Submicron Droplets Research Articles

Image-Guided Ultrasound Characterization of Volatile Sub-Micron Phase-Shift Droplets in the 20–40 MHz Frequency Range

Phase-shift perfluorocarbon droplets are designed to convert from the liquid to the gas state by the external application of acoustic or optical energy. Although droplet vaporization has been investigated extensively at ultrasonic frequencies between 1 and 10 MHz, few studies have characterized performance at the higher frequencies commonly used in small animal imaging. In this study, we use standard B-mode imaging sequences on a pre-clinical ultrasound platform to both image and activate sub-micron decafluorobutane droplet populations in vitro and in vivo at center frequencies in the range of 20–40 MHz. Results show that droplets remain stable against vaporization at low imaging pressures but are vaporized at peak negative pressures near 3.5 MPa at the three frequencies tested. This study also found that a small number of size outliers present in the distribution can greatly influence droplet performance. Removal of these outliers results in a more accurate assessment of the vaporization threshold and produces free-flowing microbubbles upon vaporization in the mouse kidney.

Influence of the concentration of a polyoxyethylene glycerol ester on the physical stability of submicron emulsions

The chemistry and technology of agrochemical products has undergone extensive changes over the last 20 years. The new formulations and ingredients should meet the needs of the agrochemical industry for products having greater safety to the user and much lower environmentally impact maintaining the same performance targets. A recent trend involves the use of the emulsion format for agrochemicals, which provides a more efficient performance than those conventionally used. Furthermore, the production of submicron stable emulsion is a key achievement especially for this product.This study has been focused on the development of fine emulsions containing ecofriendly ingredients, such as surfactants and green solvents. It has been proven that the optimal surfactant concentration not only may lead to emulsions with submicron droplet sizes but also may prevent the typical destabilization process occurring in these formulations. In this particular case, it has been demonstrated that 3wt% surfactant concentration is adequate for three reasons: (a) allowing the lowest droplet size to be achieved, (b) providing the sufficient viscosity to prevent creaming and (c) not being an excess of surfactant that leads to depletion flocculation.

Comparison of batch and continuous ultrasonic emulsification processes

Batch and continuous ultrasonic emulsification processes on both lab and pilot scales were investigated using Tween 80 or milk protein isolate (MPI) as emulsifiers. The process parameters of processing volume, residence time and ultrasonic amplitude, as well as emulsion formulations, emulsifier type and concentration, were studied for the effect on emulsion droplet size. Emulsions prepared with ultrasound yielded submicron droplets, ∼200nm, with Tween 80 and MPI, utilising all processing methodologies. Inverse power laws were obtained correlating emulsion droplet size with respect to energy density, highlighting the efficiency of the continuous over batch processing. This efficiency is ascribed to the smaller processing volumes, associated with continuous ultrasonic emulsification. Longer processing times were required for MPI to achieve submicron droplets (<200nm) in comparison to Tween 80 as greater times are necessary for interfacial adsorption and surface stabilisation, shown by interfacial tension measurements.

Assessment of Numerical Treatments in Interface Capturing Simulations for Surface-Tension-Driven Interface Motion

Effects of numerical treatments for the surface tension evaluation on predictions of the motions of droplets ranging from micron to sub-micron meters were investigated. Various combinations of schemes for evaluating the normal to the interface and interface curvature were examined, i.e. the ALE (arbitrary Lagrangian-eulerian) like scheme and BFA (balanced-force algorithm) for the normal vector and CSF (continuum surface force) and HF (height function) for the interface curvature. The interface motion was predicted using THAINC (tangent of hyperbola with adaptive slope for interface capturing) proposed in our previous study. Numerical errors in pressure and velocity were examined for neutrally buoyant drops of 1 mm in radius to validate the code, which confirmed that the results were similar to those reported in literature: the combination of BFA and HF gave the lowest errors. The droplet size was reduced to 0.1 mm to investigate the accuracy of the schemes for droplet sizes found in industrial coating processes. The static contact angle was then taken into account in the code. The effect of implementation on the errors was examined. The reduction of droplet sizes and implementation of contact angle had no substantial effect on the order of errors. A model for the dynamic contact angle was also implemented and the wetting behaviour of a drop of 1.14 mm in radius was well predicted. Finally a simulation of the wetting behaviour of a sub-micron meter droplet demonstrated that the present code combining BFA, HF and the dynamic contact angle model is accurate in predicting the motion of sub-micron meter droplets.

The effect of ultrasound treatment on the structural, physical and emulsifying properties of animal and vegetable proteins

The ultrasonic effect on the physicochemical and emulsifying properties of three animal proteins, bovine gelatin (BG), fish gelatin (FG) and egg white protein (EWP), and three vegetable proteins, pea protein isolate (PPI), soy protein isolate (SPI) and rice protein isolate (RPI), was investigated. Protein solutions (0.1–10 wt.%) were sonicated at an acoustic intensity of ∼34 W cm−2 for 2 min. The structural and physical properties of the proteins were probed in terms of changes in size, hydrodynamic volume and molecular structure using DLS and SLS, intrinsic viscosity and SDS-PAGE, respectively. The emulsifying performance of ultrasound treated animal and vegetable proteins were compared to their untreated counterparts and Brij 97.Ultrasound treatment reduced the size of all proteins, with the exception of RPI, and no reduction in the primary structure molecular weight profile of proteins was observed in all cases. Emulsions prepared with all untreated proteins yielded submicron droplets at concentrations ≤1 wt.%, whilst at concentrations >5 wt.% emulsions prepared with EWP, SPI and RPI yielded micron sized droplets (>10 μm) due to pressure denaturation of protein from homogenisation. Emulsions produced with sonicated FG, SPI and RPI had the similar droplet sizes as untreated proteins at the same concentrations, whilst sonicated BG, EWP and PPI emulsions at concentrations ≤1 wt.% had a smaller droplet size compared to emulsions prepared with their untreated counterparts. This effect was consistent with the observed reduction in the interfacial tension between these untreated and ultrasound treated proteins.

Optimal Selection of Supersonic Separators Inlet Velocity Components via Maximization of Swirl Strength and Centrifugal Acceleration

Revolutionary supersonic separator (3S) technology has been used extensively in natural gas dehydration. Static vanes angle of 3S plenum chamber controls various velocity components of rotating fluid and swirl strength. To provide highest swirl numbers and centrifugal accelerations, optimal values of axial, angular, and radial velocity components of entering fluid are found 20 m/s, 70 rps, and 60 m/s, respectively. Various definitions are employed to compute the swirl number. Furthermore, both swirl number and centrifugal acceleration are decreased with increasing of pressure and temperature. Maximum obtained centrifugal acceleration of 606294×g is achieved which enables the 3S unit to separate submicron droplets.

Pectins of different origin and their performance in forming and stabilizing oil-in-water-emulsions

The effectiveness of different commercially available pectin types in forming and stabilizing oil-in-water-emulsions was investigated. Sugar beet pectin as well as apple and citrus pectins with different degree of methoxylation were tested. In emulsions containing small molecule emulsifiers, all investigated pectins behave similarly. They show stabilizing properties by increasing the viscosity of the aqueous phase. This also influences the effective viscosity ratio of emulsions and it results in the formation and stabilization of submicron droplets. In emulsions without small molecule emulsifiers, the investigated pectins differ in their emulsifying behavior depending on their molecular structure. The higher the amount of covalently bound protein a pectin has, the smaller the characteristic droplet size of the resulting emulsions. Pectins with intermediate degrees of esterification produce the emulsions with the largest characteristic droplet size. Furthermore, differences in the surface activity of pectins were found. Sugar beet and citrus pectins lower the surface tension more than apple pectin. Upon the addition of sucrose, an increase in surface tension is detected but only for sugar beet and citrus pectin solutions.

Detection of sub-micron lipid droplets using transmission-mode attenuation measurements in emulsion phantoms and liver

In liver transplantation, donor liver viability is assessed by the both the amount and type of fat present in the organ. General guidelines dictate that livers with more than 30% fat should not be transplanted; however, a lack of available donor organs has led to the consideration of livers with more fat. As a part of this process, it is desirable to distinguish micro-vesicular fat (&amp;lt; 1 µm droplets) from macro-vesicular fat (~10 µm droplets). A method of evaluating the relative amounts of micro- and macro-fat is proposed based on transmission-mode ultrasound attenuation measurements. For an emulsion of one liquid in another, attenuation comprises both intrinsic losses in each medium and excess attenuation associated with interactions between media. Using an established coupled-phase model, the excess attenuation associated with a monodisperse population of lipid droplets was calculated with physical properties representative of both liver tissue and dairy products. Calculations predict that excess attenuation can exceed intrinsic attenuation and that a well-defined peak in excess attenuation at 1 MHz should occur for droplets around 0.8 µm in diameter. Such predictions are consistent with preliminary transmission-mode measurements in dairy products. [Work supported by NIH grants EB017857, EB007643, EB016118, and T32 DK007779.]

On the Reaction Characteristics of Miniemulsion Polymerization with Aqueous Phase Initiation – Experiments and Modeling

Miniemulsions, consisting of submicron droplets of very hydrophobic lauryl methacrylate or 4‐tert‐butyl styrene, are successfully polymerized using water‐soluble sodium persulfate. Monitoring the calorimetric profile as well as the droplet and particle size distribution with conversion manifests a process of monomer redistribution, droplet disappearance, and narrowing of the particle size distribution. The observed reaction characteristics could be modeled adequately, using thermodynamic principles. The results of the work presented do not only have predicting value, but also enfeeble the idea of a one‐to‐one translation of monomer droplets into polymer particles in miniemulsion polymerization.

Challenges in imaging of soft layers and structures at solid surfaces using atomic force microscopy

Imaging of soft, deformable fluid layers and structures, such as submicron droplets and bubbles or two-dimensional fluid patches, at solid interfaces with an atomic force microscopy (AFM) is a very challenging task. In this article, the authors describe the most common imaging AFM modes and advances in tapping mode AFM imaging of soft systems, as well as discuss the most common artifacts occurring in such experiments during imaging of soft and deformable features at solid interfaces. In general, for rigid and deformable systems, images recorded with the AFM are always a convolution of the tip geometry and the shape of the features being imaged. With deformable samples, the size and shape of the imaged features can additionally be affected by the imaging parameters such as set-point or gains. In addition, AFM images can be easily misprocessed with image enhancement software, resulting in an image that does not represent real features at the surface is created. This review will highlight the necessary procedures to ensure successful and accurate image acquisition in soft features in AFM.

Separating oil-water nanoemulsions using flux-enhanced hierarchical membranes.

Membranes that separate oil-water mixtures based on contrasting wetting properties have recently received significant attention. Separation of nanoemulsions, i.e. oil-water mixtures containing sub-micron droplets, still remains a key challenge. Tradeoffs between geometric constraints, high breakthrough pressure for selectivity, high flux, and mechanical durability make it challenging to design effective membranes. In this paper, we fabricate a hierarchical membrane by the phase inversion process that consists of a nanoporous separation skin layer supported by an integrated microporous layer. We demonstrate the separation of water-in-oil emulsions well below 1 μm in size. In addition, we tune the parameters of the hierarchical membrane fabrication to control the skin layer thickness and increase the total flux by a factor of four. These simple yet robust hierarchical membranes with engineered wetting characteristics show promise for large-scale, efficient separation systems.

Dynamics of submicron aerosol droplets in a robust optical trap formed by multiple Bessel beams

In this paper, we model the three-dimensional escape dynamics of single submicron-sized aerosol droplets in optical multiple Bessel beam traps. Trapping in counter-propagating Bessel beams (CPBBs) is compared with a newly proposed quadruple Bessel beam (QBB) trap, which consists of two perpendicularly arranged CPBB traps. Calculations are performed for perfectly and imperfectly aligned traps. Mie-theory and finite-difference time-domain methods are used to calculate the optical forces. The droplet escape kinetics are obtained from the solution of the Langevin equation using a Verlet algorithm. Provided the traps are perfectly aligned, the calculations indicate very long lifetimes for droplets trapped either in the CPBB or in the QBB trap. However, minor misalignments that are hard to control experimentally already severely diminish the stability of the CPBB trap. By contrast, such minor misalignments hardly affect the extended droplet lifetimes in a QBB trap. The QBB trap is found to be a stable, robust optical trap, which should enable the experimental investigation of submicron droplets with radii down to 100 nm. Optical binding between two droplets and its potential role in preventing coagulation when loading a CPBB trap is briefly addressed.

Simulations of femtosecond laser pulse interaction with spray target

AbstractLaser interactions with spray targets (clouds of submicron droplets) are studied here via numerical simulations using two-dimensional particle-in-cell codes. Our simulations demonstrate an efficient absorption of laser pulse energy inside the spray. The energy absorption efficiency depends on the inter-droplet distance, size of the cloud of droplets, and laser pulse intensity, as well as on the pre-evaporation of droplets due to laser pulse pedestal. We investigate in detail proton acceleration from the spray. Energy spectra of protons in various acceleration directions vary significantly depending on the density profile of the plasma created from the droplets and on laser intensity. The spray target can be alternative of foil targets for high intensity high repetition ultrahigh contrast femtosecond lasers. However, at intensities &gt;1021 W/cm2, the efficiency of laser absorption and ion acceleration from the droplets drops significantly in contrast to foils.

UHPH-processed O/W submicron emulsions stabilised with a lipid-based surfactant: Physicochemical characteristics and behaviour on in vitro TC7-cell monolayers and ex vivo pig's ear skin

Submicron O/W emulsions formulated with sesame oil plus a lipid-base surfactant, and with or without retinyl acetate (RAC) as a model hydrophobic biomolecule, were prepared by single-pass homogenisation at ≥200MPa (UHPH) and an initial fluid temperature (Tin) of 24°C. These emulsions were characterised by a monomodal distribution (peak maximum at 260nm) and a 2-year potential physical stability at ambient temperature. Submicron droplets were investigated in term of (i) physicochemical characteristics (size distribution curves; ζ-potential value), and (ii) impact on TC7-cell monolayers (MTT-assay and cell LDH-leakage). Submicron droplets±RAC did not affect or increased significantly (p=0.05) TC7-cell metabolic activity after 4–24h of exposure indicating absence of cellular impairment, except when high amounts of droplets were deposed on TC7-cells. Indeed, the lipid-based surfactant deposed alone on TC7-cells at high concentration, induced some significant (p=0.05) cell LDH-leakage, and therefore cell-membrane damage. Cellular uptake experiments revealed a significant (p=0.05) time-dependent internalisation of RAC from submicron droplets, and cellular transformation of RAC into retinol. The turnover of RAC into retinol and therefore RAC bioaccessibility appeared faster for RAC-micelles of similar size-range and prepared at atmospheric pressure with polysorbate 80, than for submicron O/W emulsions. Permeation experiments using pig's ear skin mounted on Franz-type diffusion cells, revealed RAC in dermis–epidermis, in significantly (p=0.05) higher amounts for submicron than coarse pre-emulsions. However, RAC amounts remained low for both emulsion-types and RAC was not detected in the receptor medium of Franz-type diffusion cells.

Tough blends of poly(lactide) and amorphous poly([R,S]-3-hydroxy butyrate) – morphology and properties

Polylactide (PLA), a biodegradable polymer, produced from annually renewable natural resources, has a glass transition temperature in the range of 50–60°C and is stiff and brittle at room temperature. In this communication we demonstrate that blending of PLA with atactic poly([R,S]-3-hydroxy butyrate) (a-PHB) leads to significant improvement of drawability and impact strength. The blends of PLA with a-PHB are biodegradable, similarly to plain PLA, and can be considered as a potential material for packaging, especially for food.The compositions containing up to 20wt.% of a-PHB were prepared and characterized by various techniques, including DSC, TGA, SEM, WAXS, DMTA and tensile tests. PLA and a-PHB appeared partially miscible and form phase-separated blends. Tg of PLA in blends decreases slightly with increasing content of a-PHB. SEM observations revealed sub-micron a-PHB droplets with diffuse interphases, dispersed well in the PLA matrix. Partial miscibility results in a slight modification of cold crystallization and melting temperatures of PLA.Foils produced from the blends by either compression molding or extrusion appeared completely amorphous. Tensile experiments revealed a small decrease of the elastic modulus and the yield stress, while an increase of the ultimate strain with increasing content of a-PHB. These were related to the change of the deformation behavior from brittle to ductile and its micromechanisms. Easily cavitating a-PHB inclusions initiate numerous crazes in PLA matrix. These crazes become diffuse, frequently deflected and terminated by other a-PHB inclusions. At higher content of a-PHB the dense collections of diffused crazes merge to form deformation bands and eventually a macroscopic neck. Along with improvement of drawability at low deformation rate also the impact properties, probed in tensile impact test, are substantially improved. The thin-film tensile impact resistance increases from about 50kJ/m2 in plain PLA to nearly 120kJ/m2 in 80:20 PLA/a-PHB blend.

The efficiency and stability of bubble formation by acoustic vaporization of submicron perfluorocarbon droplets

Submicron droplets of liquid perfluorocarbon converted into microbubbles with applied ultrasound have been studied, for a number of years, as potential next generation extravascular ultrasound contrast agents. In this work, we conduct an initial ultra-high-speed optical imaging study to examine the vaporization of submicron droplets and observe the newly created microbubbles in the first microseconds after vaporization. It was estimated that single pulses of ultrasound at 10MHz with pressures within the diagnostic range are able to vaporize on the order of at least 10% of the exposed droplets. However, only part of the newly created microbubbles survives immediately following vaporization – the bubbles may recondense back into the liquid droplet state within microseconds of nucleation. The probability of bubble survival within the first microseconds of vaporization was shown to depend on ultrasound excitation pressure as well as on bubble coalescence during vaporization, a behavior influenced by the presence of coating material on the newly created bubbles. The results of this study show for the first time that although initial vaporization of droplets is necessary to create echogenic bubbles, additional factors, such as coalescence and bubble shell properties, are important and should be carefully considered for the production of microbubbles for use in medical imaging.

About diagnosis of submicron droplets in a gas-droplet flow

Possibilities and limitations of the optical diagnostic methods for small-size (about 1 μm) droplets in the gasdroplet flows are discussed. Here we show the possibility for restoration of the functions of droplet distribution and droplet average size on the basis of measurements of ultradispersed particle parameters formed from microdroplet flows after droplet evaporation.

Intracellular fate of retinyl acetate-loaded submicron delivery systems by in vitro intestinal epithelial cells: A comparison between whey protein-stabilised submicron droplets and micelles stabilised with polysorbate 80

Submicron peanut oil-in-water emulsion stabilised with whey proteins, was processed by ultra-high-pressure homogenisation at 200MPa (first-stage, 2-pass homogenisation) and an initial emulsion temperature (Tin) of 24°C. Retinyl acetate (RAC) was selected as a model of a lipophilic biomolecule to be carried by submicron droplets. For comparison, micelles of retinyl acetate (RAC-micelles) were prepared at atmospheric pressure using polysorbate 80 (Tween® 80) as emulsifier. Both types of bio-particles displayed submicron diameters. Their behaviour was investigated on TC7-cell monolayers to characterise their influence on monolayer integrity (TER measurements), cell metabolic activity (MTT-assay) and cell membrane integrity (LDH-leakage). TC7-cell exposure to submicron droplets UHPH-elaborated as shuttles for RAC, and stabilised with proteins, did not impair TC7-cell viability compared with control cells (without deposit) or cells exposed to RAC-micelles. Such results demonstrated UHPH-processing innocuity in terms of Novel Food Regulation and implementation of UHPH as a novel technology. TC7-cell internalisation of whey proteins coating submicron oil droplets was observed using confocal microscopy and fluorescent probes. Cellular uptake of RAC was determined for both systems, after extraction from TC7 cells and HPLC quantitation. Results revealed RAC incorporation into TC7 cells and cellular turn-over of RAC into retinol for both systems without previous in vitro digestion. RAC bioaccessibility appeared yet better in the form of RAC-micelles than after entrapment into oily submicron droplets. Nevertheless, submicron droplets stabilised by proteins displayed a better physical stability than did RAC-micelles, which is the main feature for further developments of carrier systems.

Miniemulsions for the Production of Nanostructured Particles

AbstractNanostructured particles made from polystyrene and zinc oxide are synthesized by precipitation in miniemulsions and miniemulsion polymerization. There are two main applications for miniemulsions: the formation of sub‐micron or nano‐sized reactors for the precipitation of inorganic nanoparticles and the use of sub‐micron or nano‐sized droplets as templates for nanostructured particles. The latter includes the formation of the desired structures within a monomer droplet, which then is polymerized without changing its size or structure during the process. In this research article two approaches to combine both processes are presented: The zinc oxide nanoparticles are precipitated in an inverse miniemulsion of water droplets in a continuous monomer phase. The resulting miniemulsion is either distilled and the nanoparticles are forced into the monomer phase or the miniemulsion is used directly without distillation. In both cases the particle loaded monomer droplets are afterwards polymerized to hybrid nanoparticles. The focus is on the technological challenges in producing nano‐sized, hybrid particles, especially in regard to continuous processing.

Ethanol (C2H5OH) spray of sub-micron droplets for laser driven negative ion source

Liquid ethanol (C(2)H(5)OH) was used to generate a spray of sub-micron droplets. Sprays with different nozzle geometries have been tested and characterised using Mie scattering to find scaling properties and to generate droplets with different diameters within the spray. Nozzles having throat diameters of 470 μm and 560 μm showed generation of ethanol spray with droplet diameters of (180 ± 10) nm and (140 ± 10) nm, respectively. These investigations were motivated by the observation of copious negative ions from these target systems, e.g., negative oxygen and carbon ions measured from water and ethanol sprays irradiated with ultra-intense (5 × 10(19) W/cm(2)), ultra short (40 fs) laser pulses. It is shown that the droplet diameter and the average atomic density of the spray have a significant effect on the numbers and energies of accelerated ions, both positive and negative. These targets open new possibilities for the creation of efficient and compact sources of different negative ion species.