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 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) 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 colloidosomes). 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 very promising technique for production of monodispersed droplets with droplet throughputs of up to 100 l h
−1
.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The precise knowledge of the neutrino flux composition and kinematics is one of the biggest challenges of long-baseline experiments such as T2K. Neutrinos are made by the in-flight decay of unstable ...hadrons produced by the interactions of 31GeV/c protons in a long graphite target. Mostly π+ (π−) are created, leading to the νμ(ν¯μ) enhanced flux. As kaons and muons are also produced, an irreducible background of electron (anti-)neutrino is also present. The main source of uncertainty in the flux prediction is driven by the lack of data on the proton-carbon interaction in this energy range. The measurements performed by the NA61/SHINE large-acceptance experiment at CERN are used by the T2K collaboration to improve the flux predictions. Two datasets have been taken: using a thin target to study the primary interaction, and a replica of the T2K target to account for the re-interactions. The recently released differential multiplicity distributions of π± along the replica target measured in NA61/SHINE will be presented. This dataset is now in the process of being used by T2K to further tune the flux prediction as 90% of the neutrinos will be directly constrained.
Display omitted
This paper is an overview of the applications of microporous membranes for preparation of micro/nano- emulsions. Membrane emulsification offers compact devices for preparation of ...nanoemulsions with low energy consumption, tuneable droplet size, monomodal distribution, and high encapsulation efficiency of entrapped functional components without shear or thermal degradation. The properties and wettability modification of Shirasu Porous Glass (SPG) membrane, track-etched polymeric sheets, syringe filters, anodic alumina membrane, and nickel-based superalloy membranes were discussed, as well as the design and operation of membrane devices. Particular emphasis was placed on the effect of formulation, operating parameters, and membrane properties on the resulting droplet size in direct and premix membrane emulsification with the examples of nano-sized emulsions produced using different membranes. The application of microemulsions prepared using synthetic membranes for production of solid self-microemulsifying drug delivery systems for enhanced solubility and oral bioavailability of BSC Class II and III drugs was also reviewed, as well as production of solid nanoparticles such as nanogels, solid lipid nanoparticles, synthetic biodegradable polymer nanoparticles, silica and metal oxide nanoparticles from nanoemulsion templates prepared by membrane emulsification.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Shirasu-porous-glass (SPG) membranes with a mean pore size from 0.4–6.6 μm were used to produce O/W emulsions consisting of vegetable (rape seed) oil as the dispersed phase and Span 80 dissolved in ...demineralized water as the continuous phase. The emulsion droplets with a mean droplet size 3.5 times larger than the mean pore size and the span of the droplet size distribution between 0.26 and 0.45 were produced using 2% emulsifier at a transmembrane pressure slightly exceeding the capillary pressure. Under these conditions the dispersed phase flux through the membrane was in the range of 0.7–7 1·m
−2·h
−1 and only about 2% of the pores were active. However, if the transmembrane pressure was considerably higher than the capillary pressure, the dispersed phase flux strongly increased and droplets with a broad droplet size distribution were produced. The hydraulic resistance of the SPG membrane was inversely proportional to the square of the mean pore size, which is in agreement with the Hagen-Poiseuille law. The membrane porosity is independent on the pore size and ranged from 53–60%.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Electrospun porous fibres are produced in a single step using binary solvents.•A ternary graph shows the mixture compositions required to produce porous fibres.•The boiling point/evaporation rate of ...the good solvent determines the pore formation.•An empirical equation correlating the fibre diameter to the solution properties was developed.
Porous electrospun poly(ε-caprolactone) (PCL) fibres were produced through a non-solvent induced phase separation mechanism, using binary solvent systems with different properties. The effect of the solvent properties on the size and surface morphology of electrospun PCL fibres was investigated. Chloroform (CF), dichloromethane (DCM), tetrahydrofuran (THF) and formic acid (FA) were used as good solvents in mixtures with a poor solvent, dimethyl sulfoxide (DMSO), in order to generate pores on the fibre surface. The production of porous, bead free fibres with an average diameter ranging from 1470 to 2270nm was achieved using 12.5% w/v PCL in CF/DMSO solution with good/poor solvent ratios varying from 75% to 90% v/v at the applied voltage of 15kV, a spinning distance of 20cm, and the feed flow rate of 1ml/h. DCM and THF were proven to be less suitable good solvents for the process due to the formation of a solid skin on the jet surface, caused by the limited diffusivity of the polymer molecules from the jet surface to the liquid core and its subsequent collapse. FA was found to be unsuitable due to its similar evaporation rate to DMSO. The pore formation was favoured at high good/poor solvent ratios, whereas, the production of fibres with ribbon cross sections or fibres with beads was more pronounced at low good/poor solvent ratios. Data fitting was used for the development of a second order polynomial equation, correlating the produced fibre average diameter to the solution parameters (conductivity, surface tension, and viscosity), for the given polymer and solvent systems, under the specific experimental conditions used in this study. The ternary mixture compositions that lead to the formation of porous fibres were mapped on a ternary graph.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Display omitted
•The mechanisms of single-step formation of multi-core double emulsion were revealed.•Phase diagrams for predicting number of encapsulated inner drops were mapped out.•The jet ...pinch-off process was accompanied and affected by presence of a vortex flow.•The formation regime of inner phase affected the number of encapsulated inner drops.•Large single-core capsules were made from dual-core drops with unstable inner drops.
Single-step generation of monodisperse multi-core double emulsion drops in three-phase glass capillary microfluidic device was investigated using a micro-particle image velocimetry (micro-PIV) system. Phase diagrams were developed to predict the number of encapsulated inner drops as a function of the capillary numbers of inner, middle and outer fluid. The maximum stable number of inner drops cores in uniform double emulsion drops was six. Starting from core/shell drops, the formation of double emulsion drops with multiple cores was achieved by decreasing the capillary number of the outer fluid and increasing the capillary number of the middle fluid. A stable continuous jet of the middle fluid loaded with inner drops was formed at high capillary numbers of the middle fluid. Empirical correlations predicting the size and generation frequency of inner drops as a function of the capillary numbers and the device geometry were developed. Dual-core double emulsion drops were used as templates for the fabrication of polymeric capsules using “on-the-fly” photopolymerisation. The capsule morphology was controlled by manipulating the stability of the inner drops through adjusting the concentration of the lipophilic surfactant in the middle fluid. At low concentration of the lipophilic surfactant, inner drops coalesced during curing and single compartment capsules with thin shells were produced from dual-core drops. The core/shell capsules produced from multi-core drops were monodispersed and larger than those produced from core/shell drops in the same device.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Against a backdrop of global antibiotic resistance and increasing awareness of the importance of the human microbiota, there has been resurgent interest in the potential use of bacteriophages for ...therapeutic purposes, known as phage therapy. A number of phage therapy phase I and II clinical trials have concluded, and shown phages don't present significant adverse safety concerns. These clinical trials used simple phage suspensions without any formulation and phage stability was of secondary concern. Phages have a limited stability in solution, and undergo a significant drop in phage titre during processing and storage which is unacceptable if phages are to become regulated pharmaceuticals, where stable dosage and well defined pharmacokinetics and pharmacodynamics are de rigueur. Animal studies have shown that the efficacy of phage therapy outcomes depend on the phage concentration (i.e. the dose) delivered at the site of infection, and their ability to target and kill bacteria, arresting bacterial growth and clearing the infection. In addition, in vitro and animal studies have shown the importance of using phage cocktails rather than single phage preparations to achieve better therapy outcomes. The in vivo reduction of phage concentration due to interactions with host antibodies or other clearance mechanisms may necessitate repeated dosing of phages, or sustained release approaches. Modelling of phage-bacterium population dynamics reinforces these points. Surprisingly little attention has been devoted to the effect of formulation on phage therapy outcomes, given the need for phage cocktails, where each phage within a cocktail may require significantly different formulation to retain a high enough infective dose.
This review firstly looks at the clinical needs and challenges (informed through a review of key animal studies evaluating phage therapy) associated with treatment of acute and chronic infections and the drivers for phage encapsulation. An important driver for formulation and encapsulation is shelf life and storage of phage to ensure reproducible dosages. Other drivers include formulation of phage for encapsulation in micro- and nanoparticles for effective delivery, encapsulation in stimuli responsive systems for triggered controlled or sustained release at the targeted site of infection. Encapsulation of phage (e.g. in liposomes) may also be used to increase the circulation time of phage for treating systemic infections, for prophylactic treatment or to treat intracellular infections. We then proceed to document approaches used in the published literature on the formulation and stabilisation of phage for storage and encapsulation of bacteriophage in micro- and nanostructured materials using freeze drying (lyophilization), spray drying, in emulsions e.g. ointments, polymeric microparticles, nanoparticles and liposomes. As phage therapy moves forward towards Phase III clinical trials, the review concludes by looking at promising new approaches for micro- and nanoencapsulation of phages and how these may address gaps in the field.
Display omitted
•Review of phage therapy studies in acute infection animal models shows the need for stable high phage titres•Phage cocktails are important for therapy and their formulation needs thorough consideration•Modelling and review of phage-bacterium pharmacodynamics shows advantages of controlled and sustained release systems for high phage doses•Review of spray/freeze drying literature highlights considerable variability in phage survival and stability of the resulting product•Literature on phage encapsulation in microparticles, nanoparticles including liposomes and electrospun fibers is reviewed
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Monodispersed polymeric microcapsules loaded with CO2 solvents or chelating agents were produced by capillary microfluidics by photopolymerisation of three different UV curable materials, ...1,6‐hexanediol diacrylate (HDDA), Norland Optical Adhesive (NOA) 81, and Semicosil® 949 UV A/B (PDMS). Polymerization of HDDA and NOA 81 started after exposure to UVA light for 5 s and was completed within a minute, as confirmed by continuous FT‐IR. Corrosive aqueous solutions of tetraethylenepentamine and diisopropyl iminodiacetic acid were encapsulated with 100% efficiency into poly(HDDA) and cured NOA81 shells without any leakage during prolonged storage. Poly(HDDA) shells were mechanically more stable than cured NOA81 and PDMS shells and resistant to drying‐induced shell buckling. NOA81 and PDMS capsules underwent morphological changes during freeze drying leading to the formation of dimpled and crescent‐moon‐shaped particles, respectively. The storage stability in a hypotonic solution and buckling resistance of PDMS shells were significantly improved by embedding carbon‐based nanomaterials into PDMS matrix. The incorporation of 0.5 wt% multi‐walled carbon nanotubes into PDMS matrix led to an increase in a Shore A hardness from 1.6 to 2.3. A uniform distribution of MWCNTs in the polymer network was confirmed by XRD. All fabricated shells were thermally stable up to the temperature of 300°C.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This review focuses on recent developments in the fabrication of multiple emulsions in micro-scale systems such as membranes, microchannel array, and microfluidic emulsification devices. Membrane and ...microchannel emulsification offer great potential to manufacture multiple emulsions with uniform drop sizes and high encapsulation efficiency of encapsulated active materials. Meanwhile, microfluidic devices enable an unprecedented level of control over the number, size, and type of internal droplets at each hierarchical level but suffer from low production scale. Microfluidic methods can be used to generate high-order multiple emulsions （triple, quadruple, and quintuple）, non-spherical （discoidal and rod-like） drops, and asymmetric drops such as Janus and ternary drops with two or three distinct surface regions. Multiple emulsion droplets generated in microfabricated devices can be used as templates for vesicles like polymersomes, liposomes, and colloidosomes with multiple inner compartments for simultaneous encaosulation and release of incomoatible active materials or reactants.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
PDF
