Chris J. Wright

NanoGenotoxicology : The DNA damaging potential of engineered nanomaterials

With the rapid expansion in the nanotechnology industry, it is essential that the safety of engineered nanomaterials and the factors that influence their associated hazards are understood. A vital area governing regulatory health risk assessment is genotoxicology (the study of genetic aberrations following exposure to test agents), as DNA damage may initiate and promote carcinogenesis, or impact fertility. Of late, considerable attention has been given to the toxicity of engineered nanomaterials, but the importance of their genotoxic potential on human health has been largely overlooked. This comprehensive review focuses on the reported abilities of metal nanoparticles, metal-oxide nanoparticles, quantum dots, fullerenes, and fibrous nanomaterials, to damage or interact with DNA, and their ecogenotoxicity is also considered. Many of the engineered nanomaterials assessed were found to cause genotoxic responses, such as chromosomal fragmentation, DNA strand breakages, point mutations, oxidative DNA adducts and alterations in gene expression profiles. However, there are clear inconsistencies in the literature and it is difficult to draw conclusions on the physico-chemical features of nanomaterials that promote genotoxicity, largely due to study design. Hence, areas that require that further attention are highlighted and recommendations to improve our understanding of the genotoxic potential of engineered nanomaterials are addressed.

Characterisation and application of a novel positively charged nanofiltration membrane for the treatment of textile industry wastewaters

The present study demonstrates the high potential for the application of a novel self assembled positively charged nanofiltration membrane, PA6DT-C, in processes such as the recovery of valuable cationic macromolecules in the bioprocess and pharmaceutical industries or removal of multi-valent cations such as dyes and heavy metals in the paper and pulp, textiles, nuclear, and automotive industries. The nanofiltration membrane, prepared in this laboratory, is further characterised and then tested for the removal and recovery of Methylene Blue from a synthetic dye house wastewater. The characterisation process involved the construction of a rejection profile for NaCl over a wide range of pH and concentration, which illustrates that the optimal process conditions for the removal of small cations using this membrane is in the region pH <8.0 and concentration less than 15 mol m(-3). The salt rejection data was used to calculate the magnitude of the effective membrane charge density and this was found to be significantly higher for the PA6DT-C membrane than two commercially available membranes (Desal-DK and Nanomax-50). The membrane flux for this new membrane is also superior to the commercial membranes with an approximate increase of 3-4 fold. The PA6DT-C membrane was successful in removal of Methylene Blue dye from synthetic dye house wastewaters achieving 98% rejection and a membrane flux of ≈ 17 LMH bar(-1). Thus, this new membrane both adds to and complements the existing short supply of positively charged NF membranes.

The role of iron redox state in the genotoxicity of ultrafine superparamagnetic iron oxide nanoparticles.

Ultrafine superparamagnetic iron oxide nanoparticles (USPION) hold great potential for revolutionising biomedical applications such as MRI, localised hyperthermia, and targeted drug delivery. Though evidence is increasing regarding the influence of nanoparticle physico-chemical features on toxicity, data however, is lacking that assesses a range of such characteristics in parallel. We show that iron redox state, a subtle though important physico-chemical feature of USPION, dramatically modifies the cellular uptake of these nanoparticles and influences their induction of DNA damage. Surface chemistry was also found to have an impact and evidence to support a potential mechanism of oxidative DNA damage behind the observed responses has been demonstrated. As human exposure to ferrofluids is predicted to increase through nanomedicine based therapeutics, these findings are important in guiding the fabrication of USPION to ensure they have characteristics that support biocompatibility.

A new technique for membrane characterisation: direct measurement of the force of adhesion of a single particle using an atomic force microscope

Abstract An Atomic Force Microscope (AFM) has been used to quantify directly the adhesive force between a colloid probe and two polymeric ultrafiltration membranes of similar MWCO (4000 Da) but different materials (ES 404 and XP 117, PCI Membrane Systems (UK)). The colloid probe was made from a polystyrene sphere (diameter 11 μm) glued to a V shaped AFM cantilever. Measurements were made in 10 −2 M NaCl solution at pH 8. It was found that the adhesive force at the ES 404 membrane was more than five times greater than that at the XP 117 membrane. As it allows direct quantification of particle/membrane interactions, this technique should be invaluable in the development of new membrane materials and in the elucidation of process behaviour.

Positively charged nanofiltration membranes: Review of current fabrication methods and introduction of a novel approach

A review of the fabrication processes currently available to produce positively charged nanofiltration membranes has been conducted. The review highlights that there are few membranes and studies currently available. The preparation of a novel positively charged nanofiltration membrane is also described. This membrane was fabricated by surface modification of a prepared base membrane using polyethyleneimine followed by cross linking with butanedioldiglycidylether. The fabrication process uses standard organic solvents and avoids the need for hazardous materials, such as concentrated sulphuric acid, which significantly benefits the scale up potential of any future commercial manufacturing process. The new membrane was characterised using a number of state-of-the-art techniques, including a novel use of atomic force microscopy to determine pore size. Streaming potential measurements confirmed that this new membrane is indeed positively charged in the pH range below pH 9, which covers the majority of normal operating conditions. The performance characteristics for the new membrane were very favourable, with a pure water flux determined to be 20 LMH bar(-1) and a rejection of MgCl of 96%. Thus, this new membrane both adds to and complements the existing short supply of positively charged NF membranes and is suitable for applications such as the recovery of valuable cationic macromolecules in the bioprocess and pharmaceutical industries or removal of multi-valent cations such as dyes and heavy metals in the paper and pulp, textiles, nuclear, and automotive industries.

Atomic force microscopy comes of age

AFM (atomic force microscopy) analysis, both of fixed cells, and live cells in physiological environments, is set to offer a step change in the research of cellular function. With the ability to map cell topography and morphology, provide structural details of surface proteins and their expression patterns and to detect pico‐Newton force interactions, AFM represents an exciting addition to the arsenal of the cell biologist. With the explosion of new applications, and the advent of combined instrumentation such as AFM—confocal systems, the biological application of AFM has come of age. The use of AFM in the area of biomedical research has been proposed for some time, and is one where a significant impact could be made. Fixed cell analysis provides qualitative and quantitative subcellular and surface data capable of revealing new biomarkers in medical pathologies. Image height and contrast, surface roughness, fractal, volume and force analysis provide a platform for the multiparameter analysis of cell and protein functions. Here, we review the current status of AFM in the field and discuss the important contribution AFM is poised to make in the understanding of biological systems.

Application of atomic force microscopy to the study of micromechanical properties of biological materials

Atomic force microscopy (AFM) has been used to study the micromechanical properties of biological systems. Its unique ability to function both as an imaging device and force sensor with nanometer resolution in both gaseous and liquid environments has meant that AFM has provided unique insights into the mechanical behaviour of tissues, cells and single molecules. As a surface scanning device, AFM can map properties such as adhesion and the Youngs modulus of surfaces. As a force sensor and nanoindentor AFM can directly measure properties such as the Youngs modulus of surfaces or the binding forces of cells. As a stress-strain gauge AFM can study the stretching of single molecules or fibres and as a nanomanipulator it can dissect biological particles such as viruses or DNA strands. The present paper reviews key research that has demonstrated the versatility of AFM and how it can be exploited to study the micromechanical behaviour of biological materials.

An atomic force microscopy study of the adhesion of a silica sphere to a silica surface—effects of surface cleaning

Abstract An atomic force microscope (AFM) has been used to quantify directly the adhesive interactions between a silica sphere and a planar silica surface. Electrostatic double-layer interactions have also been quantified through analysis of approach curves. The surfaces of the sphere and planar surface were treated prior to measurements either by ethanol washing or by plasma treatment. Adhesion forces were then measured in 0.01 M NaCl solutions at pH 3 and 8. The adhesion force did not vary greatly with pH for a given cleaning procedure. However, the magnitudes of the adhesion forces were substantially less for the plasma treated surfaces. The adhesion forces did not vary systematically with the loading force. Agreement of the adhesion measurements with theory (DLVO, using a non-retarded Hamaker constant based on the latest interpretation of spectroscopic data for water) was good for the ethanol treated surface at pH 3 — conditions where double layer interactions are negligible. However, the plasma treated surface at pH 3 showed adhesion an order of magnitude lower than calculated. In contrast, adhesion at pH 8 was in both cases greater than theoretical expectations, though the lower adhesion for the plasma treated surface was in quantitative agreement with the increased electrostatic double–layer interactions induced by plasma treatment. The results show that the adhesion of such surfaces is a complex phenomenon and that non-DLVO interactions probably play a substantial overall role.

Application of AFM from microbial cell to biofilm

Atomic Force Microscopy (AFM) has proven itself over recent years as an essential tool for the analysis of microbial systems. This article will review how AFM has been used to study microbial systems to provide unique insight into their behavior and relationship with their environment. Immobilization of live cells has enabled AFM imaging and force measurement to provide understanding of the structure and function of numerous microbial cells. At the macromolecular level AFM investigation into the properties of surface macromolecules and the energies associated with their mechanical conformation and functionality has helped unravel the complex interactions of microbial cells. At the level of the whole cell AFM has provided an integrated analysis of how the microbial cell exploits its environment through its selective, adaptable interface, the cell surface. In addition to these areas of study the AFM investigation of microbial biofilms has been vital for industrial and medical process analysis. There exists a tremendous potential for the future application of AFM to microbial systems and this has been strengthened by the trend to use AFM in combination with other characterization methods, such as confocal microscopy and Raman spectroscopy, to elucidate dynamic cellular processes.

Characterization of a ceramic ultrafiltration membrane in different operational states after its use in a heavy-metal ion removal process

In the present study, the atomic force microscopy (AFM) technique has been used to characterize a Carbosep M5 ceramic membrane (MWCO=10kDa, TiO(2)-ZrO(2) active layer). This membrane was previously used in a polymer supported ultrafiltration (PSU) process to recover copper, using partially ethoxylated polyethylenimine as the water-soluble polymer. The membrane was characterized in four different operational states: new, new and cleaned, fouled in a PSU stage and cleaned after a PSU process. The influence of the membrane state on pore opening size distribution and roughness was studied, finding a 16% decrease in the former and a 20% increase in the latter due to foulant deposition upon the membrane active layer. Phase angle distribution was also analyzed to indicate the foulant spreading on the membrane surface. These phase angle measurements can be related to pore opening size and roughness, concluding that the cleaning procedure is not totally effective and that foulant presence on the membrane active layer is not remarkable. Finally, AFM was used to measure the influence of pH on adhesion forces between a silica probe and the membrane active layer. These results can be related to the flux evolution vs pH in PSU experiments, finding both lowest adhesion and highest flux at pH 6.