The adsorption and self-assembly of surfactant mixtures: How the detailed evaluation of adsorption properties provides access to the bulk behaviour.

The nature of surfactant mixing at interfaces and in bulk solution is key to understanding and optimising the diverse industrial, technological, biological and domestic applications of surfactants. The use of neutron reflectivity, NR, and small angle neutron scattering, SANS, in combination with isotopic substitution, has transformed the ability to quantify and understand the nature of surfactant mixing at the air-water interface and in self-assembled aggregates or micelles in solution. The accuracy and scope of the compositional data from NR, the application of recent developments in the pseudo phase approximation, PPA, and the availability of complementary critical micelle concentration, cmc, and micelle composition data, enables a detailed thermodynamical quantification of the mixing properties to be made. The NR data in particular, and the SANS data to a lesser extent, provides constraints on the thermodynamical analysis which reveals important properties and trends about the bulk phase which are not available from the analysis of data such as the variation in the cmc alone. The importance and impact of this approach is illustrated with an overview of a range of mixed surfactant examples from the recent literature, and which encompass mixtures with different degrees of departure from ideality.

Self-assembly in escin-nonionic surfactant mixtures: From micelles to vesicles.

HYPOTHESIS: Saponins are a class of plant derived surfactants which are widely used in food related foams and emulsions, aerated drinks, and in pharmaceuticals and cosmetics. As a potential biosourced and renewable ingredient in a wider range of surfactant based formulations their potential is intimately associated with their mixing with synthetic surfactants. As such the nature of the mixed saponin-surfactant self-assembly is an important characteristic to investigate and understand. The unconventional structure of the saponins compared to the conventional synthetic surfactants poses some interesting constraints on the structures of the mixed aggregates. EXPERIMENTS: Small angle neutron scattering, SANS, is used to investigate the structure of the saponin, escin, mixed with a range of nonionic surfactants with different ethylene oxide groups, from triethylene glycol monododecyl ether, C12E3, to dodecaethylene glycol monododecyl ether, C12E12. FINDINGS: The scattering data reveal a complex evolution in the solution self-assembled structure with varying escin / nonionic composition and ethylene oxide chain length. The rich structural development comprises of the evolution from the elongated micelle structure of escin to the micelle structure of the nonionic surfactant. At the intermediate solution compositions the structure is predominantly planar, comprising mostly of planar / micellar mixed phases. The nature of the planar structures depend upon the ethylene oxide chain length and the solution composition, and include lamellar, bilamellar vesicle, multilamellar vesicle, and nanovesicle structures, in common with what is observed in other surfactant mixtures.

Adsorption and self-assembly properties of the plant based biosurfactant, Glycyrrhizic acid.

There is an increased interest in the use of natural surfactant as replacements for synthetic surfactants due to their biosustainable and biocompatible properties. A category of natural surfactants which are attracting much current interest is the triterpenoid saponins; surface active components found extensively in a wide range of plant species. A wide range of different saponin structures exist, depending upon the plant species they are extracted from; but regardless of the variation in structural details they are all highly surface active glycosides. Greater exploitation and application requires a characterisation and understanding of their basic adsorption and self-assembly properties. HYPOTHESIS: Glycyrrhizic acid, extracted from Licorice root, is a monodesmosidic triterpenoid saponin. It is widely used in cosmetic and pharmaceutical applications due to its anti-inflammatory properties, and is an ingredient in foods as a sweetener additive. It has an additional attraction due to its gel forming properties at relatively low concentrations. Although it has attracted much recent attention, many of its basic surface active characteristics, adsorption and self-assembly, remain relatively unexplored. How the structure of the Glycyrrhizic acid saponin affects its surface active properties and the impact of gelation on these properties are important considerations, and to investigate these are the focus of the study. EXPERIMENTS: In this paper the adsorption properties at the air-water interface and the self-assembly in solution have been investigated using by neutron reflectivity and small angle neutron scattering; in non-gelling and gelling conditions. FINDINGS: The adsorption isotherm is determined in water and in the presence of gelling additives, and compared with the adsorption behaviour of other saponins. Gelation has minimal impact on the adsorption; apart from producing a rougher surface with a surface texture on a macroscopic length scale. Globular micelles are formed in aqueous solution with modest anisotropy, and are compared with the structure of other saponin micelles. The addition of gelling agents results in only minimal micelle growth, and the solutions remain isotropic under applied shear flow.

Mixing Natural and Synthetic Surfactants: Co-Adsorption of Triterpenoid Saponins and Sodium Dodecyl Sulfate at the Air-Water Interface.

Saponins are highly surface active glycosides, derived from a wide range of plant species. Their ability to produce stable foams and emulsions has stimulated their applications in beverages, foods, and cosmetics. To explore a wider range of potential applications, their surface mixing properties with conventional surfactants have been investigated. The competitive adsorption of the triterpenoid saponin escin with an anionic surfactant sodium dodecyl sulfate, SDS, at the air-water interface has been studied by neutron reflectivity, NR, and surface tension. The NR measurements, at concentrations above the mixed critical micelle concentration, demonstrate the impact of the relative surface activities of the two components. The surface mixing is highly nonideal and can be described quantitatively by the pseudophase approximation with the inclusion of the quadratic and cubic terms in the excess free energy of mixing. Hence, the surface mixing is highly asymmetrical and reflects both the electrostatic and steric contributions to the intermolecular interactions. The relative importance of the steric contribution is reinforced by the observation that the micelle mixing is even more nonideal than the surface mixing. The mixing properties result in the surface adsorption being largely dominated by the SDS over the composition and concentration range explored. The results and their interpretation provide an important insight into the wider potential for mixing saponins with more conventional surfactants.

Surfactant/biosurfactant mixing: Adsorption of saponin/nonionic surfactant mixtures at the air-water interface.

Saponins are naturally occurring biosurfactants present in a wide range of plant species. They are highly surface active glycosides, and are used to stabilise foams and emulsions in foods, beverages and cosmetics. They have great potential for an even wider range of applications, especially when mixed with different synthetic surfactants. Understanding those mixing properties are key to the exploitation of saponins in that wider range of potential applications. The surface adsorption properties of the saponin, escin, with two conventional nonionic surfactants, polyethylene glycol surfactants, have been studied at the air-water interface using neutron reflectivity, NR, and surface tension, ST. Although the saponin and polyethylene glycol, CnEOm, surfactants are both nonionic the disparity in the relative surface activities and packing constraints result in non-ideal mixing. Comparison with the predictions of the pseudo phase approximation requires the inclusion of the quadratic, cubic and quartic terms in the expansion of the excess free energy of mixing to explain the variations in the surface composition. For escin/pentaethylene glycol monododecyl ether, C12EO5, the interaction is attractive and close to ideal. For escin/octaethylene glycol monododecyl ether, C12EO8, it is repulsive and close to the criteria for demixing. The differences in mixing behaviour are attributed to greater packing constraints imposed by the larger ethylene oxide headgroup of the C12EO8 compared to C12EO5.

Adsorption properties of plant based bio-surfactants: Insights from neutron scattering techniques.

There is an increasing interest in biosustainable surfactants and surface active proteins for a range of applications, in home and personal care products, cosmetics, pharmaceuticals, and food and drink formulations. This review focuses on two plant derived biosurfactants, the surface active glycoside, saponin, and the surface active globular protein, hydrophobin. A particular emphasis in the review is on the role of neutron reflectivity in probing the adsorption, structure of the adsorbed layer, and their mixing at the interface with a range of more conventional surfactants and proteins.

The performance of surfactant mixtures at low temperatures.

Optimising detergency at lower temperatures is of increasing interest due to environmental and economic factors, and requires a greater understanding of the effects of temperature on the adsorption of surfactant mixtures at interfaces. The adsorption properties of surfactant mixtures and biosurfactant/surfactant mixtures have been studied at room temperatures and at temperatures below ambient using surface tension and neutron reflectivity measurements. For the ternary surfactant mixture of octaethylene monododecyl ether, C12E8, sodium dodecyl 6-benzene sulfonate, LAS, and sodium dioxyethylene glycol monododecyl sulfate, SLES, the surface tension at the air-water interface increases with decreasing temperature. In contrast, there is a notable reduction in the increase in the surface tension with a decrease in temperature from 25 °C to 10 °C for the 5 component rhamnolipid/surfactant mixture of the mono-rhamnose, R1, and di-rhamnose, R2, with C12E8/LAS/SLES. The associated neutron reflectivity data for the ternary C12E8/LAS/SLES mixture and the significant observation is that the 3, 4, and 5-component mixtures containing rhamnolipids in conjunction with the other surfactants show changes in composition and adsorbed amounts of the individual components which are close to the experimental error. However the significant observation is that the neutron reflectivity data indicate that the improved surface tension tolerance at lower temperatures is associated with the dominance of the rhamnolipid adsorption in such mixtures. Hence the introduction of the rhamnolipids provides a tolerance to the adverse effects associated with reduced temperatures, and a potential for improved detergency at relatively low temperatures.

Saponin Adsorption at the Air-Water Interface-Neutron Reflectivity and Surface Tension Study.

Saponins are a large group of glycosides present in many plant species. They exhibit high surface activity, which arises from a hydrophobic scaffold of triterpenoid or steroid groups and attached hydrophilic saccharide chains. The diversity of molecular structures, present in various plants, gives rise to a rich variety of physicochemical properties and biological activity and results in a wide range of applications in foods, cosmetics, medicine, and several other industrial sectors. Saponin surface activity is a key property in such applications and here the adsorption of three triterpenoid saponins, escin, tea saponins, and Quillaja saponin, is studied at the air-water interface by neutron reflectivity and surface tension. All these saponins form adsorption layers with very high surface visco-elasticity. The structure of the adsorbed layers has been determined from the neutron reflectivity data and is related to the molecular structure of the saponins. The results indicate that the structure of the saturated adsorption layers is governed by densely packed hydrophilic saccharide groups. The tight molecular packing and the strong hydrogen bonds between the neighboring saccharide groups are the main reasons for the unusual rheological properties of the saponin adsorption layers.

The impact of electrolyte on the adsorption of the anionic surfactant methyl ester sulfonate at the air-solution interface: Surface multilayer formation.

The methyl ester sulfonates represent a promising group of anionic surfactants which have the potential for improved performance and biocompatibility in a range of applications. Their solution properties, in particular their tolerance to hard water, suggests that surface ordering may occur in the presence of multi-valent counterion. Understanding their adsorption properties in a range of different circumstances is key to the exploitation of their potential. Neutron reflectivity and surface tension have been used to characterise the adsorption at the air-aqueous solution interface of the anionic surfactant sodium tetradecanoic 2-sulfo 1-methyl ester, C14MES, in the absence of electrolyte and in the presence of mono, di, and tri-valent counterions, Na+, Ca2+, and Al3+. In particular the emphasis has been on exploring the tendency to form layered structures at the interface. In the absence of electrolyte and in the presence of NaCl and CaCl2 and AlCl3 at low concentrations monolayer adsorption is observed, and the addition of electrolyte results in enhanced adsorption. In the presence of NaCl and CaCl2 only monolayer adsorption is observed. However at higher AlCl3 concentrations surface multilayer formation is observed, in which the number of bilayers at the surface depends upon the surfactant and AlCl3 concentrations.

Self-assembly in dilute mixtures of non-ionic and anionic surfactants and rhamnolipd biosurfactants.

The self-assembly of dilute aqueous solutions of a ternary surfactant mixture and rhamnolipid biosurfactant/surfactant mixtures has been studied by small angle neutron scattering. In the ternary surfactant mixture of octaethylene glycol monododecyl ether, C12E8, sodium dodecyl 6-benzene sulfonate, LAS, and sodium dioxyethylene monododecyl sulfate, SLES, small globular interacting micelles are observed over the entire composition and concentration range studied. The modelling of the scattering data strongly supports the assumption that the micelle compositions are close to the solution compositions. In the 5-component rhamnolipid/surfactant mixture of the mono-rhamnose, R1, di-rhamnose, R2, rhamnolipids with C12E8/LAS/SLES, globular micelles are observed over much of the concentration and composition range studied. However, for solutions relatively rich in rhamnolipid and LAS, lamellar/micellar coexistence is observed. The transition from globular to more planar structures arises from a synergistic packing in the 5 component mixture. It is not observed in the individual components nor in the ternary C12E8/LAS/SLES mixture at these relatively low concentrations. The results provide an insight into how synergistic packing effects can occur in the solution self-assembly of complex multi-component surfactant mixtures, and give rise to an unexpected evolution in the phase behaviour.

Adsorption of hydrophobin/ß-casein mixtures at the solid-liquid interface.

The adsorption behaviour of mixtures of the proteins ß-casein and hydrophobin at the hydrophilic solid-liquid surface have been studied by neutron reflectivity. The results of measurements from sequential adsorption and co-adsorption from solution are contrasted. The adsorption properties of protein mixtures are important for a wide range of applications. Because of competing factors the adsorption behaviour of protein mixtures at interfaces is often difficult to predict. This is particularly true for mixtures containing hydrophobin as hydrophobin possesses some unusual surface properties. At ß-casein concentrations ⩾0.1wt% ß-casein largely displaces a pre-adsorbed layer of hydrophobin at the interface, similar to that observed in hydrophobin-surfactant mixtures. In the composition and concentration range studied here for the co-adsorption of ß-casein-hydrophobin mixtures the adsorption is dominated by the ß-casein adsorption. The results provide an important insight into how the competitive adsorption in protein mixtures of hydrophobin and ß-casein can impact upon the modification of solid surface properties and the potential for a wide range of colloid stabilisation applications.

Nature of the Intermicellar Interactions in Ethoxylated Polysorbate Surfactants with High Degrees of Ethoxylation.

Ethoxylated polysorbate Tween nonionic surfactants are extensively used as foam and emulsion stabilizers and in aqueous solution form globular micelles. The ethoxylated polysorbate surfactants with higher degrees of ethoxylation than the Tween surfactants exhibit some interesting self-assembly properties. Small-angle neutron scattering, SANS, measurements have revealed intermicellar interactions which are more pronounced than the hard-sphere excluded volume interactions normally associated with nonionic surfactant micelles. The interactions are interpreted as arising from the partial charge on the ether oxygen of the ethylene oxide groups. This gives rise to an effective net negative charge on the micelles, which has been determined from the SANS data and zeta potential measurements. For degrees of ethoxylation of ⩽20, the effect is relatively small. The interaction increases with increasing ethoxylation such that for a degree of ethoxylation of 50 the interaction is comparable to that of ionic surfactant micelles. Unlike the intermicellar interaction in ionic surfactant micellar solutions, which results from the charge on the micelle arising from the partial binding of counterions, the interaction between ethoxthylated polysorbate surfactant micelles is unaffected by the addition of electrolyte.

Tuning Polyelectrolyte-Surfactant Interactions: Modification of Poly(ethylenimine) with Propylene Oxide and Blocks of Ethylene Oxide.

Significantly enhanced adsorption at the air-water interface arises in polyelectrolyte/ionic surfactant mixtures, such as poly(ethylenimine)/sodium dodecyl sulfate (PEI/SDS), down to relatively low surfactant concentrations due to a strong surface interaction between the polyelectrolyte and surfactant. In the region of charge neutralization this can result in precipitation or coacervation and give rise to undesirable properties in many applications. Ethoxylation of the PEI can avoid precipitation, but can also considerably weaken the interaction. Localization of the ethoxylation can overcome these shortcomings. Further manipulation of the polyelectrolyte-surfactant interaction can be achieved by selective ethoxylation and propoxylation of the PEI amine groups. Neutron reflectivity and surface tension data are presented here which show how the polyelectrolyte-surfactant interaction can be manipulated by tuning the PEI structure. Using deuterium labeled surfactant and polymer the neutron reflectivity measurements provide details of the surface composition and structure of the adsorbed layer. The general pattern of behavior is that at low surfactant concentrations there is enhanced surfactant adsorption due to the strong surface interaction; whereas around the region of the SDS critical micellar concentration, cmc, the surface is partially depleted of surfactant in favor bulk aggregate structures. The results presented here show how these characteristic features of the adsorption are affected by the degree of ethoxylation and propoxylation. Increasing the degree of propoxylation enhances the surfactant adsorption, whereas varying the degree of ethoxylation has a less pronounced effect. In the region of surfactant surface depletion increasing both the degree of ethoxylation and propoxylation result in an increased surface depletion.

A new generation of cancer genome diagnostics for routine clinical use: overcoming the roadblocks to personalized cancer medicine.

The identification of 'druggable' kinase gene alterations has revolutionized cancer treatment in the last decade by providing new and successfully targetable drug targets. Thus, genotyping tumors for matching the right patients with the right drugs have become a clinical routine. Today, advances in sequencing technology and computational genome analyses enable the discovery of a constantly growing number of genome alterations relevant for clinical decision making. As a consequence, several technological approaches have emerged in order to deal with these rapidly increasing demands for clinical cancer genome analyses. Here, we describe challenges on the path to the broad introduction of diagnostic cancer genome analyses and the technologies that can be applied to overcome them. We define three generations of molecular diagnostics that are in clinical use. The latest generation of these approaches involves deep and thus, highly sensitive sequencing of all therapeutically relevant types of genome alterations-mutations, copy number alterations and rearrangements/fusions-in a single assay. Such approaches therefore have substantial advantages (less time and less tissue required) over PCR-based methods that typically have to be combined with fluorescence in situ hybridization for detection of gene amplifications and fusions. Since these new technologies work reliably on routine diagnostic formalin-fixed, paraffin-embedded specimens, they can help expedite the broad introduction of personalized cancer therapy into the clinic by providing comprehensive, sensitive and accurate cancer genome diagnoses in 'real-time'.

Biogenic amine ­ surfactant interactions at the air-water interface.

The strong interaction between polyamines and anionic surfactants results in pronounced adsorption at the air-water interface and can lead to the formation of layered surface structures. The transition from monolayer adsorption to more complex surface structures depends upon solution pH, and the structure and molecular weight of the polyamine. The effects of manipulating the polyamine molecular weight and structure on the adsorption of the anionic surfactant sodium dodecyl sulphate at the air-water interface are investigated using neutron reflectivity and surface tension, for the biogenic amines putrescine, spermidine and spermine. The results show how changing the number of amine groups and the spacing between the amine groups impacts upon the surface adsorption. At lower pH, 3-7, and for the higher molecular weight polyamines, spermidine and spermine, ordered multilayer structures are observed. For putrescine at all pH and for spermidine and spermine at high pH, monolayer adsorption with enhanced surfactant adsorption compared to the pure surfactant is observed. The data for the biogenic amines, when compared with similar data for the polyamines ethylenediamine, diethylenetriamine and triethylenetetramine, indicate that the spacing between amines groups is more optimal for the formation of ordered surface multilayer structures.

Solution pH and oligoamine molecular weight dependence of the transition from monolayer to multilayer adsorption at the air-water interface from sodium dodecyl sulfate/oligoamine mixtures.

Neutron reflectivity and surface tension have been used to investigate the solution pH and oligoamine molecular weight dependence of the adsorption of sodium dodecyl sulfate (SDS)/oligoamine mixtures at the air-water interface. For diethylenetriamine, triamine, or triethylenetetramine, tetramine mixed with SDS, there is monolayer adsorption at pH 7 and 10, and multilayer adsorption at pH 3. For the slightly higher molecular weight tetraethylenepentamine, pentamine, and pentaethylenehexamine, hexamine, the adsorption is in the form of a monolayer at pH 3 and multilayers at pH 7 and 10. Hence, there is a pH driven transition from monolayer to multilayer adsorption, which shifts from low pH to higher pH as the oligoamine molecular weight increases from tetramine to pentamine. This results from the relative balance between the electrostatic attraction between the SDS and amine nitrogen group which decreases as the charge density decreases with increasing pH, the ion-dipole interaction between the amine nitrogen and SDS sulfate group which is dominant at higher pH, and the hydrophobic interalkyl chain interaction between bound SDS molecules which changes with oligoamine molecular weight.

Kinetics of surfactant desorption at an air-solution interface.

The kinetics of re-equilibration of the anionic surfactant sodium dodecylbenzene sulfonate at the air-solution interface have been studied using neutron reflectivity. The experimental arrangement incorporates a novel flow cell in which the subphase can be exchanged (diluted) using a laminar flow while the surface region remains unaltered. The rate of the re-equilibration is relatively slow and occurs over many tens of minutes, which is comparable with the dilution time scale of approximately 10-30 min. A detailed mathematical model, in which the rate of the desorption is determined by transport through a near-surface diffusion layer into a diluted bulk solution below, is developed and provides a good description of the time-dependent adsorption data. A key parameter of the model is the ratio of the depth of the diffusion layer, H(c), to the depth of the fluid, H(f), and we find that this is related to the reduced Péclet number, Pe*, for the system, via H(c)/H(f) = C/Pe*(1/2). Although from a highly idealized experimental arrangement, the results provide an important insight into the "rinse mechanism", which is applicable to a wide variety of domestic and industrial circumstances.

Adsorption of the linear poly(ethyleneimine) precursor poly(2-ethyl-2-oxazoline) and sodium dodecyl sulfate mixtures at the air-water interface: the impact of modification of the poly(ethyleneimine) functionality.

The adsorption of the polymer-surfactant mixture of poly(2-ethyl-2-oxazoline)-sodium dodecyl sulfate at the air-water interface has been studied by neutron reflectivity and surface tension. The observed patterns of adsorption more closely resemble those encountered in weakly interacting polymer-surfactant mixtures, rather than the pronounced enhancements in adsorption observed in strongly interacting polymer-surfactant mixtures, such as in the related poly(ethyleneimine)-sodium dodecyl sulfate mixtures. The adsorption was found to be strongly dependent on solution pH, polymer molecular weight, and polymer concentration. At the lower and higher molecular weights studied, there was little enhancement in the sodium dodecyl sulfate adsorption at low sodium dodecyl sulfate concentrations, whereas at the intermediate polymer molecular weights, some enhancement in the adsorption was observed. For the higher-molecular-weight polymers and at increasingly higher polymer concentrations, a significant reduction of the surfactant at the interface compared to pure sodium dodecyl sulfate occurred for sodium dodecyl sulfate concentrations between the critical aggregation concentration and the critical micellar concentration. The results illustrate the important role of modifying the functionality of poly(ethyleneimine) on surface adsorption.

Genetic insight and therapeutic targets in squamous-cell lung cancer.

Squamous-cell lung cancer is one of the most prevalent subtypes of lung cancer worldwide and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 gene and mutations of the discoidin domain receptor 2 gene as potential novel targets for the treatment of squamous-cell lung cancer patients. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lung cancer assessing the value of novel therapeutics addressing these targets.

The adsorption and self-assembly of mixtures of alkylbenzene sulfonate isomers and the role of divalent electrolyte.

In this paper, the role of the different structural isomers of the anionic surfactant sodium para-dodecyl benzene sulfonate, LAS, on surface adsorption and solution self-assembly has been studied. Using a combination of neutron reflectivity, NR, and small angle neutron scattering, SANS, the effect of mixing an isomer with a short symmetric hydrocarbon chain with one which has an asymmetric hydrocarbon chain on both the equilibrium surface adsorption behavior and the solution microstructure of the mixtures, both in the presence and absence of a divalent cation (Ca(2+)), has been investigated. In the absence of electrolyte, the LAS isomer mixtures form small charged globular micelles throughout the composition range studied. The micelle aggregation number increases with the increase in the asymmetric isomer content, reflecting an increase in the packing efficiency within the micelle. The addition of calcium ions promotes the formation of planar aggregates, as multilamellar vesicles, but only when the symmetric LAS isomer is the major component of the mixture. At a surfactant concentration just above the critical micelle concentration, CMC, and in the absence of electrolyte, the variation in the surface composition is close to the solution composition. Regular solution theory, RST, calculations show that this variation is also close to what is expected for ideal mixing. The addition of Ca(2+) ions induces a different surface behavior, resulting in the formation of multilayer structures at the interface throughout the entire composition range.