A highly oriented cubic phase formed by lipids under shear

We demonstrate the formation of a macroscopically oriented inverse bicontinuous cubic (QII) lipid phase from a sponge (L3) phase by controlled hydration during shear flow. The L3 phase was the monoolein/ butanediol/water system; the addition of water reduces the butanediol concentration, inducing the formation of a diamond (QIID) cubic phase, which is oriented by the shear flow. The phenomenon was reproduced in both capillary and Couette geometries, indicating that this represents a robust general route for the production of highly aligned bulkQII samples, with applications in nanomaterial templating and protein research.

Immunoassays, methods for carrying out immunoassays, immunoassay kits and method for manufacturing immunoassay kits

The invention relates to immunoassays, methods for carrying out immunoassays, immunoassay kits and methods for manufacturing immunoassay kits. In particular, the invention has relevance to capillary (especially microcapillary) immunoassay technology.

Relaxation of surface tension in the free-surface boundary layers of simple Lennard-Jones liquids

In this paper we use molecular dynamics to answer a classical question: how does the surface tension on a liquid/gas interface appear? After defining surface tension from the first principles and performing several consistency checks, we perform a dynamic experiment with a single simple liquid nanodroplet. At time zero, we remove all molecules of the interfacial layer of molecules, creating a fresh bare interface with the bulk arrangement of molecules. After that the system evolves towards equilibrium, and the expected surface tension is re-established. We found that the system relaxation consists of three distinct stages. First, the mechanical balance is quickly re-established. During this process the notion of surface tension is meaningless. In the second stage, the surface tension equilibrates, and the density profile broadens to a value which we call “intrinsic” interfacial width. During the third stage, the density profile continues to broaden due to capillary wave excitations, which does not however affect the surface tension.We have observed this scenario for monatomic Lennard-Jones (LJ) liquid as well as for binary LJ mixtures at different temperatures, monitoring a wide range of physical observables.

Preparation of films of a highly aligned lipid cubic phase

We demonstrate a method by which we can produce an oriented film of an inverse bicontinuous cubic phase (QII D) formed by the lipid monoolein (MO). By starting with the lipid as a disordered precursor (the L3 phase) in the presence of butanediol, we can obtain a film of the QII D phase showing a high degree of in-plane orientation by controlled dilution of the sample under shear within a linear flow cell. We demonstrate that the direction of orientation of the film is different from that found in the oriented bulk material that we have reported previously; therefore, we can now reproducibly form QII D samples oriented with either the [110] or the [100] axis aligned in the flow direction depending on the method of preparation. The deposition of MO as a film, via a moving fluid− air interface that leaves a coating of MO in the L3 phase on the capillary wall, leads to a sample in the [110] orientation. This contrasts with the bulk material that we have previously demonstrated to be oriented in the [100] direction, arising from flow producing an oriented bulk slug of material within the capillary tube. The bulk sample contains significant amounts of residual butanediol, which can be estimated from the lattice parameter of the QII D phase obtained. The sample orientation and lattice parameters are determined from synchrotron small-angle X-ray scattering patterns and confirmed by simulations. This has potential applications in the production of template materials and the growth of protein crystals for crystallography as well as deepening our understanding of the mechanisms underlying the behavior of lyotropic liquid-crystal phases.

A three-compartment model of the hemodynamic response and oxygen delivery to brain

We describe a mathematical model linking changes in cerebral blood flow, blood volume and the blood oxygenation state in response to stimulation. The model has three compartments to take into account the fact that the cerebral blood flow and volume as measured concurrently using laser Doppler flowmetry and optical imaging spectroscopy have contributions from the arterial, capillary as well as the venous compartments of the vasculature. It is an extension to previous one-compartment hemodynamic models which assume that the measured blood volume changes are from the venous compartment only. An important assumption of the model is that the tissue oxygen concentration is a time varying state variable of the system and is driven by the changes in metabolic demand resulting from changes in neural activity. The model takes into account the pre-capillary oxygen diffusion by flexibly allowing the saturation of the arterial compartment to be less than unity. Simulations are used to explore the sensitivity of the model and to optimise the parameters for experimental data. We conclude that the three-compartment model was better than the one-compartment model at capturing the hemodynamics of the response to changes in neural activation following stimulation.

A model of the hemodynamic response and oxygen delivery to brain

A recent nonlinear system by Friston et al. (2000. NeuroImage 12: 466–477) links the changes in BOLD response to changes in neural activity. The system consists of five subsystems, linking: (1) neural activity to flow changes; (2) flow changes to oxygen delivery to tissue; (3) flow changes to changes in blood volume and venous outflow; (4) changes in flow, volume, and oxygen extraction fraction to deoxyhemoglobin changes; and finally (5) volume and deoxyhemoglobin changes to the BOLD response. Friston et al. exploit, in subsystem 2, a model by Buxton and Frank coupling flow changes to changes in oxygen metabolism which assumes tissue oxygen concentration to be close to zero. We describe below a model of the coupling between flow and oxygen delivery which takes into account the modulatory effect of changes in tissue oxygen concentration. The major development has been to extend the original Buxton and Frank model for oxygen transport to a full dynamic capillary model making the model applicable to both transient and steady state conditions. Furthermore our modification enables us to determine the time series of CMRO2 changes under different conditions, including CO2 challenges. We compare the differences in the performance of the “Friston system” using the original model of Buxton and Frank and that of our model. We also compare the data predicted by our model (with appropriate parameters) to data from a series of OIS studies. The qualitative differences in the behaviour of the models are exposed by different experimental simulations and by comparison with the results of OIS data from brief and extended stimulation protocols and from experiments using hypercapnia.

A universal agro-hydrological model for water and nitrogen cycles in the soil-crop system SMCR_N: critical update and further validation

Agro-hydrological models have widely been used for optimizing resources use and minimizing environmental consequences in agriculture. SMCRN is a recently developed sophisticated model which simulates crop response to nitrogen fertilizer for a wide range of crops, and the associated leaching of nitrate from arable soils. In this paper, we describe the improvements of this model by replacing the existing approximate hydrological cascade algorithm with a new simple and explicit algorithm for the basic soil water flow equation, which not only enhanced the model performance in hydrological simulation, but also was essential to extend the model application to the situations where the capillary flow is important. As a result, the updated SMCRN model could be used for more accurate study of water dynamics in the soil-crop system. The success of the model update was demonstrated by the simulated results that the updated model consistently out-performed the original model in drainage simulations and in predicting time course soil water content in different layers in the soil-wheat system. Tests of the updated SMCRN model against data from 4 field crop experiments showed that crop nitrogen offtakes and soil mineral nitrogen in the top 90 cm were in a good agreement with the measured values, indicating that the model could make more reliable predictions of nitrogen fate in the crop-soil system, and thus provides a useful platform to assess the impacts of nitrogen fertilizer on crop yield and nitrogen leaching from different production systems. (C) 2010 Elsevier B.V. All rights reserved.

Hydrophilic interaction chromatography–mass spectrometry for anionic metabolic profiling of urine from antibiotic-treated rats

Hydrophilic interaction chromatography–mass spectrometry (HILIC–MS) was used for anionic metabolic profiling of urine from antibiotic-treated rats to study microbial–host co-metabolism. Rats were treated with the antibiotics penicillin G and streptomycin sulfate for four or eight days and compared to a control group. Urine samples were collected at day zero, four and eight, and analyzed by HILIC–MS. Multivariate data analysis was applied to the urinary metabolic profiles to identify biochemical variation between the treatment groups. Principal component analysis found a clear distinction between those animals receiving antibiotics and the control animals, with twenty-nine discriminatory compounds of which twenty were down-regulated and nine up-regulated upon treatment. In the treatment group receiving antibiotics for four days, a recovery effect was observed for seven compounds after cessation of antibiotic administration. Thirteen discriminatory compounds could be putatively identified based on their accurate mass, including aconitic acid, benzenediol sulfate, ferulic acid sulfate, hippuric acid, indoxyl sulfate, penicillin G, phenol and vanillin 4-sulfate. The rat urine samples had previously been analyzed by capillary electrophoresis (CE) with MS detection and proton nuclear magnetic resonance (1H NMR) spectroscopy. Using CE–MS and 1H NMR spectroscopy seventeen and twenty-five discriminatory compounds were found, respectively. Both hippuric acid and indoxyl sulfate were detected across all three platforms. Additionally, eight compounds were observed with both HILIC–MS and CE–MS. Overall, HILIC–MS appears to be highly complementary to CE–MS and 1H NMR spectroscopy, identifying additional compounds that discriminate the urine samples from antibiotic-treated and control rats.

A Lab-in-a-briefcase for rapid prostate specific antigen (PSA) screening from whole blood

We present a new concept for rapid and fully portable Prostate Specific Antigen (PSA) measurement, termed “Lab-in-a-Briefcase”, which integrates an affordable microfluidic ELISA platform utilising a melt-extruded fluoropolymer Micro Capillary Film (MCF) containing 10 bore, 200 μm internal diameter capillaries, a disposable multi-syringe aspirator (MSA) plus a sample tray pre-loaded with all required immunoassay reagents, and a portable film scanner for colorimetric signal digital quantitation. Each MSA can perform 10 replicate microfluidic immunoassays on 8 samples, allowing 80measurements to be made in less than 15 minutes based on semi-automated operation and norequirement of additional fluid handling equipment. An assay was optimised for measurement of a clinically relevant range of PSA from 0.9 to 60.0 ng/ml in 15 minutes with CVs in the order of 5% based on intra-assay variability when read using a consumer flatbed film scanner. The PSA assay performance in the MSA remained robust in the presence of undiluted or 1:2 diluted human serum or whole blood, and the matrix effect could simply be overcome by extending sample incubation times. The PSA "Lab-in-a-briefcase" is particularly suited to a low-resource health setting where diagnostic labs and automated immunoassay systems are not accessible, by allowing PSA measurement outside the laboratory using affordable equipment.

Experimental confirmation of transformation pathways between inverse double diamond and gyroid cubic phases

A macroscopically oriented double diamond inverse bicontinuous cubic phase (QIID) of the lipid glycerol monooleate is reversibly converted into a gyroid phase (QIIG). The initial QIID phase is prepared in the form of a film coating the inside of a capillary, deposited under flow, which produces a sample uniaxially oriented with a ⟨110⟩ axis parallel to the symmetry axis of the sample. A transformation is induced by replacing the water within the capillary tube with a solution of poly(ethylene glycol), which draws water out of the QIID sample by osmotic stress. This converts the QIID phase into a QIIG phase with two coexisting orientations, with the ⟨100⟩ and ⟨111⟩ axes parallel to the symmetry axis, as demonstrated by small-angle X-ray scattering. The process can then be reversed, to recover the initial orientation of QIID phase. The epitaxial relation between the two oriented mesophases is consistent with topologypreserving geometric pathways that have previously been hypothesized for the transformation. Furthermore, this has implications for the production of macroscopically oriented QIIG phases, in particular with applications as nanomaterial templates.

Experimental evidence for proposed transformation pathway from the inverse hexagonal to inverse diamond cubic phase from oriented lipid samples

A macroscopically oriented inverse hexagonal phase (HII) of the lipid phytantriol in water is converted to an oriented inverse double diamond bicontinuous cubic phase (QIID). The initial HII phase is uniaxially oriented about the long axis of a capillary with the cylinders parallel to the capillary axis. The HII phase is converted by cooling to a QII D phase which is also highly oriented, where the cylindrical axis of the former phase has been converted to a ⟨110⟩ axis in the latter, as demonstrated by small-angle X-ray scattering. This epitaxial relationship allows us to discriminate between two competing proposed geometric pathways to convert HII to QIID. Our findings also suggest a new route to highly oriented cubic phase coatings, with applications as nanomaterial templates.