion characteristics and cell viabilities were also examined under conditions simulating the gastro-intestinal environment. Encapsulation proved to be critical since, following successive treatments of samples with simulated gastric juice (pH 2.0) and intestinal juice (pH 7.4), it ensured viability rates of encapsulated cells as high as 85% and delivered as much as 92% of the initially encapsulated cells to the target point. The formulated emulsion systems may have a large number of applications in the food sector provided further studies on engineering properties and improvements of stability over a wide pH range are carried out.

Voltammetric Antioxidant Analysis in Mineral Oil Samples Immobilized into Boron‐Doped Diamond Micropore Array Electrodes

AbstractMineral oil microdroplets containing the model antioxidant N,N‐didodecyl‐N′,N′‐diethyl‐phenylene‐diamine (DDPD) are immobilized into a 100×100 pore‐array (ca. 10 μm individual pore diameter, 100 μm pitch) in a boron‐doped diamond electrode surface. The robust diamond surface allows pore filling, cleaning, and reuse without damage to the electrode surface. The electrode is immersed into aqueous electrolyte media, and voltammetric responses for the oxidation of DDPD are obtained. In order to further improve the current responses, 20 wt% of carbon nanofibers are co‐deposited with the oil into the pore array. Voltammetric signals are consistent with the oxidation of DDPD and the associated transfer of perchlorate anions (in aqueous 0.1 M NaClO4) or the transfer of protons (in aqueous 0.1 M HClO4). From the magnitude of the current response, the DDPD content in the mineral oil can be determined down to less than 1 wt% levels. Perhaps surprisingly, the reversible (or midpoint) potential for the DDPD oxidation in mineral oil (when immersed in 0.1 NaClO4) is shown to be concentration‐dependent and to shift to more positive potential values for more dilute DDPD in mineral oil solutions. An extraction mechanism and the formation of a separate organic product phase are proposed to explain this behavior.

Removal of compressor oil microdroplets from water with a carbon fabric

Coalescence of KHA-30 compressor oil microdroplets on a carbon fabric, aimed to remove them from air and water streams used for compressor cooling, was examined.

Effect of surfactants on the porous structure of poly(N-isopropylacrylamide) hydrogels prepared by an emulsion templating method

Stimuli-sensitive porous hydrogels prepared with an emulsion templating method developed by the authors are potentially applicable in the medical and pharmaceutical fields; thermosensitive N-isopropylacrylamide (NIPA) hydrogels having randomly distributed sphere-like cavities have been prepared by the polymerization in an aqueous phase in an oil-in-water (O/W) emulsion, followed by the washing of oil (oleyl alcohol) microdroplets. The surfactant plays a dominant role in the preparation of porous hydrogels and the pore size. This study concerns with the surfactant effects on the stability of pre-gel O/W emulsions. The porous NIPA hydrogels were successfully prepared using the surfactants forming the stable emulsion and their internal structures and swelling properties were characterized. The O/W emulsions and the porous hydrogels prepared using various amounts of oil and surfactant were characterized. The information obtained serves for preparation of porous hydrogels having suitable porous structure for their applications.

Polypyrrole Containers Grown on Oil Microdroplets: Encapsulation of Fluorescent Dyes

Polypyrrole microcapsules were synthesized by the chemical deposition of the polymer onto mineral oil droplets adsorbed onto glass or quartz substrates. The droplets act as a kind of a template that directs the polymer growth into the form of three-dimensional containers. The polymer is deposited on both the surface of oil droplets and the glass or quartz substrate entrapping the oil content. The dissolution of chemical species in oil prior to polymer deposition permits the encapsulation of these species within the cavities of the containers. This phenomenon was demonstrated through the entrapment of the fluorescent dyes, pyrene and perylene, within the polymeric capsules. It was shown that the entrapped molecules can be released from the capsules by controlling the hydration of the polymer, which in turn changes the permeability of the oil content through the polypyrrole shells. The polymer growth and encapsulation phenomena were investigated with a range of complementary physicochemical techniques, including microscopic (AFM, SEM, and confocal microscopy) and spectroscopic (steady-state fluorescence and UV-vis absorption) methods. In particular, the use of optical methods was possible due to the deposition of the capsules on transparent substrates (glass, quartz). As a consequence, the optical information on the interior of the capsules was accessible, for example, dye concentration and local polarity.

Preparation of poly( N-isopropylacrylamide) emulsion gels and their drug release behaviors

Stimuli-sensitive drug delivery systems (DDSs) have attracted considerable attention in medical and pharmaceutical fields; thermosensitive DDS dealing with poly( N-isopropylacrylamide) (poly(NIPA)) have been widely studied. Novel NIPA emulsion gels, i.e., NIPA hydrogels containing distributed oil (oleyl alcohol) microdroplets, were synthesized by means of an emulsion-gelation method in which the polymerization of hydrogels in an aqueous phase in an oil-in-water (O/W) emulsion and the loading of a lipophilic drug (indomethacin) dissolved in an oil phase were accomplished simultaneously. The pulsatile (on–off) drug release from the NIPA emulsion gel loading indomethacin to a phosphate buffered saline (PBS) solution was successfully controlled by a temperature swing between 25 °C (release off) and 40 °C (release on). The mechanism of the pulsatile drug release was discussed in relation to the diffusion rate, distribution ratio, solvent exchange of NIPA hydrogels, and drug release from an NIPA organogel. The mechanism was as follows: the solvent exchange occurred within the NIPA emulsion gel (the NIPA gel-network absorbed oleyl alcohol with indomethacin) at temperatures above the LCST, and the diffusion rate of indomethacin through the solvent-exchanged gel was higher at 40 °C than at 25 °C.

Widespread capacity to metabolize polychlorinated biphenyls by diverse microbial communities in soils with no significant exposure to PCB contamination

The purpose of this work was to determine the extent of microbial metabolic potential for polychlorinated biphenyls (PCBs) in soils that have had no previous exposure to this class of xenobiotic pollutants. Soil and sediment samples of distinct characteristics from six sites in Germany were used to inoculate PCB oil (Aroclor 1242) microdroplets. All samples yielded multispecies biofilms, as revealed by single-strand conformation polymorphism (SSCP) analyses of polymerase chain reaction (PCR) analysis of 16S rRNA genes, and sequence analysis of the main amplicons. Microbes representing 20 different operational taxonomic units (OTUs) were identified in the biofilms, but only a few were common to all biofilms, namely those closely related to Aquabacterium sp., Caulobacter sp., Imtechium assamiensis, Nevskia ramosa, Parvibaculum lavamentivorans and Burkholderia sp. The PCB biofilm communities were always distinct from control biofilms developing from the same samples in the absence of PCB. All PCB droplet-grown biofilms degraded multiple PCB congeners but differed in the congener spectra they degraded. These findings reveal that microbial potential to degrade PCBs is widespread in soils that have not been subjected to PCB contamination, and that this potential is characteristic of consortia of very diverse phylogenetic composition.

Diamagnetic Levitation With Permanent Magnets for Contactless Guiding and Trapping of Microdroplets and Particles in Air and Liquids

Diamagnetic levitation was applied to micro-positioning and trapping of diamagnetic micron-sized particles and micro-droplets. Scale reduction laws for magnetism indicate that diamagnetism is highly efficient for magnetic MEMS. We demonstrate here that diamagnetic bodies can be contactless guided along magnetic grooves or trapped in magnetic wells both in air and in liquids. Levitation of water, ethanol and oil microdroplets was achieved within a 1.6 mm bore of a cylindrical magnet and in micromachined bulk magnets. Thick permanent micromagnets were also electroplated above silicon wafers in various matrix configurations. Diamagnetic levitation on micromagnet arrays was tested with 3 mum-large diamagnetic latex beads in a paramagnetic buffered solution. Trapping and arraying of microparticles in stable spatial levitation within magnetic wells were successfully achieved

Kinetic Analysis of Ion Pair Extraction of an Alkyl Sulfate Anion across a Liquid/Liquid Interface by Fluorescence Microspectroscopy and Microelectrochemistry of Single Microdroplets

Mass transfer of an alkyl sulfate anion with a (ferrocenylmethyl)trimethylammonium cation from water into single oil microdroplets was kinetically studied by microcapillary injection, fluorescence microspectroscopy, and microelectrochemistry. The partitioning ratio and the extraction rate significantly depended on the alkyl chain length of the alkyl sulfate anion. The extraction rate for the n-dodecyl sulfate or n-tridecyl sulfate ion was proportional to both the alkyl sulfate ion and ferrocene derivative concentrations while that for the n-undecyl sulfate ion was proportional to the anion concentration alone. The results are discussed in terms of transfer of the individual ions across the microdroplet/water interface and adsorption/ion pair formation of the alkyl sulfate ion at the microdroplet/water interface.

Concentrating solutes and nanoparticles within individual aqueous microdroplets.

This paper describes a method to concentrate solutes and colloidal entities, from small ions and molecules to proteins and nanoparticles, within individual aqueous microdroplets in oil. The mechanism lies in the entrapment of the solutes within an aqueous microdroplet, while the water molecules from the droplet slowly dissolve into the organic phase. Because the rate of change in concentration scales as the fifth power of the surface-area-to-volume ratio of the droplet, this phenomenon is prominent mostly in the micrometer-length scale. This paper presents measurements that quantify the degree of solute entrapment within the microdroplet and further describes the dynamics of droplet shrinkage and the factors that influence the rate of shrinkage. In addition, this paper explains why this concentration effect does not occur for certain organic microdroplets in aqueous solutions.

Hepatic arterial injection chemotherapy for hepatocellular carcinoma with epirubicin aqueous solution as numerous vesicles in iodinated poppy-seed oil microdroplets: clinical application of water-in-oil-in-water emulsion prepared using a membrane emulsification technique

Iodinated poppy-seed oil (IPSO) accumulates selectively in hepatocellular carcinoma (HCC) when injected into the hepatic artery. This virtue has been applied to the hepatic arterial injection chemotherapy for the disease. We invented a new water-in-oil-in-water emulsion (W/O/W), in which IPSO microdroplets, 70 μm in diameter, were suspended in physiological saline enclosing numerous vesicles of an aqueous solution of epirubicin with remarkable stability. After hepatic arterial injection, the microdroplets accumulated only in HCC tissue and remained in the tissue for more than 3 weeks affecting tumor cells. Efficacy of the W/O/W has been fully proved clinically; the 6-year cumulative survival rate for 24 patients bearing HCC nodules recurrent after hepatectomy, including even 12 patients with four or more nodules, though prognosis of these patients is recognized very poor, was 24%.

Voltammetry of Electroactive Oil Droplets. Part I: Numerical Modelling for Three Mechanistic Models Using the Dual Reciprocity Finite Element Method

Diffusion problems encountered for the case of electrochemical conversion of microdroplets of an electroactive oil deposited on an electrode are studied by the dual reciprocity finite element simulation method (DRM). Three plausible mechanistic models are compared. For a microdroplet of electroactive material A) the electrochemical reaction commences from the oil–electrode surface interphase; B) there is rapid charge conduction over the droplet surface so that ion insertion occurs from the droplet–aqueous electrolyte interface; C) the electrochemical reaction occurs only at the three phase boundary oil–aqueous electrolyte–electrode. Cyclic voltammograms and potential step transient responses are simulated. The dimensionless peak current and peak separation as a function of dimensionless scan rate are presented and a comparison of the three mechanistic models shows distinctly different behaviors. The normalized transient currents as a function of normalized time are given and compared for the three mechanistic models. The results provide a clear basis for the mechanistic characterization of real systems in terms of the three models considered.

Advances in abdominal interventional radiology

Advances in abdominal interventional radiology