Polymerization-Induced Phase Segregation and Self-Assembly of Siloxane Additives to Provide Thermoset Coatings with a Defined Surface Topology and Biocidal and Self-Cleaning Properties.

In this work, we report on the incorporation of a siloxane copolymer additive, poly((2-phenylethyl) methylsiloxane)-co(1-phenylethyl) methylsiloxane)-co-dimethylsiloxane), which is fully soluble at room temperature, in a rapid-cure thermoset polyester coating formulation. The additive undergoes polymerization-induced phase segregation (PIPS) to self-assemble on the coating surface as discrete discoid nanofeatures during the resin cure process. Moreover, the copolymer facilitates surface co-segregation of titanium dioxide pigment microparticulate present in the coating. Depending on the composition, the coatings can display persistent superhydrophobicity and self-cleaning properties and, surprisingly, the titanium dioxide pigmented coatings that include the siloxane copolymer additive display high levels of antibacterial performance against Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria. This antibacterial performance is believed to be associated with the unique surface topology of these coatings, which comprise stimuli-responsive discoid nanofeatures. This paper provides details of the surface morphology of the coatings and how these relates to the antimicrobial properties of the coating.

Subtle Variations in Surface Properties of Black Silicon Surfaces Influence the Degree of Bactericidal Efficiency.

One of the major challenges faced by the biomedical industry is the development of robust synthetic surfaces that can resist bacterial colonization. Much inspiration has been drawn recently from naturally occurring mechano-bactericidal surfaces such as the wings of cicada (Psaltoda claripennis) and dragonfly (Diplacodes bipunctata) species in fabricating their synthetic analogs. However, the bactericidal activity of nanostructured surfaces is observed in a particular range of parameters reflecting the geometry of nanostructures and surface wettability. Here, several of the nanometer-scale characteristics of black silicon (bSi) surfaces including the density and height of the nanopillars that have the potential to influence the bactericidal efficiency of these nanostructured surfaces have been investigated. The results provide important evidence that minor variations in the nanoarchitecture of substrata can substantially alter their performance as bactericidal surfaces.

Role of topological scale in the differential fouling of Pseudomonas aeruginosa and Staphylococcus aureus bacterial cells on wrinkled gold-coated polystyrene surfaces.

Wrinkled patterns, which possess an extensive surface area over a limited planar space, can provide surface features ranging across the nano- and microscale that have become an engineering material with the flexibility to be tuneable for a number of technologies. Here, we investigate the surface parameters that influence the attachment response of two model bacteria (P. aeruginosa and S. aureus) to wrinkled gold-coated polystyrene surfaces having topologies at the nano- and microscale. Together with flat gold films as the controls, surface feature heights spanned 2 orders of magnitude (15 nm, 200 nm, and 1 micron). The surface wrinkle topology was shown through confocal laser scanning microscopic, atomic force microscopic and scanning electron microscopic image analyses to consist of air-water interfacial areas unavailable for bacterial attachment, which were also shown to be stable by time-lapsed contact angle measurements. Imposition of the nanoscale wrinkles reduced P. aeruginosa attachment to 57% and S. aureus attachment to 20% of their flat equivalent surfaces whereas wrinkles at the microscale further reduced these attachments to 7.5% and 14.5%, respectively. The density of attachments indicated an inherent species specific selectivity that changed with feature dimension, attributable to the scale of the air-water interfaces in contact with the bacterial cell. Parameters influencing static bacterial attachment were the total projected surface areas minus the air-water interface areas and the scale of these respective air-water interfaces (area distribution) with respect to the cell morphology. The range of these controlling parameters may provide new design principles for the evolving suite of physical anti-biofouling materials not reliant on biocidal agents under development.

Copolymers enhance selective bacterial community colonization for potential root zone applications.

Managing the impact of anthropogenic and climate induced stress on plant growth remains a challenge. Here we show that polymeric hydrogels, which maintain their hydrous state, can be designed to exploit functional interactions with soil microorganisms. This microbial enhancement may mitigate biotic and abiotic stresses limiting productivity. The presence of mannan chains within synthetic polyacrylic acid (PAA) enhanced the dynamics and selectivity of bacterial ingress in model microbial systems and soil microcosms. Pseudomonas fluorescens exhibiting high mannan binding adhesins showed higher ingress and localised microcolonies throughout the polymeric network. In contrast, ingress of Bacillus subtilis, lacking adhesins, was unaltered by mannan showing motility comparable to bulk liquids. Incubation within microcosms of an agricultural soil yielded hydrogel populations significantly increased from the corresponding soil. Bacterial diversity was markedly higher in mannan containing hydrogels compared to both control polymer and soil, indicating enhanced selectivity towards microbial families that contain plant beneficial species. Here we propose functional polymers applied to the potential root zone which can positively influence rhizobacteria colonization and potentially plant growth as a new approach to stress tolerance.

Bactericidal activity of self-assembled palmitic and stearic fatty acid crystals on highly ordered pyrolytic graphite.

The wings of insects such as cicadas and dragonflies have been found to possess nanostructure arrays that are assembled from fatty acids. These arrays can physically interact with the bacterial cell membranes, leading to the death of the cell. Such mechanobactericidal surfaces are of significant interest, as they can kill bacteria without the need for antibacterial chemicals. Here, we report on the bactericidal effect of two of the main lipid components of the insect wing epicuticle, palmitic (C16) and stearic (C18) fatty acids. Films of these fatty acids were re-crystallised on the surface of highly ordered pyrolytic graphite. It appeared that the presence of two additional CH2 groups in the alkyl chain resulted in the formation of different surface structures. Scanning electron microscopy and atomic force microscopy showed that the palmitic acid microcrystallites were more asymmetric than those of the stearic acid, where the palmitic acid microcrystallites were observed to be an angular abutment in the scanning electron micrographs. The principal differences between the two types of long-chain saturated fatty acid crystallites were the larger density of peaks in the upper contact plane of the palmitic acid crystallites, as well as their greater proportion of asymmetrical shapes, in comparison to that of the stearic acid film. These two parameters might contribute to higher bactericidal activity on surfaces derived from palmitic acid. Both the palmitic and stearic acid crystallite surfaces displayed activity against Gram-negative, rod-shaped Pseudomonas aeruginosa and Gram-positive, spherical Staphylococcus aureus cells. These microcrystallite interfaces might be a useful tool in the fabrication of effective bactericidal nanocoatings. STATEMENT OF SIGNIFICANCE: Nanostructured cicada and dragonfly wing surfaces have been discovered to be able physically kill bacterial cells. Here, we report on the successful fabrication of bactericidal three-dimensional structures of two main lipid components of the epicuticle of insect wings, palmitic (C16) and stearic (C18) acids. After crystallisation onto highly ordered pyrolytic graphite, both the palmitic and stearic acid films displayed bactericidal activity against both Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus cells. The simplicity of the production of these microcrystallite interfaces suggests that a fabrication technique, based on solution deposition, could be an effective technique for the application of bactericidal nanocoatings.

"Race for the Surface": Eukaryotic Cells Can Win.

With an aging population and the consequent increasing use of medical implants, managing the possible infections arising from implant surgery remains a global challenge. Here, we demonstrate for the first time that a precise nanotopology provides an effective intervention in bacterial cocolonization enabling the proliferation of eukaryotic cells on a substratum surface, preinfected by both live Gram-negative, Pseudomonas aeruginosa, and Gram-positive, Staphylococcus aureus, pathogenic bacteria. The topology of the model black silicon (bSi) substratum not only favors the proliferation of eukaryotic cells but is biocompatible, not triggering an inflammatory response in the host. The attachment behavior and development of filopodia when COS-7 fibroblast cells are placed in contact with the bSi surface are demonstrated in the dynamic study, which is based on the use of real-time sequential confocal imaging. Bactericidal nanotopology may enhance the prospect for further development of inherently responsive antibacterial nanomaterials for bionic applications such as prosthetics and implants.

The nature of inherent bactericidal activity: insights from the nanotopology of three species of dragonfly.

While insect wings are widely recognised as multi-functional, recent work showed that this extends to extensive bactericidal activity brought about by cell deformation and lysis on the wing nanotopology. We now quantitatively show that subtle changes to this topography result in substantial changes in bactericidal activity that are able to span an order of magnitude. Notably, the chemical composition of the lipid nanopillars was seen by XPS and synchrotron FTIR microspectroscopy to be similar across these activity differences. Modelling the interaction between bacterial cells and the wing surface lipids of 3 species of dragonflies, that inhabit similar environments, but with distinctly different behavioural repertoires, provided the relationship between surface structure and antibacterial functionality. In doing so, these principal behavioural patterns correlated with the demands for antimicrobial efficiency dictated by differences in their foraging strategies. This work now reveals a new feature in the design elegance of natural multi-functional surfaces as well providing insights into the bactericidal mechanism underlying inherently antimicrobial materials, while suggesting that nanotopology is related to the evolutionary development of a species through the demands of its behavioural repertoire. The underlying relationship between the processes of wetting, adhesion and capillarity of the lipid nanopillars and bactericidal efficiency suggests new prospects for purely mechano-responsive antibacterial surfaces.

Impact of particle nanotopology on water transport through hydrophobic soils.

The impact of non- and poorly wetting soils has become increasingly important, due to its direct influence on the water-limited potential yield of rain-fed grain crops at a time of enhanced global competition for fresh water. This study investigates the physical and compositional mechanisms underlying the influence of soil organic matter (SOM) on the wetting processes of model systems. These model systems are directly related to two sandy wheat-producing soils that have contrasting hydrophobicities. Atomic force microscopy (AFM), contact angle and Raman micro-spectroscopy measurements on model planar and particulate SOM-containing surfaces demonstrated the role of the hierarchical surface structure on the wetting dynamics of packed particulate beds. It was found that a nanoscale surface topology is superimposed over the microscale roughness of the packed particles, and this controls the extent of water ingress into particulate packed beds of these particles. Using two of the dominant component organic species found in the SOM of the two soils used in this study, it was found that the specific interactions taking place between the SOM components, rather than their absolute quantities, dictated the formation of highly hydrophobic surface nanotopologies. This hydrophobicity was demonstrated, using micro-Raman imaging, to arise from the surface being in a composite Cassie-Baxter wetting state. Raman imaging demonstrated that the particle surface nanotopography influenced the degree of air entrapment in the interstices within the particle bed. The influence of a conventional surfactant on the wetting kinetics of both the model planar surfaces and packed particulate beds was quantified in terms of their respective advancing contact angles and the capillary wetting force vector. The information obtained for all of the planar and particulate surfaces, together with that obtained for the two soils, allowed linear relationships to be obtained in plots of the contact angle data as a function of the wetting liquid surface tensions. These linear relationships were found to reflect the mechanisms underlying the surface energy parameter requirements for wetting.

Bacterial patterning at the three-phase line of contact with microtextured alkanes.

Aliphatic crystallites, characteristic of the eicosane and docosane components of naturally occurring lipids, were found to form microtextures that were structured by specific interactions with ordered graphite (HOPG) used as the underlying substratum, as confirmed by scanning electron microscopy (SEM) and fast Fourier transform (FFT) analysis. Confocal scanning laser microscopy (CLSM) showed highly directed bacterial alignment for two bacterial species (spherical and rod-shaped), reflecting the preferential orientation of the crystallite-air-water interfaces to give linear and triangular bacterial patterning. The mechanisms of bacterial attachment are demonstrated in terms of the balance between effective radial adhesional forces and the capillary forces resulting from the water contact angle of the bacteria at the three-phase line (TPL) of the lipid surface. It is suggested that these microtextured surfaces, which exhibit the ability to limit bacterial adhesion to a precise patterning at the lipid TPL, could be used as a means of controlling bacterial colonization.

A single dose biodegradable vaccine depot that induces persistently high levels of antibody over a year.

In this study, we describe a biodegradable vaccine depot which persists in vivo for at least 4-months, provides synergistic adjuvant effects and also allows dose sparing of both antigen and adjuvant. A single administration results in immediate release of a priming dose of vaccine, by a process of syneresis, which is then followed by release of remaining vaccine which maintains robust antibody levels that last for more than a year. The platform technology comprises two aqueous components; one contains chitosan and hydroxyapatite, in which the vaccine is incorporated, and the other consists of a crosslinking agent, tripolyphosphate (TPP) and chondroitin sulphate. When co-injected into tissue, they spontaneously crosslink forming a firm yet compliant vaccine-containing depot. Whole body imaging of animals inoculated with the material show that the depot persists in situ for up to 19 weeks. Vaccination of mice with depot formulations containing ovalbumin (OVA) emulsified in Montanide ISA 61 adjuvant results in the induction of robust antibody responses using doses of adjuvant 40-fold less than those recommended by the manufacturer. Dose sparing effects were also apparent with antigen when delivered in the depot. Similar dose sparing effects were observed with Montanide ISA 50, complete and incomplete Freund's adjuvants but not with aluminium hydroxide nor Quil A. Antibody titres, induced by a single dose of antigen/adjuvant formulation incorporated in the depot, persisted at high levels for at least 55 weeks following a single dose of vaccine.

Impact of confining 3-D polymer networks on dynamics of bacterial ingress and self-organisation.

Studies of microbial interactions during motility, micro-structuring and colonisation have predominately been limited to surface associated bacteria involving materials such as semi-solid biomolecular hydrogels and thin liquid films. Recently, these surfaces have been extended to synthetic polymers where they provide defined chemistries and structural properties. However, precise details of microbial ingress into the confined fluid volume of synthetic 3-D hydrogel networks and their subsequent microstructuring remain to be defined. Here, we show that Gram-positive and Gram-negative bacteria internally populate mesoporous polyacrylate hydrogels by quantifying: the dynamic advancing population front and the resultant spontaneous self-organisation into well-defined clusters and micro-colonies. Polymer chain conjugated fluorescent nanoparticles indicated that both bacterial clusters and micro-colonies associated directly with the polymer chains of the mesoporous hydrogel. Protonation of the K-polyacrylate made chains more hydrophobic and globular in conformation, reducing the swelling of the hydrogel by half. However, the bacterial population increased by 30% indicating the dominance of hydrophobic and viscoelastic interactions as well as the cation chemistry within the confined fluids of synthetic polymer hydrogels despite pore size reductions of 50%. Synthetic polymer hydrogels having a range of porosities when swollen together with controllable chemical and structural functionality can potentially offer well-defined microenvironments for bacterial populations in advancing biotechnologies such as inoculants and substrates in the production of therapeutic agents.

Nanotopography as a trigger for the microscale, autogenous and passive lysis of erythrocytes.

Microscale devices are increasingly being developed for diagnostic analysis although conventional lysis as an initial step presents limitations due to its scale or complexity. Here, we detail the physical response of erythrocytes to the surface nanoarchitecture of black Si (bSi) and foreshadow their potential in microanalysis. The physical interaction brought about by the spatial convergence of the two topologies: (a) the nanopillar array present on the bSi and (b) the erythrocyte cytoskeleton present on the red blood cells (RBCs), provides spontaneous stress-induced cell deformation, rupture and passive lysis within an elapsed time of ∼3 min from immobilisation to rupture and without external chemical or mechanical intervention. The mechano-responsive bSi surface provides highly active yet autogenous RBC lysis and a prospect as a front-end platform technology in evolving micro-fluidic platforms for cellular analyses.

Bactericidal activity of black silicon.

Black silicon is a synthetic nanomaterial that contains high aspect ratio nanoprotrusions on its surface, produced through a simple reactive-ion etching technique for use in photovoltaic applications. Surfaces with high aspect-ratio nanofeatures are also common in the natural world, for example, the wings of the dragonfly Diplacodes bipunctata. Here we show that the nanoprotrusions on the surfaces of both black silicon and D. bipunctata wings form hierarchical structures through the formation of clusters of adjacent nanoprotrusions. These structures generate a mechanical bactericidal effect, independent of chemical composition. Both surfaces are highly bactericidal against all tested Gram-negative and Gram-positive bacteria, and endospores, and exhibit estimated average killing rates of up to ~450,000 cells min(-1) cm(-2). This represents the first reported physical bactericidal activity of black silicon or indeed for any hydrophilic surface. This biomimetic analogue represents an excellent prospect for the development of a new generation of mechano-responsive, antibacterial nanomaterials.

Control of size dispersity of chitosan biopolymer microparticles and nanoparticles to influence vaccine trafficking and cell uptake.

Structurally related surfactant molecules were exploited to generate chitosan emulsions to provide systematic variation in micelle radii of curvature and size. These compositions provide precise control of chitosan particle dispersity, that is, size distribution according to three quantitative distribution parameters as well as shape distribution. This resulted in a suite of particle size distributions spanning 71 nm to 3.7 µm and a very high degree of particle sphericity, allowing the influence of particle size to be isolated in two in vivo studies relating biopolymer particle size to cellular uptake and trafficking to lymph nodes. Flow cytometry and fluorescence microscopy indicated that the three cell lines examined preferentially internalized chitosan microparticles to a greater extent than nanoparticles over a 24 h period. In an in vivo mouse model, nanoparticles initially trafficked rapidly to lymph nodes draining the site of inoculation followed by further slower uptake. Microparticles trafficked to the lymph nodes with a similar pattern except that the initial discharge was ∼50-fold less than that observed with nanoparticles indicating a profound difference in the physiological transport properties of the two particle types.

Acoustic wave immunosensing of a meningococcal antigen using gold nanoparticle-enhanced mass sensitivity.

Bacterial meningitis is an infection of the thin membranes covering the brain and spinal cord by a number of microorganisms including Neisseria meningitidis, which can lead to permanent neurological damage in the event of late diagnosis. Given the quick onset and severity of the disease, there is a clear need for a rapid, sensitive and specific diagnostic technique. Here, we describe the development and evaluation of an acoustic wave sensor, the quartz crystal microbalance (QCM), as a rapid immunosensor employing antibodies against the cell surface outer membrane protein 85 (OMP85) of N. meningitidis as an immobilized selective layer. These antibodies were directionally orientated as receptors by thin film deposition of structured polyvinylidene fluoride and Protein A. The sensitivity of this QCM immunosensor was further increased by conjugation of the OMP85 antigen to 50 nm gold nanoparticles providing reproducible detection of the target down to 300 ng/mL. Subsequent treatment of the QCM surface with an acidic glycine solution regenerated the immunosensor allowing each crystal to be used several times.

The detection of influenza A and B viruses in clinical specimens using a quartz crystal microbalance.

Current methods for the accurate diagnosis of influenza based on culture of the virus or PCR are highly sensitive and specific but require specialised laboratory facilities and highly trained personnel and, in the case of viral culture, can take up to 14 days to obtain a definitive result. In this study, a quartz crystal microbalance-based immunosensor (QCM) has been developed and its potential evaluated for the rapid and sensitive detection of both influenza A and B viruses in laboratory-cultured preparations and clinical samples. The effective limit for detection by QCM for stock preparations of both A/PR/8/34 and B/Lee/40 viruses was 1 x 10(4) pfu/mL, associated with observed frequency shifts of 30 (+/-5) and 37 (+/-6.5) Hz, respectively. Conjugation of 13 nm gold nanoparticles to the detecting antibody improved the mass sensitivity of the immunosensor, resulting in a 10-fold increase in sensitivity and a detection limit of 1 x 10(3) pfu/mL for both preparations, with resulting frequency shifts of 102 (+/-11) and 115 (+/-5) Hz, respectively. Detection of virus in nasal washes with this technique was achieved by overnight passage in MDCK cultures prior to analysis. A comparison of results obtained from 67 clinical samples using existing RT-PCR, shell vial, cell culture and ELISA methods showed that QCM techniques were comparable in sensitivity and specificity to cell culture methods.

Practical precooling: effect on cycling time trial performance in warm conditions.

The purpose of this study was to compare the effects of two practical precooling techniques (skin cooling vs. skin + core cooling) on cycling time trial performance in warm conditions. Six trained cyclists completed one maximal graded exercise test (VO2(peak) 71.4 +/- 3.2 ml x kg(-1) x min(-1)) and four approximately 40 min laboratory cycling time trials in a heat chamber (34.3 degrees C +/- 1.1 degrees C; 41.2% +/- 3.0% rh) using a fixed-power/variable-power format. Cyclists prepared for the time trial using three techniques administered in a randomised order prior to the warm-up: (1) no cooling (control), (2) cooling jacket for 40 min (jacket) or (3) 30-min water immersion followed by a cooling jacket application for 40 min (combined). Rectal temperature prior to the time trial was 37.8 degrees C +/- 0.1 degrees C in control, similar in jacket (37.8 degrees C +/- 0.3 degrees C) and lower in combined (37.1 degrees C +/- 0.2 degrees C, P < 0.01). Compared with the control trial, time trial performance was not different for jacket precooling (-16 +/- 36 s, -0.7%; P = 0.35) but was faster for combined precooling (-42 +/- 25 s, - .8%; P = 0.009). In conclusion, a practical combined precooling strategy that involves immersion in cool water followed by the use of a cooling jacket can produce decrease in rectal temperature that persist throughout a warm-up and improve laboratory cycling time trial performance in warm conditions.

Synthesis, characterization, and ab initio theoretical study of a molecularly imprinted polymer selective for biosensor materials.

Despite the complex phenomena involved in encoding template molecule information within stable synthetic polymers to yield selective and efficient molecular recognition processes, molecularly imprinted polymers (MIP) are increasingly finding broad areas of application. Molecular interactions, both during the polymerization of the functional monomers in the presence of the template and during the processes of specific recognition after template removal, are key determinants of an effective MIP. Covalent and noncovalent template imprinting have been employed to achieve specific recognition sites. In the present study, a molecularly imprinted biocompatible polymer, having a high capacity and affinity for the dye template, nickel(II) phthalocyanine tetrasulfonic acid, has been prepared. UV-visible spectroscopy, FTIR spectroscopy, and ICP analysis were used to investigate the aspects of the synthesis, binding capacity, and adsorption kinetics of the system. Poly(allylamine) cross-linked with epichlorohydrin has been used to represent an amino-functional receptor. Binding isotherms and capacities were correlated with the degree of template removal. Kinetic studies of binding allowed diffusion mechanisms to be evaluated for the fine particulate MIP. Ab initio molecular orbital calculations were performed using Hartree-Fock, MP2, and density functional theory methods to determine the most likely mechanisms of molecular imprinting. Suitable theoretical models have been constructed to mimic the interactions between the template molecule and the polymer. Simulation of the vibrational spectra was also undertaken to make meaningful assignments to experimentally determined spectral bands resulting from these template MIP receptor interactions.

The surface tension of a solid at the solid-vacuum interface, an evaluation from adsorption and wall potential calculations.

A method for the evaluation of quantities that are experimentally inaccessible such as the surface tension at the solid-vacuum interface and the superficial tension of the fluid in contact with the solid is presented. The approach is based on consideration of an equilibrium of a fluid in solid capillary wherein a balance between surface and capillary forces has been replaced by conceptual alternative interfacial and centrifugal forces. This approach involves the simultaneous numerical solution one the special forms of the Gibbs equation for solid-fluid interface and a generalized Kelvin equation derived earlier. The latter equation takes into account interactions between the solid thick cylindrical wall and confined fluid, this body-body interaction potential has been primarily calculated using the Lennard-Jones (6-12) expression for the atom-atom pair potentials and expressed by hypergeometrical functions having good convergences. All numerical calculations shown here have been performed for the model graphite-argon system at 90 K. Finally, an analysis of the accuracy of the proposed method is considered.

Flow and injection characteristics of pharmaceutical parenteral formulations using a micro-capillary rheometer.

A micro-capillary rheometer consisted of a fine needle with an internal diameter of 347 microm attached to a 1 ml removable-needle syringe within an Instron device that operated in compression mode to provide various crosshead speeds ranging from 150 to 950 mm min(-1) covering typical clinical injection rates, and that determined the resulting force on the plunger. The crosshead speed and the resulting force were used to calculate the shear rate and the shear stress respectively. These were used in standard capillary flow expressions together with an independent measurement of the wall frictional force and allowed the viscosity of parenteral Newtonian solutions and non-Newtonian suspensions to be measured quantitatively and their rheological behaviour in needles of clinical dimensions to be established. Commercial pharmaceutical parenteral formulations consisting of three oil-based solutions and three aqueous suspensions were chosen for this study. The net injection forces were also obtained and it was shown that both the oil-based solutions and the aqueous suspensions covered similar ranges. The viscosities for the parenteral solutions were determined from the slope of the linear regression (R(2)>0.97) between shear stress and shear rate and ranged between 0.029 and 0.060 Pas. For the aqueous suspensions examined, viscosities decreased from low shear rate to high shear rate, following a power-law model and indicating a pseudo plastic behaviour. Standardisation of the micro-capillary rheometer with Newtonian silicone oils calibrated with a Rheometrics Fluids Spectrometer showed viscosity values consistent between the rotational flow measurements and capillary flow measurements which were within 5% and showed very high degrees of reproducibility between replicate samples. This degree of reproducibility allowed differences in the contribution of the wall frictional force to the required plunger force for both the oil-based and aqueous parenteral formulations to be determined reliably. The wall frictional force values for all formulations were similar (0.6-1.6 N) but the frictional forces of aqueous systems were found to decline significantly with plunger speed. The micro-capillary rheometer has been used to evaluate the impact of concentration changes due to sedimentation on the injectability of one of the aqueous suspensions, where it was shown that not only the viscosity increased but the shear thinning behaviour ceased at higher shear rates. The micro-capillary rheometer which was able to operate in clinical shear rate ranges has been shown to detect deteriorations in the injectable rheology of suspensions, which in the case here was due to pre-injection sedimentation.